SARS-CoV-2 in Airway Can Trigger Lung Fibrosis; Potential Treatment Identified

NIAID Now | October 12, 2023

Image of fibrin deposits (red) associated with human lung epithelial cells infected with SARS-CoV-2.

The image shows fibrin deposits (red) associated with human lung epithelial cells infected with SARS-CoV-2.

Credit: NIAID
Image of uninfected, and an absence of fibrin deposits

The image shows the same cells uninfected, and an absence of fibrin deposits.

Credit: NIAID

NIAID scientists and colleagues have identified a cause of COVID-induced lung fibrosis, a severe and often fatal result of COVID-19 that leaves lungs scarred, clotted and leathery, and patients struggling to breathe. Their study, published in Nature Communications, also offers an explanation why traditional blood thinners have not helped patients – but why other treatments might.

Scientists from NIAID’s intramural program, with colleagues from Indiana University Medical Center, tested lung fluid samples from about two dozen COVID-19 donors, including acute, recovered, and healthy groups. This work showed that two proteins produced in the liver, fibrinogen and prothrombin, increased 50 to 100 times their normal amount during SARS-CoV-2 infection. The proteins, found in blood, can be converted to fibrin and thrombin, which assist with blood clotting. Traditional serum-based blood thinners, such as heparin, counteract the conversion to fibrin and thrombin to protect against clotting.

To explore a direct connection between viral infection and lung fibrosis, the researchers exposed human epithelial cells from the bronchial tubes and trachea to different SARS-CoV-2 virus variants. The experiments showed that SARS-CoV-2 infection of these airway cells caused a fibrin response that required the presence of thrombin and was consistent with COVID-induced lung fibrosis.

They further discovered a new cell-based mechanism within the airway that converted prothrombin to thrombin and subsequently fibrinogen to fibrin. The scientists believe blood thinners, such as heparin, have not been effective against SARS-CoV-2-induced lung fibrosis because the cell-based mechanism is independent of the serum-based fibrin and thrombin conversion.

Instead, the scientists suggest treating COVID lung fibrosis with “interventions focusing on using nebulized direct thrombin inhibitors to target airway space,” such as argatroban and dabigatran. They also suggest that physicians could evaluate patient risk of developing COVID-induced lung fibrosis by measuring prothrombin, fibrinogen, and other coagulation concentrations in lung fluid.


R Erickson, et al. SARS-CoV-2 infection of human lung epithelial cells induces TMPRSS-mediated acute fibrin deposition. Nature Communications. DOI 10.1038/s41467-023-42140-6 (2023).

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