Sequential viral introductions and spread of BA.1 across Pakistan provinces during the Omicron wave

Abstract

Background: COVID-19 waves caused by specific SARS-CoV-2 variants have occurred globally at different times. We focused on Omicron variants to understand the genomic diversity and phylogenetic relatedness of SARS-CoV-2 strains in various regions of Pakistan.

Methods: We studied 276,525 COVID-19 cases and 1,031 genomes sequenced from December 2021 to August 2022. Sequences were analyzed and visualized using phylogenetic trees.

Results: The highest case numbers and deaths were recorded in Sindh and Punjab, the most populous provinces in Pakistan. Omicron variants comprised 93% of all genomes, with BA.2 (32.6%) and BA.5 (38.4%) predominating. The first Omicron wave was associated with the sequential identification of BA.1 in Sindh, then Islamabad Capital Territory, Punjab, Khyber Pakhtunkhwa (KP), Azad Jammu Kashmir (AJK), Gilgit-Baltistan (GB) and Balochistan. Phylogenetic analysis revealed Sindh to be the source of BA.1 and BA.2 introductions into Punjab and Balochistan during early 2022. BA.4 was first introduced in AJK and BA.5 in Punjab. Most recent common ancestor (MRCA) analysis revealed relatedness between the earliest BA.1 genome from Sindh with Balochistan, AJK, Punjab and ICT, and that of first BA.1 from Punjab with strains from KPK and GB.

Conclusions: Phylogenetic analysis provides insights into the introduction and transmission dynamics of the Omicron variant in Pakistan, identifying Sindh as a hotspot for viral dissemination. Such data linked with public health efforts can help limit surges of new infections.

Keywords: Omicron; Phylogenetics; SARS-CoV-2; Transmission dynamics; Variants of concern.

Fig. 1

Population density, COVID -19 cases, deaths, and CFR across Pakistan. The graphs depict nationwide data from December 1, 2021 until August 14, 2022. A The region-wise population density of Azad Jammu and Kashmir (AJK), Balochistan, Gilgit-Baltistan (GB), Islamabad Capital Territory (ICT), Khyber Pakhtunkhwa (KPK), Punjab and Sindh is presented. The scale bar displays population values in millions of persons shaded by color. B Left panel x-axis shows number of COVID-19 cases, the middle panel shows number of COVID-19 related deaths, and the right panel shows the case fatality rate (CFR %) per regions colered as: ICT (light blue), Punjab (dark blue), Sindh (green), KPK (orange), Balochistan (purple), GB (yellow) and AJK (red)

Fig. 2

Trend of COVID-19 cases in Pakistan. The figure depicts the weekly count of COVID-19 cases through the period from December 1, 2021, until August 14, 2022. Cases are shown region-wise; ICT (light blue), Punjab (dark blue), Sindh (green), Khyber Pakhtunkhwa (KPK, orange), Balochistan (purple), GB (yellow) and AJK (red)

Fig. 3

Frequency of Omicron variants across Pakistan. The graph shows all Omicron (n = 955) genomes submitted from each region between December 1, 2021, and August 14, 2022. BA.1 (blue), BA.2 (orange), BA.4 (yellow) and BA.5 (green)

Fig. 4

Phylogenetics of early Omicron variants in Pakistan. The tree illustrates the relatedness of 944 omicron sequences submitted from Pakistan between December 1, 2021, and August 14, 2022. The tree uses color coding to identify the travel origin of each case reported

Fig. 5

Introduction and linkage of omicron variants in Pakistan. Phylogenetic trees depict the first case report for each variant as a red circle in the identified timeline with relatedness to later isolates. Panels A-D depict the first case of each variant identified by a red circle for A, BA.1; B, BA.2; C, BA.4 and D, BA.5. Regional locations are identified by colors; Sindh in light yellow, Balochistan in pink, AJK in blue, Punjab in light green, GB in dark green and ICT, light blue. Data are presented as auspice output of the tree generated using IQ-TREE v. 2.2.0

Fig. 6

Evolutionary relatedness of the first reported Omicron variant from each region of Pakistan. A Phylogenetic tree for 944 Omicron genomes and related strains sharing the most recent common ancestor (MRCA). The first BA.1 sequence from each region, B Balochistan (purple); C Sindh (green); D AJK (light red); E Gilgit-Baltistan and KPK (yellow); F Punjab and ICT (light blue). Data are presented as Figtree v. 1.4.4 outputs using the maximum-likelihood tree generated using IQTREE v. 2.2.0. Grey triangles represent collapsed nodes of relatively distant sequences from the first Omicron sequences in each region. Scale bar presents nucleotide substitution/site