Scientific Reports (Dec 2022)

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

  • 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,
  • 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,
  • John Shon,
  • Daouda Ndiaye,
  • Adam Wisnewski,
  • Sunil Parikh,
  • Akiko Iwasaki,
  • Craig B. Wilen,
  • Albert I. Ko,
  • Aaron M. Ring,
  • Amy K. Bei

DOI
https://doi.org/10.1038/s41598-022-26709-7
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 16

Abstract

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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.