Emergence of B.1.524(G) SARS-CoV-2 in Malaysia during the third COVID-19 epidemic wave

Abstract

The COVID-19 pandemic first emerged in Malaysia in Jan 2020. As of 12th Sept 2021, 1,979,698 COVID-19 cases that occurred over three major epidemic waves were confirmed. The virus contributing to the three epidemic waves has not been well-studied. We sequenced the genome of 22 SARS-CoV-2 strains detected in Malaysia during the second and the ongoing third wave of the COVID-19 epidemic. Detailed phylogenetic and genetic variation analyses of the SARS-CoV-2 isolate genomes were performed using these newly determined sequences and all other available sequences. Results from the analyses suggested multiple independent introductions of SARS-CoV-2 into Malaysia. A new B.1.524(G) lineage with S-D614G mutation was detected in Sabah, East Malaysia and Selangor, Peninsular Malaysia on 7th October 2020 and 14th October 2020, respectively. This new B.1.524(G) group was not the direct descendant of any of the previously detected lineages. The new B.1.524(G) carried a set of genetic variations, including A701V (position variant frequency = 0.0007) in Spike protein and a novel G114T mutation at the 5’UTR. The biological importance of the specific mutations remained unknown. The sequential appearance of the mutations, however, suggests that the spread of the new B.1.524(G) lineages likely begun in Sabah and then spread to Selangor. The findings presented here support the importance of SARS-CoV-2 full genome sequencing as a tool to establish an epidemiological link between cases or clusters of COVID-19 worldwide.

SARS-CoV-2 Amino Acid Mutations Detection in Greek Patients Infected in the First Wave of the Pandemic

“…Finally, the two mutations that were first identified in the present study (ORF3a_T269del, M_L54F) concern residues with previously detected variation (CoV-GLUE Mutations), which could partly explain our findings. These data, including the presence of less common mutations that were identified in the randomly selected SARS-CoV-2 genome sequences of our study and of previous studies with small cohorts of patients [ 39 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 ], further confirm the existence of variation in the genomic sequence, regardless of whether these mutations have been established worldwide producing new viral lineages or not. Viral genome evolution during the first wave of the pandemic has been characterized by the emergence of sets of substitutions that led to the establishment of more than one new viral strain [ 115 , 116 ].…”

“…ORF1ab_L3606F, which has been described as a homoplastic mutation [ 75 ], was observed in China for the first time [ 59 ] and has also been reported in studies concerning Italy [ 59 ], Brazil [ 59 ], Iran [ 108 ], Africa [ 109 ] and in other studies that do not specify geographic regions [ 62 , 67 , 68 , 69 , 120 ]. Moreover, ORF1ab_Y4847Y, which was not present in China at the early stages of the worldwide viral spread [ 110 ], was detected in large-scale studies [ 59 , 65 , 76 , 77 ] and placed in Malaysia in the third wave of the pandemic [ 110 ], in Thailand in the first wave [ 111 ], in Korea [ 112 ], in Oceania [ 77 ], in Europe [ 76 , 77 ], in Spain, in North America and in Australia [ 76 ]. ORF3a_G251V is speculated to have spread at least in January 2020 or earlier in Sweden, Italy, Brazil, Australia and the USA [ 70 ], and reached a peak in the months after, followed by its disappearance in April 2021 [ 113 ].…”

Assessing the Spatiotemporal Spread Pattern of the COVID-19 Pandemic in Malaysia

“…From November 2020 to 24, February 2021, the high-high clusters shifted from Sabah to Selangor and Negeri Sembilan, then to Pahang, Johor, and Sarawak. Phylogenetic analysis of new B.1.524(G) lineages support claims that the cases in Selangor came from Sabah (38). Spatiotemporal clustering obtained using space-time scan statistics provided additional information on the dispersal of the disease.…”

Decrease in RT-PCR Ct values among SARS-CoV-2 positive samples during the emergence of the B.1.617.2 (Delta) variant in Malaysia

“…A noticeable decrease in the lowest Ct value unit of samples obtained from each month was noted from the scatter plot (Figure 2). For example, the lowest Ct value of samples taken in April 2020 was 21 Ct value is inversely proportional to the viral load [1]. In the SARS-CoV-2 clinical test reports, the inclusion of Ct values in the report are commonly inessential, especially during the surge of epidemic waves [2].…”

“…Genomic studies of SARS-CoV-2 detected in Malaysia have shown that several strains of SARS-CoV-2 variants circulated earlier [20,21]. The earliest COVID-19 outbreaks were associated with the dominant B.6 lineages and the rst three pandemic SARS-CoV-2 waves in Malaysia were commonly contributed by the B.6(O) [20] and B.1.524(G) lineages, mainly due to importation and subsequent human-to-human transmission [21] However, to date, no sustained transmission of a single SARS-CoV-2 strain was observed in Malaysia [21]. The emergence of the B.…”