The race between Coronavirus mutants and COVID vaccines

Random Musing: The increase in transmissibility poses an exponential risk whereas a rise in fatality is just a linear risk.


Representational image (PHOTO: Unsplash)

Till date, three vaccines have been approved globally: Pfizer, Moderna and AstraZeneca vaccines. About 18.9 million doses of one or other of these have been administered in 39 countries. The US alone has so far administered about 7.05 million doses (Bloomberg, January 9, 2021). In addition, there are the Sputnik-V and Sinopharm vaccines already used in Russia, China and a limited number of countries. Israel holds the record for the highest rate of vaccinations, 17.6 doses per 100 people. The Pfizer vaccine has been cleared for use in North America, Europe, and the Middle East. However, for the majority of the global population in Africa, South America, Asia, and Oceania the vaccine rollouts are yet to begin.

As vaccine stocks of Pfizer, Moderna, and AstraZeneca are still limited, and the major chunk have been already pre-ordered by a few rich nations; for the foreseeable future, there will be a highly inequitable vaccine distribution across the globe.

Indian Vaccine Scenario

India has so far granted conditional approval for 2 vaccines: CoviShield and Covaxin.

Dr Gagandeep Kang, a leading vaccinologist in India, took strong exception to the manner in which vaccines were approved in India, especially that of BB's Covaxin.

The major controversies pertain to:

1. Phase-3 trial data conducted outside India (CoviShield).

2. The bridging study conducted with Indian volunteers is based on a small set (CoviShield).

3. Covaxin's approval on 'clinical trial mode' is rather confusing (if and when it's administered, will it be a part of vaccination or that of phase-3 trial?).

4. Efficacy data is lacking (Covaxin) or confusing (60 per cent or 90 per cent, CoviShield). CoviShield-the Indian version of the Oxford vaccine-has been shown to exhibit 60 per cent efficacy after 2 full doses and 90 per cent from a half dose followed by a full dose (The Wire, January 5, 2021). This is rather a very messy efficacy data for CoviShield (AstraZeneca vaccine). But experts opine that though CoviShield's efficacy is confusing, that of Covaxin is altogether missing.

Much more care is needed for approving vaccines for wide usage as compared to drugs. The former is to be used in healthy persons whereas the latter is intended for administration in only sick individuals. For approving a vaccine, three sets of data are very critical: safety, immunogenicity, and efficacy. It seems, for Covaxin, data regarding safety and immunogenicity is available from phase-1/2 studies that have been published as pre-prints (not peer-reviewed papers) but efficacy data would come only after ongoing phase-3 trials are completed and published. Only when the obvious benefits outweigh the possible risks must a vaccine be approved.

That does not seem to be the case for Covaxin. Therefore, relevant authorities have projected it as a 'backup vaccine' or for limited use in 'clinical trial mode.'  Even for CoviShield, several questions remain unanswered. For example, what's the recommended dosage regimen? Two doses separated by 3-4 weeks or 8-12 weeks? Should the second dose be delayed so that more people can be given the first dose as has been done in the UK? Or, is a mixed dosing advisable-AstraZeneca combined with Sputnik-V, as is being considered in England?

Three strong reasons for concern have been cited by some experts (The Wire Science, Jan. 5, 2021):

1. Opaque approval process.

2. Approval for 'clinical trial' mode without efficacy data (for Covaxin).

3. CoviShield's confusing efficacy data.

At least two prominent experts have publicly raised doubts especially about Covaxin: Drs Gagandeep Kang and Shahid Jameel, leading virologists in India.

1. What's the efficacy data?

2. Does Covaxin actually work against the mutant virus (one good reason for its quick approval was the alleged capacity to act against the mutant strain)?

Asian data seems to be lacking for Oxford vaccine as well as Moderna and Pfizer vaccines. Though Ebola and Nipah vaccines were approved without phase-3 trial data, the same relaxation doesn't apply to Covid vaccine. For CoviShield, of course, even though Indian data is limited, the large-scale phase 3 trial results have been peer-reviewed and published in the prestigious journal Lancet (December 8, 2020). It's heartening news that CoviShield is posed to start vaccination campaign across India on January 16, 2021. It would be even more reassuring if the final efficacy and safety date are soon peer-reviewed and published.

Some unsettled questions are also concerning. Can the second dose be delayed and for how long? How long does the immune response after vaccination last? Viruses differ greatly in this aspect. For some viruses, e.g. chickenpox and measles, the immunity lasts for life. For some others, such as MERS and SARS, it may last a few years. For SARS-CoV-2, we're still not sure. But most studies indicate that it may last for a few months to about 6 months.

Therefore, booster shots against COVID-19 maybe required a few years down the line. Or, the vaccine has to be tweaked after a few months/years to tackle mutant strains. Worse still, the vaccine needs to be re-designed afresh, if vaccine escape mutants emerge!

New Coronavirus Strains

As Zeynep Tufekci wrote in The Atlantic (December 31, 2020), "the mutated virus is a ticking time bomb." Comparing the risks posed by the rise in transmissibility versus that in lethality, he says that "a small percentage of a big number can easily be much, much bigger than a big percentage of a small number." Let's look at some data he explained in this article.

Let's assume a virus R-value (basic reproduction rate) of 1.1 and an infection fatality of 0.8 per cent and 10,000 active COVID-19 infections. In this scenario, we may expect about 129 deaths in a month. If the fatality rate increases by about 50 per cent, the number of deaths would then shoot up to 193 deaths in a month. In contrast, let's consider a 50 per cent rise in transmissibility (assuming that fatality rate remains the same). This would lead to a whopping 978 deaths in just a month. Therefore, the increase in transmissibility poses an exponential risk whereas a rise in fatality is just a linear risk. Tufekci's example is based on data from mathematical modelling done by Dr Adam Kucharski, a mathematical epidemiologist based in the London School of Hygiene and Tropical Medicine.

The worrisome development is that, as of January 9, 2021, there're already 90 confirmed cases of UK Covid Strain in India. We may rest assured for the time being, as no variant cases have been detected in Manipur so far. But constant vigil, surveillance, and control measures are warranted for several months more or till herd immunity is achieved through vaccinations in our state.

So, in the meantime, we must not let our guards down and we must still strictly observe the non-pharmaceutical interventions such as the major SOPs of the use of face masks, physical distancing, and hand hygiene and avoidance of 3 Cs: crowded places, close-contact settings, and closed spaces (with poor ventilation).

The silver bullet for Covid-19 is an efficacious, safe, and affordable vaccine and/or drug. But we don't have it yet. But as Derek Thompson writes in The Atlantic magazine (October 12, 2020), there are "bronze bullets abound." The 3 Ws (watch your distance, wear a mask, and wash your hands regularly) and 3 Cs (avoidance of crowded places, closed contact settings, and closed spaces) are some of these bronze bullets. At this critical point of the pandemic, it's we-hoi polloi, common people-who with our (in)appropriate behaviour will determine the trajectory of Covid-19 in Manipur. Once again I humbly appeal to fellow citizens to abide by the 3 Ws and 3 Cs guidelines strictly!

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First Published:Jan. 10, 2021, 1:19 a.m.

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