In reply—COVID-19: Precision Medicine and Vascular Endothelium

To The Editor:

We appreciate the kind comments provided by Travagli et al regarding our article on interindividual variability¹ and fully agree with their statement that recognition of coronavirus disease 2019 (COVID-19) host/genetic factors should inform the design of precision clinical trials in this disease. We also acknowledge that inflammatory changes in the vascular endothelium are an important component of the response to COVID-19 infection. However, the studies cited by the authors do not provide evidence of interindividual variability in these processes (small vessel endotheliitis, vascular endothelial glycocalyx levels, or neutrophil extracellular trap formation and/or dysregulation) that could contribute to the variability observed in COVID-19 susceptibility, severity, and outcome. The question also arises whether the endothelial changes that occur in COVID-19 are a downstream change to variability observed in upstream processes that involve angiotensin-converting enzyme 2, transmembrane serine protease 2, toll-like receptors, and other factors as described in our article. We do look forward to future agnostic multi-omic (proteomic, transcriptomic, and metabolomic) studies that could explore the role of such pathways and find their association, or lack thereof, with interindividual variation in COVID-19.