Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia #MMPMID34051147
Kreutmair S; Unger S; Nunez NG; Ingelfinger F; Alberti C; De Feo D; Krishnarajah S; Kauffmann M; Friebel E; Babaei S; Gaborit B; Lutz M; Jurado NP; Malek NP; Goepel S; Rosenberger P; Haberle HA; Ayoub I; Al-Hajj S; Nilsson J; Claassen M; Liblau R; Martin-Blondel G; Bitzer M; Roquilly A; Becher B
Immunity 2021[Jul]; 54 (7): 1578-1593.e5 PMID34051147show ga
Immune profiling of COVID-19 patients has identified numerous alterations in both innate and adaptive immunity. However, whether those changes are specific to SARS-CoV-2 or driven by a general inflammatory response shared across severely ill pneumonia patients remains unknown. Here, we compared the immune profile of severe COVID-19 with non-SARS-CoV-2 pneumonia ICU patients using longitudinal, high-dimensional single-cell spectral cytometry and algorithm-guided analysis. COVID-19 and non-SARS-CoV-2 pneumonia both showed increased emergency myelopoiesis and displayed features of adaptive immune paralysis. However, pathological immune signatures suggestive of T cell exhaustion were exclusive to COVID-19. The integration of single-cell profiling with a predicted binding capacity of SARS-CoV-2 peptides to the patients' HLA profile further linked the COVID-19 immunopathology to impaired virus recognition. Toward clinical translation, circulating NKT cell frequency was identified as a predictive biomarker for patient outcome. Our comparative immune map serves to delineate treatment strategies to interfere with the immunopathologic cascade exclusive to severe COVID-19.
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Immunity 2021 ; 54 (7): 1578-1593.e5
