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Updated guidance for COVID vaccination in rheumatology patients arrives amid continued hesitancy
As rheumatologists contend with vaccine hesitancy among certain subsets of patients, the American College of Rheumatology has released updated clinical guidelines on COVID-19 vaccination for patients with rheumatic and musculoskeletal diseases (RMDs), including new recommendations on supplemental and booster doses.
The revised guidance from this fifth version of the ACR guidelines includes strongly recommending that all RMD patients receive a booster after their primary vaccine series, regardless of whether they have been naturally infected with COVID-19. In addition, they strongly recommend third supplemental doses for patients with autoimmune inflammatory rheumatic diseases (AIIRDs) who likely mounted an inadequate vaccine response, which would then be followed by a fourth booster dose as advised by the Centers for Disease Control and Prevention for immunocompromised individuals.
Other recommendations include pre-exposure prophylaxis monoclonal antibody treatment for high-risk AIIRD patients, defined as those with moderate to severely compromised immune systems who may not mount an adequate immune response to COVID-19 vaccination, when it is available and authorized for emergency use by the Food and Drug Administration, as well as monoclonal antibody therapy for postexposure prophylaxis of asymptomatic, recently exposed high-risk AIIRD patients or as treatment for newly symptomatic, high-risk AIIRD patients. The ACR guidance notes that, currently, neither the monoclonal antibodies bamlanivimab and etesevimab (administered together) nor casirivimab and imdevimab (REGEN-COV), are licensed or available under an emergency use authorization given their lack of activity against the Omicron variant, the dominant strain of SARS-CoV-2 circulating in the United States.
Finally, the guidance clarified that the timing of intravenous immunoglobulin doses does not need to be modified around the administration of COVID vaccine doses, based on moderate consensus among task force members.
Vaccine hesitancy in community rheumatology practices
The revised guidelines were released just as Arthritis & Rheumatology published a new study that assessed vaccine hesitancy among rheumatology patients on immunomodulatory therapies. A three-item electronic survey was conducted at 101 offices within a community practice–based rheumatology research network and ultimately collected responses from 58,529 patients, 20,987 of whom had an AIIRD and were receiving targeted therapies like biologics or Janus kinase inhibitors.
Of the total respondents, 77% (n = 43,675) had been vaccinated, 16.9% were not vaccinated and did not plan to be, and 6.1% were not vaccinated but planned to be. However, AIIRD patients were 16% less likely to be vaccinated, compared with the other patients, such as those with osteoarthritis or osteoporosis who were not receiving disease-modifying antirheumatic drugs (76.9% vs. 87%; odds ratio, 0.84; 95% confidence interval, 0.77-0.92; P < .001). Multivariable analysis also found that older patients (OR, 1.49 per 10 years) and Asians (OR, 2.42; 95% CI, 1.77-3.33) were more likely to be vaccinated.
“Rheumatologists need to be asking their patients more than just: ‘Are you vaccinated?’ ” Jeffrey Curtis, MD, MPH, head of the ACR COVID-19 vaccine task force and a coauthor of the vaccine hesitancy study, said in an interview. “A year ago, that was a fine approach, but now they need to be asking whether you’ve been vaccinated, and with what, and how many times, and how recently. There are a whole lot of subtleties there; ‘vaccinated: yes or no’ is just the tip of the iceberg.”
His research into the vaccine hesitant includes recent anecdotal data from thousands of patients treated in local rheumatology community practices, many of whom cited long-term safety data and potential side effects as reasons why they were unwilling to get vaccinated. But despite their on-paper responses, he cautioned rheumatologists to think critically when determining which patients may truly be open to vaccination.
“If you’re designing strategies to affect vaccine hesitancy, you may be wasting your time with some people,” said Dr. Curtis, professor of medicine at the University of Alabama at Birmingham. “A critical need is to figure out who are the patients who may be amendable to more information or an intervention or a little bit more time and care, and who are the people where you know, this is a lost cause: You don’t get a flu shot, you haven’t been vaccinated for shingles, [and] you’re not going to get this one either.
“In terms of a research agenda, how do we develop efficient, simple, short screening tools?” he added. “Something with a few helpful questions, on a patient portal or an iPad, that will do a good job identifying your patients at risk who haven’t had vaccination but that you might be able to spend time with, intervene, and actually change their mind. If you spend gobs of time with everyone, you’ll help some people, but clinicians don’t have an infinite amount of time.”
One of the authors of the vaccine hesitancy study acknowledged being employed by the rheumatology research network that hosted the survey. Several others, including Dr. Curtis, reported receiving grants and consulting fees from various pharmaceutical companies.
As rheumatologists contend with vaccine hesitancy among certain subsets of patients, the American College of Rheumatology has released updated clinical guidelines on COVID-19 vaccination for patients with rheumatic and musculoskeletal diseases (RMDs), including new recommendations on supplemental and booster doses.
The revised guidance from this fifth version of the ACR guidelines includes strongly recommending that all RMD patients receive a booster after their primary vaccine series, regardless of whether they have been naturally infected with COVID-19. In addition, they strongly recommend third supplemental doses for patients with autoimmune inflammatory rheumatic diseases (AIIRDs) who likely mounted an inadequate vaccine response, which would then be followed by a fourth booster dose as advised by the Centers for Disease Control and Prevention for immunocompromised individuals.
Other recommendations include pre-exposure prophylaxis monoclonal antibody treatment for high-risk AIIRD patients, defined as those with moderate to severely compromised immune systems who may not mount an adequate immune response to COVID-19 vaccination, when it is available and authorized for emergency use by the Food and Drug Administration, as well as monoclonal antibody therapy for postexposure prophylaxis of asymptomatic, recently exposed high-risk AIIRD patients or as treatment for newly symptomatic, high-risk AIIRD patients. The ACR guidance notes that, currently, neither the monoclonal antibodies bamlanivimab and etesevimab (administered together) nor casirivimab and imdevimab (REGEN-COV), are licensed or available under an emergency use authorization given their lack of activity against the Omicron variant, the dominant strain of SARS-CoV-2 circulating in the United States.
Finally, the guidance clarified that the timing of intravenous immunoglobulin doses does not need to be modified around the administration of COVID vaccine doses, based on moderate consensus among task force members.
Vaccine hesitancy in community rheumatology practices
The revised guidelines were released just as Arthritis & Rheumatology published a new study that assessed vaccine hesitancy among rheumatology patients on immunomodulatory therapies. A three-item electronic survey was conducted at 101 offices within a community practice–based rheumatology research network and ultimately collected responses from 58,529 patients, 20,987 of whom had an AIIRD and were receiving targeted therapies like biologics or Janus kinase inhibitors.
Of the total respondents, 77% (n = 43,675) had been vaccinated, 16.9% were not vaccinated and did not plan to be, and 6.1% were not vaccinated but planned to be. However, AIIRD patients were 16% less likely to be vaccinated, compared with the other patients, such as those with osteoarthritis or osteoporosis who were not receiving disease-modifying antirheumatic drugs (76.9% vs. 87%; odds ratio, 0.84; 95% confidence interval, 0.77-0.92; P < .001). Multivariable analysis also found that older patients (OR, 1.49 per 10 years) and Asians (OR, 2.42; 95% CI, 1.77-3.33) were more likely to be vaccinated.
“Rheumatologists need to be asking their patients more than just: ‘Are you vaccinated?’ ” Jeffrey Curtis, MD, MPH, head of the ACR COVID-19 vaccine task force and a coauthor of the vaccine hesitancy study, said in an interview. “A year ago, that was a fine approach, but now they need to be asking whether you’ve been vaccinated, and with what, and how many times, and how recently. There are a whole lot of subtleties there; ‘vaccinated: yes or no’ is just the tip of the iceberg.”
His research into the vaccine hesitant includes recent anecdotal data from thousands of patients treated in local rheumatology community practices, many of whom cited long-term safety data and potential side effects as reasons why they were unwilling to get vaccinated. But despite their on-paper responses, he cautioned rheumatologists to think critically when determining which patients may truly be open to vaccination.
“If you’re designing strategies to affect vaccine hesitancy, you may be wasting your time with some people,” said Dr. Curtis, professor of medicine at the University of Alabama at Birmingham. “A critical need is to figure out who are the patients who may be amendable to more information or an intervention or a little bit more time and care, and who are the people where you know, this is a lost cause: You don’t get a flu shot, you haven’t been vaccinated for shingles, [and] you’re not going to get this one either.
“In terms of a research agenda, how do we develop efficient, simple, short screening tools?” he added. “Something with a few helpful questions, on a patient portal or an iPad, that will do a good job identifying your patients at risk who haven’t had vaccination but that you might be able to spend time with, intervene, and actually change their mind. If you spend gobs of time with everyone, you’ll help some people, but clinicians don’t have an infinite amount of time.”
One of the authors of the vaccine hesitancy study acknowledged being employed by the rheumatology research network that hosted the survey. Several others, including Dr. Curtis, reported receiving grants and consulting fees from various pharmaceutical companies.
As rheumatologists contend with vaccine hesitancy among certain subsets of patients, the American College of Rheumatology has released updated clinical guidelines on COVID-19 vaccination for patients with rheumatic and musculoskeletal diseases (RMDs), including new recommendations on supplemental and booster doses.
The revised guidance from this fifth version of the ACR guidelines includes strongly recommending that all RMD patients receive a booster after their primary vaccine series, regardless of whether they have been naturally infected with COVID-19. In addition, they strongly recommend third supplemental doses for patients with autoimmune inflammatory rheumatic diseases (AIIRDs) who likely mounted an inadequate vaccine response, which would then be followed by a fourth booster dose as advised by the Centers for Disease Control and Prevention for immunocompromised individuals.
Other recommendations include pre-exposure prophylaxis monoclonal antibody treatment for high-risk AIIRD patients, defined as those with moderate to severely compromised immune systems who may not mount an adequate immune response to COVID-19 vaccination, when it is available and authorized for emergency use by the Food and Drug Administration, as well as monoclonal antibody therapy for postexposure prophylaxis of asymptomatic, recently exposed high-risk AIIRD patients or as treatment for newly symptomatic, high-risk AIIRD patients. The ACR guidance notes that, currently, neither the monoclonal antibodies bamlanivimab and etesevimab (administered together) nor casirivimab and imdevimab (REGEN-COV), are licensed or available under an emergency use authorization given their lack of activity against the Omicron variant, the dominant strain of SARS-CoV-2 circulating in the United States.
Finally, the guidance clarified that the timing of intravenous immunoglobulin doses does not need to be modified around the administration of COVID vaccine doses, based on moderate consensus among task force members.
Vaccine hesitancy in community rheumatology practices
The revised guidelines were released just as Arthritis & Rheumatology published a new study that assessed vaccine hesitancy among rheumatology patients on immunomodulatory therapies. A three-item electronic survey was conducted at 101 offices within a community practice–based rheumatology research network and ultimately collected responses from 58,529 patients, 20,987 of whom had an AIIRD and were receiving targeted therapies like biologics or Janus kinase inhibitors.
Of the total respondents, 77% (n = 43,675) had been vaccinated, 16.9% were not vaccinated and did not plan to be, and 6.1% were not vaccinated but planned to be. However, AIIRD patients were 16% less likely to be vaccinated, compared with the other patients, such as those with osteoarthritis or osteoporosis who were not receiving disease-modifying antirheumatic drugs (76.9% vs. 87%; odds ratio, 0.84; 95% confidence interval, 0.77-0.92; P < .001). Multivariable analysis also found that older patients (OR, 1.49 per 10 years) and Asians (OR, 2.42; 95% CI, 1.77-3.33) were more likely to be vaccinated.
“Rheumatologists need to be asking their patients more than just: ‘Are you vaccinated?’ ” Jeffrey Curtis, MD, MPH, head of the ACR COVID-19 vaccine task force and a coauthor of the vaccine hesitancy study, said in an interview. “A year ago, that was a fine approach, but now they need to be asking whether you’ve been vaccinated, and with what, and how many times, and how recently. There are a whole lot of subtleties there; ‘vaccinated: yes or no’ is just the tip of the iceberg.”
His research into the vaccine hesitant includes recent anecdotal data from thousands of patients treated in local rheumatology community practices, many of whom cited long-term safety data and potential side effects as reasons why they were unwilling to get vaccinated. But despite their on-paper responses, he cautioned rheumatologists to think critically when determining which patients may truly be open to vaccination.
“If you’re designing strategies to affect vaccine hesitancy, you may be wasting your time with some people,” said Dr. Curtis, professor of medicine at the University of Alabama at Birmingham. “A critical need is to figure out who are the patients who may be amendable to more information or an intervention or a little bit more time and care, and who are the people where you know, this is a lost cause: You don’t get a flu shot, you haven’t been vaccinated for shingles, [and] you’re not going to get this one either.
“In terms of a research agenda, how do we develop efficient, simple, short screening tools?” he added. “Something with a few helpful questions, on a patient portal or an iPad, that will do a good job identifying your patients at risk who haven’t had vaccination but that you might be able to spend time with, intervene, and actually change their mind. If you spend gobs of time with everyone, you’ll help some people, but clinicians don’t have an infinite amount of time.”
One of the authors of the vaccine hesitancy study acknowledged being employed by the rheumatology research network that hosted the survey. Several others, including Dr. Curtis, reported receiving grants and consulting fees from various pharmaceutical companies.
FROM ARTHRITIS & RHEUMATOLOGY
Childhood trauma may influence vaccine hesitancy
, data published Feb. 1 suggest.
The findings by Mark A. Bellis, DSc, College of Human Sciences, Bangor (Wales) University, and colleagues were published online in BMJ Open.
The results are especially significant, the authors say, because of the prevalence of adverse childhood experiences (ACEs) globally, with proportions of people having multiple traumas in some countries at 10% or more of the population.
The authors wrote that hesitancy or refusal to get the vaccine increased with the number of traumas reported.
For example, hesitancy was three times higher among people who had experienced four or more types of childhood trauma than among those who did not report any traumatic events.
Dr. Bellis told this news organization that though their work suggests that higher levels of ACEs are linked with higher vaccine hesitancy, it is by no means the only reason people choose not to get vaccinated.
However, he said, the association they found may have key messages for clinicians.
“For clinicians, simply being trauma informed can help,” Dr. Bellis said. “Understanding how such childhood adversity can affect people may help them when discussing vaccines, and in understanding resistance to what is a complex medical issue and one that requires considerable trust. What can appear routine to a clinician may be a difficult leap of faith especially for those who have poorer experiences of trusting even within family settings.”
More trauma, less trust
The authors used responses to a nationally representative telephone survey of adults in Wales taken between December 2020 and March 2021, when COVID-19 restrictions were in force. Out of 6,763 people contacted, 2,285 met all criteria and answered all the questions and were included in the final analysis.
The survey asked about nine types of ACEs before the age of 18, including: parental separation; physical, verbal, and sexual abuse; exposure to domestic violence; and living with a household member who has mental illness, misuses alcohol and/or drugs, or who was incarcerated.
It also included personal details and long-term health information.
About half of the respondents said they hadn’t experienced any childhood trauma. Of those who did, one in five said they had experienced one type, 17% reported two to three types, and 10% reported four or more.
According to the authors, prevalence of ACEs reported was consistent with other comparable population surveys, including those conducted face to face.
They also investigated measures of trust and preference for different health regulations.
People with more ACEs were more likely to have low trust in National Health Service COVID-19 information.
“Other sociodemographics and a history of either chronic disease or COVID-19 infection were not significantly associated with low trust,” the authors pointed out.
People reporting higher ACEs also were more likely to report that they felt they were unfairly restricted by the government. People with four or more ACEs were twice as likely than were those with no ACEs to say they felt unfairly restricted and wanted rules such as mandatory masking to stop.
People with four or more types of trauma were almost twice as likely to ignore the restrictions as were those who hadn’t experienced any – 38% versus 21% – to ignore the restrictions, even after the researchers accounted for associations with sociodemographic factors and previous COVID-19 infection or a history of long-term conditions.
“Clinicians can be a powerful voice to counter more alarmist or even conspiratorial messages that might otherwise resonate with those who find trust difficult,” Dr. Bellis said.
He said that the effect of childhood adversity needs to be considered at all levels in health systems. Overarching public health strategists should include ways to earn trust to counter resistance in some of the most vulnerable communities where ACEs can be higher.
It will also be important in the short-term to “provide reassurance, build community champions, and understand the low base from which trust needs to be built,” he said.
Loss of control
“Past traumatic experiences can predispose someone to avoid things that remind them of that trauma. This avoidance protects them from re-experiencing the negative symptoms and behaviors that come with it. Whether this results into hesitancy of something that would benefit their health is not well known,” Consuelo Cagande, MD, senior associate program director and fellowship adviser in the department of child and adolescent psychiatry and behavioral sciences, Children’s Hospital of Philadelphia, told this news organization.
She pointed out a limitation the authors mention that is common when using ACEs as a measure linking to future negative behaviors – that people self-report them and may misremember or misreport them.
Another limitation is the potential for self-selection bias, as participation level was 36.4%, though the authors noted that is not unusual for unsolicited telephone surveys.
Dr. Cagande said that fearing loss of control may be another factor at play in having to follow restrictions, such as quarantining and masking, social distancing, or mandated vaccinations.
She said it’s important to understand a person’s reason for hesitancy to vaccines and work with the person with the help of the community, to help them trust and feel safe.
Young adults of particular concern
The 18- to 29-year-old age group is of particular concern, Dr. Bellis said.
The researchers estimated the likely rates of vaccine hesitancy according to childhood trauma and age, and the numbers ranged from around 3.5% among those aged 70 and older with no experience of childhood adversity to 38% among 18- to 29-year-olds who had experienced four or more types of childhood trauma.
“Childhood adversity can be an especially raw issue in this group,” he explained. “Some have already been obliged to sacrifice substantial proportions of their teenage lives and some will have suffered greater exposure to adverse childhood experiences as a result of being isolated during the pandemic, sometimes in difficult home environments. Our results suggest that this age group and especially those with high levels of ACEs are some of the most likely to be vaccine hesitant.”
This work was supported by Public Health Wales. The study authors and Dr. Cagande reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, data published Feb. 1 suggest.
The findings by Mark A. Bellis, DSc, College of Human Sciences, Bangor (Wales) University, and colleagues were published online in BMJ Open.
The results are especially significant, the authors say, because of the prevalence of adverse childhood experiences (ACEs) globally, with proportions of people having multiple traumas in some countries at 10% or more of the population.
The authors wrote that hesitancy or refusal to get the vaccine increased with the number of traumas reported.
For example, hesitancy was three times higher among people who had experienced four or more types of childhood trauma than among those who did not report any traumatic events.
Dr. Bellis told this news organization that though their work suggests that higher levels of ACEs are linked with higher vaccine hesitancy, it is by no means the only reason people choose not to get vaccinated.
However, he said, the association they found may have key messages for clinicians.
“For clinicians, simply being trauma informed can help,” Dr. Bellis said. “Understanding how such childhood adversity can affect people may help them when discussing vaccines, and in understanding resistance to what is a complex medical issue and one that requires considerable trust. What can appear routine to a clinician may be a difficult leap of faith especially for those who have poorer experiences of trusting even within family settings.”
More trauma, less trust
The authors used responses to a nationally representative telephone survey of adults in Wales taken between December 2020 and March 2021, when COVID-19 restrictions were in force. Out of 6,763 people contacted, 2,285 met all criteria and answered all the questions and were included in the final analysis.
The survey asked about nine types of ACEs before the age of 18, including: parental separation; physical, verbal, and sexual abuse; exposure to domestic violence; and living with a household member who has mental illness, misuses alcohol and/or drugs, or who was incarcerated.
It also included personal details and long-term health information.
About half of the respondents said they hadn’t experienced any childhood trauma. Of those who did, one in five said they had experienced one type, 17% reported two to three types, and 10% reported four or more.
According to the authors, prevalence of ACEs reported was consistent with other comparable population surveys, including those conducted face to face.
They also investigated measures of trust and preference for different health regulations.
People with more ACEs were more likely to have low trust in National Health Service COVID-19 information.
“Other sociodemographics and a history of either chronic disease or COVID-19 infection were not significantly associated with low trust,” the authors pointed out.
People reporting higher ACEs also were more likely to report that they felt they were unfairly restricted by the government. People with four or more ACEs were twice as likely than were those with no ACEs to say they felt unfairly restricted and wanted rules such as mandatory masking to stop.
People with four or more types of trauma were almost twice as likely to ignore the restrictions as were those who hadn’t experienced any – 38% versus 21% – to ignore the restrictions, even after the researchers accounted for associations with sociodemographic factors and previous COVID-19 infection or a history of long-term conditions.
“Clinicians can be a powerful voice to counter more alarmist or even conspiratorial messages that might otherwise resonate with those who find trust difficult,” Dr. Bellis said.
He said that the effect of childhood adversity needs to be considered at all levels in health systems. Overarching public health strategists should include ways to earn trust to counter resistance in some of the most vulnerable communities where ACEs can be higher.
It will also be important in the short-term to “provide reassurance, build community champions, and understand the low base from which trust needs to be built,” he said.
Loss of control
“Past traumatic experiences can predispose someone to avoid things that remind them of that trauma. This avoidance protects them from re-experiencing the negative symptoms and behaviors that come with it. Whether this results into hesitancy of something that would benefit their health is not well known,” Consuelo Cagande, MD, senior associate program director and fellowship adviser in the department of child and adolescent psychiatry and behavioral sciences, Children’s Hospital of Philadelphia, told this news organization.
She pointed out a limitation the authors mention that is common when using ACEs as a measure linking to future negative behaviors – that people self-report them and may misremember or misreport them.
Another limitation is the potential for self-selection bias, as participation level was 36.4%, though the authors noted that is not unusual for unsolicited telephone surveys.
Dr. Cagande said that fearing loss of control may be another factor at play in having to follow restrictions, such as quarantining and masking, social distancing, or mandated vaccinations.
She said it’s important to understand a person’s reason for hesitancy to vaccines and work with the person with the help of the community, to help them trust and feel safe.
Young adults of particular concern
The 18- to 29-year-old age group is of particular concern, Dr. Bellis said.
The researchers estimated the likely rates of vaccine hesitancy according to childhood trauma and age, and the numbers ranged from around 3.5% among those aged 70 and older with no experience of childhood adversity to 38% among 18- to 29-year-olds who had experienced four or more types of childhood trauma.
“Childhood adversity can be an especially raw issue in this group,” he explained. “Some have already been obliged to sacrifice substantial proportions of their teenage lives and some will have suffered greater exposure to adverse childhood experiences as a result of being isolated during the pandemic, sometimes in difficult home environments. Our results suggest that this age group and especially those with high levels of ACEs are some of the most likely to be vaccine hesitant.”
This work was supported by Public Health Wales. The study authors and Dr. Cagande reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, data published Feb. 1 suggest.
The findings by Mark A. Bellis, DSc, College of Human Sciences, Bangor (Wales) University, and colleagues were published online in BMJ Open.
The results are especially significant, the authors say, because of the prevalence of adverse childhood experiences (ACEs) globally, with proportions of people having multiple traumas in some countries at 10% or more of the population.
The authors wrote that hesitancy or refusal to get the vaccine increased with the number of traumas reported.
For example, hesitancy was three times higher among people who had experienced four or more types of childhood trauma than among those who did not report any traumatic events.
Dr. Bellis told this news organization that though their work suggests that higher levels of ACEs are linked with higher vaccine hesitancy, it is by no means the only reason people choose not to get vaccinated.
However, he said, the association they found may have key messages for clinicians.
“For clinicians, simply being trauma informed can help,” Dr. Bellis said. “Understanding how such childhood adversity can affect people may help them when discussing vaccines, and in understanding resistance to what is a complex medical issue and one that requires considerable trust. What can appear routine to a clinician may be a difficult leap of faith especially for those who have poorer experiences of trusting even within family settings.”
More trauma, less trust
The authors used responses to a nationally representative telephone survey of adults in Wales taken between December 2020 and March 2021, when COVID-19 restrictions were in force. Out of 6,763 people contacted, 2,285 met all criteria and answered all the questions and were included in the final analysis.
The survey asked about nine types of ACEs before the age of 18, including: parental separation; physical, verbal, and sexual abuse; exposure to domestic violence; and living with a household member who has mental illness, misuses alcohol and/or drugs, or who was incarcerated.
It also included personal details and long-term health information.
About half of the respondents said they hadn’t experienced any childhood trauma. Of those who did, one in five said they had experienced one type, 17% reported two to three types, and 10% reported four or more.
According to the authors, prevalence of ACEs reported was consistent with other comparable population surveys, including those conducted face to face.
They also investigated measures of trust and preference for different health regulations.
People with more ACEs were more likely to have low trust in National Health Service COVID-19 information.
“Other sociodemographics and a history of either chronic disease or COVID-19 infection were not significantly associated with low trust,” the authors pointed out.
People reporting higher ACEs also were more likely to report that they felt they were unfairly restricted by the government. People with four or more ACEs were twice as likely than were those with no ACEs to say they felt unfairly restricted and wanted rules such as mandatory masking to stop.
People with four or more types of trauma were almost twice as likely to ignore the restrictions as were those who hadn’t experienced any – 38% versus 21% – to ignore the restrictions, even after the researchers accounted for associations with sociodemographic factors and previous COVID-19 infection or a history of long-term conditions.
“Clinicians can be a powerful voice to counter more alarmist or even conspiratorial messages that might otherwise resonate with those who find trust difficult,” Dr. Bellis said.
He said that the effect of childhood adversity needs to be considered at all levels in health systems. Overarching public health strategists should include ways to earn trust to counter resistance in some of the most vulnerable communities where ACEs can be higher.
It will also be important in the short-term to “provide reassurance, build community champions, and understand the low base from which trust needs to be built,” he said.
Loss of control
“Past traumatic experiences can predispose someone to avoid things that remind them of that trauma. This avoidance protects them from re-experiencing the negative symptoms and behaviors that come with it. Whether this results into hesitancy of something that would benefit their health is not well known,” Consuelo Cagande, MD, senior associate program director and fellowship adviser in the department of child and adolescent psychiatry and behavioral sciences, Children’s Hospital of Philadelphia, told this news organization.
She pointed out a limitation the authors mention that is common when using ACEs as a measure linking to future negative behaviors – that people self-report them and may misremember or misreport them.
Another limitation is the potential for self-selection bias, as participation level was 36.4%, though the authors noted that is not unusual for unsolicited telephone surveys.
Dr. Cagande said that fearing loss of control may be another factor at play in having to follow restrictions, such as quarantining and masking, social distancing, or mandated vaccinations.
She said it’s important to understand a person’s reason for hesitancy to vaccines and work with the person with the help of the community, to help them trust and feel safe.
Young adults of particular concern
The 18- to 29-year-old age group is of particular concern, Dr. Bellis said.
The researchers estimated the likely rates of vaccine hesitancy according to childhood trauma and age, and the numbers ranged from around 3.5% among those aged 70 and older with no experience of childhood adversity to 38% among 18- to 29-year-olds who had experienced four or more types of childhood trauma.
“Childhood adversity can be an especially raw issue in this group,” he explained. “Some have already been obliged to sacrifice substantial proportions of their teenage lives and some will have suffered greater exposure to adverse childhood experiences as a result of being isolated during the pandemic, sometimes in difficult home environments. Our results suggest that this age group and especially those with high levels of ACEs are some of the most likely to be vaccine hesitant.”
This work was supported by Public Health Wales. The study authors and Dr. Cagande reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM BMJ OPEN
CDC issues new pneumococcal vaccine recommendations for adults
The recommendations, voted on by the CDC’s Advisory Committee on Immunization Practices (ACIP) in October and made final in January with publication in the agency’s Morbidity and Mortality Weekly Report (MMWR), call for use of the 15-valent pneumococcal conjugate vaccine (PCV15; Vaxneuvance, Merck Sharp & Dohme) or 20-valent PCV (PREVNAR20; Wyeth Pharmaceuticals).
The recommendations apply to PCV-naive adults in the United States who are either aged 65 years or older, or who are aged 19-64 years and have underlying conditions such as diabetes, chronic heart or liver disease, or HIV, and have not previously received a PCV or whose previous vaccination history is unknown.
If the PCV15 vaccine is used, a subsequent dose of the 23-valent pneumococcal polysaccharide vaccine (PPSV23; Pneumovax23, Merck Sharp & Dohme) should be provided, typically at least 1 year later, under the recommendations.
As reported by this news organization, PCV15 and PREVNAR20 received approval from the Food and Drug Administration last July.
Those approvals provided an impetus for the revised recommendations, “offer[ing] an opportunity to review the existing recommendations and available data,” Miwako Kobayashi, MD, first author of the MMWR report and a medical epidemiologist with the National Center for Immunization and Respiratory Diseases, CDC, in Atlanta, said in an interview.
“As part of that process, ACIP strived to simplify the recommendations,” she said.
The previous recommendations called for the PCV13 vaccine and the PPSV23 and had varying conditions (depending on certain age and risk groups) that added complexity to the process. Under the new approach, the same recommendation applies regardless of specific medical conditions or other risk factors.
“With the simplified recommendation for adults 19 through 64, we expect coverage may increase among this population,” Dr. Kobayashi said.
Compared with the PCV13 vaccine, PREVNAR20 protects against seven additional serotypes involved in cases of invasive pneumococcal disease (IPD) and pneumonia, which are responsible for up to 40% of all cases of pneumococcal disease and related deaths in the United States.
While the PREVNAR20 includes five more pneumococcal serotypes than PCV15, the
CDC does not recommend one over the other, Dr. Kobayashi noted.
More than 90% of cases of adult IPD involve older adults and adults with chronic medical conditions or immunocompromising conditions, cerebrospinal fluid leaks, or cochlear implants, the MMWR report notes.
Commenting on the recommendations, Amit A. Shah, MD, a geriatrician with the Mayo Clinic in Phoenix, Ariz., underscored the need for clinicians to be proactive in recommending the vaccines to those patients.
“Despite only needing one vaccine dose after turning 65 to be considered vaccinated, only about 70% of people in this group have received any pneumococcal vaccination,” he said in an interview. “This percentage has not increased much over the past several years.”
The new approach should help change that, he said.
“These new recommendations are a significant simplification from the prior confusing and challenging-to-implement recommendations from 2019,” Dr. Shah explained.
Among the 2019 recommendations was a stipulation for “shared decision-making” with PCV13, and a conversation that often only complicated matters, he noted.
“Patients and providers alike had confusion about this since it was not a clear-cut ‘yes, give it’ or ‘no, do not give it any longer’ recommendation.”
“Now that this new recommendation will require no extra time for a discussion in the clinic, and just a simple ‘it’s time for your pneumonia shot’ offer, this may become more feasible,” Dr. Shah added. “In addition, removal of the shared decision-making stipulation allows for this immunization to be easily protocolized in the clinic, similar to automatic offers to the flu vaccine for patients each year.”
According to the CDC, pneumococcal pneumonia causes an estimated 150,000 hospitalizations each year in the United States, while pneumococcal meningitis and bacteremia killed approximately 3,250 people in the United States in 2019.
“Clinicians are patients’ most trusted resource when it comes to vaccine recommendations,” Dr. Kobayashi said. “We encourage all clinicians to recommend pneumococcal vaccines when indicated.”
Dr. Kobayashi and Dr. Shah have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The recommendations, voted on by the CDC’s Advisory Committee on Immunization Practices (ACIP) in October and made final in January with publication in the agency’s Morbidity and Mortality Weekly Report (MMWR), call for use of the 15-valent pneumococcal conjugate vaccine (PCV15; Vaxneuvance, Merck Sharp & Dohme) or 20-valent PCV (PREVNAR20; Wyeth Pharmaceuticals).
The recommendations apply to PCV-naive adults in the United States who are either aged 65 years or older, or who are aged 19-64 years and have underlying conditions such as diabetes, chronic heart or liver disease, or HIV, and have not previously received a PCV or whose previous vaccination history is unknown.
If the PCV15 vaccine is used, a subsequent dose of the 23-valent pneumococcal polysaccharide vaccine (PPSV23; Pneumovax23, Merck Sharp & Dohme) should be provided, typically at least 1 year later, under the recommendations.
As reported by this news organization, PCV15 and PREVNAR20 received approval from the Food and Drug Administration last July.
Those approvals provided an impetus for the revised recommendations, “offer[ing] an opportunity to review the existing recommendations and available data,” Miwako Kobayashi, MD, first author of the MMWR report and a medical epidemiologist with the National Center for Immunization and Respiratory Diseases, CDC, in Atlanta, said in an interview.
“As part of that process, ACIP strived to simplify the recommendations,” she said.
The previous recommendations called for the PCV13 vaccine and the PPSV23 and had varying conditions (depending on certain age and risk groups) that added complexity to the process. Under the new approach, the same recommendation applies regardless of specific medical conditions or other risk factors.
“With the simplified recommendation for adults 19 through 64, we expect coverage may increase among this population,” Dr. Kobayashi said.
Compared with the PCV13 vaccine, PREVNAR20 protects against seven additional serotypes involved in cases of invasive pneumococcal disease (IPD) and pneumonia, which are responsible for up to 40% of all cases of pneumococcal disease and related deaths in the United States.
While the PREVNAR20 includes five more pneumococcal serotypes than PCV15, the
CDC does not recommend one over the other, Dr. Kobayashi noted.
More than 90% of cases of adult IPD involve older adults and adults with chronic medical conditions or immunocompromising conditions, cerebrospinal fluid leaks, or cochlear implants, the MMWR report notes.
Commenting on the recommendations, Amit A. Shah, MD, a geriatrician with the Mayo Clinic in Phoenix, Ariz., underscored the need for clinicians to be proactive in recommending the vaccines to those patients.
“Despite only needing one vaccine dose after turning 65 to be considered vaccinated, only about 70% of people in this group have received any pneumococcal vaccination,” he said in an interview. “This percentage has not increased much over the past several years.”
The new approach should help change that, he said.
“These new recommendations are a significant simplification from the prior confusing and challenging-to-implement recommendations from 2019,” Dr. Shah explained.
Among the 2019 recommendations was a stipulation for “shared decision-making” with PCV13, and a conversation that often only complicated matters, he noted.
“Patients and providers alike had confusion about this since it was not a clear-cut ‘yes, give it’ or ‘no, do not give it any longer’ recommendation.”
“Now that this new recommendation will require no extra time for a discussion in the clinic, and just a simple ‘it’s time for your pneumonia shot’ offer, this may become more feasible,” Dr. Shah added. “In addition, removal of the shared decision-making stipulation allows for this immunization to be easily protocolized in the clinic, similar to automatic offers to the flu vaccine for patients each year.”
According to the CDC, pneumococcal pneumonia causes an estimated 150,000 hospitalizations each year in the United States, while pneumococcal meningitis and bacteremia killed approximately 3,250 people in the United States in 2019.
“Clinicians are patients’ most trusted resource when it comes to vaccine recommendations,” Dr. Kobayashi said. “We encourage all clinicians to recommend pneumococcal vaccines when indicated.”
Dr. Kobayashi and Dr. Shah have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The recommendations, voted on by the CDC’s Advisory Committee on Immunization Practices (ACIP) in October and made final in January with publication in the agency’s Morbidity and Mortality Weekly Report (MMWR), call for use of the 15-valent pneumococcal conjugate vaccine (PCV15; Vaxneuvance, Merck Sharp & Dohme) or 20-valent PCV (PREVNAR20; Wyeth Pharmaceuticals).
The recommendations apply to PCV-naive adults in the United States who are either aged 65 years or older, or who are aged 19-64 years and have underlying conditions such as diabetes, chronic heart or liver disease, or HIV, and have not previously received a PCV or whose previous vaccination history is unknown.
If the PCV15 vaccine is used, a subsequent dose of the 23-valent pneumococcal polysaccharide vaccine (PPSV23; Pneumovax23, Merck Sharp & Dohme) should be provided, typically at least 1 year later, under the recommendations.
As reported by this news organization, PCV15 and PREVNAR20 received approval from the Food and Drug Administration last July.
Those approvals provided an impetus for the revised recommendations, “offer[ing] an opportunity to review the existing recommendations and available data,” Miwako Kobayashi, MD, first author of the MMWR report and a medical epidemiologist with the National Center for Immunization and Respiratory Diseases, CDC, in Atlanta, said in an interview.
“As part of that process, ACIP strived to simplify the recommendations,” she said.
The previous recommendations called for the PCV13 vaccine and the PPSV23 and had varying conditions (depending on certain age and risk groups) that added complexity to the process. Under the new approach, the same recommendation applies regardless of specific medical conditions or other risk factors.
“With the simplified recommendation for adults 19 through 64, we expect coverage may increase among this population,” Dr. Kobayashi said.
Compared with the PCV13 vaccine, PREVNAR20 protects against seven additional serotypes involved in cases of invasive pneumococcal disease (IPD) and pneumonia, which are responsible for up to 40% of all cases of pneumococcal disease and related deaths in the United States.
While the PREVNAR20 includes five more pneumococcal serotypes than PCV15, the
CDC does not recommend one over the other, Dr. Kobayashi noted.
More than 90% of cases of adult IPD involve older adults and adults with chronic medical conditions or immunocompromising conditions, cerebrospinal fluid leaks, or cochlear implants, the MMWR report notes.
Commenting on the recommendations, Amit A. Shah, MD, a geriatrician with the Mayo Clinic in Phoenix, Ariz., underscored the need for clinicians to be proactive in recommending the vaccines to those patients.
“Despite only needing one vaccine dose after turning 65 to be considered vaccinated, only about 70% of people in this group have received any pneumococcal vaccination,” he said in an interview. “This percentage has not increased much over the past several years.”
The new approach should help change that, he said.
“These new recommendations are a significant simplification from the prior confusing and challenging-to-implement recommendations from 2019,” Dr. Shah explained.
Among the 2019 recommendations was a stipulation for “shared decision-making” with PCV13, and a conversation that often only complicated matters, he noted.
“Patients and providers alike had confusion about this since it was not a clear-cut ‘yes, give it’ or ‘no, do not give it any longer’ recommendation.”
“Now that this new recommendation will require no extra time for a discussion in the clinic, and just a simple ‘it’s time for your pneumonia shot’ offer, this may become more feasible,” Dr. Shah added. “In addition, removal of the shared decision-making stipulation allows for this immunization to be easily protocolized in the clinic, similar to automatic offers to the flu vaccine for patients each year.”
According to the CDC, pneumococcal pneumonia causes an estimated 150,000 hospitalizations each year in the United States, while pneumococcal meningitis and bacteremia killed approximately 3,250 people in the United States in 2019.
“Clinicians are patients’ most trusted resource when it comes to vaccine recommendations,” Dr. Kobayashi said. “We encourage all clinicians to recommend pneumococcal vaccines when indicated.”
Dr. Kobayashi and Dr. Shah have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE MMWR
Moderna launches clinical trials for HIV vaccine
Human clinical trials have started for an experimental HIV vaccine that uses the same kind of mRNA technology found in Moderna’s successful COVID-19 vaccine, the drug company has announced.
The first vaccinations were given Jan. 27 at George Washington University School of Medicine and Health Sciences, Washington, the company said in a news release. Phase I trials will also be run at the Hope Clinic of Emory Vaccine Center, Atlanta, the Fred Hutchinson Cancer Research Center, Seattle, and the University of Texas Health Science Center, San Antonio.
The vaccine is designed to prompt white blood cells to turn into antibodies that can neutralize HIV, ABC News reported. A booster shot to work with the HIV vaccine is also being studied.
For 4 decades, the human immunodeficiency virus has managed to dodge the immune system’s attempts to destroy it. Scientists have not been able to develop a vaccine, though they have made advancements in treatments, such as long-acting injectables for pre- and post-exposure prevention and treatment. HIV can lead to AIDS, which can be fatal.
The release said 56 healthy HIV-negative adults are taking part in the clinical trial, with 48 getting one or two doses of the mRNA vaccine and 32 also getting the booster. Eight people will just get the booster. All of them will be monitored for up to 6 months after receiving a final dose.
The immunogens – antigens that elicit an immune response – that are being tested were developed by the International AIDS Vaccine Initiative (IAVI) and Scripps Research. They will be delivered using the same messenger RNA (mRNA) technology in Moderna’s successful COVID-19 vaccine, the news release said.
About 1.2 million people in the United States had HIV at the end of 2019, according to the CDC, with more than 36,000 people being diagnosed in 2019.
The World Health Organization says 37.7 million people in the world had HIV in 2020.
“We are tremendously excited to be advancing this new direction in HIV vaccine design with Moderna’s mRNA platform,” Mark Feinberg, MD, president and CEO of IAVI, said in the news release. “The search for an HIV vaccine has been long and challenging, and having new tools in terms of immunogens and platforms could be the key to making rapid progress toward an urgently needed, effective HIV vaccine.”
A version of this article first appeared on WebMD.com.
Human clinical trials have started for an experimental HIV vaccine that uses the same kind of mRNA technology found in Moderna’s successful COVID-19 vaccine, the drug company has announced.
The first vaccinations were given Jan. 27 at George Washington University School of Medicine and Health Sciences, Washington, the company said in a news release. Phase I trials will also be run at the Hope Clinic of Emory Vaccine Center, Atlanta, the Fred Hutchinson Cancer Research Center, Seattle, and the University of Texas Health Science Center, San Antonio.
The vaccine is designed to prompt white blood cells to turn into antibodies that can neutralize HIV, ABC News reported. A booster shot to work with the HIV vaccine is also being studied.
For 4 decades, the human immunodeficiency virus has managed to dodge the immune system’s attempts to destroy it. Scientists have not been able to develop a vaccine, though they have made advancements in treatments, such as long-acting injectables for pre- and post-exposure prevention and treatment. HIV can lead to AIDS, which can be fatal.
The release said 56 healthy HIV-negative adults are taking part in the clinical trial, with 48 getting one or two doses of the mRNA vaccine and 32 also getting the booster. Eight people will just get the booster. All of them will be monitored for up to 6 months after receiving a final dose.
The immunogens – antigens that elicit an immune response – that are being tested were developed by the International AIDS Vaccine Initiative (IAVI) and Scripps Research. They will be delivered using the same messenger RNA (mRNA) technology in Moderna’s successful COVID-19 vaccine, the news release said.
About 1.2 million people in the United States had HIV at the end of 2019, according to the CDC, with more than 36,000 people being diagnosed in 2019.
The World Health Organization says 37.7 million people in the world had HIV in 2020.
“We are tremendously excited to be advancing this new direction in HIV vaccine design with Moderna’s mRNA platform,” Mark Feinberg, MD, president and CEO of IAVI, said in the news release. “The search for an HIV vaccine has been long and challenging, and having new tools in terms of immunogens and platforms could be the key to making rapid progress toward an urgently needed, effective HIV vaccine.”
A version of this article first appeared on WebMD.com.
Human clinical trials have started for an experimental HIV vaccine that uses the same kind of mRNA technology found in Moderna’s successful COVID-19 vaccine, the drug company has announced.
The first vaccinations were given Jan. 27 at George Washington University School of Medicine and Health Sciences, Washington, the company said in a news release. Phase I trials will also be run at the Hope Clinic of Emory Vaccine Center, Atlanta, the Fred Hutchinson Cancer Research Center, Seattle, and the University of Texas Health Science Center, San Antonio.
The vaccine is designed to prompt white blood cells to turn into antibodies that can neutralize HIV, ABC News reported. A booster shot to work with the HIV vaccine is also being studied.
For 4 decades, the human immunodeficiency virus has managed to dodge the immune system’s attempts to destroy it. Scientists have not been able to develop a vaccine, though they have made advancements in treatments, such as long-acting injectables for pre- and post-exposure prevention and treatment. HIV can lead to AIDS, which can be fatal.
The release said 56 healthy HIV-negative adults are taking part in the clinical trial, with 48 getting one or two doses of the mRNA vaccine and 32 also getting the booster. Eight people will just get the booster. All of them will be monitored for up to 6 months after receiving a final dose.
The immunogens – antigens that elicit an immune response – that are being tested were developed by the International AIDS Vaccine Initiative (IAVI) and Scripps Research. They will be delivered using the same messenger RNA (mRNA) technology in Moderna’s successful COVID-19 vaccine, the news release said.
About 1.2 million people in the United States had HIV at the end of 2019, according to the CDC, with more than 36,000 people being diagnosed in 2019.
The World Health Organization says 37.7 million people in the world had HIV in 2020.
“We are tremendously excited to be advancing this new direction in HIV vaccine design with Moderna’s mRNA platform,” Mark Feinberg, MD, president and CEO of IAVI, said in the news release. “The search for an HIV vaccine has been long and challenging, and having new tools in terms of immunogens and platforms could be the key to making rapid progress toward an urgently needed, effective HIV vaccine.”
A version of this article first appeared on WebMD.com.
Immunocompromised patients should receive fourth COVID shot: CDC
The Centers for Disease Control and Prevention contacted pharmacies on Jan. 26 to reinforce the message that people with moderate to severe immune suppression should receive a fourth COVID-19 vaccine, according to Kaiser Health News.
The conference call came a day after the news outlet reported that immunocompromised people were being turned away by pharmacies. White House officials also emphasized on Jan. 26 that immunocompromised people should receive an additional shot.
During the call, the CDC “reiterated the recommendations, running through case examples,” Mitchel Rothholz, RPh, MBA, chief of governance and state affiliates for the American Pharmacists Association, told KHN.
While on the call, Mr. Rothholz asked for a “prepared document” with the CDC’s recommendations “so we can clearly and consistently communicate the message.” The CDC officials on the call said they would create a document but “don’t know how long that will take,” Mr. Rothholz told KHN.
The CDC recommends an additional shot -– or a fourth shot – for those who have weak immune systems, which makes them more at risk for severe COVID-19 and death. About 7 million American adults are considered immunocompromised, KHN reported, which includes people who have certain medical conditions that impair their immune response or who take immune-suppressing drugs because of organ transplants, cancer, or autoimmune diseases.
The CDC first recommended fourth shots for immunocompromised people in October. This month, the CDC shortened the time for booster shots from 6 months to 5 months, and some immunocompromised people who are due for another shot have begun to seek them. The agency has been educating pharmacists and other health providers since then, a CDC spokesperson told KHN.
While patients don’t need to provide proof that they are immunocompromised, according to the CDC, some have been turned away, KHN reported.
To improve communication with the public, large pharmacies could issue news releases and update their websites “explicitly stating that they are offering fourth doses” to immunocompromised people, Ameet Kini, MD, a professor of pathology and laboratory medicine at Loyola University Medical Center in Chicago, told KHN.
Pharmacies should also update their patient portals and provide “clear guidance for their pharmacists,” he said.
A version of this article first appeared on WebMD.com.
The Centers for Disease Control and Prevention contacted pharmacies on Jan. 26 to reinforce the message that people with moderate to severe immune suppression should receive a fourth COVID-19 vaccine, according to Kaiser Health News.
The conference call came a day after the news outlet reported that immunocompromised people were being turned away by pharmacies. White House officials also emphasized on Jan. 26 that immunocompromised people should receive an additional shot.
During the call, the CDC “reiterated the recommendations, running through case examples,” Mitchel Rothholz, RPh, MBA, chief of governance and state affiliates for the American Pharmacists Association, told KHN.
While on the call, Mr. Rothholz asked for a “prepared document” with the CDC’s recommendations “so we can clearly and consistently communicate the message.” The CDC officials on the call said they would create a document but “don’t know how long that will take,” Mr. Rothholz told KHN.
The CDC recommends an additional shot -– or a fourth shot – for those who have weak immune systems, which makes them more at risk for severe COVID-19 and death. About 7 million American adults are considered immunocompromised, KHN reported, which includes people who have certain medical conditions that impair their immune response or who take immune-suppressing drugs because of organ transplants, cancer, or autoimmune diseases.
The CDC first recommended fourth shots for immunocompromised people in October. This month, the CDC shortened the time for booster shots from 6 months to 5 months, and some immunocompromised people who are due for another shot have begun to seek them. The agency has been educating pharmacists and other health providers since then, a CDC spokesperson told KHN.
While patients don’t need to provide proof that they are immunocompromised, according to the CDC, some have been turned away, KHN reported.
To improve communication with the public, large pharmacies could issue news releases and update their websites “explicitly stating that they are offering fourth doses” to immunocompromised people, Ameet Kini, MD, a professor of pathology and laboratory medicine at Loyola University Medical Center in Chicago, told KHN.
Pharmacies should also update their patient portals and provide “clear guidance for their pharmacists,” he said.
A version of this article first appeared on WebMD.com.
The Centers for Disease Control and Prevention contacted pharmacies on Jan. 26 to reinforce the message that people with moderate to severe immune suppression should receive a fourth COVID-19 vaccine, according to Kaiser Health News.
The conference call came a day after the news outlet reported that immunocompromised people were being turned away by pharmacies. White House officials also emphasized on Jan. 26 that immunocompromised people should receive an additional shot.
During the call, the CDC “reiterated the recommendations, running through case examples,” Mitchel Rothholz, RPh, MBA, chief of governance and state affiliates for the American Pharmacists Association, told KHN.
While on the call, Mr. Rothholz asked for a “prepared document” with the CDC’s recommendations “so we can clearly and consistently communicate the message.” The CDC officials on the call said they would create a document but “don’t know how long that will take,” Mr. Rothholz told KHN.
The CDC recommends an additional shot -– or a fourth shot – for those who have weak immune systems, which makes them more at risk for severe COVID-19 and death. About 7 million American adults are considered immunocompromised, KHN reported, which includes people who have certain medical conditions that impair their immune response or who take immune-suppressing drugs because of organ transplants, cancer, or autoimmune diseases.
The CDC first recommended fourth shots for immunocompromised people in October. This month, the CDC shortened the time for booster shots from 6 months to 5 months, and some immunocompromised people who are due for another shot have begun to seek them. The agency has been educating pharmacists and other health providers since then, a CDC spokesperson told KHN.
While patients don’t need to provide proof that they are immunocompromised, according to the CDC, some have been turned away, KHN reported.
To improve communication with the public, large pharmacies could issue news releases and update their websites “explicitly stating that they are offering fourth doses” to immunocompromised people, Ameet Kini, MD, a professor of pathology and laboratory medicine at Loyola University Medical Center in Chicago, told KHN.
Pharmacies should also update their patient portals and provide “clear guidance for their pharmacists,” he said.
A version of this article first appeared on WebMD.com.
Rituximab and COVID-19 vaccines: Studies begin to answer key questions
Rituximab has presented something of a conundrum for patients taking the monoclonal antibody during the COVID-19 pandemic.
Used to manage a variety of autoimmune diseases and cancers, rituximab acts against CD20 proteins expressed on the surface of B cells, causing B-cell depletion. However, it is this B-cell depletion that may put these patients at greater risk of COVID-19 development, progression to more severe disease, and in-hospital mortality. Evidence for this appears to be mixed, with studies showing both that patients using rituximab to manage various diseases are and are not at increased risk for SARS-CoV-2 infection, COVID-19 progression, and mortality.
As COVID-19 vaccine rollouts take place across the world, more questions have been raised about the relationship between B-cell depletion from anti-CD20 therapies and COVID-19 vaccines. Do rituximab and other anti-CD20 therapies affect a patient’s response to COVID-19 vaccines? If this is the case, does the timing of anti-CD20 treatment matter to maximize B-cell levels and improve the vaccine’s effectiveness? And how do COVID-19 vaccine booster doses factor into the equation?
Humoral and cell-mediated responses following COVID-19 vaccination
First, the bad news: The vaccine is unquestionably safe to administer in patients taking rituximab, but one thing that has been well established is that antibody response to COVID-19 vaccination in these individuals does is reduced. This isn’t entirely unprecedented, as previous studies have shown a weakened immune response to pneumococcal polysaccharide and keyhole limpet hemocyanin vaccines among patients taking rituximab.
“Compromised immunogenicity to the SARS-CoV-2 vaccines has been demonstrated in rituximab-treated patients, which is of particular concern given the observation that B-cell–depleting therapies may be associated with worse COVID outcomes,” Robert F. Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at the Hospital for Special Surgery in New York, said in an interview.
For example, in a recent study from the Medical University of Vienna, 29 (39%) of 74 patients receiving rituximab (43% as monotherapy, 57% with conventional-synthetic disease-modifying antirheumatic drugs) who were vaccinated with either the Comirnaty (Pfizer-BioNTech) or Spikevax (Moderna) COVID-19 vaccine achieved seroconversion, compared with 100% of patients in a healthy control group, and all but 1 patient without detectable CD19+ peripheral B cells did not develop anti–SARS-CoV-2 receptor-binding domain antibodies.
“There is an increasing number of studies in this field, and they confirm that patients treated with rituximab and other anti-CD20 agents have severely reduced serological responses to COVID-19 vaccines,” Ingrid Jyssum, MD, of the division of rheumatology and research at Diakonhjemmet Hospital in Oslo, said in an interview.
One silver lining is that patients treated with anti-CD20 therapies appear to have a cell-mediated response following vaccination even if they don’t develop SARS-CoV-2 antibodies. “Studies that also investigate T-cell responses are starting to emerge, and so far, they show that, even if the patients do not have antibodies, they may have T-cell responses,” Dr. Jyssum said.
One study of 24 patients with autoimmune diseases taking rituximab that evaluated humoral and T-cell responses following vaccination with the Comirnaty vaccine found that none had a humoral response to the vaccine, but the T-cell response from that group did not significantly differ from 35 patients receiving other immunosuppressants and 26 patients in a healthy control group. In another study of rituximab- or ocrelizumab-treated patients who received mRNA-based COVID-19 vaccines, 69.4% developed SARS-CoV-2–specific antibodies, compared with a control group, but 96.2% of patients taking ocrelizumab and 81.8% of patients taking rituximab mounted a spike-specific CD8+ T-cell response, compared with 66.7% in the control group, and there were comparable rates (85%-90%) of spike-specific CD4+ T cells in all groups. In the study from the Medical University of Vienna, T-cell response was detected in rituximab-treated patients who both did and did not mount an antibody response.
The clinical relevance of how a blunted humoral immune response but a respectable T-cell response to COVID-19 vaccines affects patients treated with anti-CD20 therapies isn’t currently known, Dr. Jyssum said.
While these data are reassuring, they’re also incomplete, Dr. Spiera noted. “The ultimate outcome of relevance to assess vaccine efficacy is protection from COVID and from severe outcomes of COVID infection (i.e., hospitalization, mechanical ventilation, death). That data will require assessment of very large numbers of rituximab-treated vaccinated patients to be compared with rituximab-treated unvaccinated patients, and is unlikely to be forthcoming in the very near future.
“In the meantime, however, achieving serologic positivity, meaning having evidence of serologic as well as cellular immunity following vaccination, is a desired outcome, and likely implies more robust immunity.”
Does treatment timing impact COVID-19 vaccine response?
Given enough time, B-cell reconstitution will occur in patients taking rituximab. With that in mind, is it beneficial to wait a certain amount of time after a patient has stopped rituximab therapy or time since their last dose before giving them a COVID-19 vaccine? In their guidance on COVID-19 vaccines for patients with rheumatic and musculoskeletal diseases, the American College of Rheumatology said there is moderate evidence to consider “optimal timing of dosing and vaccination with the rheumatology provider before proceeding.”
“Guidelines and preliminary studies of serologic response to COVID vaccine in rituximab-treated patients have suggested that longer time from last rituximab exposure is associated with a greater likelihood of a serologic response,” Dr. Spiera said.
In a brief report published in Arthritis & Rheumatology, Dr. Spiera and colleagues performed a retrospective chart review of 56 patients with varying levels of last exposure to rituximab who received a COVID-19 vaccine. Their results showed that, when patients were vaccinated 6-12 months after the last rituximab dose, 55% were seronegative, and when this was more than 12 months, only 13% were seronegative, compared with seronegativity in 86% who were vaccinated less than 6 months after their last rituximab dose.
The RituxiVac trial, conducted by researchers in Switzerland, also examined vaccine responses of 96 rituximab-treated patients who received Comirnaty or Spikevax; results recently published in The Lancet Rheumatology showed findings similar to other studies, with reduced humoral and cell-mediated responses. In the RituxiVac trial, the median time to last anti-CD20 treatment was 1.07 years.
“The typical interval between rituximab doses [for treatment of rheumatoid arthritis, as well as for remission maintenance in antineutrophil cytoplasmic antibody–associated vasculitis] is typically 6 months, and this has become widely used as the interval from last rituximab to time of COVID vaccination, with a recommendation to wait 4 weeks (if possible) from time of vaccination until the next rituximab administration,” Dr. Spiera explained. However, this window seems to vary depending on the study.
Recent research published in Arthritis & Rheumatology indicates B-cell levels could be a relevant indicator for humoral and cell-mediated response in patients with rheumatic diseases treated with rituximab, with a level of 10 B cells/mcL (0.4% of lymphocytes) identified as one potential marker for likely seroconversion following COVID-19 vaccination.
“In some smaller case series, it has been further recognized that rituximab-treated patients who were beginning to reconstitute peripheral B cells were most likely to respond serologically. Our present study confirmed those findings, demonstrating that the presence of detectable B cells was strongly associated with vaccine responsiveness, and affords complementary information to time from last [rituximab dose] in informing the likelihood of a vaccine response,” Dr. Spiera said.
However, the literature is limited in this area, and an exact cutoff for B-cell counts in these patients isn’t currently known, Dr. Jyssum said. A better metric is time away from anti-CD20 therapies, with CD19 cell count being highly correlated with last infusion.
Dr. Spiera agreed that there is no consistent B-cell percentage that works as a cutoff. “In our study, we looked at it as a binary variable, although we did find that a higher percentage of B cells in the peripheral lymphocyte population was associated with a higher likelihood of seroconversion. We did not, however, identify a ‘threshold’ for vaccine serologic responsiveness.”
Should clinicians measure antibodies?
The Food and Drug Administration and the Centers for Disease Control and Prevention have recommended that health care providers and the public not use COVID-19 antibody tests as a way to gauge immunity after exposure to SARS-CoV-2 and after receiving a COVID-19 vaccination. The ACR’s guidance on COVID-19 vaccination for patients with rheumatic and musculoskeletal diseases strongly recommends against ordering antibody tests for patients with autoimmune inflammatory rheumatic diseases as a way to measure immunity.
“Generally, such measurements are not recommended as the clinical correlate of various antibody levels are not known,” Dr. Jyssum said. “With regular infusions of rituximab or other anti-CD20 agents, one cannot expect that these patients will develop significant levels of antibodies.”
However, she said there might be situations where it’s useful to know whether a patient has developed antibodies at all. “Assessing the significance of specific antibody levels is difficult, and the subject of scientific studies. Patients lacking a humoral vaccine response are left to rely on their T-cell responses and on infectious control measures to prevent disease.”
Dr. Spiera said he disagreed with guidelines recommending against checking antibody levels after vaccination, “particularly in patients treated with immunosuppressive medications that might be expected to blunt their serologic response to the vaccines.
“Although we cannot be sure what level of measurable antibodies offer what level of protection, most clinicians would agree that patients who demonstrate no detectable antibodies (which is a common finding in rituximab-treated patients) should be considered at higher risk,” he said. “Indeed, recommendations regarding booster vaccine administration in general was initially based on the observation of declining antibody levels with longer time from vaccination.”
Do COVID-19 vaccine boosters help patients on anti-CD20 therapy?
As of January 2022, the FDA and CDC have recommended a third primary series shot of COVID-19 vaccines for some moderately to severely immunocompromised patients as young as 5 years old (for Comirnaty vaccine) or a booster shot of either Comirnaty or Spikevax for everyone aged 12 years and older, including immunocompromised people, while the ACR goes into more detail and recommends clinicians time a patient’s booster shot with temporary treatment interruption.
In The Lancet Rheumatology, Dr. Jyssum and colleagues recently published results from the prospective Nor-vaC study examining the humoral and cell-mediated immune responses of 87 patients with RA being treated with rituximab who received the Comirnaty, Spikevax, or Vaxzevria (AstraZeneca) COVID-19 vaccines; of these, 49 patients received a booster dose at a median of 70 days after completing their primary series. The results showed 19 patients (28.1%) had a serologic response after their primary series, while 8 of 49 patients (16.3%) who received their booster dose had a serologic response.
All patients who received a third dose in the study had a T-cell response, Dr. Jyssum said. “This is reassuring for patients and clinicians. T cells have been found to be important in countering COVID-19 disease, but whether we can rely on the T-cell response alone in the absence of antibodies to protect patients from infection or from serious COVID disease is still not determined,” she said.
When asked if she would recommend COVID-19 vaccine booster doses for patients on rituximab, Dr. Jyssum replied: “Absolutely.”
Another study, recently published in Annals of the Rheumatic Diseases, examined heterologous and homologous booster doses for 60 patients receiving rituximab without seroconversion after their COVID-19 vaccine primary series. The results showed no significant difference in new seroconversion at 4 weeks based on whether the patient received a vector or mRNA vaccine (22% vs. 32%), but all patients who received a booster dose with a vector vaccine had specific T-cell responses, compared with 81% of patients who received an mRNA vaccine booster. There was a new humoral and/or cellular response in 9 of 11 patients (82%), and most patients with peripheral B cells (12 of 18 patients; 67%) achieved seroconversion.
“Our data show that a cellular and/or humoral immune response can be achieved on a third COVID-19 vaccination in most of the patients who initially developed neither a humoral nor a cellular immune response,” the researchers concluded. “The efficacy data together with the safety data seen in our trial provide a favorable risk/benefit ratio and support the implementation of a third vaccination for nonseroconverted high-risk autoimmune disease patients treated with B-cell–depleting agents.”
Dr. Spiera said booster doses are an important part of the equation, and “it is important to consider factors that would be associated with a greater likelihood of achieving a serologic response, particularly in those patients who did not demonstrate a serologic response to the initial vaccines series.
“Preliminary data shows that the beginnings of B-cell reconstitution is also associated with a positive serologic response following a booster of the COVID-19 vaccine,” he said.
The authors of the cited studies reported numerous relevant financial disclosures. Dr. Spiera and Dr. Jyssum reported no relevant financial disclosures.
Rituximab has presented something of a conundrum for patients taking the monoclonal antibody during the COVID-19 pandemic.
Used to manage a variety of autoimmune diseases and cancers, rituximab acts against CD20 proteins expressed on the surface of B cells, causing B-cell depletion. However, it is this B-cell depletion that may put these patients at greater risk of COVID-19 development, progression to more severe disease, and in-hospital mortality. Evidence for this appears to be mixed, with studies showing both that patients using rituximab to manage various diseases are and are not at increased risk for SARS-CoV-2 infection, COVID-19 progression, and mortality.
As COVID-19 vaccine rollouts take place across the world, more questions have been raised about the relationship between B-cell depletion from anti-CD20 therapies and COVID-19 vaccines. Do rituximab and other anti-CD20 therapies affect a patient’s response to COVID-19 vaccines? If this is the case, does the timing of anti-CD20 treatment matter to maximize B-cell levels and improve the vaccine’s effectiveness? And how do COVID-19 vaccine booster doses factor into the equation?
Humoral and cell-mediated responses following COVID-19 vaccination
First, the bad news: The vaccine is unquestionably safe to administer in patients taking rituximab, but one thing that has been well established is that antibody response to COVID-19 vaccination in these individuals does is reduced. This isn’t entirely unprecedented, as previous studies have shown a weakened immune response to pneumococcal polysaccharide and keyhole limpet hemocyanin vaccines among patients taking rituximab.
“Compromised immunogenicity to the SARS-CoV-2 vaccines has been demonstrated in rituximab-treated patients, which is of particular concern given the observation that B-cell–depleting therapies may be associated with worse COVID outcomes,” Robert F. Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at the Hospital for Special Surgery in New York, said in an interview.
For example, in a recent study from the Medical University of Vienna, 29 (39%) of 74 patients receiving rituximab (43% as monotherapy, 57% with conventional-synthetic disease-modifying antirheumatic drugs) who were vaccinated with either the Comirnaty (Pfizer-BioNTech) or Spikevax (Moderna) COVID-19 vaccine achieved seroconversion, compared with 100% of patients in a healthy control group, and all but 1 patient without detectable CD19+ peripheral B cells did not develop anti–SARS-CoV-2 receptor-binding domain antibodies.
“There is an increasing number of studies in this field, and they confirm that patients treated with rituximab and other anti-CD20 agents have severely reduced serological responses to COVID-19 vaccines,” Ingrid Jyssum, MD, of the division of rheumatology and research at Diakonhjemmet Hospital in Oslo, said in an interview.
One silver lining is that patients treated with anti-CD20 therapies appear to have a cell-mediated response following vaccination even if they don’t develop SARS-CoV-2 antibodies. “Studies that also investigate T-cell responses are starting to emerge, and so far, they show that, even if the patients do not have antibodies, they may have T-cell responses,” Dr. Jyssum said.
One study of 24 patients with autoimmune diseases taking rituximab that evaluated humoral and T-cell responses following vaccination with the Comirnaty vaccine found that none had a humoral response to the vaccine, but the T-cell response from that group did not significantly differ from 35 patients receiving other immunosuppressants and 26 patients in a healthy control group. In another study of rituximab- or ocrelizumab-treated patients who received mRNA-based COVID-19 vaccines, 69.4% developed SARS-CoV-2–specific antibodies, compared with a control group, but 96.2% of patients taking ocrelizumab and 81.8% of patients taking rituximab mounted a spike-specific CD8+ T-cell response, compared with 66.7% in the control group, and there were comparable rates (85%-90%) of spike-specific CD4+ T cells in all groups. In the study from the Medical University of Vienna, T-cell response was detected in rituximab-treated patients who both did and did not mount an antibody response.
The clinical relevance of how a blunted humoral immune response but a respectable T-cell response to COVID-19 vaccines affects patients treated with anti-CD20 therapies isn’t currently known, Dr. Jyssum said.
While these data are reassuring, they’re also incomplete, Dr. Spiera noted. “The ultimate outcome of relevance to assess vaccine efficacy is protection from COVID and from severe outcomes of COVID infection (i.e., hospitalization, mechanical ventilation, death). That data will require assessment of very large numbers of rituximab-treated vaccinated patients to be compared with rituximab-treated unvaccinated patients, and is unlikely to be forthcoming in the very near future.
“In the meantime, however, achieving serologic positivity, meaning having evidence of serologic as well as cellular immunity following vaccination, is a desired outcome, and likely implies more robust immunity.”
Does treatment timing impact COVID-19 vaccine response?
Given enough time, B-cell reconstitution will occur in patients taking rituximab. With that in mind, is it beneficial to wait a certain amount of time after a patient has stopped rituximab therapy or time since their last dose before giving them a COVID-19 vaccine? In their guidance on COVID-19 vaccines for patients with rheumatic and musculoskeletal diseases, the American College of Rheumatology said there is moderate evidence to consider “optimal timing of dosing and vaccination with the rheumatology provider before proceeding.”
“Guidelines and preliminary studies of serologic response to COVID vaccine in rituximab-treated patients have suggested that longer time from last rituximab exposure is associated with a greater likelihood of a serologic response,” Dr. Spiera said.
In a brief report published in Arthritis & Rheumatology, Dr. Spiera and colleagues performed a retrospective chart review of 56 patients with varying levels of last exposure to rituximab who received a COVID-19 vaccine. Their results showed that, when patients were vaccinated 6-12 months after the last rituximab dose, 55% were seronegative, and when this was more than 12 months, only 13% were seronegative, compared with seronegativity in 86% who were vaccinated less than 6 months after their last rituximab dose.
The RituxiVac trial, conducted by researchers in Switzerland, also examined vaccine responses of 96 rituximab-treated patients who received Comirnaty or Spikevax; results recently published in The Lancet Rheumatology showed findings similar to other studies, with reduced humoral and cell-mediated responses. In the RituxiVac trial, the median time to last anti-CD20 treatment was 1.07 years.
“The typical interval between rituximab doses [for treatment of rheumatoid arthritis, as well as for remission maintenance in antineutrophil cytoplasmic antibody–associated vasculitis] is typically 6 months, and this has become widely used as the interval from last rituximab to time of COVID vaccination, with a recommendation to wait 4 weeks (if possible) from time of vaccination until the next rituximab administration,” Dr. Spiera explained. However, this window seems to vary depending on the study.
Recent research published in Arthritis & Rheumatology indicates B-cell levels could be a relevant indicator for humoral and cell-mediated response in patients with rheumatic diseases treated with rituximab, with a level of 10 B cells/mcL (0.4% of lymphocytes) identified as one potential marker for likely seroconversion following COVID-19 vaccination.
“In some smaller case series, it has been further recognized that rituximab-treated patients who were beginning to reconstitute peripheral B cells were most likely to respond serologically. Our present study confirmed those findings, demonstrating that the presence of detectable B cells was strongly associated with vaccine responsiveness, and affords complementary information to time from last [rituximab dose] in informing the likelihood of a vaccine response,” Dr. Spiera said.
However, the literature is limited in this area, and an exact cutoff for B-cell counts in these patients isn’t currently known, Dr. Jyssum said. A better metric is time away from anti-CD20 therapies, with CD19 cell count being highly correlated with last infusion.
Dr. Spiera agreed that there is no consistent B-cell percentage that works as a cutoff. “In our study, we looked at it as a binary variable, although we did find that a higher percentage of B cells in the peripheral lymphocyte population was associated with a higher likelihood of seroconversion. We did not, however, identify a ‘threshold’ for vaccine serologic responsiveness.”
Should clinicians measure antibodies?
The Food and Drug Administration and the Centers for Disease Control and Prevention have recommended that health care providers and the public not use COVID-19 antibody tests as a way to gauge immunity after exposure to SARS-CoV-2 and after receiving a COVID-19 vaccination. The ACR’s guidance on COVID-19 vaccination for patients with rheumatic and musculoskeletal diseases strongly recommends against ordering antibody tests for patients with autoimmune inflammatory rheumatic diseases as a way to measure immunity.
“Generally, such measurements are not recommended as the clinical correlate of various antibody levels are not known,” Dr. Jyssum said. “With regular infusions of rituximab or other anti-CD20 agents, one cannot expect that these patients will develop significant levels of antibodies.”
However, she said there might be situations where it’s useful to know whether a patient has developed antibodies at all. “Assessing the significance of specific antibody levels is difficult, and the subject of scientific studies. Patients lacking a humoral vaccine response are left to rely on their T-cell responses and on infectious control measures to prevent disease.”
Dr. Spiera said he disagreed with guidelines recommending against checking antibody levels after vaccination, “particularly in patients treated with immunosuppressive medications that might be expected to blunt their serologic response to the vaccines.
“Although we cannot be sure what level of measurable antibodies offer what level of protection, most clinicians would agree that patients who demonstrate no detectable antibodies (which is a common finding in rituximab-treated patients) should be considered at higher risk,” he said. “Indeed, recommendations regarding booster vaccine administration in general was initially based on the observation of declining antibody levels with longer time from vaccination.”
Do COVID-19 vaccine boosters help patients on anti-CD20 therapy?
As of January 2022, the FDA and CDC have recommended a third primary series shot of COVID-19 vaccines for some moderately to severely immunocompromised patients as young as 5 years old (for Comirnaty vaccine) or a booster shot of either Comirnaty or Spikevax for everyone aged 12 years and older, including immunocompromised people, while the ACR goes into more detail and recommends clinicians time a patient’s booster shot with temporary treatment interruption.
In The Lancet Rheumatology, Dr. Jyssum and colleagues recently published results from the prospective Nor-vaC study examining the humoral and cell-mediated immune responses of 87 patients with RA being treated with rituximab who received the Comirnaty, Spikevax, or Vaxzevria (AstraZeneca) COVID-19 vaccines; of these, 49 patients received a booster dose at a median of 70 days after completing their primary series. The results showed 19 patients (28.1%) had a serologic response after their primary series, while 8 of 49 patients (16.3%) who received their booster dose had a serologic response.
All patients who received a third dose in the study had a T-cell response, Dr. Jyssum said. “This is reassuring for patients and clinicians. T cells have been found to be important in countering COVID-19 disease, but whether we can rely on the T-cell response alone in the absence of antibodies to protect patients from infection or from serious COVID disease is still not determined,” she said.
When asked if she would recommend COVID-19 vaccine booster doses for patients on rituximab, Dr. Jyssum replied: “Absolutely.”
Another study, recently published in Annals of the Rheumatic Diseases, examined heterologous and homologous booster doses for 60 patients receiving rituximab without seroconversion after their COVID-19 vaccine primary series. The results showed no significant difference in new seroconversion at 4 weeks based on whether the patient received a vector or mRNA vaccine (22% vs. 32%), but all patients who received a booster dose with a vector vaccine had specific T-cell responses, compared with 81% of patients who received an mRNA vaccine booster. There was a new humoral and/or cellular response in 9 of 11 patients (82%), and most patients with peripheral B cells (12 of 18 patients; 67%) achieved seroconversion.
“Our data show that a cellular and/or humoral immune response can be achieved on a third COVID-19 vaccination in most of the patients who initially developed neither a humoral nor a cellular immune response,” the researchers concluded. “The efficacy data together with the safety data seen in our trial provide a favorable risk/benefit ratio and support the implementation of a third vaccination for nonseroconverted high-risk autoimmune disease patients treated with B-cell–depleting agents.”
Dr. Spiera said booster doses are an important part of the equation, and “it is important to consider factors that would be associated with a greater likelihood of achieving a serologic response, particularly in those patients who did not demonstrate a serologic response to the initial vaccines series.
“Preliminary data shows that the beginnings of B-cell reconstitution is also associated with a positive serologic response following a booster of the COVID-19 vaccine,” he said.
The authors of the cited studies reported numerous relevant financial disclosures. Dr. Spiera and Dr. Jyssum reported no relevant financial disclosures.
Rituximab has presented something of a conundrum for patients taking the monoclonal antibody during the COVID-19 pandemic.
Used to manage a variety of autoimmune diseases and cancers, rituximab acts against CD20 proteins expressed on the surface of B cells, causing B-cell depletion. However, it is this B-cell depletion that may put these patients at greater risk of COVID-19 development, progression to more severe disease, and in-hospital mortality. Evidence for this appears to be mixed, with studies showing both that patients using rituximab to manage various diseases are and are not at increased risk for SARS-CoV-2 infection, COVID-19 progression, and mortality.
As COVID-19 vaccine rollouts take place across the world, more questions have been raised about the relationship between B-cell depletion from anti-CD20 therapies and COVID-19 vaccines. Do rituximab and other anti-CD20 therapies affect a patient’s response to COVID-19 vaccines? If this is the case, does the timing of anti-CD20 treatment matter to maximize B-cell levels and improve the vaccine’s effectiveness? And how do COVID-19 vaccine booster doses factor into the equation?
Humoral and cell-mediated responses following COVID-19 vaccination
First, the bad news: The vaccine is unquestionably safe to administer in patients taking rituximab, but one thing that has been well established is that antibody response to COVID-19 vaccination in these individuals does is reduced. This isn’t entirely unprecedented, as previous studies have shown a weakened immune response to pneumococcal polysaccharide and keyhole limpet hemocyanin vaccines among patients taking rituximab.
“Compromised immunogenicity to the SARS-CoV-2 vaccines has been demonstrated in rituximab-treated patients, which is of particular concern given the observation that B-cell–depleting therapies may be associated with worse COVID outcomes,” Robert F. Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at the Hospital for Special Surgery in New York, said in an interview.
For example, in a recent study from the Medical University of Vienna, 29 (39%) of 74 patients receiving rituximab (43% as monotherapy, 57% with conventional-synthetic disease-modifying antirheumatic drugs) who were vaccinated with either the Comirnaty (Pfizer-BioNTech) or Spikevax (Moderna) COVID-19 vaccine achieved seroconversion, compared with 100% of patients in a healthy control group, and all but 1 patient without detectable CD19+ peripheral B cells did not develop anti–SARS-CoV-2 receptor-binding domain antibodies.
“There is an increasing number of studies in this field, and they confirm that patients treated with rituximab and other anti-CD20 agents have severely reduced serological responses to COVID-19 vaccines,” Ingrid Jyssum, MD, of the division of rheumatology and research at Diakonhjemmet Hospital in Oslo, said in an interview.
One silver lining is that patients treated with anti-CD20 therapies appear to have a cell-mediated response following vaccination even if they don’t develop SARS-CoV-2 antibodies. “Studies that also investigate T-cell responses are starting to emerge, and so far, they show that, even if the patients do not have antibodies, they may have T-cell responses,” Dr. Jyssum said.
One study of 24 patients with autoimmune diseases taking rituximab that evaluated humoral and T-cell responses following vaccination with the Comirnaty vaccine found that none had a humoral response to the vaccine, but the T-cell response from that group did not significantly differ from 35 patients receiving other immunosuppressants and 26 patients in a healthy control group. In another study of rituximab- or ocrelizumab-treated patients who received mRNA-based COVID-19 vaccines, 69.4% developed SARS-CoV-2–specific antibodies, compared with a control group, but 96.2% of patients taking ocrelizumab and 81.8% of patients taking rituximab mounted a spike-specific CD8+ T-cell response, compared with 66.7% in the control group, and there were comparable rates (85%-90%) of spike-specific CD4+ T cells in all groups. In the study from the Medical University of Vienna, T-cell response was detected in rituximab-treated patients who both did and did not mount an antibody response.
The clinical relevance of how a blunted humoral immune response but a respectable T-cell response to COVID-19 vaccines affects patients treated with anti-CD20 therapies isn’t currently known, Dr. Jyssum said.
While these data are reassuring, they’re also incomplete, Dr. Spiera noted. “The ultimate outcome of relevance to assess vaccine efficacy is protection from COVID and from severe outcomes of COVID infection (i.e., hospitalization, mechanical ventilation, death). That data will require assessment of very large numbers of rituximab-treated vaccinated patients to be compared with rituximab-treated unvaccinated patients, and is unlikely to be forthcoming in the very near future.
“In the meantime, however, achieving serologic positivity, meaning having evidence of serologic as well as cellular immunity following vaccination, is a desired outcome, and likely implies more robust immunity.”
Does treatment timing impact COVID-19 vaccine response?
Given enough time, B-cell reconstitution will occur in patients taking rituximab. With that in mind, is it beneficial to wait a certain amount of time after a patient has stopped rituximab therapy or time since their last dose before giving them a COVID-19 vaccine? In their guidance on COVID-19 vaccines for patients with rheumatic and musculoskeletal diseases, the American College of Rheumatology said there is moderate evidence to consider “optimal timing of dosing and vaccination with the rheumatology provider before proceeding.”
“Guidelines and preliminary studies of serologic response to COVID vaccine in rituximab-treated patients have suggested that longer time from last rituximab exposure is associated with a greater likelihood of a serologic response,” Dr. Spiera said.
In a brief report published in Arthritis & Rheumatology, Dr. Spiera and colleagues performed a retrospective chart review of 56 patients with varying levels of last exposure to rituximab who received a COVID-19 vaccine. Their results showed that, when patients were vaccinated 6-12 months after the last rituximab dose, 55% were seronegative, and when this was more than 12 months, only 13% were seronegative, compared with seronegativity in 86% who were vaccinated less than 6 months after their last rituximab dose.
The RituxiVac trial, conducted by researchers in Switzerland, also examined vaccine responses of 96 rituximab-treated patients who received Comirnaty or Spikevax; results recently published in The Lancet Rheumatology showed findings similar to other studies, with reduced humoral and cell-mediated responses. In the RituxiVac trial, the median time to last anti-CD20 treatment was 1.07 years.
“The typical interval between rituximab doses [for treatment of rheumatoid arthritis, as well as for remission maintenance in antineutrophil cytoplasmic antibody–associated vasculitis] is typically 6 months, and this has become widely used as the interval from last rituximab to time of COVID vaccination, with a recommendation to wait 4 weeks (if possible) from time of vaccination until the next rituximab administration,” Dr. Spiera explained. However, this window seems to vary depending on the study.
Recent research published in Arthritis & Rheumatology indicates B-cell levels could be a relevant indicator for humoral and cell-mediated response in patients with rheumatic diseases treated with rituximab, with a level of 10 B cells/mcL (0.4% of lymphocytes) identified as one potential marker for likely seroconversion following COVID-19 vaccination.
“In some smaller case series, it has been further recognized that rituximab-treated patients who were beginning to reconstitute peripheral B cells were most likely to respond serologically. Our present study confirmed those findings, demonstrating that the presence of detectable B cells was strongly associated with vaccine responsiveness, and affords complementary information to time from last [rituximab dose] in informing the likelihood of a vaccine response,” Dr. Spiera said.
However, the literature is limited in this area, and an exact cutoff for B-cell counts in these patients isn’t currently known, Dr. Jyssum said. A better metric is time away from anti-CD20 therapies, with CD19 cell count being highly correlated with last infusion.
Dr. Spiera agreed that there is no consistent B-cell percentage that works as a cutoff. “In our study, we looked at it as a binary variable, although we did find that a higher percentage of B cells in the peripheral lymphocyte population was associated with a higher likelihood of seroconversion. We did not, however, identify a ‘threshold’ for vaccine serologic responsiveness.”
Should clinicians measure antibodies?
The Food and Drug Administration and the Centers for Disease Control and Prevention have recommended that health care providers and the public not use COVID-19 antibody tests as a way to gauge immunity after exposure to SARS-CoV-2 and after receiving a COVID-19 vaccination. The ACR’s guidance on COVID-19 vaccination for patients with rheumatic and musculoskeletal diseases strongly recommends against ordering antibody tests for patients with autoimmune inflammatory rheumatic diseases as a way to measure immunity.
“Generally, such measurements are not recommended as the clinical correlate of various antibody levels are not known,” Dr. Jyssum said. “With regular infusions of rituximab or other anti-CD20 agents, one cannot expect that these patients will develop significant levels of antibodies.”
However, she said there might be situations where it’s useful to know whether a patient has developed antibodies at all. “Assessing the significance of specific antibody levels is difficult, and the subject of scientific studies. Patients lacking a humoral vaccine response are left to rely on their T-cell responses and on infectious control measures to prevent disease.”
Dr. Spiera said he disagreed with guidelines recommending against checking antibody levels after vaccination, “particularly in patients treated with immunosuppressive medications that might be expected to blunt their serologic response to the vaccines.
“Although we cannot be sure what level of measurable antibodies offer what level of protection, most clinicians would agree that patients who demonstrate no detectable antibodies (which is a common finding in rituximab-treated patients) should be considered at higher risk,” he said. “Indeed, recommendations regarding booster vaccine administration in general was initially based on the observation of declining antibody levels with longer time from vaccination.”
Do COVID-19 vaccine boosters help patients on anti-CD20 therapy?
As of January 2022, the FDA and CDC have recommended a third primary series shot of COVID-19 vaccines for some moderately to severely immunocompromised patients as young as 5 years old (for Comirnaty vaccine) or a booster shot of either Comirnaty or Spikevax for everyone aged 12 years and older, including immunocompromised people, while the ACR goes into more detail and recommends clinicians time a patient’s booster shot with temporary treatment interruption.
In The Lancet Rheumatology, Dr. Jyssum and colleagues recently published results from the prospective Nor-vaC study examining the humoral and cell-mediated immune responses of 87 patients with RA being treated with rituximab who received the Comirnaty, Spikevax, or Vaxzevria (AstraZeneca) COVID-19 vaccines; of these, 49 patients received a booster dose at a median of 70 days after completing their primary series. The results showed 19 patients (28.1%) had a serologic response after their primary series, while 8 of 49 patients (16.3%) who received their booster dose had a serologic response.
All patients who received a third dose in the study had a T-cell response, Dr. Jyssum said. “This is reassuring for patients and clinicians. T cells have been found to be important in countering COVID-19 disease, but whether we can rely on the T-cell response alone in the absence of antibodies to protect patients from infection or from serious COVID disease is still not determined,” she said.
When asked if she would recommend COVID-19 vaccine booster doses for patients on rituximab, Dr. Jyssum replied: “Absolutely.”
Another study, recently published in Annals of the Rheumatic Diseases, examined heterologous and homologous booster doses for 60 patients receiving rituximab without seroconversion after their COVID-19 vaccine primary series. The results showed no significant difference in new seroconversion at 4 weeks based on whether the patient received a vector or mRNA vaccine (22% vs. 32%), but all patients who received a booster dose with a vector vaccine had specific T-cell responses, compared with 81% of patients who received an mRNA vaccine booster. There was a new humoral and/or cellular response in 9 of 11 patients (82%), and most patients with peripheral B cells (12 of 18 patients; 67%) achieved seroconversion.
“Our data show that a cellular and/or humoral immune response can be achieved on a third COVID-19 vaccination in most of the patients who initially developed neither a humoral nor a cellular immune response,” the researchers concluded. “The efficacy data together with the safety data seen in our trial provide a favorable risk/benefit ratio and support the implementation of a third vaccination for nonseroconverted high-risk autoimmune disease patients treated with B-cell–depleting agents.”
Dr. Spiera said booster doses are an important part of the equation, and “it is important to consider factors that would be associated with a greater likelihood of achieving a serologic response, particularly in those patients who did not demonstrate a serologic response to the initial vaccines series.
“Preliminary data shows that the beginnings of B-cell reconstitution is also associated with a positive serologic response following a booster of the COVID-19 vaccine,” he said.
The authors of the cited studies reported numerous relevant financial disclosures. Dr. Spiera and Dr. Jyssum reported no relevant financial disclosures.
Fourth vaccine shot less effective against Omicron, Israeli study says
, according to new research at an Israeli hospital.
The preliminary results, released on Jan. 17, challenge the idea of giving a second booster dose to slow the spread of the coronavirus, according to USA Today.
“Despite increased antibody levels, the fourth vaccine only offers a partial defense against the virus,” Gili Regev-Yochay, MD, director of the hospital’s infection prevention and control units, told reporters.
“The vaccines, which were more effective against previous variants, offer less protection versus Omicron,” she said.
In a clinical trial, 274 medical workers at Sheba Medical Center near Tel Aviv received a fourth vaccine dose in December – 154 got the Pfizer vaccine and 120 got the Moderna vaccine – after previously getting three Pfizer shots.
Both groups received a boost in antibodies that was “slightly higher” than after the third shot, Dr. Regev-Yochay said. But when compared with a control group that didn’t receive the fourth dose, the extra boost didn’t prevent the spread of Omicron.
“We see many infected with Omicron who received the fourth dose,” Dr. Regev-Yochay said. “Granted, a bit less than in the control group, but still a lot of infections.”
Some public health officials in Israel say the campaign for fourth doses is still worthwhile, according to The Times of Israel. The vaccine still works well against the Alpha and Delta variants, Dr. Regev-Yochay said, and a fourth shot should go to older adults and those who face higher risks for severe COVID-19.
Hours after releasing the preliminary results, Sheba Medical Center published a statement calling for “continuing the vaccination drive for risk groups at this time, even though the vaccine doesn’t provide optimal protection against getting infected with the variant.” News outlets reported that the hospital was pressured into issuing the statement after Israel’s Health Ministry didn’t like the release of the early study results, The Times of Israel reported.
The second booster “returns the level of antibodies to what it was at the beginning of the third booster,” Nachman Ash, MD, director of Israel’s Health Ministry, told Channel 13 TV in Israel, according to The Associated Press.
“That has great importance, especially among the older population,” he said.
As of Sunday, more than 500,000 people in Israel had received fourth doses since the country began offering them last month to medical workers, immunocompromised patients, and people ages 60 years and older, the AP reported. At the same time, the country has faced a recent coronavirus surge that has led to record-breaking numbers of cases and rising hospitalizations.
On Tuesday, the Israeli government said it would shorten the mandatory quarantine period from 7 days to 5 days, the AP reported.
“This decision will enable us to continue safeguarding public health on the one hand and to keep the economy going at this time on the other, even though it is difficult, so that we can get through this wave safely,” Prime Minister Naftali Bennett said.
A version of this article first appeared on WebMD.com.
, according to new research at an Israeli hospital.
The preliminary results, released on Jan. 17, challenge the idea of giving a second booster dose to slow the spread of the coronavirus, according to USA Today.
“Despite increased antibody levels, the fourth vaccine only offers a partial defense against the virus,” Gili Regev-Yochay, MD, director of the hospital’s infection prevention and control units, told reporters.
“The vaccines, which were more effective against previous variants, offer less protection versus Omicron,” she said.
In a clinical trial, 274 medical workers at Sheba Medical Center near Tel Aviv received a fourth vaccine dose in December – 154 got the Pfizer vaccine and 120 got the Moderna vaccine – after previously getting three Pfizer shots.
Both groups received a boost in antibodies that was “slightly higher” than after the third shot, Dr. Regev-Yochay said. But when compared with a control group that didn’t receive the fourth dose, the extra boost didn’t prevent the spread of Omicron.
“We see many infected with Omicron who received the fourth dose,” Dr. Regev-Yochay said. “Granted, a bit less than in the control group, but still a lot of infections.”
Some public health officials in Israel say the campaign for fourth doses is still worthwhile, according to The Times of Israel. The vaccine still works well against the Alpha and Delta variants, Dr. Regev-Yochay said, and a fourth shot should go to older adults and those who face higher risks for severe COVID-19.
Hours after releasing the preliminary results, Sheba Medical Center published a statement calling for “continuing the vaccination drive for risk groups at this time, even though the vaccine doesn’t provide optimal protection against getting infected with the variant.” News outlets reported that the hospital was pressured into issuing the statement after Israel’s Health Ministry didn’t like the release of the early study results, The Times of Israel reported.
The second booster “returns the level of antibodies to what it was at the beginning of the third booster,” Nachman Ash, MD, director of Israel’s Health Ministry, told Channel 13 TV in Israel, according to The Associated Press.
“That has great importance, especially among the older population,” he said.
As of Sunday, more than 500,000 people in Israel had received fourth doses since the country began offering them last month to medical workers, immunocompromised patients, and people ages 60 years and older, the AP reported. At the same time, the country has faced a recent coronavirus surge that has led to record-breaking numbers of cases and rising hospitalizations.
On Tuesday, the Israeli government said it would shorten the mandatory quarantine period from 7 days to 5 days, the AP reported.
“This decision will enable us to continue safeguarding public health on the one hand and to keep the economy going at this time on the other, even though it is difficult, so that we can get through this wave safely,” Prime Minister Naftali Bennett said.
A version of this article first appeared on WebMD.com.
, according to new research at an Israeli hospital.
The preliminary results, released on Jan. 17, challenge the idea of giving a second booster dose to slow the spread of the coronavirus, according to USA Today.
“Despite increased antibody levels, the fourth vaccine only offers a partial defense against the virus,” Gili Regev-Yochay, MD, director of the hospital’s infection prevention and control units, told reporters.
“The vaccines, which were more effective against previous variants, offer less protection versus Omicron,” she said.
In a clinical trial, 274 medical workers at Sheba Medical Center near Tel Aviv received a fourth vaccine dose in December – 154 got the Pfizer vaccine and 120 got the Moderna vaccine – after previously getting three Pfizer shots.
Both groups received a boost in antibodies that was “slightly higher” than after the third shot, Dr. Regev-Yochay said. But when compared with a control group that didn’t receive the fourth dose, the extra boost didn’t prevent the spread of Omicron.
“We see many infected with Omicron who received the fourth dose,” Dr. Regev-Yochay said. “Granted, a bit less than in the control group, but still a lot of infections.”
Some public health officials in Israel say the campaign for fourth doses is still worthwhile, according to The Times of Israel. The vaccine still works well against the Alpha and Delta variants, Dr. Regev-Yochay said, and a fourth shot should go to older adults and those who face higher risks for severe COVID-19.
Hours after releasing the preliminary results, Sheba Medical Center published a statement calling for “continuing the vaccination drive for risk groups at this time, even though the vaccine doesn’t provide optimal protection against getting infected with the variant.” News outlets reported that the hospital was pressured into issuing the statement after Israel’s Health Ministry didn’t like the release of the early study results, The Times of Israel reported.
The second booster “returns the level of antibodies to what it was at the beginning of the third booster,” Nachman Ash, MD, director of Israel’s Health Ministry, told Channel 13 TV in Israel, according to The Associated Press.
“That has great importance, especially among the older population,” he said.
As of Sunday, more than 500,000 people in Israel had received fourth doses since the country began offering them last month to medical workers, immunocompromised patients, and people ages 60 years and older, the AP reported. At the same time, the country has faced a recent coronavirus surge that has led to record-breaking numbers of cases and rising hospitalizations.
On Tuesday, the Israeli government said it would shorten the mandatory quarantine period from 7 days to 5 days, the AP reported.
“This decision will enable us to continue safeguarding public health on the one hand and to keep the economy going at this time on the other, even though it is difficult, so that we can get through this wave safely,” Prime Minister Naftali Bennett said.
A version of this article first appeared on WebMD.com.
ACIP releases new dengue vaccine recommendations
The vaccine is only to be used for children aged 9-16 who live in endemic areas and who have evidence with a specific diagnostic test of prior dengue infection.
Dengue is a mosquito-borne virus found throughout the world, primarily in tropical or subtropical climates. Cases had steadily been increasing to 5.2 million in 2019, and the geographic distribution of cases is broadening with climate change and urbanization. About half of the world’s population is now at risk.
The dengue virus has four serotypes. The first infection may be mild or asymptomatic, but the second one can be life-threatening because of a phenomenon called antibody-dependent enhancement.
The lead author of the new recommendations is Gabriela Paz-Bailey, MD, PhD, division of vector-borne diseases, dengue branch, CDC. She told this news organization that, during the second infection, when there are “low levels of antibodies from that first infection, the antibodies help the virus get inside the cells. There the virus is not killed, and that results in increased viral load, and then that can result in more severe disease and the plasma leakage” syndrome, which can lead to shock, severe bleeding, and organ failure. The death rate for severe dengue is up to 13%.
Previous infection with Zika virus, common in the same areas where dengue is endemic, can also increase the risk for symptomatic and severe dengue for subsequent infections.
In the United States, Puerto Rico is the main focus of control efforts because 95% of domestic dengue cases originate there – almost 30,000 cases between 2010 and 2020, with 11,000 cases and 4,000 hospitalizations occurring in children between the ages of 10 and 19.
Because Aedes aegypti, the primary mosquito vector transmitting dengue, is resistant to all commonly used insecticides in Puerto Rico, preventive efforts have shifted from insecticides to vaccination.
Antibody tests prevaccination
The main concern with the Sanofi’s dengue vaccine is that it could act as an asymptomatic primary dengue infection, in effect priming the body for a severe reaction from antibody-dependent enhancement with a subsequent infection. That is why it’s critical that the vaccine only be given to children with evidence of prior disease.
Dr. Paz-Bailey said: “The CDC came up with recommendations of what the performance of the test used for prevaccination screening should be. And it was 98% specificity and 75% sensitivity. ... But no test by itself was found to have a specificity of 98%, and this is why we’re recommending the two-test algorithm,” in which two different assays are run off the same blood sample, drawn at a prevaccination visit.
If the child has evidence of prior dengue, they can proceed with vaccination to protect against recurrent infection. Dengvaxia is given as a series of three shots over 6 months. Vaccine efficacy is 82% – so not everyone is protected, and additionally, that protection declines over time.
There is concern that it will be difficult to achieve compliance with such a complex regimen. Dr. Paz-Bailey said, “But I think that the trust in vaccines that is highly prevalent for [Puerto] Rico and trusting the health care system, and sort of the importance that is assigned to dengue by providers and by parents because of previous outbreaks and previous experiences is going to help us.” She added, “I think that the COVID experience has been very revealing. And what we have learned is that Puerto Rico has a very strong health care system, a very strong network of vaccine providers. ... Coverage for COVID vaccine is higher than in other parts of the U.S.”
One of the interesting things about dengue is that the first infection can range from asymptomatic to life-threatening. The second infection is generally worse because of this antibody-dependent enhancement phenomenon. Eng Eong Ooi, MD, PhD, professor of microbiology and immunology, National University of Singapore, told this news organization, “After you have two infections, you seem to be protected quite well against the remaining two [serotypes]. The vaccine serves as another episode of infection in those who had prior dengue, so then any natural infections after the vaccination in the seropositive become like the outcome of a third or fourth infection.”
Vaccination alone will not solve dengue. Dr. Ooi said, “There’s not one method that would fully control dengue. You need both vaccines as well as control measures, whether it’s Wolbachia or something else. At the same time, I think we need antiviral drugs, because hitting this virus in just one part of its life cycle wouldn’t make a huge, lasting impact.” Dr. Ooi added that as “the spread of the virus and the population immunity drops, you’re actually now more vulnerable to dengue outbreaks when they do get introduced. So, suppressing transmission alone isn’t the answer. You also have to keep herd immunity levels high. So if we can reduce the virus transmission by controlling either mosquito population or transmission and at the same time vaccinate to keep the immunity levels high, then I think we have a chance of controlling dengue.”
Dr. Paz-Bailey concluded: “I do want to emphasize that we are excited about having these tools, because for years and years, we have had really limited options to prevent and control dengue. It’s an important addition to have the vaccine be approved to be used within the U.S., and it’s going to pave the road for future vaccines.”
Dr. Paz-Bailey and Dr. Ooi reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The vaccine is only to be used for children aged 9-16 who live in endemic areas and who have evidence with a specific diagnostic test of prior dengue infection.
Dengue is a mosquito-borne virus found throughout the world, primarily in tropical or subtropical climates. Cases had steadily been increasing to 5.2 million in 2019, and the geographic distribution of cases is broadening with climate change and urbanization. About half of the world’s population is now at risk.
The dengue virus has four serotypes. The first infection may be mild or asymptomatic, but the second one can be life-threatening because of a phenomenon called antibody-dependent enhancement.
The lead author of the new recommendations is Gabriela Paz-Bailey, MD, PhD, division of vector-borne diseases, dengue branch, CDC. She told this news organization that, during the second infection, when there are “low levels of antibodies from that first infection, the antibodies help the virus get inside the cells. There the virus is not killed, and that results in increased viral load, and then that can result in more severe disease and the plasma leakage” syndrome, which can lead to shock, severe bleeding, and organ failure. The death rate for severe dengue is up to 13%.
Previous infection with Zika virus, common in the same areas where dengue is endemic, can also increase the risk for symptomatic and severe dengue for subsequent infections.
In the United States, Puerto Rico is the main focus of control efforts because 95% of domestic dengue cases originate there – almost 30,000 cases between 2010 and 2020, with 11,000 cases and 4,000 hospitalizations occurring in children between the ages of 10 and 19.
Because Aedes aegypti, the primary mosquito vector transmitting dengue, is resistant to all commonly used insecticides in Puerto Rico, preventive efforts have shifted from insecticides to vaccination.
Antibody tests prevaccination
The main concern with the Sanofi’s dengue vaccine is that it could act as an asymptomatic primary dengue infection, in effect priming the body for a severe reaction from antibody-dependent enhancement with a subsequent infection. That is why it’s critical that the vaccine only be given to children with evidence of prior disease.
Dr. Paz-Bailey said: “The CDC came up with recommendations of what the performance of the test used for prevaccination screening should be. And it was 98% specificity and 75% sensitivity. ... But no test by itself was found to have a specificity of 98%, and this is why we’re recommending the two-test algorithm,” in which two different assays are run off the same blood sample, drawn at a prevaccination visit.
If the child has evidence of prior dengue, they can proceed with vaccination to protect against recurrent infection. Dengvaxia is given as a series of three shots over 6 months. Vaccine efficacy is 82% – so not everyone is protected, and additionally, that protection declines over time.
There is concern that it will be difficult to achieve compliance with such a complex regimen. Dr. Paz-Bailey said, “But I think that the trust in vaccines that is highly prevalent for [Puerto] Rico and trusting the health care system, and sort of the importance that is assigned to dengue by providers and by parents because of previous outbreaks and previous experiences is going to help us.” She added, “I think that the COVID experience has been very revealing. And what we have learned is that Puerto Rico has a very strong health care system, a very strong network of vaccine providers. ... Coverage for COVID vaccine is higher than in other parts of the U.S.”
One of the interesting things about dengue is that the first infection can range from asymptomatic to life-threatening. The second infection is generally worse because of this antibody-dependent enhancement phenomenon. Eng Eong Ooi, MD, PhD, professor of microbiology and immunology, National University of Singapore, told this news organization, “After you have two infections, you seem to be protected quite well against the remaining two [serotypes]. The vaccine serves as another episode of infection in those who had prior dengue, so then any natural infections after the vaccination in the seropositive become like the outcome of a third or fourth infection.”
Vaccination alone will not solve dengue. Dr. Ooi said, “There’s not one method that would fully control dengue. You need both vaccines as well as control measures, whether it’s Wolbachia or something else. At the same time, I think we need antiviral drugs, because hitting this virus in just one part of its life cycle wouldn’t make a huge, lasting impact.” Dr. Ooi added that as “the spread of the virus and the population immunity drops, you’re actually now more vulnerable to dengue outbreaks when they do get introduced. So, suppressing transmission alone isn’t the answer. You also have to keep herd immunity levels high. So if we can reduce the virus transmission by controlling either mosquito population or transmission and at the same time vaccinate to keep the immunity levels high, then I think we have a chance of controlling dengue.”
Dr. Paz-Bailey concluded: “I do want to emphasize that we are excited about having these tools, because for years and years, we have had really limited options to prevent and control dengue. It’s an important addition to have the vaccine be approved to be used within the U.S., and it’s going to pave the road for future vaccines.”
Dr. Paz-Bailey and Dr. Ooi reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The vaccine is only to be used for children aged 9-16 who live in endemic areas and who have evidence with a specific diagnostic test of prior dengue infection.
Dengue is a mosquito-borne virus found throughout the world, primarily in tropical or subtropical climates. Cases had steadily been increasing to 5.2 million in 2019, and the geographic distribution of cases is broadening with climate change and urbanization. About half of the world’s population is now at risk.
The dengue virus has four serotypes. The first infection may be mild or asymptomatic, but the second one can be life-threatening because of a phenomenon called antibody-dependent enhancement.
The lead author of the new recommendations is Gabriela Paz-Bailey, MD, PhD, division of vector-borne diseases, dengue branch, CDC. She told this news organization that, during the second infection, when there are “low levels of antibodies from that first infection, the antibodies help the virus get inside the cells. There the virus is not killed, and that results in increased viral load, and then that can result in more severe disease and the plasma leakage” syndrome, which can lead to shock, severe bleeding, and organ failure. The death rate for severe dengue is up to 13%.
Previous infection with Zika virus, common in the same areas where dengue is endemic, can also increase the risk for symptomatic and severe dengue for subsequent infections.
In the United States, Puerto Rico is the main focus of control efforts because 95% of domestic dengue cases originate there – almost 30,000 cases between 2010 and 2020, with 11,000 cases and 4,000 hospitalizations occurring in children between the ages of 10 and 19.
Because Aedes aegypti, the primary mosquito vector transmitting dengue, is resistant to all commonly used insecticides in Puerto Rico, preventive efforts have shifted from insecticides to vaccination.
Antibody tests prevaccination
The main concern with the Sanofi’s dengue vaccine is that it could act as an asymptomatic primary dengue infection, in effect priming the body for a severe reaction from antibody-dependent enhancement with a subsequent infection. That is why it’s critical that the vaccine only be given to children with evidence of prior disease.
Dr. Paz-Bailey said: “The CDC came up with recommendations of what the performance of the test used for prevaccination screening should be. And it was 98% specificity and 75% sensitivity. ... But no test by itself was found to have a specificity of 98%, and this is why we’re recommending the two-test algorithm,” in which two different assays are run off the same blood sample, drawn at a prevaccination visit.
If the child has evidence of prior dengue, they can proceed with vaccination to protect against recurrent infection. Dengvaxia is given as a series of three shots over 6 months. Vaccine efficacy is 82% – so not everyone is protected, and additionally, that protection declines over time.
There is concern that it will be difficult to achieve compliance with such a complex regimen. Dr. Paz-Bailey said, “But I think that the trust in vaccines that is highly prevalent for [Puerto] Rico and trusting the health care system, and sort of the importance that is assigned to dengue by providers and by parents because of previous outbreaks and previous experiences is going to help us.” She added, “I think that the COVID experience has been very revealing. And what we have learned is that Puerto Rico has a very strong health care system, a very strong network of vaccine providers. ... Coverage for COVID vaccine is higher than in other parts of the U.S.”
One of the interesting things about dengue is that the first infection can range from asymptomatic to life-threatening. The second infection is generally worse because of this antibody-dependent enhancement phenomenon. Eng Eong Ooi, MD, PhD, professor of microbiology and immunology, National University of Singapore, told this news organization, “After you have two infections, you seem to be protected quite well against the remaining two [serotypes]. The vaccine serves as another episode of infection in those who had prior dengue, so then any natural infections after the vaccination in the seropositive become like the outcome of a third or fourth infection.”
Vaccination alone will not solve dengue. Dr. Ooi said, “There’s not one method that would fully control dengue. You need both vaccines as well as control measures, whether it’s Wolbachia or something else. At the same time, I think we need antiviral drugs, because hitting this virus in just one part of its life cycle wouldn’t make a huge, lasting impact.” Dr. Ooi added that as “the spread of the virus and the population immunity drops, you’re actually now more vulnerable to dengue outbreaks when they do get introduced. So, suppressing transmission alone isn’t the answer. You also have to keep herd immunity levels high. So if we can reduce the virus transmission by controlling either mosquito population or transmission and at the same time vaccinate to keep the immunity levels high, then I think we have a chance of controlling dengue.”
Dr. Paz-Bailey concluded: “I do want to emphasize that we are excited about having these tools, because for years and years, we have had really limited options to prevent and control dengue. It’s an important addition to have the vaccine be approved to be used within the U.S., and it’s going to pave the road for future vaccines.”
Dr. Paz-Bailey and Dr. Ooi reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM MMWR RECOMMENDATIONS AND REPORTS
Quebec plans to fine unvaccinated adults
The amount hasn’t been decided yet, but it will be “significant” and more than $100. More details will be released at a later date, The Associated Press reported.
“Those who refuse to get their first doses in the coming weeks will have to pay a new health contribution,” Premier Francois Legault said during a news conference.
Not getting vaccinated burdens the health care system, and not all residents should pay for it, he said. About 10% of adults in Quebec are unvaccinated, but they represent about 50% of intensive care patients.
“I think it’s reasonable a majority of the population is asking that there be consequences,” he said. “It’s a question of fairness for the 90% of the population that have made some sacrifices. We owe them.”
The fine will apply to those who don’t qualify for a medical exemption, Mr. Legault said.
Provinces across Canada have reported a surge in COVID-19 cases due to the Omicron variant, with Quebec being one of the hardest-hit, according to Reuters. The province is regularly recording the highest daily case count across the country.
Quebec also has announced a 10 p.m. to 5 a.m. curfew, the AP reported. Starting Jan. 18, liquor and cannabis stores in the province will require proof of vaccination, and shopping malls and hair salons could soon require them as well.
About a quarter of all Canadians live in Quebec, according to CNN. The province was one of the first in Canada to require proof of vaccination for residents to eat in restaurants, go to the gym, or attend sporting events.
Some European countries have announced fees for unvaccinated residents, the AP reported, but Quebec is the first in Canada to announce a financial penalty for those who don’t get a shot.
In Greece, people older than 60 have until Jan. 16 to receive the first dose, or they will be fined 100 euros for every month they remain unvaccinated, the AP reported.
Austria will impose fines up to 3,600 euros for those who don’t follow the vaccine mandate for ages 14 and older, which is slated to start in February.
In Italy, residents who are 50 and older are required to be vaccinated. In mid-February, those who are unvaccinated could be fined up to 1,600 euros if they enter their workplaces, the AP reported.
A version of this article first appeared on WebMD.com.
The amount hasn’t been decided yet, but it will be “significant” and more than $100. More details will be released at a later date, The Associated Press reported.
“Those who refuse to get their first doses in the coming weeks will have to pay a new health contribution,” Premier Francois Legault said during a news conference.
Not getting vaccinated burdens the health care system, and not all residents should pay for it, he said. About 10% of adults in Quebec are unvaccinated, but they represent about 50% of intensive care patients.
“I think it’s reasonable a majority of the population is asking that there be consequences,” he said. “It’s a question of fairness for the 90% of the population that have made some sacrifices. We owe them.”
The fine will apply to those who don’t qualify for a medical exemption, Mr. Legault said.
Provinces across Canada have reported a surge in COVID-19 cases due to the Omicron variant, with Quebec being one of the hardest-hit, according to Reuters. The province is regularly recording the highest daily case count across the country.
Quebec also has announced a 10 p.m. to 5 a.m. curfew, the AP reported. Starting Jan. 18, liquor and cannabis stores in the province will require proof of vaccination, and shopping malls and hair salons could soon require them as well.
About a quarter of all Canadians live in Quebec, according to CNN. The province was one of the first in Canada to require proof of vaccination for residents to eat in restaurants, go to the gym, or attend sporting events.
Some European countries have announced fees for unvaccinated residents, the AP reported, but Quebec is the first in Canada to announce a financial penalty for those who don’t get a shot.
In Greece, people older than 60 have until Jan. 16 to receive the first dose, or they will be fined 100 euros for every month they remain unvaccinated, the AP reported.
Austria will impose fines up to 3,600 euros for those who don’t follow the vaccine mandate for ages 14 and older, which is slated to start in February.
In Italy, residents who are 50 and older are required to be vaccinated. In mid-February, those who are unvaccinated could be fined up to 1,600 euros if they enter their workplaces, the AP reported.
A version of this article first appeared on WebMD.com.
The amount hasn’t been decided yet, but it will be “significant” and more than $100. More details will be released at a later date, The Associated Press reported.
“Those who refuse to get their first doses in the coming weeks will have to pay a new health contribution,” Premier Francois Legault said during a news conference.
Not getting vaccinated burdens the health care system, and not all residents should pay for it, he said. About 10% of adults in Quebec are unvaccinated, but they represent about 50% of intensive care patients.
“I think it’s reasonable a majority of the population is asking that there be consequences,” he said. “It’s a question of fairness for the 90% of the population that have made some sacrifices. We owe them.”
The fine will apply to those who don’t qualify for a medical exemption, Mr. Legault said.
Provinces across Canada have reported a surge in COVID-19 cases due to the Omicron variant, with Quebec being one of the hardest-hit, according to Reuters. The province is regularly recording the highest daily case count across the country.
Quebec also has announced a 10 p.m. to 5 a.m. curfew, the AP reported. Starting Jan. 18, liquor and cannabis stores in the province will require proof of vaccination, and shopping malls and hair salons could soon require them as well.
About a quarter of all Canadians live in Quebec, according to CNN. The province was one of the first in Canada to require proof of vaccination for residents to eat in restaurants, go to the gym, or attend sporting events.
Some European countries have announced fees for unvaccinated residents, the AP reported, but Quebec is the first in Canada to announce a financial penalty for those who don’t get a shot.
In Greece, people older than 60 have until Jan. 16 to receive the first dose, or they will be fined 100 euros for every month they remain unvaccinated, the AP reported.
Austria will impose fines up to 3,600 euros for those who don’t follow the vaccine mandate for ages 14 and older, which is slated to start in February.
In Italy, residents who are 50 and older are required to be vaccinated. In mid-February, those who are unvaccinated could be fined up to 1,600 euros if they enter their workplaces, the AP reported.
A version of this article first appeared on WebMD.com.
The limits of education
For more than a decade, studies on the dubious value of education in the face of vaccine refusal and hesitancy have been accumulating. But, too often, the research has been ignored by folks who believe that they can teach the “misinformed” into dropping their resistance. Among some circles education ranks right up there with apple pie and motherhood as one of the pillars of Americana. Those wedded to the education mantra may acknowledge that teaching and preaching hasn’t worked well in the past. But, they may claim it’s because we haven’t done enough of it or hit the right buttons. The notion that if we can just share the facts with the uninformed everything will be fine is a myth that obviously is going to die slowly.
In a recent op-ed piece in the New York Times two physicians at Harvard Medical School reported on their study of about three-quarters of a million children who were eligible to receive HPV vaccines (2021 Dec 21. “Facts alone aren’t going to win over the unvaccinated. This might,” Anupam B. Jena and Christopher M. Worsham). The researchers found that children whose mothers had been diagnosed with cervical cancer were no more likely to be immunized than those children whose mothers had not had the disease. Who could be better informed about risks and hazards of contracting HPV than women with cervical cancer? If the facts won’t motivate, where does that leave us?
Those of you born before 1960 may remember or at least have heard about a television show called “Truth or Consequences.” It was a silly farce of a game show which has no bearing on our nation’s crisis of widespread vaccine refusal. However, buried in its title is the answer. If the truth isn’t convincing the resistors, then the obvious choice is consequences.
I hope that you have discovered that same strategy when counseling parents of misbehaving children. Talk is cheap and often ineffective. Explaining the error of his ways to a child who probably already knows what he is doing wrong is a waste of everyone’s time and unpleasant for those within earshot. At some point, sooner better than later, it’s time to say there is going to be a consequence for this misbehavior – going home from the playground, spending a few minutes in time-out, removing a privilege, etc. If consequences are chosen well and instituted with a minimum of idle threats, they work.
And, we are beginning to see it work in the face of pandemic shot refusal. Here in Maine the governor mandated that all health care workers be vaccinated. There was plenty of gnashing of teeth and threats of mass job walk offs. And, there were a few hospital workers who quit, but in the end it worked.
The trick is choosing consequences that have some teeth and make sense. Clearly, some folks who have read about the consequences of not getting vaccinated and may have even lost family members to the disease don’t see those losses as significant consequences for whatever reason. The threat of losing a job is likely to get their attention.
Threats must be carried out even though they may be disruptive in the short term. The good thing about well-crafted mandates is that they can be a win-win for everyone. The vaccine resisters don’t need to admit they were wrong. “Those shots are B.S., but the governor made me do it.” The problem is finding leaders who understand that education has its limits and who have the courage to create and administer the consequences.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.
For more than a decade, studies on the dubious value of education in the face of vaccine refusal and hesitancy have been accumulating. But, too often, the research has been ignored by folks who believe that they can teach the “misinformed” into dropping their resistance. Among some circles education ranks right up there with apple pie and motherhood as one of the pillars of Americana. Those wedded to the education mantra may acknowledge that teaching and preaching hasn’t worked well in the past. But, they may claim it’s because we haven’t done enough of it or hit the right buttons. The notion that if we can just share the facts with the uninformed everything will be fine is a myth that obviously is going to die slowly.
In a recent op-ed piece in the New York Times two physicians at Harvard Medical School reported on their study of about three-quarters of a million children who were eligible to receive HPV vaccines (2021 Dec 21. “Facts alone aren’t going to win over the unvaccinated. This might,” Anupam B. Jena and Christopher M. Worsham). The researchers found that children whose mothers had been diagnosed with cervical cancer were no more likely to be immunized than those children whose mothers had not had the disease. Who could be better informed about risks and hazards of contracting HPV than women with cervical cancer? If the facts won’t motivate, where does that leave us?
Those of you born before 1960 may remember or at least have heard about a television show called “Truth or Consequences.” It was a silly farce of a game show which has no bearing on our nation’s crisis of widespread vaccine refusal. However, buried in its title is the answer. If the truth isn’t convincing the resistors, then the obvious choice is consequences.
I hope that you have discovered that same strategy when counseling parents of misbehaving children. Talk is cheap and often ineffective. Explaining the error of his ways to a child who probably already knows what he is doing wrong is a waste of everyone’s time and unpleasant for those within earshot. At some point, sooner better than later, it’s time to say there is going to be a consequence for this misbehavior – going home from the playground, spending a few minutes in time-out, removing a privilege, etc. If consequences are chosen well and instituted with a minimum of idle threats, they work.
And, we are beginning to see it work in the face of pandemic shot refusal. Here in Maine the governor mandated that all health care workers be vaccinated. There was plenty of gnashing of teeth and threats of mass job walk offs. And, there were a few hospital workers who quit, but in the end it worked.
The trick is choosing consequences that have some teeth and make sense. Clearly, some folks who have read about the consequences of not getting vaccinated and may have even lost family members to the disease don’t see those losses as significant consequences for whatever reason. The threat of losing a job is likely to get their attention.
Threats must be carried out even though they may be disruptive in the short term. The good thing about well-crafted mandates is that they can be a win-win for everyone. The vaccine resisters don’t need to admit they were wrong. “Those shots are B.S., but the governor made me do it.” The problem is finding leaders who understand that education has its limits and who have the courage to create and administer the consequences.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.
For more than a decade, studies on the dubious value of education in the face of vaccine refusal and hesitancy have been accumulating. But, too often, the research has been ignored by folks who believe that they can teach the “misinformed” into dropping their resistance. Among some circles education ranks right up there with apple pie and motherhood as one of the pillars of Americana. Those wedded to the education mantra may acknowledge that teaching and preaching hasn’t worked well in the past. But, they may claim it’s because we haven’t done enough of it or hit the right buttons. The notion that if we can just share the facts with the uninformed everything will be fine is a myth that obviously is going to die slowly.
In a recent op-ed piece in the New York Times two physicians at Harvard Medical School reported on their study of about three-quarters of a million children who were eligible to receive HPV vaccines (2021 Dec 21. “Facts alone aren’t going to win over the unvaccinated. This might,” Anupam B. Jena and Christopher M. Worsham). The researchers found that children whose mothers had been diagnosed with cervical cancer were no more likely to be immunized than those children whose mothers had not had the disease. Who could be better informed about risks and hazards of contracting HPV than women with cervical cancer? If the facts won’t motivate, where does that leave us?
Those of you born before 1960 may remember or at least have heard about a television show called “Truth or Consequences.” It was a silly farce of a game show which has no bearing on our nation’s crisis of widespread vaccine refusal. However, buried in its title is the answer. If the truth isn’t convincing the resistors, then the obvious choice is consequences.
I hope that you have discovered that same strategy when counseling parents of misbehaving children. Talk is cheap and often ineffective. Explaining the error of his ways to a child who probably already knows what he is doing wrong is a waste of everyone’s time and unpleasant for those within earshot. At some point, sooner better than later, it’s time to say there is going to be a consequence for this misbehavior – going home from the playground, spending a few minutes in time-out, removing a privilege, etc. If consequences are chosen well and instituted with a minimum of idle threats, they work.
And, we are beginning to see it work in the face of pandemic shot refusal. Here in Maine the governor mandated that all health care workers be vaccinated. There was plenty of gnashing of teeth and threats of mass job walk offs. And, there were a few hospital workers who quit, but in the end it worked.
The trick is choosing consequences that have some teeth and make sense. Clearly, some folks who have read about the consequences of not getting vaccinated and may have even lost family members to the disease don’t see those losses as significant consequences for whatever reason. The threat of losing a job is likely to get their attention.
Threats must be carried out even though they may be disruptive in the short term. The good thing about well-crafted mandates is that they can be a win-win for everyone. The vaccine resisters don’t need to admit they were wrong. “Those shots are B.S., but the governor made me do it.” The problem is finding leaders who understand that education has its limits and who have the courage to create and administer the consequences.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.