Immuno-proteomic profiling reveals aberrant immune cell regulation in the airways of individuals with ongoing post-COVID-19 respiratory disease

• Published in: Immunity (Cambridge, Mass.) Vol. 55; no. 3; pp. 542 - 556.e5
• Main Authors: Vijayakumar, Bavithra, Boustani, Karim, Ogger, Patricia P., Papadaki, Artemis, Tonkin, James, Orton, Christopher M., Ghai, Poonam, Suveizdyte, Kornelija, Hewitt, Richard J., Desai, Sujal R., Devaraj, Anand, Snelgrove, Robert J., Molyneaux, Philip L., Garner, Justin L., Peters, James E., Shah, Pallav L., Lloyd, Clare M., Harker, James A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.03.2022; Cell Press
• Subjects: Adult; Aged; airways; B-Lymphocytes - immunology; COVID-19; COVID-19 - complications; COVID-19 - immunology; Female; Follow-Up Studies; Humans; Immunity, Cellular; Immunoproteins; long COVID; Male; Middle Aged; Monocytes - immunology; Proteome; proteomics; Respiration Disorders - etiology; Respiration Disorders - immunology; Respiratory System - immunology; Respiratory System - pathology; respiratory tract; respiratory viral infection; SARS-CoV-2; SARS-CoV-2 - physiology; T cells; T-Lymphocytes, Cytotoxic - immunology; tissue-resident memory; COVID-19; SARS-CoV-2; proteomics; respiratory viral infection; tissue-resident memory; respiratory tract; airways; long COVID; T cells
• ISSN: 1074-7613; 1097-4180; 1097-4180
• DOI: 10.1016/j.immuni.2022.01.017

Some patients hospitalized with acute COVID-19 suffer respiratory symptoms that persist for many months. We delineated the immune-proteomic landscape in the airways and peripheral blood of healthy controls and post-COVID-19 patients 3 to 6 months after hospital discharge. Post-COVID-19 patients showed abnormal airway (but not plasma) proteomes, with an elevated concentration of proteins associated with apoptosis, tissue repair, and epithelial injury versus healthy individuals. Increased numbers of cytotoxic lymphocytes were observed in individuals with greater airway dysfunction, while increased B cell numbers and altered monocyte subsets were associated with more widespread lung abnormalities. A one-year follow-up of some post-COVID-19 patients indicated that these abnormalities resolved over time. In summary, COVID-19 causes a prolonged change to the airway immune landscape in those with persistent lung disease, with evidence of cell death and tissue repair linked to the ongoing activation of cytotoxic T cells. [Display omitted] •Post-COVID-19 airways, but not blood, show immune and proteomic changes•Different post-COVID-19 lung abnormalities relate to distinct immunological features•Increased BAL cytotoxic T cells are linked to epithelial damage and airway disease•BAL myeloid and B cell numbers correlate with the degree of lung CT abnormality Many individuals recovering from acute SARS-CoV-2 infection suffer prolonged respiratory dysfunction for months to years after viral clearance. Vijayakumar, Boustani, Ogger, Papadaki et al. Show that individuals with persistent symptoms 3–6 months after infection have an altered airway immune cell landscape and evidence of ongoing lung damage. Importantly, different immune cell types correlate with the severity of distinct aspects of ongoing respiratory disease.