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No country in the world is fully prepared to handle a pandemic

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We will have to learn to live with COVID-19 at least for some time until we have the right vaccine and cure. Suresh Subramani, Global Director, Tata Institute for Genetics and Society (TIGS), further talks to Akanki Sharma about potential treatments for COVID-19 and human’s co-existence with it, amidst others… 

The pandemic has hit the global healthcare system hard. What according to you will the future look like for the industry? 

First, with extreme social distancing, lockdowns and fear of getting COVID-19, other routine health examinations and procedures are being seriously delayed, and likely neglected. This has a cost, both for the medical professionals and to the general public seeking healthcare. Second, there are effects of this also in terms of transmission of other diseases – if most resources and attention are devoted to COVID-19, then other disease control measures, such as vector control for malaria and dengue or vaccinations, are being affected and these will also add to the financial impact. Third, the financial burden faced by people, especially the poor, will impact their healthcare spendings over other immediate priorities, such as food and shelter. Finally, as a good portion of GDP goes towards recovery from COVID-19, in a zero-sum game, that leaves less for another healthcare spending. The companies that will flourish are those lending a hand to solve the COVID-19 crisis directly or indirectly.

Shed some light on the basic biological aspects of coronaviruses, especially SARS-CoV-2.

SARS-CoV-2 belongs to a family of viruses known as coronaviruses, which derive their name from their appearance under an electron microscope. The spike protein present on the surface of SARS-CoV-2 forms a crown or a halo around it – thus being the inspiration behind the term ‘corona’. Viruses need a host – a live cell to replicate in and produce more copies for viral spread. The SARS-CoV-2 virus is no different, it also needs a host. With a size of 125 nanometers and a genome of 30,000 genetic bases called nucleotides, it is one of the larger replicating viruses with an RNA and not a DNA genome. Upon viral entry into host cells, because this RNA can be read directly by the cellular protein synthesis machinery and an efficient RNA replication mechanism encoded by the virus, SARS-CoV-2 can rapidly infect and take over a host cell.

Many RNA viruses have a high error or mutation rate when copying themselves because of the viral enzyme that replicates RNA is error-prone. However, an interesting fact about coronaviruses is that they are also one of the few RNA viruses with an inbuilt error-correcting mechanism that protects them from accumulating harmful mutations. This is potentially good news for vaccines and drugs because new variants of the virus that can become resistant to drugs or enhance the virulence of the virus will happen at a lower frequency.

In what terms does SARS CoV-2 relate to past epidemics, and what can we expect in terms of long-term co-existence with such viruses?

SARS-CoV-2 is likely to stay and exist in the population for a number of years because it is a new virus that humans have not seen. It has a long asymptomatic phase, spreads quickly, the antibody response to it is slower than for many other viruses, and it has a low mortality rate. These properties allow it to evade each detection due to lack of early symptoms, even while the infected person is shedding virus and spreading it. Additionally, the low mortality rate allows it to spread further because more infected people will be moving about and disseminating the virus.

Relative to SARS and MERS, also caused by coronaviruses, it is less lethal, which will permit it to adapt better to humans and last longer.
Finally, we have only seen short-term immunity against other coronaviruses (up to two years) and not life-long immunity. So, if there is a vaccine, we will need periodic boosters.

Tell us about the potential treatments and the different types of vaccines that can be explored to combat COVID-19?

Several drug trials (more than 1,000) are being conducted in the search for an effective treatment against COVID-19. Many of these are re-purposed drugs, i.e. drugs that are already in use or have been investigated for similar infections or other conditions. These drugs may target either the virus life cycle inside the host, or a host function that the virus needs, or boost the host’s innate and/or adaptive immunity. Since we already know that these re-purposed drugs are relatively safe and are effective against certain infections, these may be the ones that are initially approved and deployed for COVID-19.

More than 100 vaccine candidates are also currently in development for COVID-19. These are of different types: whole inactivated, live/attenuated, subunit vaccines against viral proteins, DNA- or RNA-based vaccines, and recombinant viral vectors. It typically takes five to 10 years for a vaccine to be developed, tested and approved. However, with new technologies in place and international collaborations, we could see one for COVID-19 much sooner.

What role can genome sequencing play in this regard?

The sequencing of the SARS CoV-2 genome will tell whether there’s a SARS CoV-2 infection currently. However, there are cheaper ways than doing whole-genome sequencing, such as (a) RT-PCR; (b) what strain is in the person; (c) where this strain could have come from, using epidemiological comparisons with sequenced strains from other parts of the country or world; (d) what the mutation rate is for the virus and whether more virulent mutations are arising in the virus; (e) when a vaccine or drug is available; all these will allow us to detect the cause of viral resistance to these therapies.

With anti-microbial resistance being a global threat, can it also lead to a pandemic in future like the current one? If yes, what steps can be taken ‘at the moment’ to prevent such a  catastrophe in future?

Yes, there have been bacterial and viral epidemics in the past — cholera, plague, Spanish flu and so on. Bacterial multi-drug resistance is already an epidemic (e.g. MDR TB), that could, if uncurbed, turn into a pandemic. Very few new antibiotics have been developed in the past 50 years, and with increasing globalisation and higher people density, diseases can spread far more easily today than they did 50 or 100 years ago. In general, as is seen with COVID-19, no country in the world is fully prepared to handle a pandemic. People need to understand that spending on preparation for a pandemic is like spending on insurance, where the goal is to avoid a catastrophe.

How can we build India’s capabilities in research for undertaking genome sequencing projects?

Invest for the long-term (i.e. two to three decades) in the best scientists, use the best instrumentation and technology, encourage and build the data sciences and bioinformatics pipeline. It needs a national vision and strategic road map, but Indian scientists and medical professionals are fully capable of delivering.

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