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Inflammasome activation and pulmonary viral loads define two distinct clinical outcomes in COVID-19
Preprint
in English
| medRxiv
| ID: ppmedrxiv-22276878
ABSTRACT
Inflammasome activation is associated with disease severity in patients who are infected with SARS-CoV-2 and influenza viruses, but the specific cell types involved in inflammasome activation, as well as the balance of inflammasome activation versus viral replication in COVID-19 exacerbation and the induction of patient death, are unknown. In this study, we assessed lung autopsies of 47 COVID-19 and 12 influenza fatal cases and examined the inflammatory profiles and inflammasome activation; additionally, we correlated these factors with clinical and histopathological patient conditions. We observed an overall stronger inflammasome activation in lethal cases of SARS-CoV-2 compared to influenza and found a different profile of inflammasome-activating cells during these diseases. In COVID-19 patients, inflammasome activation is mostly mediated by macrophages and endothelial cells, whereas in influenza, type I and type II pneumocytes contribute more significantly. An analysis of gene expression allowed for the classification of COVID-19 patients into two different clusters. Cluster 1 (n=16 patients) died with higher viral loads and exhibited a reduced inflammatory profile than Cluster 2 (n=31 patients). Illness time, mechanical ventilation time, pulmonary fibrosis, respiratory functions, histopathological status, thrombosis, and inflammasome activation significantly differed between the two clusters. Our data demonstrated two distinct profiles in lethal cases of COVID-19, thus indicating that the balance of viral replication and inflammasome-mediated pulmonary inflammation may lead to different clinical conditions, yet both lead to patient death. An understanding of this process is critical for decisions between immune-mediated or antiviral-mediated therapies for the treatment of critical cases of COVID-19.
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Full text:
Available
Collection:
Preprints
Database:
medRxiv
Type of study:
Prognostic study
Language:
English
Year:
2022
Document type:
Preprint