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.
Trial registration: ClinicalTrials.gov NCT04385108 .
Keywords: COVID-19; GM-CSF; HLA typing; SARS-CoV-2; biomarker; high-dimensional single cell analysis; immune profiling; immunophenotyping; peptide binding strength; spectral flow cytometry.
【저자키워드】 COVID-19, SARS-CoV-2, Biomarker, GM-CSF, Immunophenotyping, immune profiling, spectral flow cytometry., HLA typing, high-dimensional single cell analysis, peptide binding strength, 【초록키워드】 Biomarker, adaptive, severe COVID-19, Immunity, Pneumonia, translation, GM-CSF, peptide, Immune profile, immunopathology, SARS-CoV-2 peptides, outcome, flow cytometry, immune, T cell, Immunophenotyping, immune profiling, Patient, peptides, Single Cell, ICU Patients, HLA, longitudinal, change, single-cell, binding, Inflammatory response, Frequency, Analysis, integration, treatment strategy, COVID-19 patient, Cytometry, Predictive, Treatment strategies, alteration, ClinicalTrials, circulating, cascade, paralysis, virus recognition, feature, Cell, ICU patient, NKT, immune signature, predicted, the patient, interfere, driven by, SARS-CoV-2 peptide, 【제목키워드】 Critical, immunological,