Management of Severe and Critical COVID-19 Infection with Immunotherapies

Following the reduction in mortality demonstrated by dexamethasone treatment in severe COVID-19, many targeted immunotherapies have been investigated. Thus far, inhibition of IL-6 and JAK pathways have the most robust data and have been granted Emergency Use Authorization for treatment of severe disease. However, it must be noted that critically ill patients comprised a relatively small proportion of most of the trials of COVID-19 therapeutics, despite bearing a disproportionate burden of morbidity and mortality. Furthermore, the rapidity and fluidity with which clinical trials have been conducted in the pandemic setting have contributed to difficulty in extrapolating available trial data to critically ill patients. The exclusion of many patients requiring invasive mechanical ventilation, preponderance of ordinal scale based endpoints, and frequent lack of blinding are particular challenges. More data is needed to identify beneficial treatments in the complex milieu of critical illness from COVID-19 infection.