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.
Subject(s)
COVID-19 , Lung , SARS-CoV-2 , Viral Load , Virus Replication , COVID-19/virology , COVID-19/mortality , COVID-19/immunology , COVID-19/pathology , Animals , Humans , Mice , Female , Male , Lung/virology , Lung/pathology , Lung/immunology , Middle Aged , Inflammasomes/immunology , Inflammasomes/metabolism , Aged , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Mice, Transgenic , Pneumonia/virology , Pneumonia/mortality , Pneumonia/immunology , Pneumonia/pathology , Angiotensin-Converting Enzyme 2/metabolism , Angiotensin-Converting Enzyme 2/genetics , Mice, Knockout , AdultABSTRACT
We conducted a prospective cohort study in a population with diverse ethnic backgrounds from Brazil to assess clinically meaningful symptoms after surviving coronavirus disease. For most of the 175 patients in the study, clinically meaningful symptoms, including fatigue, dyspnea, cough, headache, and muscle weakness, persisted for >120 days after disease onset.
Subject(s)
COVID-19 , Brazil/epidemiology , Humans , Prospective Studies , SARS-CoV-2 , SurvivorsABSTRACT
In 2005, we reported an acute myocardial infarction secondary to a left anterior descending coronary artery injury sustained in a motorcycle accident. The treatment was late myocardial revascularization with in situ left internal thoracic artery-to-left anterior descending coronary artery anastomosis. There is little information available about the natural history of acute myocardial infarction after blunt chest trauma, especially when treated in this manner. This present communication reports the 14-year outcome in our patient.