Abnormalities in the respiratory immune response of patients with COVID-19 are reported in a paper in Nature Medicine. The study, which analyzed bronchoalveolar immune cells of nine patients with COVID-19, may aid in the understanding of potential mechanisms underlying immune responses to SARS-CoV-2 (the coronavirus that causes COVID-19).
Abnormal immune responses to coronavirus infections have been shown in animal models. However, human respiratory immune responses to SARS-CoV-2 have remained unclear.
Zheng Zhang and colleagues used single-cell RNA sequencing to analyze samples of immune cells extracted from bronchoalveolar lavage fluid (BALF) from nine patients with COVID-19. Bronchoalveolar lavage is a diagnostic procedure in which a tube is inserted through the nose or mouth and is passed into the lungs. The tube is used to flush the lungs with fluid, which is then recollected for testing. Six of the patients were categorized as severe/critical, with most requiring mechanical ventilation, and three were categorized as moderate, with fever and pneumonia. The patients had a median age of 57 and included six males and three females. The authors also examined three healthy control subjects and a publicly available BALF sample.
The authors found that BALF samples from the patients with severe/critical disease contained higher concentrations of macrophages and neutrophils (types of white blood cell) than did those from the moderate and control groups. The patients with severe/critical disease also had higher levels of inflammatory cytokines and chemokines ― signaling proteins released by immune cells. From this the authors infer that an inflammatory macrophage microenvironment is present in the lungs of patients with severe/critical COVID-19. The authors also analyzed the diversity of T cells, another type of white blood cell, in these samples. They found that in patients with severe/critical disease, there were higher proportions of proliferating T cells. However, the proportion of CD8+ T cells, which serve an important role in anti-viral immune responses by killing infected cells, were lower than in patients with moderate disease.
The findings reveal potential irregular macrophage and T cell responses during COVID-19, but the authors caution that there are limitations to the study, including a limited sample size and lack of longitudinal samples collected before and after infection.
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