Vaccination protects against COVID-associated pulmonary fibrin deposition.

Understanding the protective mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines against severe COVID is important for therapeutic development to mitigate disease-associated lung pathologies. Here, we investigated the association between vaccination and the disease severity with a particular emphasis on viral-induced pulmonary fibrin formation in 43 COVID individuals. While COVID vaccination reduced the disease severity in this cohort, their plasma coagulation indices, including prothrombin time (PT), partial thromboplastin time (PTT), and D-dimer concentrations, remain unchanged between the vaccinated and non-vaccinated individuals. In contrast, vaccination lowered pulmonary inflammatory and coagulation signatures, reduced fibrinogen concentrations, and prevented prothrombin activation in bronchoalveolar lavage fluid (BALF), such that no viral-induced fibrin was observed in the vaccinated BALF. The formation of viral-induced fibrin correlated with the disease severity and was observed in non-vaccinated BALF samples containing high concentrations of fibrinogen and prothrombin, suggesting vaccination protected against the viral-induced pulmonary fibrin formation. Our finding highlights the use of pulmonary rather than plasma fibrinogen levels as a risk indicator for severe COVID disease.IMPORTANCEUnderstanding the protective mechanism of COVID-19 vaccines against the severity of the disease is important for therapeutic development, and thus, subject to intense investigation. Here, we studied a cohort of 43 COVID patients based on their vaccination status. We showed that (i) COVID disease severity is associated with the formation of SARS-CoV-2-induced pulmonary fibrin, (ii) vaccination protected against severe COVID disease by reducing infiltration of coagulants, preventing prothrombin activation and fibrin deposition in infected lungs, and (iii) plasma coagulation indices are not useful indicators for fibrin deposition in infected lungs. Rather, the level of pulmonary fibrinogen provides an informative indicator for COVID-associated coagulation in lung.