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Published September 7, 2022 | Version v1
Dataset Open

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

  • 1. Yale University
  • 2. Cheikh Anta Diop University
  • 3. Institut Pasteur de Dakar
  • 4. Oswaldo Cruz Foundation
  • 5. Faculdades Oswaldo Cruz
  • 6. Douala Military Hospital*
  • 7. Northwestern University
  • 8. Stanford University
  • 9. Serimmune (United States)
  • 10. University of Antioquia
  • 11. Noguchi Memorial Institute for Medical Research
  • 12. South London Specialist Virology Centre, Kings College Hospital*
  • 13. Imperial College London
  • 14. Institut de Recherche en Sciences de la Santé
  • 15. Center Pasteur Cameroon*
  • 16. Université de Yaoundé I

Description

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.

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