How Will the Coronavirus Evolve? – Scientific American

With declining rates of new infections and the rollout of vaccines, some are beginning to speak of an end to COVID-19. But that rhetoric, in my opinion, is ill-considered and premature. Based on what we know now of SARS-CoV-2, it may no longer be a question of months before an end to the pandemic but a question of years, if not decades. We should plan for it.

Viruses exist to thrive. Those that infect humans are faced with an impressive array of defensive weaponry, not just our natural adaptive immunity but also our intelligently designed defensesvaccines, drugs and social controls. For a virus to survive, it must be adapted to its chosen ecological nichein this case, usand capable of further intricate adaptation to overcome our best efforts at prevention and treatment.

Initially, many assumed that coronaviruses in general and SARS-CoV-2 in particular were more stable and less prone to adaptation than other RNA viruses because of their error-proofing mechanisms. But we have since been proven wrong. Last summer, a researcher in Texas noticed that a mutated SARS-CoV-2 virus with a substitution in the spike protein had overtaken previous forms to become the dominant strain. Since then, multiple new variants have emerged with mutations that can make the virus more transmissible, more lethal and more able to evade our immune defenses.

These variants have seemingly been forged in fires of our own making. In Boston, a middle-aged man struggled with a COVID-19 infection for five months before succumbing to the disease. He was undergoing treatment with immunosuppressive drugs when he fell ill, and, during his illness, he received multiple rounds of additional treatment, with remdesivir nonimmune gamma globulin, and with monoclonal antibodies. Under this intense immune pressure, key mutations in the virus emerged. The doctors and scientists who witnessed their birth called it accelerated viral evolution.

Other viruses, like influenza, have shown themselves similarly capable of rapid evolution when faced with our best defenses. Indeed, based on what weve seen of SARS-CoV-2 and its capacity for variation, Id say this virus is much more like influenza than any other virus known to date.

Which means influenzas evolutionary pathway may hold important clues about the road COVID-19 will follow.

Influenza, as we know, comes and goes in seasonal waves in the Northern and Southern Hemispheres. In the tropics it occurs throughout the year, with only shallow peaks. This pattern mimics what we know of cold-causing coronaviruses, which, ever since their discovery in the 1960s, have returned annually to infect us. For the flu, antigenic driftthe accumulation of small genetic changes in the virushas been the primary explanation for recurrent seasonal epidemics. Dominant flu strains evolve from year to year, and the immunity we develop in response to a previous strain has only a muted effect on the new strain. Weve learned more recently that immunity to influenza also fades, often disappearing within a year, which also makes us susceptible to reinfection.

We used to believe that the cold-causing coronaviruses were stablemeaning no antigenic driftbut returned yearly because of faded immune protection. But over the past year, our understanding of coronaviruses has improved and we now know that at least one of the cold-causing coronaviruses, designated 229E, undergoes antigenic drift similar to that of influenza.

SARS-CoV-2, like 229E, has already shown that it can drift. But, like influenza, it has also shown itself capable of much more abrupt and substantial changes.One way these major changes happen occurs when a virus jumps to a new population, for example from animals to humans or back again. When a virus makes this jump, big thingsand often bad thingsmaterialize. Both influenza and SARS-CoV-2 have huge animal reservoirs. Coronaviruses have infected every type of vertebrate, from whales and bats to salamanders and snakes. Influenza is similar. This means they both have the potential to evolve to become much more damaging to our population. The two previous coronavirus outbreaks both started when coronaviruses jumped from animals to humans, from civet cats in 2003 with SARS and from camels with MERS in 2012. The 1918 influenza pandemic likely started with a jump from animals too.

If were lucky, SARS-CoV-2 will evolve, like the 1918 virus dubbed the Spanish flu, to become less lethal. After infecting an estimated 500 million worldwide and killing at least 50 million, the 1918 flu virus receded. But hope that this coronavirus will attenuate over time is no guarantee that it will. We already know that coronaviruses can become much more lethal; we need look no further than SARS-CoV-1, which killed 50 percent of those aged 65 and older, and MERS, which killed one out of three infected.

So where does that leave us?

First, we must accept the harsh truth told by this virus and its variants. We can expect it to come backpotentially for years to comeand we need to prepare ourselves for the possibility that when it does, it may be more lethal and even more transmissible than the variants that exist today. We must adjust our vaccine development pipelines and public health interventions to account for emergent and future variations. Much like what has been proposed with influenza, we must develop COVID risk assessment tools that can identify the viral properties of dominant strainshow transmissible they may be or how resistant they are to current drugs or vaccinesto help us align our public health response with the level of risk. Otherwise, well be setting ourselves up for failure once more.

I have often likened SARS-CoV-2 to the mythical Proteus in Homers Odyssey. Like Proteus, SARS-CoV-2 is the quintessential shape-shifter, able to alter its form whenever grasped. It is only through sheer persistence that Menelaus, the great hero, is able to wrestle Proteus to a standstill. By claiming victory too soon, we risk losing our battle with this shape-shifting virus, a tragedy that would unfold this time not in words but in many more millions of lives lost.

This is an opinion and analysis article.

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How Will the Coronavirus Evolve? - Scientific American