Chennai: One year into the COVID-19 pandemic, new evidence is casting doubts over India's pathway through and out of the pandemic, with epidemics of different contours now evident deep below national and state averages. Nowhere does this multi-speed epidemic seem more evident than in Maharashtra.

From the beginning of the pandemic, Maharashtra has dominated the Indian curve on account of its sheer number of cases. Maharashtra's 'peak' and 'fall' in mid-September was closely mirrored by India's overall trajectory. What this could mean is that Maharashtra's new surge may dictate how things look in India again.


Not just the plain numbers, the disease's progression could contain clues for how the pandemic may move through the rest of the country--the way the virus progresses in Maharashtra's rural districts, which were earlier relatively unaffected, and its big cities that were hit hard by the 'first wave'.

Pradeep Awate, Maharashtra's chief epidemiologist, attributes the current surge in the state to three factors. "One, the cold conditions seen in north India in the early part of the year led to cold weather in parts of Maharashtra, including in the north-east Vidarbha region, and this could have aided the spread of the virus. Two, on January 15 there were local body elections across 14,000 villages in the state, and many people returned from cities to cast their votes in the villages, potentially taking the virus with them. Three, weddings and other social functions that had been put on hold were held again after we began unlocking, leading to the congregation of large numbers of people," Awate said.

From the numbers, it does not appear that this was an urban-to-rural wave, in that the surge of cases in Pune and Mumbai did not precede that in rural districts, points out Murad Banaji, lecturer of mathematics at Middlesex University in the UK, who has been tracking India's COVID-19 numbers closely.

But what is undeniable is that a far larger pool of uninfected people still exists in rural areas compared to urban areas. "From the sero-surveys, we know that there is still a high uninfected population in rural areas. It is only in the big cities with high sero-positivity like Mumbai and Pune where we are approaching herd immunity," Manoj Murhekar, director of the National Institute for Epidemiology, and lead author of the Indian Council of Medical Research's (ICMR) national sero-surveys for COVID-19, told IndiaSpend. Indeed in districts like Akola and Amaravati, the new daily COVID-19 numbers are higher than they were when the state experienced its September 'peak', while in other districts like Buldhana and Wardha, the new numbers are approaching the respective districts' highest so far.

The bigger mystery is what is happening in cities like Mumbai and Pune, where sero-prevalence in the population is estimated to have surpassed 50%. For one, there could be parts of these cities' populations that are only now getting exposed to the virus, as they were able to better protect themselves during the earlier surge. "Our sero-surveys showed a small increase in sero-positivity in non-slum areas and a slight decline in sero-positivity [on account of antibody decay] in slums areas between the first and second rounds," Sandeep Juneja, professor at the Tata Institute for Fundamental Research (TIFR), and co-investigator of the Mumbai sero-surveys conducted jointly by TIFR and the Municipal Corporation of Greater Mumbai, told IndiaSpend. The numbers could have been biased downwards because the antibodies tested for have been found in some studies to serorevert [ meaning to disappear] quickly, Juneja added.

"Although the numbers in Mumbai fell from the September peak, the COVID-19 epidemic never really died out," said Banaji. "With that low but constant level of prevalence, if you have congregations and improved testing, you're going to once again see new clusters or waves," he said. One such opportunity for congregation that the TIFR team's modelling had predicted was the partial re-starting of local train travel, although the current surge is above what they had estimated, Juneja said. In addition, one reason for the higher intensity of current surge may be that people have become much less compliant to social distancing rules over time as the cases in India have been coming down, Juneja added.

Then there is more testing in wealthier areas, said Banaji. Juneja's analysis of their sero-survey data found that detection rates are much higher in non-slum than in slum areas--people in their non-slum sample were four to six times more likely to get tested as in their sample of slum people, even as far back as August 2020 when the epidemic was raging.

This impact of better detection was clearly visible in the recent Bengaluru housing society outbreak, Giridhar Babu, epidemiologist with the Public Health Foundation of India, and co-chair of the city municipal corporation's Task Force on COVID-19 Public Health Response, told IndiaSpend. Three days after a party in a housing complex in the city, some residents took a COVID-19 test ahead of a planned trip to Dehradun; when they tested positive, the municipal corporation tested over 1,000 residents of the complex and found over 100 positive cases. Given that the majority of positive cases were asymptomatic, the discovery of the cluster was a clear outcome of testing, Babu said.

It is possible also that sero-surveys have artificially created certainty about a situation in which uncertainty still dominates. This was demonstrated recently by research around Manaus, a city at the edge of the Amazon rainforest in northwest Brazil that has become the epicentre of discussions around "herd immunity". Manaus experienced a COVID-19 surge that peaked by April 2020, and by October 2020, analysis from the sera of blood donors in the city had led researchers to believe that 76% of the city's population had been infected. Herd immunity, it appeared, was imminent.

Yet in January 2021, the city saw a resurgence, prompting the investigators of its first study to re-examine the causes of the new surge. They observed that there could be at least four reasons for this, in a study published in The Lancet medical journal on January 27, 2021. First, the attack rate of SARS-CoV-2--the virus that causes COVID-19--could have been overestimated during the first wave in Manaus on account of some mathematical and epidemiological assumptions that could have contained errors. Second, immunity against infection might have already begun to wane by December 2020, and there could have been re-infections. Third, immunity acquired from the first wave might not guard against infection from new variants. Lastly, the authors suggested, new variants could be more transmissible.

"Exactly what Manaus is showing, and now other regions of Brazil and Latin America, is that high attack rate in the first wave with prevalences higher than the theoretical value for herd immunity does not prevent a second wave," Ester Sabino, lead author of The Lancet study, said in an email to IndiaSpend, when asked about Mumbai's numbers. "Sero-surveys are helpful to understand attack rate but not the duration of immunity. Being antibody positive does not mean that the individuals will not be reinfected, especially for variants with mutations on the spike protein that help the virus to escape the immune system," she said. Continuous, well-designed studies in accordance with the available resources are the only solution, even in resource-constrained low- and middle-income countries, she added.

On that count, India has been slow to move, with its genomic surveillance lagging far behind other badly-hit countries. "There is huge [genome] sequencing capacity in India. Out of the approximately 300,000 [genome sequenced] strains that were globally available by the middle of January 2021, 150,000 of them are from the UK, and that's why the UK is able to pick up new strains. Other places that are doing good sequencing are South Africa, and to an extent Brazil. So we are seeing variants in places where they are sequencing more," Gagandeep Kang, virologist and professor of microbiology at Christian Medical College, Vellore, told IndiaSpend. "In India there was initially a huge pitch to sequence, but it turns out we have virtually no strains sequenced after July 2020. Now they are going to start sequencing again," she said.

At the end of December 2020, the government launched the Indian SARS-CoV-2 Genomic Consortia (INSACOG), comprising 10 laboratories to monitor genomic variations on a regular basis. While Maharashtra has sent samples from Amaravati, Akola and elsewhere in the state to the National Institute of Virology in Pune, there is no clarity yet that a new variant is resulting in the surge or is more transmissible, both Awate and Murhekar said. What this also means is that the efficacy of vaccines, which are being tested against the UK and South African variants in other parts of the world, will need study and updation if and when Indian variants are sequenced, Murhekar said.

Re-infection, too, remains poorly studied, despite some emerging evidence--a minister in Maharashtra's COVID-19-hit cabinet is among the most high profile people to have publicly announced that he recently tested positive for the second time. The ICMR's sero-surveys returned to the same districts, but not to the same individuals in subsequent rounds, meaning that the possibility of re-infection remains untested. "We have the sera. We could test to see if antibodies are produced against newer variants," Murhekar said. In Amravati, some of the samples sent for sequencing are from people who tested positive twice, the head of the district's molecular lab said, but the lab no longer has the blood samples from the first time that tested positive. These were reportedly destroyed for lack of storage capacity.

In October 2020, Manaus and Mumbai appeared to show the future pathway--and potential end-point--for the COVID-19 pandemic. That certainty has been irreparably dented, say experts, adding that this is reason for renewed humility. "We need to recognise that we don't know yet much about the disease and with the data we have today, it is hard to predict the future," Sabino said.

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