Dados do Trabalho

Título

Why is COVID-19 a more severe disease than influenza?

Introdução

Inflammasome activation is associated with disease severity in patients infected with SARS-CoV-2 and influenza, but the specific cell types that drive inflammasome activation as well as the inflammatory profile associated with inflammation-mediated disease exacerbation is unknown.

Objetivo(s)

The aim of this project is understand the molecular mechanisms underlying the pathological processes that lead to death of COVID-19 and Influenza patients.

Material e Métodos

In the present study, lung autopsy tissue samples from 47 fatal COVID-19 patients and 12 fatal influenza patients were examined for inflammasome activation, gene expression and correlated with the clinical conditions of the patients.

Resultados e Conclusão

We demonstrated the presence of more robust 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. Analysis of gene expression allows classification of COVID-19 patients in two different clusters, cluster 1 (n=16 patients) died with higher viral loads and reduced inflammatory profile than oppose to cluster 2 (n=31). Illness time, mechanical ventilation time, pulmonary fibrosis, respiratory functions, histopathological status, and inflammasome activation differed in the two clusters. Our data reveal two distinct profiles in lethal cases of COVID19, indicating that the balance of viral replication and inflammasome-mediated pulmonary inflammation may lead to opposed clinical conditions, yet both lead to patient death. Understanding this process is critical for decisions concerning the higher efficacy of immune-mediated or antiviral-mediated therapies for the treatment of critical cases of COVID-19.

Palavras-chave

COVID-19, Influenza, Inflamassome