Serology is the study of antibodies in blood serum. Antibodies are part of the body’s immune response to infection. Antibodies that work against SARS-CoV-2 and the virus that causes COVID-19, are usually detectable in the first few weeks after infection. The presence of antibodies indicates that a person was infected with SARS-CoV-2, irrespective of whether the individual had severe or mild disease, or no symptoms.
Seroprevalence studies are conducted to measure the extent of infection, as measured by antibody levels, in a population under study. The initial seroprevalence in the population is assumed to be low or non-existent due to the fact that the virus has not been circulated before.
Serological Survey
Serological surveys are conducted by taking blood samples and checking for a specific class of antibodies called Immunoglobulin G (IgG) that appear within two weeks of an infection. The antibodies are proteins produced by the immune system to fight external organisms like viruses that try to enter the body. These antibodies are produced only after the infection takes place and are specific to the attacking virus. The presence of antibodies is an indication that an infection by SARS-CoV-2 virus has already occurred. Subsequent attempts by the virus to infect the body could be countered by antibodies.
There are many studies underway to better understand the antibody response following infection to SARS-CoV-2. Several studies have shown that most people who have been infected with SARS-CoV-2 develop antibodies specific to this virus. However, the levels of these antibodies vary between those who have severe disease (higher levels of antibodies) and those with milder disease or asymptomatic infections (lower levels of antibodies). The serological surveys are not designed to assess the quantity of antibodies present or detect the presence of neutralising antibodies. However, till now, there is no documented evidence of re-infection of SARS-CoV-2.
Serological Surveys in India
In India, three nation-wide serological surveys have been carried out by the Indian Council of Medical Research (ICMR) to assess the spread of SARS-CoV-2. Apart from nation-wide serological surveys, many states in India, too, have conducted serological surveys to assess the extent of infection of SARS-CoV-2 virus.
In such a huge population, it is difficult to test everyone. It is even unclear how people are infected, as most of the patients do not show any symptoms of the disease. Detecting antibodies in random sets of people is an indirect way of estimating the extent of the disease in a community.
Serological survey helps to identify the percentage of general population that has been infected by the virus, the occurrences of community transmission of SARS-CoV-2, herd immunity, people who are at higher risk of getting infected, and the areas where containment efforts need to be strengthened, etc.
First Survey: The first serological survey was conducted between May 2020 and June 2020. It was a randomly sampled, community-based survey. In the survey 700 villages and wards, selected from around 70 districts in 21 states across the country were covered. During the survey, ICMR reportedly tested blood samples obtained from 28,000 individuals for IgG antibodies using the COVID Kavach ELISA kit. Survey reveals the following things.
- Population-weighted sero-prevalence after adjusting for test performance was 0.73 per cent.
- Infection fatality rate was very low at 0.08 per cent.
- The worst-affected were those between the age group of 18 and 45 years, as 43.3 per cent had developed antibodies against SARS-CoV-2, which causes Covid-19.
- Though lockdown/containment had been successful in keeping the number of cases low and preventing rapid spread of SARS-CoV-2, but a large proportion of the population were still susceptible.
Second Survey: It was conducted between August 2020 and September 2020. Following are the findings of the survey.
- It covered the same population as the first serological survey.
- The survey showed that a considerable population was still vulnerable and susceptible to the SARS-CoV-2 infection.
- Urban slum and urban non-slum areas had higher SARS-CoV-2 infection prevalence than that of the rural population of the country.
- Of the 29,082 people surveyed, 6.6 per cent showed evidence of past exposure to SARS-CoV-2 infection.
- Due to substantial increase in testing and detection after the first serological survey in May, 2020 the second serological survey showed lower infection ratio.
- Adult population showed 7.1 per cent of past exposure to SARS-CoV-2.
Third Survey: This survey was conducted between December 2020 and January 2021 covering the same population as the first and second surveys. Salient things about this survey are—
- In this survey, the antibody test employed was specifically designed to check for antibodies produced against the spike protein.
- A general population of 28,589 individuals and 7,171 healthcare workers were included in the third national serological survey.
- It found that nearly one in five Indians had been infected by the SARS-CoV-2 until December 2020. This is roughly a three-fold increase since the second survey and a 30-fold increase since the first survey when previous rounds of the survey were conducted.
- The ICMR reported that 21.5 per cent of the population surveyed showed evidence of past exposure to SARS-CoV-2 virus.
- Seroprevalence above the age of 18 years was found to be 21.4 per cent.
- Amongst healthcare workers, seroprevalence was highest overall with 25.7 per cent. It was highest among doctors and nurses.
- Seropositivity was highest in urban slums at 31.7 per cent, dipped to 26.2 per cent in urban non-slum areas, and was lowest in rural areas at 19.1 per cent.
Major Findings
Seroprevalence surveys have provided insights into the pandemic that are not readily visible in data on cases or recorded deaths.
The surveys have shown that urban spread can be very rapid, particularly in city slums. New surges are possible even when a large part of a population has had the disease (as in Mumbai and Delhi).
The surveys have highlighted highly variable disease surveillance across the country, with weaker surveillance in some states, in rural areas, and in city slums. It has also indicated that fatality recording is probably extremely variable.
The higher prevalence of SARS-CoV-2 in urban slums was also noted in both second and third national serosurveys. It also suggested that housing poverty is a key predictor of how fast virus infection spreads in cities.
Rural spread has, in general, been slower than urban spread. This was observed in the second national serosurvey, in the third national serosurvey, and also in several state serosurveys.
These results suggest that a rural-urban divide in detection would simply reflect levels of rural/urban development and poverty.
The surveys did not report any community transmission of SARS-CoV-2.
Community transmission or spread of SARS-CoV-2 is said to happen when the source of the contagion is not known. That is, when one is unable to trace an infection back to a carrier who has travelled in an affected area, or through contact with a person who has the disease.
A state of community spread implies that the virus is now circulating in the community. The virus could infect people with no history, either of travelling in the affected areas, or contact with affected people. At this stage, it is theoretically possible for everyone to catch the infection.
Although the data is patchy, the three seroprevalence survey reports from around the country has deepened the understanding of spreading of the SARS-CoV-2 pandemic in India.
While the three nationwide seroprevalence data is in general, a more reliable indicator of disease spread than case data, it is not free of problems. More analysis needs to be done on the antibody responses. It is also possible that some tests become less sensitive to old infections over a period of time. Ideally, it should always be checked if serosurvey conclusions are consistent with other pandemic data. It should also be checked whether the results could be affected by how a population was sampled or the timing of the survey.
The information in the sero surveys may be incomplete, inaccurate or misreported due to various reasons. It would be more authentic if the survey reports are accompanied with technical reports as well.
Is SARS-CoV-2 on the Decline in India
Though the overall infection in the country is showing a declining trend, however, in some of the states, it is still on the surge. The fatality rate, too, has reduced considerably. If effective mitigation continues to play an important role in keeping infections low, the country could still be far from herd immunity. If there is a pause or slowdown in the mitigation then there can be a significant new upswing in the infections.
Herd Immunity
Herd immunity is a stage of any epidemic in which some members of a population group remain protected from infection. This may be because a majority of those around them have already developed immunity, either through vaccination or because they have been infected earlier. This is an important area of research and would vary according to the community. However, scientists caution against herd immunity calculations as presently it maybe inconclusive.
Is India on the Threshold of Herd Immunity: With most early spread occurring in cities and additionally better surveillance in cities, the nationwide statistics for the early cases and deaths due to SARS-CoV-2 was predominantly urban data. It is this urban data on which national estimates are being calculated. Perhaps, if the government had been able to adequately disentangle rural data from the total, then it would have found that rural spread is naturally slower. It has been witnessed that cities were surging after high levels of infection. Even the natural speed at which the disease spreads in rural areas is probably highly variable given different patterns of rural development. Moreover, mitigation is almost certainly still playing a part in limiting transmission in some parts of the country, at least.
To safely achieve herd immunity against SARS-CoV-2, a substantial proportion of a population would require successful vaccination, lowering the overall amount of virus able to spread in the entire population. Vaccines train our immune systems to create proteins that fight the disease and vaccinated people are protected from getting the disease and passing on the pathogens, breaking any chains of transmission.
With the current vaccination drive, started by the Government of India, herd immunity against SARS-CoV-2 should be achieved by protecting people through vaccination.
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