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Am J Physiol Lung Cell Mol Physiol ; 322(5): L712-L721, 2022 05 01.
Article Dans Anglais | MEDLINE | ID: covidwho-1759484


Accumulating evidence has confirmed that chronic obstructive pulmonary disease (COPD) is a risk factor for development of severe pathological changes in the peripheral lungs of patients with COVID-19. However, the underlying molecular mechanisms remain unclear. Because bronchiolar club cells are crucial for maintaining small airway homeostasis, we sought to explore whether the altered susceptibility to SARS-CoV-2 infection of the club cells might have contributed to the severe COVID-19 pneumonia in COPD patients. Our investigation on the quantity and distribution patterns of angiotensin-converting enzyme 2 (ACE2) in airway epithelium via immunofluorescence staining revealed that the mean fluorescence intensity of the ACE2-positive epithelial cells was significantly higher in club cells than those in other epithelial cells (including ciliated cells, basal cells, goblet cells, neuroendocrine cells, and alveolar type 2 cells). Compared with nonsmokers, the median percentage of club cells in bronchiolar epithelium and ACE2-positive club cells was significantly higher in COPD patients. In vitro, SARS-CoV-2 infection (at a multiplicity of infection of 1.0) of primary small airway epithelial cells, cultured on air-liquid interface, confirmed a higher percentage of infected ACE2-positive club cells in COPD patients than in nonsmokers. Our findings have indicated the role of club cells in modulating the pathogenesis of SARS-CoV-2-related severe pneumonia and the poor clinical outcomes, which may help physicians to formulate a novel therapeutic strategy for COVID-19 patients with coexisting COPD.

COVID-19 , Broncho-pneumopathie chronique obstructive , Angiotensin-converting enzyme 2 , Cellules épithéliales , Humains , Poumon , Peptidyl-Dipeptidase A , SARS-CoV-2
FEBS Lett ; 595(13): 1819-1824, 2021 07.
Article Dans Anglais | MEDLINE | ID: covidwho-1220171


We previously observed enhanced immunoglobulin A (IgA) responses in severe COVID-19, which might confer damaging effects. Given the important role of IgA in immune and inflammatory responses, the aim of this study was to investigate the dynamic response of the IgA isotype switch factor TGF-ß1 in COVID-19 patients. We observed, in a total of 153 COVID-19 patients, that the serum levels of TGF-ß1 were increased significantly at the early and middle stages of COVID-19, and correlated with the levels of SARS-CoV-2-specific IgA, as well as with the APACHE II score in patients with severe disease. In view of the genetic association of the TGF-ß1 activator THBS3 with severe COVID-19 identified by the COVID-19 Host Genetics Initiative, this study suggests TGF-ß1 may play a key role in COVID-19.

COVID-19/immunologie , Immunoglobuline A/sang , SARS-CoV-2/immunologie , Thrombospondines/génétique , Facteur de croissance transformant bêta-1/sang , Indice APACHE , Adulte , Sujet âgé , Anticorps antiviraux/sang , COVID-19/sang , COVID-19/génétique , Femelle , Humains , Immunoglobuline A/métabolisme , Mâle , Adulte d'âge moyen , Polymorphisme de nucléotide simple
J Med Virol ; 93(5): 3257-3260, 2021 05.
Article Dans Anglais | MEDLINE | ID: covidwho-1196531


Previous studies have revealed a diagnostic role of pathogen-specific IgA in respiratory infections. However, co-detection of serum specific IgA for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and common respiratory pathogens remains largely unexplored. This study utilizes a protein microarray technology for simultaneous and quantitative measurements of specific IgAs for eight different respiratory pathogens including adenovirus, respiratory syncytial virus, influenza virus type A, influenza virus type B, parainfluenza virus, mycoplasma pneumoniae, chlamydia pneumoniae, and SARS-CoV-2 in serum sample of patients with coronavirus disease 2019 (COVID-19). A total of 42 patients with COVID-19 were included and categorized into severe cases (20 cases) and nonsevere cases (22 cases). The results showed that co-detection rate of specific-IgA for SARS-CoV-2 with at least one pathogen were significantly higher in severe cases than that of nonsevere cases (72.2% vs. 46.2%, p = .014). Our study indicates that co-detection of IgA antibodies for respiratory pathogens might provide diagnostic value for the clinics and also be informative for risk stratification and disease management in patients with COVID-19.

Anticorps antiviraux/sang , COVID-19/immunologie , Immunoglobuline A/sang , SARS-CoV-2/immunologie , Adulte , Spécificité des anticorps , COVID-19/anatomopathologie , Femelle , Humains , Mâle , Adulte d'âge moyen
Détails de la recherche