Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia
Stefanie Kreutmair, Susanne Unger, Nicolás Gonzalo Núñez, Florian Ingelfinger, Chiara Alberti, Donatella De Feo, Sinduya Krishnarajah, Manuel Kauffmann, Ekaterina Friebel, Sepideh Babaei, Benjamin Gaborit, Mirjam Lutz, Nicole Puertas Jurado, Nisar P. Malek, Siri Goepel, Peter Rosenberger, Helene A. Häberle, Ikram Ayoub, Sally Al-Hajj, Jakob Nilsson, Manfred Claassen, Roland Liblau, Guillaume Martin‐Blondel, Michael Bitzer, Antoine Roquilly, Burkhard Becher
Abstract
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.