Erroneous to conclude that we have attained herd immunity, says Srinath Reddy

While 67.6% of the Indian population appears to have antibodies either from natural infection or vaccination, as per the fourth sero survey , Dr. Srinath Reddy dispels the wrong notion that India is close to reaching herd immunity and explains the uncertainty of protection even among those already infected.

The fourth sero survey conducted across India found that on an average 67.6% of the population has been infected. Also, over 25% of people have been vaccinated with one dose.

In an email, Dr. Srinath Reddy, President of the Public Health Foundation of India and member of the National COVID-19 Technical Taskforce dispels the wrong notion that India is close to reaching herd immunity and explains the uncertainty of protection even among those already infected.

Nearly 29,000 people from the general population and over 7,200 healthcare workers were randomly tested from 70 districts across 21 States. How representative is the sampling for the whole country?

Scientists from ICMR have themselves clarified that this survey is not representative of the whole country. They have called for state level, preferably district level, surveys across the country using standardised methodology. If we wish to have a truly nationally representative survey, we must sample from every postal code area in the country. That will be highly resource intensive and not feasible during a pandemic period when health system has many competing demands.

The national surveys of ICMR are valuable, even if they are not fully representative of the whole country. By conducting repetitive surveys in the same districts, these studies provide information on how proportions of infected people in the population have increased over time. That helps us to understand how effective our efforts to contain viral transmission have been during the periods between surveys. Kerala, for example, has a low level of seroprevalence because they have adopted public health strategies which slow down transmission. While the survey results are also interpreted to estimate the numbers of immune and susceptible persons in the population, there are reasons to question those assumptions.

The seroprevalence is 67.6%, which is far higher than the last survey figure of over 24%. But this is only an average and many States, such as Kerala, have far lower seroprevalence. So is it correct to assume that a vast percentage of the population, both in urban and rural areas, is uniformly protected?

There is a great deal of variation across the country, between states. If we do district level surveys, we will find even greater variation. We must bear in mind that, while the sample size may be adequate at the national level, to provide estimates with a narrow uncertainty band (confidence interval), individual state sample numbers would be small and have wider uncertainty bands.

If we accept the figures provided for each state, ignoring such concerns about wider uncertainty bands around the estimates, it is clear that there is no uniformity across the country. That is to be expected, as there are marked variations between states on levels of urbanisation, population density, travel intensity, extent of control measures implemented and super spreader events permitted, speed and level of opening up of various sectors of activity and vaccination rates since January.

It would, however, be erroneous to conclude that all persons who tested positive are immune to infection by the virus. We do not know for sure how long the antibodies last either after infection or vaccination, as there are conflicting reports emerging on both types of induced immunity. More important, the tests employed in the surveys only identify antibodies to two viral proteins (nucleocapsid and the spike) but do not measure the ability of those antibodies to neutralise the virus. Estimating the neutralisation power is important in the context of the variants which are displaying capacity for evading the immune response. Will the antibodies produced against the wild ancestral virus infection in January or the Alpha variant in February be effective against the Delta virus in July? There is a possibility that some of those who tested positive for antibodies, especially children, may have cross-reactive antibodies generated by other corona viruses which produce common cold. Counter-posed against such ‘false positives’, we may also have ‘false negatives’ of persons in whom antibody levels may have fallen some months after infection but still may have immunity from memory T cells and other forms of cellular immunity. So, definitive conclusions about individual or population immunity should not be drawn from antibody surveys. 

Are there chances that people who were infected early during the pandemic last year might not have the antibodies and hence might have been missed by the latest survey? 

People who were infected early during the pandemic would have a greater chance of testing negative during surveys due to the waning of antibodies over time. The time taken for such disappearance has been variably reported to be between three and six months. There would be a great deal of individual variation, based on the dose of viral exposure, severity of the infection, nature of the variant, age of the infected person, associated health conditions and use of steroids or other immunosuppressive drugs for treatment during the illness. So, there are likely to be several persons who may have been infected some months ago but were missed by the recent survey.

Will infection with the old strain provide sufficient protection particularly against the Delta variant?

The answer has been provided by laboratory studies which have shown a diminished neutralisation efficacy of antibodies produced by previous infections against the Delta variant. The study by the Pasteur Institute in France is particularly informative in this regard. However, some protection is still likely. Even if the variant has spike protein mutations that make it vaccine evasive, natural infection with an earlier form of the virus would have also evoked immune responses against other antigens of the virus. Those non-Spike directed immune defences can still provide some protection. We do not know how strong and long lasting that immunity would be in any individual, as there would be considerable variation among those infected.

Like Manaus, Brazil reporting a huge surge in cases despite 76% seropositivity rate, the metro cities in India with high seropositivity rate reported a large number of fresh cases during the second wave. Will we still see a large number of cases in these cities if and when a third wave begins in India?

There is no guarantee that seropositivity in a survey is a proof of permanent protection against fresh infection, especially when the virus is frequently changing form. Vaccines, with a standardised dose of antigenic challenge, provide a greater assurance of protection than a previous infection with a variable viral dose and a different form of the virus than the one that is currently circulating. The numbers infected in the third wave will depend on the numbers of people still susceptible, the numbers among them who are exposed to the virus and the nature of variants in circulation. By adopting strong containment measures everywhere, we can protect the susceptible persons even against current and new variants. A new and more infectious variant can rapidly spread everywhere if we offer opportunities for easy transmission. That is why we must intensify genomic testing for detection of variants.

Is it at all correct to assume that large parts of the country is quite close to reaching herd immunity due to the high seropositivity rate?

It is erroneous to conclude that we have attained herd immunity as a population, when there are many variations across the country even according to the antibody survey. This is for several reasons. We do not know if all who tested positive for antibodies have neutralising capacity against the currently circulating variants. We do not also know how long those antibodies will last. Even if the antibodies are protective today, that protection could fade in a month or two. The herd immunity threshold (HIT) is high for the more infectious variants. For the Delta, it may be 85% or higher. We are below that level in all states that were surveyed.

Herd immunity is a population attribute, not an assured individual safeguard. It operates on the principle that if a large majority of persons in a population acquire immunity, through infection or vaccination, they will block the transmission of the virus to the smaller group who do not have such acquired immunity. However, if these non-immune persons travel to any other part of the city, country or the world, where the proportion of persons who have acquired immunity is low and below the HIT while the virus is still in active circulation, there is no protective cordon to prevent infection. We live in a world of high mobility. It is best that each individual acquires immunity, preferably through vaccination, rather than risking one’s life by betting on the uncertain charity of someone else’s immunity offering protection everywhere.

Considering that two-third of India is already infected and has some level of protection and over 25% of the adults have received at least one dose of the vaccine, will the third wave be as severe as the second wave both in terms of daily fresh cases and deaths?

The third wave should be milder for those reasons, if no new variant sweeps through with higher infectivity and undiminished virulence. That does not appear likely at the moment but we must prepare for such an occurrence. Even if there are many infections, the immunity provided by vaccines and prior viral exposure should reduce the risk of severe illness or death. That is what we have seen recently in the UK and parts of USA, where it is now considered an epidemic mostly of the unvaccinated and any infections among vaccinated persons are associated with very mild symptoms. We should acquire that status as quickly as possible, though I believe we should also create vaccine confidence to keep the numbers of unvaccinated persons extremely low.

Published in The Hindu on July 31, 2021