Based on the serosurvey conducted in Delhi towards the end of June, Dr. Sanjay Rai , Professor of Community Medicine at the AIIMS, Delhi who also heads the Covaxin trial at the Institute, says the number of infections in the city could be almost a 100 times the detected number. The results also point to community transmission and trend toward herd immunity.
The serosurvey in Delhi by the National Centre of Disease Control tells us that out of the 21,000-odd people whose blood samples were tested, at least 22.86% — or one in five — had antibodies specific to SARS-COV2. What inferences can we draw from this about the disease and the way it spreads?
The sero-surveillance in Delhi showed, if I recall correctly, 23.8%. That means around 24% of the people had antibodies against this SARS-COV-2. This means that around 50 lakh population of Delhi was infected with COVID-19 around mid-June, because we require a minimum 15 days to develop antibodies. At this time, the recorded number of cases for Delhi was something around 50,000. This means there are hundred times more cases than detected. So that means undetected cases are either mild or asymptomatic. This is the inference I draw from this [sero-survey] report.
Do the others continue to be vulnerable to the virus?
This could be possible. There are some limitations to the test. This test cannot detect 100%of the infected people. But overall, the sensitivity of this test is good and the specificity is also good. That means if the person has detectable levels of antibodies, then this test can detect it. There are a few reports that after two to three months of infection, the antibody levels are going down. In some proportion of the population if this [antibodies] go down, that means this test will not detect them. But I can say 24% of the population is infected [as per the sero-survey report].
How does this sero-survey impact our understanding of the infection fatality rate and the case fatality rate? And how does it inform our fight against COVID-19? Everyone is talking about herd immunity. Is it possible at all without a vaccine? And if so, at what cost?
Case fatality rate means total number of deaths vs total number of identified cases. In Delhi it’s around 3% currently. If only 1% of cases have been detected — based on the sero-survey report at that time, the cases should have been around 50 lakh whereas it was around 50,000 then. So we detected only this much. Then infection fatality ratio would be very low. The case fatality rate is already known to everybody, but infection fatality rate is very low, based on this [sero-survey report].
Then what is herd immunity? Indirectly you are protecting others through an immunised group of people. It means indirect protection from infection conferred to susceptible individuals — those who are around these infected individuals.
We are definitely [moving] towards herd immunity, but we have not reached it yet. For herd immunity you need at least 50 to 60% of the population to be infected. But, yes, we are very far from herd immunity but we are moving in that direction. Herd immunity means we will stop the transmission. Transmission has not stopped at this stage but gradually we are moving towards that.
The survey suggests that about 50 lakh people in Delhi were infected. And this means that they were infected at least two weeks before the sero-survey was started on June 27. So what does this tell us about the effectiveness of lockdowns? Is there actually a scientific case to make for a lockdown?
We have to understand the overall goal and objectives of the lockdown. It should be health system preparedness, right? We know we cannot prevent this disease, we can [only] delay it. This disease mainly transmits from one person to another through droplets.
So, if people are not mixing, then this will delay the transmission. But we can’t prevent complete mixing either in the family or in very close circuits, or in various other [settings] like in healthcare facilities. You can’t close the hospitals. That means you cannot prevent, but you can delay.
So, this was the objective of our lockdown — if you delay the infections and are able to spread it over time, the health system will not be burdened and serious patients will get proper treatment. So, the overall objective was to reduce this burden of the health system. Hence the mortality rate will go down.
Strict lockdowns going on in some other States may delay the infection rate but now it’s been four or five months. So at this moment just for delaying [infections], I can’t justify that. I don’t know the objective of these lockdowns.
In India, during the initial phase, our country was not ready so I can support the first lockdown. But the current lockdown, definitely we cannot support as a public health specialist.
There is no scientific basis for the continued lockdown is what you are saying?
I can say there’s no scientific basis now. During the initial phase, there was some basis — like we wanted to prepare ourselves for the increased number of cases, and the country was not prepared. So we can support that. But not now. And there are also other health problems that need attention other than COVID. And this lockdown has disrupted all these health-related activities. So they are really suffering.
About the antigen kit used for the Delhi sero-survey — can you explain how the sensitivity and specificity of the testing kit has a bearing on the final results?
This kit was evaluated by ICMR, and it has good sensitivity and specificity. The sensitivity was 93% and the specificity was also very high.
What does high sensitivity mean for the test results?
So, if antibodies are present in a hundred people, this test can correctly detect 93 people. So this is the sensitivity. So if sensitivity is more than 90%, we can say it is good sensitivity. And specificity was also more than 95% — exactly I don’t recall. As I mentioned earlier the kit was validated by ICMR.
So the kit would still slightly under-estimate, but very slightly, of sero-positive people because of high sensitivity, 93 percent. So that is why I said these are the bare minimum numbers.
An earlier serosurvey conducted by ICMR, the study of which has not yet been published, but the results of which were shared at various points suggested that 0.73%prevalence of the virus in India. So what would be the picture now because many models are suggesting that we could eventually have maybe 200 million infections. Is that possible?
The Indian scenario was entirely different. The lockdown was announced on March 25. That time there were only 600-something cases, right? As per this report, the prevalence of the virus in India was 0.73 %. The baseline was around April 30. And this means, if you extrapolate to the entire country with a 137 crore population, just multiply with 0.73 — it is around one crore-something (10 million-odd). And the models predicting 200-300 million infections eventually, seem to be very far [off]. This sero-surveillance, this was based on some scientific data. And these models are based on only assumptions.
What do you feel about the ICMR still refusing to accept community transmission?
Again what is community transmission? As part of our knowledge, our understanding of community transmission is if you are unable to detect the source of the majority of the cases. So, currently, in Delhi or Maharashtra and in many parts, except the northern eastern parts, I believe, in the majority of cases we are unable to detect the source. So, I can say widespread community transmission is already going on.
The sero-survey showed the presence of SARS COV-2 antibodies. Does this mean that the person is protected against the disease or that they've had the disease and developed the antibodies. And are these two different things?
According to the knowledge we have till date, this indicates that the presence of antibodies [are] protecting [the person]. This virus is a self-limiting virus. We don't have any treatment. If you see the recovery rate is around 80% currently. So that means they are recovering without any treatment for this virus. So they are [recovering] because of the presence of antibodies. The body prepares antibodies to fight against this virus, and that’s why it’s a self-limiting virus.
So currently, [with] whatever knowledge we have, we can say this virus is protecting [us] up to six months. It’s a six-month-old virus so I can’t predict in the future what will happen...Currently with whatever knowledge we have, I can say it's protecting, so those who had the infection, are protected at least for six months, I can say.
So, how long are these antibodies present in your body? Do stay for several months?
There are various mechanisms – immunity related. Once the SARS Coronavirus-2 [is there], the body develops immunological memory against this virus. So, even in the absence of detectable antibodies, it may be possible that we are protected. Although we don’t have sufficient evidence, we may say.
Could you talk to us a little bit about the Covaxin trial?
There are two vaccine trials. One has just started, one had already started — both are in phase one. So there are three phases. Both are indigenous vaccines. Abroad there are many candidate vaccines.
The first one, the virus was isolated by ICMR a few months ago, and then both ICMR and Bharat Biotech developed this vaccine. And phase one has already started in 12 centres in India. And our AIIMS is one of them. Still we are in phase I; we have not started phase II. After completing phase I we will start phase II and then finally phase III. The main objective of phase I is to establish the safety — that this vaccine is safe. Although we check the immunogenicity — that means production of antibodies level — but that is not the main objective. The main objective is the safety profile of this vaccine. In subsequent phases like phase II and III, our main objective is to see the immunogenicity along with the safety profile.
How soon can we expect the vaccine?
It’s very difficult to predict anything about how soon you will get the vaccine. It's dependent on what is the effectiveness of this vaccine, what is the safety profile, and all this. But if everything goes as per our plan, — like this vaccine is very effective and safe for human use — then you may get a vaccine by the end of this year or early next year.
