Interferon-responsive neutrophils and macrophages extricate SARS-CoV-2 Omicron critical patients from the nasty fate of sepsis

Immune characteristics associated with the SARS-CoV-2 Omicron variant of critical-ill patients are currently unclear. Severe disease has been associated with reconfiguration in the immune activity of the lung. Here we investigated the immune cell characteristics including myeloid cells, lymphocytes and alveolar epithelial cells in the bronchoalveolar lavage fluid (BALF) of 26 critical mechanical ventilation-required patients. The whole alveolar microenvironment of critical Omicron manifested apparent heterogeneous proinflammatory and interferon-stimulated gene (ISG) signature. CXCL5+ macrophages, VCAN+ macrophages, PI3+ neutrophils and CST7+ neutrophils contributed to the most proinflammatory phenotypes and were positively correlated with disease severity whereas ISG15+ neutrophils and CXCL10+ macrophages contributed to the most ISG phenotype and were negatively correlated with disease severity. Lymphocyte subsets were rare manifesting the lymphopenia in the alveoli and these lymphocyte subsets did not express substantial proinflammatory cytokines. Four different epithelial cell subsets were observed in BALF. The percentages of ISG15+ neutrophils were accompanied by more protective alveolar epithelial cells and may serve as the reshaping of exhaustive phenotype for CD4+ T cells. The CXCL10+ macrophages may promote plasmablast/plasma cell survival and activation. This atlas reveals a potential immune landscape in the bronchoalveolar microenvironment for severe and critical Omicron disease.