SARS-CoV-2 genomic surveillance in southern Vietnam (2020-2023): Tracking variant evolution and public health impact in a limited-resource setting

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Data may be preliminary. 10 April 2025 V1 Latest version Share on SARS-CoV-2 genomic surveillance in southern Vietnam (2020-2023): Tracking variant evolution and public health impact in a limited-resource setting Authors : Minh Thang Cao , Huy Manh Dao , Minh Hang Duong 0009-0009-6212-6905 [email protected] , Pham Hong Nhung Vu , Thi Nhu Dao Hoang , Minh Hieu Le , Viet Thinh Nguyen , Chan Quang Luong , Duy Quang Pham , Vu Thuong Nguyen , and Vu Trung Nguyen Authors Info & Affiliations https://doi.org/10.22541/au.174427036.61422801/v1 Published Acta Tropica Version of record Peer review timeline 407 views 154 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract The COVID-19 pandemic highlighted the urgent need for genomic surveillance to monitor viral evolution and guide public health responses, especially in limited-resource settings. This study describes the establishment and implementation of a SARS-CoV-2 genomic surveillance system by Pasteur Institute in Ho Chi Minh City (PIHCM), covering 20 provinces in southern Vietnam from January 2020 to June 2023. Nasopharyngeal swabs were systematically collected, screened by RT-PCR (Ct < 28), and sequenced using adaptable Next-Generation Sequencing technologies, including Illumina MiSeq and later Oxford Nanopore MinION, supported by international training and resources. Phylogenetic analyses tracked viral lineage dynamics across five pandemic phases. A total of 2207 genomes were sequenced, revealing temporal shifts in variant dominance, particularly Delta and Omicron variants and an average mutation count of 52.5 per sample. The data were instrumental in managing local outbreaks, informing national responses, and contributing to global databases like GISAID. This study demonstrates that adaptive genomic surveillance is both feasible and effective in resource-constrained settings. It underscores the critical role of real-time genomic data in pandemic response and advocates for sustained investment in capacity building, infrastructure and global collaboration, offering a scalable model for future preparedness in low - and middle - income countries. INTRODUCTION The COVID-19 pandemic in Vietnam, particularly in the southern provinces, progressed through distinct phases, reflecting the country’s dynamic response strategies. The first phase (January – July 2020) saw strict containment efforts, including mandated 24-hour case reporting, which kept cases and fatalities low despite rising global numbers. In the second phase (July 2020 – January 2021), Vietnam intensified its control measures with early detection, rapid contact tracing, daily health declarations, and strict quarantine protocols. The third phase (January – April 2021) was marked by increased cases linked to international travel, with localized outbreaks, particularly among airport personnel. The fourth phase (April – October 2021) saw widespread community transmission, notably in Ho Chi Minh City, prompting lockdowns, extended restrictions, school closures, and event cancellations. By the fifth phase (November 2021 – June 2023), declining death rates and widespread vaccine coverage enabled a gradual easing of restrictions, reflecting improved public health outcomes. Genomic surveillance has become to be a critical tool in managing pandemics, offering valuable insights for public health interventions. It enables the identification of pathogens, tracking of virus evolution, and tracing of transmission chains 1 . This approach has proven particularly effective during the COVID-19 pandemic, aiding in the detection of variants like Delta and Omicron 1 . Despite its benefits, there are significant disparities in access to genomic surveillance tools globally, particularly in countries with less developed economies 2 . Consequently, COVID-19 genome sequencing strategies vary among countries. For instance, the U.S. maintains an extensive genomic surveillance initiative, employing diverse sequencing technologies and collaborations between research bodies and public health agencies 3 , 4 . This comprehensive program enables large-scale monitoring of viral variants and their dissemination. In contrast, Vietnam, despite resource constraints, has proactively pursued sequencing endeavors, focusing on targeted sequencing during specific outbreaks and monitoring at-risk groups. In the initial year of the COVID-19 pandemic, genomic surveillance emerged as a pivotal research tool, leading to the establishment of a dedicated monitoring system in southern Vietnam. Leveraging our experience with pathogens such as influenza, SARS-CoV-2, Dengue, and Zika, Pasteur Institute in Ho Chi Minh City (PIHCM) played a crucial role in integrating genomic surveillance into Vietnam’s public health strategy. This approach has been essential not only for local disease control but also for contributing to global databases like GenBank and GISAID 5 , 6 , 7 . Despite facing challenges such as limited funding, workforce shortages, and insufficient lab capacities, PIHCM’s efforts have significantly strengthened Vietnam’s health infrastructure. The government’s rapid containment strategies and comprehensive public health initiatives demonstrate that effective management is possible even under resource constraints 8 , 9 . This study explores PIHCM’s adaptive approach (Jan 2020–June 2023) to SARS-CoV-2 genomic surveillance in southern Vietnam and its impact on outbreak preparedness. MATERIALS AND METHODS Study setting The Southern region of Vietnam includes 20 provinces and is a crowded region, encompassing approximately 37.6 million people, making it one of the most densely populated areas in the country with diverse healthcare infrastructure, ranging from advanced central hospitals in urban areas to basic health stations in rural parts. Throughout the COVID-19 pandemic, these provinces experienced a substantial burden of the disease, necessitating rigorous healthcare interventions. Provincial Centers for Disease Control (CDCs) and central hospitals in southern Vietnam played a pivotal role in COVID-19 surveillance by sending samples to PIHCM for case confirmation and sequencing analysis. The study, encompassing five distinct phases of the COVID-19 pandemic in Vietnam, was conducted at PIHCM and approved by its Institutional Review Ethical Board (reference number: 05/GCN‐PAS). Sample collection Sample collection for SARS-CoV-2 genomic surveillance across southern Vietnam, from January 2020 to June 2023, covering all 20 provinces (An Giang, Ba Ria-Vung Tau, Bac Lieu, Ben Tre, Binh Duong, Binh Phuoc, Ca Mau, Can Tho, Dong Nai, Dong Thap, Hau Giang, Ho Chi Minh, Kien Giang, Lam Dong, Long An, Soc Trang, Tay Ninh, Tien Giang, Tra Vinh, Vinh Long), including major urban centers and international border entries. Nasopharyngeal swabs were collected from COVID-19 designated areas such as hospitals and quarantine centers, under the coordination of provincial CDCs and central hospitals. Swab collection was performed by personnel trained in healthcare, life sciences or equivalent, with specialized training in biosafety and sampling techniques. Appropriate personal protective equipment (PPE), including powder-free gloves and medical masks, was used to ensure the safety of both healthcare personnel and patients. The nasopharyngeal swabs utilized were synthetic fiber-tipped with plastic shafts. Each swab was carefully inserted through the nasal passage until resistance indicated contact with the nasopharyngeal wall, where it was rotated gently to collect cellular material and secretions. To maximize viral recovery, the swab was held in place for approximately 5 seconds before withdrawal. After collection, the swab was immediately placed into a sterile 15 mL conical centrifuge tube containing 500 µL of viral transport medium. The swab’s tip was fully immersed in the medium, and the shaft was adjusted if necessary to fit the tube securely. Samples were then triple-sealed—initially in the transport tube secured with parafilm, followed by placement in an absorbent material and a secondary durable plastic bag or container. This secondary container was further secured within an outer sturdy container that was clearly labeled and included relevant patient and sample information. The specimens were initially kept at 2-8°C for up to 72 hours; those requiring longer storage were frozen at temperatures below -70°C and transported with dry ice or pre-cooled ice packs to minimize freeze-thaw cycles. Samples were re-confirmed by real-time reverse transcription – polymerase chain reaction (RT-PCR) at PIHCM, and those with a cycle threshold (Ct) value < 28 were selected for Next Generation Sequencing (NGS). This threshold was chosen because lower Ct values indicate higher viral RNA concentrations, which are associated with improved sequencing coverage and quality. Studies have demonstrated that samples with Ct values below 28 yield optimal sequencing results, facilitating accurate genome assembly and variant identification 10 , 11 . Along with the samples, provincial CDCs and central hospitals also send metadata to PIHCM, including the patient’s gender, age, address (within the province), sample collection date, clinical conditions and travel history. Sequencing training In the early days of the pandemic, a team of three staff with experience in Zika virus sequencing were selected. Drawing on their 2016 expertise, they used metagenomic approaches following cell culture to sequence the first two SARS-CoV-2 cases in Vietnam. As demand for sequencing surged, the team rapidly expanded to seven members, adopting a targeted amplicon-based sequencing protocol with ARTIC primers to streamline the process and handle more samples. Recognizing the need for ongoing knowledge, the team collaborated with the U.S. CDC and the Association of Public Health Laboratories (APHL) to receive advanced online training in May 2021. This ensured they stayed abreast of the latest sequencing and bioinformatics advancements. With COVID-19 cases multiplying rapidly, the team was mobilized to participate in COVID-19 response activities. The sequencing team was divided into two groups to alternate between performing COVID-19 prevention activities through real-time RT-PCR testing and conducting genomic sequencing for COVID-19 variants. As the situation evolved, the team diversified their tools by sending two members to Thailand for Oxford Nanopore Technology (ONT) sequencing training; thus, PIHCM established this advanced sequencing technique in Vietnam for the first time. A team leader conducted meticulous quality control and data review to monitor the virus’s mutation rate, identify the effectiveness of primers, and develop a strategy to adjust primers to match the virus’s mutation rate. Sequencing technology Two different platforms for genomic surveillance were used during the study period. Illumina Miseq (Illumina InC, CA, USA), was used from January 2020 to September 2022, supported by training, reagents, and technical assistance from the U.S. Centers for Disease Control and Prevention (CDC). Since October 2022, the MinION Mk1C platform (ONT, Oxford, UK) has been implemented. The switch to ONT coincided with a gradual decrease in SARS-CoV-2 case numbers following the pandemic peak prior to October 2022, making the ONT platform more feasible in terms of reagents, operational cost, and logistical considerations. Between January 2020 and March 2021, selected SARS-CoV-2 samples (Ct value < 28) were inoculated into Vero E6 cell culture. Cytopathic effect was first observed on the second day post-inoculation and harvested viral supernatant on the day later. The collected viral lysates were used for nucleic acid extraction. Any remaining DNA was removed from the RNA preparations using the Turbo DNA-free kit® (Cat: AM1907, Life Technologies, USA). Next, cDNA synthesis was performed using the SuperScript®III first strand synthesis system (Cat: 18080051, Invitrogen, USA), and ds DNA was synthesized using the NEBNext®Ultra II Non-Directional RNA Second Strand Synthesis module (Cat: E6111S, New England Biolabs, USA). Libraries were prepared by using Nextera XT DNA Library preparation kit (Cat: FC-131-1096, Illumina, USA), and they were purified using Agencourt AMPure XP Bead-Based Reagent (Cat: A63881, Beckman Coulter, USA). DNA quantification was performed with the Qubit 3.0 Fluorometer (Invitrogen™) using the Qubit™ dsDNA HS Assay Kit (Cat: Q32854, Invitrogen™, USA). Sequencing was conducted using Illumina MiSeq equipment (San Diego, CA, USA) with Miseq Reagent Kit v2 (300 cycles) for pair-end sequencing in approximately 24 hours. Data output was assessed using FastQC, and the assembly of complete virus genomes was achieved through the map-to-reference method using CLC Main Workbench v.10.1.1 (CLC bio, Cambridge, MA). Since mid-2021, PIHCM adopted a flexible prepared Illumina sequencing library using targeted amplicon-based method. All primary clinical samples with Ct value < 28 were directly used for RNA extraction. RNA extraction was performed using the QIAmp viral RNA mini kit ® (Cat: 52906, Qiagen, Germany). The ARTIC V3 primer panel was utilized from December 2021 to February 2022, the Varskip short 2a primer panel from March 2022 to Septemeber 2022 that was included in the NEBNext ARTIC SARS-CoV-2 library Prep Kit (E7650, New England Biolabs, USA), and the NEBNext ARTIC SARS-CoV-2 FS library Prep Kit (Cat: E7658, New England Biolabs, USA) for the sequencing library generation step and update to ARTIC V4 primer panel from October 2022 The FASTQ files generated from the Illumina platform were processed and analyzed using workflows Titan_Illumina_PE and TheiaCoV_Illumina_PE on Terra.bio. From the fourth quarter of 2022 until June 2023 the ONT platform was applied using the Midnight RT-PCR expansion pack (Cat: EXP-MRT001, Nanopore Rapid Barcoding kit (SQK-RBK110.96). In the processing of Fast5 files, the raw electrical signals were converted into nucleotide sequences using Guppy version 6.4.2 (ONT, UK). All the sequences were preprocessed, aligned, and mapped to the SARS-CoV-2 reference genome (Genbank accession: MN908947) following steps similar to those outlined using workflow TheiaCoV_ONT and TheiaCoV_ONT_PHB on Terra.bio as described above. Data analysis All FASTA files, which are text-based formats commonly used to represent nucleotide sequences, that met the following criteria underwent variant calling, clade assignment, and phylogenetic tree analysis: a minimum of 90% alignment with the SARS-CoV-2 virus amplicon target, fewer than 5000 N-nucleotides, and an assembly length exceeding 24000 base pairs with unambiguous sequences. Variants were determined using the Pangolin tool, version v.4.3 12 and Nextstrain clades. Two workflows, namely Augur Prep and Augur Run, were sequentially executed to generate the necessary inputs for visualization. Augur Prep processed the data, produced the properly formatted metadata table, and concatenated FASTA files necessary for subsequent Augur Run analyses. Augur Run, in turn, generated the inputs required for phylogenetic inference using Auspice. Employing the input data from Augur Run, Auspice evaluated genetic relatedness among sequences, drew phylogenetic inferences, and enabled interactive visualization. Available demographic data associated with sequenced samples were analyzed using R studio software (version 2023.06.01+421), Microsoft Excel (version 16.68). Sequencing result reporting Sequencing data from PIHCM’s COVID-19 surveillance informed outbreak investigations at local, national, and global levels. Locally, it supported cluster identification; nationally, it contributed to weekly reports for the Ministry of Health; and globally, it was shared via GISAID to aid variant tracking. All sequences used in this study are available on GISAID’s EpiCoV database. Demographic and distribution of SARS-CoV-2 variants in southern Vietnam A total of 2207 PCR-confirmed COVID-19 samples from the southern provinces of Vietnam were sequenced between January 2020 and June 2023. The mean age was 40.8 ± 19.5 years and 46.1% (1018/2207) of the patients were female. Ho Chi Minh City, the most populous and densely populated area in southern Vietnam, recorded the highest number of cases, accounting for 545 sequences (24.7%). The analysis revealed a diverse distribution of viral lineages, with the Omicron variant (1471 sequences, 66.7%) and the Delta variant (499 sequences, 22.6%) being the most sequenced. The sequences were distributed across the pandemic phases as follows: Phase 1 (January – July 2020) had 27 sequences, Phase 2 (July 2020 – January 2021) had 2 sequences, Phase 3 (January – April 2021) had 4 sequences, Phase 4 (April – October 2021) had 216 sequences, and Phase 5 (November 2021 – June 2023) had 1958 sequences (Supplement 1). Phylogenetic analysis of SARS-CoV-2 sequences from southern Vietnam The SARS-CoV-2 phylogenetic tree depicts distinct evolutionary phases in southern Vietnam’s COVID-19 landscape (Figure 1). Emerging in early 2020, the first two detected cases in Vietnam were classified as the 19A variant (lineage B) 13 . Between January and April 2020, most COVID-19 cases were imported 7 , 13 and included a range of variants such as 19A, 19B, and 20A–D, corresponding to lineages A and B and their sub-lineages (A, A1, A2, B.1, B.1.1, B.1.1.1, and B.3. In December 2020, the Alpha variant (lineages B.1.1.7) emerged. Local outbreaks in early 2021 revealed the 19B variant (lineages A.23.1). The Delta variant (lineages AY.57) dominated from July 2021 until the emergence of the Omicron variant in early 2022, with BA.1 and BA.2 sub-variants evolving separately. BA.1 emerged between January and March 2022, while BA.2 peaked from February to June 2022. In the third quarter of 2022, the 22B variant (BA.5, Omicron) was the most dominant. Subsequent variants, including 21L, 22B, 22D, 22F, 23A, 23B, 23C, 23D (lineages BA.2, BA.5, BA.2.75, XBB, XBB.1.5, XBB.1.16, CH.1.1, XBB.1.9) have successively dominated from the fourth quarter of 2022 to June 2023. Genomic mutations in SARS-CoV-2 sequences from southern Vietnam SARS-CoV-2 sequences from southern Vietnam exhibited mutations across various genome regions, with the highest rates and densities observed in the Spike protein (48735 mutations) and ORF1a region (23057 mutations). Among 2207 sequences, 115875 mutations were identified, averaging 52.5 mutations per sample. In total, 2613 distinct mutation types were identified across all sequences with 2398 different substitution mutations and 215 different deletion mutations. The most prevalent mutations were P314L in the ORF1b region (99.18%) and D614G in the Spike protein (98.82%). Other notable mutations, including G142D, P10S, R203K, P13L and G204R, were detected in approximately 75% of sequences (Supplement 2). DISCUSSION Sequencing results The phylogenetic analysis of 2207 SARS-CoV-2 sequences from southern Vietnam (2020–2023) reveals a clear correlation between variant emergence and the distinct phases of public health interventions implemented during the pandemic. During the initial phase (January – July 2020), few viral lineages were identified, with 27 sequences analyzed, indicating limited community spread and effective containment efforts mandated by rapid case reporting. The phylogenetic tree supports this observation, showing sparse sequence distribution, reflecting constrained viral evolution during this early containment phase. The 19A variant (lineage B), first detected globally in Wuhan, China on December 24, 2019, was similarly identified in southern Vietnam on January 22, 2020. Subsequently, several sub-lineages of B were identified in multiple countries, including Vietnam 14 . In the second phase (July 2020–January 2021), despite increased global circulation of the virus, Vietnam’s rigorous strategy involving rapid contact tracing, strict quarantine protocols, and early detection limited viral diversification. Only 2 sequences were analyzed in this phase, evident in the phylogenetic tree where sequences remain relatively clustered with limited branching, indicating minimal local transmission chains and effective suppression of emerging variants. The alpha variant from the 20E and 20I/Alpha variant (lineage B.1.1.7) emerged in mid-December 2020, resulting in significantly higher transmission rates 15 , 16 . The third phase (January–April 2021), with 4 sequences analyzed, marked a period characterized by sporadic introductions linked primarily to international travel, generating localized clusters. This phase witnessed a rise in cases, mostly involving individuals who had recently traveled to Vietnam. Local person-to-person transmission led to outbreaks, particularly among airport employees associated with the 19B variant (lineage A.23.1). The phylogenetic data from this period depict isolated branches associated with limited outbreaks, particularly involving airport personnel and incoming travelers. This supports the targeted nature of the outbreaks rather than widespread community transmission. The ongoing fourth phase, starting in April 2021, involved significant community transmission driven primarily by the Delta and subsequently Omicron variants. This phase marked a sharp rise in cases and the highest death rate in Ho Chi Minh City, with 215 out of 216 sequences identified as the highly virulent Delta variant. Globally, Delta was associated with significantly increased risks: 105–108% for hospitalization, 235–241% for ICU admission, and 121–133% for death 17 . In this period, the government imposed lockdowns, extended restrictions, closed schools, and canceled events 18 . The fifth and final phase (November 2021 – June 2023), which included the largest number of sequences analyzed (1958), coincided with widespread vaccination and the gradual easing of restrictions. Phylogenetic analysis showed rapid diversification and extensive branching, reflecting high transmission and viral evolution, particularly as the dominant Delta variant was replaced by Omicron sublineages. Despite higher infection rates, this phase saw fewer clusters and reduced disease severity compared to the fourth phase, supported by improved clinical outcomes and declining mortality. This pattern is consistent with findings from international studies, which indicate that Omicron infections were associated with a lower risk of death and lower risk of hospitalization compared to Delta 19 , 20 ,and hospitalized patients showed milder illness and faster recovery, with mortality dropping from 14% in the early to 9% in the later Omicron period 21 . These findings highlight the combined role of vaccine-induced immunity and the lower virulence of Omicron in reducing disease severity during this phase. Overall, the phylogenetic analysis correlates strongly with epidemiological data and public health measures across each pandemic phase, underscoring the critical impact of timely interventions and vaccination strategies in controlling SARS-CoV-2 transmission dynamics in southern Vietnam. The analysis of SARS-CoV-2 sequences from southern Vietnam revealed significant insights into the virus’s mutation patterns and their implications for managing and surveilling COVID-19 in the region. The high mutation rates, particularly in the Spike protein and ORF1a region, underscore the virus’s adaptability and its impact on transmission dynamics 22 . The Spike protein’s pivotal role in receptor recognition and cell membrane fusion contributed to the increasing infection rates, necessitating a more robust and responsive public health strategy 22 , 23 . The identification of 115875 mutations across 2207 sequences, with an average of 52.5 mutations per sample. This mutation rate is considerably higher compared to other geographical regions. For comparison, an analysis of 3734 SARS-CoV-2 sequences from Georgia, USA, revealed an average of approximately 20.2 mutations per sample 24 , significantly lower than our findings. Similarly, global analyses of 48635 SARS-CoV-2 genomes reported an average of 7.23 mutations per sample, with slightly higher averages in India (8.40 mutations per sample) and Bangladesh (9.83 mutations per sample) 25 . This striking difference points to distinct viral evolutionary dynamics in southern Vietnam, likely influenced by prolonged community transmission, local selection pressures, or sequencing methodologies. The elevated mutation rates observed reflect unique viral adaptation within the population. Further research is needed to explore the epidemiological and clinical implications of this heightened genetic diversity, which could guide more targeted public health responses and surveillance strategies. Additionally, key mutations identified in our study, such as the P314L and D614G substitution detected in more than 98% of sequences, align closely with global patterns. These mutations have been identified as significant variants with implications for viral infectivity and transmissibility 26 . Singh et al. (2020) noted that P314L co-occurs with other mutations in globally dominant strains, suggesting its role in the virus’s geo-clonal evolution. The P314L mutation has been linked to the D614G substitution in the Spike protein, complicating the interpretation of their individual impacts on infection rates 27 . Mutations in the ORF1ab region, including P314L, have been recognized for their role in viral replication and pathogenicity, suggesting a potential influence on disease severity 28 , 29 . Other notable mutations, including G142D, P10S, R203K, P13L and G204R , were found in approximately 75% of Vietnamese samples and have also been reported in international studies 30 , 31 . Among these, the R203K/G204R mutations in the nucleocapsid (N) protein are particularly significant. These mutations are associated with highly transmissible lineages such as B.1.1.7 and have shown a rapid rise in global prevalence. Studies have demonstrated that R203K/G204R mutations confer a replication advantage, increase infectivity in human lung cells, and enhance virulence in animal models 31 . These mutations have implications for viral transmission dynamics and may influence vaccine effectiveness, underscoring the need for continuous monitoring to inform public health responses and vaccination strategies 6 , 24 , 32 . Impact and applications of COVID-19 surveillance data from PIHCM The COVID-19 surveillance data from PIHCM proved invaluable in the fight against the pandemic, serving as a powerful tool for epidemiological investigations at the local, national, and global levels. Locally, this data provided information for epidemiologists to investigate transmission hotspots in various settings, for instance, PIHCM have reported clusters of cases at a bar in Ho Chi Minh City and at Tan Son Nhat Airport 6 , 13 . On a national level, data from COVID-19 surveillance provided weekly reports to the Ministry of Health, promptly identifying the arrival of new variants that were imported to Vietnam 7 . Moreover, PIHCM’s data contributed to both COVID-19 pandemic prevention and global research efforts through sharing data to GISAID, helping identify emerging variants and contributing valuable insights to academic publications 6 , 33 , 34 (see Supplement 1 for GISAID ID list). This comprehensive utilization transformed mere statistics into a powerful tool, empowering Vietnam to navigate the pandemic with greater precision and effectiveness, ultimately shaping and refining Vietnam’s COVID-19 surveillance and prevention strategies. Adaptive solutions for resource challenges The COVID-19 pandemic has underscored the vital role of genomic surveillance in understanding virus evolution and enhancing public health responses, particularly in low-and middle-income countries (LMICs) 35 , 36 . Despite achieving significant advancements, LMICs like Vietnam and Pakistan have faced notable challenges. These include constraints in resource allocation, technical capacity, and the sustainability of their genomic sequencing efforts, reflecting broader disparities in global health preparedness and response capabilities 36 , 37 . Both PIHCM from Vietnam and Aga Khan University (AKU) from Pakistan have grappled with the complexities of setting up and maintaining advanced sequencing technologies. PIHCM has managed a comprehensive system, utilizing a wide network for sample collection and adopting both Illumina and ONT for sequencing. Conversely, AKU’s experience highlights significant barriers related to equipment procurement and the high costs associated with overcoming import restrictions, which are prevalent challenges in LMICs 36 . Efforts to enhance technical capacity at PIHCM included substantial training in NGS with the support from international organizations like U.S. CDC and WHO, crucial during the pandemic’s peak phases. Similarly, AKU’s strategy involved leveraging international partnerships to bolster local expertise, demonstrating the importance of collaborative North-South relationships that support technology transfer and capacity building. The sustainability of these surveillance systems poses a significant challenge, demanding ongoing funding and strategic resource management to develop a local workforce skilled in genomic technologies. Both institutes underscore the feasibility of establishing robust genomic surveillance in resource-limited settings, provided there is adequate support from international partners and strategic local management. These examples illustrate the shared hurdles and the potential for LMICs to harness genomic surveillance for public health, emphasizing the need for strategic partnerships, continuous training, and robust infrastructure investments to maintain and expand these capabilities. CONCLUSION This study highlights the successful implementation of an adaptive SARS-CoV-2 genomic surveillance system by the Pasteur Institute in Ho Chi Minh City. Through efficient resource utilization and international collaboration, the system effectively monitored viral evolution and variant transitions across distinct pandemic phases. The findings revealed high regional mutation rates and provided critical data for local outbreak control, national health strategies, and global databases. 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Keywords coronavirus endemic infection epidemiology genetic variation genetics pandemics sars coronavirus virus classification Authors Affiliations Minh Thang Cao Pasteur Institute in Ho Chi Minh City View all articles by this author Huy Manh Dao Pasteur Institute in Ho Chi Minh City View all articles by this author Minh Hang Duong 0009-0009-6212-6905 [email protected] Pasteur Institute in Ho Chi Minh City View all articles by this author Pham Hong Nhung Vu Pasteur Institute in Ho Chi Minh City View all articles by this author Thi Nhu Dao Hoang Pasteur Institute in Ho Chi Minh City View all articles by this author Minh Hieu Le Pasteur Institute in Ho Chi Minh City View all articles by this author Viet Thinh Nguyen Pasteur Institute in Ho Chi Minh City View all articles by this author Chan Quang Luong Pasteur Institute in Ho Chi Minh City View all articles by this author Duy Quang Pham Pasteur Institute in Ho Chi Minh City View all articles by this author Vu Thuong Nguyen Pasteur Institute in Ho Chi Minh City View all articles by this author Vu Trung Nguyen Pasteur Institute in Ho Chi Minh City View all articles by this author Metrics & Citations Metrics Article Usage 407 views 154 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Minh Thang Cao, Huy Manh Dao, Minh Hang Duong, et al. SARS-CoV-2 genomic surveillance in southern Vietnam (2020-2023): Tracking variant evolution and public health impact in a limited-resource setting. Authorea . 10 April 2025. DOI: https://doi.org/10.22541/au.174427036.61422801/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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