This virus has many secrets: why will coronaviruses remain a mystery to scientists so far?

US, WASHINGTON (ORDO NEWS) — The first coronavirus that causes acute respiratory infections in humans, scientists discovered more than half a century ago. Since then, they have discovered several more strains, but it remains unclear why some coronaviruses cause the common cold, while others have a high mortality rate among those infected.

In 2016, a 45-year-old teacher was taken to the emergency room of the Hygeia Hospital in Athens. For a person who never smoked and had no serious health problems, she had strange symptoms: dry cough, severe headache and a temperature exceeding 39.4 ºС. An ambulance doctor revealed wheezing in the lower part of the patient’s left lung while listening. An x-ray of the chest confirmed the presence of lesions in the lungs.

Doctors concluded that the patient developed bacterial pneumonia and prescribed a course of antibiotics. But over the next two days, the woman only got worse, and the laboratory said that the test for bacterial pneumonia gave a negative result. When a woman began to have breathing problems, she was connected to a ventilator. She was also prescribed a new course of medicine and tested for a variety of potential respiratory tract infections, from various strains of the influenza virus to Legionella, whooping cough and other pathogens that cause respiratory infections. The results of all these tests were also negative. The analyzes also confirmed that it was not SARS and the Middle East Respiratory Syndrome (MERS).

Only one test showed a positive result. This surprised the doctors so much that they repeated the analysis, but the result remained unchanged. The patient had a well-known, but still mysterious disease – a respiratory viral infection caused by the coronavirus HCoV-229E. Behind this combination of letters and numbers is the first known coronavirus known to scientists, which can be transmitted to humans.

In the early 1960s, the grave condition of a Greek teacher might have puzzled researchers who discovered the coronavirus HCoV-229E. This is due to the fact that in fact they initially conducted their research to find the causative agent of the common cold. At that time, scientists had already developed methods for isolating some viruses, but many strains were not well understood. In about 35% of people, colds were caused by viruses that scientists could not identify.

This was a challenge for Dorothy Hamre of the University of Chicago. She plunged into the study of tissue cultures of colds and in 1965 discovered a new type of virus, which later became known as HCoV-229E.

At the same time, in the UK, a group of scientists led by Dr. David Tyrrell conducted a similar study to more fully examine the causes of the common cold. They also managed to isolate a new type of virus. When scientists examined it under an electron microscope, they found it to be similar to a virus isolated back in the 1930s from tissues of chicken suffering from bronchitis. It was a coronavirus. Scientists for the first time managed to prove that it can be transmitted to humans.

“Animal viruses have always been very important,” says Dr. Ken Mackintosh of Harvard Medical School. “In birds, avian infectious bronchitis occurs. This poses a great threat to commercial poultry farming. Therefore, vaccines are available – their availability is very important for the industry, ”says the scientist.

In the work of the scientists of Tyrrell, their methods are of particular interest. Today, biological research is carried out in conditions of strict isolation and in compliance with all safety procedures. However, more than half a century ago, everything was completely different. To make sure that the virus they isolated was not initially present in the tissues in which they planned to cultivate it, scientists took an unusual step.

“They placed samples of the medium in the nasopharynx of 113 subjects who voluntarily agreed to participate in the experiment. In the end, only one of them got a cold. The experiment helped to clarify, ”the journalist of one of the modern newspapers described the research results.

In parallel with Hamre and Tyrrell, the causes of the common cold were sought by researchers at the US National Institute of Health. “It was an independent study,” emphasizes Dr. Ken Mackintosh, who took part in it, alluding to the fact that neither Hamre nor the British had yet to publish the results of their research. His team discovered HCoV-OC43, another coronavirus that can be transmitted to humans and still causes respiratory infections in humans.

The term “coronavirus” was coined only in 1968. This name is directly related to the structure of the virus, since under the microscope its spike-like processes resemble the solar corona – the outer layers of the solar atmosphere.

The discovery of new coronaviruses such as HCoV-229E and HCoV-OC43 aroused great interest in the media. The author of one of the articles on this topic even made a bold statement that “science has managed to triple its chances of winning the fight against the common cold.”

However, Dr. Mackintosh recalls that the scientific community did not pay much attention to coronavirus research until an outbreak of SARS in China, also known as severe acute respiratory syndrome, began in China in 2003. Since people who became infected with HCoV-229E and HCoV-OC43 coronaviruses had relatively easy illnesses, doctors treated them in much the same way as people with colds caused by other viruses. They prescribed antipyretic drugs and cough suppressants to patients, and also recommended drinking chicken stock more often.

The outbreak of SARS, which began in China and eventually spread to 29 countries, was caused by another strain of coronavirus, called SARS-CoV-1. In the world, 8096 confirmed cases of the disease were recorded, of which 774 were fatal. Because of the unusually high mortality rate, scientists decided to re-examine this virus family. “When the SARS-CoV-1 outbreak started, everyone suddenly remembered coronaviruses. New strains have been discovered. In addition, they began to be studied much more thoroughly, including from the point of view of structure, ”recalls Dr. Mackintosh.

Since then, scientists have discovered two more strains of coronavirus, which are considered causative agents of the common cold. They are called HCoV-NL63 and HCoV-HKU1. The genome of the coronavirus HCoV-229E was fully decrypted only in 2012, that is, almost 50 years after scientists first discovered it. The researchers concluded that in immunocompromised patients, a respiratory infection caused by HCoV-229E could potentially be severe. However, they agreed that in most healthy people the disease goes in the form of a common cold.

Despite the fact that after an outbreak of SARS, scientists began to actively study coronaviruses, they still cannot say why the diseases caused by only three strains (SARS-CoV-1, MERS-CoV and, of course, SARS-CoV-2, which caused the pandemic COVID-19), proceed in a severe form and lead to a high mortality rate among those infected. At the same time, the other four species cause diseases that are much milder.

All of them are united by only one thing – bats. They are considered the primary source of all known coronaviruses that infect humans. From bats, the virus is usually transmitted to other animals. Large meat and seafood markets and open food stalls are an ideal medium for the spread of such viruses among animals. Ultimately, coronavirus is sooner or later transmitted to humans. So, for example, the species HCoV-OC43 was transmitted to humans from cattle. Some scholars suggest that it has been ubiquitous since the 18th century. The MERS-CoV virus, in turn, was transmitted to humans from camels. Researchers believe that animals are somehow involved in the transmission to humans of all types of coronaviruses, including SARS-CoV-2.

In the end, a Greek teacher recovered from her illness and, fortunately, she never needed an artificial lung ventilation apparatus again. Two years after emergency hospitalization, she did a computed tomography of the lungs, from which it became clear that the structure of her lung tissue was restored, and the lungs themselves were completely healthy. Nevertheless, such a severe reaction to an infection caused by a “common cold” can be called one of the most difficult aspects of the fight against coronaviruses, which cause a wide range of symptoms and entail many consequences for the health of the entire population.

“If you study the forms of modern coronavirus infection, you can see that in some people the disease is asymptomatic. At the same time, it becomes fatal for other people, ”said Wayne Marasco, a research fellow at the Boston Cancer Research Institute Dana – Farber, who studies outbreaks of SARS, Middle East respiratory syndrome and COVID-19.

Dr. Mackintosh suggests that coronaviruses will remain a mystery to scientists for now. Firstly, this is due to the wide variety of all kinds of subspecies, which are difficult to study thoroughly. Secondly, in strains of coronaviruses, a huge number of changes are constantly occurring at the genetic level. Mac notes that coronaviruses can relatively easily recombine within the same cell. According to the scientist, such mutations may have led to the emergence of the SARS-CoV-1 and SARS-CoV-2 viruses, which caused an outbreak of SARS and the COVID-19 pandemic.

“Coronaviruses have the longest RNA sequence of all animal viruses. And she has many secrets, ”adds Dr. Mac.

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