How SARS-CoV-2 evolved through the pandemic

A new study from researchers at Weill Cornell Medicine-Qatar (WCM-Q) reveals how the SARS-CoV-2 virus evolved from initially prioritizing increased transmissibility to enhanced immune evasion after the omicron variant emerged.

Over the course of the pandemic, the virus has undergone rapid genetic mutations that have led to multiple variants with differing abilities to spread between individuals, cause severe infections and evade the immune system.

The study, published in Nature, was conducted through a Qatar-based collaboration of six institutions and presents population-level epidemiological analyses on over 1.5 million people, covering the four-year span from when the pandemic began.

The study revealed that before the omicron variant emerged in late 2021, natural immunity gained from a previous infection provided sustained and robust protection against reinfection with around 80% effectiveness. However, after omicron became the dominant strain, immune protection was strong only in recently infected individuals and rapidly declined to negligible levels within a year. These trends were consistent whether reinfection was considered as any infection or limited to symptomatic cases.

“This ongoing evolution and immune evasion make it challenging to achieve long-term population immunity against the virus,” said Hiam Chemaitelly, first author of the study and assistant professor of research in population health sciences at WCM-Q. “The short-lived immunity leads to repeated waves of infection, mirroring patterns observed with common cold coronaviruses and influenza.”

The findings indicate that the emergence of omicron marked a turning point in the pandemic. Before omicron—when most of the population remained uninfected due to widespread public health interventions—the virus evolved by genetic mutations that increased its ability to spread from person to person. In this phase, more transmissible variants, such as alpha and delta, emerged.

In contrast, during the omicron era, prior infections and vaccinations generated widespread immunity that pressured the virus to evolve mechanisms to escape a person’s immune defenses, leading to a rapid decline in natural immunity against reinfection. This shift gave rise to highly genetically diverse subvariants of omicron, such as XBB and JN.1.

“This virus is here to stay and will continue to reinfect us,” Chemaitelly said. “Regular vaccine updates are critical for renewing immunity and protecting vulnerable populations, particularly the elderly and those with underlying health conditions.”

“The virus has shown remarkable adaptability, allowing it to persist in human populations and cause repeated reinfections,” said Laith Abu-Raddad, the senior author of the study and professor of population health sciences at WCM-Q. “Fortunately, these are almost always mild or asymptomatic. While the virus will remain part of our lives, it will no longer pose the same severe threat as it did when it first emerged.”