What is driving the second wave in India?

Understanding the infectiousness of the double mutant variant becomes all the more important as noncompliance to COVID-19 appropriate behaviour is uniformly poor across India. Yet, the surge in cases is seen only in 19 States, and mainly in about a dozen States. In the absence of timely results of such studies, which will help policy making, placing all the blame on people appears to be the easy way out.

With a steady increase in the daily fresh cases since the third week of February, with over 89,000 cases reported on April 2, the seven-day average test positivity rate climbing to 6.8% as on April 2, and with the reproduction number (R0) — how many people each infected person will infect on average — above 1.5 and steadily increasing over the last two-three weeks, the second wave has well and truly begun in many States.

The rate of increase in cases in India during March has been faster than at any other time during the pandemic, which is also reflected in the modelling studies by Indian researchers, including Dr. Gautam Menon, Professor of Physics and Biology at Ashoka University. Modelling suggests that the previous peak in the number of cases (about 98,000) will soon be exceeded.

While the onset of the festival season since the pandemic peaked in mid-September in India, winter, no restrictions on movement, large gatherings, and not-so-good adherence to mask wearing and other non-pharmaceutical interventions did not cause any spike in cases across the country, what is driving the current surge in cases in many States?

The Health Ministry has cited the general laxity among people regarding COVID-19 appropriate behaviour, including mask wearing, and lack of containment and management strategy at the ground level as reasons for the surge in cases. The role of variants, either the imported ones or those that have originated in India, are not seen to be responsible.

Epidemiological triad

But Dr. Giridhara Babu, epidemiologist at the Public Health Foundation of India (PHFI), Bengaluru cites three important factors — the virus, the host, and the environment — constituting the epidemiological triad for the surge in cases in many States. Explaining the contribution of the three factors, Dr. Babu says: “New variants of concern might be in circulation, which is probably more infectious, and some can be an immune escape as well.” The host factors include waning antibodies, not following COVID-19 appropriate behaviour and incomplete vaccination, while the environmental factors include super spreader events and poor compliance with preventive measures. The misconception that vaccination prevents even infection might also be contributing to rising cases.

“We just don’t know enough about the Indian variants to say whether they are more transmissible or more virulent, at this stage. I would personally think, extrapolating from the very high levels of seropositivity in the cities that several surveys have detected across the past several months, that a more transmissible, immune escape variant is responsible,” says Dr. Menon in an email.

In an email, virologist Dr. Shahid Jameel, Director of the Trivedi School of Biosciences at Ashoka University says variants, both imported and home-grown, are increasingly seen but have so far not been linked epidemiologically to the surge. “It is possible that may be the case, but there is no data to either support or negate that possibility,” he points out.

Explaining the tricky question of why no surge was seen between mid-September 2020 to end-February this year despite perfect conditions for the virus to spread wildly, Dr. Babu says the threshold for population immunity cannot be held as a yardstick when the virus is changing or when the immunity is waning. “Any infectious disease will have outbreaks whenever the susceptible pool builds up. Also, there has been the introduction of other variants due to international travel in some parts of the country, which can be more infectious than the earlier strain,” he says.

Why large cities are again witnessing a surge  

Large cities including Mumbai and Pune, which had recorded large infection rates during the first wave, are witnessing a surge. It is unclear if cases in such cities are only in virus-naïve people or if reinfections constitute a significant proportion. “There is no data I know of that is available in the public domain to address this question. Specifically, we don’t know what fraction of these new cases might reflect a new, more transmissible, immune escape variant that is responsible for reinfections,” says Dr. Menon. An ICMR study covering January-October 2020 found reinfection, most likely due to older strains, accounting for about 4.5% of cases.

According to Dr. Babu, in the cities that reported more than 50% of seroprevalence (at least in some parts), resurgence of cases would either suggest that the antibodies are rapidly waning (and are below threshold levels to mount a response) or presence of newer variants.

But Dr. Jameel says that ground reports from Mumbai and Pune suggest that fresh cases are being reported from areas that were spared earlier. “For example, in Mumbai it is from upmarket areas and apartment buildings instead of slums. In Pune also, it is from new areas,” he says.

Will Kerala too see a surge in cases?

While Kerala has still been reporting over 2,000 cases daily, the seroprevalence is only 10-11%, which is half the national average. So a surge in cases seems almost inevitable in Kerala. “Kerala is an unusual case because its case numbers never really dropped to low levels even after the India-wide numbers peaked in mid-September. INSACOG has reported about 10%  of cases so far in Kerala as arising from the N440K variant associated with immune escape. Nothing, in principle, would prevent Kerala numbers from rising,” says Dr. Menon. “Indeed, the R0 value for Kerala has just crossed 1 very recently. However, one might hope that any increase might be slower, reflecting a larger State-wide seroprevalence and perhaps overall  slower rates of reinfection.”

Dr. Babu says that fresh Covid-19 infections can continue to crop up in Kerala. “The State needs to continue enhanced containment measures (robust contact tracing and testing),” he says. 

No conclusive proof

An imported variant of concern — the B.1.1.7 variant first found in Britain — has been recorded in a few States. Also, a double mutant variant that originated in India has been identified in at least a few States but all three experts feel that it is too early to conclusively say if this variant is responsible for higher transmission leading to a surge in cases or increased disease severity and death. This is because epidemiological link has so far not been established. That said, the B.1.1.7 UK variant and the double mutant variant are considered to be more infectious and therefore more likely to contribute to intense transmission resulting in a faster peak wherever the variants are found. 

One way to know if the double mutant variant is more infectious is by undertaking concurrent genomic sequencing of the cluster of cases and establishing the chain of transmission of the variants among the contacts, says Dr. Babu. Only such a systematic study will help establish the epidemiological linkage of the variant. Also, in vitro testing is necessary to establish infectiousness. Similarly, the extent of morbidity caused by the variant can be established by tracking the clinical parameters of individual patients. “I am not sure if these studies are being done at sufficient scale, and results are certainly not available in the public domain,” says Dr. Menon.

Also, against a target of sequencing at least 5% of positive samples across India to know the emergence of variants of concern, only 7,664 samples — less than 1% of the total positive samples from January to March 18, 2021 — have been sequenced. “The 5% is an aspiration, a vision. It can’t happen overnight. Capacity, systems and logistics have to be built for it. Since the INSACOG came together, India has seen about one million cases, and 11,000 sequences have been done. So, the rate is 1%. It needs to go up,” says Dr. Jameel. The INSACOG group came together only in January and started working in February, so there’s been relatively less time to ramp up, says Dr. Menon.

Undertaking studies to understand infectiousness of the double mutant variant becomes all the more important as noncompliance to COVID-19 appropriate behaviour is uniformly poor across India. Yet, the surge in cases is seen only in 19 States, and mainly in about a dozen States. In the absence of timely results of such studies, which will help policy making, the government has taken the easy way out by placing all the blame on people.

Published in The Hindu on April 3, 2021