Assessing the risk of vaccine-driven virulence evolution in SARS-CoV-2

Abstract

Vaccines that reduce clinical severity but not infection or transmission could drive the evolution of increased rates of pathogen-inflicted damage, or virulence. Preliminary evidence suggests that COVID-19 vaccines might have such differential effects, conferring greater protection in the lower respiratory tract, where viral growth most impacts severity, than in the upper respiratory tract, where infection is chiefly determined. However, the evolution of increased virulence can only occur under certain conditions, which include the existence of a positive association between transmission and severity linked to viral genetic variation. Here, we review the current evidence for these conditions, which does not point to a risk of vaccine driven virulence evolution. An evo-epidemiological model also indicates that upper respiratory tract protection can minimize or negate selection for increased virulence should these conditions be met. Despite low apparent risks, SARS-CoV-2 virulence should be monitored, and transmission-limiting characteristics should be prioritized for ‘second-wave’ vaccines.

Epidemiological and evolutionary considerations of SARS-CoV-2 vaccine dosing regimes

“…4A), adaptive immune responses following waned natural, one dose, and two dose vaccinal immunity all lead to similar intermediate levels of immune pressure and high rates of viral adaptation. In all cases, we assume for tractability that viral immune escape is not correlated with clinical severity (27). The relative potential viral adaptation rates [see (17) for more details] corresponding to each scenario are presented in the top rows of Fig.…”

“…4A), adaptive immune responses after waned natural, one-dose, and two-dose vaccinal immunity all lead to similar intermediate levels of immune pressure and high rates of viral adaptation. In all cases, we assume, for tractability, that viral immune escape is not correlated with clinical severity (27).…”

COVID-19 adaptive evolution during the pandemic – Implications of new SARS-CoV-2 variants on public health policies

“…In other words, this policy risks inadvertently selecting for variants that are better able to infect children, with higher titers and greater pathology in this previously largely refractory age group. Secondly, although vaccine driven virulence evolution remains only a theoretical possibility, the risks of a more virulent strain spreading into an under-vaccinated population could be more severe [ 15 ].…”

The adaptation of SARS-CoV-2 to humans

“…The increased virulence of some virus variants is regarded as a transitory phenomenon due to host immunity constraints. (239) Since, at present, there is a lack of compelling evidence of an overall increase of SARS-CoV-2 virulence, (240,241,242,243) there is no plausible reason to expect a future worsening of the COVID-19 pandemic.…”

“…(240) Although several variants of the virus have been detected worldwide, some associated with increased viral loads and transmissibility, there is so far no compelling evidence of an overall increase of SARS-CoV-2 virulence capable of leading to a worsening of the pandemic. (240,241,242,243,259,260) The most plausible scenario for SARS-CoV-2 evolution is to become part of the respiratory tract virome and occasionally give rise to seasonal outbreaks of common cold, as happens with the four other coronaviruses.…”