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

tetano

Editor, Senior Moderator
Sci Rep


. 2022 Dec 22;12(1):22175.
doi: 10.1038/s41598-022-26709-7.
Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein


Sarah Lapidus[SUP] 1 [/SUP], Feimei Liu[SUP] 2 [/SUP], Arnau Casanovas-Massana[SUP] 1 [/SUP], Yile Dai[SUP] 2 [/SUP], John D Huck[SUP] 2 [/SUP], Carolina Lucas[SUP] 2 [/SUP], Jon Klein[SUP] 2 [/SUP], Renata B Filler[SUP] 2 3 [/SUP], Madison S Strine[SUP] 2 3 [/SUP], Mouhamad Sy[SUP] 1 4 [/SUP], Awa B Deme[SUP] 1 4 [/SUP], Aida S Badiane[SUP] 4 [/SUP], Baba Dieye[SUP] 4 [/SUP], Ibrahima Mbaye Ndiaye[SUP] 4 [/SUP], Younous Diedhiou[SUP] 4 [/SUP], Amadou Moctar Mbaye[SUP] 4 [/SUP], Cheikh Tidiane Diagne[SUP] 5 [/SUP], Inés Vigan-Womas[SUP] 6 [/SUP], Alassane Mbengue[SUP] 7 [/SUP], Bacary D Sadio[SUP] 8 [/SUP], Moussa M Diagne[SUP] 8 [/SUP], Adam J Moore[SUP] 1 [/SUP], Khadidiatou Mangou[SUP] 7 [/SUP], Fatoumata Diallo[SUP] 7 [/SUP], Seynabou D Sene[SUP] 7 [/SUP], Mariama N Pouye[SUP] 7 [/SUP], Rokhaya Faye[SUP] 6 [/SUP], Babacar Diouf[SUP] 6 [/SUP], Nivison Nery Jr[SUP] 9 10 [/SUP], Federico Costa[SUP] 1 9 11 [/SUP], Mitermayer G Reis[SUP] 1 11 12 [/SUP], M Catherine Muenker[SUP] 1 [/SUP], Daniel Z Hodson[SUP] 1 [/SUP], Yannick Mbarga[SUP] 13 [/SUP], Ben Z Katz[SUP] 14 [/SUP], Jason R Andrews[SUP] 15 [/SUP], Melissa Campbell[SUP] 16 [/SUP], Ariktha Srivathsan[SUP] 1 [/SUP], Kathy Kamath[SUP] 17 [/SUP], Elisabeth Baum-Jones[SUP] 17 [/SUP], Ousmane Faye[SUP] 8 [/SUP], Amadou Alpha Sall[SUP] 8 [/SUP], Juan Carlos Quintero Vélez[SUP] 1 18 19 [/SUP], Michael Cappello[SUP] 1 20 [/SUP], Michael Wilson[SUP] 21 [/SUP], Choukri Ben-Mamoun[SUP] 22 [/SUP], Richard Tedder[SUP] 23 24 [/SUP], Myra McClure[SUP] 23 [/SUP], Peter Cherepanov[SUP] 23 25 26 [/SUP], Fabrice A Somé[SUP] 27 [/SUP], Roch K Dabiré[SUP] 27 [/SUP], Carole Else Eboumbou Moukoko[SUP] 28 29 [/SUP], Jean Bosco Ouédraogo[SUP] 27 [/SUP], Yap Boum 2nd[SUP] 30 [/SUP], John Shon[SUP] 17 [/SUP], Daouda Ndiaye[SUP] 4 [/SUP], Adam Wisnewski[SUP] 10 [/SUP], Sunil Parikh[SUP] 1 [/SUP], Akiko Iwasaki[SUP] 1 2 31 [/SUP], Craig B Wilen[SUP] 2 [/SUP], Albert I Ko[SUP] 1 11 [/SUP], Aaron M Ring[SUP] 2 [/SUP], Amy K Bei[SUP] 32 33 34 [/SUP]



Affiliations

Abstract

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.
 
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