Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike proteinMore about Open Access at the Crick
Authors listSarah Lapidus Feimei Liu Arnau Casanovas-Massana Yile Dai John D Huck Carolina Lucas Jon Klein Renata B Filler Madison S Strine Mouhamad Sy Awa B Deme Aida S Badiane Baba Dieye Ibrahima Mbaye Ndiaye Younous Diedhiou Amadou Moctar Mbaye Cheikh Tidiane Diagne Inés Vigan-Womas Alassane Mbengue Bacary D Sadio Moussa M Diagne Adam J Moore Khadidiatou Mangou Fatoumata Diallo Seynabou D Sene Mariama N Pouye Rokhaya Faye Babacar Diouf Nivison Nery Jr Federico Costa Mitermayer G Reis M Catherine Muenker Daniel Z Hodson Yannick Mbarga Ben Z Katz Jason R Andrews Melissa Campbell Ariktha Srivathsan Kathy Kamath Elisabeth Baum-Jones Ousmane Faye Amadou Alpha Sall Juan Carlos Quintero Vélez Michael Cappello Michael Wilson Choukri Ben-Mamoun Richard Tedder Myra McClure Peter Cherepanov Fabrice A Somé Roch K Dabiré Carole Else Eboumbou Moukoko Jean Bosco Ouédraogo Yap Boum II John Shon Daouda Ndiaye Adam Wisnewski Sunil Parikh Akiko Iwasaki Craig B Wilen Albert I Ko Aaron M Ring Amy K Bei
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Sero-surveillance can monitor and project disease burden and risk. However, SARS-CoV-2 antibody test results can produce false positive results, limiting their efficacy as a sero-surveillance tool. False positive SARS-CoV-2 antibody results are associated with malaria exposure, and understanding this association is essential to interpret sero-surveillance results from malaria-endemic countries. Here, pre-pandemic samples from eight malaria endemic and non-endemic countries and four continents were tested by ELISA to measure SARS-CoV-2 Spike S1 subunit reactivity. Individuals with acute malaria infection generated substantial SARS-CoV-2 reactivity. Cross-reactivity was not associated with reactivity to other human coronaviruses or other SARS-CoV-2 proteins, as measured by peptide and protein arrays. ELISAs with deglycosylated and desialated Spike S1 subunits revealed that cross-reactive antibodies target sialic acid on N-linked glycans of the Spike protein. The functional activity of cross-reactive antibodies measured by neutralization assays showed that cross-reactive antibodies did not neutralize SARS-CoV-2 in vitro. Since routine use of glycosylated or sialated assays could result in false positive SARS-CoV-2 antibody results in malaria endemic regions, which could overestimate exposure and population-level immunity, we explored methods to increase specificity by reducing cross-reactivity. Overestimating population-level exposure to SARS-CoV-2 could lead to underestimates of risk of continued COVID-19 transmission in sub-Saharan Africa.
Journal Scientific Reports
Issue number 1