P. Szabo, P. Dogra, J. Gray, S. B. Wells, T. Connors, S. Weisberg, I. Krupska, R. Matsumoto, M. M. Poon, E. Idzikowski, S. E. Morris, P. Chloe, A. Yates, A. Ku, M. Chait, J. Davis-Porada, J. Zhou, M. Steinle, S. Mackay, A. Saqi, M. Baldwin, P. Sims, D. Farber
medRxiv, 2020
Immune responses to respiratory viruses like SARS-CoV-2 originate and function in the lung, yet assessments of human immunity are often limited to blood. Here, we conducted longitudinal, high-dimensional profiling of paired airway and blood samples from patients with severe COVID-19, revealing immune processes in the respiratory tract linked to disease pathogenesis. Survival from severe disease was associated with increased CD4+T cells and decreased monocyte/macrophage frequencies in the airway, but not in blood. Airway T cells and macrophages exhibited tissue-resident phenotypes and activation signatures, including high level expression and secretion of monocyte chemoattractants CCL2 and CCL3 by airway macrophages. By contrast, monocytes in blood expressed the CCL2-receptor CCR2 and aberrant CD163+ and immature phenotypes. Extensive accumulation of CD163+monocyte/macrophages within alveolar spaces in COVID-19 lung autopsies suggested recruitment from circulation. Our findings provide evidence that COVID-19 pathogenesis is driven by respiratory immunity, and rationale for site-specific treatment and prevention strategies.
Cited by 17 publications.
Field of study: Medicine