The Recent Rise of Indian Covid-19 Cases Display The Dangers Of SARS-CoV-2 Variants

(Posted on Friday, April 23, 2021)

In mere weeks, the second wave of Covid-19 to hit India has gone from bad to worse. At the beginning of March, seven-day averages in India were around 15,000 cases per day. By late April, the rate reached almost 300,000. Today, infection numbers are spiraling out of control. The new B.1.617 variant, while not the only contributing factor, is likely the driving force behind the surge, displaying for all to see the dangers of the mutant SARS-CoV-2 variants circulating in India and around the world.

After a modest increase in cases last summer, infection rates dropped and remained low, raising hopes that India might escape the disastrous fate of similarly populous countries like the United States and Brazil. It was widely believed that the higher temperatures of the spring months, which hover around 90 degrees Fahrenheit in major metropolitan areas, would slow the virus and keep people safely outdoors. But despite the heat, case numbers climbed to heights never before seen. This suggests not only that the summer won’t offer a reprieve, but also that the new variants are likely far more contagious than previous strains.

In addition to the B.1.617, which I described in detail in a previous article, a number of strains with additional mutations are also circulating that are currently less prevalent, but still cause for concern. These mutations, which are heavily concentrated in the N-terminal and receptor-binding domains of the spike protein, likely make their respective variants more resistant to convalescent sera and vaccine-administered antibodies.

Among these mutations is W152L, located in the N-terminal domain, which is thought to be a neutralizing antibody binding site due to its high antigenicity. Mutations to this area could reduce neutralization capability and make the virus more resistant to convalescent sera and vaccines. Another mutation, V382L, is also located in the receptor-binding domain. The variants we’ve seen so far don’t usually have many mutations in this region, which is a target site of potential antibody therapies. This mutation may work against that prospect, making the virus less susceptible to neutralizing antibodies.

Further mutations found in India include N450K, which is also found in the Belgian B.1.214 variant; S477N, which is also seen in the New York B.1.526 variant; and a series of others, all heavily concentrated in the receptor-binding domain. Mutations to this region affect both binding to human ACE2 receptors and potential resistance to neutralization.

All these mutations, in addition to the rise of the B.1.617 variant, display the swift capability of variants growing out of control, possibly foreshadowing what’s to come in other countries. Take the United States for example. The B.1.1.7 variant is circulating widely throughout the United States, as is the South African B.1.351 variant. In addition, there is an infectious New York B.1.526 variant and a Californian B.1.427/9 variant. All the while in Oregon, a strain of B.1.1.7 has been detected that has a new addition of E484K, or EEK!, which confers greater immune resistance to the virus. How many variants can the United States reasonably deal with before our Covid-19 case counts are as out of control as those in India?

One recent article claimed that first-generation Covid-19 vaccines protect against the New York variant. But a deeper analysis into the referenced study reveals that protection may last only as long as neutralizing titers do. The study found that B.1.526 virus is neutralized four to five times less for vaccinees in comparison to older strains. In other words, vaccines may cover the New York variant at first, but protection may fade much more quickly than against the wild-type virus. This may well be the case for many of the variants circulating in the United States.

As we have seen with the B.1.617 variant in India and the mutated B.1.1.7 variant in Oregon, SARS-CoV-2 will only continue to mutate. For the general population, this means being vaccinated is not necessarily a reason to go out and live as normal again. Though any protection against the variants is better than none, it is no time to relax. We must remain vigilant in our Covid-19 mitigation efforts if we are to avoid the fate India currently faces.