The Journal of allergy and clinical immunology · 2022
Preexisting comorbidities shape the immune response associated with severe COVID-19.
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Kreutmair Stefanie, Kauffmann Manuel, Unger Susanne, Ingelfinger Florian, Núñez Nicolás Gonzalo, Alberti Chiara, De Feo Donatella, Krishnarajah Sinduya, Friebel Ekaterina, Ulutekin Can, Babaei Sepideh, Gaborit Benjamin, Lutz Mirjam, Jurado Nicole Puertas, Malek Nisar P, Göpel Siri, Rosenberger Peter, Häberle Helene A, Ayoub Ikram, Al-Hajj Sally, Claassen Manfred, Liblau Roland, Martin-Blondel Guillaume, Bitzer Michael, Roquilly Antoine, Becher Burkhard
Аннотация
BACKGROUND: Comorbidities are risk factors for development of severe coronavirus disease 2019 (COVID-19). However, the extent to which an underlying comorbidity influences the immune response to severe acute respiratory syndrome coronavirus 2 remains unknown.
OBJECTIVE: Our aim was to investigate the complex interrelations of comorbidities, the immune response, and patient outcome in COVID-19.
METHODS: We used high-throughput, high-dimensional, single-cell mapping of peripheral blood leukocytes and algorithm-guided analysis.
RESULTS: We discovered characteristic immune signatures associated not only with severe COVID-19 but also with the underlying medical condition. Different factors of the metabolic syndrome (obesity, hypertension, and diabetes) affected distinct immune populations, thereby additively increasing the immunodysregulatory effect when present in a single patient. Patients with disorders affecting the lung or heart, together with factors of metabolic syndrome, were clustered together, whereas immune disorder and chronic kidney disease displayed a distinct immune profile in COVID-19. In particular, severe acute respiratory syndrome coronavirus 2-infected patients with preexisting chronic kidney disease were characterized by the highest number of altered immune signatures of both lymphoid and myeloid immune branches. This overall major immune dysregulation could be the underlying mechanism for the estimated odds ratio of 16.3 for development of severe COVID-19 in this burdened cohort.
CONCLUSION: The combinatorial systematic analysis of the immune signatures, comorbidities, and outcomes of patients with COVID-19 has provided the mechanistic immunologic underpinnings of comorbidity-driven patient risk and uncovered comorbidity-driven immune signatures.
OBJECTIVE: Our aim was to investigate the complex interrelations of comorbidities, the immune response, and patient outcome in COVID-19.
METHODS: We used high-throughput, high-dimensional, single-cell mapping of peripheral blood leukocytes and algorithm-guided analysis.
RESULTS: We discovered characteristic immune signatures associated not only with severe COVID-19 but also with the underlying medical condition. Different factors of the metabolic syndrome (obesity, hypertension, and diabetes) affected distinct immune populations, thereby additively increasing the immunodysregulatory effect when present in a single patient. Patients with disorders affecting the lung or heart, together with factors of metabolic syndrome, were clustered together, whereas immune disorder and chronic kidney disease displayed a distinct immune profile in COVID-19. In particular, severe acute respiratory syndrome coronavirus 2-infected patients with preexisting chronic kidney disease were characterized by the highest number of altered immune signatures of both lymphoid and myeloid immune branches. This overall major immune dysregulation could be the underlying mechanism for the estimated odds ratio of 16.3 for development of severe COVID-19 in this burdened cohort.
CONCLUSION: The combinatorial systematic analysis of the immune signatures, comorbidities, and outcomes of patients with COVID-19 has provided the mechanistic immunologic underpinnings of comorbidity-driven patient risk and uncovered comorbidity-driven immune signatures.