Reply to Khatun et al. SARS-CoV2 Endotheliopathy: Insights from Single Cell RNAseq - Sorbonne Université Access content directly
Journal Articles (Data Paper) American Journal of Respiratory and Critical Care Medicine Year : 2022

Reply to Khatun et al. SARS-CoV2 Endotheliopathy: Insights from Single Cell RNAseq

Michael A Matthay
  • Function : Author
Judith Hellman


We thank Khatun and colleagues for their insightful comments on our recent manuscript describing the in vitro effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and of coronavirus disease (COVID-19) patient sera on human endothelial cells (1). We are pleased that the authors found our proposed model of COVID-19-associated endotheliopathy to be consistent with their published data (2, 3). We apologize for not citing these important publications. In our study, we detected SARS-CoV-2 RNA in lysates of primary human lung microvascular endothelial cells (HMVEC) treated with live SARS-CoV-2 and observed that exposure to live virus induced an increase in permeability and activation of HMVEC. We also found increased permeability of HMVEC treated with sera from COVID-19 patients that correlated with disease severity. We postulated that COVID-19-associated endotheliopathy results from a combination of the actions of systemic and localized inflammatory mediators and cells on the endothelium, and by SARS-CoV-2 infection of the endothelium. Using a model of severe COVID-19 in K18-hACE2 mice, the authors previously reported SARS-CoV-2 in lung capillary endothelial cells in both the early and delayed stages of severe COVID-19, as well as lung edema, perivascular inflammation, upregulated adhesion molecule expression, and decreased vascular endothelial-cadherin expression (2, 3). Similarly, they observed co-localization of SARS-CoV-2 viral proteins with the endothelial marker CD31 in nonhuman primates with severe COVID-19, and also in autopsy samples from a patient that died of COVID-19. In their comment, the authors present additional single-cell RNAseq data on samples from SARS-CoV-2-infected mice. Their data confirm the presence of viral RNA within endothelial cells and demonstrate increased expression of Ifi27l2a and Irf7, and decreased expression of Cldn5 by infected endothelial cells. These new data further support the concept that SARS-CoV-2 infection of endothelial Author disclosures are available with the text of this letter at
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hal-04022299 , version 1 (12-06-2023)



Jérémie Joffre, Michael A Matthay, Judith Hellman. Reply to Khatun et al. SARS-CoV2 Endotheliopathy: Insights from Single Cell RNAseq. American Journal of Respiratory and Critical Care Medicine, 2022, 206 (9), pp.1179-1180. ⟨10.1164/rccm.202207-1309LE⟩. ⟨hal-04022299⟩
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