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Natural killer cell immunotypes related to COVID-19 disease severity

2020; American Association for the Advancement of Science; Volume: 5; Issue: 50 Linguagem: Inglês

10.1126/sciimmunol.abd6832

2470-9468

Christopher Maucourant, Iva Filipovic, Andrea Ponzetta, Soo Aleman, Martin Cornillet, Laura Hertwig, Benedikt Strunz, Antonio Lentini, Björn Reinius, Demi Brownlie, Angélica Cuapio, Eivind Heggernes Ask, Ryan M. Hull, Alvaro Haroun-Izquierdo, Marie Schaffer, Jonas Klingström, Elin Folkesson, Marcus Buggert, Johan K. Sandberg, Lars I. Eriksson, Olav Rooyackers, Hans‐Gustaf Ljunggren, Karl‐Johan Malmberg, Jakob Michaëlsson, Nicole Marquardt, Quirin Hammer, Kristoffer Strålin, Niklas K. Björkström,

COVID-19 and Mental Health

Understanding innate immune responses in COVID-19 is important to decipher mechanisms of host responses and interpret disease pathogenesis. Natural killer (NK) cells are innate effector lymphocytes that respond to acute viral infections but might also contribute to immunopathology. Using 28-color flow cytometry, we here reveal strong NK cell activation across distinct subsets in peripheral blood of COVID-19 patients. This pattern was mirrored in scRNA-seq signatures of NK cells in bronchoalveolar lavage from COVID-19 patients. Unsupervised high-dimensional analysis of peripheral blood NK cells furthermore identified distinct NK cell immunotypes that were linked to disease severity. Hallmarks of these immunotypes were high expression of perforin, NKG2C, and Ksp37, reflecting increased presence of adaptive NK cells in circulation of patients with severe disease. Finally, arming of CD56bright NK cells was observed across COVID-19 disease states, driven by a defined protein-protein interaction network of inflammatory soluble factors. This study provides a detailed map of the NK cell activation landscape in COVID-19 disease.