Immune responses to SARS-CoV-2 in sub-Saharan Africa and western Europe: a retrospective, population-based, cross-sectional study
Moustapha Mbow, Dennis Hoving, Marouba Cisse, Ibrahima Diallo, Yabo Josiane Honkpéhèdji, Wesley Huisman, Cilia R. Pothast, Marlieke L.M. Jongsma, Marion König, Alicia C. de Kroon, Le Thi Kieu Linh, Shohreh Azimi, Tamar Tak, Yvonne C. M. Kruize, Farid Kurniawan, Yacine Amet Dia, Jaimie L. H. Zhang, Corine Prins, Anna H.E. Roukens, Jutte J.C. de Vries, Linda J. Wammes, Hermelijn H. Smits, Ayôla Akim Adégnika, Mihaela Zlei, Taco W. Kuijpers, Luuk Wieske, Alioune Dièye, Souleymane Mboup, Peter G. Kremsner, Filip Eftimov, Thirumalaisamy P. Velavan, Ilana Berlin, Mirjam H.M. Heemskerk, Maria Yazdanbakhsh, Simon P. Jochems, Simon P Jochems, M. Sesmu Arbous, Bernard M. van den Berg, Jurriaan J. van der Brand, Sandra de Bruin-Versteeg, Suzanne Cannegieter, Kirsten Canté, Christa M. Cobbaert, Esther J.C. Coenen - van Vroonhoven, Anne M. van der Does, Jacques J.M. van Dongen, Jeroen Eikenboom, Mariet C.W. Feltkamp, Annemieke Geluk, Jelle J. Goeman, Martin Giera, Rick J. Groenland, Thomas Hankemeier, Mirjam H.M. Heemskerk, Pieter S. Hiemstra, Cornelis H. Hokke, Rosalie van der Holst, Jacqueline J. Janse, Simon P. Jochems, Simon P. Jochems, Simone A. Joosten, Marjolein Kikkert, Stefanie Klaver Flores, Lieke Lamont, Judith Manniën, Bas de Mooij, Tom H.M. Ottenhoff, Karin Pike-Overzet, Tamás Pongrácz, Michael R. del Prado, Núria Queralt Rosinach, Meta Roestenberg, Marco Roos, Anna H.E. Roukens, Marlies Schrevel, Alita J. van der Sluijs-Gelling, Hermelijn H. Smits, Eric J. Snijder, Frank J.T. Staal, Marloes D. Stradmeijer, Alouette P. Strik, Leendert A. Trouw, Roula Tsonaka, Aswin Verhoeven, Leo G. Visser, Jutte J.C. de Vries, David J. van Westerloo, Jeanette Wigbers, Henk J. van der Wijk, Robin C. van Wissen, Manfred Wuhrer, Maria Yazdanbakhsh, Mihaela Zlei, Diane de Zwart-Slats, Josine A. Oud, Meryem Baysan, Jeanette Wigbers, Lieke J. van Heurn, Susan B. ter Haar, Alexandra G.L. Toppenberg
Abstract
Background SARS-CoV-2 has been associated with a higher proportion of asymptomatic infections and lower mortality in sub-Saharan Africa than high-income countries. However, there is currently a lack of data on cellular immune responses to SARS-CoV-2 in people living in Africa compared with people in high-income regions of the world. We aimed to assess geographical variation in peripheral and mucosal immune responses. Methods In this retrospective, population-based, cross-sectional study, we analysed peripheral blood and nasal curettage samples from seven clinical studies involving individuals from Senegal (Senegalese cohort), the Netherlands, and Germany (European cohort). Samples were collected between Nov 1, 2018, and Dec 20, 2021. We included samples from individuals with no, mild, or severe COVID-19. A validation cohort of individuals from Senegal and Gabon (n=64) was used to validate key findings from the main cohort. Matching of individuals between geographical regions by age, sex, viral load, and infection severity and duration was used to address confounding factors. We examined the cellular, humoral, and cytokine immune responses using cytometry by time of flight, spectral flow cytometry, ELISA, and Luminex. Findings We included 133 individuals (59 from the Senegalese cohort and 74 from the European cohort). In contrast to the European cohort, mild COVID-19 in the Senegalese cohort was not associated with any statistically significant perturbations in blood or nasal immune cell profiles, nor with increased pro-inflammatory cytokines, although SARS-CoV-2-specific adaptive immunity was readily induced, as seen in Europeans. In severe COVID-19, both the Senegalese and European cohorts showed lymphopenia (Senegal: 2·9-times decrease, p=0·0010 vs Europe: 1·6-times decrease, p=0·0046) and increased neutrophil frequencies in blood (Senegal: 2·0-times increase, p=0·0044 vs Europe: 1·3-times increase, p=0·026) and the nasal mucosa CD66b + CD16 low neutrophils (Senegal: 9·9-times increase, p=0·045 vs Europe: 392-times increase, p<0·0001). However, in contrast to Europeans, the Senegalese cohort had no significant expansion of immature immune populations, inflammasome activation, or monocyte recruitment to the nasal mucosa. Interpretation The observed divergent immunological trajectories during SARS-CoV-2 infection offer a potential explanation for the reported attenuated disease course in sub-Saharan Africa and highlight the need to further investigate immune responses to SARS-CoV-2 in understudied populations. Funding European and Developing Countries Clinical Trials Partnership 2 programme (AIDCO), LUMC Gisela Thier Fellowship, Dutch Research Council (NWO), European Research Council, and Leids Universitair Fonds.