Immune responses to SARS-CoV-2 in sub-Saharan Africa and western Europe: a retrospective, population-based, cross-sectional study.
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Mbow Moustapha, Hoving Dennis, Cisse Marouba, Diallo Ibrahima, Honkpehedji Yabo J, Huisman Wesley, Pothast Cilia R, Jongsma Marlieke L M, König Marion H, de Kroon Alicia C, Linh Le Thi Kieu, Azimi Shohreh, Tak Tamar, Kruize Yvonne C M, Kurniawan Farid, Dia Yacine Amet, Zhang Jaimie L H, Prins Corine, Roukens Anna H E, de Vries Jutte J C, Wammes Linda J, Smits Hermelijn H, Adegnika Ayola A, Zlei Mihaela, Kuijpers Taco W, Wieske Luuk, Dieye Alioune, Mboup Souleymane, Kremsner Peter G, Eftimov Filip, Velavan Thirumalaisamy P, Berlin Ilana, Heemskerk Mirjam H M, Yazdanbakhsh Maria, Jochems Simon P, BEAT-COVID consortium, COVID-19 Leiden University Medical Center study team
Аннотация
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+CD16low 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.