Matthew J Cummings, Barnabas Bakamutumaho, Julius J Lutwama, Nicholas Owor, Xiaoyu Che, Maider Astorkia, Thomas S Postler, John Kayiwa, Jocelyn Kiconco, Moses Muwanga, Christopher Nsereko, Emmanuel Rwamutwe, Irene Nayiga, Stephen Kyebambe, Mercy Haumba, Henry Kyobe Bosa, Felix Ocom, Benjamin Watyaba, Bernard Kikaire, Alin S Tomoiaga, Stevens Kisaka, Noah Kiwanuka, W Ian Lipkin, Max R O'Donnell
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...
February 17, 2024: Nature Communications