Two local mutations found in Estonia

Photo: Sander Ilvest

All samples analyzed in a pilot study conducted by University of Tartu researchers belonged to a single group of viral strains that likely originated in Northern Italy. Scientists found both the internationally significant D-614-G mutation, as well as two previously unknown mutations.

Since the COVID-19 outbreak reached Estonia, several experts, including University of Tartu professor Eero Vasar and chief of medicine at the Kuressaare Hospital Edward Laane, have described scientific claims that at least two strains of the virus are spreading in Europe – the milder so-called Austrian strain and the especially deadly so-called Italian strain. These hypotheses have been based on purely epidemiological data and have not been backed up by specific studies.

The recent University of Tartu study is the first to shed light on strains of SARS-CoV-2 in Estonia. It can be said in summary that all nine test samples collected in March represented the A2a group that likely originated in Italy, while all exhibited the D-614-G mutation. Additionally, two mutations were found that likely originated in Estonia as they have not been found elsewhere in the world.

Virus under pressure

University of Tartu bioinformatics specialist Aare Abroi said that new strains developing is to be expected as SARS-CoV-2 is known to produce two or three mutations per genome every month, while the flu virus is three to five times quicker to mutate.

“Compared to other RNA viruses, it (SARS-CoV-2) is rather run-of-the-mill. The speed at which it mutates is nothing to be alarmed about,” Abroi said.

According to the researcher, concerning the eight mutations the study came across and that can also be found elsewhere in the world, it is too soon to say whether they make the virus more dangerous or render it more benign instead. Five mutations out of eight cause changes in the sequence of corresponding proteins. As put by University of Tartu senior research fellow of medical virology Radko Avi, it is an indication of where the epidemic stands today.

“Mutations manifesting on the level of proteins reflects considerable immune system pressure and the virus still looking for its path in the human organism. This in turn suggests that the virus is relatively new in the human population, which we already knew, of course,” Avi said.

Viruses do not generally benefit from killing the host, which is why they tend to become less dangerous over time. Because SARS-CoV-2 is still in the early stages of development, mutations that help it spread faster take precedence, while those that could make it less dangerous will probably come later. As emphasized by researchers, it is too early to draw conclusions in terms of reduced pathogenicity.

It is also unlikely that new mutations could be able to disarm immune responses developed after recovering from COVID-19 – antibodies are effective in several different areas and while individual mutations can weaken the response, they rarely overcome it completely. However, the effectiveness of drugs aimed at fighting specific parts of the virus could prove problematic.

“The question of resistance is paramount in terms of treating human populations – there will be a plethora of drugs on the market sooner or later, and I’m sure we will see drug resistance mutations rather soon,” Avi said.

One of the mutations found by researchers could prove significant in terms of drug resistance. The mutation C-14408-T is found in the RdRP enzyme that is in charge of copying the viral gene. Because the gene’s coded mechanisms are susceptible to Remdevisir that has already been approved for use in Estonia and Favipiravir, samples of which should soon be arriving from Japan to be used in medical trials in Estonia, mutations of the gene could have unwanted side-effects.

“Therefore, it would be absolutely necessary to sequence the patient’s virus before prescribing Remdesivir or Favipiravir treatment,” authors of the study write.

Risks need to be contained

Analyzing viral genomes makes it possible to estimate the pathogen’s directions of travel and take appropriate scientific measures when responding to new waves of infection.

After the initial pilot study, researchers want to sequence further genomes that could shed light on the virus reaching Estonia and its spread here. The long-term goal is to have a systematic approach for future epidemics.