The dynamics of circulating SARS-CoV-2 lineages in Bogor and surrounding areas reflect variant shifting during the first and second waves of COVID-19 in Indonesia

Abstract

Background: Indonesia is one of the Southeast Asian countries with high case numbers of COVID-19 with up to 4.2 million confirmed cases by 29 October 2021. Understanding the genome of SARS-CoV-2 is crucial for delivering public health intervention as certain variants may have different attributes that can potentially affect their transmissibility, as well as the performance of diagnostics, vaccines, and therapeutics.

Objectives: We aimed to investigate the dynamics of circulating SARS-CoV-2 variants over a 15-month period in Bogor and its surrounding areas in correlation with the first and second wave of COVID-19 in Indonesia.

Methods: Nasopharyngeal and oropharyngeal swab samples collected from suspected patients from Bogor, Jakarta and Tangerang were confirmed for SARS-CoV-2 infection with RT-PCR. RNA samples of those confirmed patients were subjected to whole genome sequencing using the ARTIC Network protocol and sequencer platform from Oxford Nanopore Technologies (ONT).

Results: We successfully identified 16 lineages and six clades out of 202 samples (male n = 116, female n = 86). Genome analysis revealed that Indonesian lineage B.1.466.2 dominated during the first wave (n = 48, 23.8%) while Delta variants (AY.23, AY.24, AY.39, AY.42, AY.43 dan AY.79) were dominant during the second wave (n = 53, 26.2%) following the highest number of confirmed cases in Indonesia. In the spike protein gene, S_D614G and S_P681R changes were dominant in both B.1.466.2 and Delta variants, while N439K was only observed in B.1.466.2 (n = 44) and B.1.470 (n = 1). Additionally, the S_T19R, S_E156G, S_F157del, S_R158del, S_L452R, S_T478K, S_D950N and S_V1264L changes were only detected in Delta variants, consistent with those changes being characteristic of Delta variants in general.

Conclusions: We demonstrated a shift in SARS-CoV-2 variants from the first wave of COVID-19 to Delta variants in the second wave, during which the number of confirmed cases surpassed those in the first wave of COVID-19 pandemic. Higher proportion of unique mutations detected in Delta variants compared to the first wave variants indicated potential mutational effects on viral transmissibility that correlated with a higher incidence of confirmed cases. Genomic surveillance of circulating variants, especially those with higher transmissibility, should be continuously conducted to rapidly inform decision making and support outbreak preparedness, prevention, and public health response.

Keywords: Bogor; COVID-19; Delta variants; Genomic surveillance; Indonesian lineages; Nanopore; SARS-CoV-2; Variant shifting.

Figure 1. A map of locations from which samples were obtained in Bogor and surrounding areas.

Samples were obtained from laboratories located in Bogor (1 and 2), Tangerang (3 and 4) and Jakarta (5), and subsequently subjected to qRT-PCR confirmation and whole genome sequencing at the Biosafety Laboratory Level 2 and 3 BRIN, Cibinong Science Center-Botanical Garden.

Figure 2. Summary of the patients’ profiles.

Composition of males and females are shown across sampling locations (A), age groups (B) and lineage distribution (C) from the 202 SARS-CoV-2 genomes sequenced. Others in male lineages (5.2%, 6/116) include B.56 (n = 2), B.1.36.19, AY.39, AY.42 and AY.79; while others in female lineages (5.8%, 5/86) include B.1.1, B.1.1.53, B.1.1.10, AY.43 and unclassified.The samples were mainly obtained from originating laboratory in Bogor (69.8%). Over 50% of samples in both males and females were from patients aged 35–64 years. A higher proportion of lineages B.1.1.398 and B.1.470 were observed in male patients compared to females, whereas lineages B.1 and B.1.459 were more prevalent in females compared to males.

Figure 3. Phylogenetic tree from 202 viruses, representing 17 lineages and six GISAID clades.

The clustering of certain lineages is indicative of the extent of genomic variations within the genomes. Three major clades were observed, including GH, GR and GK, while the minor clades were L, O and G. Clades GH and GR include several Indonesian lineages, while clade GK consists of Delta variants (AY lineages). Phylogenetic tree was built using Augur utility from the Nexstrain bioinformatic pipeline by employing MAFFT, IQ-TREE and 1000 bootstrap replications (UFBoot).

Figure 4. Lineage distribution of SARS-CoV-2 genomes compared to the national statistics.

Side-by-side comparison of lineage distribution is shown across dates of sampling (A) and the official statistics of deaths, recovered and new confirmed cases of COVID-19 (B) at national level (https://covid19.go.id/peta-sebaran), demonstrates two peaks at similar timelines, representing the first and second wave of pandemic.

Figure 5. Amino acid substitutions among lineages identified in this study.

Only the top 50 substitutions with the highest number of incidences are shown. Several unique substitutions were observed in Delta variants and other variants circulating during the first wave, with the Delta variants having the majority of amino acid substitutions. The highest incidence of substitutions includes S_D614G (n = 199) and NSP12_P323L (n = 197). Two viruses from B.56 lineages were found to carry the least number of mutations (n = 4) and no S_D614G substitution. One virus (hCoV-19/Indonesia/JK-LIPI135/2021) not shown in this figure was found to carry multiple amino acid changes, including S_D614G, S_P681R, S_T478K, S_L452R, NSP6_T77A, NSP3_P1228L, NSP12_P323L, NSP12_G671S, and NSP14_A394V.