Dermatology News

Mounting evidence suggests it’s a mistake to reject the diagnosis of drug reaction with eosinophilia and systemic symptoms, or DRESS, simply because the interval between initiating a drug and symptom onset is less than 15 days, Sarah Walsh, MD, said at the virtual annual congress of the European Academy of Dermatology and Venereology.

The standard dictum has been that diagnosis of this severe T-cell-mediated drug reaction requires more than a 2-week delay in symptom onset following initial drug intake. But this can steer physicians in the wrong direction and lead to stopping an innocent drug while the true culprit medication remains on board. This adversely affects patient prognosis, since a longer duration of drug exposure after symptom onset is associated with increased hospital length of stay and greater mortality risk, explained Dr. Walsh, clinical lead for dermatology at King’s College Hospital, London.

In addition to sharing recent data demonstrating that DRESS symptoms often occur within just a week or 2 of drug exposure, she highlighted several recent advances in the ability to predict DRESS severity. These include clues provided by rash morphology and histopathology, HLA testing, and a novel scoring system to assess DRESS severity and the risk of potentially fatal cytomegalovirus reactivation.

Short-delay DRESS onset

In a retrospective study of 41 patients with a first episode of DRESS in three French dermatology departments, 14 (34%) had onset within 15 days or less of initial exposure to the causative drug. In 6 of 14 patients in the rapid-onset group the offending drug was an antibiotic, while in another 5 the culprit was iodinated contrast media. In the delayed-onset DRESS group, the chief sensitizers were allopurinol in 8 patients, lamotrigine in 6, carbamazepine in 4, and sulfasalazine in 2; of note, none of these 4 delayed-onset DRESS drugs were implicated in any cases of rapid-onset DRESS. There were no differences in the clinical manifestations of DRESS between the rapid- and delayed-onset groups.

Similarly, dermatologists at Government Medical College in Kerala, India, reported in a retrospective study of 100 consecutive patients with DRESS, the drug reaction emerged within 2 weeks after starting the culprit medication in 36% of cases. Indeed, 11 patients became symptomatic within 3-7 days after beginning the medication; in 10 of the 11 cases, the offending agent was an antibiotic, and in 1 patient it was terbinafine. In the 25 cases of DRESS that arose on day 8-14 of drug therapy, the culprit was phenytoin in 14, antibiotics in 6, and 1 each for clopidogrel, hydroxychloroquine, sodium valproate, lamotrigine, and vitamin D₃.

Both groups of investigators concluded that a short time lag between starting a drug and development of symptoms of a drug reaction shouldn’t rule out DRESS as a possibility provided other criteria consistent with the diagnosis are present. Hallmarks of DRESS include an acute extensive rash, fever greater than 38 degrees C, enlarged lymph nodes at two or more sites, internal organ involvement, a low platelet count, elevated eosinophils, and abnormal lymphocyte levels.
 

Rash morphology and histology as prognostic indicators

Dr. Walsh was the lead investigator in a study that identified four distinct patterns of skin involvement in patients with DRESS. The most common type of rash in this single-center retrospective study of 27 consecutive patients was an urticated papular exanthem, present in 13 of the 27 patients. An erythema multiforme-like reaction was present in 8, exfoliative erythroderma in 3, and a morbilliform erythema in 3 others. The worst prognosis was in the subgroup with an erythema multiforme-like rash.

All 27 patients had hepatic involvement, which was severe in 9 cases. Six of the 9 with severe liver impairment had an erythema multiforme-like rash, compared with just 2 of the 18 with mild or moderate liver involvement; thus, an erythema multiforme-like skin eruption was associated with a fivefold increased likelihood of severe hepatic involvement.

“It is a clinical sign that we take seriously at presentation if atypical target lesions are present,” the dermatologist said.

Separately, Taiwanese investigators compared clinical and histopathologic features in a study of 32 patients with DRESS and 17 with maculopapular exanthem. Interface vacuolization, which was present in 29 of the 32 patients with DRESS, was far more prominent than in the comparator group. Moreover, severe dyskeratosis was significantly associated with more severe liver impairment in the DRESS group.
 

HLA testing

Testing for HLA haplotypes associated with severe drug reactions has a useful role as a screening tool prior to prescribing selected high-risk drugs, Dr. Walsh said. For example, it’s known that 6.8% of individuals of European ancestry carry HLA-A*32:01, an allele that was strongly associated with an increased rate of vancomycin-associated DRESS in a case-control study at Vanderbilt University, Nashville, Tenn. Indeed, 19 of 23 individuals with vancomycin-associated DRESS were HLA-A*32:01 positive, compared with none of 46 vancomycin-tolerant controls. Nineteen percent of HLA-A*32:01-positive patients developed DRESS during treatment with vancomycin, and the drug reaction occurred within 4 weeks.

The investigators noted that testing for HLA-A*32:01 is also useful in DRESS occurring in patients on vancomycin and multiple other drugs because the test’s high negative predictive value may safely allow continued therapy with this potent antibiotic for Gram-positive infections.
 

A DRESS prognostic scoring system

Japanese researchers have developed a scoring system for DRESS for use in monitoring severity of the drug reaction, predicting prognosis, and estimating the risk of developing cytomegalovirus disease and its potentially fatal complications. The scoring system incorporates patient factors, including age, duration of drug exposure after symptom onset; rash characteristics, such as percentage of body surface area involved and presence or absence of erythroderma; appetite loss; and laboratory values.

“It yields a prognostic score that can be used to determine treatment choices, such as immediate intervention with anti-CMV agents. It’s a very useful tool,” Dr. Walsh said.

She reported having no financial conflicts regarding her presentation.

bjancin@mdedge.com

Mounting evidence suggests it’s a mistake to reject the diagnosis of drug reaction with eosinophilia and systemic symptoms, or DRESS, simply because the interval between initiating a drug and symptom onset is less than 15 days, Sarah Walsh, MD, said at the virtual annual congress of the European Academy of Dermatology and Venereology.

The standard dictum has been that diagnosis of this severe T-cell-mediated drug reaction requires more than a 2-week delay in symptom onset following initial drug intake. But this can steer physicians in the wrong direction and lead to stopping an innocent drug while the true culprit medication remains on board. This adversely affects patient prognosis, since a longer duration of drug exposure after symptom onset is associated with increased hospital length of stay and greater mortality risk, explained Dr. Walsh, clinical lead for dermatology at King’s College Hospital, London.

In addition to sharing recent data demonstrating that DRESS symptoms often occur within just a week or 2 of drug exposure, she highlighted several recent advances in the ability to predict DRESS severity. These include clues provided by rash morphology and histopathology, HLA testing, and a novel scoring system to assess DRESS severity and the risk of potentially fatal cytomegalovirus reactivation.

Short-delay DRESS onset

In a retrospective study of 41 patients with a first episode of DRESS in three French dermatology departments, 14 (34%) had onset within 15 days or less of initial exposure to the causative drug. In 6 of 14 patients in the rapid-onset group the offending drug was an antibiotic, while in another 5 the culprit was iodinated contrast media. In the delayed-onset DRESS group, the chief sensitizers were allopurinol in 8 patients, lamotrigine in 6, carbamazepine in 4, and sulfasalazine in 2; of note, none of these 4 delayed-onset DRESS drugs were implicated in any cases of rapid-onset DRESS. There were no differences in the clinical manifestations of DRESS between the rapid- and delayed-onset groups.

Similarly, dermatologists at Government Medical College in Kerala, India, reported in a retrospective study of 100 consecutive patients with DRESS, the drug reaction emerged within 2 weeks after starting the culprit medication in 36% of cases. Indeed, 11 patients became symptomatic within 3-7 days after beginning the medication; in 10 of the 11 cases, the offending agent was an antibiotic, and in 1 patient it was terbinafine. In the 25 cases of DRESS that arose on day 8-14 of drug therapy, the culprit was phenytoin in 14, antibiotics in 6, and 1 each for clopidogrel, hydroxychloroquine, sodium valproate, lamotrigine, and vitamin D₃.

Both groups of investigators concluded that a short time lag between starting a drug and development of symptoms of a drug reaction shouldn’t rule out DRESS as a possibility provided other criteria consistent with the diagnosis are present. Hallmarks of DRESS include an acute extensive rash, fever greater than 38 degrees C, enlarged lymph nodes at two or more sites, internal organ involvement, a low platelet count, elevated eosinophils, and abnormal lymphocyte levels.
 

Rash morphology and histology as prognostic indicators

Dr. Walsh was the lead investigator in a study that identified four distinct patterns of skin involvement in patients with DRESS. The most common type of rash in this single-center retrospective study of 27 consecutive patients was an urticated papular exanthem, present in 13 of the 27 patients. An erythema multiforme-like reaction was present in 8, exfoliative erythroderma in 3, and a morbilliform erythema in 3 others. The worst prognosis was in the subgroup with an erythema multiforme-like rash.

All 27 patients had hepatic involvement, which was severe in 9 cases. Six of the 9 with severe liver impairment had an erythema multiforme-like rash, compared with just 2 of the 18 with mild or moderate liver involvement; thus, an erythema multiforme-like skin eruption was associated with a fivefold increased likelihood of severe hepatic involvement.

“It is a clinical sign that we take seriously at presentation if atypical target lesions are present,” the dermatologist said.

Separately, Taiwanese investigators compared clinical and histopathologic features in a study of 32 patients with DRESS and 17 with maculopapular exanthem. Interface vacuolization, which was present in 29 of the 32 patients with DRESS, was far more prominent than in the comparator group. Moreover, severe dyskeratosis was significantly associated with more severe liver impairment in the DRESS group.
 

HLA testing

Testing for HLA haplotypes associated with severe drug reactions has a useful role as a screening tool prior to prescribing selected high-risk drugs, Dr. Walsh said. For example, it’s known that 6.8% of individuals of European ancestry carry HLA-A*32:01, an allele that was strongly associated with an increased rate of vancomycin-associated DRESS in a case-control study at Vanderbilt University, Nashville, Tenn. Indeed, 19 of 23 individuals with vancomycin-associated DRESS were HLA-A*32:01 positive, compared with none of 46 vancomycin-tolerant controls. Nineteen percent of HLA-A*32:01-positive patients developed DRESS during treatment with vancomycin, and the drug reaction occurred within 4 weeks.

The investigators noted that testing for HLA-A*32:01 is also useful in DRESS occurring in patients on vancomycin and multiple other drugs because the test’s high negative predictive value may safely allow continued therapy with this potent antibiotic for Gram-positive infections.
 

A DRESS prognostic scoring system

Japanese researchers have developed a scoring system for DRESS for use in monitoring severity of the drug reaction, predicting prognosis, and estimating the risk of developing cytomegalovirus disease and its potentially fatal complications. The scoring system incorporates patient factors, including age, duration of drug exposure after symptom onset; rash characteristics, such as percentage of body surface area involved and presence or absence of erythroderma; appetite loss; and laboratory values.

“It yields a prognostic score that can be used to determine treatment choices, such as immediate intervention with anti-CMV agents. It’s a very useful tool,” Dr. Walsh said.

She reported having no financial conflicts regarding her presentation.

bjancin@mdedge.com

Mounting evidence suggests it’s a mistake to reject the diagnosis of drug reaction with eosinophilia and systemic symptoms, or DRESS, simply because the interval between initiating a drug and symptom onset is less than 15 days, Sarah Walsh, MD, said at the virtual annual congress of the European Academy of Dermatology and Venereology.

The standard dictum has been that diagnosis of this severe T-cell-mediated drug reaction requires more than a 2-week delay in symptom onset following initial drug intake. But this can steer physicians in the wrong direction and lead to stopping an innocent drug while the true culprit medication remains on board. This adversely affects patient prognosis, since a longer duration of drug exposure after symptom onset is associated with increased hospital length of stay and greater mortality risk, explained Dr. Walsh, clinical lead for dermatology at King’s College Hospital, London.

In addition to sharing recent data demonstrating that DRESS symptoms often occur within just a week or 2 of drug exposure, she highlighted several recent advances in the ability to predict DRESS severity. These include clues provided by rash morphology and histopathology, HLA testing, and a novel scoring system to assess DRESS severity and the risk of potentially fatal cytomegalovirus reactivation.

Short-delay DRESS onset

In a retrospective study of 41 patients with a first episode of DRESS in three French dermatology departments, 14 (34%) had onset within 15 days or less of initial exposure to the causative drug. In 6 of 14 patients in the rapid-onset group the offending drug was an antibiotic, while in another 5 the culprit was iodinated contrast media. In the delayed-onset DRESS group, the chief sensitizers were allopurinol in 8 patients, lamotrigine in 6, carbamazepine in 4, and sulfasalazine in 2; of note, none of these 4 delayed-onset DRESS drugs were implicated in any cases of rapid-onset DRESS. There were no differences in the clinical manifestations of DRESS between the rapid- and delayed-onset groups.

Similarly, dermatologists at Government Medical College in Kerala, India, reported in a retrospective study of 100 consecutive patients with DRESS, the drug reaction emerged within 2 weeks after starting the culprit medication in 36% of cases. Indeed, 11 patients became symptomatic within 3-7 days after beginning the medication; in 10 of the 11 cases, the offending agent was an antibiotic, and in 1 patient it was terbinafine. In the 25 cases of DRESS that arose on day 8-14 of drug therapy, the culprit was phenytoin in 14, antibiotics in 6, and 1 each for clopidogrel, hydroxychloroquine, sodium valproate, lamotrigine, and vitamin D₃.

Both groups of investigators concluded that a short time lag between starting a drug and development of symptoms of a drug reaction shouldn’t rule out DRESS as a possibility provided other criteria consistent with the diagnosis are present. Hallmarks of DRESS include an acute extensive rash, fever greater than 38 degrees C, enlarged lymph nodes at two or more sites, internal organ involvement, a low platelet count, elevated eosinophils, and abnormal lymphocyte levels.
 

Rash morphology and histology as prognostic indicators

Dr. Walsh was the lead investigator in a study that identified four distinct patterns of skin involvement in patients with DRESS. The most common type of rash in this single-center retrospective study of 27 consecutive patients was an urticated papular exanthem, present in 13 of the 27 patients. An erythema multiforme-like reaction was present in 8, exfoliative erythroderma in 3, and a morbilliform erythema in 3 others. The worst prognosis was in the subgroup with an erythema multiforme-like rash.

All 27 patients had hepatic involvement, which was severe in 9 cases. Six of the 9 with severe liver impairment had an erythema multiforme-like rash, compared with just 2 of the 18 with mild or moderate liver involvement; thus, an erythema multiforme-like skin eruption was associated with a fivefold increased likelihood of severe hepatic involvement.

“It is a clinical sign that we take seriously at presentation if atypical target lesions are present,” the dermatologist said.

Separately, Taiwanese investigators compared clinical and histopathologic features in a study of 32 patients with DRESS and 17 with maculopapular exanthem. Interface vacuolization, which was present in 29 of the 32 patients with DRESS, was far more prominent than in the comparator group. Moreover, severe dyskeratosis was significantly associated with more severe liver impairment in the DRESS group.
 

HLA testing

Testing for HLA haplotypes associated with severe drug reactions has a useful role as a screening tool prior to prescribing selected high-risk drugs, Dr. Walsh said. For example, it’s known that 6.8% of individuals of European ancestry carry HLA-A*32:01, an allele that was strongly associated with an increased rate of vancomycin-associated DRESS in a case-control study at Vanderbilt University, Nashville, Tenn. Indeed, 19 of 23 individuals with vancomycin-associated DRESS were HLA-A*32:01 positive, compared with none of 46 vancomycin-tolerant controls. Nineteen percent of HLA-A*32:01-positive patients developed DRESS during treatment with vancomycin, and the drug reaction occurred within 4 weeks.

The investigators noted that testing for HLA-A*32:01 is also useful in DRESS occurring in patients on vancomycin and multiple other drugs because the test’s high negative predictive value may safely allow continued therapy with this potent antibiotic for Gram-positive infections.
 

A DRESS prognostic scoring system

Japanese researchers have developed a scoring system for DRESS for use in monitoring severity of the drug reaction, predicting prognosis, and estimating the risk of developing cytomegalovirus disease and its potentially fatal complications. The scoring system incorporates patient factors, including age, duration of drug exposure after symptom onset; rash characteristics, such as percentage of body surface area involved and presence or absence of erythroderma; appetite loss; and laboratory values.

“It yields a prognostic score that can be used to determine treatment choices, such as immediate intervention with anti-CMV agents. It’s a very useful tool,” Dr. Walsh said.

She reported having no financial conflicts regarding her presentation.

bjancin@mdedge.com

The United States is nearly 6 weeks into its historic campaign to vaccinate Americans against the virus that causes COVID-19, and so far, the two vaccines in use look remarkably low risk, according to new data presented today at a meeting of vaccine experts that advise the Centers for Disease Control and Prevention.

With 23.5 million doses of the Pfizer and Moderna vaccines now given, there have been very few serious side effects. In addition, deaths reported after people got the vaccine do not seem to be related to it.

The most common symptoms reported after vaccination were pain where people got the shot, fatigue, headache, and muscle soreness. These were more common after the second dose. In addition, about one in four people reported fever and chills after the second shot.

“On the whole, I thought it was very reassuring,” said William Schaffner, MD, an infectious disease expert with Vanderbilt University, Nashville, Tenn., who listened to the presentations.

The CDC is collecting safety information through multiple channels. These include a new smartphone-based app called V-Safe, which collects daily information from people who’ve been vaccinated; the federal Vaccine Adverse Event Reporting System, which accepts reports from anyone; and the Vaccine Safety Datalink, which is a collaboration between the CDC and nine major hospital systems. There’s also the Clinical Immunization Safety Assessment Project, a collaboration between the CDC and vaccine safety experts.

After surveying these systems, experts heading the safety committee for the CDC’s Advisory Committee on Immunization Practices said there have been few serious side effects reported.

Very rarely, severe allergic reactions – called anaphylaxis – have occurred after vaccination. There have been 50 of these cases reported after the Pfizer vaccine and 21 cases reported after the Moderna vaccine to date. Nearly all of them – 94% of the anaphylaxis cases after Pfizer vaccines and 100% of those after Moderna’s vaccine – have been in women, though it’s not clear why.

That translates to a rate of about five cases of anaphylaxis for every million doses of the Pfizer vaccine and about three for every million doses of the Moderna vaccine. Most of these occur within 15 minutes after getting a vaccine dose, with one reported as long as 20 hours after the shot.

The CDC suspects these may be related to an ingredient called polyethylene glycol (PEG). PEG is a part of the particles that slip the vaccines’ mRNA into cells with instructions to make the spike protein of the virus. Cells then express these spikes on their surfaces so the immune system can learn to recognize them and make defenses against them. PEG is a common ingredient in many drugs and occasionally triggers anaphylaxis.
 

Reported deaths seem unrelated to vaccines

Through Jan. 18, 196 people have died after getting a vaccine.

Most of these deaths (129) were in patients in long term care facilities. These deaths are still being investigated, but when they were compared with the number of deaths that might be expected over the same period because of natural causes, they seemed to be coincidental and not caused by the vaccine, said Tom Shimabukuro, MD, deputy director of the Immunization Safety Office at the CDC, who studied the data.

In fact, death rates were lower among vaccinated nursing home residents, compared with those who had not been vaccinated.

“These findings suggest that short-term mortality rates appear unrelated to vaccination for COVID-19,” Dr. Shimabukuro said.

This also appeared to be true for younger adults who died after their shots.

There were 28 people aged under 65 years who died after being vaccinated. Most of these deaths were heart related, according to autopsy reports. When investigators compared the number of sudden cardiac deaths expected to occur in this population naturally, they found people who were vaccinated had a lower rate than would have been expected without vaccination. This suggests that these deaths were also unrelated to the vaccine.
 

More vaccines on the horizon

The panel also heard an update from drug company AstraZeneca on its vaccine. It’s being used in 18 countries but has not yet been authorized in the United States.

That vaccine is currently in phase 3 of its U.S. clinical trials, and more than 26,000 people who have volunteered to get the shot had received their second dose as of Jan. 21, the company said.

The Food and Drug Administration requires at least 2 months of follow-up before it will evaluate a vaccine for an emergency-use authorization, which means the company would be ready to submit by the end of March, with a possible approval by April.

The AstraZeneca vaccine uses a more traditional method to create immunity, slipping a key part of the virus that causes COVID-19 into the shell of an adenovirus – a virus that causes cold-like symptoms – that normally infects monkeys. When the immune system sees the virus, it generates protective defenses against it.

The two-dose vaccine can be stored in a regular refrigerator for up to 6 months, which makes it easier to handle than the mRNA vaccines, which require much colder storage. Another advantage appears to be that it’s less likely to trigger severe allergic reactions. So far, there have been no cases of anaphylaxis reported after this shot.

In total, four serious side effects have been reported with the AstraZeneca vaccine, including two cases of transverse myelitis, a serious condition that causes swelling of the spinal cord, leading to pain, muscle weakness, and paralysis. One of these was in the group that got the placebo. The reports paused the trial, but it was allowed to continue after a safety review.

This vaccine also appears to be less effective than the mRNA shots. Data presented to the panel show it appears to cut the risk of developing a COVID infection that has symptoms by 62%. That’s over the 50% threshold the FDA set for approval but less than seen with the mRNA vaccines, which are more than 90% effective at preventing infections.

“Is the average person going to want to take the AstraZeneca shot? What role is this going to play in our vaccination program?” Dr. Schaffner said.

Johnson & Johnson will have enough data from its clinical trials to submit it to the FDA within the next week, the company said in a call with shareholders on Tuesday. So far, its one-dose shots looks to be about as effective as both the Pfizer and Moderna vaccines.

“It could be that we wind up with four vaccines: Three that can run very fast, and one that’s not so fast,” Dr. Schaffner said.

A version of this article first appeared on Medscape.com.

The United States is nearly 6 weeks into its historic campaign to vaccinate Americans against the virus that causes COVID-19, and so far, the two vaccines in use look remarkably low risk, according to new data presented today at a meeting of vaccine experts that advise the Centers for Disease Control and Prevention.

With 23.5 million doses of the Pfizer and Moderna vaccines now given, there have been very few serious side effects. In addition, deaths reported after people got the vaccine do not seem to be related to it.

The most common symptoms reported after vaccination were pain where people got the shot, fatigue, headache, and muscle soreness. These were more common after the second dose. In addition, about one in four people reported fever and chills after the second shot.

“On the whole, I thought it was very reassuring,” said William Schaffner, MD, an infectious disease expert with Vanderbilt University, Nashville, Tenn., who listened to the presentations.

The CDC is collecting safety information through multiple channels. These include a new smartphone-based app called V-Safe, which collects daily information from people who’ve been vaccinated; the federal Vaccine Adverse Event Reporting System, which accepts reports from anyone; and the Vaccine Safety Datalink, which is a collaboration between the CDC and nine major hospital systems. There’s also the Clinical Immunization Safety Assessment Project, a collaboration between the CDC and vaccine safety experts.

After surveying these systems, experts heading the safety committee for the CDC’s Advisory Committee on Immunization Practices said there have been few serious side effects reported.

Very rarely, severe allergic reactions – called anaphylaxis – have occurred after vaccination. There have been 50 of these cases reported after the Pfizer vaccine and 21 cases reported after the Moderna vaccine to date. Nearly all of them – 94% of the anaphylaxis cases after Pfizer vaccines and 100% of those after Moderna’s vaccine – have been in women, though it’s not clear why.

That translates to a rate of about five cases of anaphylaxis for every million doses of the Pfizer vaccine and about three for every million doses of the Moderna vaccine. Most of these occur within 15 minutes after getting a vaccine dose, with one reported as long as 20 hours after the shot.

The CDC suspects these may be related to an ingredient called polyethylene glycol (PEG). PEG is a part of the particles that slip the vaccines’ mRNA into cells with instructions to make the spike protein of the virus. Cells then express these spikes on their surfaces so the immune system can learn to recognize them and make defenses against them. PEG is a common ingredient in many drugs and occasionally triggers anaphylaxis.
 

Reported deaths seem unrelated to vaccines

Through Jan. 18, 196 people have died after getting a vaccine.

Most of these deaths (129) were in patients in long term care facilities. These deaths are still being investigated, but when they were compared with the number of deaths that might be expected over the same period because of natural causes, they seemed to be coincidental and not caused by the vaccine, said Tom Shimabukuro, MD, deputy director of the Immunization Safety Office at the CDC, who studied the data.

In fact, death rates were lower among vaccinated nursing home residents, compared with those who had not been vaccinated.

“These findings suggest that short-term mortality rates appear unrelated to vaccination for COVID-19,” Dr. Shimabukuro said.

This also appeared to be true for younger adults who died after their shots.

There were 28 people aged under 65 years who died after being vaccinated. Most of these deaths were heart related, according to autopsy reports. When investigators compared the number of sudden cardiac deaths expected to occur in this population naturally, they found people who were vaccinated had a lower rate than would have been expected without vaccination. This suggests that these deaths were also unrelated to the vaccine.
 

More vaccines on the horizon

The panel also heard an update from drug company AstraZeneca on its vaccine. It’s being used in 18 countries but has not yet been authorized in the United States.

That vaccine is currently in phase 3 of its U.S. clinical trials, and more than 26,000 people who have volunteered to get the shot had received their second dose as of Jan. 21, the company said.

The Food and Drug Administration requires at least 2 months of follow-up before it will evaluate a vaccine for an emergency-use authorization, which means the company would be ready to submit by the end of March, with a possible approval by April.

The AstraZeneca vaccine uses a more traditional method to create immunity, slipping a key part of the virus that causes COVID-19 into the shell of an adenovirus – a virus that causes cold-like symptoms – that normally infects monkeys. When the immune system sees the virus, it generates protective defenses against it.

The two-dose vaccine can be stored in a regular refrigerator for up to 6 months, which makes it easier to handle than the mRNA vaccines, which require much colder storage. Another advantage appears to be that it’s less likely to trigger severe allergic reactions. So far, there have been no cases of anaphylaxis reported after this shot.

In total, four serious side effects have been reported with the AstraZeneca vaccine, including two cases of transverse myelitis, a serious condition that causes swelling of the spinal cord, leading to pain, muscle weakness, and paralysis. One of these was in the group that got the placebo. The reports paused the trial, but it was allowed to continue after a safety review.

This vaccine also appears to be less effective than the mRNA shots. Data presented to the panel show it appears to cut the risk of developing a COVID infection that has symptoms by 62%. That’s over the 50% threshold the FDA set for approval but less than seen with the mRNA vaccines, which are more than 90% effective at preventing infections.

“Is the average person going to want to take the AstraZeneca shot? What role is this going to play in our vaccination program?” Dr. Schaffner said.

Johnson & Johnson will have enough data from its clinical trials to submit it to the FDA within the next week, the company said in a call with shareholders on Tuesday. So far, its one-dose shots looks to be about as effective as both the Pfizer and Moderna vaccines.

“It could be that we wind up with four vaccines: Three that can run very fast, and one that’s not so fast,” Dr. Schaffner said.

A version of this article first appeared on Medscape.com.

The United States is nearly 6 weeks into its historic campaign to vaccinate Americans against the virus that causes COVID-19, and so far, the two vaccines in use look remarkably low risk, according to new data presented today at a meeting of vaccine experts that advise the Centers for Disease Control and Prevention.

With 23.5 million doses of the Pfizer and Moderna vaccines now given, there have been very few serious side effects. In addition, deaths reported after people got the vaccine do not seem to be related to it.

The most common symptoms reported after vaccination were pain where people got the shot, fatigue, headache, and muscle soreness. These were more common after the second dose. In addition, about one in four people reported fever and chills after the second shot.

“On the whole, I thought it was very reassuring,” said William Schaffner, MD, an infectious disease expert with Vanderbilt University, Nashville, Tenn., who listened to the presentations.

The CDC is collecting safety information through multiple channels. These include a new smartphone-based app called V-Safe, which collects daily information from people who’ve been vaccinated; the federal Vaccine Adverse Event Reporting System, which accepts reports from anyone; and the Vaccine Safety Datalink, which is a collaboration between the CDC and nine major hospital systems. There’s also the Clinical Immunization Safety Assessment Project, a collaboration between the CDC and vaccine safety experts.

After surveying these systems, experts heading the safety committee for the CDC’s Advisory Committee on Immunization Practices said there have been few serious side effects reported.

Very rarely, severe allergic reactions – called anaphylaxis – have occurred after vaccination. There have been 50 of these cases reported after the Pfizer vaccine and 21 cases reported after the Moderna vaccine to date. Nearly all of them – 94% of the anaphylaxis cases after Pfizer vaccines and 100% of those after Moderna’s vaccine – have been in women, though it’s not clear why.

That translates to a rate of about five cases of anaphylaxis for every million doses of the Pfizer vaccine and about three for every million doses of the Moderna vaccine. Most of these occur within 15 minutes after getting a vaccine dose, with one reported as long as 20 hours after the shot.

The CDC suspects these may be related to an ingredient called polyethylene glycol (PEG). PEG is a part of the particles that slip the vaccines’ mRNA into cells with instructions to make the spike protein of the virus. Cells then express these spikes on their surfaces so the immune system can learn to recognize them and make defenses against them. PEG is a common ingredient in many drugs and occasionally triggers anaphylaxis.
 

Reported deaths seem unrelated to vaccines

Through Jan. 18, 196 people have died after getting a vaccine.

Most of these deaths (129) were in patients in long term care facilities. These deaths are still being investigated, but when they were compared with the number of deaths that might be expected over the same period because of natural causes, they seemed to be coincidental and not caused by the vaccine, said Tom Shimabukuro, MD, deputy director of the Immunization Safety Office at the CDC, who studied the data.

In fact, death rates were lower among vaccinated nursing home residents, compared with those who had not been vaccinated.

“These findings suggest that short-term mortality rates appear unrelated to vaccination for COVID-19,” Dr. Shimabukuro said.

This also appeared to be true for younger adults who died after their shots.

There were 28 people aged under 65 years who died after being vaccinated. Most of these deaths were heart related, according to autopsy reports. When investigators compared the number of sudden cardiac deaths expected to occur in this population naturally, they found people who were vaccinated had a lower rate than would have been expected without vaccination. This suggests that these deaths were also unrelated to the vaccine.
 

More vaccines on the horizon

The panel also heard an update from drug company AstraZeneca on its vaccine. It’s being used in 18 countries but has not yet been authorized in the United States.

That vaccine is currently in phase 3 of its U.S. clinical trials, and more than 26,000 people who have volunteered to get the shot had received their second dose as of Jan. 21, the company said.

The Food and Drug Administration requires at least 2 months of follow-up before it will evaluate a vaccine for an emergency-use authorization, which means the company would be ready to submit by the end of March, with a possible approval by April.

The AstraZeneca vaccine uses a more traditional method to create immunity, slipping a key part of the virus that causes COVID-19 into the shell of an adenovirus – a virus that causes cold-like symptoms – that normally infects monkeys. When the immune system sees the virus, it generates protective defenses against it.

The two-dose vaccine can be stored in a regular refrigerator for up to 6 months, which makes it easier to handle than the mRNA vaccines, which require much colder storage. Another advantage appears to be that it’s less likely to trigger severe allergic reactions. So far, there have been no cases of anaphylaxis reported after this shot.

In total, four serious side effects have been reported with the AstraZeneca vaccine, including two cases of transverse myelitis, a serious condition that causes swelling of the spinal cord, leading to pain, muscle weakness, and paralysis. One of these was in the group that got the placebo. The reports paused the trial, but it was allowed to continue after a safety review.

This vaccine also appears to be less effective than the mRNA shots. Data presented to the panel show it appears to cut the risk of developing a COVID infection that has symptoms by 62%. That’s over the 50% threshold the FDA set for approval but less than seen with the mRNA vaccines, which are more than 90% effective at preventing infections.

“Is the average person going to want to take the AstraZeneca shot? What role is this going to play in our vaccination program?” Dr. Schaffner said.

Johnson & Johnson will have enough data from its clinical trials to submit it to the FDA within the next week, the company said in a call with shareholders on Tuesday. So far, its one-dose shots looks to be about as effective as both the Pfizer and Moderna vaccines.

“It could be that we wind up with four vaccines: Three that can run very fast, and one that’s not so fast,” Dr. Schaffner said.

A version of this article first appeared on Medscape.com.

Cosmetic procedures continued to increase in popularity in 2019, and body sculpting and laser/light/energy-based procedures led the way, according to a survey by the American Society of Dermatologic Surgery.

The number of cosmetic procedures performed by dermatologic surgeons increased by 14% from 2018 to 2019, with body-sculpting procedures jumping by almost 62%, the largest proportional rise among the major categories of cosmetic procedures, the ASDS reported in its annual member survey.

Use of laser/light/energy-based devices was up by a much lower 18%, but the increase in the actual number of procedures – nearly 637,000 more than 2018 – was larger than any other category, the ASDS said.

Procedures categorized as “other rejuvenation” – microneedling, platelet-rich plasma, hair rejuvenation, and thread lifts – were another bright spot in the cosmetic lineup in 2019, rising 38% over their 2018 volume. Injectable neuromodulator treatments, which were second in overall volume with almost 2.4 million procedures, were up by 12.5% in 2019, compared with 2018, the ASDS said.

The injectable soft-tissue fillers, however, did not produce any noteworthy gain in the volume of procedures for the second consecutive year. Meanwhile, the number of chemical peel procedures dropped by almost 16% in 2019 after rising for the last 2 years, the ASDS reported.

A closer look at the body-sculpting sector also shows some declines in 2019, despite the overall success: Cryolipolysis procedures were down by 10.3% and deoxycholic acid procedures slipped 13.7%. The biggest addition – over 157,000 procedures – came from muscle-toning devices, which were new to the survey last year, the ASDS noted.

The survey was conducted among the society’s members from May 7 to July 31, 2020, and the 514 responses were generalized to the entire ASDS membership of over 6,400 physicians.

rfranki@mdedge.com

Cosmetic procedures continued to increase in popularity in 2019, and body sculpting and laser/light/energy-based procedures led the way, according to a survey by the American Society of Dermatologic Surgery.

The number of cosmetic procedures performed by dermatologic surgeons increased by 14% from 2018 to 2019, with body-sculpting procedures jumping by almost 62%, the largest proportional rise among the major categories of cosmetic procedures, the ASDS reported in its annual member survey.

Use of laser/light/energy-based devices was up by a much lower 18%, but the increase in the actual number of procedures – nearly 637,000 more than 2018 – was larger than any other category, the ASDS said.

Procedures categorized as “other rejuvenation” – microneedling, platelet-rich plasma, hair rejuvenation, and thread lifts – were another bright spot in the cosmetic lineup in 2019, rising 38% over their 2018 volume. Injectable neuromodulator treatments, which were second in overall volume with almost 2.4 million procedures, were up by 12.5% in 2019, compared with 2018, the ASDS said.

The injectable soft-tissue fillers, however, did not produce any noteworthy gain in the volume of procedures for the second consecutive year. Meanwhile, the number of chemical peel procedures dropped by almost 16% in 2019 after rising for the last 2 years, the ASDS reported.

A closer look at the body-sculpting sector also shows some declines in 2019, despite the overall success: Cryolipolysis procedures were down by 10.3% and deoxycholic acid procedures slipped 13.7%. The biggest addition – over 157,000 procedures – came from muscle-toning devices, which were new to the survey last year, the ASDS noted.

The survey was conducted among the society’s members from May 7 to July 31, 2020, and the 514 responses were generalized to the entire ASDS membership of over 6,400 physicians.

rfranki@mdedge.com

Cosmetic procedures continued to increase in popularity in 2019, and body sculpting and laser/light/energy-based procedures led the way, according to a survey by the American Society of Dermatologic Surgery.

The number of cosmetic procedures performed by dermatologic surgeons increased by 14% from 2018 to 2019, with body-sculpting procedures jumping by almost 62%, the largest proportional rise among the major categories of cosmetic procedures, the ASDS reported in its annual member survey.

Use of laser/light/energy-based devices was up by a much lower 18%, but the increase in the actual number of procedures – nearly 637,000 more than 2018 – was larger than any other category, the ASDS said.

Procedures categorized as “other rejuvenation” – microneedling, platelet-rich plasma, hair rejuvenation, and thread lifts – were another bright spot in the cosmetic lineup in 2019, rising 38% over their 2018 volume. Injectable neuromodulator treatments, which were second in overall volume with almost 2.4 million procedures, were up by 12.5% in 2019, compared with 2018, the ASDS said.

The injectable soft-tissue fillers, however, did not produce any noteworthy gain in the volume of procedures for the second consecutive year. Meanwhile, the number of chemical peel procedures dropped by almost 16% in 2019 after rising for the last 2 years, the ASDS reported.

A closer look at the body-sculpting sector also shows some declines in 2019, despite the overall success: Cryolipolysis procedures were down by 10.3% and deoxycholic acid procedures slipped 13.7%. The biggest addition – over 157,000 procedures – came from muscle-toning devices, which were new to the survey last year, the ASDS noted.

The survey was conducted among the society’s members from May 7 to July 31, 2020, and the 514 responses were generalized to the entire ASDS membership of over 6,400 physicians.

rfranki@mdedge.com

A follow-up look at an international registry suggests that some people may have persistent, long-lasting dermatologic manifestations – especially so-called “COVID toes” – as a result of infection with or exposure to the SARS-CoV-2 virus, but some dermatologists question if the skin signs and symptoms are truly related.

In their commentary in the Lancet Infectious Diseases, Esther P. Freeman, MD, PhD, and colleagues who lead and participate in the American Academy of Dermatology’s international registry said their analysis “revealed a previously unreported subset of patients who experience long-haul symptoms in dermatology-dominant COVID-19.”

Some of the data was presented at the 29th European Academy of Dermatology and Venereology in late October 2020, but has since been updated with more cases.

Dermatologists who spoke with this news organization said it has not been settled that some skin manifestations – such as pernio/chilblains rashes, seen primarily in nonhospitalized patients, and described in the registry – are definitively caused by COVID. They also noted that in some cases, patients who initially test negative for COVID-19 by polymerase chain reaction (PCR) sometimes do not ever develop antibodies, which could mean they were never actually exposed to SARS-CoV-2.

M. Alexander Otto/MDedge News

“I still question whether the perniosis is directly related to infection with SARS-CoV-2 or not,” said Anthony Fernandez, MD, PhD, director of medical and inpatient dermatology and assistant professor of dermatopathology at the Cleveland Clinic. His uncertainty is driven by the lack of seroconversion and that few cases were seen over the summer in the United States – suggesting that it may still be a result of cold temperatures.

“I’m not sure there is a definitive correct answer, definitely not that everyone would agree on,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn.

Dr. Freeman, however, believed that pernio and especially persistent lesions are caused by an immune response to COVID.

In an interview, she noted the multiple cases of patients in the registry who did seroconvert and that, while a registry is not a perfect means of getting an answer, it is good for generating questions. Taken collectively, the cases in the registry can “tell a story for further hypotheses,” said Dr. Freeman, who is director of global health dermatology at Massachusetts General Hospital and assistant professor of dermatology at Harvard University, both in Boston.

“We were noticing this signal across the world” that patients “developed these toe lesions and they never got better,” said Dr. Freeman. Generally, people who experience pernio, also described as COVID toes or “COVID fingers,” recover in 4-8 weeks. But in the registry, “we did have this subset of patients who really were experiencing these very longstanding symptoms,” she added.

Two patients with lab-confirmed COVID have had long-lasting pernio of 133 days and 150 days. “I’m caring for a cohort in Boston who have had long COVID of the skin and symptoms for over 10 months,” Dr. Freeman said.
 

Pernio dominates

The registry – a collaboration between the AAD and the International League of Dermatological Societies – was launched in April 2020. Any medical professional can enter case information. From April to October, 1,030 total cases and 331 laboratory-confirmed or suspected COVID-19 cases with dermatological manifestations were entered from 41 countries.

Most of the cases were just recorded at a single time point, which is an acknowledged limitation of the study.

Dr. Freeman and colleagues reached out to registry participants in June and August to get updates on COVID lab test results and sign and symptom duration. Overall, 234 total and 96 lab-confirmed COVID infections had more lengthy data about sign and symptom duration.

Pernio lasted a median of 15 days in patients with suspected disease and 12 days for those with lab-confirmed COVID, compared with a median of 7 days for morbilliform eruptions, 4 days for urticarial eruptions, and 20 days for papulosquamous eruptions – all in patients with lab-confirmed disease.

Of the 103 cases of pernio, 7 had symptoms lasting more than 60 days. Only two of those seven patients had lab-confirmed COVID. Initially, the one patient tested negative with nasopharyngeal PCR, and serum IgM and IgG. Six weeks after pernio onset, the patient – still experiencing fatigue and pernio – seroconverted to anti–SARS-CoV-2 IgM positivity.

The other long-haul patient, after a negative PCR, tested positive for SARS-CoV-2 serum IgG 1 month after pernio onset.

Robust immune response?

Dr. Freeman said these patients might have a very high interferon response initially to the virus, which makes for a mild to nonexistent disease, but could create inflammation elsewhere. “I almost view the toes as an innocent bystander of a robust immune response to SARS-CoV-2.”

Although he has not seen extended pernio or other skin manifestations in his patients, Dr. Fernandez said the interferon hypothesis is “fair,” and “the best that’s out there.” Dr. Fernandez is currently studying cutaneous manifestations of COVID-19 as a principal investigator of a trial sponsored by the Clinical and Translational Science Collaborative of Cleveland.

Dr. Ko said in an interview that she has not observed long-haul skin issues in her patients, but Yale colleagues have.

In a study, she and Yale colleagues published in September, SARS-CoV-2 spike protein was detected in perniotic lesions, but not nuclear protein or viral RNA. The test they used – immunohistochemistry – can be nonspecific, which muddied results.

She does not think there is replicating virus in the skin or the lesions. Instead, said Dr. Ko, “either there is viral spike protein that has somehow become disassociated from actively replicating virus that somehow got deposited in endothelial cells,” or the staining “was spurious,” or some other protein is cross-reacting. “And the people who are unlucky enough to have that protein in their endothelial cells can manifest this COVID-toe, COVID-finger phenomenon.”

To her, it’s an unsolved mystery. “The weird thing is, we’ve never before had this much perniosis,” Dr. Ko said.

Dr. Fernandez is not convinced yet, noting that, in Cleveland, more pernio cases were observed in March and April than in the summer. “If it is a manifestation of the infection then you also need the right environment, the cold weather for this manifestation to present,” he said. “Or, it really isn’t a direct manifestation of COVID-19 but may be more related to other factors,” such as lifestyle changes related to limitations implemented to help mitigate the spread of the disease.

“To me the jury is still out whether or not the perniotic lesions really can tell us something about a patient’s exposure and infection with SARS-CoV-2,” he said.

Dr. Freeman reported receiving a grant from the International League of Dermatological Societies and nonfinancial support from the AAD for the study. Dr. Ko reported no conflicts. Dr. Fernadnez had no disclosures.

A follow-up look at an international registry suggests that some people may have persistent, long-lasting dermatologic manifestations – especially so-called “COVID toes” – as a result of infection with or exposure to the SARS-CoV-2 virus, but some dermatologists question if the skin signs and symptoms are truly related.

In their commentary in the Lancet Infectious Diseases, Esther P. Freeman, MD, PhD, and colleagues who lead and participate in the American Academy of Dermatology’s international registry said their analysis “revealed a previously unreported subset of patients who experience long-haul symptoms in dermatology-dominant COVID-19.”

Some of the data was presented at the 29th European Academy of Dermatology and Venereology in late October 2020, but has since been updated with more cases.

Dermatologists who spoke with this news organization said it has not been settled that some skin manifestations – such as pernio/chilblains rashes, seen primarily in nonhospitalized patients, and described in the registry – are definitively caused by COVID. They also noted that in some cases, patients who initially test negative for COVID-19 by polymerase chain reaction (PCR) sometimes do not ever develop antibodies, which could mean they were never actually exposed to SARS-CoV-2.

M. Alexander Otto/MDedge News

“I still question whether the perniosis is directly related to infection with SARS-CoV-2 or not,” said Anthony Fernandez, MD, PhD, director of medical and inpatient dermatology and assistant professor of dermatopathology at the Cleveland Clinic. His uncertainty is driven by the lack of seroconversion and that few cases were seen over the summer in the United States – suggesting that it may still be a result of cold temperatures.

“I’m not sure there is a definitive correct answer, definitely not that everyone would agree on,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn.

Dr. Freeman, however, believed that pernio and especially persistent lesions are caused by an immune response to COVID.

In an interview, she noted the multiple cases of patients in the registry who did seroconvert and that, while a registry is not a perfect means of getting an answer, it is good for generating questions. Taken collectively, the cases in the registry can “tell a story for further hypotheses,” said Dr. Freeman, who is director of global health dermatology at Massachusetts General Hospital and assistant professor of dermatology at Harvard University, both in Boston.

“We were noticing this signal across the world” that patients “developed these toe lesions and they never got better,” said Dr. Freeman. Generally, people who experience pernio, also described as COVID toes or “COVID fingers,” recover in 4-8 weeks. But in the registry, “we did have this subset of patients who really were experiencing these very longstanding symptoms,” she added.

Two patients with lab-confirmed COVID have had long-lasting pernio of 133 days and 150 days. “I’m caring for a cohort in Boston who have had long COVID of the skin and symptoms for over 10 months,” Dr. Freeman said.
 

Pernio dominates

The registry – a collaboration between the AAD and the International League of Dermatological Societies – was launched in April 2020. Any medical professional can enter case information. From April to October, 1,030 total cases and 331 laboratory-confirmed or suspected COVID-19 cases with dermatological manifestations were entered from 41 countries.

Most of the cases were just recorded at a single time point, which is an acknowledged limitation of the study.

Dr. Freeman and colleagues reached out to registry participants in June and August to get updates on COVID lab test results and sign and symptom duration. Overall, 234 total and 96 lab-confirmed COVID infections had more lengthy data about sign and symptom duration.

Pernio lasted a median of 15 days in patients with suspected disease and 12 days for those with lab-confirmed COVID, compared with a median of 7 days for morbilliform eruptions, 4 days for urticarial eruptions, and 20 days for papulosquamous eruptions – all in patients with lab-confirmed disease.

Of the 103 cases of pernio, 7 had symptoms lasting more than 60 days. Only two of those seven patients had lab-confirmed COVID. Initially, the one patient tested negative with nasopharyngeal PCR, and serum IgM and IgG. Six weeks after pernio onset, the patient – still experiencing fatigue and pernio – seroconverted to anti–SARS-CoV-2 IgM positivity.

The other long-haul patient, after a negative PCR, tested positive for SARS-CoV-2 serum IgG 1 month after pernio onset.

Robust immune response?

Dr. Freeman said these patients might have a very high interferon response initially to the virus, which makes for a mild to nonexistent disease, but could create inflammation elsewhere. “I almost view the toes as an innocent bystander of a robust immune response to SARS-CoV-2.”

Although he has not seen extended pernio or other skin manifestations in his patients, Dr. Fernandez said the interferon hypothesis is “fair,” and “the best that’s out there.” Dr. Fernandez is currently studying cutaneous manifestations of COVID-19 as a principal investigator of a trial sponsored by the Clinical and Translational Science Collaborative of Cleveland.

Dr. Ko said in an interview that she has not observed long-haul skin issues in her patients, but Yale colleagues have.

In a study, she and Yale colleagues published in September, SARS-CoV-2 spike protein was detected in perniotic lesions, but not nuclear protein or viral RNA. The test they used – immunohistochemistry – can be nonspecific, which muddied results.

She does not think there is replicating virus in the skin or the lesions. Instead, said Dr. Ko, “either there is viral spike protein that has somehow become disassociated from actively replicating virus that somehow got deposited in endothelial cells,” or the staining “was spurious,” or some other protein is cross-reacting. “And the people who are unlucky enough to have that protein in their endothelial cells can manifest this COVID-toe, COVID-finger phenomenon.”

To her, it’s an unsolved mystery. “The weird thing is, we’ve never before had this much perniosis,” Dr. Ko said.

Dr. Fernandez is not convinced yet, noting that, in Cleveland, more pernio cases were observed in March and April than in the summer. “If it is a manifestation of the infection then you also need the right environment, the cold weather for this manifestation to present,” he said. “Or, it really isn’t a direct manifestation of COVID-19 but may be more related to other factors,” such as lifestyle changes related to limitations implemented to help mitigate the spread of the disease.

“To me the jury is still out whether or not the perniotic lesions really can tell us something about a patient’s exposure and infection with SARS-CoV-2,” he said.

Dr. Freeman reported receiving a grant from the International League of Dermatological Societies and nonfinancial support from the AAD for the study. Dr. Ko reported no conflicts. Dr. Fernadnez had no disclosures.

A follow-up look at an international registry suggests that some people may have persistent, long-lasting dermatologic manifestations – especially so-called “COVID toes” – as a result of infection with or exposure to the SARS-CoV-2 virus, but some dermatologists question if the skin signs and symptoms are truly related.

In their commentary in the Lancet Infectious Diseases, Esther P. Freeman, MD, PhD, and colleagues who lead and participate in the American Academy of Dermatology’s international registry said their analysis “revealed a previously unreported subset of patients who experience long-haul symptoms in dermatology-dominant COVID-19.”

Some of the data was presented at the 29th European Academy of Dermatology and Venereology in late October 2020, but has since been updated with more cases.

Dermatologists who spoke with this news organization said it has not been settled that some skin manifestations – such as pernio/chilblains rashes, seen primarily in nonhospitalized patients, and described in the registry – are definitively caused by COVID. They also noted that in some cases, patients who initially test negative for COVID-19 by polymerase chain reaction (PCR) sometimes do not ever develop antibodies, which could mean they were never actually exposed to SARS-CoV-2.

M. Alexander Otto/MDedge News

“I still question whether the perniosis is directly related to infection with SARS-CoV-2 or not,” said Anthony Fernandez, MD, PhD, director of medical and inpatient dermatology and assistant professor of dermatopathology at the Cleveland Clinic. His uncertainty is driven by the lack of seroconversion and that few cases were seen over the summer in the United States – suggesting that it may still be a result of cold temperatures.

“I’m not sure there is a definitive correct answer, definitely not that everyone would agree on,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn.

Dr. Freeman, however, believed that pernio and especially persistent lesions are caused by an immune response to COVID.

In an interview, she noted the multiple cases of patients in the registry who did seroconvert and that, while a registry is not a perfect means of getting an answer, it is good for generating questions. Taken collectively, the cases in the registry can “tell a story for further hypotheses,” said Dr. Freeman, who is director of global health dermatology at Massachusetts General Hospital and assistant professor of dermatology at Harvard University, both in Boston.

“We were noticing this signal across the world” that patients “developed these toe lesions and they never got better,” said Dr. Freeman. Generally, people who experience pernio, also described as COVID toes or “COVID fingers,” recover in 4-8 weeks. But in the registry, “we did have this subset of patients who really were experiencing these very longstanding symptoms,” she added.

Two patients with lab-confirmed COVID have had long-lasting pernio of 133 days and 150 days. “I’m caring for a cohort in Boston who have had long COVID of the skin and symptoms for over 10 months,” Dr. Freeman said.
 

Pernio dominates

The registry – a collaboration between the AAD and the International League of Dermatological Societies – was launched in April 2020. Any medical professional can enter case information. From April to October, 1,030 total cases and 331 laboratory-confirmed or suspected COVID-19 cases with dermatological manifestations were entered from 41 countries.

Most of the cases were just recorded at a single time point, which is an acknowledged limitation of the study.

Dr. Freeman and colleagues reached out to registry participants in June and August to get updates on COVID lab test results and sign and symptom duration. Overall, 234 total and 96 lab-confirmed COVID infections had more lengthy data about sign and symptom duration.

Pernio lasted a median of 15 days in patients with suspected disease and 12 days for those with lab-confirmed COVID, compared with a median of 7 days for morbilliform eruptions, 4 days for urticarial eruptions, and 20 days for papulosquamous eruptions – all in patients with lab-confirmed disease.

Of the 103 cases of pernio, 7 had symptoms lasting more than 60 days. Only two of those seven patients had lab-confirmed COVID. Initially, the one patient tested negative with nasopharyngeal PCR, and serum IgM and IgG. Six weeks after pernio onset, the patient – still experiencing fatigue and pernio – seroconverted to anti–SARS-CoV-2 IgM positivity.

The other long-haul patient, after a negative PCR, tested positive for SARS-CoV-2 serum IgG 1 month after pernio onset.

Robust immune response?

Dr. Freeman said these patients might have a very high interferon response initially to the virus, which makes for a mild to nonexistent disease, but could create inflammation elsewhere. “I almost view the toes as an innocent bystander of a robust immune response to SARS-CoV-2.”

Although he has not seen extended pernio or other skin manifestations in his patients, Dr. Fernandez said the interferon hypothesis is “fair,” and “the best that’s out there.” Dr. Fernandez is currently studying cutaneous manifestations of COVID-19 as a principal investigator of a trial sponsored by the Clinical and Translational Science Collaborative of Cleveland.

Dr. Ko said in an interview that she has not observed long-haul skin issues in her patients, but Yale colleagues have.

In a study, she and Yale colleagues published in September, SARS-CoV-2 spike protein was detected in perniotic lesions, but not nuclear protein or viral RNA. The test they used – immunohistochemistry – can be nonspecific, which muddied results.

She does not think there is replicating virus in the skin or the lesions. Instead, said Dr. Ko, “either there is viral spike protein that has somehow become disassociated from actively replicating virus that somehow got deposited in endothelial cells,” or the staining “was spurious,” or some other protein is cross-reacting. “And the people who are unlucky enough to have that protein in their endothelial cells can manifest this COVID-toe, COVID-finger phenomenon.”

To her, it’s an unsolved mystery. “The weird thing is, we’ve never before had this much perniosis,” Dr. Ko said.

Dr. Fernandez is not convinced yet, noting that, in Cleveland, more pernio cases were observed in March and April than in the summer. “If it is a manifestation of the infection then you also need the right environment, the cold weather for this manifestation to present,” he said. “Or, it really isn’t a direct manifestation of COVID-19 but may be more related to other factors,” such as lifestyle changes related to limitations implemented to help mitigate the spread of the disease.

“To me the jury is still out whether or not the perniotic lesions really can tell us something about a patient’s exposure and infection with SARS-CoV-2,” he said.

Dr. Freeman reported receiving a grant from the International League of Dermatological Societies and nonfinancial support from the AAD for the study. Dr. Ko reported no conflicts. Dr. Fernadnez had no disclosures.

The Step 2 Clinical Skills (CS) test for medical school students and graduates has been permanently canceled, cosponsors of the U.S. Medical Licensing Examination (USMLE) announced in a press release this afternoon.

As previously reported by this news organization, the USMLE cosponsors, the Federation of State Medical Boards and the National Board of Medical Examiners, had announced in May that they would take the following 12-18 months to revamp the required test.

COVID-19 had forced a suspension of the all-day test, which requires test takers to have physical contact with standardized patients. It’s designed to gauge how soon-to-be doctors gather information from patients, perform physical exams, and communicate their findings to patients and colleagues.

However, the cosponsors said today, “we have no plans to bring back Step 2 CS, but we intend to take this opportunity to focus on working with our colleagues in medical education and at the state medical boards to determine innovative ways to assess clinical skills.”

David Johnson, FSMB’s chief assessment officer, said in an interview that, after months of study, “it became clear that the relaunch of a modified Step 2 CS exam would not meet our expectations to be appreciably better than the prior exam.”
 

Only weeks ago, NBME was hiring for the revamp

The news came as a huge surprise. Just weeks earlier, NBME was advertising for a position key to modifying the exam. The description for the position read: “This role will focus on operational planning and coordination both within the NBME and with ECFMG [Educational Commission for Foreign Medical Graduates] to effectively deliver a modified Step 2 Clinical Skills exam.”

Bryan Carmody, MD, MPH, an assistant professor at Eastern Virginia Medical School, Norfolk, noted in a Jan. 15 tweet that the position requires extensive information technology experience, “suggesting plans for a virtual test remain intact.”

Dr. Johnson said that, although the opportunities for helping lead the revamp of the test were posted until the announcement, no one had been hired for the position.

Today’s announcement stated that the USMLE still believes independent standardized tests for medical knowledge and clinical skills are important; however, it now feels clinical reasoning and communication skills will be able to be assessed in other steps.

“Computer-based case simulations in Step 3 and communication content recently bolstered in Step 1 are examples of these efforts that will continue,” the press release stated. “While not a replacement for Step 2 CS, these formats continue to contribute positively, e.g., measuring critical knowledge of medical communication.”

Critics ‘thrilled’ by test termination

Lydia Flier, MD, from the department of internal medicine at Harvard Medical School, Boston – who wrote an editorial for this news organization in August 2020 advocating that Step 2 CS be changed completely or ended entirely – said in an interview that she was “surprised and thrilled” by the announcement.

She said the cosponsors hadn’t initially appeared to agree with the growing sentiment that disruption from the pandemic had “proven the test was unnecessary and it looked like they really were going to try and keep it.”

“I’m thrilled for future generations,” she said. “It is proof of what many people have known all along, which is that the test is a no-value-add proposition that did not actually help determine people’s clinical skills.”

The test “met a breaking point” during the pandemic, she said, “from which CS could not recover.”

She noted in her editorial that the test costs $1,300 plus travel fees, as the test had been offered at only five sites. She agreed that the skills assessed by the Step 2 CS are already covered in medical school and through other Steps.

“It seems as though they could not justify it anymore. It’s the obvious right answer,” said Dr. Flier, who in 2016 cofounded #EndStep2CS, a nationwide movement demanding an end to the exam.

Another cofounder in that movement, Christopher Henderson, MD, a staff physician with Kaiser Permanente in Seattle, said in an interview that “this decision represents tremendous progress in the fight to reduce unnecessary costs in medical education, and is a win for future students. Credit goes to the many women and men who organized and voiced their desire for change.” He added that his views are his own and “do not reflect or imply the views of my organization.”

For the FSMB’s part, Dr. Johnson acknowledged that “the consideration of cost and value were two of many important factors for the Step 2 CS revitalization work.”

Dr. Johnson, Dr. Flier, and Dr. Henderson have declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The Step 2 Clinical Skills (CS) test for medical school students and graduates has been permanently canceled, cosponsors of the U.S. Medical Licensing Examination (USMLE) announced in a press release this afternoon.

As previously reported by this news organization, the USMLE cosponsors, the Federation of State Medical Boards and the National Board of Medical Examiners, had announced in May that they would take the following 12-18 months to revamp the required test.

COVID-19 had forced a suspension of the all-day test, which requires test takers to have physical contact with standardized patients. It’s designed to gauge how soon-to-be doctors gather information from patients, perform physical exams, and communicate their findings to patients and colleagues.

However, the cosponsors said today, “we have no plans to bring back Step 2 CS, but we intend to take this opportunity to focus on working with our colleagues in medical education and at the state medical boards to determine innovative ways to assess clinical skills.”

David Johnson, FSMB’s chief assessment officer, said in an interview that, after months of study, “it became clear that the relaunch of a modified Step 2 CS exam would not meet our expectations to be appreciably better than the prior exam.”
 

Only weeks ago, NBME was hiring for the revamp

The news came as a huge surprise. Just weeks earlier, NBME was advertising for a position key to modifying the exam. The description for the position read: “This role will focus on operational planning and coordination both within the NBME and with ECFMG [Educational Commission for Foreign Medical Graduates] to effectively deliver a modified Step 2 Clinical Skills exam.”

Bryan Carmody, MD, MPH, an assistant professor at Eastern Virginia Medical School, Norfolk, noted in a Jan. 15 tweet that the position requires extensive information technology experience, “suggesting plans for a virtual test remain intact.”

Dr. Johnson said that, although the opportunities for helping lead the revamp of the test were posted until the announcement, no one had been hired for the position.

Today’s announcement stated that the USMLE still believes independent standardized tests for medical knowledge and clinical skills are important; however, it now feels clinical reasoning and communication skills will be able to be assessed in other steps.

“Computer-based case simulations in Step 3 and communication content recently bolstered in Step 1 are examples of these efforts that will continue,” the press release stated. “While not a replacement for Step 2 CS, these formats continue to contribute positively, e.g., measuring critical knowledge of medical communication.”

Critics ‘thrilled’ by test termination

Lydia Flier, MD, from the department of internal medicine at Harvard Medical School, Boston – who wrote an editorial for this news organization in August 2020 advocating that Step 2 CS be changed completely or ended entirely – said in an interview that she was “surprised and thrilled” by the announcement.

She said the cosponsors hadn’t initially appeared to agree with the growing sentiment that disruption from the pandemic had “proven the test was unnecessary and it looked like they really were going to try and keep it.”

“I’m thrilled for future generations,” she said. “It is proof of what many people have known all along, which is that the test is a no-value-add proposition that did not actually help determine people’s clinical skills.”

The test “met a breaking point” during the pandemic, she said, “from which CS could not recover.”

She noted in her editorial that the test costs $1,300 plus travel fees, as the test had been offered at only five sites. She agreed that the skills assessed by the Step 2 CS are already covered in medical school and through other Steps.

“It seems as though they could not justify it anymore. It’s the obvious right answer,” said Dr. Flier, who in 2016 cofounded #EndStep2CS, a nationwide movement demanding an end to the exam.

Another cofounder in that movement, Christopher Henderson, MD, a staff physician with Kaiser Permanente in Seattle, said in an interview that “this decision represents tremendous progress in the fight to reduce unnecessary costs in medical education, and is a win for future students. Credit goes to the many women and men who organized and voiced their desire for change.” He added that his views are his own and “do not reflect or imply the views of my organization.”

For the FSMB’s part, Dr. Johnson acknowledged that “the consideration of cost and value were two of many important factors for the Step 2 CS revitalization work.”

Dr. Johnson, Dr. Flier, and Dr. Henderson have declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The Step 2 Clinical Skills (CS) test for medical school students and graduates has been permanently canceled, cosponsors of the U.S. Medical Licensing Examination (USMLE) announced in a press release this afternoon.

As previously reported by this news organization, the USMLE cosponsors, the Federation of State Medical Boards and the National Board of Medical Examiners, had announced in May that they would take the following 12-18 months to revamp the required test.

COVID-19 had forced a suspension of the all-day test, which requires test takers to have physical contact with standardized patients. It’s designed to gauge how soon-to-be doctors gather information from patients, perform physical exams, and communicate their findings to patients and colleagues.

However, the cosponsors said today, “we have no plans to bring back Step 2 CS, but we intend to take this opportunity to focus on working with our colleagues in medical education and at the state medical boards to determine innovative ways to assess clinical skills.”

David Johnson, FSMB’s chief assessment officer, said in an interview that, after months of study, “it became clear that the relaunch of a modified Step 2 CS exam would not meet our expectations to be appreciably better than the prior exam.”
 

Only weeks ago, NBME was hiring for the revamp

The news came as a huge surprise. Just weeks earlier, NBME was advertising for a position key to modifying the exam. The description for the position read: “This role will focus on operational planning and coordination both within the NBME and with ECFMG [Educational Commission for Foreign Medical Graduates] to effectively deliver a modified Step 2 Clinical Skills exam.”

Bryan Carmody, MD, MPH, an assistant professor at Eastern Virginia Medical School, Norfolk, noted in a Jan. 15 tweet that the position requires extensive information technology experience, “suggesting plans for a virtual test remain intact.”

Dr. Johnson said that, although the opportunities for helping lead the revamp of the test were posted until the announcement, no one had been hired for the position.

Today’s announcement stated that the USMLE still believes independent standardized tests for medical knowledge and clinical skills are important; however, it now feels clinical reasoning and communication skills will be able to be assessed in other steps.

“Computer-based case simulations in Step 3 and communication content recently bolstered in Step 1 are examples of these efforts that will continue,” the press release stated. “While not a replacement for Step 2 CS, these formats continue to contribute positively, e.g., measuring critical knowledge of medical communication.”

Critics ‘thrilled’ by test termination

Lydia Flier, MD, from the department of internal medicine at Harvard Medical School, Boston – who wrote an editorial for this news organization in August 2020 advocating that Step 2 CS be changed completely or ended entirely – said in an interview that she was “surprised and thrilled” by the announcement.

She said the cosponsors hadn’t initially appeared to agree with the growing sentiment that disruption from the pandemic had “proven the test was unnecessary and it looked like they really were going to try and keep it.”

“I’m thrilled for future generations,” she said. “It is proof of what many people have known all along, which is that the test is a no-value-add proposition that did not actually help determine people’s clinical skills.”

The test “met a breaking point” during the pandemic, she said, “from which CS could not recover.”

She noted in her editorial that the test costs $1,300 plus travel fees, as the test had been offered at only five sites. She agreed that the skills assessed by the Step 2 CS are already covered in medical school and through other Steps.

“It seems as though they could not justify it anymore. It’s the obvious right answer,” said Dr. Flier, who in 2016 cofounded #EndStep2CS, a nationwide movement demanding an end to the exam.

Another cofounder in that movement, Christopher Henderson, MD, a staff physician with Kaiser Permanente in Seattle, said in an interview that “this decision represents tremendous progress in the fight to reduce unnecessary costs in medical education, and is a win for future students. Credit goes to the many women and men who organized and voiced their desire for change.” He added that his views are his own and “do not reflect or imply the views of my organization.”

For the FSMB’s part, Dr. Johnson acknowledged that “the consideration of cost and value were two of many important factors for the Step 2 CS revitalization work.”

Dr. Johnson, Dr. Flier, and Dr. Henderson have declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The U.K.’s B117 variant is circulating in at least 24 states, according to new data from the Centers for Disease Control and Prevention COVID-19 variant surveillance. The CDC projects that the U.K. variant will become the dominant strain in the United States by March.

From any vantage point, the United Kingdom appears to be in the crosshairs of COVID-19: Weeks after a new, highly contagious variant emerged that fueled a surge in cases and fresh lockdowns, the United Kingdom was revealed to have the world’s highest coronavirus death rate.

But the United Kingdom also has a not-so-secret weapon of its own: A genomic sequencing program widely believed to be the most coordinated and advanced any nation has forged. In the vise grip of the virus, the Brits have gleaned key insights into the behavior and consequences of SARS-CoV-2.

But B117 is also notable for what it is missing: In this case, producing a negative result on certain polymerase chain reaction (PCR) tests in the spike protein, or S-gene.

One of the S-gene mutations specific to the variant deletes two amino acids, causing that portion of the PCR test to show up negative. The coincidental finding known as an S-gene target failure has become an integral proxy to help track where and when the variant is spreading in the United Kingdom, where about 5% of samples from COVID-19–infected patients are sequenced, said Sharon Peacock, PhD, executive director and chair of the COVID-19 Genomics U.K. Consortium.

That same tactic could prove valuable to clinicians similarly overwhelmed with cases and deaths but lacking high-level sequencing information on the virus, Dr. Peacock said in an interview. A British report released Friday stated that there is a “realistic possibility” that the variant has a higher death rate than other cases of SARS-CoV-2.

“In this particular variant, a deletion in the genome leads to one part of the diagnostic test failing,” Dr. Peacock explained. “Several targets are positive, but this is negative. In the U.K., this has been used as a surrogate marker.”
 

Targeting an invisible adversary

B117 is not the only variant that produces this result, Dr. Peacock cautioned, “but in screening for it, you can have this in mind.”

“Since the U.K. is sequencing about 5% of the cases they detect, this gives them really important clues about what’s happening there,” said Anderson Brito, PhD, a virologist and postdoctoral researcher at Yale University, New Haven, Conn., where investigators are creating custom PCR tests to detect the B117 variant.

Dr. Brito, who lived in the United Kingdom for 4 years while studying for his doctorate at Imperial College London, said a “major advantage” is the more unified process to collect and sequence samples. Crucial information – including the date and place of collection – comes with each sample, which fuels not only sequencing, but an epidemiologic perspective.

“They’re not in the dark at all,” Dr. Brito said in an interview. “I think no other country in the world knows better which virus lineages are circulating.”

The CDC launched the SPHERES consortium in May 2020 to coordinate the sequencing of SARS-CoV-2 genomes across the United States.

But American genomic efforts are “not as centralized,” said Dr. Brito, whose lab detected the first two cases of the U.K. variant in Connecticut on Jan. 6. “We struggle to get samples, because they’re decentralized to a level where there’s little coordination between hospitals and research centers. They’re not as connected as in the U.K. If we just get a sample and it has no date of collection and no origin information, for example, it’s basically useless.”

Global genomic collaborations include GISAID, an international database where researchers share new genomes from various coronaviruses. As of mid-January, the United States had submitted about 68,000 sequences to GISAID, adding about 3,000 new samples every week and expecting even more from commercial labs in coming days, according to the CDC.

“The U.K. is definitely much more on top of looking for variants as they pop up,” said Gigi Gronvall, PhD, an immunologist and senior scholar at Johns Hopkins Center for Health Security in Baltimore. “The U.S. has now turned that up.”
 

Warning from British scientists to the world

Despite these genomic accomplishments, some British scientists said they have regrets too, wishing they’d known just how rapidly SARS-CoV-2 was actually spreading a year ago, when it hit western Europe.

That information was crucial not only for preventive efforts, but because viruses inevitably mutate faster the more people who are infected, said Igor Rudan, MD, PhD, director of the Center for Global Health Research at University of Edinburgh.

“Italy showed us just how fast it was spreading and how deadly it is for the very old and people with multiple comorbidities,” said Dr. Rudan, who also editor in chief of the Journal of Global Health. “We wish we knew it was spreading so fast, and we wish we knew the threshold of cases we could allow to be infected before the virus would mutate.”

More mutations mean more new strains of SARS-CoV-2, Dr. Rudan said in an interview. “We’ve reached that threshold now and will see more of these mutations.”

Despite its current struggles, the United Kingdom is reaching beyond tracking its new variant’s spread and trying to identify new mutations that might change the way the virus behaves.

Three features of any emerging variant are particularly important, Dr. Peacock explained: Is it more transmissible? Is it more lethal? And does it cut the ability of natural- or vaccine-induced immunity to protect people from infection?

“We need to sequence people coming to the hospital who are sicker,” said Dr. Peacock, also a professor of public health and microbiology at the University of Cambridge (England). “Also, if anyone has the infection after they’ve already been sick or had the vaccine, we really want to know what that looks like” genomically.

SARS-CoV-2 has already logged more than 4,000 mutations, Dr. Peacock said. But “knowing that viruses mutate all the time is not sufficient reason not to look. We really want to know if mutations lead to changes in amino acids, and if that can lead to changes in functionality.”

For the moment, however, experts say they’re relieved that the U.K. strain doesn’t seem able to evade COVID-19 vaccines or render them less effective.

“Even though mutations are common, those able to change the viral coding are rare,” Dr. Brito explained. If necessary, vaccines could be tweaked to replace the spike gene sequence “within a matter of weeks. We already do this for flu vaccines. Every year, we have to monitor variants of the virus circulating to develop a vaccine that covers most of them. If we end up having to do it for SARS-CoV-2, I would not be surprised.”

But variant-fueled increases in infections will require more people to be vaccinated before herd immunity can be achieved, Dr. Rudan warned. “If it spreads faster, we’ll need to vaccinate probably 85% of people versus 70% to reach herd immunity.”

One lesson the COVID-19 pandemic has driven home “is to always be on your guard about what happens next,” Dr. Peacock said. Although confident about the genomic efforts in the United Kingdom to date, she and her colleagues feel they’re still reaching for a complete understanding of the evolutionary changes of the virus.

“We’re ahead of the curve right now, but we want to get in front of the curve,” Dr. Peacock said. “It’s essential to get ahead of what might be around the corner because we don’t know how the virus is going to evolve.”

A version of this article first appeared on Medscape.com.

The U.K.’s B117 variant is circulating in at least 24 states, according to new data from the Centers for Disease Control and Prevention COVID-19 variant surveillance. The CDC projects that the U.K. variant will become the dominant strain in the United States by March.

From any vantage point, the United Kingdom appears to be in the crosshairs of COVID-19: Weeks after a new, highly contagious variant emerged that fueled a surge in cases and fresh lockdowns, the United Kingdom was revealed to have the world’s highest coronavirus death rate.

But the United Kingdom also has a not-so-secret weapon of its own: A genomic sequencing program widely believed to be the most coordinated and advanced any nation has forged. In the vise grip of the virus, the Brits have gleaned key insights into the behavior and consequences of SARS-CoV-2.

But B117 is also notable for what it is missing: In this case, producing a negative result on certain polymerase chain reaction (PCR) tests in the spike protein, or S-gene.

One of the S-gene mutations specific to the variant deletes two amino acids, causing that portion of the PCR test to show up negative. The coincidental finding known as an S-gene target failure has become an integral proxy to help track where and when the variant is spreading in the United Kingdom, where about 5% of samples from COVID-19–infected patients are sequenced, said Sharon Peacock, PhD, executive director and chair of the COVID-19 Genomics U.K. Consortium.

That same tactic could prove valuable to clinicians similarly overwhelmed with cases and deaths but lacking high-level sequencing information on the virus, Dr. Peacock said in an interview. A British report released Friday stated that there is a “realistic possibility” that the variant has a higher death rate than other cases of SARS-CoV-2.

“In this particular variant, a deletion in the genome leads to one part of the diagnostic test failing,” Dr. Peacock explained. “Several targets are positive, but this is negative. In the U.K., this has been used as a surrogate marker.”
 

Targeting an invisible adversary

B117 is not the only variant that produces this result, Dr. Peacock cautioned, “but in screening for it, you can have this in mind.”

“Since the U.K. is sequencing about 5% of the cases they detect, this gives them really important clues about what’s happening there,” said Anderson Brito, PhD, a virologist and postdoctoral researcher at Yale University, New Haven, Conn., where investigators are creating custom PCR tests to detect the B117 variant.

Dr. Brito, who lived in the United Kingdom for 4 years while studying for his doctorate at Imperial College London, said a “major advantage” is the more unified process to collect and sequence samples. Crucial information – including the date and place of collection – comes with each sample, which fuels not only sequencing, but an epidemiologic perspective.

“They’re not in the dark at all,” Dr. Brito said in an interview. “I think no other country in the world knows better which virus lineages are circulating.”

The CDC launched the SPHERES consortium in May 2020 to coordinate the sequencing of SARS-CoV-2 genomes across the United States.

But American genomic efforts are “not as centralized,” said Dr. Brito, whose lab detected the first two cases of the U.K. variant in Connecticut on Jan. 6. “We struggle to get samples, because they’re decentralized to a level where there’s little coordination between hospitals and research centers. They’re not as connected as in the U.K. If we just get a sample and it has no date of collection and no origin information, for example, it’s basically useless.”

Global genomic collaborations include GISAID, an international database where researchers share new genomes from various coronaviruses. As of mid-January, the United States had submitted about 68,000 sequences to GISAID, adding about 3,000 new samples every week and expecting even more from commercial labs in coming days, according to the CDC.

“The U.K. is definitely much more on top of looking for variants as they pop up,” said Gigi Gronvall, PhD, an immunologist and senior scholar at Johns Hopkins Center for Health Security in Baltimore. “The U.S. has now turned that up.”
 

Warning from British scientists to the world

Despite these genomic accomplishments, some British scientists said they have regrets too, wishing they’d known just how rapidly SARS-CoV-2 was actually spreading a year ago, when it hit western Europe.

That information was crucial not only for preventive efforts, but because viruses inevitably mutate faster the more people who are infected, said Igor Rudan, MD, PhD, director of the Center for Global Health Research at University of Edinburgh.

“Italy showed us just how fast it was spreading and how deadly it is for the very old and people with multiple comorbidities,” said Dr. Rudan, who also editor in chief of the Journal of Global Health. “We wish we knew it was spreading so fast, and we wish we knew the threshold of cases we could allow to be infected before the virus would mutate.”

More mutations mean more new strains of SARS-CoV-2, Dr. Rudan said in an interview. “We’ve reached that threshold now and will see more of these mutations.”

Despite its current struggles, the United Kingdom is reaching beyond tracking its new variant’s spread and trying to identify new mutations that might change the way the virus behaves.

Three features of any emerging variant are particularly important, Dr. Peacock explained: Is it more transmissible? Is it more lethal? And does it cut the ability of natural- or vaccine-induced immunity to protect people from infection?

“We need to sequence people coming to the hospital who are sicker,” said Dr. Peacock, also a professor of public health and microbiology at the University of Cambridge (England). “Also, if anyone has the infection after they’ve already been sick or had the vaccine, we really want to know what that looks like” genomically.

SARS-CoV-2 has already logged more than 4,000 mutations, Dr. Peacock said. But “knowing that viruses mutate all the time is not sufficient reason not to look. We really want to know if mutations lead to changes in amino acids, and if that can lead to changes in functionality.”

For the moment, however, experts say they’re relieved that the U.K. strain doesn’t seem able to evade COVID-19 vaccines or render them less effective.

“Even though mutations are common, those able to change the viral coding are rare,” Dr. Brito explained. If necessary, vaccines could be tweaked to replace the spike gene sequence “within a matter of weeks. We already do this for flu vaccines. Every year, we have to monitor variants of the virus circulating to develop a vaccine that covers most of them. If we end up having to do it for SARS-CoV-2, I would not be surprised.”

But variant-fueled increases in infections will require more people to be vaccinated before herd immunity can be achieved, Dr. Rudan warned. “If it spreads faster, we’ll need to vaccinate probably 85% of people versus 70% to reach herd immunity.”

One lesson the COVID-19 pandemic has driven home “is to always be on your guard about what happens next,” Dr. Peacock said. Although confident about the genomic efforts in the United Kingdom to date, she and her colleagues feel they’re still reaching for a complete understanding of the evolutionary changes of the virus.

“We’re ahead of the curve right now, but we want to get in front of the curve,” Dr. Peacock said. “It’s essential to get ahead of what might be around the corner because we don’t know how the virus is going to evolve.”

A version of this article first appeared on Medscape.com.

The U.K.’s B117 variant is circulating in at least 24 states, according to new data from the Centers for Disease Control and Prevention COVID-19 variant surveillance. The CDC projects that the U.K. variant will become the dominant strain in the United States by March.

From any vantage point, the United Kingdom appears to be in the crosshairs of COVID-19: Weeks after a new, highly contagious variant emerged that fueled a surge in cases and fresh lockdowns, the United Kingdom was revealed to have the world’s highest coronavirus death rate.

But the United Kingdom also has a not-so-secret weapon of its own: A genomic sequencing program widely believed to be the most coordinated and advanced any nation has forged. In the vise grip of the virus, the Brits have gleaned key insights into the behavior and consequences of SARS-CoV-2.

But B117 is also notable for what it is missing: In this case, producing a negative result on certain polymerase chain reaction (PCR) tests in the spike protein, or S-gene.

One of the S-gene mutations specific to the variant deletes two amino acids, causing that portion of the PCR test to show up negative. The coincidental finding known as an S-gene target failure has become an integral proxy to help track where and when the variant is spreading in the United Kingdom, where about 5% of samples from COVID-19–infected patients are sequenced, said Sharon Peacock, PhD, executive director and chair of the COVID-19 Genomics U.K. Consortium.

That same tactic could prove valuable to clinicians similarly overwhelmed with cases and deaths but lacking high-level sequencing information on the virus, Dr. Peacock said in an interview. A British report released Friday stated that there is a “realistic possibility” that the variant has a higher death rate than other cases of SARS-CoV-2.

“In this particular variant, a deletion in the genome leads to one part of the diagnostic test failing,” Dr. Peacock explained. “Several targets are positive, but this is negative. In the U.K., this has been used as a surrogate marker.”
 

Targeting an invisible adversary

B117 is not the only variant that produces this result, Dr. Peacock cautioned, “but in screening for it, you can have this in mind.”

“Since the U.K. is sequencing about 5% of the cases they detect, this gives them really important clues about what’s happening there,” said Anderson Brito, PhD, a virologist and postdoctoral researcher at Yale University, New Haven, Conn., where investigators are creating custom PCR tests to detect the B117 variant.

Dr. Brito, who lived in the United Kingdom for 4 years while studying for his doctorate at Imperial College London, said a “major advantage” is the more unified process to collect and sequence samples. Crucial information – including the date and place of collection – comes with each sample, which fuels not only sequencing, but an epidemiologic perspective.

“They’re not in the dark at all,” Dr. Brito said in an interview. “I think no other country in the world knows better which virus lineages are circulating.”

The CDC launched the SPHERES consortium in May 2020 to coordinate the sequencing of SARS-CoV-2 genomes across the United States.

But American genomic efforts are “not as centralized,” said Dr. Brito, whose lab detected the first two cases of the U.K. variant in Connecticut on Jan. 6. “We struggle to get samples, because they’re decentralized to a level where there’s little coordination between hospitals and research centers. They’re not as connected as in the U.K. If we just get a sample and it has no date of collection and no origin information, for example, it’s basically useless.”

Global genomic collaborations include GISAID, an international database where researchers share new genomes from various coronaviruses. As of mid-January, the United States had submitted about 68,000 sequences to GISAID, adding about 3,000 new samples every week and expecting even more from commercial labs in coming days, according to the CDC.

“The U.K. is definitely much more on top of looking for variants as they pop up,” said Gigi Gronvall, PhD, an immunologist and senior scholar at Johns Hopkins Center for Health Security in Baltimore. “The U.S. has now turned that up.”
 

Warning from British scientists to the world

Despite these genomic accomplishments, some British scientists said they have regrets too, wishing they’d known just how rapidly SARS-CoV-2 was actually spreading a year ago, when it hit western Europe.

That information was crucial not only for preventive efforts, but because viruses inevitably mutate faster the more people who are infected, said Igor Rudan, MD, PhD, director of the Center for Global Health Research at University of Edinburgh.

“Italy showed us just how fast it was spreading and how deadly it is for the very old and people with multiple comorbidities,” said Dr. Rudan, who also editor in chief of the Journal of Global Health. “We wish we knew it was spreading so fast, and we wish we knew the threshold of cases we could allow to be infected before the virus would mutate.”

More mutations mean more new strains of SARS-CoV-2, Dr. Rudan said in an interview. “We’ve reached that threshold now and will see more of these mutations.”

Despite its current struggles, the United Kingdom is reaching beyond tracking its new variant’s spread and trying to identify new mutations that might change the way the virus behaves.

Three features of any emerging variant are particularly important, Dr. Peacock explained: Is it more transmissible? Is it more lethal? And does it cut the ability of natural- or vaccine-induced immunity to protect people from infection?

“We need to sequence people coming to the hospital who are sicker,” said Dr. Peacock, also a professor of public health and microbiology at the University of Cambridge (England). “Also, if anyone has the infection after they’ve already been sick or had the vaccine, we really want to know what that looks like” genomically.

SARS-CoV-2 has already logged more than 4,000 mutations, Dr. Peacock said. But “knowing that viruses mutate all the time is not sufficient reason not to look. We really want to know if mutations lead to changes in amino acids, and if that can lead to changes in functionality.”

For the moment, however, experts say they’re relieved that the U.K. strain doesn’t seem able to evade COVID-19 vaccines or render them less effective.

“Even though mutations are common, those able to change the viral coding are rare,” Dr. Brito explained. If necessary, vaccines could be tweaked to replace the spike gene sequence “within a matter of weeks. We already do this for flu vaccines. Every year, we have to monitor variants of the virus circulating to develop a vaccine that covers most of them. If we end up having to do it for SARS-CoV-2, I would not be surprised.”

But variant-fueled increases in infections will require more people to be vaccinated before herd immunity can be achieved, Dr. Rudan warned. “If it spreads faster, we’ll need to vaccinate probably 85% of people versus 70% to reach herd immunity.”

One lesson the COVID-19 pandemic has driven home “is to always be on your guard about what happens next,” Dr. Peacock said. Although confident about the genomic efforts in the United Kingdom to date, she and her colleagues feel they’re still reaching for a complete understanding of the evolutionary changes of the virus.

“We’re ahead of the curve right now, but we want to get in front of the curve,” Dr. Peacock said. “It’s essential to get ahead of what might be around the corner because we don’t know how the virus is going to evolve.”

A version of this article first appeared on Medscape.com.

Just as Brazil surpassed 200,000 deaths from COVID-19 on Jan. 7, news from Bahia added another layer of concern: A platform case report in a preprint detailed the first case of reinfection in that state, apparently caused by a new strain, one having the E484K mutation.

That variant, now called Brazil P.1, has migrated to the United States. The Minnesota Department of Health announced on Jan. 25 the nation’s first known COVID-19 case associated with it.

The mutation is located in the protein gene of the virus’ spike, which forms the crown structure of coronaviruses and is responsible for the virus’ binding to human cells. The E484K mutation is now the focus because it’s associated with mutations that escape the immune system’s neutralizing antibodies.

“This mutation is at the center of worldwide concern, and it is the first time that it has appeared in a reinfection,” the study’s first author, Bruno Solano de Freitas Souza, MD, a researcher at the Salvador regional unit of Instituto D’Or of Teaching and Research, based at Hospital São Rafael, Salvador, Brazil, explained in an interview.

“We will wait for the sample from Bahia to confirm the case from the perspective of the Ministry of Health’s surveillance network,” said Fernando Motta, PhD, deputy head of the Laboratory for Respiratory Virus and Measles at the Oswaldo Cruz Institute in Rio de Janeiro, which acts as a national reference center for respiratory viruses with the Brazilian Ministry of Health (MS) and as a reference for the World Health Organization.
 

A case of reinfection

The case patient that led to the alarm was a 45-year-old woman who is a health care executive. She had no comorbidities. The team had been following health care professionals and patients who had tested positive on reverse transcription–polymerase chain reaction (RT-PCR) testing more than once to understand whether they represented cases of prolonged viral persistence or new infections.

The woman had symptoms of viral infection on two occasions (May 26 and Oct. 26). On both occasions, results of RT-PCR testing for SARS-CoV-2 on nasopharyngeal samples were positive. In the first episode, the patient had diarrhea, myalgia, asthenia, and odynophagia for about 7 days. She returned to activities 21 days later. In the second episode, she had more severe symptoms that lasted longer, but she still did not require hospitalization.

“It was the first confirmed case of reinfection in Bahia, and in the second episode, we observed a mutation that could have an impact on the ability of antibodies to neutralize the virus,” Dr. Souza said. “The research continues with the investigation of cases in which the patient has a positive SARS-CoV-2 RT-PCR more than once in an interval greater than 45 days, to have a higher level of evidence.”

He stressed that “it is very important to reinforce measures to control the pandemic, social distance, use of masks, and speed up vaccination to be able to control the circulation of the virus, while monitoring the evolution of it.”
 

On alert for more cases

A person who twice tests positive for SARS-CoV-2 on real-time RT-PCR is suspected of having been reinfected, provided 90 or more days have elapsed between the two episodes, regardless of the condition observed. To confirm the suspected case, the samples must be sent to reference laboratories according to a plan established by the Ministry of Health in Brazil.

A health professional living in the Brazilian city of Natal represented the first confirmed case of reinfection by the new coronavirus in Brazil. That case was announced on Dec. 10, 2020.

“We communicated this case of reinfection to the MS in early December 2020. And the second sample already had the E484K mutation on the spike, as in the case of Bahia,” said Dr. Motta.

The first step in differentiating reinfection from persistence is to observe differences in the genotyping of the virus. For the technique to be successful, Dr. Souza said, researchers need a large amount of viral genetic material, which usually cannot be obtained.

“That is why there are many more suspected than confirmed cases,” Dr. Souza explained. He admitted that, although there are few cases, “it is increasingly clear that reinfection is a reality.”
 

Markers of mutations

What worried the researchers most was not only the possibility of reinfection but also the fact that preliminary analyses showed a specific mutation.

“The E484K mutation is present in a group of variants identified in South Africa that have been associated with increased infectivity and has been observed in a strain recently described in Brazil,” Dr. Souza said.

Mutations are expected, appear spontaneously, and in most cases have no effects on transmission or clinical outcome – they are simply used as markers and are useful for contact tracing or studying transmission routes. But some mutations can last because they provide an advantage for the pathogen, even if only momentary. In the case of SARS-CoV-2, mutations in the protein spike gene (S) are relevant because they may give clues to that advantage – as well as to changes in infectivity, transmission potential, antibodies, and response to vaccines.

A variant of the virus that has eight changes that affect the protein S gene – and several others in different genes – is behind the increase in the number of cases in London and southeastern England. Researchers from the University of São Paulo identified one of the factors that made this new variant – classified as B.1.1.7 – more infectious.

With bioinformatics tools, they found that the protein S gene in the new viral strain has a stronger molecular interaction with the ACE2 receptor, which is on the surface of human cells and to which the virus binds, making infection possible. The variant has already spread to the rest of the world, and the first two cases have been confirmed in Brazil by the Adolf Lutz Institute.

The alert for a new variant in Africa – similar to B.1.1.7 in the United Kingdom in that it carries nine changes in protein S at position 501 – was made by the Brazilian virologist Tulio de Oliveira, PhD.

“We found that this strain seems to be spreading much faster,” Dr. Oliveira, who is with the University of KwaZulu Natal, told the journal Science. His work first alerted British scientists to the importance of the position N501Y.

“The new variants just described in the United Kingdom and South Africa are slightly more transmissible and have already been identified in cases imported into Brazil,” Dr. Motta said. “Unfortunately, we believe it is only a matter of time before it becomes indigenous.”
 

The viral family grows

Viruses such as SARS-CoV-2 are classified into strains on the basis of small differences in their genetic material. Since Dec. 26, 2020, in addition to the British and South African variants, it appears the Carioca lineage also is a player.

In a preprint article, researchers analyzed the evolution of the epidemic in Rio de Janeiro from April 2020 until just before the new increase in incidence in December. They compared the complete sequences of the viral genome of 180 patients from different municipalities. The study, which is being jointly conducted by members of the Federal University of Rio de Janeiro and the National Laboratory for Scientific Computing, identified a new variant of SARS-CoV-2 that has five unique mutations (from one of the predominant strains). Concern arose because, in addition to those five genetic changes, many of the samples had a sixth – the well-known E484K mutation.

“The three lines – the U.K., South Africa, and Brazil – were almost synchronous publications, but there is no clear evidence that they have any kind of common ancestry,” Carolina M. Voloch, PhD, the article’s first author and a biologist and researcher at the Molecular Virology Laboratory and associate professor in the department of genetics at the Federal University of Rio de Janeiro, said in an interview.

Dr. Voloch’s research focuses on the use of bioinformatics tools to study the molecular, phylogenetic, and genomic evolution of viruses.

“The emergence of new strains is common for viruses,” she said. “It can be happening anywhere in the world at any time.”

She stressed that identifying when mutations emerge will help to define the new Brazilian lineage. Researchers are working to determine whether the neutralizing antibodies of patients who have been infected with other strains respond to this Rio de Janeiro strain.

“We hope to soon be sharing these results,” Dr. Voloch said.

The article’s authors estimated that the new strain likely appeared in early July. They say more analysis is needed to predict whether the changes have a major effect on viral infectivity, the host’s immune response, or the severity of the disease. Asked about the lineage that caused the reinfection in Bahia, Dr. Voloch said she hadn’t yet contacted the authors to conduct a joint analysis but added that the data disclosed in the preprint would not represent the same variant.

“There are only two of the five mutations that characterize the Rio de Janeiro lineage. However, it has the E484K mutation that is present in more than 94% of the samples of the new variant of Rio,” she said.

She added that there’s a possibility of reinfection by the lineage that’s circulating in Rio de Janeiro and in other states, as well as countries such as the United States, the United Kingdom, and Japan.

“The Carioca virus is being exported to the rest of the world,” Dr. Voloch said.
 

Virus’ diversity still unknown

Researchers now know that SARS-CoV-2 probably circulated silently in Brazil as early as February 2020 and reached all the nation’s regions before air travel was restricted. Since the first half of 2020, there have been two predominant strains.

“More than a dozen strains have been identified in Brazil, but more important than counting strains to identify the speed with which they arise – which is directly associated with the rate of infection, which is very high in the country,” said Dr. Motta.

The so-called variant of Rio de Janeiro, he said, has also been detected in other states in four regions of Brazil. The key to documenting variants is to get a more representative sample with genomes from other parts of the country.

As of Jan. 10, a total of 347,000 complete genome sequences had been shared globally through open databases since SARS-CoV-2 was first identified, but the contribution of countries is uneven. Although the cost and complexity of genetic sequencing has dropped significantly over time, effective sequencing programs still require substantial investments in personnel, equipment, reagents, and bioinformatics infrastructure.

According to Dr. Voloch, it will only be possible to combat the new coronavirus by knowing its diversity and understanding how it evolves. The Fiocruz Genomic Network has made an infographic available so researchers can track the strains circulating in Brazil. It›s the result of collaboration between researchers from Fiocruz and the GISAID Initiative, an international partnership that promotes rapid data sharing.

As of Jan. 5, researchers in Brazil had studied 1,897 genomes – not nearly enough.

“In Brazil, there is little testing and even less sequencing,” lamented Dr. Souza.

“In the U.K., 1 in 600 cases is sequenced. In Brazil it is less than 1 in 10 million cases,” Dr. Voloch added.

So far, no decisive factors for public health, such as greater virulence or greater transmissibility, have been identified in any of the strains established in Brazil. The million-dollar question is whether the emergence of new strains could have an impact on the effectiveness of vaccines being administered today.

“In one way or another, the vaccine is our best bet ever, even if in the future we identify escapist mutants and have to modify it,” Dr. Motta said. “It is what we do annually with influenza.”

Dr. Voloch, Dr. Motta, and Dr. Souza disclosed no relevant financial relationships.

A version of this article first appeared on the Portuguese edition of Medscape.com.

Just as Brazil surpassed 200,000 deaths from COVID-19 on Jan. 7, news from Bahia added another layer of concern: A platform case report in a preprint detailed the first case of reinfection in that state, apparently caused by a new strain, one having the E484K mutation.

That variant, now called Brazil P.1, has migrated to the United States. The Minnesota Department of Health announced on Jan. 25 the nation’s first known COVID-19 case associated with it.

The mutation is located in the protein gene of the virus’ spike, which forms the crown structure of coronaviruses and is responsible for the virus’ binding to human cells. The E484K mutation is now the focus because it’s associated with mutations that escape the immune system’s neutralizing antibodies.

“This mutation is at the center of worldwide concern, and it is the first time that it has appeared in a reinfection,” the study’s first author, Bruno Solano de Freitas Souza, MD, a researcher at the Salvador regional unit of Instituto D’Or of Teaching and Research, based at Hospital São Rafael, Salvador, Brazil, explained in an interview.

“We will wait for the sample from Bahia to confirm the case from the perspective of the Ministry of Health’s surveillance network,” said Fernando Motta, PhD, deputy head of the Laboratory for Respiratory Virus and Measles at the Oswaldo Cruz Institute in Rio de Janeiro, which acts as a national reference center for respiratory viruses with the Brazilian Ministry of Health (MS) and as a reference for the World Health Organization.
 

A case of reinfection

The case patient that led to the alarm was a 45-year-old woman who is a health care executive. She had no comorbidities. The team had been following health care professionals and patients who had tested positive on reverse transcription–polymerase chain reaction (RT-PCR) testing more than once to understand whether they represented cases of prolonged viral persistence or new infections.

The woman had symptoms of viral infection on two occasions (May 26 and Oct. 26). On both occasions, results of RT-PCR testing for SARS-CoV-2 on nasopharyngeal samples were positive. In the first episode, the patient had diarrhea, myalgia, asthenia, and odynophagia for about 7 days. She returned to activities 21 days later. In the second episode, she had more severe symptoms that lasted longer, but she still did not require hospitalization.

“It was the first confirmed case of reinfection in Bahia, and in the second episode, we observed a mutation that could have an impact on the ability of antibodies to neutralize the virus,” Dr. Souza said. “The research continues with the investigation of cases in which the patient has a positive SARS-CoV-2 RT-PCR more than once in an interval greater than 45 days, to have a higher level of evidence.”

He stressed that “it is very important to reinforce measures to control the pandemic, social distance, use of masks, and speed up vaccination to be able to control the circulation of the virus, while monitoring the evolution of it.”
 

On alert for more cases

A person who twice tests positive for SARS-CoV-2 on real-time RT-PCR is suspected of having been reinfected, provided 90 or more days have elapsed between the two episodes, regardless of the condition observed. To confirm the suspected case, the samples must be sent to reference laboratories according to a plan established by the Ministry of Health in Brazil.

A health professional living in the Brazilian city of Natal represented the first confirmed case of reinfection by the new coronavirus in Brazil. That case was announced on Dec. 10, 2020.

“We communicated this case of reinfection to the MS in early December 2020. And the second sample already had the E484K mutation on the spike, as in the case of Bahia,” said Dr. Motta.

The first step in differentiating reinfection from persistence is to observe differences in the genotyping of the virus. For the technique to be successful, Dr. Souza said, researchers need a large amount of viral genetic material, which usually cannot be obtained.

“That is why there are many more suspected than confirmed cases,” Dr. Souza explained. He admitted that, although there are few cases, “it is increasingly clear that reinfection is a reality.”
 

Markers of mutations

What worried the researchers most was not only the possibility of reinfection but also the fact that preliminary analyses showed a specific mutation.

“The E484K mutation is present in a group of variants identified in South Africa that have been associated with increased infectivity and has been observed in a strain recently described in Brazil,” Dr. Souza said.

Mutations are expected, appear spontaneously, and in most cases have no effects on transmission or clinical outcome – they are simply used as markers and are useful for contact tracing or studying transmission routes. But some mutations can last because they provide an advantage for the pathogen, even if only momentary. In the case of SARS-CoV-2, mutations in the protein spike gene (S) are relevant because they may give clues to that advantage – as well as to changes in infectivity, transmission potential, antibodies, and response to vaccines.

A variant of the virus that has eight changes that affect the protein S gene – and several others in different genes – is behind the increase in the number of cases in London and southeastern England. Researchers from the University of São Paulo identified one of the factors that made this new variant – classified as B.1.1.7 – more infectious.

With bioinformatics tools, they found that the protein S gene in the new viral strain has a stronger molecular interaction with the ACE2 receptor, which is on the surface of human cells and to which the virus binds, making infection possible. The variant has already spread to the rest of the world, and the first two cases have been confirmed in Brazil by the Adolf Lutz Institute.

The alert for a new variant in Africa – similar to B.1.1.7 in the United Kingdom in that it carries nine changes in protein S at position 501 – was made by the Brazilian virologist Tulio de Oliveira, PhD.

“We found that this strain seems to be spreading much faster,” Dr. Oliveira, who is with the University of KwaZulu Natal, told the journal Science. His work first alerted British scientists to the importance of the position N501Y.

“The new variants just described in the United Kingdom and South Africa are slightly more transmissible and have already been identified in cases imported into Brazil,” Dr. Motta said. “Unfortunately, we believe it is only a matter of time before it becomes indigenous.”
 

The viral family grows

Viruses such as SARS-CoV-2 are classified into strains on the basis of small differences in their genetic material. Since Dec. 26, 2020, in addition to the British and South African variants, it appears the Carioca lineage also is a player.

In a preprint article, researchers analyzed the evolution of the epidemic in Rio de Janeiro from April 2020 until just before the new increase in incidence in December. They compared the complete sequences of the viral genome of 180 patients from different municipalities. The study, which is being jointly conducted by members of the Federal University of Rio de Janeiro and the National Laboratory for Scientific Computing, identified a new variant of SARS-CoV-2 that has five unique mutations (from one of the predominant strains). Concern arose because, in addition to those five genetic changes, many of the samples had a sixth – the well-known E484K mutation.

“The three lines – the U.K., South Africa, and Brazil – were almost synchronous publications, but there is no clear evidence that they have any kind of common ancestry,” Carolina M. Voloch, PhD, the article’s first author and a biologist and researcher at the Molecular Virology Laboratory and associate professor in the department of genetics at the Federal University of Rio de Janeiro, said in an interview.

Dr. Voloch’s research focuses on the use of bioinformatics tools to study the molecular, phylogenetic, and genomic evolution of viruses.

“The emergence of new strains is common for viruses,” she said. “It can be happening anywhere in the world at any time.”

She stressed that identifying when mutations emerge will help to define the new Brazilian lineage. Researchers are working to determine whether the neutralizing antibodies of patients who have been infected with other strains respond to this Rio de Janeiro strain.

“We hope to soon be sharing these results,” Dr. Voloch said.

The article’s authors estimated that the new strain likely appeared in early July. They say more analysis is needed to predict whether the changes have a major effect on viral infectivity, the host’s immune response, or the severity of the disease. Asked about the lineage that caused the reinfection in Bahia, Dr. Voloch said she hadn’t yet contacted the authors to conduct a joint analysis but added that the data disclosed in the preprint would not represent the same variant.

“There are only two of the five mutations that characterize the Rio de Janeiro lineage. However, it has the E484K mutation that is present in more than 94% of the samples of the new variant of Rio,” she said.

She added that there’s a possibility of reinfection by the lineage that’s circulating in Rio de Janeiro and in other states, as well as countries such as the United States, the United Kingdom, and Japan.

“The Carioca virus is being exported to the rest of the world,” Dr. Voloch said.
 

Virus’ diversity still unknown

Researchers now know that SARS-CoV-2 probably circulated silently in Brazil as early as February 2020 and reached all the nation’s regions before air travel was restricted. Since the first half of 2020, there have been two predominant strains.

“More than a dozen strains have been identified in Brazil, but more important than counting strains to identify the speed with which they arise – which is directly associated with the rate of infection, which is very high in the country,” said Dr. Motta.

The so-called variant of Rio de Janeiro, he said, has also been detected in other states in four regions of Brazil. The key to documenting variants is to get a more representative sample with genomes from other parts of the country.

As of Jan. 10, a total of 347,000 complete genome sequences had been shared globally through open databases since SARS-CoV-2 was first identified, but the contribution of countries is uneven. Although the cost and complexity of genetic sequencing has dropped significantly over time, effective sequencing programs still require substantial investments in personnel, equipment, reagents, and bioinformatics infrastructure.

According to Dr. Voloch, it will only be possible to combat the new coronavirus by knowing its diversity and understanding how it evolves. The Fiocruz Genomic Network has made an infographic available so researchers can track the strains circulating in Brazil. It›s the result of collaboration between researchers from Fiocruz and the GISAID Initiative, an international partnership that promotes rapid data sharing.

As of Jan. 5, researchers in Brazil had studied 1,897 genomes – not nearly enough.

“In Brazil, there is little testing and even less sequencing,” lamented Dr. Souza.

“In the U.K., 1 in 600 cases is sequenced. In Brazil it is less than 1 in 10 million cases,” Dr. Voloch added.

So far, no decisive factors for public health, such as greater virulence or greater transmissibility, have been identified in any of the strains established in Brazil. The million-dollar question is whether the emergence of new strains could have an impact on the effectiveness of vaccines being administered today.

“In one way or another, the vaccine is our best bet ever, even if in the future we identify escapist mutants and have to modify it,” Dr. Motta said. “It is what we do annually with influenza.”

Dr. Voloch, Dr. Motta, and Dr. Souza disclosed no relevant financial relationships.

A version of this article first appeared on the Portuguese edition of Medscape.com.

Just as Brazil surpassed 200,000 deaths from COVID-19 on Jan. 7, news from Bahia added another layer of concern: A platform case report in a preprint detailed the first case of reinfection in that state, apparently caused by a new strain, one having the E484K mutation.

That variant, now called Brazil P.1, has migrated to the United States. The Minnesota Department of Health announced on Jan. 25 the nation’s first known COVID-19 case associated with it.

The mutation is located in the protein gene of the virus’ spike, which forms the crown structure of coronaviruses and is responsible for the virus’ binding to human cells. The E484K mutation is now the focus because it’s associated with mutations that escape the immune system’s neutralizing antibodies.

“This mutation is at the center of worldwide concern, and it is the first time that it has appeared in a reinfection,” the study’s first author, Bruno Solano de Freitas Souza, MD, a researcher at the Salvador regional unit of Instituto D’Or of Teaching and Research, based at Hospital São Rafael, Salvador, Brazil, explained in an interview.

“We will wait for the sample from Bahia to confirm the case from the perspective of the Ministry of Health’s surveillance network,” said Fernando Motta, PhD, deputy head of the Laboratory for Respiratory Virus and Measles at the Oswaldo Cruz Institute in Rio de Janeiro, which acts as a national reference center for respiratory viruses with the Brazilian Ministry of Health (MS) and as a reference for the World Health Organization.
 

A case of reinfection

The case patient that led to the alarm was a 45-year-old woman who is a health care executive. She had no comorbidities. The team had been following health care professionals and patients who had tested positive on reverse transcription–polymerase chain reaction (RT-PCR) testing more than once to understand whether they represented cases of prolonged viral persistence or new infections.

The woman had symptoms of viral infection on two occasions (May 26 and Oct. 26). On both occasions, results of RT-PCR testing for SARS-CoV-2 on nasopharyngeal samples were positive. In the first episode, the patient had diarrhea, myalgia, asthenia, and odynophagia for about 7 days. She returned to activities 21 days later. In the second episode, she had more severe symptoms that lasted longer, but she still did not require hospitalization.

“It was the first confirmed case of reinfection in Bahia, and in the second episode, we observed a mutation that could have an impact on the ability of antibodies to neutralize the virus,” Dr. Souza said. “The research continues with the investigation of cases in which the patient has a positive SARS-CoV-2 RT-PCR more than once in an interval greater than 45 days, to have a higher level of evidence.”

He stressed that “it is very important to reinforce measures to control the pandemic, social distance, use of masks, and speed up vaccination to be able to control the circulation of the virus, while monitoring the evolution of it.”
 

On alert for more cases

A person who twice tests positive for SARS-CoV-2 on real-time RT-PCR is suspected of having been reinfected, provided 90 or more days have elapsed between the two episodes, regardless of the condition observed. To confirm the suspected case, the samples must be sent to reference laboratories according to a plan established by the Ministry of Health in Brazil.

A health professional living in the Brazilian city of Natal represented the first confirmed case of reinfection by the new coronavirus in Brazil. That case was announced on Dec. 10, 2020.

“We communicated this case of reinfection to the MS in early December 2020. And the second sample already had the E484K mutation on the spike, as in the case of Bahia,” said Dr. Motta.

The first step in differentiating reinfection from persistence is to observe differences in the genotyping of the virus. For the technique to be successful, Dr. Souza said, researchers need a large amount of viral genetic material, which usually cannot be obtained.

“That is why there are many more suspected than confirmed cases,” Dr. Souza explained. He admitted that, although there are few cases, “it is increasingly clear that reinfection is a reality.”
 

Markers of mutations

What worried the researchers most was not only the possibility of reinfection but also the fact that preliminary analyses showed a specific mutation.

“The E484K mutation is present in a group of variants identified in South Africa that have been associated with increased infectivity and has been observed in a strain recently described in Brazil,” Dr. Souza said.

Mutations are expected, appear spontaneously, and in most cases have no effects on transmission or clinical outcome – they are simply used as markers and are useful for contact tracing or studying transmission routes. But some mutations can last because they provide an advantage for the pathogen, even if only momentary. In the case of SARS-CoV-2, mutations in the protein spike gene (S) are relevant because they may give clues to that advantage – as well as to changes in infectivity, transmission potential, antibodies, and response to vaccines.

A variant of the virus that has eight changes that affect the protein S gene – and several others in different genes – is behind the increase in the number of cases in London and southeastern England. Researchers from the University of São Paulo identified one of the factors that made this new variant – classified as B.1.1.7 – more infectious.

With bioinformatics tools, they found that the protein S gene in the new viral strain has a stronger molecular interaction with the ACE2 receptor, which is on the surface of human cells and to which the virus binds, making infection possible. The variant has already spread to the rest of the world, and the first two cases have been confirmed in Brazil by the Adolf Lutz Institute.

The alert for a new variant in Africa – similar to B.1.1.7 in the United Kingdom in that it carries nine changes in protein S at position 501 – was made by the Brazilian virologist Tulio de Oliveira, PhD.

“We found that this strain seems to be spreading much faster,” Dr. Oliveira, who is with the University of KwaZulu Natal, told the journal Science. His work first alerted British scientists to the importance of the position N501Y.

“The new variants just described in the United Kingdom and South Africa are slightly more transmissible and have already been identified in cases imported into Brazil,” Dr. Motta said. “Unfortunately, we believe it is only a matter of time before it becomes indigenous.”
 

The viral family grows

Viruses such as SARS-CoV-2 are classified into strains on the basis of small differences in their genetic material. Since Dec. 26, 2020, in addition to the British and South African variants, it appears the Carioca lineage also is a player.

In a preprint article, researchers analyzed the evolution of the epidemic in Rio de Janeiro from April 2020 until just before the new increase in incidence in December. They compared the complete sequences of the viral genome of 180 patients from different municipalities. The study, which is being jointly conducted by members of the Federal University of Rio de Janeiro and the National Laboratory for Scientific Computing, identified a new variant of SARS-CoV-2 that has five unique mutations (from one of the predominant strains). Concern arose because, in addition to those five genetic changes, many of the samples had a sixth – the well-known E484K mutation.

“The three lines – the U.K., South Africa, and Brazil – were almost synchronous publications, but there is no clear evidence that they have any kind of common ancestry,” Carolina M. Voloch, PhD, the article’s first author and a biologist and researcher at the Molecular Virology Laboratory and associate professor in the department of genetics at the Federal University of Rio de Janeiro, said in an interview.

Dr. Voloch’s research focuses on the use of bioinformatics tools to study the molecular, phylogenetic, and genomic evolution of viruses.

“The emergence of new strains is common for viruses,” she said. “It can be happening anywhere in the world at any time.”

She stressed that identifying when mutations emerge will help to define the new Brazilian lineage. Researchers are working to determine whether the neutralizing antibodies of patients who have been infected with other strains respond to this Rio de Janeiro strain.

“We hope to soon be sharing these results,” Dr. Voloch said.

The article’s authors estimated that the new strain likely appeared in early July. They say more analysis is needed to predict whether the changes have a major effect on viral infectivity, the host’s immune response, or the severity of the disease. Asked about the lineage that caused the reinfection in Bahia, Dr. Voloch said she hadn’t yet contacted the authors to conduct a joint analysis but added that the data disclosed in the preprint would not represent the same variant.

“There are only two of the five mutations that characterize the Rio de Janeiro lineage. However, it has the E484K mutation that is present in more than 94% of the samples of the new variant of Rio,” she said.

She added that there’s a possibility of reinfection by the lineage that’s circulating in Rio de Janeiro and in other states, as well as countries such as the United States, the United Kingdom, and Japan.

“The Carioca virus is being exported to the rest of the world,” Dr. Voloch said.
 

Virus’ diversity still unknown

Researchers now know that SARS-CoV-2 probably circulated silently in Brazil as early as February 2020 and reached all the nation’s regions before air travel was restricted. Since the first half of 2020, there have been two predominant strains.

“More than a dozen strains have been identified in Brazil, but more important than counting strains to identify the speed with which they arise – which is directly associated with the rate of infection, which is very high in the country,” said Dr. Motta.

The so-called variant of Rio de Janeiro, he said, has also been detected in other states in four regions of Brazil. The key to documenting variants is to get a more representative sample with genomes from other parts of the country.

As of Jan. 10, a total of 347,000 complete genome sequences had been shared globally through open databases since SARS-CoV-2 was first identified, but the contribution of countries is uneven. Although the cost and complexity of genetic sequencing has dropped significantly over time, effective sequencing programs still require substantial investments in personnel, equipment, reagents, and bioinformatics infrastructure.

According to Dr. Voloch, it will only be possible to combat the new coronavirus by knowing its diversity and understanding how it evolves. The Fiocruz Genomic Network has made an infographic available so researchers can track the strains circulating in Brazil. It›s the result of collaboration between researchers from Fiocruz and the GISAID Initiative, an international partnership that promotes rapid data sharing.

As of Jan. 5, researchers in Brazil had studied 1,897 genomes – not nearly enough.

“In Brazil, there is little testing and even less sequencing,” lamented Dr. Souza.

“In the U.K., 1 in 600 cases is sequenced. In Brazil it is less than 1 in 10 million cases,” Dr. Voloch added.

So far, no decisive factors for public health, such as greater virulence or greater transmissibility, have been identified in any of the strains established in Brazil. The million-dollar question is whether the emergence of new strains could have an impact on the effectiveness of vaccines being administered today.

“In one way or another, the vaccine is our best bet ever, even if in the future we identify escapist mutants and have to modify it,” Dr. Motta said. “It is what we do annually with influenza.”

Dr. Voloch, Dr. Motta, and Dr. Souza disclosed no relevant financial relationships.

A version of this article first appeared on the Portuguese edition of Medscape.com.

Seven days into his presidency, Joe Biden announced that he is taking new steps to speed vaccines to Americans.

The president said he would increase the supply of vaccines to states from 8.6 million doses to 10 million doses per week, a 16% increase, for at least the next 3 weeks.

He said he was working to give states more advanced notice of their allotments so they could better plan their campaigns. He also said doses would be doled out based on population.

“We will both increase the supply and give our state and local partners more certainty about when doses will arrive,” he said Tuesday.

Finally, Mr. Biden announced that the United States would “soon be able to confirm” the purchase of 200 million more doses of the Pfizer and Moderna vaccines – 100 million of each – to effectively double the nation’s supply by “early summer.” That would increase the nation’s supply enough to fully vaccinate 300 million Americans by fall.

Mr. Biden said he was also working to shift the focus to getting more doses to economically disadvantaged communities and rural areas, which have fallen further behind as the vaccine rollout has faltered.

Even with these steps, Mr. Biden stressed that it would take months for vaccines to curb infections and deaths. He said, for the time being, masks, not vaccines, are the best way to save lives.

“The brutal truth is its going to take months before we get the majority of Americans vaccinated. Months,” he said, adding that wearing masks until at least April could save to save 50,000 lives.

“Let me be clear,” Mr. Biden said, “Things are going to get worse before they get better.

“We didn’t get into this mess overnight. It’s going to take months for us to turn things around. But let me be equally clear we’re going to get through this. We will defeat this pandemic,” he said.

A version of this article first appeared on WebMD.com.

Seven days into his presidency, Joe Biden announced that he is taking new steps to speed vaccines to Americans.

The president said he would increase the supply of vaccines to states from 8.6 million doses to 10 million doses per week, a 16% increase, for at least the next 3 weeks.

He said he was working to give states more advanced notice of their allotments so they could better plan their campaigns. He also said doses would be doled out based on population.

“We will both increase the supply and give our state and local partners more certainty about when doses will arrive,” he said Tuesday.

Finally, Mr. Biden announced that the United States would “soon be able to confirm” the purchase of 200 million more doses of the Pfizer and Moderna vaccines – 100 million of each – to effectively double the nation’s supply by “early summer.” That would increase the nation’s supply enough to fully vaccinate 300 million Americans by fall.

Mr. Biden said he was also working to shift the focus to getting more doses to economically disadvantaged communities and rural areas, which have fallen further behind as the vaccine rollout has faltered.

Even with these steps, Mr. Biden stressed that it would take months for vaccines to curb infections and deaths. He said, for the time being, masks, not vaccines, are the best way to save lives.

“The brutal truth is its going to take months before we get the majority of Americans vaccinated. Months,” he said, adding that wearing masks until at least April could save to save 50,000 lives.

“Let me be clear,” Mr. Biden said, “Things are going to get worse before they get better.

“We didn’t get into this mess overnight. It’s going to take months for us to turn things around. But let me be equally clear we’re going to get through this. We will defeat this pandemic,” he said.

A version of this article first appeared on WebMD.com.

Seven days into his presidency, Joe Biden announced that he is taking new steps to speed vaccines to Americans.

The president said he would increase the supply of vaccines to states from 8.6 million doses to 10 million doses per week, a 16% increase, for at least the next 3 weeks.

He said he was working to give states more advanced notice of their allotments so they could better plan their campaigns. He also said doses would be doled out based on population.

“We will both increase the supply and give our state and local partners more certainty about when doses will arrive,” he said Tuesday.

Finally, Mr. Biden announced that the United States would “soon be able to confirm” the purchase of 200 million more doses of the Pfizer and Moderna vaccines – 100 million of each – to effectively double the nation’s supply by “early summer.” That would increase the nation’s supply enough to fully vaccinate 300 million Americans by fall.

Mr. Biden said he was also working to shift the focus to getting more doses to economically disadvantaged communities and rural areas, which have fallen further behind as the vaccine rollout has faltered.

Even with these steps, Mr. Biden stressed that it would take months for vaccines to curb infections and deaths. He said, for the time being, masks, not vaccines, are the best way to save lives.

“The brutal truth is its going to take months before we get the majority of Americans vaccinated. Months,” he said, adding that wearing masks until at least April could save to save 50,000 lives.

“Let me be clear,” Mr. Biden said, “Things are going to get worse before they get better.

“We didn’t get into this mess overnight. It’s going to take months for us to turn things around. But let me be equally clear we’re going to get through this. We will defeat this pandemic,” he said.

A version of this article first appeared on WebMD.com.

According to Noreen Heer Nicol, PhD, RN, FNP, frustration still exists for patients, families, and health care providers regarding the lack of consensus that routine bathing is good for patients with atopic dermatitis.

monkeybusinessimages/Getty Images

During the Revolutionizing Atopic Dermatitis symposium, she said that conflicting and vague guidelines currently exist on the topic.

“This stems from the fact that we just don’t have good studies,” said Dr. Nicol, associate dean and associate professor of nursing at the University of Colorado at Denver, Aurora. “Particularly, we don’t have randomized, controlled trials on the effects of water and bathing. It’s not just parents that are frustrated, but health care providers are as well.”

In an observational analysis, researchers evaluated results from three online surveys of dermatologists, allergists, and immunologists, and primary care physicians regarding routine bathing frequency recommendations for children with AD. It found that PCPs recommended daily bathing less than 50% of the time, while specialists recommended daily bathing more than 50% of the time.

“It seems like the PCPs have embraced that old dermatology notion when bathing was avoided in patients with AD,” Dr. Nicol said. “This lack of consensus on the basic daily care steps in AD management causes a great deal of confusion amongst patients, families, and young health care providers, in particular,” she added.

She believes that this goes back to a century-long debate about the pros and cons of bathing in AD. “We used to say that bathing will dry the skin out if you take a bath or a shower without immediately applying something like a good moisturizer. That’s where the 3-minute rule came along from the National Eczema Association, meaning that bathing hydrates the stratum corneum if you take a bath or a shower and you immediately apply that good moisturizer within 3 minutes to retain that hydration and keep the barrier intact and flexible.”

Dr. Nicol presented a stepwise management model that she has published many times over the years (see Pediatr Nursing 2020;46[2]:92-8 and J Allergy Clin Immunol Pract 2019;7[1]:1-16).

Step 1 consists of basic care, including skin hydration/bathing, application of a daily moisturizer, avoiding irritants, and identifying and addressing specific triggers. “This is the foundation for every step as you go forward,” she explained. Soak and seal has been a mainstay of treatment at National Jewish Health, she noted. “By that, I mean taking a soaking 10-15 minute bath in warm water daily. Gently pat away excess water. Immediately apply skin medications or moisturizer within 3 minutes. Using a gentle fragrance-free, dye-free cleanser to clean skin is also important. Avoid scrubbing.”

A review article on bathing and associated treatments in AD was published in 2017 and includes 144 references to bathing studies. A separate recommendation known as the “AD Yardstick” published by Dr. Nicol’s colleague at National Jewish Health, Mark Boguniewicz, MD, and coauthors, elaborated on the definition of basic skin care for nonlesional AD. Besides recommending the liberal and frequent application of moisturizers, it suggests management with warm baths or showers using nonsoap cleansers, usually once per day, followed by application of a moisturizer, even on clear areas.

“This is now what people are thinking as the basis of skin care in patients with AD,” Dr. Nicol said. “Warm baths and showers don’t look so controversial anymore. This model nicely lays out what we want people to remember. In the past, many times we just skipped that important step of telling people about bathing.”

In a small 2009 study, researchers conducted a quantitative assessment of combination bathing and moisturizing regimens on skin hydration in AD. They found that bathing followed by application of a moisturizer provides modest hydration benefits, though less than that of simply applying moisturizer alone. “That has not been the case for most of us who are bathing advocates,” Dr. Nicol said. “We believe that there is an additional hydration that’s gained from bathing and moisturizers done properly.”

In an earlier retrospective study of 28 patients referred to a tertiary care center for refractory chronic pruritic eruptions, researchers found that a plain-water 20-minute soak followed by smearing of midstrength corticosteroid ointment led to clearing or dramatic improvement of the lesions (Arch Dermatol 2005;14:1556-9). The authors recommended prospective studies to confirm the findings.

In a separate review of medical literature, researchers explored the role of frequent bathing in the treatment of pediatric AD (Ann Allergy Asthma Immunol 2016;117[1]:9-13). They found that the weight of evidence suggests that the frequent soak and smear bathing is preferred to infrequent bathing in the management of AD. Frequent bathing was defined as bathing at least once a day, while infrequent bathing was defined as bathing less than once a day.

“Bleach baths have received much attention in recent years, and have been endorsed by multiple AD guidelines, though not to the same degree as regular bathing,” Dr. Nicol said. “Right now, you can find almost as much literature for this practice as against it. The populations that seem to value from beach baths the most, however, are those with frequent infections, particularly those who are methicillin resistant. Most people recommend a maximum of two to three times per week but only with an active infection. Care must be taken to avoid additional drying or irritation of the skin from bleach.”

Many bleach bath recipes call for adding one-eighth to one-half of a cup of bleach to a tub full or water.

Dr. Nicol disclosed that she has served as an advisory board member for Eli Lilly.

dbrunk@mdedge.com

According to Noreen Heer Nicol, PhD, RN, FNP, frustration still exists for patients, families, and health care providers regarding the lack of consensus that routine bathing is good for patients with atopic dermatitis.

monkeybusinessimages/Getty Images

During the Revolutionizing Atopic Dermatitis symposium, she said that conflicting and vague guidelines currently exist on the topic.

“This stems from the fact that we just don’t have good studies,” said Dr. Nicol, associate dean and associate professor of nursing at the University of Colorado at Denver, Aurora. “Particularly, we don’t have randomized, controlled trials on the effects of water and bathing. It’s not just parents that are frustrated, but health care providers are as well.”

In an observational analysis, researchers evaluated results from three online surveys of dermatologists, allergists, and immunologists, and primary care physicians regarding routine bathing frequency recommendations for children with AD. It found that PCPs recommended daily bathing less than 50% of the time, while specialists recommended daily bathing more than 50% of the time.

“It seems like the PCPs have embraced that old dermatology notion when bathing was avoided in patients with AD,” Dr. Nicol said. “This lack of consensus on the basic daily care steps in AD management causes a great deal of confusion amongst patients, families, and young health care providers, in particular,” she added.

She believes that this goes back to a century-long debate about the pros and cons of bathing in AD. “We used to say that bathing will dry the skin out if you take a bath or a shower without immediately applying something like a good moisturizer. That’s where the 3-minute rule came along from the National Eczema Association, meaning that bathing hydrates the stratum corneum if you take a bath or a shower and you immediately apply that good moisturizer within 3 minutes to retain that hydration and keep the barrier intact and flexible.”

Dr. Nicol presented a stepwise management model that she has published many times over the years (see Pediatr Nursing 2020;46[2]:92-8 and J Allergy Clin Immunol Pract 2019;7[1]:1-16).

Step 1 consists of basic care, including skin hydration/bathing, application of a daily moisturizer, avoiding irritants, and identifying and addressing specific triggers. “This is the foundation for every step as you go forward,” she explained. Soak and seal has been a mainstay of treatment at National Jewish Health, she noted. “By that, I mean taking a soaking 10-15 minute bath in warm water daily. Gently pat away excess water. Immediately apply skin medications or moisturizer within 3 minutes. Using a gentle fragrance-free, dye-free cleanser to clean skin is also important. Avoid scrubbing.”

A review article on bathing and associated treatments in AD was published in 2017 and includes 144 references to bathing studies. A separate recommendation known as the “AD Yardstick” published by Dr. Nicol’s colleague at National Jewish Health, Mark Boguniewicz, MD, and coauthors, elaborated on the definition of basic skin care for nonlesional AD. Besides recommending the liberal and frequent application of moisturizers, it suggests management with warm baths or showers using nonsoap cleansers, usually once per day, followed by application of a moisturizer, even on clear areas.

“This is now what people are thinking as the basis of skin care in patients with AD,” Dr. Nicol said. “Warm baths and showers don’t look so controversial anymore. This model nicely lays out what we want people to remember. In the past, many times we just skipped that important step of telling people about bathing.”

In a small 2009 study, researchers conducted a quantitative assessment of combination bathing and moisturizing regimens on skin hydration in AD. They found that bathing followed by application of a moisturizer provides modest hydration benefits, though less than that of simply applying moisturizer alone. “That has not been the case for most of us who are bathing advocates,” Dr. Nicol said. “We believe that there is an additional hydration that’s gained from bathing and moisturizers done properly.”

In an earlier retrospective study of 28 patients referred to a tertiary care center for refractory chronic pruritic eruptions, researchers found that a plain-water 20-minute soak followed by smearing of midstrength corticosteroid ointment led to clearing or dramatic improvement of the lesions (Arch Dermatol 2005;14:1556-9). The authors recommended prospective studies to confirm the findings.

In a separate review of medical literature, researchers explored the role of frequent bathing in the treatment of pediatric AD (Ann Allergy Asthma Immunol 2016;117[1]:9-13). They found that the weight of evidence suggests that the frequent soak and smear bathing is preferred to infrequent bathing in the management of AD. Frequent bathing was defined as bathing at least once a day, while infrequent bathing was defined as bathing less than once a day.

“Bleach baths have received much attention in recent years, and have been endorsed by multiple AD guidelines, though not to the same degree as regular bathing,” Dr. Nicol said. “Right now, you can find almost as much literature for this practice as against it. The populations that seem to value from beach baths the most, however, are those with frequent infections, particularly those who are methicillin resistant. Most people recommend a maximum of two to three times per week but only with an active infection. Care must be taken to avoid additional drying or irritation of the skin from bleach.”

Many bleach bath recipes call for adding one-eighth to one-half of a cup of bleach to a tub full or water.

Dr. Nicol disclosed that she has served as an advisory board member for Eli Lilly.

dbrunk@mdedge.com

According to Noreen Heer Nicol, PhD, RN, FNP, frustration still exists for patients, families, and health care providers regarding the lack of consensus that routine bathing is good for patients with atopic dermatitis.

monkeybusinessimages/Getty Images

During the Revolutionizing Atopic Dermatitis symposium, she said that conflicting and vague guidelines currently exist on the topic.

“This stems from the fact that we just don’t have good studies,” said Dr. Nicol, associate dean and associate professor of nursing at the University of Colorado at Denver, Aurora. “Particularly, we don’t have randomized, controlled trials on the effects of water and bathing. It’s not just parents that are frustrated, but health care providers are as well.”

In an observational analysis, researchers evaluated results from three online surveys of dermatologists, allergists, and immunologists, and primary care physicians regarding routine bathing frequency recommendations for children with AD. It found that PCPs recommended daily bathing less than 50% of the time, while specialists recommended daily bathing more than 50% of the time.

“It seems like the PCPs have embraced that old dermatology notion when bathing was avoided in patients with AD,” Dr. Nicol said. “This lack of consensus on the basic daily care steps in AD management causes a great deal of confusion amongst patients, families, and young health care providers, in particular,” she added.

She believes that this goes back to a century-long debate about the pros and cons of bathing in AD. “We used to say that bathing will dry the skin out if you take a bath or a shower without immediately applying something like a good moisturizer. That’s where the 3-minute rule came along from the National Eczema Association, meaning that bathing hydrates the stratum corneum if you take a bath or a shower and you immediately apply that good moisturizer within 3 minutes to retain that hydration and keep the barrier intact and flexible.”

Dr. Nicol presented a stepwise management model that she has published many times over the years (see Pediatr Nursing 2020;46[2]:92-8 and J Allergy Clin Immunol Pract 2019;7[1]:1-16).

Step 1 consists of basic care, including skin hydration/bathing, application of a daily moisturizer, avoiding irritants, and identifying and addressing specific triggers. “This is the foundation for every step as you go forward,” she explained. Soak and seal has been a mainstay of treatment at National Jewish Health, she noted. “By that, I mean taking a soaking 10-15 minute bath in warm water daily. Gently pat away excess water. Immediately apply skin medications or moisturizer within 3 minutes. Using a gentle fragrance-free, dye-free cleanser to clean skin is also important. Avoid scrubbing.”

A review article on bathing and associated treatments in AD was published in 2017 and includes 144 references to bathing studies. A separate recommendation known as the “AD Yardstick” published by Dr. Nicol’s colleague at National Jewish Health, Mark Boguniewicz, MD, and coauthors, elaborated on the definition of basic skin care for nonlesional AD. Besides recommending the liberal and frequent application of moisturizers, it suggests management with warm baths or showers using nonsoap cleansers, usually once per day, followed by application of a moisturizer, even on clear areas.

“This is now what people are thinking as the basis of skin care in patients with AD,” Dr. Nicol said. “Warm baths and showers don’t look so controversial anymore. This model nicely lays out what we want people to remember. In the past, many times we just skipped that important step of telling people about bathing.”

In a small 2009 study, researchers conducted a quantitative assessment of combination bathing and moisturizing regimens on skin hydration in AD. They found that bathing followed by application of a moisturizer provides modest hydration benefits, though less than that of simply applying moisturizer alone. “That has not been the case for most of us who are bathing advocates,” Dr. Nicol said. “We believe that there is an additional hydration that’s gained from bathing and moisturizers done properly.”

In an earlier retrospective study of 28 patients referred to a tertiary care center for refractory chronic pruritic eruptions, researchers found that a plain-water 20-minute soak followed by smearing of midstrength corticosteroid ointment led to clearing or dramatic improvement of the lesions (Arch Dermatol 2005;14:1556-9). The authors recommended prospective studies to confirm the findings.

In a separate review of medical literature, researchers explored the role of frequent bathing in the treatment of pediatric AD (Ann Allergy Asthma Immunol 2016;117[1]:9-13). They found that the weight of evidence suggests that the frequent soak and smear bathing is preferred to infrequent bathing in the management of AD. Frequent bathing was defined as bathing at least once a day, while infrequent bathing was defined as bathing less than once a day.

“Bleach baths have received much attention in recent years, and have been endorsed by multiple AD guidelines, though not to the same degree as regular bathing,” Dr. Nicol said. “Right now, you can find almost as much literature for this practice as against it. The populations that seem to value from beach baths the most, however, are those with frequent infections, particularly those who are methicillin resistant. Most people recommend a maximum of two to three times per week but only with an active infection. Care must be taken to avoid additional drying or irritation of the skin from bleach.”

Many bleach bath recipes call for adding one-eighth to one-half of a cup of bleach to a tub full or water.

Dr. Nicol disclosed that she has served as an advisory board member for Eli Lilly.

dbrunk@mdedge.com

A once-daily oral selective Janus kinase 1 inhibitor demonstrated promising safety and efficacy for the treatment of moderate to severe hidradenitis suppurativa (HS) in a pair of small, randomized, phase 2 studies that established proof-of-concept for the novel agent, Afsaneh Alavi, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

These favorable clinical findings were buttressed by a proteomic analysis demonstrating dose-dependent reductions in circulating inflammatory mediators, added Dr. Alavi, a dermatologist at the Mayo Clinic in Rochester, Minn.

The investigational oral small molecule, known for now as INCB54707, is 52 times more selective for JAK1 than JAK2.

Both multicenter studies entailed 8 weeks of active treatment with INCB54707 followed by a 4-week safety observation. In one study, 10 patients received 15 mg of the investigational agent once daily in open-label fashion. The other trial randomized 35 patients to the JAK1 inhibitor at 30 mg, 60 mg, or 90 mg per day or placebo. About 70% of participants in the studies had Hurley stage II HS; the rest were stage III.

Safety and tolerability were the primary outcomes in the two studies. One patient in the open-label study dropped out because of a flare of fibromyalgia. In the larger randomized trial, four patients – all in the group assigned to 90 mg/day of the JAK1 inhibitor – developed thrombocytopenia, resulting in temporary discontinuation of treatment for up to 2 weeks. In all four instances, the laboratory abnormality was reversed after temporary interruption of treatment, with no sequelae upon restarting the drug. There were no serious treatment-emergent adverse events in either study.

In the low-dose, open-label study, four of nine completers (44%) experienced a Hidradenitis Suppurativa Clinical Response (HiSCR) at week 8, defined as at least a 50% reduction in inflammatory lesion count with no increase in abscesses or draining fistulae compared to baseline. In the randomized trial, the week-8 HiSCR rate was 57% in placebo-treated controls, 56% in those on 30 mg/day or 60 mg/day of the JAK1 inhibitor, and significantly better at 88% in the group on 90 mg/day.

The rapidity of response to the JAK1 inhibitor was noteworthy. After just 1 week of treatment, an abscess and inflammatory nodule count of zero to two lesions was present in 22% of patients on INCB54707 at 60 mg/day and 29% of those on 90 mg/day, compared with none of the patients on 30 mg/day or placebo. At week 2, an abscess and nodule count of 0-2 was documented in 33% of participants on the JAK1 inhibitor at 30 mg/day, 58% at 60 mg/day, and 50% with 90 mg/day. At week 8, the rates were 57% with placebo, 44% with active treatment at 30 or 60 mg/day, and 63% in patients on 90 mg/day.

A dose-dependent significant improvement in Hidradenitis Suppurativa Quality of Life scores was documented in response to the JAK1 inhibitor.

There is an unmet need for effective therapies for HS, a chronic, extremely painful inflammatory condition with a large negative impact on quality of life. At present, the only Food and Drug Administration–approved medication for HS is the tumor necrosis factor inhibitor, adalimumab (Humira), noted Dr. Alavi. Ongoing studies are evaluating other JAK inhibitors, as well as TNF inhibitors and interleukin-17 and -23 blockers.

She reported receiving research funding from and serving as a consultant to Incyte, the studies’ sponsor, and more than a dozen other pharmaceutical companies.

bjancin@mdedge.com

A once-daily oral selective Janus kinase 1 inhibitor demonstrated promising safety and efficacy for the treatment of moderate to severe hidradenitis suppurativa (HS) in a pair of small, randomized, phase 2 studies that established proof-of-concept for the novel agent, Afsaneh Alavi, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

These favorable clinical findings were buttressed by a proteomic analysis demonstrating dose-dependent reductions in circulating inflammatory mediators, added Dr. Alavi, a dermatologist at the Mayo Clinic in Rochester, Minn.

The investigational oral small molecule, known for now as INCB54707, is 52 times more selective for JAK1 than JAK2.

Both multicenter studies entailed 8 weeks of active treatment with INCB54707 followed by a 4-week safety observation. In one study, 10 patients received 15 mg of the investigational agent once daily in open-label fashion. The other trial randomized 35 patients to the JAK1 inhibitor at 30 mg, 60 mg, or 90 mg per day or placebo. About 70% of participants in the studies had Hurley stage II HS; the rest were stage III.

Safety and tolerability were the primary outcomes in the two studies. One patient in the open-label study dropped out because of a flare of fibromyalgia. In the larger randomized trial, four patients – all in the group assigned to 90 mg/day of the JAK1 inhibitor – developed thrombocytopenia, resulting in temporary discontinuation of treatment for up to 2 weeks. In all four instances, the laboratory abnormality was reversed after temporary interruption of treatment, with no sequelae upon restarting the drug. There were no serious treatment-emergent adverse events in either study.

In the low-dose, open-label study, four of nine completers (44%) experienced a Hidradenitis Suppurativa Clinical Response (HiSCR) at week 8, defined as at least a 50% reduction in inflammatory lesion count with no increase in abscesses or draining fistulae compared to baseline. In the randomized trial, the week-8 HiSCR rate was 57% in placebo-treated controls, 56% in those on 30 mg/day or 60 mg/day of the JAK1 inhibitor, and significantly better at 88% in the group on 90 mg/day.

The rapidity of response to the JAK1 inhibitor was noteworthy. After just 1 week of treatment, an abscess and inflammatory nodule count of zero to two lesions was present in 22% of patients on INCB54707 at 60 mg/day and 29% of those on 90 mg/day, compared with none of the patients on 30 mg/day or placebo. At week 2, an abscess and nodule count of 0-2 was documented in 33% of participants on the JAK1 inhibitor at 30 mg/day, 58% at 60 mg/day, and 50% with 90 mg/day. At week 8, the rates were 57% with placebo, 44% with active treatment at 30 or 60 mg/day, and 63% in patients on 90 mg/day.

A dose-dependent significant improvement in Hidradenitis Suppurativa Quality of Life scores was documented in response to the JAK1 inhibitor.

There is an unmet need for effective therapies for HS, a chronic, extremely painful inflammatory condition with a large negative impact on quality of life. At present, the only Food and Drug Administration–approved medication for HS is the tumor necrosis factor inhibitor, adalimumab (Humira), noted Dr. Alavi. Ongoing studies are evaluating other JAK inhibitors, as well as TNF inhibitors and interleukin-17 and -23 blockers.

She reported receiving research funding from and serving as a consultant to Incyte, the studies’ sponsor, and more than a dozen other pharmaceutical companies.

bjancin@mdedge.com

A once-daily oral selective Janus kinase 1 inhibitor demonstrated promising safety and efficacy for the treatment of moderate to severe hidradenitis suppurativa (HS) in a pair of small, randomized, phase 2 studies that established proof-of-concept for the novel agent, Afsaneh Alavi, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

These favorable clinical findings were buttressed by a proteomic analysis demonstrating dose-dependent reductions in circulating inflammatory mediators, added Dr. Alavi, a dermatologist at the Mayo Clinic in Rochester, Minn.

The investigational oral small molecule, known for now as INCB54707, is 52 times more selective for JAK1 than JAK2.

Both multicenter studies entailed 8 weeks of active treatment with INCB54707 followed by a 4-week safety observation. In one study, 10 patients received 15 mg of the investigational agent once daily in open-label fashion. The other trial randomized 35 patients to the JAK1 inhibitor at 30 mg, 60 mg, or 90 mg per day or placebo. About 70% of participants in the studies had Hurley stage II HS; the rest were stage III.

Safety and tolerability were the primary outcomes in the two studies. One patient in the open-label study dropped out because of a flare of fibromyalgia. In the larger randomized trial, four patients – all in the group assigned to 90 mg/day of the JAK1 inhibitor – developed thrombocytopenia, resulting in temporary discontinuation of treatment for up to 2 weeks. In all four instances, the laboratory abnormality was reversed after temporary interruption of treatment, with no sequelae upon restarting the drug. There were no serious treatment-emergent adverse events in either study.

In the low-dose, open-label study, four of nine completers (44%) experienced a Hidradenitis Suppurativa Clinical Response (HiSCR) at week 8, defined as at least a 50% reduction in inflammatory lesion count with no increase in abscesses or draining fistulae compared to baseline. In the randomized trial, the week-8 HiSCR rate was 57% in placebo-treated controls, 56% in those on 30 mg/day or 60 mg/day of the JAK1 inhibitor, and significantly better at 88% in the group on 90 mg/day.

The rapidity of response to the JAK1 inhibitor was noteworthy. After just 1 week of treatment, an abscess and inflammatory nodule count of zero to two lesions was present in 22% of patients on INCB54707 at 60 mg/day and 29% of those on 90 mg/day, compared with none of the patients on 30 mg/day or placebo. At week 2, an abscess and nodule count of 0-2 was documented in 33% of participants on the JAK1 inhibitor at 30 mg/day, 58% at 60 mg/day, and 50% with 90 mg/day. At week 8, the rates were 57% with placebo, 44% with active treatment at 30 or 60 mg/day, and 63% in patients on 90 mg/day.

A dose-dependent significant improvement in Hidradenitis Suppurativa Quality of Life scores was documented in response to the JAK1 inhibitor.

There is an unmet need for effective therapies for HS, a chronic, extremely painful inflammatory condition with a large negative impact on quality of life. At present, the only Food and Drug Administration–approved medication for HS is the tumor necrosis factor inhibitor, adalimumab (Humira), noted Dr. Alavi. Ongoing studies are evaluating other JAK inhibitors, as well as TNF inhibitors and interleukin-17 and -23 blockers.

She reported receiving research funding from and serving as a consultant to Incyte, the studies’ sponsor, and more than a dozen other pharmaceutical companies.

bjancin@mdedge.com