COVID-19 immune signatures in Uganda persist in HIV co-infection and diverge by pandemic phase.

Autor: Cummings MJ; Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA. mjc2244@columbia.edu.; Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA. mjc2244@columbia.edu., Bakamutumaho B; Department of Arbovirology, Emerging and Re-emerging Infectious Diseases, Uganda Virus Research Institute, Entebbe, Uganda., Lutwama JJ; Department of Arbovirology, Emerging and Re-emerging Infectious Diseases, Uganda Virus Research Institute, Entebbe, Uganda., Owor N; Department of Arbovirology, Emerging and Re-emerging Infectious Diseases, Uganda Virus Research Institute, Entebbe, Uganda., Che X; Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA.; Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA., Astorkia M; Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA., Postler TS; Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA., Kayiwa J; Department of Arbovirology, Emerging and Re-emerging Infectious Diseases, Uganda Virus Research Institute, Entebbe, Uganda., Kiconco J; Department of Arbovirology, Emerging and Re-emerging Infectious Diseases, Uganda Virus Research Institute, Entebbe, Uganda., Muwanga M; Entebbe Regional Referral Hospital, Entebbe, Uganda., Nsereko C; Entebbe Regional Referral Hospital, Entebbe, Uganda., Rwamutwe E; Entebbe Regional Referral Hospital, Entebbe, Uganda., Nayiga I; Entebbe Regional Referral Hospital, Entebbe, Uganda., Kyebambe S; Entebbe Regional Referral Hospital, Entebbe, Uganda., Haumba M; Department of Arbovirology, Emerging and Re-emerging Infectious Diseases, Uganda Virus Research Institute, Entebbe, Uganda., Bosa HK; Uganda Peoples' Defence Forces, Kampala, Uganda.; Ministry of Health, Kampala, Uganda., Ocom F; Ministry of Health, Kampala, Uganda., Watyaba B; European and Developing Countries Clinical Trials Partnership-Eastern Africa Consortium for Clinical Research, Uganda Virus Research Institute, Entebbe, Uganda., Kikaire B; European and Developing Countries Clinical Trials Partnership-Eastern Africa Consortium for Clinical Research, Uganda Virus Research Institute, Entebbe, Uganda.; Department of Pediatrics, Makerere University College of Health Sciences, Kampala, Uganda., Tomoiaga AS; Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.; Department of Accounting, Business Analytics, Computer Information Systems, and Law, Manhattan College, New York, NY, USA., Kisaka S; Department of Epidemiology and Biostatistics, Makerere University School of Public Health, Kampala, Uganda.; Institute of Tropical and Infectious Diseases, University of Nairobi, Nairobi, Kenya., Kiwanuka N; Department of Epidemiology and Biostatistics, Makerere University School of Public Health, Kampala, Uganda., Lipkin WI; Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA.; Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA., O'Donnell MR; Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.; Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA.; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Feb 17; Vol. 15 (1), pp. 1475. Date of Electronic Publication: 2024 Feb 17.
DOI: 10.1038/s41467-024-45204-3
Abstrakt: Little is known about the pathobiology of SARS-CoV-2 infection in sub-Saharan Africa, where severe COVID-19 fatality rates are among the highest in the world and the immunological landscape is unique. In a prospective cohort study of 306 adults encompassing the entire clinical spectrum of SARS-CoV-2 infection in Uganda, we profile the peripheral blood proteome and transcriptome to characterize the immunopathology of COVID-19 across multiple phases of the pandemic. Beyond the prognostic importance of myeloid cell-driven immune activation and lymphopenia, we show that multifaceted impairment of host protein synthesis and redox imbalance define core biological signatures of severe COVID-19, with central roles for IL-7, IL-15, and lymphotoxin-α in COVID-19 respiratory failure. While prognostic signatures are generally consistent in SARS-CoV-2/HIV-coinfection, type I interferon responses uniquely scale with COVID-19 severity in persons living with HIV. Throughout the pandemic, COVID-19 severity peaked during phases dominated by A.23/A.23.1 and Delta B.1.617.2/AY variants. Independent of clinical severity, Delta phase COVID-19 is distinguished by exaggerated pro-inflammatory myeloid cell and inflammasome activation, NK and CD8 + T cell depletion, and impaired host protein synthesis. Combining these analyses with a contemporary Ugandan cohort of adults hospitalized with influenza and other severe acute respiratory infections, we show that activation of epidermal and platelet-derived growth factor pathways are distinct features of COVID-19, deepening translational understanding of mechanisms potentially underlying SARS-CoV-2-associated pulmonary fibrosis. Collectively, our findings provide biological rationale for use of broad and targeted immunotherapies for severe COVID-19 in sub-Saharan Africa, illustrate the relevance of local viral and host factors to SARS-CoV-2 immunopathology, and highlight underemphasized yet therapeutically exploitable immune pathways driving COVID-19 severity.
(© 2024. The Author(s).)
Databáze: MEDLINE
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