Vitamin K metabolism as the potential missing link between lung damage and thromboembolism in Coronavirus disease 2019

Br J Nutr. 2021 Jul 28;126(2):191-198. doi: 10.1017/S0007114520003979. Epub 2020 Oct 7.


Coronavirus disease 2019 (Covid-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2, exerts far-reaching effects on public health and socio-economic welfare. The majority of infected individuals have mild to moderate symptoms, but a significant proportion develops respiratory failure due to pneumonia. Thrombosis is another frequent manifestation of Covid-19 that contributes to poor outcomes. Vitamin K plays a crucial role in the activation of both pro- and anticlotting factors in the liver and the activation of extrahepatically synthesised protein S which seems to be important in local thrombosis prevention. However, the role of vitamin K extends beyond coagulation. Matrix Gla protein (MGP) is a vitamin K-dependent inhibitor of soft tissue calcification and elastic fibre degradation. Severe extrahepatic vitamin K insufficiency was recently demonstrated in Covid-19 patients, with high inactive MGP levels correlating with elastic fibre degradation rates. This suggests that insufficient vitamin K-dependent MGP activation leaves elastic fibres unprotected against SARS-CoV-2-induced proteolysis. In contrast to MGP, Covid-19 patients have normal levels of activated factor II, in line with previous observations that vitamin K is preferentially transported to the liver for activation of procoagulant factors. We therefore expect that vitamin K-dependent endothelial protein S activation is also compromised, which would be compatible with enhanced thrombogenicity. Taking these data together, we propose a mechanism of pneumonia-induced vitamin K depletion, leading to a decrease in activated MGP and protein S, aggravating pulmonary damage and coagulopathy, respectively. Intervention trials should be conducted to assess whether vitamin K administration plays a role in the prevention and treatment of severe Covid-19.

Keywords: Covid-19; Matrix Gla protein; Protein S; Prothrombin; Vitamin K.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19 / complications
  • COVID-19 / pathology*
  • Calcium-Binding Proteins / metabolism
  • Extracellular Matrix Proteins / metabolism
  • Humans
  • Lung / physiopathology*
  • Protein S / metabolism
  • SARS-CoV-2*
  • Thromboembolism / etiology
  • Thromboembolism / prevention & control*
  • Thrombosis / etiology
  • Thrombosis / prevention & control*
  • Vitamin K / antagonists & inhibitors
  • Vitamin K / metabolism*
  • Vitamin K Deficiency / etiology
  • Vitamin K Deficiency / metabolism*


  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • Protein S
  • matrix Gla protein
  • Vitamin K