Open AccessHigh-dimensional profiling reveals phenotypic heterogeneity and disease-specific alterations of granulocytes in COVID-19
Author(s) -
Magda Lourda,
Majda Dzidic,
Laura Hertwig,
Helena Bergsten,
Laura M Palma Medina,
Indranil Sinha,
Egle Kvedaraite,
Puran Chen,
Jagadeeswara Rao Muvva,
JeanBaptiste Gorin,
Martin Cornillet,
Johanna Emgård,
Kirsten Moll,
Marina García,
Kimia T. Maleki,
Jonas Klingström,
Jakob Michaëlsson,
Malin FlodströmTullberg,
Susanna Brighenti,
Marcus Buggert,
Jenny Mjösberg,
KarlJohan Malmberg,
Johan K. Sandberg,
JanInge Henter,
Elin Folkesson,
Sara GredmarkRuss,
Anders Sönnerborg,
Lars Eriksson,
Olav Rooyackers,
Soo Aleman,
Kristoffer Strålin,
HansGustaf Ljunggren,
Niklas K. Björkström,
Mattias Svensson,
Andrea Ponzetta,
AnorrbyTeglund,
Benedict J. Chambers,
Karolinska Ki
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2109123118
Subject(s) - immunophenotyping , cd63 , immunology , granulocyte , phenotype , coronavirus , biology , flow cytometry , immune system , innate immune system , medicine , covid-19 , disease , pathology , infectious disease (medical specialty) , microrna , microvesicles , gene , biochemistry
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.