The question India is asking right now is who to give the Covid-19 vaccine to first, and the obvious answer is to all — and that is the root of the lack of knowledge on the coronavirus issue. Have you ever seen a beam of sunlight cutting across an apparently dust-free room? Then you would have seen the innumerable floating dust particles that were not visible until then. This is a reflection of our experience with Covid — we are not looking for what we should but are engrossed in serologic testing statistics instead.
It was estimated by the West that India would have several deaths on the street, our hospitals would be flooded, and doctors would be dying by the dozens. In fact, it was surmised that the combination of air pollution with Covid-19 would lead to almost two lakh cases per day by August. That is not happening, as is obvious. Yes, some hospitals are only seeing Covid-19 cases, and hence the doctors do not handle routine non-Covid cases. In such hospitals, doctors have 14-day shifts and then get one month off. So, they would be really unlucky to get Covid-19. But there are some hospitals, mainly central government hospitals, such as Ram Manohar Lohia Hospital (RML) in New Delhi where we have been handling routine non-Covid as well as Covid-19 cases day in and day out, and doctor haven’t died by the dozens. If we had no immunity, how would this be possible?
There was an inexplicable incident in our hospital where one resident doctor, who had lunch across a table with four other residents, turned out to be Covid-positive while the rest did not. Mind you, the guidelines state that mask-less exposure of more than 15 minutes within six metres is high risk. And then there are numerous stories of families where all except a few got the virus. Of course, the reverse is also true where one family member inexplicably dies and the other members are not even seropositive. An explanation for this has great implications because obviously, not everyone in a country is going to contract the virus in its full glory — the question is why.
We often trivialise the enormous complexity of the body’s defences also known as the immune system. What we test is just one small part of it, the antibody, the so-called “serological test” that gives short-term protection. And now we know that its results and responses are pretty non-uniform, as can be seen by the failures of the much-vaunted plasma trials. In fact, not all who have been exposed to coronavirus have positive antibodies, but they still may be immune.
To understand our immune system, let us compare it with India’s defence. We have the Border Security Force (BSF) and the Indo-Tibetan Border Police (ITBP) on the border — that may be the inborn or initial defence. But if that fails to control the invasion of the enemy, the Army steps in— let us call that the adaptive response. In both these immune responses, there is the superlative role of a important cell of the body called the ‘T-cells’ — but tests for them aren’t widely available. But they exist, there is no doubt about that, and they mitigate and protect against the infection.
Now, evidence suggests that not all are contracting the virus even in a Covid-rich setting like New Delhi. The novel coronavirus or SAR-CoV-2 belongs to the same family that is known to cause a common cold. And we have all been getting the common cold for years. In fact, in India, the biggest selling over-the-counter drug (OTC) brands are of cough syrups. Now, each common cold infection leaves an imprint on the body, similar to how each small skirmish with our neighbours leaves behind a memory. So, it is logical that these viruses can lead to a memory T-cell immunity, and be protective.
It is known that ‘unexposed individuals to Covid have a pre existing cross-reactive memory in 20 to 50 per cent of people’. A paper by Jose Mateus published in Science in October showed that patients who were apparently healthy had immune cells that targeted both the SARS-CoV-2 and the common cold coronaviruses. Another paper, by Nina Le Bert published in Nature in August, showed that there were SARS-CoV-2-specific T-cells in individuals with no history of SARS, Covid-19, or contact with individuals who had SARS and/or Covid-19. And more good news, even those with a mild infection have long-lasting immunity, according to the famous Karolinska Covid-19 Study Group. More remarkably, this very response is poor in individuals greater than 65-years old, thus accounting for the poor disease outcomes, as per a paper from La Jolla Institute for Immunology in the US. So, in simple terms, it seems like a similar virus causing common cold and other viruses that caused respiratory symptoms even before Covid arrived can lead to cross-immunity, which is protective. And even exposure to asymptomatic Covid patients can lead to long-term immunity. Significantly, those who get a mild or undetected infection will still get long-lasting immunity even though their sero test is negative.
Role of the vaccine
Let us consider New Delhi — with around 33 per cent seropositivity and considering a mean of 30 per cent of prior immunity, as per the Science paper, we have close to 60 per cent T-cell immunity. It’s hard to believe that those 30 per cent Covid-Positive people will not spread to others, and in addition, considering that children are largely immune, one does not need to vaccinate the whole population. This T-cell immunity explains why some of our resident doctors got the virus and others didn’t while eating across the same lunch table, even without masks. The commonality of cold-causing viruses explains why some RT-PCR positive cases are hale and hearty — maybe the common cold coronaviruses were picked up by the RT-PCR test (possibly). The implications are huge and go beyond the former Pfizer Chief Scientist Dr Michael Yeadon’s article on the futility of vaccines, which may not be entirely believable.
Three things are clear. First, we have the wrong way of assessing immunity — the sero test. Second, we are also using the wrong method of treating plasma that just contains short-term antibodies, which probably don’t do much by themselves. Third, all the medicines currently being used don’t even look at the T-cell response, which is crucial and may be as important as the drugs.
While vaccinating is a great way to kickstart long-term immunity, will it be needed in those who have no T-cell response? A piquant issue is how to pick up a T-cell naïve population in the absence of testing. This is actually quite simple — those who have been exposed and have been shown to be positive on either serotesting or RT-PCR don’t need it as they will in all likelihood have a T-cell response. The cases of reinfection even reported by genetic mapping are minuscule if you look at the size of positive cases in India, and have little real life meaning. And if we consider Delhi’s data as a true reflection of concerted testing and the lack of social distancing then possibly only a fraction of the susceptible population actually needs the vaccine, largely the elderly. So what is the use of administering vaccines to everyone? Unless it’s free of cost, which it isn’t. While I will not dwell on the side effects, which is the domain of the regulatory agencies, to expect large populations to be compliant with a two-dose vaccine, apart from the stupendous infrastructure and administration issues, is a logistical nightmare.
Who benefits from mass vaccination, tests that look for short-term immune markers, and the sales of multiple drugs is not rocket science. We must remember that no virus in the history of humankind has ever been cured, not even the herpes virus — so don’t look for a cure. It is the past imprint of infections, in this case, similar viral infections, that will save us ultimately.
There may be a sense of fatalism and a lack of do-ership in all this, as people believe they should do something, but the ‘do-ership’ has been done by nature. Nature has been building our long-term immunity over the years, and that is probably the best bet we have for now. Despite the fancy treatments with even fancier costs in private hospitals, the vast and overwhelming majority get better even in public hospitals, which is ample proof that probably it is just immunity that is the ultimate winner. And in all likelihood, that hidden immunity is probably the natural coronavirus infection that acts as ‘nature’s vaccine’ that a sizeable number, have already been exposed to in India.
The author is a professor of dermatology at RML Hospital, New Delhi, with an active interest in the immunology of chronic infections. Views are personal.