Learning to live with Covid
Dr Anurag Agrawal, Director of Institute of Genomics and Integrative Biology
Are we done with Covid19? This is a question that seems to be on everyone’s minds. While Covid19 is not over, perhaps what we need is to answer the sub-text to the question – Can we get on with a normal life, while keeping risks of severe sickness or death within the normal range. The short answer is – yes, we can, through vaccines.
The severity of an infection is best seen through the lens of host immunity. Chickenpox and measles, which strike no fear in our hearts, decimated the native American population during the European colonization. It was the lack of previous exposure and immunity that made the infections much more severe in natives compared to their European counterparts. When Covid-9 started, we had little immunity to a rapidly transmitting respiratory virus, SARS-CoV2. Even then, only a few infections led to severe disease and death. The true infection fatality rate varied from less than one per 1,000 in healthy children to about 1% in high-risk adults. However, with huge number of infections in a short period and 5-10% of high-risk infections needing hospital care, the healthcare system was overwhelmed. Global adjusted estimates of Covid deaths, since 2019, are about three per 1,000 people. To provide perspective, the normal annual death rate is about eight per 1,000. The deep psychological impact of Covid came from tsunami-like waves of infections, where many people fell severely ill and faced difficulty in getting adequate healthcare, ultimately leading to many unexpected deaths within short periods. This sequence of events is what the public has in mind when they ask --Is Covid-9 over?.
The severity and fatality rate of any infection falls once the population becomes progressively immune. Vaccination is the preferred mechanism of acquiring immunity, when compared to infection, since infection carries the risks discussed above. To argue otherwise, based on adverse events after vaccination, betrays a lack of quantitative understanding of immediate and long-term risks. Reported short-term adverse reactions of vaccination, such as thrombosis or myocarditis, or even death, are more than hundred-fold more likely with infection, compared to vaccines. We are continuing to discover long-term health problems after infection, but so far there have not been any such problems for vaccination despite multiple doses. Last, but not least, unlike vaccination, infection transmits, putting others at risk!
We have seen that the virus evolves to escape immunity. This is true for natural infection as well as vaccines. Despite this, the presence of prior immunity sharply reduces the risk of severe disease during infections, even with newer variants. Further, recovery is faster and long Covid less likely in vaccinated people. During the severe Delta wave in India, breakthrough infections despite vaccination and reinfection despite prior infection, were both common. However, severe disease and deaths were mostly in vulnerable people who were neither vaccinated, nor previously infected. This vulnerable group was then sufficiently large that the health care system came under severe stress.
Today, things are very different. Immunity is much higher, partly due to the massive Delta wave, and partly due to one of the largest mass-vaccination programs the world has ever seen. Health care capacity has also been substantially upgraded. While Omicron was a less virulent variant than Delta, it was quite capable of causing severe disease and death in vulnerable people, as seen clearly in America, Hong Kong, and elsewhere. The much milder third surge in India compared to such places is thus a good sign for the future. In my opinion, even if Omicron had been as virulent as Delta, the third surge would not have been very severe. The main difference is immunity, and vaccines have played a critical role towards higher population immunity and minimising the number of vulnerable people. The next wave is again likely to be driven by a highly transmissible and immune evasive variant. Whether it will be less or more virulent, is a matter of chance. Betting entirely on progressive decline of virulence is unscientific and equivalent to playing Russian roulette. Relying on better immunity to reduce disease severity, independent of variants, is a much better bet. We are currently at a point where future outbreaks are expected to be manageable unless the virus changes drastically. The best way of minimising the risk of major changes to the virus is by denying it opportunities to replicate, spread and evolve.
How will we get there? First, we need better vaccines that can prevent infection and transmission. Nasal vaccines, creating higher level of immunity at the point of entry for a respiratory virus, are expected to be game changers. Second, we need a more diverse immune response targeting many mutable regions and/or a strong immune response targeting selected immutable regions of the virus. Such vaccines, covering both current and future variants, are under development. Given the huge strides we are making in vaccinology during the Covid pandemic, the day is not far away when we speak of respiratory vaccines directed against a multitude of viruses, rather than just one virus.
Vaccines have played an important role in limiting the impact of the Covid pandemic and are our best way forward. Relying on natural immunity alone to stop pandemics is analogous to taking comfort in an old surgical adage – all bleeding stops. On the national vaccine day, we must reflect on how vaccines saved lives in the recent past and imagine how innovations in vaccine-science can make our lives even safer in the immediate future.
(Dr Anurag Agrawal, Director, Institute of Genomics and Integrative Biology)