In 1965, researchers discovered a nasty respiratory tract infection called 229E. Today we know it as the common cold, but this is the first coronavirus discovered. Sometimes this “common cold” causes serious complications. This is one of the main challenges in the fight against coronaviruses.
In 2016, a 45-year-old schoolteacher was admitted to the emergency department at Hygeia Hospital in Athens. The nonsmoking woman, who had never complained of her health before, had unusual symptoms - a fever of forty, a dry cough, and a severe headache. An ambulance doctor examined her and noted wheezing in the lower left lung. The pathology was confirmed by a chest x-ray.
Believing that they were dealing with bacterial pneumonia, the doctors prescribed antibiotics to the woman. But in the next two days, her condition worsened, and laboratory tests did not find pneumonia. When her breathing began to stop, she was given oxygen and a new set of drugs. In parallel, the patient was tested for a wide range of possible pathogens, including various strains of influenza, Legionella, whooping cough and other serious respiratory diseases up to severe acute respiratory syndrome (SARS / SARS) and Middle East respiratory syndrome (MERS) - but found nothing.
In fact, only one analysis was positive. It was so amazing that the doctors double-checked everything. Everything was confirmed: the patient had a familiar, but mysterious infection called 229E - the first of the detected coronaviruses.
Researchers in the early 1960s who discovered 229E would have been startled by the severity of a schoolteacher's condition. They were actually looking for which virus is causing the common cold. By the middle of the twentieth century, methods for isolating individual viruses appeared, but they did not always work: for example, in about 35% of patients with colds, viruses were found that could not be identified.
In 1965, University of Chicago researcher Dorothy Hamre took up the challenge and decided to close the blind spot. While studying tissue cultures of students with colds, she discovered a new type of virus called 229E.
At the same time, a group of English researchers led by Dr. David Tyrrell (David Tyrrell) studied the common cold. They also isolated in tissue culture what they thought was a new type of virus. When Tyrrell's team examined it under an electron microscope, they found it resembled a virus isolated in the 1930s from chickens with bronchitis. This was the coronavirus - the first one about which it is known for certain that it infected a person.
“Animals have always had these viruses,” explains Dr. Ken McIntosh of Harvard Medical School. - For example, the virus of infectious avian bronchitis. It has long been known in the poultry industry, and there are vaccines for it."
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This early research is a kind of time machine. Biological research today follows strict safety rules and isolation procedures, but half a century ago these issues were treated more simply. Here is how a newspaper article of that time told about Tyrrell's findings: “Scientists placed samples of the medium in the nasal cavity of 113 volunteers. Only one caught a cold. It turned out to be enough. This is how his team determined the absence of isolated virus in the crops where it was grown.
At the time of Hamre and Tyrrell's discoveries, Dr. McIntosh was part of a team at the National Institutes of Health that was also studying the causes of the common cold. ("Completely independent," he adds, as no studies have ever been published). Dr. McIntosh's team discovered the so-called OC43, another common human coronavirus that still causes respiratory infections. In 1968, the term "coronavirus" appeared - because under an electron microscope, its surface resembles the outer layers of the solar atmosphere, the corona.
At the time, the discovery of new coronaviruses like 229E and OC43 attracted a lot of media attention. One article recklessly proclaimed that science had "tripled its chance of fighting the common cold." However, Macintosh recalls that the scientific community did not pay due attention to the study of coronaviruses until the appearance of SARS in 2003. Since 229E and OC43 caused relatively mild illnesses, doctors treated them like a common cold: antipyretic, expectorant, and hot chicken broth.
Then, in 2003, an outbreak of SARS broke out. It started with the coronavirus in China and ended up in 29 countries. Although the virus ultimately infected only 8,096 people, it was credited with 774 deaths - such a staggeringly high mortality rate made researchers look at it in a new way. “When SARS came along, the world of coronaviruses suddenly changed - it got much broader and more technical,” recalls Dr. McIntosh.
Since then, two more coronaviruses have been discovered that also cause the common cold - NL63 and HKU1. And only in 2012 - almost 50 years after its discovery - the complete 229E genome was finally sequenced. In the meantime, cases have been reported of 229E causing severe respiratory symptoms in immunocompromised patients - although most healthy people get off with a cold.
Despite careful study of coronaviruses following the SARS outbreak, it is not yet clear why three of them - SARS-CoV-1, MERS-CoV, and SARS-CoV-2 (the source of the COVID-19 pandemic) - cause more severe symptoms and lead to more high mortality rates, while the other four known human coronaviruses are much weaker.
However, they still have one thing in common: bats. All known coronaviruses that infect humans appear to come from bats. Then the viruses were transmitted to another animal (a fertile environment for them - game markets and open-air food markets), and eventually reached humans. Thus, OC43 appears to have been circulating since the 18th century, and was transmitted to humans from livestock. MERS-CoV was transmitted to humans from camels. Intermediary animals are also suspected of transmitting other coronaviruses to humans, up to SARS-CoV-2.
The Greek teacher eventually recovered - fortunately, artificial ventilation was not needed. A lung scan two years after treatment showed that they had recovered and made a full recovery. Nevertheless, such serious complications of the "common cold" are one of the main difficulties in the fight against coronaviruses: they cause a whole range of symptoms of varying severity.
“If you look at the spread of disease in the current outbreak, right now,” says Dr. Wayne Marasco, a researcher at the Dana Farber Cancer Institute in Boston, a specialist in SARS, LRS and COVID-19, “some people have the disease. completely asymptomatic, while others die."
Dr. Mackintosh suspects coronaviruses will continue to confuse researchers. First, they are large and complex, and second, they can be changed relatively easily at the genetic level. He notes that these viruses are also relatively easy to disassemble and assemble in the same cell. It is these mutations that seem to have caused both SARS and today's pandemic.
“Coronaviruses have the largest RNA genome of any animal virus,” says Dr. McIntosh. "So they have a lot of secrets."
Alex Knapp