Do Viral or Host Factors Explain the Varying Clinical Course of COVID-19?

The clinical course of COVID-19 infection varies markedly — from asymptomatic infection to mild pneumonia to overwhelming acute respiratory distress syndrome with concurrent fulminant sepsis. Is this variation caused by genomic changes in the virus or by host factors? Preliminary data addressing this question come from an analysis of 326 patients in Shanghai who had COVID-19 in January and February 2020; viral sequence data were available from 94 patients.

Most had mild disease with fever and radiologic findings, but 12 had more-severe disease, and 16 were critically ill and required mechanical ventilation or extracorporeal membrane oxygenation. Viral genomic analysis that included both the patients' viral sequences and 221 additional genomes from the Global Initiative on Sharing All Influenza Data international database identified two major clades, with multiple subclades. The patients' isolates were scattered throughout both clades, and no differences in clinical outcomes were apparent between the clades. In contrast, there was marked variation in the clinical outcome associated with the degree of lymphocytopenia and the number of CD3, CD4, and CD8 T cells. Multivariate analysis showed that the two independent clinical factors were patient age and lymphocytopenia.