Immunomodulation as Treatment for Severe COVID-19: a systematic review of current modalities and future directions

Clin Infect Dis. 2020 Nov 20;ciaa1759. doi: 10.1093/cid/ciaa1759. Online ahead of print.


In SARS-CoV-2 infection, the viral load peaks early setting off a cascade of immune dysregulation that persists well after viral clearance. Severe COVID-19 is marked by aberrant innate and adaptive immune responses with an abnormal cytokine profile and a prolonged illness course with multisystem organ dysfunction. Antiviral treatments have yet to show benefit later in critical illness. Taken together, this raises the concern that a purely antiviral treatment approach may be insufficient. A number of immunomodulatory strategies are being tested, including corticosteroids, cytokine and anti-cytokine therapies, small molecule inhibitors, and cellular therapeutics. The only drug to date to show a mortality benefit for COVID-19 in a randomized control trial is dexamethasone, but there remains uncertainty about which patients may benefit most and longer-term complications including secondary infections. Here we review the immune dysregulation of severe COVID-19, the existing data behind various immunomodulatory strategies, and consider future directions of study.

Keywords: COVID-19; SARS-CoV-2; cytokine storm; hyperinflammatory; immunomodulation; treatments.