Defining the COVID19 risk in the Greater Mekong Subregion

National Institute Of Allergy And Infectious Diseases

Investigators

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Abstract

METAGENOMIC CHARACTERIZATION OF SARS-COV-2 AND ITS VARIANTS AID CAMBODIAN PUBLIC HEALTH RESPONSE TO COVID19 PANDEMIC. NIAID Cambodia ICER quickly repurposed an existing metagenomics pipeline, originally set up for vector-borne diseases, to genetically characterize index cases of COVID-19 in January 2020. At this early pre-pandemic timepoint, sequencing COVID-19 cases was critical given the SARS-CoV-2 genetic diversity in humans and animals was not completely known, and thus mutation rates and the consequences thereof were not understood. Further, non-specificity of tests combined with variable sample quality limited confidence in field diagnostics. Despite limited sequencing capacity in-country, ICER Cambodia successfully identified and sequenced the novel SARS-CoV-2 pathogen, after developing enrichment methods to overcome handicaps of low coverage of the genome. Since that time, ICER Cambodia has upgraded to a NextSeq 2000 that allows full recovery of SARS-CoV-2 genomes without enrichment or amplicon-based methods. We have assisted the Royal Cambodian Governments Ministry of Health in sequencing several outbreaks for containment and mitigation of SARS-CoV-2 in Cambodia and have expanded the NIAID collaboration to include the Cambodian Communicable Disease Center. MALARIA-EXPERIENCED CAMBODIANS DEMONSTRATE HIGHER-THAN-EXPECTED SARS-COV-2 SEROPOSITIVITY. Southeast Asians are exposed to pathogens, zoonotic and otherwise, that may influence SARS-CoV-2 seroreactivity. We performed a pre-pandemic (2005 to 2011) serosurvey of 528 malaria-experienced Cambodians. Our results demonstrated higher-than-expected (up to 13.8%) positivity of non-neutralizing IgG to SARS-CoV-2 spike and RBD antigens. This SARS-CoV-2 serological cross-reactivity is linked to higher AMA-1 antibody levels, a marker of malaria immunity and is not associated with levels of common cold respiratory betacoronaviruses. However, it is possible other zoonotic betacoronavirus exposure (e.g. from common agriculture practice with bat guano) may also contribute to the cross-reactivity. These findings have implications for interpreting large-scale SARS-CoV-2 serosurveys from malaria-endemic areas and understanding the diversity of coronavirus exposure in Southeast Asia.