Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein.

Lapidus, Sarah; Liu, Feimei; Casanovas-Massana, Arnau; Dai, Yile; Huck, John D; Lucas, Carolina; Klein, Jon; Filler, Renata B; Strine, Madison S; Sy, Mouhamad; Deme, Awa B; Badiane, Aida S; Dieye, Baba; Ndiaye, Ibrahima Mbaye; Diedhiou, Younous; Mbaye, Amadou Moctar; Diagne, Cheikh Tidiane; Vigan-Womas, Inés; Mbengue, Alassane; Sadio, Bacary D; Diagne, Moussa M; Moore, Adam J; Mangou, Khadidiatou; Diallo, Fatoumata; Sene, Seynabou D; Pouye, Mariama N; Faye, Rokhaya; Diouf, Babacar; Nery, Nivison; Costa, Federico; Reis, Mitermayer G; Muenker, M Catherine; Hodson, Daniel Z; Mbarga, Yannick; Katz, Ben Z; Andrews, Jason R; Campbell, Melissa; Srivathsan, Ariktha; Kamath, Kathy; Baum-Jones, Elisabeth; Faye, Ousmane; Sall, Amadou Alpha; Vélez, Juan Carlos Quintero; Cappello, Michael; Wilson, Michael; Ben-Mamoun, Choukri; Tedder, Richard; McClure, Myra; Cherepanov, Peter; Somé, Fabrice A; Dabiré, Roch K; Moukoko, Carole Else Eboumbou; Ouédraogo, Jean Bosco; Boum, Yap; Shon, John; Ndiaye, Daouda; Wisnewski, Adam; Parikh, Sunil; Iwasaki, Akiko; Wilen, Craig B; Ko, Albert I; Ring, Aaron M; Bei, Amy K

doi:10.25418/crick.21806010.v1

s41598-022-26709-7.pdf (7.66 MB)

Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein.

journal contribution

posted on 2023-01-03, 13:01 authored by Sarah 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

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.