An interesting article published in the Scientific American by William Haseltine looks at this issue.
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 Haseltine’s opinion is ill considered and premature. He feels that based on what we know about SARS-CoV-2, it will be a question of years if not decades. He wonders how 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 defences – vaccines, drugs and social controls.
For a virus to survive, it must be adapted to its chosen ecological needs – in this case, us – and capable of further intricate adaptations 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 unfortunately, this has been proved wrong.
Last summer a researcher in Texas noted 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 defences.
These variants have seemingly been forged as a result 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, non-immune gamma globulin, and with monoclonal antibodies. Under this intense immune pressure, key mutations in the virus emerged. The doctors and scientists who witnessed their emergence called it accelerated viral evolution.
It would appear that this virus is more like influenza than any other virus known to date and this has a key. This may mean that influenza’s evolutionary pathway may hold important clues about how COVID-19 will evolve.
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 drift, the accumulations of small genetic changes in the virus has been the primary explanation for current 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. We have learned more recently that immunity to influenza also fades, often disappearing within a year, which also makes us susceptible to reinfection.
SARS-CoV-2 has 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 things – and often bad things happen. 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 becoming much more damaging to our population. The two previous coronavirus outbreaks both started when coronaviruses jumped from animals to humans, from civet cats since 2003 with SARS and camels with MERS in 2012. The 1918 influenza pandemic likely started with a jump from animals too.
If we are fortunate, 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.
However, while the hope is that this coronavirus will attenuate over time, there is no guarantee that it will. We already know that coronaviruses can become much more lethal; we need to look no further than SARS-CoV-1, which killed 50% of those aged 65 and older and MERS, which killed one of three infected.
So what does this mean?
First, we must accept the harsh truth told by this virus and its variants. We can expect it to come back – potentially for years to come – and 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 strains – how transmissible they may be or how resistant they are to current drugs or vaccines – to help us align our public health response with the level of risk. Otherwise, we will be setting ourselves up for failure once more.
SARS-CoV-2 can be likened to the mythical Proteus in Homer’s 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 is not in words but in many more millions of lives lost.
Dr Paul Ettlinger
BM, DRCOG, FRCGP, FRIPH, DOccMed