'India Must Record Suspected COVID Cases As Well'

What could be India's way out of this second wave? What vaccination strategies should India pursue? We ask Dileep Mavalankar, director of the Indian Institute of Public Health, Gandhinagar, and Sanket Mankad, an infectious diseases consultant who sounded a warning back in November 2020 that we should focus on an imminent second wave, for the view from Ahmedabad.

Edited excerpts:

Dr Mavalankar, when we last spoke in August 2020, you had done a study looking at the prevalence of COVID-19 within families. One of your key findings was that the disease was not spreading as intensely within families as it was outside, and in 70-80% of cases, family members of COVID-19 persons were not affected. Was that because of the behaviour of the virus at that time? How have things changed in this second wave?

DM: The first major change we see in this second wave, at least anecdotally, is that entire families are affected, save maybe one person. We are planning to do a similar study again now, and have asked for government permission to access the data.

The second major change is the rapid increase in cases. The first wave started in March-April 2020 and peaked half a year later in September, whereas this second wave has started in mid-February 2021, has rapidly surpassed last year's wave by a margin of two and has not yet peaked.

The third major change is that more younger people are getting infected in this wave than in the first. Earlier it seemed there was low mortality in the second wave, but now it seems that mortality is catching up and is also rapidly increasing.

Fourth, again anecdotally, rural areas are also seeing quite a few cases, unlike in the first wave, despite there being less testing in rural areas compared to big cities.

Dr Mankad, tell us what changes you are seeing while treating patients at the front line.

SM: The major change we are observing currently as clinicians and infectious disease specialists is that the virulence of the virus is a bit higher compared to what we saw last April, May, October and November. As Dr Mavalankar rightly said, currently we find entire families to be positive. Second, young adults are also being infected, who earlier were relatively safer. Third, the virulence of the virus in younger adults is also currently high and it's worrying that younger adults are developing pneumonia faster.

One more thing is the altered coagulability of blood secondary to COVID-19 infection is also notable in this particular subset of patients. The acute respiratory distress syndrome (ARDS), i.e. the development of lung infiltrates in both lungs is also increasing in young adults. That is a point to ponder about in this second wave.

Currently, the second wave that we are seeing is by and large restricted to the four major cities of Gujarat--Ahmedabad, Rajkot, Vadodara and Surat. But, as Dr Mavalankar said, the urban peripheries are also not being spared in this second wave.

One more notable thing about this second wave is the unusual presentation of cases. Patients are presenting with acute diarrhoea, dehydration and multi-organ involvement. In the earlier phases, we were not seeing children getting infected, but now young mothers between 35 and 45 years old are getting infected and subsequent transmission to children is also being increasingly seen. In children, we find multi-system inflammatory syndromes. These are the differences in the clinical presentation of the patient profile that we clinicians are seeing.

On TV, we have been seeing ambulances with sick persons lined up outside hospitals in Gujarat and also ambulances with persons awaiting cremation. Why is there such a surge? Is it due to people not getting tested and therefore not getting treatment in time?

SM: In January and February, there was a drastic fall in the number of active COVID-19 cases, which was widely documented. Therefore, one year and a quarter into the pandemic, pandemic fatigue set in. We human beings are social animals. So when people found that cases are low, weddings, get-togethers and all sorts of gatherings did occur during that period of time. One thing we definitely forgot was the importance of SMS--social distancing, masks and sanitisation. Vaccination was introduced, which might have given a false sense of security to a certain group of people who received the vaccine. These all are the factors that contributed to indifference towards the development of the second wave, which was definitely an impending second wave.

You talked about blood conditions as well as lung conditions in younger people. Are these more prevalent in younger people now and not seen in older people, including during the first wave?

SM: No, we definitely see senior citizens, diabetics, hypertensive patients with coronary artery disease, who are prone to develop bilateral pneumonia and ARDS. They are definitely presenting with these things. But earlier during the first wave, the younger adults were not so highly susceptible. The clinical implication is that the virulence of COVID-19 might have increased.

One more thing we need to think about is that the sequencing of this particular virus also needs to be done, to find out whether it has changed its genetic structure, has undergone any mutation, or has acquired new virulence factors (invading the hosts' immune systems) and thereby enhancing the attachment of the virus to the respiratory epithelium. Whether it is attaching more to the gastrointestinal epithelium and developing a multi-system disorder also needs to be ascertained by doing detailed DNA sequencing of this particular virus: Are we facing the Wuhan virus we saw during the first wave, or is it a variant, or is it a mixture of the UK, Brazil and South African variants.

Dr Mavalankar, it's quite clear that we do have new COVID-19 mutations, but though mutations can change characteristics, they don't necessarily change in their entire composition. Some behaviours of new COVID-19 mutants should be the same, and some new. Are we underprepared, given all these new characteristics that we are now seeing?

DM: I agree with Dr Mankad that given the decline in infections from September to February, and the arrival of vaccines in January, we were all thinking that the virus is gone and even some senior ministers [said] now we are out of it. Everybody seemed to have changed their behaviour. Then mid-February onwards, suddenly we started seeing this rise, which was initially gradual and then in April, it has become exponential. We can learn what an exponential curve looks like. Epidemiologist Bhramar Mukherjee from University of Michigan has modelled by how much cases and deaths can go up per day. We are still not at the peak.

This very rapid rise is not explained only by the second wave. I'm sure there is some kind of change in the virus because this wave should have been less intense, because at least 20% of India's population had COVID-19 infection, as serosurveillance across the country showed, plus we had some vaccine coverage. Despite this, we are seeing a rapid rise. It is very, very worrying.

We also don't have hospitalisation numbers, that is one thing missing in Indian data. We only show positive COVID-19 cases and deaths and not how many hospitalisations. That's why the media is showing that many people outside hospitals. Anecdotally also we know that many hospitals are full. In some places, only 10-15% of ICU beds are vacant. I don't know why they are not able to monitor this metric of how much percentage of hospital beds are free or filled, which is a critical thing to save people's lives. The cases will increase but if your hospital capacity is exceeded, then many people may die at home, which we will not be able to capture.

Dr Mavalankar, is it that people in Gujarat are not even getting tested and thus reaching a point of no return because they did not get the right treatment?

DM: In the big cities, people would get tested, but now laboratory capacities are also overstretched. Laboratories that were doing 800-1,000 cases a day are doing 5,000-10,000 now, so reports are delayed, may take up to 2-3 days. Second is after paying, private laboratories will say that they can't send anybody to your home to collect samples because their capacity is also stretched; patients have to go to the laboratory and wait in a queue to get tested. So there are many reasons why if people delay in getting tested, they may not get the report before they even die. As Sanket said, many [people's conditions] are rapidly deteriorating--especially poor people who may not have resources for tests because the public laboratories are also crowded.

The roadside testing is very good. They are doing the rapid antigen test, but there are two handicaps to that. One is that sensitivity is 50% for the best rapid antigen test, so 50% of cases are being missed. Another doubt is if the test sensitivity may be as low as 30% with this mutant virus. So validation of the rapid test also needs to be done by epidemiological and other methods to see if these are functioning as well as before. So there may be people who are testing negative and then finding out later on that they are positive.

The other issue is we have no definition of COVID-19 cases in the country, which I really want to highlight. For suspected cases of COVID-19, we have either black or white. You're either not a COVID-19 case, or you are, even if your high-resolution computerised tomography (HRCT) test shows your lungs are filled. If anybody can say that this is nothing except COVID-19, it should be labeled as a suspected case. In chikungunya, we had two levels of definition: suspected and confirmed. So for COVID-19, two or even three levels of definition--probable case, suspected case and confirmed case--are needed. Probable means not a doctor but a health worker confirms the case; suspected is when the doctor sees and confirms in a pro-clinical diagnosis; and confirmed is with laboratory diagnosis. Somehow we have missed this whole spectrum of COVID-19 cases and that's why many people who may be positive are missed, especially in rural areas. Sometimes the rural samples have to go to the next district to get tested. And of course there are asymptomatic cases

Dr Mankad, anecdotally the fatalities that we're seeing in Gujarat, are these younger people compared to last time, broadly? Or is it the same age profile?

SM: By and large it is the same profile--those aged more than 65 years, patients with comorbidities like diabetes, hypertension and coronary artery disease or patients who are immunosuppressed, form the major chunk of the pie diagram. One notable thing would be that the prevalence of mortality in the younger adults is in the range of zero to 10% this time, currently. So by and large, the susceptible age group remains [older]. But the newer thing is that the invasion of the virus into the lungs in young adults also is being seen pretty quickly. Earlier we used to find a patient's HRCT scan to be positive on the fifth, sixth or seventh day. Currently, we see it on the third or fourth day. So that straight away indicates the rapidity of the invasion of the respiratory epithelium by this particular virus. Whether it is the same COVID-19 virus or a variant needs to be defined by the genetic community that is in charge of DNA sequencing as of now.

Dr Mankad, while the virus is progressing faster among younger people, as you say, are they also recovering?

SM: Definitely they are recovering if they get diagnosed early and treated in time. Turnaround time of the test is also very important. Currently all the laboratories are hyper-saturated so the delivery of the RT-PCR report might require 36 to 72 hours. So if in between, an individual worsens, it might be very difficult to pick out that particular individual in the current setting.

Secondly, remdesivir is not the only injection that saves lives. It is imperative that we understand that it is not just remdesiver that is going to be helpful in this particular situation. It is a combination of oxygen therapy, antioxidants, vitamins and anti-inflammatory drugs. So an individual who in time finds a bed, good doctors, a good pulmonologist and a good setup has every chance to be saved.

Dr Mavalankar, since we are far from practising safe behaviour, you've argued that vaccination is really the only solution going forward and India should really focus its vaccination efforts on a fixed number of districts where there are a majority of the cases at this point, rather than spreading them out evenly. Could this approach be picked up?

DM: Unfortunately there is not much discussion on this. There is a two-fold purpose to vaccination. One is to reach herd immunity and the other is to protect individuals. These are two different strategies. What India has opted to do is protect older individuals, which Western countries also did, because they have smaller populations. We started with 60 years and above, now we have come to 45 years and above, but the transmission is happening in younger people. So even if you vaccinate everybody above 45 years, the transmission may not stop because you have not reached herd immunity.

Our statistician Dr Awasthi and I calculated that out of 740 districts of India, there are 50 where the maximum COVID-19 cases and deaths have occured. Just 6% of total districts had 60% of cases and deaths two months ago. By now it may have changed a bit but the idea is the same as the Pareto Principle [uneven distribution]. So you vaccinate everybody above 15 or 18 years of age in those 50 or 60 districts, so that you reach herd immunity there. Don't start vaccinating all over because somebody who is very old in a district in Assam or Meghalaya or Tripura, where there are very few cases, does not require protection, so vaccinating there doesn't protect anyone. On the other hand, you need vaccinations in highly endemic areas like Mumbai, Delhi, Ahmedabad or Surat.

Let me give a hypothetical example. India has conducted 100 million vaccinations. So our argument was that with limited vaccines, one strategic choice could have been to give all these vaccinations only in Maharashtra, Punjab or Kerala, which were the three top states in terms of caseload at that time. People below 15 or 18 years of age aren't going to get vaccinated because the vaccines are not approved for that age group, which forms about 40% of the population. If you give 100 million vaccinations to the remaining 60%, you could have wiped out the disease in these three states, and they would have reached herd immunity. That would have reduced the disease by about 50% to 60%, if not more. So this idea that the whole country should equally get everything is epidemiologically not very correct. If you have limited vaccine stock, and want to vaccinate about 100 crore persons above 18 years, you require 200 crore doses. Now, where will you get 200 crore doses? No country has such large vaccine manufacturing. So, it will be a five-year programme to do that, and the virus may mutate and produce new versions, which may make the vaccine less effective.

That's why I had said to focus on those districts. Even now, if you focus on even the top 10 places where maximum cases are happening and vaccinate everybody above 18 years of age, we will reduce infections substantially. Exactly this is what was done in smallpox eradication, when vaccinating everybody in the whole world against smallpox was not possible in the 1970s. So they identified where cases are happening and vaccinated 200-300 houses around those houses. It was called ring vaccination and by doing that, they got rid of smallpox. It is a similar strategy which I have suggested.

Dr Mankad, you mentioned SMS--sanitising, masks and social distancing--but what should people do apart from taking these precautions? What are the symptoms they should be looking out for, given that the virus is still spreading fast. And what should they not do?

SM: The most important thing is SMS, i.e. sanitisation along with social distancing and using masks. Vaccination is also the key if you want to eradicate this particular disease from the surface of the Earth. Vaccination might not prevent infection, but it definitely reduces the incidence of serious disease, which we are more worried about with COVID-19. Vaccination at least prevents lung and multi-organ dysfunction syndrome, so from our clinicians' point of view, patients are not getting sick and patients are not getting admitted to the ICU. They are not requiring oxygen if they are vaccinated, and have enough antibodies to fight [the infection]. Therefore SMSV should be the correct mantra by which I think India should go forward, and definitely that is what we are focusing currently on in Gujarat also.

Dr Mavalankar, what should India be doing now, even as we grapple with the vaccine shortage?

DM: As I said, a different vaccination strategy, which is one 'V', to which I will add two more: ventilation, which is not emphasised as much, because many people are getting infected in closed, air-conditioned spaces. So you must have windows and doors open and have as much ventilation as possible. I would also say people should do double masking, and even go further and say use N95 masks, if you can. Lastly, the vulnerable population is the third 'V': people who are younger who have to go out to earn, the elderly, the sick, the people with comorbidities have to be protected as much as possible. So these are the strategies--plus, if required, lockdown. That word has become very bad, but one can have restrictions on no more than four people gathering together, given the tsunami of cases. Even in shops, we have all forgotten that earlier we had these circles and people used to stand in those. All of that is forgotten. So, bring it back. Practice very serious social distancing. Don't go out without any pressing reason.

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