Management of Severe and Critical COVID-19 Infection with Immunotherapies

Abstract

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.

Keywords: Critical COVID-19 infection; Immunotherapy; Severe COVID-19 infection.

Fig. 1

Comparison of treatment recommendations for severe and critical COVID-19 infection and the relevance of clinical trial evidence to the ICU population. (A) Algorithm of currently recommended treatment guidelines for severe and critical COVID-19 infection. (B) Visual representation of the applicability and generalizability of the results of the cited trials to a critically ill population by comparing 3 aspects of study design with the magnitude of treatment effect observed in the trials. Treatment effect is a qualitative measure that includes comparison across multiple types of reported results including odds ratios, hazard ratios, survival analyses. The size of the circle corresponds to the size of the trial. ACTT, Adaptive COVID-19 Treatment Trial; CDX, CODEX; CO AN, CORIMMUNO-ANA-1; COV BAR, COVID BARRIER; CN CO, CAN-COVID; CP CO, CAPE COVID; CT CO, CounterCovid; CVTA, COVACTA; LA, LIVE AIR; OSC, OSCAR; RCVY dex, RECOVERY dexamethasone; RCVY IL6, RECOVERY tocilizumab; RMP IL1, REMAP CAP anakinra; RMP IL6, REMAP CAP tocilizumab/sarilumab; SM, SAVE MORE.