Optimizing Remdesivir's Use for COVID-19: Infection vs. Inflammation

Initiating remdesivir within 5 to 7 days of developing COVID-19 symptoms maximizes this agent's benefits by targeting the viral phase of illness before the onset of secondary inflammation. However, the transition between “viral” and “inflammatory” phases is variable and not discrete, making remdesivir's benefits difficult to determine on an individual level. Padilla and colleagues assessed 28-day mortality and need for invasive mechanical ventilation in a cohort of 1368 patients hospitalized with COVID-19 at one hospital in Spain between March 2020 and April 2021. The cohort was stratified by baseline SARS-CoV-2 viral load (high load defined as PCR cycle threshold [ct] <25) and degree of systemic inflammation (low-grade inflammation defined as C-reactive protein (CRP) <38 mg/L). Despite the early timeline within the pandemic, therapy was provided according to an institutional protocol that included dexamethasone and tocilizumab starting in March 2020, with remdesivir becoming available in July 2020. All participants received glucocorticoids; 74% also received tocilizumab, 63% remdesivir, and 56% tocilizumab plus remdesivir.

Among patients receiving both glucocorticoid and tocilizumab, 28-day mortality was differentially affected by receipt of remdesivir depending on viral load and inflammation. The adjusted hazard ratio (aHR) was 0.48 for those with high viral load, 0.12 for those with high viral load and <5 days of symptoms, and 0.13 for those with low-grade inflammation. The aHR for invasive mechanical ventilation in remdesivir recipients was 0.32 among those with high viral load.