The Novel Coronavirus Variants and India’s Uncertain Future

 The number of COVID-19 cases in India increased at a relatively slow pace after the first case was recorded on January 31, 2020. Daily cases peaked at about 98,000 cases around September 15, declining steadily for five months thereafter. A month into 2021, it seemed possible that India’s experience would be unlike those of the US or Brazil, both of which saw multiple waves of the disease and recorded many deaths within the past year. Not any longer. Since the middle of February, 2021, when daily infections first began to rise, the numbers of daily cases have risen more steeply than they did at any point in the previous year. While the state of Maharashtra dominates case counts at the moment, the numbers of infected all across India continue to rise inexorably, in the classic pattern of a second wave. 

       COVID-19 is caused by the SARS-CoV-2 virus, a member of the coronavirus family. Viruses have been referred to as a “piece of bad news wrapped up in a protein” by the biologists Jean and Peter Medawar. This phrase describes both the shell of protein molecules that protects the genetic material of the virus, as well as the genetic material, in this case a single RNA molecule, the “bad news”. This molecule contains everything the virus needs to copy itself once it attaches to, and then enters, a living cell.

The variants

With this background, here’s a guess for the first wave of COVID-19 in India. This was primarily led by the major Indian cities, Mumbai and Delhi among them, and to a lesser extent somewhat smaller urban areas. Infections during this wave were dominated by a small number of variants that behaved roughly the same way, defining what is called a strain of the virus. The conditions surrounding the lockdown ensured that the disease spread relatively slowly outside these areas. This can be attributed to the relatively slow opening up of the country after about August, 2020 and some reasonable level of compliance with restrictions on public gatherings and masking in the months after that.

Where the virus spread outside the major cities it spread silently, aided by gaps in public health and mortality surveillance. An overall younger population in rural India, as well as lower densities or people, may have helped reduce the impact of the disease. Some prior immunity may have also played a role, although it is hard to square this possibility with what we are seeing currently.

Extrapolating from the recent seroprevalence survey results, we can estimate that between 30-40% or so of India had been infected by the end of January 2021. This is an estimate confirmed by our own models. It is far from the numbers of 60% or more that some models have suggested.However the numbers of those infected should vary greatly across India. The fraction of those with a prior infection is likely in the neighbourhood of 50% or more in major Indian cities while being at least 10-20% lower in rural India. Such numbers would suggest that a large fraction of India still remains susceptible to infection by the original strain. Why did cases begin to rise across India since the middle of February? Certainly, increased laxity played a role. Across the board, fatigue with anti-COVID measures seems to have come to a head by January, once the festival season in November and December did not lead to a spike in cases. (To hope that the new year would usher in normalcy, especially in the background of steadily decreasing case numbers, was perhaps natural.) But even granted that much of India remained to be infected by January of 2021, would that account for the pace of the current rise?

Almost certainly, no. Variants are the most likely answer. Globally, three significant VOCs have been identified, informally associated with the name of the country where they were first noted. They are referred to as the “UK” (B.1.1.7), the “South Africa” (B.1.351) and the “Brazil” (P1) variants, with the terms in brackets being their formal names. Some variants are specific to regions of India, including one called B.1.36, found to be present in a good fraction of cases tested in Bengaluru. The specific mutation carried by the B.1.36 variant, called N440K, is widespread in cases from the southern states. Although data is skimpy, there is some evidence that the B.1.36 variant may be responsible for some reinfections. The B.1.1.7 variant currently dominates new cases in Punjab.

Another variant, recently named B.1.617, figures prominently in the sudden increase of cases in Maharashtra. This variant contains two specific mutations, called E484Q and L452R. Both these mutations alter the spike region, allowing it to bind more easily to cells. This variant appears to spread more easily between people. But more worryingly, recent studies show that the L452R mutation is also capable of immune escape, dodging both antibodies generated by a prior infection or a dose of vaccine as well as other forms of immunity that do not rely on antibodies. That the circulation of the new, potentially more infectious variants is responsible for the spike in cases after January 2021 seems increasingly inescapable. The parameters that enter models of how cases might increase now need to be changed by unrealistic amounts to account for the current rise. Beyond a point, the conservative assumption of continuity from the past must be abandoned.