SARS-CoV-2 and viral sepsis: observations and hypotheses

Lancet. 2020 May 9;395(10235):1517-1520. doi: 10.1016/S0140-6736(20)30920-X. Epub 2020 Apr 17.


Since the outbreak of coronavirus disease 2019 (COVID-19), clinicians have tried every effort to understand the disease, and a brief portrait of its clinical features have been identified. In clinical practice, we noticed that many severe or critically ill COVID-19 patients developed typical clinical manifestations of shock, including cold extremities and weak peripheral pulses, even in the absence of overt hypotension. Understanding the mechanism of viral sepsis in COVID-19 is warranted for exploring better clinical care for these patients. With evidence collected from autopsy studies on COVID-19 and basic science research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV, we have put forward several hypotheses about SARS-CoV-2 pathogenesis after multiple rounds of discussion among basic science researchers, pathologists, and clinicians working on COVID-19. We hypothesise that a process called viral sepsis is crucial to the disease mechanism of COVID-19. Although these ideas might be proven imperfect or even wrong later, we believe they can provide inputs and guide directions for basic research at this moment.

MeSH terms

  • Autopsy
  • Betacoronavirus / pathogenicity*
  • Blood Coagulation Disorders / virology
  • COVID-19
  • Coronavirus Infections* / complications
  • Critical Illness
  • Cytokines / metabolism*
  • Endothelium
  • Epithelium
  • Humans
  • Inflammation
  • Lung* / immunology
  • Lung* / pathology
  • Macrophages
  • Pandemics*
  • Pneumonia, Viral* / complications
  • SARS-CoV-2
  • Sepsis / virology*
  • Severity of Illness Index
  • Shock / etiology


  • Cytokines