Abstract

BackgroundMore than a year after its first appearance in December 2019, the COVID-19 pandemic is still on a rampage in many parts of the world. Although several vaccines have been approved for emergency use, the emergence and rapid spread of new SARS-CoV-2 variants have sparked fears of vaccine failure due to immune evasion. Massive viral genome sequencing has been recommended to track the genetic changes that could lead to adverse consequences.MethodsWe sequenced SARS-CoV-2 respiratory isolates from the National Public Health Laboratory, Malaysia and examined them together with viral genomes deposited in GISAID by other Malaysian researchers, to understand the evolutionary trend of the virus circulating in the country. We studied the distribution of virus lineages and site-wise mutations, analysed genetic clustering with the goeBURST full Minimum Spanning Tree algorithm, examined the trend of viral nucleotide diversity over time and performed nucleotide substitution association analyses.ResultsWe identified 22 sub-lineages, 13 clonal complexes, 178 sequence types and seven sites of linkage disequilibrium in 277 SARS-CoV-2 genomes sequenced between January and December 2020. B.1.524 was the largest lineage group. The number of mutations per genome ranged from 0 to 19. The mean genomic diversity value over 12 months was 3.26 × 10−4. Of 359 mutations detected, 60.5% of which were non-synonymous, the most frequent were in the ORF1ab (P4715L), S (D614G and A701V) and N (S194L) genes.ConclusionThe SARS-CoV-2 virus accumulated an abundance of mutations in the first year of the COVID-19 pandemic in Malaysia. Its overall genetic diversity, however, is relatively low compared to other Asian countries with larger populations. Continuous genomic and epidemiological surveillance will help to clarify the evolutionary processes determining viral diversity and impacting on human health.

Highlights

  • Despite world-wide control efforts, the COVID-19 pandemic continues to ravage many populations since it was first reported in December 2019

  • Other prominent outbreaks included the Pesantren cluster in April that was linked to Malaysian students returning from a religious school in East Java, Indonesia, and the Sivaganga cluster in July-August that was traced to a Malaysian who returned from India carrying the D614G variant (Danial et al, 2020)

  • From October 2020 onwards, increasing cases occurred in the East Malaysian states of Sabah and Sarawak causing the incidence and the effective reproduction number (Rt) of COVID-19 there to exceed those in Peninsular Malaysia (WHO, 2021)

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Summary

Introduction

Despite world-wide control efforts, the COVID-19 pandemic continues to ravage many populations since it was first reported in December 2019 This protraction has been attributed partially to the emergence of SARS-CoV-2 mutants that have been linked with increased infectivity and the ability to resist host immune responses. Local transmission and further importation from different parts of the world increased the number of confirmed cases to 115,078 (an incidence of 352.14/100,000) with 474 (0.41%) deaths by 1 January 2021 and 514 clusters of infection reported in the 12-month period (Fun et al, 2021). One of the largest was associated with a Tablighi Jamaat religious mass gathering held in Kuala Lumpur between February 27 and March 3, 2020, that was attended by about 16,000 people (10% foreigners from many different countries) and 34 deaths among 3,375 infected individuals (Fun et al, 2021). Continuous genomic and epidemiological surveillance will help to clarify the evolutionary processes determining viral diversity and impacting on human health

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