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DR TANJA JOVANOVIĆ, VIROLOGIST, SPEAKS WITH KURIR: 'It is possible to have Covid and get multiple negative PCR test results.'
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DR TANJA JOVANOVIĆ, VIROLOGIST, SPEAKS WITH KURIR: 'It is possible to have Covid and get multiple negative PCR test results.'


'If the sample is taken at the right time and from the right place, and is adequately processed, the result is reliable. If taken late, this may result in false negatives.'

"Not only is it possible for someone to have the coronavirus and get a negative PCR test result, but also for the test results to be negative several times. The reasons for this are many. A false negative may result from selecting an inappropriate sample or an inadequate sample-taking. The selection depends on the phase in which the infected person is. The nasopharyngeal swab, i.e. a swab from the nose and the pharynx, is used at the start of the infection.

"When the virus reaches the lungs and causes pneumonia, a saliva specimen is obtained. It is important that the specimen is not kept at room temperature for extended periods of time, as this may destroy its genetic material," Professor Tanja Jovanović, virologist and Vice-Dean for Teaching Provision at the Faculty of Medicine in Belgrade, said in an interview with Kurir. We also asked her how it was possible for someone to have Covid-19 twice and get negative PCR test results on both occasions, as was the case with Professor Marija Zdravković, Director of the Bežanijska Kosa Medical Centre.

When the throat or nose PCR test is negative, how often is a saliva specimen used to check for the coronavirus?

It is important for a patient to arrive in time, at the very start of the disease. If the sample is taken at the right time and from the right place, and is adequately transported and processed at the laboratory, then there is no mistake – the result cannot be a false negative. If, however, the disease has gone on for some time, and the virus is present in the lower respiratory tract, the throat and nose swab can be negative. In such cases it is better to examine the saliva specimen. Also, at the end of the disease, the throat and nose swab test results can be positive again as the virus is actively secreted from the body. This usually happens after two weeks.

What should be done when the PCR test result is negative, but Covid-19 is suspected?

The serological test is used as an additional test for this group of patients. This is a blood test which detects the presence of the IgM antibodies. Even if this test is negative, the clinical doctor assesses whether to treat such patients as Covid-19 patients based on the blood count and the laboratory and radiological findings.

So, it is all down to how good the doctor is?

It is always important for the doctor to monitor the patient.

How exactly does the coronavirus travel through the body?

The coronavirus is transmitted through droplets or an aerosol which is formed when an infected person coughs, sneezes, or talks. The virus remains infectious in droplets and aerosols for about two hours, depending on air temperature and humidity. The coronavirus receptors are located on the epithelial cells of the nose, pharynx, and the lung alveoli, where they are the most numerous, and the virus has a high affinity for binding to them. The virus actively replicates in the cells, producing a great many new particles. The outcome of the infection depends on the body's ability to fight it. If the virus is not eliminated from the respiratory tract, it goes on to attack the organs and organ systems which have the specific receptor for it.

What exactly does the virus do to the organs that it goes through?

There are two types of epithelial cells in the lung alveoli. The first type is involved in the gas exchange between the blood and the lungs, and the other in the production of the liquids which prevent the alveoli from collapsing. The coronavirus attacks just these cells and replicates inside them, which results in initiating a programmed death of the alveolar epithelial cells. So, the cells deteriorate, and lungs cannot work properly. The body then initiates the innate immune response, which is accompanied by the production of molecules recruiting white blood cells for the fight against the virus in the lungs. They also initiate the production of interferon, which has an antiviral effect. Most infected people manage to stop the further spread of the infection by secreting the virus fully into the environment through respiratory secretions. In people whose immune system is compromised, the virus can spread further and lead to a multi-system disease. The further replication of the virus in the body triggers a powerful immune response of the specialized lymphocytes. This in turn results in the production of excessive quantities of molecules which damage the infected organs in the fight against the virus. Especially important are infections of the heart, the kidneys, the gastrointestinal tract, and the central nervous system.

What does the clinical presentation of a person infected with Covid-19 depend on?

Most people will not have any significant symptoms of the disease. In epidemiological terms, these people are especially important as they spread the infection without knowing they are infected. Most infected people develop the clinical presentation of a respiratory infection. Pneumonia is the most frequent and often requires the patient to be hospitalized. Only a fraction of those infected develop multi-system diseases, and death occurs in three to five percent of symptomatic patients. Many host factors impacting on the severity of the clinical presentation have not been discovered yet. These factors are probably related to specific genes determining the quality of the immune response, or genes that the virus uses to successfully replicate in the body, e.g. the gene for a specific receptor that the virus exploits to infect cells. At the moment, what is known is that people with comorbidities, such as chronic non-infectious lung conditions and cardiovascular and metabolic diseases, as well as obese people and those older than 65, develop a more severe clinical presentation.

How and to what extent does the coronavirus mutate?

Coronaviruses do not mutate fast, as they have developed the capacity to correct errors which occur during replication. What we know now is that mutations occur in the entire genome, but mostly in the virus genes whose products are important for the interaction of the virus with the host. Research has shown that point mutations are the most frequent. At the moment, they do not have a big effect on the behaviour of the virus. Over time, however, as they accumulate, they can result in a significant change of virus virulence, in both directions (decreasing or increasing), which is relevant to the infection outcome. A mutated virus can still circulate in nature and cause new seasonal coronavirus infection epidemics.

Is there a specific coronavirus genome in Serbia?

European isolates are characterized by a specific mutation within the gene encoding the basic protein structure of the virus particle. This mutation is responsible for a faster transmission of the virus and is present in the virus isolates in Serbia.


'Both the production of antibodies and the cell immune response.'

How long will we have to wait for the coronavirus vaccine?

So far, there have been 160 Covid-19 vaccine candidates. Some of them are still in the preclinical stage of research conducted on animal models, and some have reached the final phases of clinical trials, with their efficiency tested on tens of thousands of people. The protocols are defined very strictly.

Does the vaccine provide lifelong protection against the virus?

There are various types of vaccines: those that have a whole-agent inactivated virus particle, or an attenuated virus particle, or subunit vaccines, made from virus particle fragments. The new vaccine production technology uses vector or gene vaccines which stimulate the immune response of the vaccinated persons to the virus proteins which are instrumental for the infection to take place. The best vaccines stimulate both the production of the antibodies and the cell immune response to a specific virus. The immunity that develops through immunization can be lifelong or short-term, depending on the type of virus vaccine, as well as on the specific features of the virus and the infection.


The infection mystery

How long-lasting are the coronavirus antibodies and what does that depend on?

What we know now is that the antibody titer is higher in persons with a more severe clinical presentation than in asymptomatic ones. At the moment, it is known for certain that the antibodies persist for several months, but also that there are people for whom we cannot prove the presence of antibodies, regardless of the previous infection. This is yet another mystery related to the coronavirus infection. It is not known whether after the infection the memory response of the immune system could produce the antibodies when it encounters the virus again, and prevent thus the development of the disease.


'It will be harmless at one point.'

Some claim that we will never get rid of the coronavirus. Are we going to live with it forever?

Little attention is paid to the 19th century pandemic, when over one million people died of a severe pneumonia. Danish scientists have recently discovered that the pandemic was caused by a coronavirus which, incidentally, was discovered as a human pathogen in the 1960s. This coronavirus causes seasonal epidemics of the common cold and mild respiratory disease in small children and the elderly in the winter. To make an analogy, we can assume that the new coronavirus will continue to circulate, but that over time, as we develop collective immunity, it will become a far less dangerous virus, causing seasonal epidemics of mild diseases.


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