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Severe COVID 19
How I Manage People With Severe COVID-19

Released: January 10, 2025

Expiration: January 09, 2026

Rajesh T. Gandhi
Rajesh T. Gandhi, MD
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Key Takeaways
  • People hospitalized with severe COVID-19 should be treated with immunomodulators and antiviral therapy.
  • Several gaps in COVID-19 management exist such as the need for a better understanding of the role of biomarkers in guiding therapy and the optimal approach to antiviral therapy in immunocompromised patients with prolonged SARS-CoV-2 replication.

Recently, I was asked for recommendations on how to manage COVID-19 in a 54-year-old patient with rheumatoid arthritis; the patient received rituximab approximately 1 year ago after not responding to TNF inhibitor therapy.

The patient presented to the emergency department, where they were noted to be tachypneic and had an oxygen saturation of 88%. They received the COVID-19 vaccine in 2021 but no subsequent boosters. They were doing well until 3 days ago, when they developed fever, cough and shortness of breath. 

Their chest x-ray showed bilateral pulmonary infiltrates. Their SARS-CoV-2 test was positive, and C-reactive protein (CRP) level was 100 mg/L. They were admitted to the hospital and, over the next 12 hours, they required increasing amounts of oxygen to maintain their saturation above 92%. At the time I was called, they were receiving 5 liters of oxygen.

Immunomodulators
The first step in deciding appropriate treatment is to assess COVID-19 severity. This patient had severe COVID-19, requiring oxygen supplementation. One of the main drivers of severe COVID-19 is hyperinflammation and, for that reason, immunomodulatory therapy is a highly effective treatment option.

The RECOVERY trial found that dexamethasone decreased mortality in people hospitalized with COVID-19 who required supplemental oxygen or mechanical ventilation. Subsequent studies found that adding baricitinib (a Janus kinase inhibitor) or tocilizumab (an interleukin-6 inhibitor) was beneficial in people like our patient—that is, individuals with severe and progressive COVID-19 and elevated inflammatory markers (in this case, CRP). For this reason, I would start this patient on dexamethasone and baricitinib. If baricitinib was not available, I would substitute tocilizumab.

Antiviral Therapy
In addition to dual immunomodulators, I would also start antiviral therapy with remdesivir, which inhibits SARS-CoV-2 replication. Like most antivirals, remdesivir is most effective when started early after symptom onset. For example, in the clinical trial ACTT-1, remdesivir conferred the greatest benefit in hospitalized patients when started within 10 days of symptom onset. 

This patient was treated with dexamethasone, baricitinib, and remdesivir. Over the ensuing 5 days, the patient improved and was ultimately discharged from the hospital. The patient was counseled to receive the latest COVID-19 vaccine booster, which they did about 3 months after hospitalization. 

Gaps in COVID-19 Care
The care of this patient illustrates what we have learned about the use of immunomodulators and antivirals in people hospitalized with COVID-19. However, several gaps in our knowledge about COVID-19 exist, including:

  • Are there specific biomarkers that can be used to identify which people should be treated with immunomodulators and which immunomodulators will be most effective?
  • Will more potent antivirals improve outcomes in hospitalized individuals with high baseline SARS-CoV-2 levels?
  • Is there a role for new antiviral agents (eg, small molecules, novel monoclonal antibodies, convalescent plasma) or combinations of antivirals in immunocompromised patients with severe COVID-19 and prolonged SARS-CoV-2 replication?

We look forward to future studies to answer these and other important questions about the management of severe or critical COVID-19 as well as mild or moderate COVID-19 and its treatment.

Your Thoughts?
What COVID-19 therapies would you recommend for this patient? Join the discussion by posting a comment below.