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

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...

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Vydané v:	Nature communications Ročník 15; číslo 1; s. 1475 - 18
Hlavní autori:	Cummings, Matthew J., Bakamutumaho, Barnabas, Lutwama, Julius J., Owor, Nicholas, Che, Xiaoyu, Astorkia, Maider, Postler, Thomas S., Kayiwa, John, Kiconco, Jocelyn, Muwanga, Moses, Nsereko, Christopher, Rwamutwe, Emmanuel, Nayiga, Irene, Kyebambe, Stephen, Haumba, Mercy, Bosa, Henry Kyobe, Ocom, Felix, Watyaba, Benjamin, Kikaire, Bernard, Tomoiaga, Alin S., Kisaka, Stevens, Kiwanuka, Noah, Lipkin, W. Ian, O’Donnell, Max R.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 17.02.2024 Nature Publishing Group Nature Portfolio
Predmet:	631/250/2502 631/250/2520 631/250/254 631/250/255/2514 692/420/254 Adult Adults CD8 antigen Cell activation Coinfection - epidemiology COVID-19 Fibrosis Growth factors HIV HIV Infections - complications HIV Infections - epidemiology Human immunodeficiency virus Humanities and Social Sciences Humans Immune response Immune system Immunology Immunopathology Immunotherapy Infections Inflammasomes Inflammation Lung diseases Lymphocytes Lymphocytes T Lymphopenia Lymphotoxin multidisciplinary Pandemics Peripheral blood Platelet-derived growth factor Prospective Studies Protein biosynthesis Protein synthesis Proteins Proteomes Respiratory tract infection SARS-CoV-2 Science Science (multidisciplinary) Severe acute respiratory syndrome coronavirus 2 Transcriptomes Tumor necrosis factor-β Uganda - epidemiology Viral diseases Uganda Africa
ISSN:	2041-1723, 2041-1723
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Shrnutí:	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. Less is known about SARS-CoV-2 infection in unstudied geographical areas such as sub-Saharan Africa. Here the authors use multi-omics to characterize the immune response to SARS-CoV-2 in Uganda and consider how people living with HIV immunologically differentially respond to the virus.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-024-45204-3