Is Omicron the beginning of Covid’s endgame?

Some experts are beginning to compare the ongoing Omicron wave to the last (“exit”) wave of the Great Influenza Pandemic of 1918. The implication is that SARS-CoV-2 has progressively mutated into a milder variant, and the pandemic could be coming to an end. Let’s try to understand some of the science behind this supposition.

Infections during a pandemic are sustained depending upon two important factors: The virus’s ability to mutate, and the population’s level of immunity against the infection. Mutations are random copying errors in the virus’s genetic material that occur every time it replicates. During a pandemic, mutations are common because of the billions of times the virus replicates in infected people. In the beginning, when the entire population is susceptible — no one has any immunity whatsoever — the mutants that dominate are predominantly the ones that make the virus more transmissible (the ones that allow the virus to be more easily passed on from person to person). This is a simple consequence of natural selection. In this pandemic, for instance, the more transmissible Alpha variant replaced the original strain, and then, the Delta variant replaced all previous variants. Two years into the pandemic, things have changed. A large chunk of the population is now immune to the virus, either through vaccination or through prior infection. In India, for example, 70 per cent of the adult population is fully immunised, and some more have perhaps acquired immunity through infection.

At this stage, therefore, the mutations that provide the virus with an evolutionary advantage are the ones that help it evade immunity — more than the ones that make it more transmissible. Simultaneously, there is one other important pressure on natural selection constantly at play. Variants that rapidly debilitate or kill off their human hosts are at a disadvantage because they have less opportunity to infect other humans. On the other hand, the variants which produce milder illnesses (or cause no symptoms) make for more ambulant humans who can efficiently spread the virus. The emergence of the Omicron variant, possibly, illustrates this sequence of events.

So far, so good. But how do we know that future mutations will not result in producing variants which produce severe disease? Of course, we can’t be sure. Mutations are random events — akin to rolling a dice that has a million sides — but there is hope, nevertheless. There are two broad reasons why this may not happen. First, as a larger part of the population becomes at least partially immune (due to infections by previous variants, and vaccinations), our ability to fight off the virus progressively improves, resulting in less severe illness. In addition, we have also begun to realise that prior infections with other seasonal coronaviruses afford some protection against SARS-CoV-2, highlighting the importance of more general immune responses that are less dependent on specific proteins on the virus.

The second reason is that additional mutations may have evolutionary costs for the virus. This is particularly so when mutations that cause immune evasion must involve the structure of one relatively small region of the virus (the spike protein in this case), a part of which is also responsible for its ability to infect. For example, the Omicron variant has a whole bunch of mutations affecting the spike protein, and research suggests that it is not as efficient in infecting lung cells as its predecessors. This may partly explain the conclusion in some preliminary studies of a 70 per cent reduction in the odds of dying from an Omicron infection compared to infection with Delta. In short, because this target region is small, there may be constraints on the number of possible mutations that would ensure immune evasion, transmissibility, and the ability to cause serious illness.

What happens after the pandemic ends, is a subject of even greater speculation. As has already become evident, we aren’t going to have lifelong protection after infection or vaccination. It is reasonable to expect that the virus will continue to mutate to evade immunity. Of the several unsavoury scenarios, one optimistic (and perhaps also likely) possibility is that the virus continues to circulate but infects only people without immunity — children born after the pandemic, older adults, or others with waning immunity. These vulnerable individuals will continue to require vaccination. This is presumably what happened after the 1918 pandemic. That virus now causes seasonal influenza.

Some will undoubtedly consider this to be too optimistic an account of what may transpire in the coming months and years. But there is no denying that this is a
plausible scenario, at this point in the pandemic. We must limit the number of new cases around the world — by masking, distancing, and vaccinations — so that the chances of another new, more troublesome variant emerging are reduced. That is something to wish for in the New Year.

Karthikeyan is a Professor of Cardiology at the All India Institute of Medical Sciences, New Delhi. Views are personal