Applied Evidence

COVID-19 therapy: What works? What doesn’t? And what’s on the horizon?   

Author and Disclosure Information

Here is the latest evidence on the efficacy and safety of treatments that are FDA approved or authorized, in clinical trials, or not recommended to combat COVID-19.


› Use antivirals (eg, molnupiravir, nirmatrelvir packaged with ritonavir [Paxlovid], and remdesivir) and monoclonal antibody agents (eg, bebtelovimab) effective against the circulating Omicron variant, to treat symptoms of mild-to-moderate COVID-19 illness. C

› Treat severely ill hospitalized COVID-19 patients who require supplemental oxygen with dexamethasone, alone or in combination with remdesivir, to produce better outcomes. B

› Consider administering baricitinib or tocilizumab, in addition to dexamethasone with or without remdesivir, to COVID-19 patients with rapidly increasing oxygen requirements. B

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series



The ongoing COVID-19 pandemic has caused more than 1 million deaths in the United States and continues to be a major public health challenge. Cases can be asymptomatic, or symptoms can range from a mild respiratory tract infection to acute respiratory distress and multiorgan failure.

Three strategies can successfully contain the pandemic and its consequences:

  • Public health measures, such as masking and social distancing
  • Prophylactic vaccines to reduce transmission
  • Safe and effective drugs for reducing morbidity and mortality among infected patients.

Optimal treatment strategies for patients in ambulatory and hospital settings continue to evolve as new studies are reported and new strains of the virus arise. Many medical and scientific organizations, including the National Institutes of Health (NIH) COVID-19 treatment panel,1 Infectious Diseases Society of America (IDSA),2 World Health Organization (WHO),3 and Centers for Disease Control and Prevention,4 provide recommendations for managing patients with ­COVID-19. Their guidance is based on the strongest research available and is updated intermittently; nevertheless, a plethora of new data emerges weekly and controversies surround several treatments.

In this article, we summarize evidence for the efficacy of treatments for COVID-19. We present data based on the severity of illness, and review special considerations for some patient populations, including pregnant women and children. We focus on practical therapeutic information for primary care providers practicing in a variety of settings, including outpatient and inpatient care.

We encourage clinicians, in planning treatment, to consider:

  • The availability of medications (ie, use the COVID-19 Public Therapeutic Locatora)
  • The local COVID-19 situation
  • Patient factors and preferences
  • Evolving evidence regarding new and existing treatments.

When planning treatment, consider the availability of medications; the local COVID-19 situation; patient factors and preferences; and evolving evidence about treatments.

Most evidence about the treatment of COVID-19 comes from studies conducted when the Omicron variant of SARS-CoV-2 was not the dominant variant, as it is today in the United States. As such, drugs authorized or approved by the US Food and Drug Administration (FDA) to treat COVID-19 or used off-label for that purpose might not be as efficacious today as they were almost a year ago. Furthermore, many trials of potential therapies against new viral variants are ongoing; if your patient is interested in enrolling in a clinical trial of an investigational COVID-19 treatment, refer them to

General managementof COVID-19

Patients with COVID-19 experience a range of illness severity—from asymptomatic to mild symptoms, such as fever and myalgia, to critical illness requiring intensive care (TABLE 11,2). Patients with COVID-19 should therefore be monitored for progression, remotely or in person, until full recovery is achieved. Key concepts of general management include:

Assess and monitor patients’ oxygenation status by pulse oximetry; identify those with low or declining oxygen saturation before further clinical deterioration.

Severity classification of coronavirus disease 2019

Continue to: Consider the patient's age and general health


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