Biphasic Thrombus Development During Coronavirus Infection
Manuel Salzmann, Ph.D.
Division of Cardiology
Medical University of Vienna
SARS-CoV-2 causes the disease known as COVID-19. It most commonly presents with influenza-like illness and viral pneumonia, but in its most severe manifestation progresses to acute respiratory distress syndrome and multi-organ failure. To date, the viral pandemic has resulted in millions of infections worldwide. In COVID-19, elevated levels of blood neutrophils predict severe respiratory disease and unfavorable outcomes. Neutrophil-derived extracellular traps (NETs) play a pathogenic role in many thrombo-inflammatory states including sepsis, thrombosis, and respiratory failure. NETs are extracellular webs of chromatin and microbicidal proteins that are an evolutionarily conserved aspect of innate immune host defense; however, NETs also have potential to initiate and propagate inflammation and thrombosis. Thrombosis and activation of neutrophils are bystanders of a SARS-CoV-2 infection in humans. However, these events seem to appear late during the disease and might represent a skewed activation of the immune system. Manuel Salzmann of the Medical University of Vienna, Division of Cardiology, in Vienna, Austria, presented findings on Sunday, July 18, 2021, around the investigation of thrombosis during a SARS-CoV infection, using murine coronavirus M-CoV, histology, high throughput image analysis, qPCR, and ELISA.
Salzmann commented that thrombus formation occurred rapidly, with 1.73 thrombi/mm2 lung section two days after M-CoV infection, which further increased to 3.92 thrombi/mm2 at day 4 and stayed stable with 4.09 thrombi/mm2 at day 10. Compared with day 2, the virus burden was already reduced twofold at day 4 and 100-fold at day 10. Day 4 thrombi were platelet rich, whereas thrombi at day 10 were positive for citrullinated histone H4, a marker for NETs, which also coincided with a decrease in neutrophils by 40% and an increase in lung cell apoptosis of 1.8% to 10.5% measured by double-strand DNA breaks via terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling, or TUNEL. The conclusion made was that while the early-phase thrombi are platelet rich, the late-phase thrombi are associated with neutrophil activation and NET formation. Targeting specific thrombotic events during the infection will ameliorate potential lung tissue damage.