Abstract

SARS-CoV-2 has spread throughout the world since its discovery in China, and Malaysia is no exception. WGS has been a crucial approach in studying the evolution and genetic diversity of SARS-CoV-2 in the ongoing pandemic. Despite considerable number of SARS-CoV-2 genome sequences have been submitted to GISAID and NCBI databases, there is still scarcity of data from Malaysia. This study aims to report new Malaysian lineages of the virus, responsible for the sustained spikes in COVID-19 cases during the third wave of the pandemic. Patients with nasopharyngeal and/or oropharyngeal swabs confirmed COVID-19 positive by real-time RT-PCR with CT value < 25 were chosen for WGS. The selected SARS-CoV-2 isolates were then sequenced, characterized and analyzed along with 986 sequences of the dominant lineages of D614G variants currently circulating throughout Malaysia. The prevalence of clade GH and G formed strong ground for the presence of two Malaysian lineages of AU.2 and B.1.524 that has caused sustained spikes of cases in the country. Statistical analysis on the association of gender and age group with Malaysian lineages revealed a significant association (p <0.05). Phylogenetic analysis revealed dispersion of 41 lineages, of these, 22 lineages are still active. Mutational analysis showed presence of unique G1223C missense mutation in transmembrane domain of the spike protein. For better understanding of the SARS-CoV-2 evolution in Malaysia especially with reference to the reported lineages, large scale studies based on WGS are warranted.

Highlights

  • The emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Wuhan, China in December 2019 resulted in an unprecedented global outbreak and soon recognized as pandemic, referred to as COVID-19 [1,2,3,4]

  • This study reports new Malaysian lineages that are responsible in causing sustained spikes in COVID-19 cases throughout the third wave of the pandemic in Malaysia

  • Of the 1,502 SARS-CoV-2 complete genomes deposited to Global Initiative on Sharing All Influenza Data (GISAID) database, 1,356 contained spike D614G mutation in their genomes

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Summary

Introduction

The emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Wuhan, China in December 2019 resulted in an unprecedented global outbreak and soon recognized as pandemic, referred to as COVID-19 [1,2,3,4]. SARS-CoV-2 actively propagates in lungs as a primary site of infection. This active propagation leads to the storm of inflammatory cytokines that if not curtailed advances the pathology of the disease [5]. By November 2021, more than 260 million confirmed cases of COVID-19, with over 5 million deaths have been reported by the World Health Organization (WHO) [6]. The cumulative number of confirmed cases of COVID-19 in Malaysia has reached over 2.6 million, of which over 30,000 died from the disease. Malaysia is facing a much tougher task in curbing the COVID-19 pandemic in its third wave which began on September 8, 2020 due to the Benteng LD cluster in Sabah [8]. The highest lineage contributor during the third wave of pandemic appeared to be B.1.524, with D614G and A701V mutations in the spike protein of the virus [9]

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