Genome Profiling of SARS-CoV-2 in Indonesia, ASEAN, and the Neighbouring East Asian Countries: Features, Challenges, and Achievements

Abstract

A year after the World Health Organisation declared COVID-19 as a pandemic, much has been learned with respect to SARS-CoV-2 epidemiology, vaccine production and disease treatment. Whole-genome sequencing (WGS) has played a significant role in contributing to our understanding of the epidemiology and biology of this virus. In this paper, we investigate the use of SARS-CoV-2 WGS in Southeast and East Asia and the impact of technological development, access to resources, and demography of individual countries on its uptake. Facilitated by the Nottingham-Indonesia Collaboration for Clinical Research and Training (NICCRAT) initiative, we showcased a bilateral collaboration between the University of Nottingham and the Indonesian Institute of Sciences (LIPI/Lembaga Ilmu Pengetahuan Indonesia) to establish WGS of SARS-CoV-2 using Oxford Nanopore Technology® in Indonesia. Analyses of SARS-CoV-2 genomes deposited on GISAID from Southeast and East Asian countries reveals the importance of collecting clinical and demographic metadata and the importance of open access and data sharing. Lineage and phylogenetic analyses per 1 June 2021 found that: 1) B.1.466.2 variants were the most predominant in Indonesia, with mutations in the spike protein including D614G at 100%, N439K at 99.1%, and P681R at 69.7% frequency, 2) The variants of concern, B.1.1.7 (Alpha), B.1.351 (Beta) and B.1.617.2 (Delta) were first detected in Indonesia in January 2021, 2) B.1.470 was first detected in Indonesia and spread to the neighbouring regions, and 3) The highest rate of virus transmissions between Indonesia and the rest of the world appears to be through interactions with Singapore and Japan, two neighbouring countries with high degree of access and travels to and from Indonesia. Overall, we conclude that WGS of SARS-CoV-2 using Oxford Nanopore Technology® platforms fits well with the Indonesian context and can catalyse the increase of sequencing rates in the country.

Optimization of multiplex PCR composition to screen for SARS-CoV-2 variants of concern

“…Accordingly, the sample with spike + ORF1a targets failure was assigned as Alpha variant, in line with proposed interpretation [4]. Samples with spike target failure were shown to have Δ69-70 deletions and assigned as B.1.466.2, the most predominant variant in Indonesia before the Delta outbreak [5]. The spike deletion is not specific to the Alpha variant.…”

“…Sample with ORF1a target failure was assigned as B.1.470, a variant first detected in Indonesia [5]. Deletion in the ORF1a region of several VOCs was initially predicted to cause ORF1a target failure [4].…”

Full-genome sequencing and mutation analysis of SARS-CoV-2 isolated from Makassar, South Sulawesi, Indonesia

“…These results were higher than those of another study carried out in West Java, another province in Indonesia, between September 2020 to June 2021, which found that 27% of isolates were of the B.1.466.2 lineage ( Fibriani et al, 2021 ). B.1.466.2 variants are more locally dispersed in Indonesia, and have been detected at lower rates in other Southeast Asian countries ( Cahyani et al, 2021 ) B.1.466.2 is one of the Indonesian lineages identified by PANGO, and although it has not been considered a cause for concern on a global scale, it has been designated on alert for further monitoring by the World Health Organization ( WHO, 2021b ).…”

“…Preliminary data evaluation showed that the N439K variant with a D416G background dominated the SARS-CoV-2 viral population in Indonesia ( Cahyani et al, 2021 ). This variant contains an N439K mutation in the receptor-binding motif (RBM), leading to enhanced binding affinity for the human angiotensin I-converting enzyme 2 (hACE2) receptor and resistance to several neutralizing monoclonal and polyclonal antibodies.…”

The COVID-19 surge in Indonesia: what we learned and what to expect

“…From the end of 2020 to early 2021, genomic surveillance reported a significant portion of COVID-19 in Indonesia had already shifted from the wild-type WIV 04 to other variants, most notably the B.1.466.2 variant. Two mutations that are correlated to increased infectivity [ 7 , 8 ] are commonly found in the B.1.466.2 variant: N439K (99.1%) and P681R (69.7%) [ 9 ]. Moreover, the Delta variant, which was classified as a variant of concern (VoC) by the World Health Organization (WHO) in May 2021 due to its possible ability to reduce vaccine efficacy, increased risk of hospitalisation and its increased transmissibility (as shown by its increased basic reproduction number (R 0 ) [ 10 ]), also became the predominant variant in Indonesia.…”