The next SARS coronavirus variant may be no worse than the common cold
You cannot say that in public, my friends in public health would tell me. It undermines the global vaccination campaign. I trust that the readership of MEDIUM will recognize that we do not need the scare of future variants to justify vaccination, today. The current SARS-CoV-2 Delta variant is deadly enough. I also hold with Max Weber that science needs to “distinguish between empirical knowledge and value-judgments.” What follows is not a polemic for or against specific public health measures but speculation about the direction of viral evolution.
What are the odds that the next SARS-CoV-2 variant will be the “destroyer of worlds” instead of adopting a pattern like the common cold, human coronavirus NL-63, which emerged in 2004 and has been with us ever since? Strain variants of NL-63 accounts for approximately 10% of all respiratory infections. The difference to SARS-CoV-2 is that mortality is much lower. It is concentrated in the same populations (age, immune status) that are at high risk for death from any respiratory infection.
The molecular mutation rate of SARS-CoV-2 is fixed at ~5.5E-4 nucleotide changes/ site /year. The notion of a fixed mutation rate per generation implies the more transmission events occur; the more mutations will be sampled or selected by the environment and thus have a chance to spread among the population. If there are no transmission events because everyone wears masks, it doesn’t matter which mutations emerge within any one individual. They will be not be introduced into the population.
Viral mutations are like the stock market. At any instance, a new variant can either go up or down in fitness. Value is imparted by the environment, not the agent. Whether a particular mutation is considered a gain-of-function or a loss-of-function variant is in the eye of the beholder, i.e., us shaping the environment. As I will argue below, a deadlier virus is not necessarily a better virus, i.e., a variant that accumulates in the population. The reason is that ongoing worldwide surveillance and public health interventions create an environment where “being deadly” is an evolutionary disadvantage for an emerging pathogen.
For the purpose of estimating virus evolution, we are interested in two overt characteristics or phenotypes: (i) infection/transmission and (ii) disease/ death. This gives us four scenarios to consider for an emerging variant:
- “weaker transmission and weaker disease.” We see a lot of different variants when we sequence nasal samples, but nobody cares. They are blips on the radar and disappear rapidly.
- “weaker transmission and more severe disease.” These variants are of concern in congregate living situations or professional sports, such as the NBA, because transmission is always defined in regard to specific people and circumstances. They are less of a concern for ordinary life. I would count K12 schools here since the well-known seasonal head lice outbreaks attest to a more contact-rich environment than any adult workplace.
- “stronger transmission and more severe disease.” These variants represent the worst-case scenario. They are variants of concern, and their possible emergence justifies worldwide surveillance by sequencing. This possibility motivates worldwide suppression of transmission campaigns by masks, vaccines, and travel restrictions. For the virus, however, this worst-case combination is difficult to attain. One reason that made SARS-CoV-2 accumulate more cases than SARS-1 or MERS is that symptom onset is relatively late. People spread the virus before they knew they were sick. Vaccinated persons can spread the virus without symptoms. To cause more severe disease means more rapid onset of disease, particularly under high testing rates, which lead to rapid isolation of infected persons. Very sick people do not go out and transmit the virus. More rapid disease onset in an environment where rapid tests are readily available leads to fewer contacts and, therefore, lower transmission. Hence, as long as we keep testing capacity high, severe disease variants (like Mu) have difficulty spreading.
- “stronger transmission and less severe disease.” These variants mirror the coronaviruses that cause the common cold. Once introduced, we were never able to eliminate them ever again. They have become entrenched or endemic, as population virologists call this state. Localized outbreaks come and go in multi-year cycles. Just like the rabbits (prey) determine the number of foxes (hunter), so does population (herd) immunity determine the size and timing of the common cold.
For SARS-CoV-2 (or any virus), this equilibrium at Ro = 1 represents a stable state. The most successful viruses, such as Herpesviruses, have achieved this state and only cause severe disease in particular, exceptional circumstances. “Viral success” here is measured in seropositivity, which for some herpes viruses reaches 90% or more after kindergarten. A similar story holds for West Nile Virus, which was introduced into the US in 1999 and now has a stable reservoir in birds, is another example.
Interestingly, these arguments are independent as to whether a new variant can escape vaccine immunity or not. They are agnostic as to the mechanism for more transmission or more severe disease. These arguments reflect population dynamics.
I am still optimistic. Nature’s laws will protect us from extinction and establish an equilibrium with SARS-CoV-2 similar to the equilibrium we live in with the seasonal coronaviruses or the flu.
The value judgment everyone individually and we as a society have to make is what price we want to pay to get to that equilibrium state. This value judgment cannot be answered by scientific research or the scientific community. Compared to last year we are in an enviable position. Science had done its duty by explaining the nature of the problem and by stocking our tool chest with multiple highly effective vaccines, rapid tests, novel interventions, and proven public health measures. Making the right choices is up to everyone.
