ISSN 2330-717X

Sero Surveys: What, Why And How – Analysis

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Sero prevalence is the number of persons in a population who test positive for a specific disease based on serology (blood serum) specimens; often presented as a per cent of the total specimens tested or as a proportion per 100,000 persons tested. The positive identification the occurrence of disease is usually based upon the presence of antibodies for specific disease especially with viral infections such as herpes simplex, HIV, and SARS-CoV-2. This number is not significant if the specificity of the antibody is low. The surveillance is conducted by Indian Council of Medical Research and National Centre for Disease Control in collaboration with key stakeholders and state health departments. 

Sero surveys estimate as well as monitor infection trends in the population which is specifically location-based to understand the current course of the virus. The basic role of Sero surveys isto know the exact burden of infection.

The first nationwide Sero survey was conducted in May last year and found that less than 1 per cent of the people tested had antibodies against the novel corona virus. The second Sero survey, which had commenced in August last year, showed a positivity rate of 6.6 per cent. The third survey, between December 2020 and January this year, found that more than a fifth of the people tested had contracted and recovered from COVID-19.

ICMR’s fourth, and latest, nationwide antibody survey was held between June and July reportedly in the same 70 districts across 21 states in which the first three rounds were conducted after the second wave had began to subside. The total sample size for the fourth round was 28,975 people and 7,252 health workers. The third survey had included children above 10 years while the latest edition also covered those aged 6 years and above. Interestingly antibodies were discovered in nearly half of them.

Latest Sero survey conducted by ICMR revealed that two-thirds of the general population that is above the age of six years had SARS-CoV-2 infection. More importantly, a third of the population did not have any antibodies. 40 crore population of the country is still vulnerable according to fourth Sero survey results. Apparently, though an even larger proportion of Indians may now be said to have antibodies against the disease, the need to keep our guards up is still very much there. “The implications of this large Sero survey clearly show that there is a ray of hope. But there is no room for complacency. We must maintain COVID-appropriate behaviour. It is widely held that the actual number of COVID-19 infections is substantially higher than that captured in tests. The question is: Why is this huge difference in the confirmed COVID-19 cases and the Sero prevalence? According to experts, the COVID-19 cases can be asymptomatic or there are chances that people didn’t report of the infection. Exactly here comes the role of Sero survey to gauge the prevalence of the virus in a particular area. 

Sero-surveys use tests that examine the liquid part of blood, or ‘serum’, not nose, throat and mouth fluid. And these tests detect an immune response to the virus material, not SARS-CoV-2 virus material itself. The blood serum of a group of individuals is tested using an antibody test, also known as a serology test. {Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given microorganism), against other foreign proteins (in response, for example, to a mismatched blood transfusion), or to one’s own proteins (in instances of autoimmune disease). In either case, the procedure is simple}. The antibody test looks for antibodies and examines if an individual’s immune system has responded to the infection.

Upon virus infection, the body comes up with many immune responses. One of these is making proteins called antibodies that stick (or ‘bind’) to the virus – these show up within a few days after infection. The infection itself typically disappears after a couple of weeks. 

A human body develops two kinds of antibodies – IgM (Immunoglobulin M) and IgG (Immunoglobulin G) against any infection. IgG antibodies stay for months indicating of a past infection. The Ig are a class of proteins that function as antibodies and can be found in the blood and the immune system. These antibodies are made whether the infected person was asymptomatic or had any actual illness. And of course, nobody who has not encountered the virus will have these particular antibodies.

Thus, the Sero surveys being done in India are looking for the immunoglobulin G. According to experts nearly 70 to 80 per cent of the immunoglobulins in the blood are IgG. The body can produce specific IgG antibodies during an initial infection, which form “the basis of long-term protection against microorganisms”.

Reports say the fourth Sero survey found that antibodies were present in 62.3 per cent of those who had not been vaccinated while for those with one dose, it was 81 per cent. Antibody prevalence was 89.8 per cent for people who had received both shots. According to ICMR, the antibodies (known as IgG)  tracked in a Sero survey typically start appearing after two weeks of onset of infection, once the individual has recovered after infection and last for several months. Hence, an antibody test is not useful for detecting infection, which is mainly done in India via the RT-PCR or rapid antigen test (RAT), for which an oral and nasal swab sample is collected by health workers.

The serological test, on the other hand, uses a blood sample to test for antibodies. Further, RT-PCR and RAT look for the presence of the actual virus whereas the antibody test checks for antibodies in the blood.

According to the US drugs regulator, “the performance of these tests is described by their ‘sensitivity’, or their ability to identify those with antibodies to SARS-CoV-2 (true positive rate), and their ‘specificity’, or their ability to identify those without antibodies to SARS-CoV-2 (true negative rate)”. The result can either be read as ‘reactive’, that is, IgG antibodies were detected, or ‘non-reactive’, which means antibodies were not found.

Hence if a person was infected, virus material would be detectable in their nose, throat and mouth fluid for a couple of weeks at most. If testing was not done in that time, we would never know if the person had been infected by the virus. But IgG antibodies stay in the blood of such a person for a long time. So, if we test the blood for these antibodies at any point and find them (making the person ‘Sero-positive’), we can say that this person had indeed been infected in the recent weeks/months. Everybody cannot be tested, only a few people chosen at random are tested. The results are an estimate of the proportion of people who have been infected in the past giving a wide-angle picture over time of how the virus has spread in the community. Furthermore, Sero-survey test does not detect ‘protective’ antibodies, just all antibodies (the ‘protective’ ones are much harder to test for on a large scale). Also, even if it detected ‘protective’ antibodies, we have no idea what levels of ‘protective’ antibodies are necessary for actual protection.

The key implications of a Sero survey for public health experts lie in the status of the spread of an infection among a particular sample group. According to ICMR, Sero surveys can provide data on “the proportion of population exposed to the novel corona virus, including asymptomatic individuals. But that is not the only takeaway. Surveys among specific groups, for instance, high-risk or vulnerable populations like health and frontline workers, immune-compromised individuals or those in containment zones can also be used to assess who all may be more vulnerable compared with the others. That can allow health authorities to plan pointed interventions that are tailored to a specific group, or areas, health needs.

Sero surveys also provide a chance to track how long immunity lasts after an individual has recovered from COVID-19 according to Soumya Swaminathan, the WHO Chief Scientist. Sero surveys can be used to “test the same group of people over a period of time to understand more about the immunity against this virus”. Importantly, Sero surveys also tell us who has not been infected with the novel corona virus, which is to say that health authorities can track what proportion of the population is still vulnerable to getting infected and how far a particular location is from achieving herd immunity.

Herd immunity’, a recurrent phrase in this context, is a situation in which so many people in the community are immune and protected from the virus that transmission from person to person simply grinds to a halt, even though everybody is not immune and protected.

What proportion of the community should be immune-protected to reach the ‘herd immunity’ point differs from situation to situation. We have no idea what that point is for COVID-19. While Sero-surveys are useful in examining herd immunity, they do not tell us whether that point has been reached or not.

When enough people in a given population have developed antibodies to an infection — either by contracting the disease and recovering from it or through vaccination — it can be assumed that the disease will be halted in its track as it will become difficult for it to find new people to infect. This is known as herd immunity, that is, when exposure in a sufficient section of the population ensures that the remaining people are protected.

This proportion varies for different diseases. For instance, for a highly contagious disease like measles, the threshold for herd immunity is a high 94 per cent. Which means that more than nine out of 10 people should have either recovered from the disease or been vaccinated against it to ensure there are no further cases. But since vaccination for measles and other diseases is common, we don’t hear of big outbreaks of the disease even though stray cases keep getting reported.

For the novel corona virus, herd immunity is estimated to lie at around the 70-80 per cent level. That is, about four out of every five people should have got antibodies to the infection to arrest its spread. However, experts point out that it is not as simple as that for a new infection that humanity has never encountered before, which is what the novel corona virus is?

The rise of new strains that can cause reinfection can make herd immunity a non-starter. Also, the ability of any strains to beat vaccine antibodies may pose a challenge to achieving herd immunity.

Sero survey broadly indicates two things; firstly, the percentage of the population exposed to the virus. Secondly, which groups are more exposed or have had higher rates of infection. For example, if the sample population includes health workers, children, elderly then the results can tell that among the three groups, which group has had more infections. Thirdly, how infection rates are progressing in a particular area. For this, Sero surveys need to be done regularly. The Sero positive people or convalescent COVID-19 patients break the chain of transmission because they have immunity.

According to experts, usually memory cells consisting of T-cells and B-cells retain the memory of an infection for a lifetime so that when the virus attacks the body second time, memory cells can initiate faster and quicker immune response. However, in the case of COVID-19, nobody knows for how long the immunity lasts. But according to various studies, the immunity may last for four to six months.

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Dr. Gursharan Singh Kainth

Dr. Gursharan Singh Kainth is Founder–Director of Guru Arjan Dev Institute of Development Studies

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