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

Abstract

Some patients hospitalized with acute COVID-19 suffer respiratory symptoms that persist for many months. We delineated the immune-proteomic landscape in the airway 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 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. 1 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 ongoing activation of cytotoxic T cells.

Local CCL18 and CCL21 expand lung fibrovascular niches and recruit lymphocytes, leading to tertiary lymphoid structure formation in prolonged COVID-19

“…In this study, we stratify the samples based on disease duration and include a prolonged group (7 – 15 weeks of disease duration post-infection), in which active viral infection could neither be reported in the lungs nor in the LNs. Yet, those individuals showed persistent lung damage along with the increase in lymphocyte infiltration, as reported for Long-COVID previously 11,12 . Thus, the prolonged group in this study temporally and symptomatically meets the Long-COVID criteria currently in use.…”

“…Long-COVID syndrome is usually diagnosed if symptoms persist >2 months 33 , but the mechanisms promoting and sustaining lung damage remain elusive. Recent reports highlighted the existing correlation between enriched cytotoxic lymphocytes and B cells within the airways of post-COVID-19 patients and impaired lung functionality 11,12 . In this study, we stratify the samples based on disease duration and include a prolonged group (7 – 15 weeks of disease duration post-infection), in which active viral infection could neither be reported in the lungs nor in the LNs.…”

“…Prolonged changes to the airway immune landscape with increased cytotoxic lymphocytes and B cells, which occur independently of the acute disease severity, have recently been linked to Long-COVID syndrome 11,12 . Thus, it is of utmost importance to shed light on the recruitment pathways that mediate excessive immune infiltration into the lungs and its implications for disease progression.…”

“…In addition, alternatively activated macrophages accumulating in COVID-19 lungs show a pro-fibrotic signature and have been linked to lung fibrosis 10 , although the exact mechanisms have yet to be clarified. Prolonged changes to the airway immune landscape with increased cytotoxic lymphocytes and B cells, which occur independently of the acute disease severity, have recently been linked to Long-COVID syndrome 11,12 . Thus, it is of utmost importance to shed light on the recruitment pathways that mediate excessive immune infiltration into the lungs and its implications for disease progression.…”

Pulmonary Inflammatory Response in Lethal COVID-19 Reveals Potential Therapeutic Targets and Drugs in Phases III/IV Clinical Trials

“…The infection of lung cells activates caspase-8 to trigger cell death pathways, where apoptosis, pyroptosis, and necroptosis are involved. Interestingly, Vijayakumar et al (2022) found that post-COVID-19 patients showed abnormal airway proteomes, with elevated concentration of proteins associated with apoptosis. Regarding glycolysis, scientific evidence showed that high glucose concentration and glycolysis are essential for SARS-CoV-2 replication, inflammatory response, and upregulation of ACE2 ( Codo et al, 2020 ).…”