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The Hindu 14.6.21

🛑If there is one tool in the COVID-19 pandemic response, which India has been slow in adoption and has used sub-optimally, it is genomic sequencing. An effective COVID-19 pandemic response requires, inter alia, keeping track of emerging variants (total 10 till now including variants of interest and concern) and then conducting further studies about their transmissibility, immune escape and potential to cause severe disease. Therefore, genomic sequencing becomes one of the first steps in this important process. When the success of the United States and the United Kingdom in containing the virus is discussed, a lot of credit is being given to the increasing vaccination coverage; however, it is often forgotten that alongside, these countries have scaled up genomic sequencing, tracked the emerging variants and used that evidence for timely actions. India seems to be faltering on both expanding vaccination coverage and genomic sequencing. Unfortunately, there is not enough attention to scale up genomic sequencing, which as per the original plan was supposed to cover 5% of confirmed COVID-19 cases.

Though the procedural steps such as setting up the Indian SARS-CoV2 Genomic Consortia, or INSACOG have been taken, the sequencing has remained at a very low level of a few thousand cases only. It is no surprise that we understand the Delta variant (B. 1. 617. 2, the original lineage B. 1. 617 was first reported from Maharashtra, India in October 2020) far less than the Alpha variant (B. 1. 1. 7, first reported from Kent, England in September 2020) reported just a month before Delta. The challenge of insufficient genomic sequencing is further compounded by the pace at which data is being shared, especially when the emergence of strains is so vital in tracking and responding to a pandemic. Reportedly, the Indian government took two weeks, from early March — when research scientists submitted information on new variants — to issue a public announcement on the variants on March 24, 2021.

The Delta strain

Amidst this, the release of findings of the Council of Scientific and Industrial Research-Institute of Genomics; Integrative Biology and National Centre for Disease Control and Academy of Scientific and Innovative Research study; tracking variants of SARS CoV-2 in Delhi, on a pre-print server (yet to be peer reviewed) is a welcome change and provides new insights .

Based upon the analysis of nearly 3,600 genomic sequence samples from November 2020 to April 2021, the authors have reported that by April 2021, the Delta variant became the most circulating variant in Delhi and was found in nearly 60% of the samples analysed; is 50% more transmissible than the Alpha variant (which already had 70% higher transmissibility over the ancestral virus); is likely to be associated with high viral load, as reflected by the declining Ct value (for RT-PCR) over the study period and resulted in a higher proportion of breakthrough infection (people already vaccinated getting infected). Based upon these findings, the authors attribute the Delta variant responsible for the pandemic wave (which was fourth for the city state) in Delhi in April-May 2021. However, the authors did not find any difference in severity of disease or case fatality rate due to the Delta variant and suggested the need for further studies.

This is the first detailed study of SARS CoV-2 genomic sequencing data from any Indian State and provides very useful insight on the behaviour and impact of Delta variants. Around the same time, Public Health England (PHE) reported that the Delta variant has become the most common circulating strain in the U. K. , replacing Alpha. The early data from the PHE has interpreted that the Delta variant may be responsible for more severe disease and higher rate of hospitalisation compared to all previous variants. A week before this data, on May 27, the PHE reported that the effectiveness of a single dose of vaccine (amongst symptomatic patients) was lower against the Delta strain. On June 3, medical journal The Lancet published research findings from laboratory studies which examined the neutralising capacity of antibodies from individuals vaccinated with two doses of Pfizer-BioNTech, which was nearly 5. 8 fold lower against Delta variants and 2. 6 fold less against the Alpha variant, when compared with the ancestor virus.

Our scientific knowledge and understanding about emerging strains is going to be the key to deploy public health interventions (vaccines included) to fight the pandemic. The emerging variants — with early evidence of higher transmissibility, immune escape and breakthrough infections — demand continuous re-thinking and re-strategising of the pandemic response by every country. Scientific research would make a difference only if it results in informed policy decisions. There are a few steps Indian policy makers should consider as urgent.

The steps ahead

First, India needs to scale up genomic sequencing, across all States. There should be sufficient and representative samples collected for genomic sequencing to track district-level trends in circulating variants. More genomic sequencing is needed from large urban agglomerations . A national-level analysis of collated genomic sequencing data should be done on a regular basis and findings shared publicly.

Second, the Indian government needs to invest and support more scientific and operational research on vaccine effectiveness. The data should be analysed on a regular basis and should include various stratifiers such as age, gender and comorbid conditions, etc.

Third, there are early indications of immune escape and reduced vaccine effectiveness against the Delta variant (especially after one shot). India, till the end of May, has administered at least one dose of vaccines to 43% of people older than 60 years and 37% of those older than 45 years. Does it mean the focus of vaccination should be to achieve saturation coverage of the high risk population, with both shots, than one shot to everyone? Does it mandate a need for a reduced gap between two doses of Covishield for anyone older than 45 years? Should vaccination of those 18-44 years be put on hold till vaccine supply is assured or should it be done only in districts where the Delta strain is predominant? These are the questions which experts need to deliberate and come up with the answers.

The data from genomic sequencing has both policy and operational implications. The State and district officials should engage the epidemiologists in coming up with practical and operational implications and strategies. As Indian States plan to open up after COVID-19 restrictions, the settings with predominantly the Delta variant in circulation (which has higher transmissibility) should aim for far stricter adherence to COVID appropriate behaviour, in public places.

Use evidence for actions

Continuation of many unproven and ineffective therapies in COVID-19 treatment guidelines is proof that India is not quick in adopting evidence to the practice. There is a need for rapidly expanding genomic sequencing, sharing related data in a timely and transparent manner, and understanding of the impact of new variants on transmissibility, severity and vaccine effectiveness. The only assured way to fight the pandemic is to use scientific evidence to decide policies, modify strategies and take corrective actions. As India prepares for the third wave, increasing genomic sequencing and use of scientific evidence for decision making are not a choice but an absolute essential.

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1.Inter Alia (Adv)-among other things.

2.Scaled Up (Phrasal Verb)-to increase the size, amount, or importance of something.

3.Faltering (Adj)-losing strength or momentum.

4.Integrative (Adj)-combining two or more things to form an effective unit or system. एकीकृत

5.Agglomerations (N)-a large group of many different things collected or brought together.

6.Predominant (Adj)-having superior power and influence. प्रभावी, प्रमुख

7.Deliberate (Adj)-done consciously and intentionally.

8.Epidemiologists (N)-a medical scientist who studies the transmission and control of epidemic diseases. महामारीविद्

🛑Over 17 months after WHO first reported a cluster of cases of pneumonia of unknown cause in Wuhan, China, scientists are yet to determine with certainty how the SARS-CoV-2 virus emerged. Much like other viruses, SARS-CoV-2 too could have a natural origin or somehow escaped from the coronavirus research lab in Wuhan, the epicentre of the COVID-19 outbreak. With no hard scientific evidence available to confirm the lab leak hypothesis, there are some scientific leads that support a natural origin. If it is a zoonotic spillover, the virus could have either directly crossed over from bats to humans or through an intermediate host. But till date, neither the bat species that hosts the SARS-CoV-2 virus nor the intermediate host has been found. China’s secrecy and delay in reporting the Wuhan outbreak and in finding the natural host or the intermediary have further fuelled the lab spillover hypothesis. Finding the host animal can be daunting. While the civet cat and dromedary camel were quickly identified to be the intermediate hosts of SARS and MERS, respectively, it took years to identify the horseshoe bat that harbours SARS virus strains. To date, a complete Ebola virus has never been isolated from an animal source.

If the virus had been bioengineered, the genome sequence would carry tell-tale signs. But scientists have not found any signature of genetic manipulation. While a particular site (furin cleavage) on the SARS-CoV-2 spike protein that allows the virus to infect the cells has been cited as evidence of bioengineering, the fact is that it is not unique to SARS-CoV-2. A combination of nucleotides in the furin cleavage site that encode for a particular amino acid — another feature that is forwarded as supporting laboratory manipulation — too has been shown to be not unique. For instance, the nucleotide combination encoding for the amino acid is present in other sites of the SARS-CoV-2 virus and in the 2003 SARS virus. The possibility of SARS-CoV-2 evolving via cell culture appears bleak as scientists have found the virus losing features key to transmission and virulence unless cultured using new methods. Reports of three Wuhan lab researchers falling ill in November 2019 by itself does not prove a lab leak hypothesis. There is no evidence that they were infected with the SARS-CoV-2 virus, and even if they were, it is necessary to prove that it happened from inside the lab. In the absence of conclusive evidence to support either hypothesis so far, a thorough investigation is needed. While the inquiry by the U.S. intelligence might provide clues, a scientific investigation is more likely to help reach closure; China’s cooperation, therefore, becomes vital and politicising the virus origin is not going to help.

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1.Outbreak (N)-a sudden rise in the incidence of a disease.

2.Zoonotic (Adj)-(of a disease) able to spread from animals to humans.

3.Spillover (N)-an effect that results from a problem spreading.

4.Daunting (Adj)-seeming difficult to deal with in prospect; intimidating. कठिन, चुनौतीपूर्ण

5.Civet (N)-a small animal like a cat from Africa and southern Asia. गन्धबिलाव

6.Bioengineered (V)-create or carry out using bioengineering techniques.

7.Virulence (N)-the severity or harmfulness of a disease or poison.

8.Hypothesis (N)-a supposition or proposed explanation made on the basis of limited evidence as a starting point for further investigation. परिकल्पना, अनुमान

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🛑Over 17 months after WHO first reported a cluster of cases of pneumonia of unknown cause in Wuhan, China, scientists are yet to determine with certainty how the SARS-CoV-2 virus emerged. Much like other viruses, SARS-CoV-2 too could have a natural origin or somehow escaped from the coronavirus research lab in Wuhan, the epicentre of the COVID-19 outbreak. With no hard scientific evidence available to confirm the lab leak hypothesis, there are some scientific leads that support a natural origin. If it is a zoonotic spillover, the virus could have either directly crossed over from bats to humans or through an intermediate host. But till date, neither the bat species that hosts the SARS-CoV-2 virus nor the intermediate host has been found. China’s secrecy and delay in reporting the Wuhan outbreak and in finding the natural host or the intermediary have further fuelled the lab spillover hypothesis. Finding the host animal can be daunting. While the civet cat and dromedary camel were quickly identified to be the intermediate hosts of SARS and MERS, respectively, it took years to identify the horseshoe bat that harbours SARS virus strains. To date, a complete Ebola virus has never been isolated from an animal source.

If the virus had been bioengineered, the genome sequence would carry tell-tale signs. But scientists have not found any signature of genetic manipulation. While a particular site (furin cleavage) on the SARS-CoV-2 spike protein that allows the virus to infect the cells has been cited as evidence of bioengineering, the fact is that it is not unique to SARS-CoV-2. A combination of nucleotides in the furin cleavage site that encode for a particular amino acid — another feature that is forwarded as supporting laboratory manipulation — too has been shown to be not unique. For instance, the nucleotide combination encoding for the amino acid is present in other sites of the SARS-CoV-2 virus and in the 2003 SARS virus. The possibility of SARS-CoV-2 evolving via cell culture appears bleak as scientists have found the virus losing features key to transmission and virulence unless cultured using new methods. Reports of three Wuhan lab researchers falling ill in November 2019 by itself does not prove a lab leak hypothesis. There is no evidence that they were infected with the SARS-CoV-2 virus, and even if they were, it is necessary to prove that it happened from inside the lab. In the absence of conclusive evidence to support either hypothesis so far, a thorough investigation is needed. While the inquiry by the U.S. intelligence might provide clues, a scientific investigation is more likely to help reach closure; China’s cooperation, therefore, becomes vital and politicising the virus origin is not going to help.

------------------------------------------

1.Outbreak (N)-a sudden rise in the incidence of a disease.

2.Zoonotic (Adj)-(of a disease) able to spread from animals to humans.

3.Spillover (N)-an effect that results from a problem spreading.

4.Daunting (Adj)-seeming difficult to deal with in prospect; intimidating. कठिन, चुनौतीपूर्ण

5.Civet (N)-a small animal like a cat from Africa and southern Asia. गन्धबिलाव

6.Bioengineered (V)-create or carry out using bioengineering techniques.

7.Virulence (N)-the severity or harmfulness of a disease or poison.

8.Hypothesis (N)-a supposition or proposed explanation made on the basis of limited evidence as a starting point for further investigation. परिकल्पना, अनुमान

--------------------------------

🛑

Poornima and Ashok, 80-year-old parents of two and grandparents of three, have been hunkered down in their Mumbai apartment for a year. When a COVID-19 vaccine became available in March 2021, they went to the local hospital to get their first dose of the Serum Institute of India’s Covishield vaccine — the vaccine that was supposed to save the world. Seeing long lines and not wanting to risk being infected while waiting to be vaccinated, they returned home. This happened again the next day before a very helpful staff member of the World Health Organization (WHO) stepped in to help, taking them to a health centre early one morning and making sure they did not have to wait in a line to get vaccinated. This played out again in April 2021 for their second dose. This couple was lucky.

Where the focus must be

As we look ahead to what is promised to be a transition from a lack of vaccine supply to one of greater availability, the plan must be to prioritise people like the two octogenarians in Mumbai — older adults who remain unvaccinated, and very much at risk. Ensure we vaccinate them before we open vaccination to younger adults. This would prioritise people based on the risk of severe disease, and need — essential principles if we plan with justice in mind.

Local governments and municipalities should also prioritise vaccines for the historically marginalised by focusing through the lens of equity and justice. What does it mean to focus through a lens of equity and justice? It would mean ensuring that the vaccine roll-out does not result in avoidable differences in vaccine uptake — and hence preventable disease and death — between marginalised groups and the rest of the country. It would require prioritising the poor, religious minorities, socially disadvantaged castes, Adivasi communities, those living in remote areas, and women.

In Chhattisgarh

One example of an equity-focused vaccination plan came from the Chhattisgarh government. The plan prioritised ration card holders, specifically because they are poor, and often live in multi-generation, larger households, putting them at higher risk of infection. They also often lack access to mobile phones and the Internet, which are necessary to register for vaccination. Though the High Court asked that the plan be modified to provide vaccines to the general public alongside ration card holders, we would propose prioritisation of the marginalised when vaccine supply is limited in order to minimise the risk of severe outcomes due to COVID-19. WHO’s strategic advisory group of experts on immunisation recommend prioritising sociodemographic groups at significantly higher risk of severe disease or death (for vaccination) in the context of limited supply. We should ensure that we remove barriers to vaccination for the most vulnerable in India to minimise preventable disease and deaths.

India depended, and continues to depend on the AstraZeneca vaccine because it was stable in a refrigerator for longer periods than mRNA vaccines. Presumably, this was so that vaccines could be made available where freezers do not exist. But it also enables the vaccine to be transported in vaccine carriers, and taken to the people where they are. In Indian villages, Accredited Social Health Activists (ASHAs) and Auxiliary Nurse-Midwives (ANMs) have vast experience and expertise with campaign-style pulse polio vaccination and newborn vaccination; their expertise should be harnessed to take vaccines to villagers.

Urban slums and neighbourhoods, where socially disadvantaged caste and community groups, and migrants from Adivasi communities often reside, have poor access to and low levels of trust in the health-care system. Vaccines should be provided in camps or door-to-door in such areas. Appropriately, local governments are considering providing vaccines to older adults in door-to-door campaigns. A similar approach — vaccination camps where people live and work — could also greatly enhance vaccine uptake among essential workers and the poor. We need to ensure that those who work for daily wages are able to get the vaccine without having to forego work or pay.

Adivasi communities also reside in remote and forested areas that are also being ravaged by waves of death, presumably due to COVID-19; vaccine distribution should be prioritised to districts where they live. In India today, perhaps the most marginalised are religious minorities, and, specifically, poor Muslim communities. Vaccine distribution should also be prioritised to Muslim-dominated tier-3 towns across the country. An explicit focus on justice would prioritise the engagement of trusted spokespeople to engage in effective risk communication with vulnerable and marginalised communities, and to build trust in the vaccine.

Equity and justice

Local planning will need to go hand-in-hand with a refocus on equity and justice at the national and global levels as well. Nationally, people have recognised that digital apps for registration are a recipe for inequity along age, gender, and economic dimensions, and reports have highlighted the plight of those on the wrong side of the digital divide. CoWIN data that are available to date show that vaccination rates have been inequitable between tribal and non-tribal areas, for example. Going forward, let us focus on first doing no harm — get people vaccinated to save the lives most at risk. At the national level, the recent decision to procure vaccines centrally and make COVID-19 vaccines available free of cost through the public system goes a long way towards ensuring equity and justice. WHO has been tireless in its call for the urgent need for vaccine equity at the global level. In an ideal world, vaccines would be procured and equitably distributed to countries based on need through the COVAX facility. But instead, wealthy countries have once again, as during the 2009 H1N1 flu pandemic, secured more doses than they need to vaccinate every member of their population, and even pre-ordered booster doses. This leaves only poor countries to be dependent on supplies through COVAX, and they find themselves at the end of the line. This is a wake-up call for setting up vaccine distribution systems with equity in mind for the next pandemic. At this time, unfortunately, poor countries are at the mercy of the European Union and the United States, who need to donate vaccines now. They need to vaccinate the world alongside their own communities — they need to vaccinate grandparents everywhere alongside children and adolescents within their borders. Work during the 2009 H1N1 flu pandemic showed that willingness among the U. S. public to donate vaccines to the poorer countries was appreciable. Today as well, surveys show that U. S. public support for immediate donation of COVID-19 vaccine exists. Doses need to be donated to COVAX now so that they can be distributed to countries based on need. Every life matters in this world and world leaders need to follow the lead of WHO and embody global solidarity in this pandemic.

Refocused, rejuvenated local, national, and global vaccination campaigns are possible. Let us ensure that we plan now so that we get those shots in arms when they are available. Let us get to work in India.

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1.Hunkered Down (Phrasal Verb)-to stay in a place for a period of time.

2.Stepped In (Phrasal Verb)-become involved in a difficult situation, especially in order to help.

3.Octogenarians (N)-a person who is between 80 and 89 years old. अस्सी बरस का

4.Sociodemographic (Adj)-of, relating to, or involving a combination of social and demographic factors.

5.Be Harnessed To (Phrase)-to be closely involved with someone or something.

6.Ravaged (Adj)-severely damaged; devastated. तबाह

7.Explicit (Adj)-clear and exact. स्पष्ट

8.Plight (N)-a dangerous, difficult, or otherwise unfortunate situation. दुर्दशा

9.Wake-Up Call (N)-a warning to take action concerning something that was overlooked or neglected.

10.Shots In Arms (Phrase)-something th

t quickly makes a bad situation much better.

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