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

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



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 to estimate population-level SARS-CoV-2 exposure. False positive SARS-CoV-2 antibody results have been 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 reactivity to SARS-CoV-2. 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 heavily 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.
Date made availableSep 7 2022

Cite this