Researchers have found that 10% of blood monocytes in COVID-19 patients are infected with SARS-CoV-2. These monocytes then die releasing cytokines. The study published on a pre-print server investigated how the virus triggers inflammation. They isolated mononuclear cells from 19 healthy donors and 22 COVID-19 patients. Around 11% of the monocytes in the COVID-19 patients showed signs of membrane damage.
This is a large number to detect because dying cells are difficult to detect as the body rapidly eliminates them. The researchers then analyzed the plasma from the samples and found high levels of specific markers for pyroptosis, a type of cell death, in the COVID-19 patients. IL-6, TNFa, several growth factors, and chemokines were also high in COVID-19 patients. Also, the team found higher levels of pyroptosis markers in patients with severe disease compared to those with mild disease.
Immune gene analysis of 4336 severe cases compared with 623,902 control population samples revealed the GSDMD expression quantitative loci were highly associated with respiratory failure. Two other inflammasome genes, NLRP3 and NLRC4 were also associated with severe COVID-19. Tests also revealed that a large proportion of freshly isolated monocytes in COVID-19 patients had higher levels of inflammasome adapters activated caspace-1 and ASC.
These results suggest circulating monocytes in COVID-19 patients may die of pyroptosis, releasing inflammatory cytokines and causing a cytokine storm resulting in poor clinical outcomes. About 10% of the monocytes in COVID-19 patients also showed the presence of SARS-CoV-2 nucleocapsid protein and dsDNA, while these were not seen in the blood of healthy donors. Hence, a small portion of the circulating monocytes in COVID-19 patients shows replicating the SARS-CoV-2 virus.
The observation of plasma biomarkers of pyroptosis in COVID-19 patients and their correlation to severe disease could potentially be used as a diagnostic test for identifying who might develop severe disease. Testing approved drugs that inhibit inflammatory cytokines or GSDMD could also be worth investigating.
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