tetano
Editor, Senior Moderator
Nat Commun
. 2024 Feb 17;15(1):1475.
doi: 10.1038/s41467-024-45204-3. COVID-19 immune signatures in Uganda persist in HIV co-infection and diverge by pandemic phase
Matthew J Cummings[SUP] 1 2 [/SUP], Barnabas Bakamutumaho[SUP] 3 [/SUP], Julius J Lutwama[SUP] 3 [/SUP], Nicholas Owor[SUP] 3 [/SUP], Xiaoyu Che[SUP] 4 5 [/SUP], Maider Astorkia[SUP] 4 [/SUP], Thomas S Postler[SUP] 6 [/SUP], John Kayiwa[SUP] 3 [/SUP], Jocelyn Kiconco[SUP] 3 [/SUP], Moses Muwanga[SUP] 7 [/SUP], Christopher Nsereko[SUP] 7 [/SUP], Emmanuel Rwamutwe[SUP] 7 [/SUP], Irene Nayiga[SUP] 7 [/SUP], Stephen Kyebambe[SUP] 7 [/SUP], Mercy Haumba[SUP] 3 [/SUP], Henry Kyobe Bosa[SUP] 8 9 [/SUP], Felix Ocom[SUP] 9 [/SUP], Benjamin Watyaba[SUP] 10 [/SUP], Bernard Kikaire[SUP] 10 11 [/SUP], Alin S Tomoiaga[SUP] 12 13 [/SUP], Stevens Kisaka[SUP] 14 15 [/SUP], Noah Kiwanuka[SUP] 14 [/SUP], W Ian Lipkin[SUP] 4 16 17 [/SUP], Max R O'Donnell[SUP] 12 4 17 [/SUP]; Collaboration for Clinical and Laboratory Characterization of COVID-19 in Uganda
Collaborators, Affiliations
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[SUP]+[/SUP] 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 Feb 17;15(1):1475.
doi: 10.1038/s41467-024-45204-3. COVID-19 immune signatures in Uganda persist in HIV co-infection and diverge by pandemic phase
Matthew J Cummings[SUP] 1 2 [/SUP], Barnabas Bakamutumaho[SUP] 3 [/SUP], Julius J Lutwama[SUP] 3 [/SUP], Nicholas Owor[SUP] 3 [/SUP], Xiaoyu Che[SUP] 4 5 [/SUP], Maider Astorkia[SUP] 4 [/SUP], Thomas S Postler[SUP] 6 [/SUP], John Kayiwa[SUP] 3 [/SUP], Jocelyn Kiconco[SUP] 3 [/SUP], Moses Muwanga[SUP] 7 [/SUP], Christopher Nsereko[SUP] 7 [/SUP], Emmanuel Rwamutwe[SUP] 7 [/SUP], Irene Nayiga[SUP] 7 [/SUP], Stephen Kyebambe[SUP] 7 [/SUP], Mercy Haumba[SUP] 3 [/SUP], Henry Kyobe Bosa[SUP] 8 9 [/SUP], Felix Ocom[SUP] 9 [/SUP], Benjamin Watyaba[SUP] 10 [/SUP], Bernard Kikaire[SUP] 10 11 [/SUP], Alin S Tomoiaga[SUP] 12 13 [/SUP], Stevens Kisaka[SUP] 14 15 [/SUP], Noah Kiwanuka[SUP] 14 [/SUP], W Ian Lipkin[SUP] 4 16 17 [/SUP], Max R O'Donnell[SUP] 12 4 17 [/SUP]; Collaboration for Clinical and Laboratory Characterization of COVID-19 in Uganda
Collaborators, Affiliations
- PMID: 38368384
- PMCID: PMC10874401
- DOI: 10.1038/s41467-024-45204-3
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[SUP]+[/SUP] 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.