CyTOF-mediated characterisation of the myeloid cell compartment in severe COVID-19
Abstract
Coronavirus disease 2019 (COVID-19) is a mild to moderate respiratory tract infection. However, a subset of patients progresses to severe disease and respiratory failure. The mechanism of protective immunity in mild forms and the pathogenesis of severe COVID-19 associated with increased neutrophil counts and dysregulated immune responses remain unclear. In a dual-center, two-cohort study, we applied single-cell proteomics of whole-blood and peripheral-blood mononuclear cells using mass cytometry and flow cytometry, respectively, to determine changes in immune cell composition and activation in mild versus severe COVID-19 over time. HLA-DRhiCD11chi inflammatory monocytes were elevated in mild COVID-19. Severe COVID-19 was marked by occurrence of neutrophil precursors, as evidence of emergency myelopoiesis, dysfunctional mature neutrophils, and HLA-DRlo monocytes. Our study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in the myeloid cell compartment associated with severe COVID-19.
Biosketch
Birgit is Professor of “Immune Tolerance” at the Institute of Medical Immunology. She has developed validated immune monitoring tools for application in investigator-driven clinical trials. She is coordinating the immune monitoring of three big multi-center investigator-driven clinical trials, sponsored by the European committee, aiming on e.g. personalized treatment and finally tolerance induction in solid organ transplant patients. In the last month Birgit successfully applied her expertise in deciphering the pathomechanisms of severe COVID-19.
Keywords
Immune monitoring, COVID-19, Immune cell composition and functionality
Contact
birgit.sawitzki@charite.de
Publications
1. Schulte-Schrepping J, Reusch N, Paclik D, Baßler K, Schlickeiser S, Zhang B, Krämer B, Krammer T, Brumhard S, Bonaguro L, De Domenico E, Wendisch D, Grasshoff M, Kapellos TS, Beckstette M, Pecht T, Saglam A, Dietrich O, Mei HE, Schulz AR, Conrad C, Kunkel D, Vafadarnejad E, Xu CJ, Horne A, Herbert M, Drews A, Thibeault C, Pfeiffer M, Hippenstiel S, Hocke A, Müller-Redetzky H, Heim KM, Machleidt F, Uhrig A, Bosquillon de Jarcy L, Jürgens L, Stegemann M, Glösenkamp CR, Volk HD, Goffinet C, Landthaler M, Wyler E, Georg P, Schneider M, Dang-Heine C, Neuwinger N, Kappert K, Tauber R, Corman V, Raabe J, Kaiser KM, Vinh MT, Rieke G, Meisel C, Ulas T, Becker M, Geffers R, Witzenrath M, Drosten C, Suttorp N, von Kalle C, Kurth F, Händler K, Schultze JL*, Aschenbrenner AC*, Li Y*, Nattermann J*, Sawitzki B*, Saliba AE*, Sander LE*; Deutsche COVID-19 OMICS Initiative (DeCOI). Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment. Cell. 2020 Sep 17;182(6):1419-1440.e23. doi: 10.1016/j.cell.2020.08.001. Epub 2020 Aug 5. PMID: 32810438; PMCID: PMC7405822. *shared senior author
2. Sawitzki B, Harden PN, Reinke P, Moreau A, Hutchinson JA, Game DS, Tang Q, Guinan EC, Battaglia M, Burlingham WJ, Roberts ISD, Streitz M, Josien R, Böger CA, Scottà C, Markmann JF, Hester JL, Juerchott K, Braudeau C, James B, Contreras-Ruiz L, van der Net JB, Bergler T, Caldara R, Petchey W, Edinger M, Dupas N, Kapinsky M, Mutzbauer I, Otto NM, Öllinger R, Hernandez-Fuentes MP, Issa F, Ahrens N, Meyenberg C, Karitzky S, Kunzendorf U, Knechtle SJ, Grinyó J, Morris PJ, Brent L, Bushell A, Turka LA, Bluestone JA, Lechler RI, Schlitt HJ, Cuturi MC, Schlickeiser S, Friend PJ, Miloud T, Scheffold A, Secchi A, Crisalli K, Kang SM, Hilton R, Banas B, Blancho G, Volk HD, Lombardi G, Wood KJ, Geissler EK. Regulatory cell therapy in kidney transplantation (The ONE Study): a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials. Lancet. 2020 May 23;395(10237):1627-1639. doi: 10.1016/S0140-6736(20)30167-7.
3. Truong KL, Schlickeiser S, Vogt K, Boës D, Stanko K, Appelt C, Streitz M, Grütz G, Stobutzki N, Meisel C, Iwert C, Tomiuk S, Polansky JK, Pascher A, Babel N, Stervbo U, Sauer I, Gerlach U, Sawitzki B. Killer-like receptors and GPR56 progressive expression defines cytokine production of human CD4+ memory T cells. Nat Commun. 2019 May 22;10(1):2263. doi: 10.1038/s41467-019-10018-1. PMID: 31118448; PMCID: PMC6531457.