#SARS‐CoV‐2 virulence evolution: Avirulence theory, immunity and trade‐offs - Alizon - - Journal of Evolutionary Biology - Wiley Online Library
▻https://onlinelibrary.wiley.com/doi/10.1111/jeb.13896
In the long run, immune escape strategies may not be viable for coronaviruses because they impose too many constraints on their genomes (Belshaw et al., 2008). Such reasoning largely rests on our knowledge of the current seasonal coronaviruses, for which large pandemics of immune escape mutants have not been recorded. However, recent results from a time shift experiment conducted using human serum collected from 1985 and 1990 and synthesized spike proteins of the seasonal alphacoronavirus 229E from 1984 to 2016 found that our immune system appears to be less efficient at recognizing ‘future’ coronaviruses (Eguia et al., 2021). This would mean that regular reinfections by seasonal coronaviruses may not just be related to their ability to infect URT, where the immune response is limited, but could also depend on antigenic evolution of the viral spike. Furthermore, an important lesson from this pandemic is that extreme care should be taken before comparing SARS-CoV-2 to other viruses, even human coronaviruses. Indeed, this has led to underestimating the transmission before symptoms onset, the airborne transmission and even the magnitude of the pandemic. One of the most recent seasonal coronaviruses is thought to have emerged in the 1950s (Forni et al., 2017). As suggested by Figure 1b, even though half a century ago the age pyramids were different in many countries, the IFR of a coronavirus with a virulence pattern similar to SARS-CoV-2 would not have gone unnoticed, although the baseline immunity in the population to viral infections could have been higher at the time due to higher exposition to infectious diseases. This suggests that the virulence of the new virus, which is lower than SARS-CoV and MERS, with increased transmission before symptoms, but higher than the seasonal coronaviruses, is the worst in terms of population mortality. Again, basing our strategies on immune escape patterns from known coronaviruses can be extremely hazardous.
The high virulence of SARS-CoV-2 and its evolution makes it essential to closely monitor this trait. Beyond the definition issues raised in the introduction, a major difficulty for this resides in the proportion of asymptomatic or paucisymptomatic infections, meaning that the IFR is much more difficult to measure than the CFR. To minimize the biases in virulence estimation, the random testing strategy implemented in countries such as the UK seems ideal because it allows controlling for the proportion of variants (Challen et al., 2021; Davies, Jarvis, et al., 2021). International coordination for such random testing appears to be particularly urgent, especially in the context of vaccination (Kennedy & Read, 2020).
On a more positive note, the successful implementation of RNA vaccines does change the dark picture painted by immune escape risk. Indeed, these vaccines theoretically have the potential to follow the coevolutionary race with the virus, at least whereas its genetic diversity remains limited (Dearlove et al., 2020), and this could prove decisive, given the evolutionary rates observed so far. However, we also know that virulence-blocking vaccines tend to select for strains that are more virulent in nonvaccinated hosts (Gandon et al., 2001). More than ever, we need to monitor virus evolution to avoid an arms race between SARS-CoV-2 and public health policies (Kennedy & Read, 2020; Van Baalen, 1998).
