In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 20, No. 6 ( 2024-6-5), p. e1012222-
Abstract:
COVID-19 has affected more than half a billion people worldwide, with more than 6.3 million deaths, but the pathophysiological mechanisms involved in lethal cases and the host determinants that determine the different clinical outcomes are still unclear. In this study, we assessed lung autopsies of 47 COVID-19 patients and examined the inflammatory profiles, viral loads, and inflammasome activation. Additionally, we correlated these factors with the patient’s clinical and histopathological conditions. Robust inflammasome activation was detected in the lungs of lethal cases of SARS-CoV-2. Experiments conducted on transgenic mice expressing hACE2 and infected with SARS-CoV-2 showed that Nlrp3 -/- mice were protected from disease development and lethality compared to Nlrp3 +/+ littermate mice, supporting the involvement of this inflammasome in disease exacerbation. An analysis of gene expression allowed for the classification of COVID-19 patients into two different clusters. Cluster 1 died with higher viral loads and exhibited a reduced inflammatory profile than Cluster 2. Illness time, mechanical ventilation time, pulmonary fibrosis, respiratory functions, histopathological status, thrombosis, viral loads, 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 led to different clinical outcomes. We provide important information to understand clinical variations in severe COVID-19, a process that is critical for decisions between immune-mediated or antiviral-mediated therapies for the treatment of critical cases of COVID-19.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1012222
DOI:
10.1371/journal.ppat.1012222.g001
DOI:
10.1371/journal.ppat.1012222.g002
DOI:
10.1371/journal.ppat.1012222.g003
DOI:
10.1371/journal.ppat.1012222.g004
DOI:
10.1371/journal.ppat.1012222.g005
DOI:
10.1371/journal.ppat.1012222.g006
DOI:
10.1371/journal.ppat.1012222.t001
DOI:
10.1371/journal.ppat.1012222.t002
DOI:
10.1371/journal.ppat.1012222.t003
DOI:
10.1371/journal.ppat.1012222.t004
DOI:
10.1371/journal.ppat.1012222.s001
DOI:
10.1371/journal.ppat.1012222.s002
DOI:
10.1371/journal.ppat.1012222.s003
DOI:
10.1371/journal.ppat.1012222.s004
DOI:
10.1371/journal.ppat.1012222.s005
DOI:
10.1371/journal.ppat.1012222.s006
DOI:
10.1371/journal.ppat.1012222.s007
DOI:
10.1371/journal.ppat.1012222.s008
DOI:
10.1371/journal.ppat.1012222.r001
DOI:
10.1371/journal.ppat.1012222.r002
DOI:
10.1371/journal.ppat.1012222.r003
DOI:
10.1371/journal.ppat.1012222.r004
DOI:
10.1371/journal.ppat.1012222.r005
DOI:
10.1371/journal.ppat.1012222.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2024
detail.hit.zdb_id:
2205412-1
Permalink