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Abstract 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.

Abstract Background Beta-hemolytic streptococci carrier rates in children living in low-income countries are high ranging from 10 to 50%. Although most of these children are asymptomatic, they are a reservoir and pose a risk of transmission. The aim of this study was to determine the prevalence of group a streptococcus pharyngeal carriage and clinical manifestations in school going children in Wakiso district, Uganda. Methods A cross sectional study targeting children age 5–15 years in primary schools in one sub-county of Wakiso district was carried out. Three hundred and sixty-six children from five primary schools were enrolled and evaluated for group a streptococcus (GAS) carriage. A semi-structured questionnaire was used to collect data that included social demographics, school environment and clinical findings. For every enrolled child a throat swab was taken and cultured for GAS and blood was drawn for anti-streptolysin-O titres. Analysis of data was done using STATA. Results The prevalence of GAS carriage was 16%. The children with GAS positive cultures were mainly females. The factor associated with GAS carriage was the school location, with peri-urban schools more likely to have children with GAS compared to rural schools; AOR 2.48 (95% CI: 1.01 – 6.11), P = 0.049. There was no significant difference between the characteristic of children with GAS positive verses GAS negative throat swab cultures. Conclusion There is a high prevalence of GAS pharyngeal carriage among children aged 5–15 years attending primary schools in Wakiso District, Uganda.