VU Virologist Laura Kalinienė About Coronavirus: We Have More Questions Than Answers

With coronavirus cases rapidly growing, the need for new information about this virus has become increasingly relevant. Immunologists have been constantly reviewing the situation; a new vaccine is being created and the problem seems to be addressed purposefully, yet virologist Dr Laura Kalinienė from the Life Sciences Centre of Vilnius University (VU LSC) says that the latest research data are disquieting, since they show that the virus might be much more dangerous than many assume and it might cause irreversible changes not only in the respiratory system.

Lack of validated data

Although scientists have been researching coronaviruses (Coronaviridae family) for almost 60 years, Dr Kalinienė highlights that new data emerge continuously. In terms of currently spreading SARS-CoV-2, which has been existing for quite a short time, accurate, fully validated and even certain basic information is highly lacking.

“We don’t have answers to elementary questions, for example, how many mature viruses – virions – form in a single cell, how many of them are infective, and how many virions should access the body resulting in the COVID-19 infection. These are the main data to describe a virus, yet we don’t have answers so far,” the scientist says.

Extensive laboratory tests help find the answers; however, they have been carried out for a relatively short time so far – about a half-year. According to L. Kalinienė, the findings of these tests are very important, as they can help solve certain problems not only today, but in the future as well.

“At the very beginning the world just watched what was happening and nobody knew whether it would result in an epidemic or would diminish. Afterwards, many countries declared quarantine, scientists could not access laboratories, and no tests were carried out. Therefore, today we have the most abundant volume of epidemiological and clinical research, because the bigger the number of infected people the more accurate the data we obtain. Yet there is another problem – we get clinical data on indications or symptoms that are not necessarily related to the development of this virus in a human body, thus today we have more questions than answers,” the virologist comments.

All studies are important for the sake of clarity

According to Dr L. Kalinienė, epidemiological findings show some tendencies and certain indicators do not significantly change, thus some general conclusions could be drawn. For example, the Ro index indicating the disease reproduction number remains the same – one ill person may infect two to four people, yet these data differ in different populations.

“Risk groups remain the same as well – they involve elderly people with co-morbidities; however, we do not have a definite answer why namely these persons belong to this group. We will not have an answer soon, because the main and only work we can do is cell-culture or animal testing, yet we cannot directly apply these data to a human being – the effects or symptoms present in macaques or hamsters will not necessarily be identical to those experienced by people,” Dr L. Kalinienė explains.

Certain though also non-final data are obtained through the estimates based on methods of molecular biology and mathematics. For example, it has been established that an ill person emits from 100 000 to 10 million viral nucleic acid per hour to the environment; however, it is not necessarily a sound non-damaged viral particle. It is not clear how many of these millions are viable virions capable of infecting another cell and propagating in it.

The latest data are disquieting

Virologist Dr Kalinienė notes that part of society is glad not to have respiratory disorders and they consider themselves as asymptomatic cases. However, extensive clinical trials show that the actual asymptomatic cases constitute only 20 per cent of the infected population, whereas the majority of those considered as asymptomatic cases turn out to be pre-symptomatic cases experiencing symptoms much later, and the symptoms may not necessarily be the same as the ones typical of the respiratory infection.

“Different people may feel different symptoms. It is a matter of concern, because it means that the symptoms may occur beyond the respiratory system. It has already been ascertained that asymptomatic virus carriers emit a rather considerable amount of viral nucleic acid, thus it is evident that a virus is developing, yet why is there no reaction in the body? Does the absence of symptoms mean that the body perfectly copes or the virus deceives it?” the virologist considers.

For example, recently published molecular tests show that SARS-CoV-2 may interfere with pain transmission signals thus possibly misleading a person who has symptoms but does not feel them. Therefore, as the scientist points out, you do not necessarily have to worry if you have a high temperature, fever or pain – they show that the body is fighting and the immune response is forming.

Scientists have already detected the receptor that this virus binds to, and our body is abundant in these receptors. It means that the virus may spread widely: “One of the symptoms may be diarrhea – the digestive system is affected. Hence, the virus may enter the intestines, but we do not know how. Imagining that the virus stays in the respiratory system upon entry is misleading, because it may travel to deeper tissues and access the blood system, thus being circulated to other organs and systems.”

How far the virus travels and affects our body mainly depends on our defence system. However, the virus may be circulated by blood to the central nervous system or the cardiovascular system and affect them.

“Some people often feel calm about the fact that those younger than 50 years easily or asymptomatically experience the SARS-Cov-2 infection. However, the number of clinical communications about cases of stroke among asymptomatic SARS-Cov-2 infected people under 50 years of age has been increasing. Stroke is often the first and only COVID-19 symptom for these people. It is important to note that clinical trials have been focused on symptomatic patients for a long time. However, the computed tomography scan data of asymptomatic infected people show ground glass opacity in the lungs of many of these patients, which implies a potentially irreversible damage to the respiratory system which may cause health problems in the future.

Some seemingly healthy young people have a very severe course of COVID-19 illness or even die of it. Many such cases are related to the malfunctioning interferon response: mutations in genes encoding the components of this response or the formation of antibodies against interferons. Thus neither youth nor the absence of chronic diseases guarantee that you will stay healthy upon recovering from the coronavirus infection,” the scientist comments the latest data.

Virus mutation is a natural and constant phenomenon

According to Dr L. Kalinienė, viruses are constantly mutating and mutations allow the virus to adapt to continuously changing conditions or a new host.

“A virus is not a thinking and conscious creature aiming to kill its host. A virus, particularly a new one, changes over time for an optimal development and after developing it sometimes takes the place of the more poorly adapted ones. Having found a genetic combination enabling faster propagation, better deception of the prevailing immune system, and formation of more virions that are more resistant to environmental factors, a virus will have more opportunities to survive,” the virologist explains the virus adaptation process.

Dr Kalinienė underscores that viruses are often not particularly aggressive due to the reasons that help a virus survive and establish in a new population. “In terms of SARS-Cov-2 mortality, this virus is not that aggressive as, for example, Ebola, hantavirus Sin Nombre or some other of more than 300 viruses that have newly emerged or have been discovered in the last century. SARS-Cov-1 that we have kind of controlled is relatively more deadly and “evil”. Yet we should not forget that in the event of the above mentioned more “deadly” viruses we are mainly talking about several thousands or hundreds of infected persons, thus the death-rate related to these viruses does not reflect the actual virus connected mortality.”

Although it is difficult to forecast virus mutations, various methods of structural and molecular biology allow testing the previous mutations. “D614G mutation in the spike protein of SARS-Cov-2 has been currently intensively analysed. Genomic data show that aspartic acid has been replaced by glycine in position 614 and this mutation has spread in SARS-Cov-2 circulating in both Europe and North America. Although we have quite an amount of various test data today, the impact of the above mentioned mutation on the virus, its development in the cell or its ability to cause a disease is not entirely clear,” the virologist of VU LSC adds.

According to the scientist, this mutation should not even be effective based on in silico data. Yet cell-culture testing established that it may affect virus development, since a slightly bigger output of virions has been observed under laboratory conditions.

“Talking about animals infected with a virus having this mutation, a bigger amount of nucleic acid has also been observed in their nostrils than in animals infected with a non-mutated virus. Are these data enough to say that this mutation allows the virus to infect us more easily or result in more severe illnesses? Definitely no, because we do not even know whether this mutation has spread due to the virus seeking to better adapt to our bodies or due to the so-called founder effect,” Dr L. Kalinienė states.

Today we have detected over 140 000 SARS-Cov-2 genome sequences and identified over 12 000 virus genome mutations. The majority of these mutations are synonymous, i.e. they do not change virus encoded proteins. Apart from the above mentioned D614G mutation in the spike protein, RNA polymerase mutations that copy genome and 382-nucleotide deletion in the open reading frame 8 (ORF8) could be particularly pointed out among protein sequence changing mutations. The analysis of sequencing and clinical data shows that certain RNA polymerase mutations enable faster mutation of the virus, whereas SARS-Cov-2 variants having the said ORF8 deletion might potentially cause a milder infection than viruses without this mutation.

Protection measures are important but avoiding viruses is impossible

According to the virologist, although we do not have medications directly fighting the SARS-CoV-2 virus, we have protection and prevention measures.

“Various methods of treatment have been currently applied. The most popular antiviral medication so far is Remdesivir, originally developed for Hepatitis C and subsequently adapted for Ebola. Now it seems to help fight the coronavirus and certain flaviviruses. Interferon therapy is also applied; steroids are used for treatment, as well as anticoagulants. The majority of used medications basically regulate the symptoms rather than fight the virus,” Dr Kalinienė comments.

The scientist of VU LSC notes that with the second COVID-19 wave emerging all protection measures and various ways to control the situation are important and useful: “If we did nothing, the virus spread would be more successful and wider. Following certain restrictions is helpful. Everything we need now is to live consciously until the vaccine is created.”

Since the history of humankind and current tendencies show that outbreaks of viruses are typical and repetitive, scientists have already observed potential emergence of many new human viruses.

“New G4 swine flu whose genome contains elements typical of a potential pandemic virus and which has been rapidly spreading in Chinese pig farms seems to be knocking at the door of our population. Although we have quite a lot of information about flu viruses, it is difficult to avoid new ones. Emergence of a new particularly virulent avian influenza virus is also likely. It is influenced not only by the spread of flu viruses and genetic characteristics, but also by our activities and habits. For example, our wish to consume free-range eggs of hens which could inevitably have contact with wild birds. Asian countries have a popular tradition to keep many different species of animals in cages in farms, restaurants or markets, but these animals should not generally share the same habitat,” Dr L. Kalinienė adds.

The scientist does not exclude the possibility that a new coronavirus will not disappear and we will live with it all the time, therefore we will now have the fifth coronavirus constantly circulating in the population, beside 229E, NL63, OC43 and KU1.