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Immunomodulation as Treatment for Severe Coronavirus Disease 2019: A Systematic Review of Current Modalities and
Eric A Meyerowitz1, Pritha Sen2,3, Sara R Schoenfeld3,4
1Division of Infectious Diseases, Department of Medicine, Montefiore Medical Center, Bronx, New York, USA.
Abstract:
In severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, viral load peaks early and declines quickly after symptom onset. Severe coronavirus disease 2019 (COVID-19) is marked by aberrant innate and adaptive immune responses with an abnormal cytokine profile and multiorgan system dysfunction that persists well after viral clearance. A purely antiviral treatment strategy may therefore be insufficient, and antiviral agents have not shown a benefit later in the illness course. A number of immunomodulatory strategies are being tested, including corticosteroids, cytokine and anticytokine therapies, small molecule inhibitors, and cellular therapeutics. To date, the only drug to show a mortality benefit for COVID-19 in a randomized, controlled trial is dexamethasone. However, there remains uncertainty about which patients may benefit most and about longer-term complications, including secondary infections. Here, we review the immune dysregulation of severe COVID-19 and the existing data behind various immunomodulatory strategies, and we consider future directions of study.
Insights
Severe COVID-19 involves immune system overreaction, not just the virus. Immunomodulatory therapies, like dexamethasone, show promise, but further research is needed to identify optimal patient candidates and address long-term risks.
Area of Science:
- Immunology
- Virology
- Critical Care Medicine
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to significant immune dysregulation.
- Aberrant immune responses and cytokine profiles characterize severe coronavirus disease 2019 (COVID-19), persisting post-viral clearance.
- Antiviral strategies alone are insufficient for severe COVID-19, especially later in the disease course.
Purpose of the Study:
- To review immune dysregulation in severe COVID-19.
- To analyze existing data on immunomodulatory strategies for severe COVID-19.
- To discuss future research directions for managing severe COVID-19.
Main Methods:
- Literature review of immune responses in severe COVID-19.
- Analysis of clinical trial data for immunomodulatory therapies.
- Synthesis of information on cytokine profiles and multiorgan dysfunction.
Main Results:
- Dexamethasone is the only drug demonstrating mortality benefit in randomized controlled trials for COVID-19.
- Various immunomodulatory strategies are under investigation, including corticosteroids and cytokine-targeted therapies.
- Uncertainty remains regarding patient selection for immunomodulatory treatments and potential long-term complications.
Conclusions:
- Immune dysregulation is a critical factor in severe COVID-19 pathogenesis.
- Immunomodulatory therapies represent a key therapeutic avenue, with dexamethasone showing initial promise.
- Further research is essential to optimize treatment strategies and understand long-term outcomes, including secondary infections.
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