On April 30, Sindh Minister of Health and Population Welfare, Dr Azra Fazal Pechuho, made a statement declaring that two coronavirus variants first identified in Brazil and South Africa had been detected in the
province. “13 samples were genomically sequenced at the Aga Khan University [AKU],” said Pechuho. “Out of these, 10 were the UK variant and the remaining were South Africa and Brazil variants.”
As the world remains upended by the Covid-19 pandemic, health officials and experts across the globe have been working round the clock to understand the pathogenic contagion. The practice of genomic surveillance or sequencing offers an effective tool for public health experts and officials to propose interventions that minimise the risk of spread and infection.
In the world of public health, genomics allows identification of changes in the fundamental viral structure occurring due to mutations. Genomics, therefore, identifies if different strains — due to the evolutionary characteristics and mutations within a virus — make them resistant to certain drugs. It also detects vaccine efficacy and changes in transmissibility.
Dr Zahra Hasan, professor at the Department of Pathology and Laboratory Medicine at Aga Khan University has been examining the genetic make-up and diversity of SARS-CoV-2 strains since June 2020. “Over the years, we have worked on genomics to try and address drug resistance of different pathogens,” she says. “When the Covid-19 pandemic started, we were well equipped to begin research into the novel virus. We compared our existing knowledge of the coronaviruses to the novel strain to understand the differences.”
Identification of different strains is an important task in order to interpret if the virus has a systematic advantage to survive and reproduce in a given population and environment.
Genomic sequencing can identify variants of viruses which can help in designing intervention measures to stop their spread. However, Pakistan is still only in the nascent stage of developing such capability
“As the virus mutates and evolves, some strains acquire a selective advantage,” explains Dr Hasan. “The protein gets modified and it binds more strongly, easily entering the human cells. This way, you have more viruses in the cell, resulting in more transmissions.”
Studying the genetic code through a robust genomic surveillance programme is crucial in detecting more lethal variants. The UK variant B.1.1.7 is a case in point. Identified in December 2020, it was detected in the middle of a lockdown due to an unexpected increase of Covid-19 cases in the south east of England: retrospective genomic analysis traced the variant to be first identified in Kent.
There were particular mutations detected in the virus which made it easier to infect human cells. This resulted in the variant having higher transmissibility and spreading faster than its predecessors. Similarly, the Brazilian and South African variants show a decrease in vaccine effectiveness.
Dr Hasan points out that not all genetic changes have a pathological effect on the host. Natural variations occurring in the genome (an organism’s complete set of DNA) have resulted in identification of lineages — or families — of virus strains. It is only when a mutation has a selective advantage for the virus that there is an expansion in that particular population. “We have seen this with what is called the UK variant. It has a mutation that increases the replication of the virus,” she tells Eos.
The role of Public Health Labs in Genomic Surveillance
In any crisis, the public relies on the government and an effective policy roll-out to resolve the persisting issues. For this reason, public health labs are vital in conducting surveillance by collecting data to craft suitable measures. The purpose of these labs is to act as the main diagnostic labs for events such as a disease outbreak.
Dr Muhammad Salman, a microbiologist, leads the public health lab at the National Institute of Health (NIH). He says, “The concept of public health labs was predominant for European and American countries, but recently, since 2015-2016 in Pakistan, we have started working on provincial public health labs. This is being done in collaboration with the US Centre for Disease Control and Prevention (CDC).”
In Pakistan, presently, there are four provincial public health labs. There is also a hub in Gilgit-Baltistan and a hub in Azad Jammu and Kashmir. A grant has been approved recently to build 36 labs across the country.
According to Dr Salman, the crucial function of these labs is to look at the epidemiology of the virus. “By using molecular analysis, the dynamics of the disease being studied is investigated, especially in terms of the geographical distribution of cases, tracking the variants and its sources.”
Surveillance methods provide a warning and, therefore, mitigate risks to public health. There are two types of surveillance methods: event-based and indicator-based surveillance. Pakistan is more inclined towards using event-based surveillance.
“When an event occurs, we investigate it, using the laboratory facilities. We then confirm the event,” says Dr Salman. The public health authorities are provided with the diagnostics, and a response is conducted in order to contain the event.
In the case of genomic surveillance, “It is looking at the genetics of the virus,” Dr Salman says. “[This] requires immense expertise, equipment and repetitions before we finalise the results. The whole method of surveillance is observing unusual happenings due to the virus.
Pakistan is still at its nascent phase of a proper genomic surveillance programme. A handful of labs across the country are going full steam ahead to detect changes in the virus, identifying mutated strains. “Currently, there are three centres that are actively engaged with sequencing: AKU, the National Institute of Health and Karachi University,” says Dr Bushra Jamil.
Samples from an area with a sustained high positivity rate, over a long period of time, despite interventions, are investigated to see if there are any changes in the virus that are causing the high infectivity. “For instance, [if there is] unusual clustering of cases in a certain village, town or part of the city, we investigate the strain circulating there and raise public health concerns accordingly.”
An opportunity for research
The method of genomic sequencing plays an important role in understanding the evolution of SARS-Cov-2. GISAID is a global science initiative that provides open access to genomic data of influenza viruses and the coronavirus responsible for the Covid-19 pandemic. More than 1.2 million coronavirus genome sequences from 172 countries and territories have been uploaded by scientists, on this popular online data platform, to understand the spread of Covid-19.
However, a recent study published in March 2021 — conducted by NIH and the Centres for Disease Control and Preventions in the US — reveals that data of full genomes submitted in GISAID and the American National Center for Biotechnology Information is scarce from Pakistan. “So far, there are 350 sequences [from Pakistan] in total available in the global database of GISAID and NCBI,” says Dr Salman.
Genomic surveillance is fraught with challenges for health investigators. One substantial aspect is its cost. “Sequencing is very expensive,” says Dr Bushra Jamil, a leading expert in infectious disease.
Logistics are a major factor behind the high cost of sequencing programs. Reagents that go into the sequencing machines are imported from companies based in the United States and the United Kingdom, namely Illumina and Oxford Nanopore Technologies respectively.
Correspondingly, the international halt in air travel did not streamline sequencing efforts. “Due to the severity of the lockdowns that took place, the cost of shipments had increased,” says Dr Hasan. “It is also costly to get the samples on dry ice. And since sequencing materials are in high demand right now, there is also a general shortage worldwide,” she adds.
Dr Salman outlines the tedious process of testing virus cases. “It is impossible to sequence every positive case. It is time-consuming; getting the results takes two, three days and every sequence costs between 40,000 to 50,000 rupees.
Pakistan is still at its nascent phase of a proper genomic surveillance programme. A handful of labs across the country are going full steam ahead to detect changes in the virus, identifying mutated strains. “Currently, there are three centres that are actively engaged with sequencing: AKU, the National Institute of Health and Karachi University,” says Dr Jamil. The field of bioinformatics is also relatively new, which poses the pressing challenge of “finding well-trained human resources and experts to study and analyse the situation,” she tells Eos.
Dr Salman says, “Covid-19 is offering us an opportunity to build on our laboratory capacities and to diagnose viruses. We are in the works to establish a national consortium for genomics with other labs. AKU, NIH and KU are already confirmed to be a part of it. It will include four to five labs across the country.”
However, experts are of the view that the pandemic is also an opportunity for a developing country like Pakistan to further its research and sequencing efforts. Faisal Mahmood, professor of health diseases at AKU and involved in Covid-19 response, emphasises the varied response of the research. “At AKU, the research related to Covid-19 is multifaceted, looking at clinical care, vaccine trials and the psychological impact of Covid-19. There are also studies regarding genomics which have now come in,” he adds.
Dr Salman echoes his views. He says, “Covid-19 is offering us an opportunity to build on our laboratory capacities and to diagnose viruses. We are in the works to establish a national consortium for genomics with other labs. AKU, NIH and KU are already confirmed to be a part of it. It will include four to five labs across the country.
“With the help of this consortium,” Dr Salman continues, “in collaboration with the World Health Organization (WHO), there will be a criteria for prioritisation of the specimen established. And we will be aiming to sequence 15-20 samples a week. It is very critical and selective. We are in the process of getting things working in a streamlined approach,” he tells Eos.
According to Dr Hasan the consortium “will be a national effort, which will facilitate genomic epidemiological surveillance. This will then help inform us about the kinds of pathogens circulating in the country and help understand disease transmission.”
Cohesive policy, interventions and the significance of inoculation drive
While sequencing helps to track the virus — knowing its whereabouts — the policy interventions still remain the same. The foremost concern with identifying the strain is related to its transmission. An increase in transmissibility means that stricter measures need to be implemented to avoid deaths and overburdening of the health system.
Lockdown measures have also been put in place in Pakistan. According to the Oxford Covid-19 wGovernment Response tracker — a tool developed by Oxford University in understanding policy measures based on 20 indicators — Pakistan’s stringency level between April 1, 2021 till May 7, 2021 stands at 56.02. Whereas this shows that, policy-wise, the country is adequately stringent, there are on-the-ground measures that demand scrutiny.
Tanyah Hameed, a researcher at Oxford University says that the stringency level indicated is “not a measure of compliance or implementation on the ground, the evidence for which is variable.” Hameed says, “In July 2020, the government of Pakistan transitioned to ‘smart lockdowns’, instead, by restricting non-essential business and internal movement in containment areas.” Nationwide restrictions are being put in place due to the onset of the third wave of the pandemic.
“Going forward, Pakistan will need to continue working on a robust pandemic response plan while also ensuring sufficient resources to implement this,” says Hameed. “Pakistan faces unique challenges due to a large informal economy, limited financial support from the government, and varying success in implementation and compliance with standard operating procedures [SOPs]. The pandemic response must address these specific aspects, while building on the lessons learned from the past year,” she says.
Furthermore, Pakistan cannot afford an overwhelmed situation as such with a weak healthcare system in place. “When a higher number of people are infected with SARS-Cov-2, even a small proportion of them falling sick becomes very large, putting more burden on health infrastructure”, says Dr Hasan. If the number of incoming cases are doubled or tripled, the healthcare system will be choked, according to Dr Salman.
Sequencing work has never been more critical for health investigators when it comes to vaccine research. However, a successful mass inoculation drive is indispensable in containing the spread of the virus. The Covax programme promises to supply 45 million vaccine doses to Pakistan by the end of 2021. Additionally, four million doses from China were also procured in April. With a population of 220 million, Pakistan has so far vaccinated only slightly more than two million. This is the lowest rate of vaccination in South Asia. In the most recent development, formulation and packaging of the Chinese-made Cansino Bio vaccine, Convidecia, has begun at the NIH.
“Unfortunately, there is a general shortage of vaccines worldwide,” says Dr Hasan. “We did a good job starting vaccination from February onwards, at least. But we need to tackle the underlying issues, including vaccine hesitancy.”
While there is regional hysteria over watching India struggling to breathe, it is too early to detect if a similar situation is to emerge in Pakistan. For health experts, epidemiologically, Pakistan is not in that situation and the system is not overburdened.
According to Professor Mahmood, “We have a little more foresight on how to progress.” Further observation of data is necessary to reach a conclusion. It is still too early to analyse the future outcomes.
The writer is an independent journalist and graduate in Modern South Asian Studies from the University of Oxford.
She tweets at @hajiramirza
Published in Dawn, EOS, May 16th, 2021