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COVID-19 cases across India are soaring once again, but more blatantly, boisterously this time. It becomes important to understand the gravity of the situation. What caused this sudden rise in COVID-19 cases? What must be done to tackle it? And what can be done to prevent it in future?
The answer to what must be done is complicated and is based on a major imbalance between the demand and supply of major public health resources. But we may look into the chronology of the events to help understand this sudden spike and a way forward dealing with such spikes.
Various parts of the country – including Delhi (56%), Mumbai (up to 75%) and Hyderabad (54%) – have reported high seroprevalence. But in spite of the high prevalence of protective antibodies and previous fall in cases, the number of cases in these cities is once again rising quickly. Experts have advanced various explanations, including circulation of the new B.1.617 variant. It has five mutations in the spike glycoprotein, including L452R and E484Q; Variants with L452R have also been found in California and shown to have high transmissibility. Variants with E484Q or E484K have been found to have decreased neutralisation tendency to protective antibodies, i.e. they can escape the immune system more. Notably, a variant with the E484K mutation was associated with a recent surge in Brazil despite high seroprevalence.
India’s genomic sequencing programme has been slow is low, and researchers are still investigating B.1.617’s increased infectivity and immune escape behaviour. But a sudden rise in cases along with a high detection rate of this variant in sequencing, up to 80% in samples from Maharashtra, suggests that it is circulating in the afflicted population.
Densely populated areas in Mumbai, like Dharavi, showed a high seroprevalence of 75% in October. The area also reported no cases in late December 2020. But while cases around the country were still in decline in early February, Mumbai once again began reporting a growing number of COVID-19 cases, and continued into March. The city was quickly followed by the state and then the rest of the country. A similar situation has also been reported from Brazil, where cases started to surge again after a decline, even though Brazil had reported a seroprevalence of up to 76%.
We can understand viral evolution better by contemplating the Darwinian law of survival – ‘the survival of the fittest’. For example, doctors prescribe multiple antibacterial agents to treat bacterial diseases like tuberculosis. This is done to evade the high risk of emergence of fitter bacteria, with drug resistance, when a single antibacterial agent (suboptimal therapy) is used. Similarly, neutralising antibodies to the spike protein, derived from natural infection or a vaccine, and COVID-appropriate behaviour – use of masks, physical distancing, washing hands – are in a sense ‘antiviral’ in that they prevent the spread of disease in a population. So variants of concern may emerge when this ‘antiviral’ response is suboptimal, making the virus resistant (fitter) to either or both the antibodies (increased rate of reinfections) and COVID-appropriate behaviour (increased transmissibility).
Densely populated pockets of the country reported a higher prevalence of protective antibodies and were in line with the rapid fall in cases in these areas. But the virus was still spreading at much lower levels in the susceptible population. On the other hand, the complete lack of COVID-appropriate behaviour across the nation was apparent. This included religious congregations, election rallies and even weddings. A high prevalence of protective antibodies together with a lack of appropriate behaviour would have been a suboptimal ‘antiviral’ response. This would have kept the ‘immune’ population constantly exposed to the virus and created fertile ground for the viruses to select useful mutations under the pressure of protective antibodies.
Researchers have observed another well-established suboptimal ‘antiviral’ response – in patients with compromised immune systems (such as with HIV or cancer) or those who were transferred convalescent plasma. There have been reports of increased viral evolution in these patients, with some harbouring viral particles in the body for months. These conditions have been linked to faster viral evolution. It is important here to highlight the role of vaccines with regard to such patients. Vaccines induce a polyclonal immune response, with some even triggering higher neutralising antibodies and T-cell responses than the natural infection. This has clear implications in strengthening our antiviral response and suppressing emerging variants. So such individuals should be vaccinated promptly to curtail the emergence of new variants.
According to Trevor Bedford, an associate professor of genome sciences at the University of Washington, “The currently observed rate of evolution in S1[footnote]A subunit of the spike protein[/footnote] (in SARS-CoV-2) is rapid compared to the equivalent domain in influenza virus.”
Bedford has also said that its evolution would depend on whether the virus undergoes convergence in its evolution – i.e. mutates until it has a specific set of mutations, and no further. This would suggest, in Bedford’s words, that “SARS-CoV-2 will have arrived at its destination having stacked up all the relevant mutations.” This may mean, then, that we may not observe such waves and that we can easily control the virus’s spread by establishing vaccine-induced herd immunity.
But Bedford said the virus could evolve the other way as well – taking the path of divergence. This is associated with an increased rate of viral evolution and seasonality associated with persistent surges. If this turns out to be true, the virus may continue to evolve and vaccines may need to be modified periodically according to the strain circulating at a given time.
There is also work going on to develop a ‘pan coronavirus’ vaccine – a vaccine capable of eliciting an immune response to the conserved cryptic pockets of different coronaviruses. If successful, this may help tackle current and future variants better as they emerge.
But irrespective of the possibilities and the path the virus takes, the virus is currently evolving and new variants will emerge. This in turn means the current surge could persist for longer and that there could be some more surges in future. If we are to curb its spread and evolution without overburdening our healthcare infrastructure, we must wear masks properly, maintain physical distances and wash our hands properly and regularly.
The government must also ensure that it quickly vaccinates susceptible people (including immunocompromised patients), implements contact tracing and containment exercises, enhances its genome-sequencing programme and helps its population change their behaviour become more COVID-appropriate. Laxity on just these fronts is why we are experiencing a second wave of infections, hospitalisations and fatalities of such magnitude.
Deepanshu Narang is an MBBS student at the Kasturba Medical College, Mangalore.