Proc Natl Acad Sci U S A . High-dimensional profiling reveals phenotypic heterogeneity and disease-specific alterations of granulocytes in COVID-19

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Proc Natl Acad Sci U S A


. 2021 Oct 5;118(40):e2109123118.
doi: 10.1073/pnas.2109123118.
High-dimensional profiling reveals phenotypic heterogeneity and disease-specific alterations of granulocytes in COVID-19


Magda Lourda[SUP] 1 2 [/SUP], Majda Dzidic[SUP] 3 [/SUP], Laura Hertwig[SUP] 3 [/SUP], Helena Bergsten[SUP] 3 [/SUP], Laura M Palma Medina[SUP] 3 [/SUP], Indranil Sinha[SUP] 2 [/SUP], Egle Kvedaraite[SUP] 3 2 [/SUP], Puran Chen[SUP] 3 [/SUP], Jagadeeswara R Muvva[SUP] 3 [/SUP], Jean-Baptiste Gorin[SUP] 3 [/SUP], Martin Cornillet[SUP] 3 [/SUP], Johanna Emgård[SUP] 3 [/SUP], Kirsten Moll[SUP] 3 [/SUP], Marina García[SUP] 3 [/SUP], Kimia T Maleki[SUP] 3 [/SUP], Jonas Klingström[SUP] 3 [/SUP], Jakob Michaëlsson[SUP] 3 [/SUP], Malin Flodström-Tullberg[SUP] 3 [/SUP], Susanna Brighenti[SUP] 3 [/SUP], Marcus Buggert[SUP] 3 [/SUP], Jenny Mjösberg[SUP] 3 [/SUP], Karl-Johan Malmberg[SUP] 3 [/SUP], Johan K Sandberg[SUP] 3 [/SUP], Jan-Inge Henter[SUP] 2 4 [/SUP], Elin Folkesson[SUP] 5 6 [/SUP], Sara Gredmark-Russ[SUP] 3 5 [/SUP], Anders Sönnerborg[SUP] 5 7 [/SUP], Lars I Eriksson[SUP] 8 9 [/SUP], Olav Rooyackers[SUP] 9 10 [/SUP], Soo Aleman[SUP] 5 7 [/SUP], Kristoffer Strålin[SUP] 5 7 [/SUP], Hans-Gustaf Ljunggren[SUP] 3 [/SUP], Niklas K Björkström[SUP] 3 [/SUP], Mattias Svensson[SUP] 3 [/SUP], Andrea Ponzetta[SUP] 3 [/SUP], Anna Norrby-Teglund[SUP] 3 [/SUP], Benedict J Chambers[SUP] 3 [/SUP], Karolinska KI/K COVID-19 Study Group



Affiliations

• PMID: 34548411
• DOI: 10.1073/pnas.2109123118

Abstract

Since the outset of the COVID-19 pandemic, increasing evidence suggests that the innate immune responses play an important role in the disease development. A dysregulated inflammatory state has been proposed as a key driver of clinical complications in COVID-19, with a potential detrimental role of granulocytes. However, a comprehensive phenotypic description of circulating granulocytes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients is lacking. In this study, we used high-dimensional flow cytometry for granulocyte immunophenotyping in peripheral blood collected from COVID-19 patients during acute and convalescent phases. Severe COVID-19 was associated with increased levels of both mature and immature neutrophils, and decreased counts of eosinophils and basophils. Distinct immunotypes were evident in COVID-19 patients, with altered expression of several receptors involved in activation, adhesion, and migration of granulocytes (e.g., CD62L, CD11a/b, CD69, CD63, CXCR4). Paired sampling revealed recovery and phenotypic restoration of the granulocytic signature in the convalescent phase. The identified granulocyte immunotypes correlated with distinct sets of soluble inflammatory markers, supporting pathophysiologic relevance. Furthermore, clinical features, including multiorgan dysfunction and respiratory function, could be predicted using combined laboratory measurements and immunophenotyping. This study provides a comprehensive granulocyte characterization in COVID-19 and reveals specific immunotypes with potential predictive value for key clinical features associated with COVID-19.

Keywords: COVID-19; eosinophil and basophil activation; high-dimensional flow cytometry; neutrophil heterogeneity; viral immune responses.