Postmortem single-cell studies have transformed understanding of lower respiratory tract diseases (LRTDs), including coronavirus disease 2019 (COVID-19), but there are minimal data from African settings where HIV, malaria and other environmental exposures may affect disease pathobiology and treatment targets. In this study, we used histology and high-dimensional imaging to characterize fatal lung disease in Malawian adults with (n = 9) and without (n = 7) COVID-19, and we generated single-cell transcriptomics data from lung, blood and nasal cells. Data integration with other cohorts showed a conserved COVID-19 histopathological signature, driven by contrasting immune and inflammatory mechanisms: in US, European and Asian cohorts, by type I/III interferon (IFN) responses, particularly in blood-derived monocytes, and in the Malawian cohort, by response to IFN-γ in lung-resident macrophages. HIV status had minimal impact on histology or immunopathology. Our study provides a data resource and highlights the importance of studying the cellular mechanisms of disease in underrepresented populations, indicating shared and distinct targets for treatment.

死后单细胞研究改变了对下呼吸道疾病 （LRTD） 的理解，包括 2019 年冠状病毒病 （COVID-19），但来自非洲地区的数据很少，因为 HIV、疟疾和其他环境暴露可能会影响疾病病理学和治疗目标。在这项研究中，我们使用组织学和高维成像来表征患有 （n = 9） 和没有 （n = 7） COVID-19 的马拉维成年人的致命性肺病，并从肺、血液和鼻细胞生成了单细胞转录组学数据。与其他队列的数据整合显示，由对比免疫和炎症机制驱动的保守 COVID-19 组织病理学特征：在美国、欧洲和亚洲队列中，通过 I/III 型干扰素 （IFN） 反应，特别是在血液来源的单核细胞中，在马拉维队列中，通过对肺驻留巨噬细胞中 IFN γ的反应。HIV 状态对组织学或免疫病理学的影响最小。我们的研究提供了数据资源，并强调了在代表性不足的人群中研究疾病细胞机制的重要性，表明了共同和不同的治疗靶点。