03271nas a2200745   4500000000100000000000100001008004100002260001500043653002300058653001400081653002400095653002000119100001900139700002100158700002500179700001900204700002300223700001800246700001900264700002600283700001900309700001800328700002200346700002200368700002100390700001800411700001700429700002000446700001800466700002200484700001800506700001700524700001500541700002500556700001900581700001600600700001500616700001600631700001900647700002800666700002400694700004100718700003500759700002900794700003300823700001800856700002300874700001900897700001800916700002200934700002200956700001900978700002000997700002601017700002001043700001701063700001901080700001901099700002501118245012701143856005501270300000901325520117701334022001402511       2024                            d  c2024-11-2010aImmunopathogenesis10ainfection10aSingle-cell imaging10aViral infection1 aJames Nyirenda1 aOlympia M. Hardy1 aJoão Da Silva Filho1 aVanessa Herder1 aCharalampos Attipa1 aCharles Ndovi1 aMemory Siwombo1 aTakondwa Rex Namalima1 aLeticia Suwedi1 aGeorgios Ilia1 aWatipenge Nyasulu1 aThokozile Ngulube1 aDeborah Nyirenda1 aLeonard Mvaya1 aJoseph Phiri1 aDennis Chasweka1 aChisomo Eneya1 aChikondi Makwinja1 aChisomo Phiri1 aFrank Ziwoya1 aAbel Tembo1 aKingsley Makwangwala1 aStanley Khoswe1 aPeter Banda1 aBen Morton1 aOrla Hilton1 aSarah Lawrence1 aMonique Freire dos Reis1 aGisely Cardoso Melo1 aMarcus Vinicius Guimaraes de Lacerda1 aFabio Trindade Maranhão Costa1 aWuelton Marcelo Monteiro1 aLuiz Carlos de Lima Ferreira1 aCarla Johnson1 aDagmara McGuinness1 aKondwani Jambo1 aMichael Haley1 aBenjamin Kumwenda1 aMassimo Palmarini1 aDonna M. Denno1 aWieger Voskuijl1 aSteve Bvuobvuo Kamiza1 aKayla G. Barnes1 aKevin Couper1 aMatthias Marti1 aThomas D. Otto1 aChristopher A. Moxon00aSpatially resolved single-cell atlas unveils a distinct cellular signature of fatal lung COVID-19 in a Malawian population  uhttps://www.nature.com/articles/s41591-024-03354-3  a1-133 aPostmortem 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.  a1546-170X