SARS-CoV-2 lineage B.6 is the major contributor to transmission in Malaysia

Abstract

BackgroundAs of June 30, 2020, Malaysia had confirmed 8,639 cases of COVID-19. About 39% of these were associated with a religious mass gathering event held in Kuala Lumpur between February 27 and March 1, 2020, which drove community transmission during Malaysias main wave. We analysed genome sequences of SARS-CoV-2 from Malaysia to understand the molecular epidemiology. MethodsWe obtained whole genome sequences of SARS-CoV-2 from 58 COVID-19 patients in Kuala Lumpur, Malaysia, and performed phylogenetic analyses on these and a further 50 Malaysian sequences available in the GISAID database. Malaysian lineage B.6 sequences were further analysed with all available worldwide lineage B.6 sequences. ResultsNine different SARS-CoV-2 lineages (A, B, B.1, B.1.1, B.1.1.1, B.1.36, B.2, B.3 and B.6) were detected in Malaysia. The B.6 lineage was first reported a week after the mass gathering and became predominant (63%) despite being relatively rare (1.4%) among available global sequences. Increases in reported cases and community-acquired B.6 lineage strains were temporally linked. Non-B.6 lineages were mainly associated with travel and showed limited onward transmission. There were also temporally-correlated increases in B.6 sequences in other Southeast Asian countries, India and Australia, linked to participants returning from this event. We also report the presence of a nsp3-C6310A substitution found in 40.5% of global B.6 sequences which has associated with reduced sensitivity in a commercial assay. ConclusionLineage B.6 became the predominant cause of community transmission in Malaysia after likely introduction during a religious mass gathering. This event also contributed to spikes of lineage B.6 in other countries in the region. Author SummaryThe COVID-19 pandemic in Malaysia was driven mainly by transmission following a religious mass gathering held in Kuala Lumpur at the end of February. To study the genetic epidemiology of SARS-CoV-2 in Malaysia, we analysed 50 available and 58 newly-generated Malaysian whole genome virus sequences. We found that lineage B.6, rare (1.4%) globally, first appeared after the mass gathering and became the most predominant (62.9%) in Malaysia. Increases in COVID-19 cases and locally-acquired B.6 strains were temporally linked. Non-B.6 viruses were mainly associated with travel and showed limited spread. Increases in B.6 viruses in Southeast Asian countries, India and Australia were linked to participants returning from this mass gathering. Altogether, 95.3% of global B.6 sequences originated in Asia or Australia. We also report a mutation in the virus nsP3 gene found in 40.5% of global B.6 sequences and associated with reduced detection by a commercial diagnostic test. In conclusion, the religious mass gathering in Kuala Lumpur was associated with the main wave of COVID-19 cases of predominantly B.6 lineage in Malaysia, and subsequent spread of B.6 viruses regionally. Genome sequence data provides valuable insight into virus spread and is important for monitoring continued accuracy of diagnostic kits.