Colorized scanning electron micrograph of an apoptotic cell (blue) infected with SARS-COV-2 virus particles (red), also known as novel coronavirus, isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Photo: National Institute of Allergy and Infectious Diseases, NIH/Handout via REUTERS.

In a study about how COVID-19 variants are formed, researchers in Israel have found that patients with a weakened immune system are at risk for chronic infection and can develop highly mutated forms of the virus, though these may be less likely to spread to others.

“This study highlights the importance of protecting immunocompromised individuals, who are at high risk for the virus, yet may also be an incubator for the formation of the next variant, posing a risk to all of us,” said Prof. Adi Stern at Tel Aviv University (TAU), who heads a lab dedicated to virus evolution. “In biological evolutionary terms, these patients constitute an ‘incubator’ for viruses and mutations — the virus persists in their body for a long time and succeeds in adapting to the immune system, by accumulating various mutations.”

In the study, published in the peer-reviewed Nature Medicine journal, researchers led by Stern and scientists at the Tel Aviv Sourasky Medical Center described the “puzzling” emergence of coronavirus variants characterized by a larger number of antibody-resistant mutations, observed especially since the end of 2020.

The research involved a group of 27 chronic COVID-19 patients diagnosed during 2020 or early 2021 at Sourasky’s Ichilov Hospital, with some suffering from hematologic cancers and other immune system disorders, which prevents full recovery from the virus.

They found that the “virus’ ability to survive and reproduce in the immunosuppressed patient’s body without restriction leads to the evolution of many variants.” At the same time, the study showed that there is a “low risk” for these variants to be transmitted and spread onwards.

“We suggest that most variants emerging in chronically infected patients lack the potential for substantial onwards transmission, possibly due to an absence of key mutations,” according to the researchers.

While patients with SARS-CoV-2 infections recover within a few days, chronic COVID-19 patients are infected for weeks or many months.

“Notably, chronic infection should not be confused with ‘long COVID’, where infection is cleared rapidly yet symptoms persist; in cases of chronic infections, replicative virus is detected for extended periods of time,” the researchers wrote in the study.

Stern remarked that the results of the study paint a complex picture: “on the one hand, no direct connection was found between anti-COVID-19 drug treatment and the development of variants. On the other hand, the research discovered that it is likely the weakened immune system of immunocompromised patients that creates pressure for the virus to mutate.”

“The complexity of coronavirus evolution is still being revealed, and this poses many challenges to the scientific community,” Stern said. “I believe that our research has succeeded in peeling back a missing layer of the big picture, and has opened the door for further research efforts to discover the origins of the various variants.”

“More extensive monitoring and research of chronic infections is necessary to understand the precise factors determining when and if a variant generated in chronic infection becomes highly transmissible,” the study concluded.