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COVID-19 in Immunocompromise
COVID-19 in Immunocompromise: What I Do and Why

Released: January 22, 2025

Expiration: January 21, 2026

Michele Bartoletti
Michele Bartoletti, MD, PhD
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Key Takeaways
  • Antiviral therapy should be considered for all people with COVID-19 who are immunocompromised, regardless of disease severity.
  • Use of immunomodulators for COVID-19 treatment in people who are immunocompromised remains debatable; however, if considering their use, antiviral therapy should be given concomitantly.

SARS-CoV-2 has changed dramatically over the last 2 seasons, and natural or vaccine-induced immunity is changing the epidemiologic landscape of COVID-19.

In the very early phase of the pandemic, many patients diagnosed with COVID-19, especially those aged between 60 and 65 years, were in critical condition. At present, based on my experience, few patients are hospitalized with severe COVID-19, and among those who are, most are immunocompromised.

When considering treatment for people who are immunocompromised and have COVID-19, several gaps exist because current recommendations are based on studies that often excluded this group of patients.

In this commentary, I discuss my approach to inpatient COVID-19 management in people who are immunocompromised.

Inpatient COVID-19 Management
Antiviral therapy should be considered first. Antiviral therapy is recommended for (1) patients with severe COVID-19 and (2) those with mild or moderate COVID-19 with risk factors for severe COVID-19 progression, which includes people who are immunocompromised. Recommendations vary on the use of antiviral therapy in people with critical COVID-19 who are receiving invasive mechanical ventilation and/or extracorporeal membrane oxygenation.

Among people who are immunocompromised, I think that antivirals should be considered regardless of disease severity—including for those who are critically ill—and should be prescribed before starting other COVID-19 therapies such as immunomodulators. In general, I begin with a single antiviral agent, and I might consider 2 antiviral agents if the patient continues experiencing symptoms over the next 5-7 days.

Should Immunomodulators Be Used?
Inflammatory markers such as C-reactive protein may be altered in people with severe COVID-19 who are immunocompromised. Some healthcare professionals still use these biomarkers as indicators of which patients will benefit from steroids or other anti-inflammatory drugs. However, in the first wave of the pandemic, the true threshold for determining who may benefit from steroids was the need for supplemental oxygen therapy; in patients who require oxygen therapy, steroids have been found to reduce the risk of mortality. 

Current guidelines recommend dexamethasone and other immunomodulators such as baricitinib or tocilizumab in patients requiring oxygen, whether through noninvasive or invasive mechanical ventilation.

Among people who are immunocompromised, the use of these agents is debatable because most of these patients continue to have high levels of virus replication and lower levels of inflammation than those observed in the general population.

Although there is no consensus on the use of steroids and other immunomodulators in people who are immunocompromised, most healthcare professionals prefer these drugs because they are included in the evolving guidelines. Most importantly, I believe that if you are considering the use of an immunomodulator for COVID-19 treatment in a person who is immunocompromised, antiviral therapy should be used concomitantly.

Your Thoughts?
How do you approach severe COVID-19 treatment in a person who is immunocompromised? Join the discussion by posting a comment below.