Definitions matter: Heterogeneity of COVID-19 disease severity criteria and incomplete reporting compromise meta-analysis

by Guérin PJ, McLean ARD, Rashan S, Lawal A, Watson JA, Strub-Wourgaft N, White NJ. PLOS Global Public Health 2022; 2(7): e0000561.

Summary: Therapeutic efficacy in COVID-19 depends upon disease severity, with antivirals likely to be beneficial when administered early, while immune modulating and anti-inflammatory drugs are beneficial later in the disease, however, definitions of severity vary widely. The authors reviewed the 81 studies included in the network meta-analysis (NMA) of published RCTs, the basis for the WHO’s ‘living’ guidelines for the treatment of COVID-19, comparing severity classifications with those of the international COVID-NMA initiative. They were concordant in 35% of trials. This imprecision compromises the validity of some recommendations; notably extrapolation of “lack of therapeutic benefit” in severely ill patients on respiratory support to mildly ill patients. Harmonised definitions of severity and individual patient data meta-analyses are needed to guide COVID-19 therapeutic recommendations.

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