COVID-19 Genomic Surveillance in Malaysia: Challenges and Opportunities

Written by : Muhiddin Ishak, Nor Azila Muhammad Azami & Rahman Jamal

Published date :  07 Oktober 2022

UKM Medical Molecular Biology Institute

COVID-19 Genomic Surveillance in Malaysia: Challenges and Opportunities

 

Genomic surveillance is the continuous monitoring of pathogen transmission and evolution that will aid epidemiologists, researchers, public health authorities, and relevant stakeholders in making informed decisions regarding public health safety. In March 2022, the World Health Organization (WHO) released a paper that framed a ten-year strategy called “The global genomic surveillance strategy for pathogens with pandemic and epidemic potential 2022-2032” to strengthen and expand global genomic surveillance [1]. This strategy offers a high-level unifying structure for leveraging possibilities, addressing barriers, and increasing global genomic monitoring.

Genomic surveillance utilizes next-generation sequencing applications and has been used to monitor infectious diseases such as tuberculosis, HIV, chikungunya, dengue, and Ebola [2]. Genomic surveillance has also facilitated vaccine development by providing information regarding genotype variation within the viruses and vaccine effectiveness [3]. A combination of advanced genetic analysis and conventional epidemiology strategy enabled the early detection of novel and emerging pathogens such as Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2).

During the COVID-19 pandemic, the genomic surveillance approach has become essential for monitoring the circulating strains within the community transmission and the imported cases for effective mitigating and preventive measures [4]. In addition to that, data from genomic surveillance has aided nations in making prompt and informed public health decisions in response to the constant emergence of new strains  [5]. In early 2021, the World Health Organization (WHO) proposed SARS-CoV-2 Sequencing for Public Health Emergency Response, Epidemiology and Surveillance (SPHERES) for effective prevention measures and managing the appearance of a novel variant of concern, including delta and omicron.

Genomic surveillance has aided in determining the clinical significance and infectiousness potential of the SARS-CoV-2 virus. The constant mutation in the SARS-CoV-2, especially in the spike protein, has affected the reliability of a diagnostic tests, virus transmission, vaccine efficacy, therapeutic outcomes, and responses. To track the emergence of new VOCs like delta and omicron, it is imperative to collect sufficient data to determine their virulence and the effect of these new VOCs on vaccine effectiveness [6]. In addition, identifying the novel VOC using genomic surveillance has played an essential role in managing the COVID-19 pandemic.

 

Challenges in establishing genomic surveillance in low- and middle-income countries

Monitoring the emergence of novel VOC should be a national priority, and governments should encourage the establishment of a national consortium of laboratories under the Ministry of Health, public health institutes, and academic institutions. Enhancing global genomic monitoring and sequencing initiatives is crucial for detecting and understanding these novels and emerging variants [7]. Better global detection and tracking of new variants may be possible if efforts are made to increase the capability in low-sequencing-capacity settings, such as establishing sequencing services for countries with no or low specialized sequencing capacity through reference laboratories and networks [8].

Genomic surveillance effort is scarce in low- and middle-income countries because of a lack of infrastructure and limited resources [9]. In addition, reagent shortages and lack of funding for genomic surveillance also dampen the effort. The high prevalence of COVID-19 but low numbers of cases sequenced, a flawed genetic monitoring system, strict restrictions and rules for the distribution of biological samples and associated data, and divergent public data sharing may contribute to this seemingly low sequencing rate. Decentralized genomic surveillance monitoring also plays a role in data discrepancies. Issues of genomic data security and the prospect of unequal contribution from data-sharing efforts are raised as potential problems. These factors have hindered the action of public data sharing until all sequencing centres were prepared to cooperate and granted permission to upload their data.

While platforms like GISAID offer some safeguards (including user identification, conditions of access, and data usage agreements), there is still a need to address the broader problem of safeguarding the rights of data depositors to promote data sharing. Improvements in the rate (ideally real-time) and breadth of contributing genetic information to publicly accessible databases are crucial for urgent public health interventions [10].

 

Genomics surveillance aid in pandemic response in Malaysia

In June 2021, The Malaysian Ministry of Science and Technology (MOSTI) approved a grant from its Strategic Research Fund scheme for nationwide genomic surveillance of SARS-CoV-2 to monitor better the circulating SARS-CoV-2 strains as a strategy for transition to the endemic phase. In this genome surveillance project, seven sequencing facilities from universities, research institutes, and public health laboratories partnered to scale up the genome sequencing. This enables the monitoring and expansion of genome sequencing data and the transfer of expertise and training, both of which are critical for the field’s long-term existence.

The genomic surveillance strategy has assisted in identifying the beta and delta variants during the second epidemic wave between February 27, 2020, to June 30, 2020, and the third epidemic wave on September 8, 2020, respectively. Within days, new restrictions were implemented to place the country on a greater degree of lockdown to limit disease spread and preserve lives. Since these variants are more contagious, data from genomic surveillance facilitated the government to plan and prepare for the increasing number of patients by stocking up the oxygen supply and hospital bed capacity and testing and selecting suitable vaccines.

Genomic surveillance also allowed the government to monitor the emergence of more dangerous strains from travelers at the point of entry. The genome surveillance consortium discovered the first imported cases of the Omicron variant of concern (VOC) in an international student returning from South Africa. The 19-year-old lady, who was asymptomatic and immunized, tested positive for COVID-19. Arriving in Malaysia via Singapore, she was quarantined for ten days before being released. Contact tracing and strict isolation had to be implemented as soon as a person had been diagnosed with a contagious strain to limit its spread. Malaysia temporarily restricted the entry of passengers from eight Southern African nations that have reported the variation or are considered high-risk.

Without imposing a travel ban, the country has been able to isolate the majority of positive cases and slow the spread of these more dangerous variants of concern through mandatory point-of-entry testing for all visitors from abroad. Economically, travel bans are very costly, but a good triage system and testing at the point of entry are nearly as effective.

 

How to improve genomic surveillance in Malaysia?

The goal of genomic surveillance is to improve and scale local to global public health actions in terms of quality, timeliness, and adequacy within surveillance systems [11]. Multisectoral partnerships are essential for the successful implementation of a strategy. The government has also invested in outsourcing genomic surveillance to private laboratories and fostering meaningful collaborations between university laboratories. Fortunately, we have able researchers and scientists to champion the efforts. The consortium approach has increased the whole genome sequencing (WGS) capacity for current circulating variants and future emerging variants. As viruses constantly mutate, understanding the level of danger posed by a variant can aid in developing appropriate public health measures. This can also improve the workforce’s speed, scale, and quality delivery capabilities. To ensure sustainability, this noble effort by the consortium of laboratories (now we have ten laboratories participating in genome surveillance) should continue to be funded by the relevant ministries.

Alternatively, we must sequence more in targeted clusters and at international entry points to identify and limit the transmission of emerging variants. Monitoring the impact of variants requires robust real-world data collection and analysis of case numbers, admissions, and disease severity. Additionally, we must continuously invest in Research & Development (R&D) sectors to expand our surveillance system’s personnel, expertise, and infrastructure. It allows for deploying new technologies and methods for detecting and responding to future variants and improved access to enhanced geographical representation tools.

Since the beginning of the pandemic, real-time RT-PCR has been used to analyze nasopharyngeal (NP) swabs and other upper respiratory samples. Additionally, respiratory specimens in viral transport media constitute the optimal specimen for SARS-CoV-2 genome sequencing. In early 2021, antigen-based SARS-CoV-2 detection assays, which use anterior nasal swabs for SARS-CoV-2 antigen detection, were used due to the fast turnout time but still have a high rate sensitivity and specificity to detect the presence of SARS-CoV-2 virus [12]. Thus, a protocol extracting RNA from antigen test-derived swabs should be established for WGS.

Although the capacity of laboratories to generate sequencing data has grown significantly, bioinformatic analysis is also becoming challenging in low- and middle-income countries. Many tools designed for sequence assembly and analysis are either ridiculously costly or require an advanced level of computational proficiency. Bioinformatics and genomic epidemiology-trained individuals are relatively new to applied public health sectors and have not been distributed evenly across agencies. Thus, we should create open-source and widely accessible bioinformatics workflows, establish modular channels for data visualization and exploration, and employ cloud computing to improve the scalability and accessibility of bioinformatics analysis. In addition, advancements in integrating genomic epidemiology with conventional epidemiology and developing best practices for promoting open data sharing are also required.

Another alternative that can be used for improving genome surveillance is waste water surveillance [13]. The virus can then be detected in waste water, enabling the detection of the infection of SARS-CoV-2 shed by people without or with symptoms. This allows waste water surveillance to detect the spread of COVID-19 in a community early on. Data from waste water testing contribute to strategies for public health mitigation by providing critical data regarding the incidence of COVID-19 in a community.

Last but not least, the communities comprising both public or private laboratories and clinical research centres must work together to enable the efficient and fast exchange of complex genetic and epidemiological information (e.g., GISAID) on a global scale, which can be utilized for the development of additional diagnostics and vaccines.

 

REFERENCES

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