In this study, lipidomic changes were analyzed in plasma and isolated exosomes, but not in lung tissues or sputum of COVID-19 patients, for which viral counts were expected to be highest. Based on the current study design, it is thus not possible to establish a direct association between the lipidomic changes observed with SARS-CoV-2 infection. Nonetheless, in a previous study on mice infected with RSV that analyzed both lung tissues and plasma lipid changes, multiple correlations between plasma and lung lipids altered by RSV infection were reported (Shan et al., 2018). Metabolite spillage from the lungs into the circulation may also be reasonably expected in cases with compromised alveolar-capillary barrier, such as in moderate and severe COVID-19 patients with pneumonia. While we followed a small group of five patients longitudinally to elucidate plasma metabolites associated with recovery phase (Figure S2), further validation from a larger longitudinal cohort is needed. Our results were based on a single Chinese cohort of COVID-19 patients in China, and future studies in different racial, ethnic, and geographical cohorts will be indispensable for extending our current understanding of lipid metabolic dysregulation in COVID-19 pathogenesis. In addition, while we included age, sex, and BMI as covariates in our logistic regression analyses, the statistically significant age and BMI differences between healthy controls and patients are potential confounders in the current study, due to technical constraints in recruiting age- and BMI-matched healthy controls during the outbreak. Finally, the metabolic dysregulation underlying the observed exosomal enrichment in GM3s awaits further mechanistic validation, although our preliminary evidence suggested that the selective increases in exosomal GM3s might have contributions from non-exosomal plasma components, as indicated by the decreasing GM3 content in exosome-free supernatant with increasing disease severity (Figure S5C).