Senior immunologist Dr. Dipyaman Ganguly, principal scientist, CSIR-Indian Institute of Chemical Biology in Kolkata, has seen some encouraging signs. Few cases of reinfection and effectiveness of therapy using immunosuppressants are some of those. He prescribes a combination of personal commitments and policy-level commitments in addition to mass vaccination in order to reduce the pandemic to a manageable proportion. Excerpts...
Q: So far, what have we understood about our immune response to the SARS CoV 2, and what remains to be understood?
A: We could gather quite a bit of information from the earlier stints of the pandemic in 2020. But I must say the disease caused by the coronavirus is too enigmatic to be confident that we know everything about it by now. The most important lacunae are how the new variants will affect the course of the pandemic. It was clear from the very beginning that the virus is going to be a menace for humanity for a long time in the future. It is mostly clear that the pandemic will end up as an endemic disease.
Q: We know that the immunity conferred by the natural infections, contributed by antibody-producing B cells and the T cells, is working well for one and half years. Even in this fast-evolving second wave of infection in India reports of reinfections are rare, which is a dependable testimony for this assuring conclusion.
A: The evidence gathered from all over the world in support of a hyperactivated immune response in the patients succumbing to severe disease is also being supported in the second wave as well. Thus the medical therapy using immunosuppressants like corticosteroids is saving a lot of lives.
The vaccines have been rolled out and most of the health care workers and a considerable fraction of the senior citizens in the country have received a complete regimen of the vaccines and anecdotal evidence suggests they are also not being documented to succumb to symptomatic disease in the second wave. These are all dependable positive information. Regarding the duration of immune protection conferred by the vaccines, we do not have enough data as the vaccines have been there for just six months or so. If vaccine-induced immunity also follows the pattern similar to natural infections, a lot of lives will be saved.
Q: What does the current wave of Covid-19 infections, which is worse than the first national wave, indicate, and has it surprised you in any way?
A: There are several non-mutually exclusive reasons for the much steeper and higher amplitude of the second wave. I believe a major reason has been an insidious complacency resulting from the gradual reduction in the number of cases, and more importantly too much stress upon the information that younger citizens are protected from disease severity. These had made the younger citizens too casual as the statutory lockdowns were over.
Secondly, a major fraction of the infections in this second wave is due to the newly emerging variant strains. A number of them have documented higher transmission rates, e.g. the B.1.1.7 strain or UK strain. As a result of these different factors, we are actually seeing a high-amplitude second wave with a large number of younger citizens also being afflicted with symptomatic diseases.
Q: Do you think mutation might be having a big role to play in the ongoing wave of infections?
a: As I already mentioned, the variant strains harbouring the concerning mutations are constituting a large fraction of the new infections, and some of them do have higher transmission rates, e.g. the N501Y mutation (now nicknamed Nelly) in the UK strain spike gene.
As you must have noted from myriad media reports, a large number of these variants do have abilities to somewhat escape the immune protection conferred by the natural infection with the earlier strains or vaccines, e.g. the Eek (E484K) mutation in the South African B.1.351 and the Indian double mutant (B.1.617) strains. But personally, I am keenly following reports of reinfections in the second wave among individuals with a previous history of natural infection with the earlier strain or people who are fully vaccinated. Till now such reports are rare. That is sort of indicating that the immune escape of these mutant viruses registered in the laboratories may not be getting too dangerous in real-life scenarios. It may be that even the suboptimally efficient immune protection, against these so-called escape variants, is being able to prevent severe symptomatic diseases from occurring. We will have to be actively vigilant for such occurrences, by ramping up viral sequencing efforts all over the country as well as meticulously documenting the reinfections. If this trend remains as such it will be a great relief.
I would also like to point out here that this also means that therapeutic approaches like convalescent plasma therapy should be explored in this wave too. The only antiviral therapy which is sought after leading to a temporary crisis regarding its supply is the repurposed drug Remdesivir. Interestingly, the importance that CPT was given in the first wave of the pandemic is absent in the second wave. The major reason for that has been contradicting results from different randomised control trials done in different parts of the world that explored its efficacy. Most meta-analyses failed to show a ‘universal’ efficacy of CPT in Covid-19. Of note here, the therapeutic benefit of Remdesivir was also not proven in clinical trials worldwide.
In this regard, one should keep in mind that some of the well-documented trials, both from India and abroad, did show that CPT may confer a very significant survival benefit in the younger Covid-19 patients who were succumbing to severe disease. A smaller study done in Kolkata reported significant benefits in patients below 66 years of age. A much larger trial in the USA reported a similar efficacy in patients below 65 years of age. Given the larger number of younger citizens succumbing to severe symptoms in the second wave, these data should be paid heed to. After all precision medicine is the way forward in the medical sciences and thus depriving patients of a therapy that may be beneficial to them, even if not to all patients, is not prudent. At this phase of the epidemic, the potential convalescent donors are not in dearth. Just a well-coordinated awareness campaign, smooth running plasma banks, and a prudent protocol for selecting recipients who will benefit from it can save a lot of lives.
Q: Some metropolitan cities like Delhi, Mumbai, and Pune which had seen quite a few peaks before are also seeing even a worse situation. Do you think serosurveys — showing quite high seropositivity rates in these cities- painted a misleading picture and lulled people and governments into some sort of complacence?
A: I do not think that the seropositivity rates were misleading. The serosurveys never reported a level of seroprevalence that could even theoretically prevent pandemic progression. A large number of citizens were left susceptible and they are now getting infected. As I mentioned the second wave of the epidemic in India is yet to record a significant number of reinfections. One may consider the possibility that the seroprevalence data were wrongly read by the lay citizens, which perhaps led to their complacent behaviour of doing away with the physical distancing measures.
Q: What level of Covid vaccinations should be achieved before we can see the pandemic ebbing?
A: My understanding about the pandemic tells me that vaccination alone cannot end the pandemic. The so-called ‘Swiss cheese’ model of pandemic protection, which was originally proposed in 1990 by James Reason, a cognitive psychologist, to explain how to prevent accidents from occurring, is being frequently invoked by experts in the context of the present pandemic. This tells you that a single measure cannot be full-proof in preventing the pandemic from progressing. A combination of personal commitments to pandemic-related restrictions (like mask use and physical distancing) as well as policy level commitments to contact-tracing, ramped up testing and viral sequencing, easy accessibility to necessary healthcare, in addition to the mass vaccination measures, can reduce the pandemic to a manageable proportion and save a lot of lives.