Background
The emergence of SARS-CoV-2 has been declared as a pandemic, which is an unprecedented outbreak of pneumonia that originated in China [1, 2]. Bats were considered to be the host of this virus and 96% gene sequence homology was found between SARS-CoV-2 and a bat SARS-like-CoV whereas it only shares 79.6% similarity with SARS-CoV [3, 4]. Wild animals are regarded as the most potent natural reservoir of the coronavirus family. Two previous coronavirus epidemics- SARS and MERS were also transmitted by wild animals; from palm civets and dromedary camels, respectively [3]. On 31 December 2019, a cluster of pneumonia of unrevealed etiology was identified in Wuhan city of Hubei province in China [4]. Later, it was identified by the Chinese Center for Disease Control and Prevention (CDC) as a novel coronavirus [5]. The International Committee on Taxonomy of Viruses (ICTV) named it as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) because of its similarity with SARS-CoV and the World Health Organization (WHO) termed the disease as ‘COVID-19’ [6, 7]. The virus belongs to the family of coronaviridae and is an enveloped, single-stranded, positive-sense RNA virus [8]. It is the seventh of the already identified human coronaviruses including mild respiratory syndrome disease-causing coronaviruses HKU1, NL63, 229E, and OC43. SARS-CoV and MERS-CoV are the two other strains that have previously endangered human lives by causing two epidemics in China and the Middle East, respectively [8, 9]. Phylogenetic analysis showed that SARS-CoV-2 was intimately connected to two bat-derived SARS-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, but were relatively less similar to SARS-CoV. COVID-19 is affecting 216 countries and territories around the world regardless of age, gender or race. As of 26 October 2020, around 43,837,698 confirmed cases and 1,166,142 deaths have been reported with a fatality rate of 2.66%. At the same time, 32,188,661 patients have recovered from COVID-19. Around 10,482,895 patients were taking treatment and of them, only 79,053 (less than 1%) were critical till 26 October 2020 [10]. The USA is the most affected country to date with more than 8.9 million confirmed COVID-19 cases constituting more than 20% of the total infected patients and had 231,486 deaths up to 26 October 2020. On 30 January 2020, WHO has announced the disease as a public health emergency of international concern [11]. The South Asian countries have also been devastated by this highly infectious disease with 8,856,017 infected cases and 133,969 deaths up to 26 October 2020. South Asia consists of Afghanistan, Bangladesh, Bhutan, India, Iran, Maldives, Nepal, Pakistan, and Sri Lanka. India is facing its severe ramifications being the second-most-infected country with more than 7.9 million infected patients and 119,014 COVID-19 related deaths [12]. This review aims to outline the genome variations, epidemiological characteristics, diagnostic approaches, and treatment and prevention tactics of COVID-19 in the South Asian countries.
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Genomic variations
Analysis based on accessible documented data of genetic variation of this virus suggests that like all RNA viruses, SARS-CoV-2 contains indistinguishable mutation frequency and potential mutant distributions. Among the identified variants, fewer variants can cause long-standing infections. As RNA viruses have high mutation rates, this virus is likely to develop mutations to invade the host defense mechanism. Among the South Asian countries, India has sequenced the maximum number of the SARS-CoV-2 genome (570) among South Asian countries, followed by Bangladesh (231), Pakistan (11), Sri Lanka (4) and Nepal (1) as of 15 October 2020 [13]. Afghanistan, Bhutan and Maldives have not reported any genome sequencing yet.
An investigation on genomes of 184 SARS-CoV-2 virus strains from Bangladesh showed that 634 mutations were located in the entire genome resulting in 274 substitutions (non-synonymous) of amino acid in 22 unrelated proteins. Amino acid substitutions were prevalent at 48 different positions of the papain-like protease (nsp3) and no mutation was detected in nsp7, nsp9, nsp10, and nsp11. Moreover, nine unique mutations were observed in comparison with the global strains in the spike proteins [14]. Another analysis of 207 genomes from different areas of the country showed that 2602 mutations were observed of which 1602 were missense mutations, 612 were synonymous, 36 were insertions and deletions, and 352 were various types. Phylogenetic analysis implicated that the virus originated from Europe and GR clade was most prevalent in this region. A significant finding in these SARS-CoV-2 genomes was 7 unique alterations of amino acid from various proteins [15].
Analysis of 566 complete or almost complete Indian SARS-CoV-2 genomes found 3384 unique mutation points of which 933, 2449 and 2 were substitutions, deletions and insertions, respectively. Besides, 64 single nucleotide polymorphisms (SNP) were found. Of them, 57 SNPs were present in six coding regions and 7 SNPs were present in 5′-UTR and 3′-UTR [16]. One comparative study found that the Indian SARS-CoV-2 strain showed a distinctive mutation in the spike glycoprotein (A930V (24351C>T)) which was absent in further strains [17]. Additionally, another analysis showed the origin of Indian SARS-CoV-2 strains from Europe and South-East Asia followed by local transmission. All the analyzed genomes were divided into four major clades 19A, 19B, 20A and 20B along with the new Nextstrain clade nomenclature and a rare clade 19B was identified which has a low occurrence in India [18].
The SARS-CoV-2 genome strain from Nepalese isolates revealed that it was more than 99.99% identical to two previously sequenced SARS-CoV-2 genomes (MN988668 and NC_045512) from Wuhan, China with seven additional sequences. Besides, five mutations were also identified based on the reference sequence EPI_ISL_405839 [19].
Full and partial genome sequencing of eight Pakistani isolates revealed that SARS-CoV-2 strains circulating in Pakistan were GH, S, L and I clade strains which are clustered with strains from Saudi Arabia, India, USA, Australia and China. Of the eight strains, five were GH clade with mutations in S glycoprotein D614G, Ns3 gene Q57H, and RNA dependent RNA polymerase P4715L. Among others, three were L clade, two were S clade, and one strain was I clade. Additionally, Orf1ab variant L3606F was observed in one GH and one L strain which indicates further evolutionary transitions [20]. In another analysis of 4 whole genome sequences, 31 variants were identified including two causing alterations in ORF1ab gene, ORF1a and N genes with functional replication and translation. Mutations in N & ORF1a proteins showed alterations at the amino acid level [21].
Genome analysis of four SARS-CoV-2 isolates from Sri Lanka showed that the strains were clustered with strains from mostly Europe. SNP analysis revealed that the genome sequence of the first isolates showed variation in 6 nucleotides (nt) positions compared to the reference genome. The other three sequences have differed in 6 nt positions, 5 nt positions, and 4 nt positions, respectively. Amino acid variants were found in the ORF1ab protein, S protein, ORF3a gene, M gene, and N protein of four Sri Lankan whole-genome strains, while the rest of the amino acids in the genes were unaltered [22].
Epidemiological Characteristics
Among the affected South Asian countries, India continues to be the most infected country. Almost 90% of the infected individuals in the South Asian region are from India, followed by Bangladesh, Pakistan and Afghanistan. In terms of COVID-19 deaths, Pakistan was in 2nd position after India and followed by Bangladesh. Afghanistan had the highest mortality rate (3.70%), followed by Pakistan (2.05%) and India (1.50%) as of 26 October (Table 1). Bhutan had the lowest number of infected patients; 342 individuals were infected while no one died. Around the same time, 7,923,759 (90%) patients of the South Asian nations have been cured of the disease [12].
Table1: Case distribution of COVID-19 in South Asian countries
Country | Total confirmed case | Total deaths | Mortality rate (%) | Total recovered |
Afghanistan | 40,833 | 1,514 | 3.70 | 34,129 |
Bangladesh | 398,815 | 5,803 | 1.45 | 315,023 |
Bhutan | 342 | 0 | 0 | 307 |
India | 7,909,959 | 119,014 | 1.50 | 7,137,228 |
Maldives | 11,505 | 37 | 0.32 | 10,524 |
Nepal | 158,089 | 847 | 0.53 | 111,670 |
Pakistan | 328,602 | 6,739 | 2.05 | 311,075 |
Sri Lanka | 7,872 | 15 | 0.19 | 3,803 |