Cross-Reactivity of SARS-CoV-2 Laboratory Diagnostics to Endemic Diseases in Africa: A Diagnostic Accuracy Study

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Diagne, Cheikh Tidiane | Ndiaye, Oumar | Talla, Cheikh | Dia, Fatou | Faye, Rokhaya | Diouf, Babacar | Tall, Billo | Mbengue, Alassane | Diop, Mamadou | Diallo, Khardiata | Cisse, Vivianne Marie Pierre | Ndoye, Amadou Moustapha | Barry, Aliou | Niang, Makhtar | Loucoubar, Cheikh | Dia, Ndongo | Bei, Amy, K. | Fitchett, Joseph, R. A. | Taieb, Fabien | Faye, Ousmane | Peeling, Rosanna, W. | Vigan-Womas, Inés | Sall, Amadou

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Background: Serology is a great tool to assess the level of immunity against SARS-CoV-2 in settings with limited access to molecular diagnostics. However, African populations displays a particular immunological profile with massive circulation of infectious agents from different aetiologies that can affect assays performance.Methods: We evaluated the OMEGA Diagnostics COVID-19 ELISA-IgG and the ID Screen® SARS-CoV-2-N IgG Indirect in Senegal using a panel of 636 blood samples covering several African-endemic diseases and healthy donors to determine test sensitivity and specificity. The sensitivity panel of sera includes 461 serum samples collected from 91 patients hospitalized for COVID-19 disease. COVID-19 cases were confirmed by qRT-PCR and samples were collected on an interval of three days until viral clearance. In addition, 272 sera obtained from COVID-19 negative individuals were selected from a well-documented biobank of sera collected before the COVID-19 outbreak.Finding: High-cross reactivity have been found in individuals with a history of exposure to Chikungunya, HIV, malaria (Plasmodium falciparum), rheumatoid factor as well as healthy donors with respective specificities of 55%, 41.8%, 70%, 70% and 75%. ELISA experiments with commercial assays targeting either SARS-CoV-2 Nucleocapsid protein and Spike 2 protein or nucleocapsid protein only suggest that cross-reactivity might be directed against Spike 2 protein and not Nucleocapsid protein. Further samples characterisation reveals that anti-malaria IgG is the leading cause of such poor specificities, but exposure to other diseases contributed as well.Interpretation: We anticipate that COVID-19 seroprevalence can be biased if assays are not contextualized. Since malaria is endemic in African settings, we propose that a particular attention must be given in serological surveillance of COVID-19 or anti-SARS-CoV-2 antibodies quantification as vaccines are being rolled out.

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