Fibrinogen, Fibrin, and Fibrin Degradation Products in COVID-19

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the highly pathogenicand highly transmissible human coronavirus that is the causative agent for the worldwideCOVID-19 pandemic. COVID-19 manifests predominantly as a respiratory illness with symptomsconsistent with viral pneumonia, but other organ systems (e.g., kidney, heart, brain) can also becomeperturbed in COVID-19 patients. Accumulating data suggest that significant activation of thehemostatic system is a common pathological manifestation of SARS-CoV-2 infection. The clottingprotein fibrinogen is one of the most abundant plasma proteins. Following activation of coagulation,the central coagulation protease thrombin converts fibrinogen to fibrin monomers, which selfassembleto form a matrix, the primary structural component of the blood clot. Severe COVID-19 isassociated with a profound perturbation of circulating fibrinogen, intra- and extravascular fibrindeposition and persistence, and fibrin degradation. Current findings suggest high levels of fibrinogenand the fibrin degradation product D-dimer are biomarkers of poor prognosis in COVID-19.Moreover, emerging studies with in vitro and animal models indicate fibrin(ogen) as an active playerin COVID-19 pathogenesis. Here, we review the current literature regarding fibrin(ogen) andCOVID-19, including possible pathogenic mechanisms and treatment strategies centered on clottingand fibrin(ogen) function.