SARS-CoV-2 mutants develop in patients with chronic immunosuppression

Subspecies of SARS-CoV-2 have played an important role in the conversation and public health response of the COVID-19 pandemic. But where did the COVID-19 variant come from? New studies now show that many SARS-CoV-2 mutants are likely to form in patients with chronic COVID-19 who suffer from immunosuppression. This study suggests that weakened antibody responses, especially in the lower respiratory tract of these chronic patients, may prevent complete recovery from the virus and may mutate the virus multiple times during long-term infections. increase. The ability of the virus to survive and propagate in the body of immunosuppressed patients without restriction leads to the evolution of many mutants.

In addition, mutations found in people who are chronically affected with COVID-19 have evolved many of the same mutations present in severe disease concern mutants (VOCs), especially those associated with antibody avoidance. Bring to. New discoveries show that among many strains born from immunosuppressed patients, rapidly spreading mutations are rare, but more likely and occur when global infection rates skyrocket. increase.

This study is published at Nature medicineIn the article, “A driving force for adaptive evolution during chronic SARS-CoV-2 infection.“

Since the inception of COVID-19, the rate at which the virus evolves has been somewhat puzzling to Dr. Addistern, a professor of biotechnology in Schmnis biomedicine and cancer research at the Wise Life Sciences Department at Tel Aviv University. During the first year of the pandemic, a relatively slow but constant mutation rate was observed. However, since the end of 2020, the world has witnessed the emergence of mutants characterized by a large number of mutations far exceeding the rates observed in the first year. Various scientific hypotheses have emerged regarding the association between chronic COVID-19 patients and mutation accumulation, but none have been proven definitive.

“Coronavirus is characterized by the fact that there are people who are chronically infected in all populations,” Stern said. For these patients, the virus stays in the body for long periods of time, increasing the risk of recurrent infection. In all cases observed so far, these were immunocompromised patients. In biological evolution, these patients constitute an “incubator” of viruses and mutations. The virus survives for a long time in the body and succeeds in adapting to the immune system by accumulating various mutations. “

This study searched for drivers of VOC-like emergence by integrating sequence results from a set of 27 chronic infections in patients at the Tel Aviv Surahsky Medical Center.

According to Stern, the results reveal a complex situation. Although no direct relationship was found between anti-COVID-19 drug treatment and the development of variants, researchers found that it is the weakening of the immune system in immunocompromised patients that creates the pressure for the virus to mutate. I found that it is likely to be.

The authors stated that most of the substitutions in this set reflect the VOC mutations that define the lineage. However, a subset of mutations associated with successful global transmission were not present in chronic infections.

In fact, researchers have found that some chronic patients show a clear pattern of recovery and then the viral infection recurs. Mutant viruses appeared in all these patients, suggesting that recovery was not achieved. This is partly reminiscent of HIV after inappropriate medication.

A closer look at some patients showed that if such a clear pattern of recovery was observed (based on a negative nasopharyngeal swab), the virus would continue to propagate in the patient’s lungs. Therefore, researchers suggest that the virus accumulates mutations in the lungs and then returns to the upper respiratory tract.

The authors believe that evidence of a dynamic polymorphic virus population has been found in most patients, suggesting that weakened immune systems opt for antibody avoidance in specific niches within the patient’s body. .. In addition, there are trade-offs between antibody avoidance and infectivity, and extensive monitoring of chronic infections is needed to better understand the emergence of VOCs.