A year later, we still don't know the origin of the covid: the new clues to the enigma

The intermediate host that served as a bridge to the coronavirus between bats and humans remains unknown, but the pangolin hypothesis loses strength to other species

Much has changed our lives since the first news from China reached us a year ago about a strange new virus. We already have about 100 million confirmed infections worldwide, according to official figures, and two million lives have been left behind. In these months, scientists have learned a lot about covid and have managed to develop several vaccines in record time. On the contrary, the origin of the pandemic remains a mystery.

The World Health Organization (WHO) wants to finally clarify this issue, so it has sent an international team of experts to Wuhan, the city in the Chinese province of Hubei where it all began. So far, the lack of transparency from local authorities has not helped much, so the certainties are almost as rare as at the beginning and the clues, very similar. Animal provenance and a “wet market” where wild species were slaughtered remain in the spotlight. Will we know something else in the near future?

“As of today we are very clear that SARS-CoV-2 has come from wild animals, probably bats,” recalls Joaquim Segales, a veterinarian at the IRTA-CReSA Animal Health Research Center of the Generalitat of Catalonia and professor from the Autonomous University of Barcelona.

This hypothesis is the most credible because the most similar virus was found years ago in these flying mammals, but scientists still believe that before reaching humans it had to pass through another animal, an intermediate host that remains unknown.

In the beginning, the most notable species was the pangolin, a curious mammal with scales victim of the illegal trafficking of species. Chinese scientists found in this animal a virus very similar to human. However, subsequent research has not been able to confirm that it is the link between bats and people. One of the latest studies, published in December in the scientific journal ‘Viruses’, compares the genes of the different coronaviruses found in these species, but does not clarify how the jump occurred.

“The pangolin becomes infected with viruses that closely resemble SARS-CoV-2, but are different,” Segales highlights.

“This tells us that the pangolin virus probably has a common ancestor with the human coronavirus. They are lines of evolution that may have been parallel but independent.”

However, in recent months, research has provided new clues by identifying other animals that are susceptible to infection: a species of Chinese shrew, the raccoon and even the white-tailed deer can become infected naturally. Could any of them be the intermediate host? At the moment, it cannot be ruled out or confirmed, so scientists have a job ahead of them.

Although some of these findings may offer the key to finding the origin of the covid, as time passes, the investigation becomes more complex. If the SARS-CoV-2 virus now appears in a certain species, a question will immediately arise: was it already infected before the pandemic or has it been spread through contact with humans?

“The only way we would have to know is by doing retrospective serological studies. Therefore, in addition to looking for the virus in different species, we should try to see if they have antibodies against it because this would give us an idea of the time that has passed since these infections occurred,” says the expert.

An example of how the investigation is complicated is the discovery of a wild mink in the US last December infected with SARS-CoV-2. The specimen was in the vicinity of a mink farm in Utah and its positive is only partly surprising since these animals have been massively infected in captivity (in Denmark it was found that they had, in turn, infected humans, so they sacrificed millions of minks and closed the fur business). However, the Utah mink became the first wild animal to be infected with the new human coronavirus.

There are also many mink farms in China, but they do not seem to have been studied much. In addition, the inhabitants of this country have another type of skin among their favorites.

“If they gave me hundreds of thousands of dollars and free access to China to find the source of the virus, I would search the places where raccoons breed,” said the well-known German virologist Christian Drosten, director of the Hospital’s Institute of Virology at Charite Hospital in Berlin, a few months ago.

In addition to being hunted in the wild, raccoons are a veritable industry in China due to their fur, so raccoon farms are also plentiful and there are studies where they have been experimentally infected.

What will WHO find?

Will the WHO mission have the resources, time and permission to carry out this type of tracking? Clearly not. Several experts explained the situation in the journal ‘Science’ a few days ago: it is unrealistic to think that the researchers sent by the international organization can make extraordinary discoveries or find the famous intermediate host. Rather, it is hoped that they will improve communication with Chinese scientists working in the field. And it won’t be much.

So far, the collaboration has left a lot to be desired. For months the WHO has tried to launch this investigation without success – including a recent failed travel attempt – with a plan in place since mid-2020 that has yet to be executed, so try to be as diplomatic as possible:

“We are looking for answers that can save us in the future, not guilty,” said the director of Health Emergencies of the WHO, Michael Ryan, when he presented the mission.

Since then, everything has been more complicated than expected. Of the 15 designated experts (virologists, epidemiologist and specialists in other subjects ranging from animal health to food safety), only 13 traveled to China, as two tested positive and were isolated in Singapore. And the 13 who landed have to do a preventive quarantine for two weeks in a hotel. So they will actually only have another two weeks to visit key sites in Wuhan and return before the Chinese New Year celebrates the country in mid-February.

To make matters worse, Chinese authorities have defended the theory that the epidemic originated outside the country, clinging to studies such as the one that found antibodies in blood samples from Italian patients stored since September 2019. In general, experts are skeptical of such findings, which should be confirmed. In addition, even if corroborated by new data, they would not show that the virus originated in Europe, as interpreted by China, but rather that it left Asia earlier than previously thought.

In any case, the step of WHO experts should provide new elements for the retrospective study of what happened. The registration of the first hospitalized patients, their movements, the animals sold in Wuhan and the supply chain of their markets are key aspects.

“They have to look for maximum traceability of cases and analyze what kind of contacts they had,” Segales says.

If the Huanan market was the first major focus of the pandemic, as was said at the beginning, or at least starred in a decisive ‘super contagion’ event in its beginnings, “not only would we have to analyze what animals were there, but also trace the contacts between people. They could be from relatively distant areas of Wuhan, but it is not easy to find out when so much time has passed,” says the IRTA-CReSA researcher.

In his opinion, the challenge is complex because “when phylogenetic analyzes of viruses are carried out, including those found in pangolins and bats, we realize that probably the area of influence is not only Wuhan and its surroundings, but is much broader.”

Some studies suggest that there may be animals that have helped the coronavirus evolve outside of China, in Myanmar, Vietnam or Laos.

“It would be necessary to make a retrospective tracing in origin and the ideal would be to be able to study wild animals from all over Southeast Asia to see if they are infected with this same coronavirus or with other similar ones that could have a direct relationship”, he says.

To do this, it would be necessary to have as many animals as possible – sometimes capturing them is also a challenge – taking samples through pharyngeal or fecal swabs, doing PCR and sequencing.

The need to monitor zoonosis

Anyway, at this point, does it really matter how the pandemic started? Scientists believe that having that information would be critical. The main reason is that the possibility of the same thing happening again at any time cannot be ignored. Research over the past year have also served to verify viruses closely related to SARS-CoV-2.

On the other hand, the jumps of this coronavirus between different species – from human to animal and back to human – constitute a new threat, so it is convenient to have as much information as possible about these processes. “The virus continues to evolve and new variants are generated, some of which may have greater transmission and replication capacity, and that has consequences. Any generation of animal reservoirs is going to be bad news,” Segales says. In fact, there are companies that are even thinking about developing mink vaccines (to avoid risks to human health, to save the skin business or both).

That is why veterinarians believe that an epidemiological surveillance system must be established that includes animals. In this sense, they are increasingly talking about the concept ‘One Health’, which refers to the fact that human health and animal health are interdependent and, furthermore, are closely related to the environment and ecosystems.

“We are talking about the wild world, pets and people. Monitoring, control and communication efforts must be coordinated in these three areas that unite biology, veterinary medicine and human medicine,” points out the expert.

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