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

Simple item page
dc.contributor.authorCummings, Matthew J
dc.contributor.authorBakamutumaho, Barnabas
dc.contributor.authorLutwama, Julius J
dc.contributor.authorOwor, Nicholas
dc.contributor.authorChe, Xiaoyu
dc.contributor.authorAstorkia, Maider
dc.contributor.authorPostler, Thomas S
dc.contributor.authorKayiwa, John
dc.contributor.authorKiconco, Jocelyn
dc.contributor.authorMuwanga, Moses
dc.contributor.authorNsereko, Christopher
dc.contributor.authorwamutwe, Emmanuel
dc.contributor.authorNayiga, Irene
dc.contributor.authorKyebambe, Stephen
dc.contributor.authorHaumba, Mercy
dc.contributor.authorBosa, Henry Kyobe
dc.contributor.authorOcom, Felix
dc.contributor.authorWatyaba, Benjamin
dc.contributor.authorTKikaire, Bernard
dc.contributor.authorTomoiaga, Alin S
dc.contributor.authorKisaka, Stevens
dc.contributor.authorKiwanuka, Noah
dc.contributor.authorLipkin, W Ian
dc.contributor.authorO'Donnell, Max R
dc.date.accessioned2024-02-23T12:31:16Z
dc.date.available2024-02-23T12:31:16Z
dc.date.issued2024-02
dc.description.abstractLittle 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.en_US
dc.identifier.citationCummings, Matthew J., Barnabas Bakamutumaho, Julius J. Lutwama, et al. 'COVID-19 Immune Signatures in Uganda Persist in HIV Co-Infection and Diverge by Pandemic Phase', Nature Communications, vol. 15/no. 1, (2024), pp. 1475.en_US
dc.identifier.issnEISSN 2041-1723
dc.identifier.urihttps://nru.uncst.go.ug/handle/123456789/9412
dc.language.isoenen_US
dc.publisherNature Publishing Groupen_US
dc.subjectCOVID-19; immune signatures; HIV co-infection; Ugandaen_US
dc.titleCOVID-19 immune signatures in Uganda persist in HIV co-infection and diverge by pandemic phaseen_US
dc.typeArticleen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
s41467-024-45204-3.pdf
Size:
5.01 MB
Format:
Adobe Portable Document Format
Description:
Journal Article
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Medical and Health Sciences