Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein.
Creators: name: Lapidus, Sarah
name: Liu, Feimei
name: Casanovas-Massana, Arnau
name: Dai, Yile
name: Huck, John D
name: Lucas, Carolina
name: Klein, Jon
name: Filler, Renata B
name: Strine, Madison S
name: Sy, Mouhamad
name: Deme, Awa B
name: Badiane, Aida S
name: Dieye, Baba
name: Ndiaye, Ibrahima Mbaye
name: Diedhiou, Younous
name: Mbaye, Amadou Moctar
name: Diagne, Cheikh Tidiane
name: Vigan-Womas, Inés
name: Mbengue, Alassane
name: Sadio, Bacary D
name: Diagne, Moussa M
name: Moore, Adam J
name: Mangou, Khadidiatou
name: Diallo, Fatoumata
name: Sene, Seynabou D
name: Pouye, Mariama N
name: Faye, Rokhaya
name: Diouf, Babacar
name: Nery, Nivison
name: Costa, Federico
name: Reis, Mitermayer G
name: Muenker, M Catherine
name: Hodson, Daniel Z
name: Mbarga, Yannick
name: Katz, Ben Z
name: Andrews, Jason R
name: Campbell, Melissa
name: Srivathsan, Ariktha
name: Kamath, Kathy
name: Baum-Jones, Elisabeth
name: Faye, Ousmane
name: Sall, Amadou Alpha
name: Vélez, Juan Carlos Quintero
name: Cappello, Michael
name: Wilson, Michael
name: Ben-Mamoun, Choukri
name: Tedder, Richard
name: McClure, Myra
name: Cherepanov, Peter
name: Somé, Fabrice A
name: Dabiré, Roch K
name: Moukoko, Carole Else Eboumbou
name: Ouédraogo, Jean Bosco
name: Boum, Yap
name: Shon, John
name: Ndiaye, Daouda
name: Wisnewski, Adam
name: Parikh, Sunil
name: Iwasaki, Akiko
name: Wilen, Craig B
name: Ko, Albert I
name: Ring, Aaron M
name: Bei, Amy K
Publisher: name: The Francis Crick Institute
Year: 2023
Subjects: classificationCode: Biochemistry & Proteomics
subject: Biochemistry &amp; Proteomics
classificationCode: Genome Integrity & Repair
subject: Genome Integrity &amp; Repair
classificationCode: Structural Biology & Biophysics
subject: Structural Biology &amp; Biophysics
classificationCode: Cell Cycle & Chromosomes
subject: Cell Cycle &amp; Chromosomes

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. 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.