Antiviral treatment promotes formation of new variants of SARS  CoV  2

Antiviral treatment promotes formation of new variants of SARS CoV 2

Just as some drug therapies work to prevent serious courses of Covid-19, they also apparently harbor the risk of developing resistance. German scientists have already proved this. In “Cell Reports Medicine” they published the results of a study in corona patients treated with remdesivir.

The research team from the University Medical Center Hamburg-Eppendorf (UKE) and the Leibniz Institute for Virology (LIV) investigated whether patients with long-term infections contribute to the development of new variants of SARS-CoV-2. The experts, led by Nicole Fischer (UKE/Virology) and Adam Grundhoff (LIV/Virus Genomics), investigated whether Covid-19 carriers with infections that have not been controlled for a long time generally have an increased evolution of the virus or if certain forms of treatment stimulate the emergence of new ones that promote mutations.

“evolutionary bottleneck”

The focus was in particular on antiviral therapies, for example with remdesivir or convalescent plasma. “Our work shows that it is not the long duration of the infection itself that leads to the formation of new variants, but rather that an ‘evolutionary bottleneck’ is needed, such as can arise, for example, with antiviral treatment,” Nicole said. Fischer.

The study examined genomic diversity in longitudinal samples from 14 patients with prolonged viral exposure (30 to 146 days) during severe Covid-19 illness. This also included immunocompromised and immunocompetent patients with or without antiviral treatment to assess the occurrence of mutations with and without selection pressure in the study.

The result: patients with prolonged SARS-CoV-2 infection and antiviral treatment with remdesivir showed a significant increase in viral diversity with new mutations. In contrast, the emergence of new variants was observed only sporadically in patients who received only anti-inflammatory treatment.

“Overall, the virus was surprisingly stable in most people examined. However, in one patient who was treated with remdesivir, we observed that a large number of mutations developed immediately after starting treatment – including at least one mutation associated with high probability of increased resistance to remdesivir,” explained Grundhoff.

In recent months, isolated scientific studies have emerged that have pointed to the possibility of developing resistance to Covid-19 therapy. Monoclonal antibodies have repeatedly lost their effectiveness because of new virus variants, because they are specifically targeted against one or a few variants. So far, this has been less dramatic with substances like Paxlovid, which is around 90% effective. On the other hand, no new virus variants developed noticeable resistance during treatment.