Temporal dynamics and fatality of SARS‐CoV‐2 variants in Bangladesh

Abstract

Background and Aims

Since the beginning of the SARS‐CoV‐2 pandemic, multiple new variants have emerged posing an increased risk to global public health. This study aimed to investigate SARS‐CoV‐2 variants, their temporal dynamics, infection rate (IFR) and case fatality rate (CFR) in Bangladesh by analyzing the published genomes.

Methods

We retrieved 6610 complete whole genome sequences of the SARS‐CoV‐2 from the GISAID (Global Initiative on Sharing all Influenza Data) platform from March 2020 to October 2022, and performed different in‐silico bioinformatics analyses. The clade and Pango lineages were assigned by using Nextclade v2.8.1. SARS‐CoV‐2 infections and fatality data were collected from the Institute of Epidemiology Disease Control and Research (IEDCR), Bangladesh. The average IFR was calculated from the monthly COVID‐19 cases and population size while average CFR was calculated from the number of monthly deaths and number of confirmed COVID‐19 cases.

Results

SARS‐CoV‐2 first emerged in Bangladesh on March 3, 2020 and created three pandemic waves so far. The phylogenetic analysis revealed multiple introductions of SARS‐CoV‐2 variant(s) into Bangladesh with at least 22 Nextstrain clades and 107 Pangolin lineages with respect to the SARS‐CoV‐2 reference genome of Wuhan/Hu‐1/2019. The Delta variant was detected as the most predominant (48.06%) variant followed by Omicron (27.88%), Beta (7.65%), Alpha (1.56%), Eta (0.33%) and Gamma (0.03%) variant. The overall IFR and CFR from circulating variants were 13.59% and 1.45%, respectively. A time‐dependent monthly analysis showed significant variations in the IFR (p = 0.012, Kruskal–Wallis test) and CFR (p = 0.032, Kruskal–Wallis test) throughout the study period. We found the highest IFR (14.35%) in 2020 while Delta (20A) and Beta (20H) variants were circulating in Bangladesh. Remarkably, the highest CFR (1.91%) from SARS‐CoV‐2 variants was recorded in 2021.

Conclusion

Our findings highlight the importance of genomic surveillance for careful monitoring of variants of concern emergence to interpret correctly their relative IFR and CFR, and thus, for implementation of strengthened public health and social measures to control the spread of the virus. Furthermore, the results of the present study may provide important context for sequence‐based inference in SARS‐CoV‐2 variant(s) evolution and clinical epidemiology beyond Bangladesh.

1. INTRODUCTION

The novel coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was first emerged in China, in late December 2019. ¹ , ² The COVID‐19 has spread to more than 230 countries and territories, affected more than 640 million people and resulted in over 6.6 million deaths worldwide since the beginning in December 2019. ³ Globally, COVID‐19 patients demonstrated substantial variability in the course of the disease, ranging from asymptomatic infection to death. The infection rate (IFR) and case fatality rate (CFR) of COVID‐19 cases may also vary according to population demographics, smoking rates and prevalence of other concurrent comorbidities. ⁴ , ⁵ Overall, worldwide mortality is approximately 6% of clinically confirmed cases. ³ In Bangladesh, the first case of COVID19 was detected on March 8, 2020. ⁶ The virus has quickly spread across Bangladesh from March 2020 to October 2022, and the number of confirmed cases reportedly has risen to 2 million, with 29,430 deaths. ³ To combat COVID‐19, the Government of the People's Republic of Bangladesh has fully approved seven COVID‐19 vaccines, such as AstraZeneca, Pfizer, Sinopharm, Moderna, Sinovac, Janssen (Johnson & Johnson), Pfizer‐PF (Comirnaty). ⁷ , ⁸ In Bangladesh, vaccine against corona virus was initiated in January 2021 to the frontline health workers while mass vaccination started on February 7, 2021. ⁹ As of October 6, 2022, a total of 12.749 billion doses have been administered globally whereas more than 298 million doses have been administered in Bangladesh (https://www.bloomberg.com/graphics/covid-vaccine-tracker-global-distribution/).

The whole‐genome sequencing (WGS) and the genetic analysis studies had revealed that SARS‐CoV‐2 is an enveloped, nonsegmented, single‐stranded, and positive sense RNA virus under family Coronaviridae. ¹⁰ , ¹¹ The high rate of viral replication, dissemination, and prevalence is associated with the emergence of new viral variants because these properties are associated with the acquisition of mutations in their genome. Within the few months of its emergence (i.e., December 2020 to May 2021), several variants of the SARS‐CoV‐2 have been detected across the globe which are more transmissible, possibly escapes the natural and vaccine‐induced immunity, and could lead to increased SARS‐CoV‐2 infection compared to its ancestral strains. ¹² , ¹³ The SARS‐CoV‐2 underwent a mutation rate of about (1.19–1.31) × 10⁻³/site/year. ¹⁴ The angiotensin‐converting enzyme‐2 (ACE‐2) sequence alignment reveals that pangolin, mink, cat and dog can become the potential host of SARS‐CoV‐2. ¹⁵

RNA viruses like SARS‐CoV‐2 continuously evolve as changes in the genetic code (caused by genetic mutations or viral recombination) occur during replication of the genome. Based on the potential threats of these viral variants in terms of transmission, disease severity, immune escape, and so forth, the Center for Disease Control and Prevention (CDC) has classified SARS‐CoV‐2 variants into four categories, Variant of Interest (VOI), Variant of Concern (VOC), Variants Being Monitored (VBM) and Variant of High Consequences (VOHC). ¹⁶ Different variants of SARS‐CoV‐2 are also named according to different nomenclature systems such as Phylogenetic Assignment of Named Global Outbreak (PANGO), GISAID, and Nextstrain. ¹⁴ , ¹⁷ Nextstrain is an open‐source project ¹⁸ to harness the scientific and public health potential of pathogen genome data to define the chronological emergence of new variants of SARS‐CoV‐2. The Alpha variant was first reported in late December 2020 in the United Kingdom. ¹⁹ SARS‐CoV‐2 Beta variant, first detected in December 2020 in South Africa, ²⁰ is the most dreadful and prevalent lineage in 115 countries. ¹³ The Gamma variant of SARS‐CoV‐2 was reported in early January 2021 in Brazil ²¹ whereas the Delta variant was first isolated in India in December 2020. ²² So far, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529) have been designated as VOC, while Lambda (C.37) and Mu (B.1.621) as VOI. ¹⁵ , ²³ For viral transmissibility, the reported studies have yielded good evidence that all VOCs are more transmissible than the wild‐type virus. ²¹ The VOHC variants which show suggestively low or no efficacy against available therapeutic or preventive regimens, have not been identified till now. ²⁴ Variant escape from antibody neutralization can reduce the effectiveness of vaccination programs and necessitate the development of modified vaccines or administration of booster doses. ²⁵ Furthermore, tracking the emergence of new variants and/or clades of SARS‐CoV‐2 is one of the top priorities throughout the globe. The genomic alterations such as amino acid substitutions in the SARS‐CoV‐2 genome could be related to viral evolution, alterations in biological properties, and virulence. ²⁶

Since first detection on March 8, 2020, scientists from Bangladesh have generated more than 6500 complete genomes of the SARS‐CoV‐2, and deposited their data to publicly available database that is, GISAID. This massive genome sequencing effort has informed us about the evolution and spread of variants of SARS‐CoV‐2. ²⁶ In this study, we have primarily used the Nextstrain and PANGO nomenclature, which names strains according to the year they most spread. The adequate information on in‐depth epidemiological features of the COVID‐19 pandemic and genomic analysis is deficient in developing countries, particularly Bangladesh. Through an in‐depth investigation into the emergence and pursuit of VOC, such as Alpha, Beta, Gamma, and Delta, and VOIs, such as Eta, several Nextstrain clades and/or PANGO lineages, this study reported the emergence and spread of the SARS‐CoV‐2 variants, clades and lineages, their evolution, transmissibility and association with relevant clinical traits (IFR and CFR) in Bangladesh from March 2020 to October 2022. In addition, using a phylogenetic tree, we attempt to trace back the spread of the variants within the country and from outside the country. The findings of this study shed light on the history of emergence of SARS‐CoV‐2 variants, clades and lineages, possible transmission of VOC or VOIs, and their consequences upon human health in Bangladesh.

2. METHODS

2.1. Genomic data retrieval and filtering

The first SARS‐CoV‐2 complete whole genome sequence (WGS) was submitted January 5, 2020 on the GenBank (Access number: NC_045512.2). As of October 30, 2022, 215 countries and territories shared more than 13 million SARS‐COV‐2 genome sequences (partial or complete) from human cases of COVID‐19 to the GISAID (Global Initiative on Sharing all Influenza Data) since January 2020 (https://www.gisaid.org/). We performed BLAST searches against all SARS‐CoV‐2 genomes for each of the current study's SARS‐CoV‐2 isolates available in the GISAID database. In this study, we retrieved 7321 SARS‐CoV‐2 complete or partial genomes deposited to the GISAID from Bangladesh till 30 October, 2022. We filtered these sequences (N = 7321) based on some specific criteria (e.g., complete whole genome sequence, high coverage read, with patient status, collection date). Only complete genomes with a size of greater than 29,000 bp were selected and those with low coverage that is, possessing >5% of N's, were filtered out. After thorough filtering, 6610 complete genome sequences of SARS‐CoV‐2 were retained and selected finally for this study. The clade and Pango lineages were assigned by using Nextclade v2.8.1 (https://clades.nextstrain.org/). The infection and the death case related data were collected from the Institute of Epidemiology Disease Control and Research (IEDCR), Bangladesh (http://dashboard.dghs.gov.bd/webportal/pages/covid19.php). All the metadata (Submission date, strain, GISAID ID number, region/location, division, length, host, age, sex, Pangolin lineage, GISAID/Nextstrain clade, originating and submitting lab, authors) from GISAID were collected for analysis (Supporting Information: Data S1).

2.2. Data analysis

The average incidence (IFR) was calculated by the monthly COVID‐19 cases and population size. The average CFR was calculated by the number of monthly deaths and number of confirmed COVID‐19 cases. ²⁷ , ²⁸ Stacked bar plot and line plot were visualized in R and RStudio ggplot2 package. ²⁹ We used Nextstrain SARS‐CoV‐2 phylogenetic tree generation pipeline (https://nextstrain.org/sars-cov-2/) to reconstruct the phylogenetic tree with Nextstrain clade of the sequence. ¹⁸ MAFFT v7.470 was used to align the sequences to the Wuhan (Wuhan/Hu‐1/2019) reference genome. ³⁰ IQ‐TREE v1.6.12 ³¹ and TreeTime, ³² Nextstrain's phylodynamic pipeline, were used to perform phylogenetic analysis. The initial phylogenetic tree was constructed using IQTREE v1.6.12 ³¹ which implements the GTR (generalized time‐reversible) model and bootstraps the tree topology for ensuring a high degree of confidence. The raw tree was rooted using the reference genome. The tree was further processed using TreeTime v0.8.1 ³² to generate a time‐resolved phylogeny based on maximum likelihood. Auspice web server (https://auspice.us/) was used to visualize the tree. Mutations and clades were assigned from CoVserver mutation app of the GISAID (https://gisaid.org/database-features/covsurver-mutations-app/) where hCoV‐19/Wuhan/WIV04 (GenBank accession no. MN996528.1) was used as a reference genome. ³³

2.3. Statistical analysis

The nonparametric Kruskal–Wallis rank sum test was used to determine statistically significant differences between two or more groups. ³⁴ The statistical analysis was performed using the R statistical environment package v 3.6.3 (https://cran.r-project.org/bin/windows/base/old/3.6.3/).

3. RESULTS

3.1. Temporal distribution of SARS‐CoV‐2 variants and associated lineages in Bangladesh

Bangladesh recorded its first confirmed COVID‐19 case on March 8, 2020 in Dhaka, the capital city of Bangladesh. Subsequently, COVID‐19 cases were detected in all of 64 districts. Since the beginning of the pandemic, Bangladesh has experienced three waves of COVID‐19 outbreaks. Here we describe the emergence and spread of SARS‐CoV‐2 variants and related lineages in Bangladesh that contains several synonymous and nonsynonymous mutations that may have functional importance. The sequenced SARS‐COV‐2 genomes and their respective genome diversity with distinct viral lineages are summarized in Supporting Information: Data S1. We evaluated 6610 genomes of the SARS‐CoV‐2, and these sequences were submitted to the GISAID database from Bangladesh during March 2020 to October 2022. Before delving into details of the sequences, it would be pertinent to analyze the test positivity (confirmed) and case fatality (death) rates of SARS‐CoV‐2 infection over the course of the three examined years, 2020 to 2022. Of the 6610 SARS‐COV‐2 genomes, the Delta VOC (48.06%) was predominant, followed by Omicron (27.88%), Beta (7.65%), Alpha (1.56%), Eta (0.33%), and Gamma (0.03%) (Figure 1). However, among these SARS‐CoV‐2 genomes, 14.47% were found to be unassigned to any particular variant. SARS‐CoV‐2 variants are grouped according to their lineage and component mutations. Nextstrain clade's results contained 22 unique clades (Figure 2) whereas Pangolin's contained 107 lineages across these clades/subclades (Figure 3).

Figure 1.

Phylogenetic representation of the SARS‐CoV‐2 variants and clades exist in Bangladesh from 2020 to 2022. The maximum likelihood phylogenetic tree was constructed using Nextstrain's SARS‐CoV‐2 phylogenetic tree generation pipeline and the default parameters were used for IQ‐TREE. The time‐resolved phylogenetic tree with selected metadata information was constructed using TreeTime and visualized in Auspice. Different color represents different clade. The data set was taken from the Global Initiative on Sharing all Influenza Data (GISAID) with high coverage flag.

Figure 2.

Temporal dynamics (evolution) of SARS‐CoV‐2 variants and Nextstrain clades in Bangladesh. (A) Temporal dynamics of SARS‐CoV‐2 variants and clades in Bangladesh during 2020–2022. (B) Relative prevalence of the of detected SARS‐CoV‐2 variants and clades in Bangladesh from March 2020 to October 2022.

Figure 3.

Relative prevalence of the of Pangolin lineages of SARS‐CoV‐2 variants in Bangladesh from March 2020 to October 2022.

The Alpha strain was the most common VOC in Bangladesh from December 2020 to July 2021 (Figure 2A). The 20I clade was found to be predominantly circulating in January (13.51%), February (30.16%), and March (13.40%) of 2021, and with a relatively lower prevalence (<10.0%) during rest of the months (Figure 2B). The Beta variant (20H), emerged in South Africa in May 2020, was first detected on November 2020 in Bangladesh. ³⁵ The 20H clade or South African variant was found to be circulating widely in Bangladesh from November 2020 to July 2021 (Figure 2A). However, the prevalence of the 20H clade was found to be predominantly higher in March (68.12%), April (77.60%), and May (44.50%) of 2021 in Bangladesh (Figure 2B). By comparing temporal distribution and prevalence of the Nextstrain clades of the SARS‐CoV‐2 in Bangladesh, we found that the Delta variant clades were circulating from October 2020 to February 2022 in Bangladesh (Figure 2A). During these 14 months of outbreak, 23.76%, 2.18%, and 59.76% of the SARS‐CoV‐2 genomes sequenced belonged to the 21A, 21I, and 21J clades of in Bangladesh. We found that clade 21A was circulating in Bangladesh from October 2020 to December 2021 (Figure 2A), and remained mostly prevalent during May to August (33.50%–53.85%) of 2021, keeping the highest prevalence in June (53.85%) (Figure 2B). Similarly, clade 21J was found to be circulating in Bangladesh from April 2021 to February 2022 (Figure 2A), and the highest prevalence of clade 21J was found in November (96.15%) followed by 91.43% in October and 86.20% December, 2021 (Figure 2B). Likewise, clade 21I was circulating in Bangladesh from April 2021 to January 2022 (Figure 2A), and had the highest prevalence (14.61%) in January 2022, and this clade had relatively lower prevalence (<2.0%) in the rest of the months (Figure 2B). The 20J clade of Gamma variant prevailed in Bangladesh for a shorter period of 2 months (February–March, 2021) (Figure 2A) with comparatively lower prevalence (<2.0%) than other clades (Figure 2B). The 21D clade of the Eta variant circulated in Bangladesh from April to June 2021 (Figure 2A), and the prevalence of this clade always remained comparatively lower (<5.0%) (Figure 2B).

The Omicron variant was found to be emerged in November 2021 in Bangladesh (Figure 2A). Initially, most COVID‐19 positive cases were from the 21K clade (during the first 2 weeks of January 2022). The 21L clade emerged from the third week of January 2022, and circulated until March 2022 by replacing the 21K clade over time. During the SARS‐CoV‐2 pandemic from December 2020 to October 2021, the Delta variant showed global dominance, and afterwards, the Omicron variant showed global dominance. Eight Nextstrain clades (e.g., 21K, 21L, 21M, 22A‐22D, 22F) of Omicron variant were detected in Bangladesh from November 2021 to October 2022 (Figure 2A). Among these Omicron variant clades, 21K had the highest prevalence (43.24%) in January 2022 while 21L clade was mostly prevalent (>82.0%) during February to May 2022, with the highest prevalence of 93.88% in March. Likewise, clade 22B was mostly prevalent in June (92.57%) and July (90.14%), and clade 22F in September (55.44%) and October (94.0%) of 2022. Rest of the clades of Omicron variant were circulating in Bangladesh with a comparatively lower prevalence (<30.0%) (Figure 2B).

The SARS‐CoV‐2 Nextstrain clades 20A and 20B were found to be circulated in Bangladesh from April 2020 to January 2021 (Figure 2A). Immediately after emergence, the clade 20A had the highest prevalence (40.0%) in April, 2020 followed by 31.25% in October, 18.95% in June, 14.88% in May, 12.87% in July and 12.15% in August and September of 2020 (Figure 2B). Simultaneously, clade 20B was found to be mostly circulating from April 2020 to January 2021 (Figure 2A), with ≥60.0% prevalence (range 60.0%–88.0%), and thereafter, the prevalence of this clade gradually declined (Figure 2B). Moreover, clade 20C derived from 20A, first identified in April to May 2020 for 0.88% of all genome sequences, was increased to 1.47% in November 2020 and 1.69% in April 2021. Two clades derived from clade 20B, clade 20D (first detected in January 2021) and clade 20F (emerged in September 2020) were also detected (Figure 2A), and the relative prevalence of these two clades always remained much lower (≤1.0%) than other clades reported in this study (Figure 2B). We found that Nextstrain clades 19A and 19B were circulating in Bangladesh between March 2021 and May 2021 (Figure 2A) with a relatively lower prevalence rate (1.0%) (Figure 2B).

We next investigated the Pango lineages (n = 107) of the SARS‐CoV‐2 variants infecting individuals and circulating over the course of 3 years in Bangladesh. The ongoing uncontrolled spreading of the SARS‐CoV‐2 worldwide creates the ideal condition for virus evolution. On this respect, several Pango lineages of the SARS‐CoV‐2 emerged in Bangladesh from December 2020 to October 2022. These lineages showed significand differences in their emergence time and overall prevalence. Among the three Nextstrain clades of Delta variant, 23 Pangolin lineages were found to be circulating in Bangladesh, and of them, the B.1.617.2 was detected as the mostly prevalent SARS‐CoV‐2 lineage during May 2021 to January 2022, with relatively higher prevalence in June (80.31%) and July (88.55%) followed 77.54% in September, 75.0% in October and 41.26% November of 2021 (Figure 3). Among the rest of the coexisting Pango lineages of Delta variant, had relatively lower prevalence, AY.122 and AY.127 lineages had the highest prevalence in September (10.40%) and November (16.08%) 2021. Similarly, AY.131 was found as the mostly circulating lineage in November (34.61%) and December (57.37%) 2021, and rest of the lineages of the Delta clades had relatively lower prevalence (<2.0%) over the course of their outbreaks (Figure 3). During the course of 12 months (November 2021–October 2022) of outbreaks, the Omicron variant emerged with 61 Pango lineages in Bangladesh. Out of these lineages, only 11 lineages had comparatively higher prevalence (≥10.0) and rest of the lineages been circulating in Bangladesh with a comparatively lower prevalence (<5.0%). For instance, BA.1 (14.01%) and BA.1.1 (19.94%) lineages in January 2022, BA.2 and BA.2.10 lineages in January–April (20.0%–42.0%), and BE.4 lineage in June–August (11.0%–60.0%) were the most prevalent lineages of the Omicron variant (Figure 3). Likewise, the Alpha variant also had two Pango lineages (e.g., B.1.1.7 and Q.4), and of them, B.1.1.7 lineage had the highest prevalence in February (30.16%) followed by March (13.41%) and January (12.61%) of 2021. The Beta variant of the SARS‐CoV‐2 however had only two circulating Pango lineages (i.e., B.1.351 and B.1.351.3), of which B.1.351.3 was found as the most predominantly circulating lineage in March (58.33%), April (66.79%) and May (40.11%) of 2021. Conversely, the Gamma and Eta variant had only one Pango lineage in each (i.e., P.1.14 for Gamma and B.1.525 for Eta), and both of these lineages had relatively lower prevalence (<3.0%) during February to June, 2021 (Figure 3). With the dominance of the lineages of the other variants in Bangladesh, the cumulative prevalence of Gamma and Eta was reported to be less than 3% (Figure 3).

3.2. Temporal changes infection and case fatality rates of SARS‐CoV‐2 variants

The overall infection rate (IFR) and case fatality rate (CFR) from circulating variants of the SARS‐CoV‐2 were 13.59% and 1.45%, respectively during 3 years (Table 1). By comparing the year‐wise IFR and CFR, we found the highest IFR (14.35%) in 2020 followed by 10.44% in 2021 and 8.66% in 2022. On the other hand, the highest CFR (1.91%) was recorded in 2021 followed 1.47% in 2020 and only 0.3% in 2022 from SARS‐CoV‐2 infections in Bangladesh (Table 1). A time‐dependent monthly analysis showed significant variations in the IFR (p = 0.012, nonparametric Kruskal–Wallis test) and CFR (p = 0.032, nonparametric Kruskal–Wallis test) throughout the study period. The highest IFR (29.70%) was found in July 2021 followed by 22.46% in July 2020, 21.61% in January 2022, 21.35% in June 2020, 21.15% in August 2021, and rest of the months had <20.0% IFR during the study period. Likewise, the highest CFR (2.82%) was recoded in May 2021 followed by 2.63% in January and October (in each) 2021, 2.54% February 2021, 2.38% in September 2021, 2.2% in August 2021, and 2.14% in April 2020, and rest of the months had <2.0% CFR from SARS‐CoV‐2 infections (Table 1).

Table 1.

Monthly infection rate (IFR) and case fatality rate (CFR) of SARS‐CoV‐2 variants during 2020–2022 in Bangladesh.

Months	Year	Tested samples	Confirmed cases	No. of deaths	Infection rate	Case fatality rate
March	2020	1482	49	5	3.31	10.2
April	2020	62,528	7611	163	12.17	2.14
May	2020	244,234	39,486	482	16.17	1.22
June	2020	460,534	98,330	1197	21.35	1.22
July	2020	410,399	92,178	1264	22.46	1.37
August	2020	373,394	75,335	1170	20.18	1.55
September	2020	397,452	50,483	970	12.70	1.92
October	2020	388,607	44,205	672	11.38	1.52
November	2020	436,439	57,248	721	13.12	1.6
December	2020	454,897	48,578	915	10.68	1.88
January	2021	424,124	21,629	568	5.10	2.63
February	2021	392,305	11,077	281	2.82	2.54
March	2021	626,549	65,079	638	10.39	0.98
April	2021	799,627	147,837	2404	18.49	1.63
May	2021	477,809	41,408	1169	8.67	2.82
June	2021	661,414	112,718	1884	17.04	1.67
July	2021	11,31,967	336,226	6182	29.70	1.84
August	2021	11,87,451	251,134	5510	21.15	2.2
September	2021	802,946	55,293	1315	6.89	2.38
October	2021	618,579	13,628	358	2.20	2.63
November	2021	538,881	6745	113	1.25	1.68
December	2021	602,757	9255	91	1.54	0.98
January	2022	987,194	213,294	322	21.61	0.15
February	2022	922,657	144,744	643	15.69	0.44
March	2022	422,668	8000	85	1.89	1.06
April	2022	166,459	1114	5	0.67	0.45
May	2022	134,756	816	4	0.61	0.49
June	2022	225,463	20,278	18	8.99	0.08
July	2022	260,652	31,472	142	12.07	0.45
August	2022	143,087	6689	33	4.67	0.49
September	2022	125,364	13,251	40	10.57	0.3
October	2022	83,907	8222	47	9.80	0.57
Mean infection and fatality rates					13.59	1.45

By comparing the month‐wise IFR and CFR of different variant and clades of the SARS‐CoV‐2 throughout the study period, we found that five genome sequences from Bangladesh were distributed throughout clade 19A, with a 13.5% IFR and 1.68% CFR between April 2020 and May 2020 whereas 3.60% genomes of SARS‐CoV‐2 were found to representing clade 19B with 16% IFR and 1.22% CFR in May 2020 (Table 1). The basal 20A lineage seeded outbreaks from April 2020 to June 2021 with 16.0% and 1.76% IFR and CFR, respectively. The SARS‐CoV‐2 lineage 20B, predominantly circulating from April 2020 to June 2021 had an IFR of 13.0% and 1.7% CFR (Table 1). The overall IFR and CFR of clade 20C were 12.0% and 1.9%, respectively during November 2020–May 2021. The clade 20D had 5.0% and 2.6% IFR and CFR, respectively in January 2021. Clade 20F derived from 20B in November 2020 had 13.0% and 1.3% IFR and CFR, respectively (Table 1). The Alpha strain was the most common VOC in Bangladesh, accounting for a 12.87% IFR, and a 2.0% CFR across the country from December 2020 to July 2021. The Beta variant B.1.351 (20H/501Y.V2) or South African variant was circulating widely in Bangladesh from January to July 2021 with an average IFR and CFR of 13.14% and 2.0%, respectively (Table 1). This variant is found to be more prevalent in young individuals (without any comorbidity), and is deemed responsible for the second wave of COVID‐19 in Bangladesh. The 20J/501Y.V3 clade of the Gamma variant had an IFR and CFR of 16.0% and 0.4%, respectively in February to March, 2021. We found 13.5% IFR and 1.8% CFR for clade 21D of the Eta variant during March to June 2021 (Table 1). The B.1.617.2 lineage of the Delta variant had an IFR and CFR of 13.18% and 1.7%, respectively from April 2021 to February 2022 (Table 1). The risk of infection and mortality were much higher in Delta variant than that of other variants in Bangladesh. In Bangladesh, the IFR and CFR from Omicron variant were 10.5% and 0.7%, respectively during December 2021 to March 2022.

4. DISCUSSION

Bangladesh is the second‐most country in the South Asia that has experienced a catastrophe from SARS‐CoV‐2 pandemic. ³⁵ In this study, we evaluated 6610 genomes of the SARS‐CoV‐2, and these sequences were submitted to the GISAID database, which were collected from various areas in Bangladesh between March 2020 to October 2022. Though this in‐silico research is based on secondary source, it will contribute to a better understanding of the virus dissemination, prevalence of circulating variants, clades or lineages, and summarize the confirmed cases of SARS‐CoV‐2 (IFR) and case fatality rates (CFR) of SARS‐CoV‐2 infection in Bangladesh over the course of the three examined years. According to the current sequence analysis, all the VOCs were introduced in Bangladesh including multiple introductions at the same time. The Alpha, Beta, Delta, and Omicron VOCs switched quickly and overtook each other during this analysis period. After arriving in Bangladesh, the SARS‐CoV‐2 began to spread at a neighborhood level and expanded throughout the county quickly. The Alpha variant of concern that emerged in the United Kingdom in September 2020, was first identified in Bangladesh on December 31, 2020. ³⁵ The Alpha 20I was found to be predominating in Bangladesh in early 2021 (January to March) with a decreasing trend of prevalence until July 2021. Our results corroborate with the reports India, one of the neighboring countries of Bangladesh, where the e Alpha (B.1.1.7) variant dominated in March 2021, and was rapidly replaced by the Delta (B.1.617.2) variant in April and May 2021. ³⁶ The prevalence of this variant increased rapidly in Bangladesh owing to an increase in infection and/or transmission efficiency. The Alpha was estimated to be 70%–80% more transmissible than its ancestor ¹⁹ and quickly spread worldwide. The Alpha variant is a VOC because of its increased transmissibility, and therefore, remained as a subject of intense research since its emergence. ³⁷

The Beta (20H) VOC circulated from November 2020 to July 2021 in Bangladesh with predominantly higher prevalence in March to May, 2021. This variant is found to be more prevalent in young individuals (without any comorbidity), and is deemed responsible for the second wave of COVID‐19 in Bangladesh. The Beta variant has multiple mutations (12 nonsynonymous mutations and one deletion) in the spike, nucleocapsid and envelop proteins and open reading frame (ORF1a). ³⁸ Beta variant is an addition to the genome of the SARS‐CoV‐2 pandemic situation, and known to be one of the highly transmissible SARS‐CoV‐2 variants. ¹³ The Delta variant (with 21A, 21I, and 21J clades) was circulating in Bangladesh over a period of 14 months (i.e., from October 2020 to February 2022). The Delta (B.1.617.2) variant was first identified in Maharashtra, India, in late 2020. ³⁹ The B.1.617.2 clade of the Delta variant is one of the alarming clades of the SARS‐CoV‐2 that has been immensely detrimental and a significant cause of the prolonged pandemic. This variant is responsible for about 70% of cases in the Indian subcontinent. ⁴⁰ Our results corroborates with the findings of the one of the earlier studies from Bangladesh which reported that the AY.122 lineage increased significantly from September 2021 while B.1.617.2 was declining. ⁴¹ The 20J clade of Gamma variant and 21D clade of the Eta variant were found to be circulating in Bangladesh for only 2–3 months (March to June, 2021) with relatively lower prevalence (<5.0%) than other clades. The Gamma variant is associated with a higher degree of transmissibility. ²¹ Although, this variant displayed high infection rates as compared to previous variants, the case fatality rate was lower indicating poor virulence of this variant in Bangladesh. Using dynamic modeling that integrates genomic and mortality data, Faria et al. ²¹ estimated that the transmissibility of the Gamma variant could be 1.4–2.2 times higher than that of the wild‐type virus, which was consistent with our findings. The timing of emergence of Eta variant roughly coincided with the occurrence of the majority of the variants in Bangladesh. The Eta variant was a dominant variant in Nigeria and classified as a VOI. ⁴² The Gamma variant first documented in Brazil in November 2020, was found to be emerged in Bangladesh on February 2, 2021. ³⁵ The Eta variant, emerged in December 2020 in the United Kingdom and Nigeria, ⁴³ was first documented in Bangladesh on April 2021. ³⁵

The Omicron variant, first identified in November 2021, was found to be circulated in Bangladesh with two distinct clades such as 21K clade with 43.24% prevalence in January 2022 and 21L clade with >82.0% during February to May 2022. The SARS‐CoV‐2 Omicron variant was found as the second predominating SARS‐CoV‐2 variant in Bangladesh. The SARS‐CoV‐2 Omicron variant has caused global concern, and it is a highly transmissible variant with significantly lower IFR than those of previous variants of SARS‐CoV‐2. ⁴⁴ The findings of the present study show a strong association with the earlier findings on the global dispersion of the virus and pandemic waves of the Omicron variant and/or it's circulating lineages. ⁴⁵ , ⁴⁶ Omicron variant of SARS‐CoV‐2 was designated as a VOC by the WHO. ⁴⁷ Initially, Omicron had three subvariants or sister lineages (e.g., BA.1, BA.2 and BA.3. BA.1) were predominant during the fourth wave of the pandemic in South Africa. ⁴⁶ After emergence in South Africa in November 2021, several subvariants/lineages including BA.1, BA.2, BA.4, BA.5, BA.2.12.1, and BA.2.75 of the Omicron variant rapidly spread across the globe, ⁴⁵ , ⁴⁶ and classified as VOC‐subvariants under monitoring in the subsequent months (up to August 2022). Rest of the variants identified in this study has lower prevalence and considered to be the non‐VOC or non‐VOI in Bangladesh.

According to GISAID data, different Pango lineages of the Delta variant (e.g., AY.122, AY.127, and AY.131) emerged in Bangladesh from June 2020 to September 2021. Delta caused a resurgence of COVID‐19 in regional countries such as India, Bangladesh, Singapore, Indonesia, Russia, and Nepal with a cumulative prevalence of more than 95% as of September 5, 2021. ⁴⁸ In the course of the COVID‐19 pandemic, multiple lineages of the Beta (e.g., B.1.351, B.1.1.7) and Alpha (e.g., B.1.1.7 and Q.4) have emerged. ⁴⁹ , ⁵⁰ The lineage B.1.1.7 of the Beta variant of the SARS‐CoV‐2 was first identified in the UK in October 2020 whereas the B.1.351 and P.1 lineages were identified in South Africa and Brazil, respectively in October 2020. ⁵¹ These lineages are associated with increased transmissibility, virulence, or resistance to neutralization by sera from vaccinated and convalescent individuals who were infected with the original strain of the SARS‐CoV‐2. ⁴⁹ The emergence and rapid increase of the B.1.1.7 (Alpha) lineage of SARS‐CoV‐2 is well documented in different areas of the world and considered as a global public health concern (VOC) because of its increased transmissibility. ⁵² The continuous evolution of SARS‐CoV‐2 is an expected phenomenon that will continue to happen due to the high number of new lineages worldwide. The emergence of the Brazilian VOC, Gamma lineage (P.1), impacted the epidemiological profile of COVID‐19 cases due to its higher transmissibility rate and immune evasion ability. ⁵³ The B.1.525 lineage of the Eta variant has grabbed special attention within the predominance over other VOC. Still, the presence of the lineages of the Gamma and Eta variants is worrisome as they carry several mutations in the SARS‐CoV‐2 genome ⁵³ , ⁵⁴ which help the virus to escape the body's immune response hence called “Escape mutation.” The risk of infection and mortality were much higher in Delta variant than that of other variants in Bangladesh. A series of earlier studies reported higher risk of ICU admission 3.35% (95% CI: 2.5–4.2) and mortality 2.33% (95% CI: 1.45–3.21) in Delta variant compared to other VOC or VOI. ⁵⁵ , ⁵⁶ One of the recent studies from India, the closest neighboring country of Bangladesh, reported that the majority of the breakthrough COVID‐19 cases in India were infected with the Delta variant, ⁵⁷ with only 9.8% cases requiring hospitalization, and 0.4% fatalities, corroborating our findings. In Bangladesh, the IFR and CFR from Omicron variant were 10.5% and 0.7%, respectively during December 2021 to March 2022. Our estimated IFR of Omicron variant is much higher than what reported other countries. For instance, the calculated IFR among adult individuals without comorbidity was 6·2 (CI: 5·1–7·5) per 100,000 infections in Denmark. ⁵⁸ In a retrospective population‐wide matched cohort study of patients infected with the Omicron variant in Canada ⁵⁹ reported that hospitalizations and deaths rates among confirmed Omicron cases were 0.06% and 0.03%, respectively. Our results on the CFR of the Delta and Omicron VOCs are consistent with the findings of the African countries. As for example, the overall CFR for Delta and Omicron VOCs in South Africa were 2.6% and 0.78%, respectively during November 2021 to January 2022. ²⁷ Moreover, the Omicron variant has been associated with an increased risk of re‐infection and vaccine breakthrough infection although no specific rates have yet been reported. ⁶⁰ The identification of SARS‐CoV‐2 variants has laid a foundation to solve important puzzle about the emergence, spreading and virulence of the associated clades and/or lineages in Bangladesh. Therefore, these findings emphasize the importance of international collaboration on virus mutant surveillance, not only for SARS‐CoV‐2 but also for other epidemic viruses.

5. CONCLUSIONS

Genome‐wide variations in SARS‐CoV‐2 reveal evolution and transmission dynamics of several variants which are critical considerations for control and prevention of COVID‐19. In this study, we investigated SARS‐CoV‐2 variants, their temporal dynamics, IFR and CFR in Bangladesh by analyzing more than 6600 complete genomes from March 2020 to October 2022. Different variants of SARS‐CoV‐2 represented by at least 22 clades and 107 lineages were found to be circulated in Bangladesh with distinct variations in their IFR and CFR during 2020–2022. The dynamics of the SARS‐CoV‐2 variants in Bangladesh showed an intriguing epidemic pattern. The Delta VOC was the most predominantly circulating variant in Bangladesh followed by Omicron, Beta, Alpha, Eta, and Gamma variants. We found significant variations in the IFR and CFR throughout the study period. The highest IFR was recorded for clade 20A and clade 20H of the Delta and Beta variants, respectively. However, the highest CFR (~2%) was recorded in 2021 while most of the SARS‐CoV‐2 variants (e.g., Alpha, Beta, Delta, Eta, and Gamma) were found to be circulating in Bangladesh. A continued global effort towards ever‐expanding SARS‐CoV‐2 genome sequencing will help to further the knowledge of potential novel VOCs or VOIs and to understand the evolution of the virus regarding its temporal emergence, transmission and epidemiology. Further epidemiological and experimental work is needed to discriminate transient demographic factors from the permanent contribution to increased transmissibility (IFR) and fatality (CFR) conferred by the different emerging variants of the SARS‐CoV‐2.

AUTHOR CONTRIBUTIONS

M. Shaminur Rahman: Conceptualization; data curation; formal analysis; software; writing—original draft. M. Nazmul Hoque: Conceptualization; data curation; formal analysis; visualization; writing—original draft. Susmita Roy Chowdhury: Data curation; formal analysis; writing—original draft. Md. Moradul Siddique: Data curation; formal analysis; visualization; writing—original draft. Ovinu Kibria Islam: Data curation; formal analysis; writing—original draft. Syed Md. Galib: Resources; software; supervision; writing—review & editing. Md. Tanvir Islam: Data curation; formal analysis; writing—original draft. M. Anwar Hossain: Conceptualization; supervision; writing—review & editing.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest.

TRANSPARENCY STATEMENT

The lead author M. Anwar Hossain affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

Supporting information

Supporting information.

Rahman MS, Hoque MN, Chowdhury SR, et al. Temporal dynamics and fatality of SARS‐CoV‐2 variants in Bangladesh. Health Sci Rep. 2023;6:e1209. 10.1002/hsr2.1209

DATA AVAILABILITY STATEMENT

All the sequences used in the current study are available in the GISAID that are available at https://www.gisaid.org/login/. The information on the metadata (submission date, strain, GISAID ID number, region/location, division, length, host, age, sex, Pangolin lineage, GISAID/Nextstrain clade, originating and submitting lab, authors) is available in Supporting Information: Data S1.