In the thick of things – coronavirus research

The pandemic currently gripping the world has brought virus research into the spotlight. What do we know about similar viruses? What is new about the SARS-CoV-2 virus? Virologist Lennart Svensson is sure of one thing: this is not the last time we will see an outbreak of a coronavirus.

coronaviruses, virus that causes respiratory infectionsAs of today, seven coronaviruses are known to infect humans. Photo credit Bertrand BlayThe pandemic caused by the SARS-CoV-2 coronavirus is not the first pandemic to sweep through the human population, and it won’t be the last one. The world was hit by several pandemics during the 20th century, which all had in common that they were caused by variants of influenza viruses. In 1918, immediately after the First World War, a pandemic caused by Spanish flu spread across the world, to be followed by Asian flu in 1957, and Hong Kong flu in 1968. In the new millennium, we have the swine flu pandemic in 2009, also caused by an influenza virus. The swine flu virus and the virus that caused the Hong Kong flu pandemic are still in circulation and cause seasonal influenzas. The current pandemic, while giving symptoms similar to those of influenza, is caused by a member of another large family of viruses, the coronaviruses – a fact of which by now surely everyone must be aware.Lennart Svensson. Photo credit Thor Balkhed

“Seven types of coronavirus that infect humans are known. Four of them give the symptoms of a common cold in children, and have probably infected humans for at least a hundred years. Around 15-20% of all cases of the common cold in young children are caused by a coronavirus. And the virus can sometimes also be found in the stools of children with gastrointestinal infections”, says Lennart Svensson, professor of molecular virology in the Department of Biomedical and Clinical Sciences (BKV).

The other three of the seven known coronaviruses have jumped from animals to humans, and caused outbreaks during the past 20 years. The first of these, SARS-CoV-1 (severe acute respiratory syndrome coronavirus 1), was discovered in 2002. It gave rise to an epidemic in parts of Asia and Canada. (An epidemic occurs when a disease spreads through a large region and many people fall ill at the same time, while a pandemic is a particularly serious epidemic that affects an even larger geographical region and a significant part of the population).

Ten years later, in 2012, a similar coronavirus, MERS-CoV (Middle East respiratory syndrome-related coronavirus), was discovered. It occurs principally on the Arabian Peninsula.

“We virologists are not at all surprised by what’s happening. Coronaviruses have several properties that lead to this phenomenon happening again. The viruses are found in many other animal species. And coronaviruses are RNA viruses, which can mutate, and this means that they can jump between species”, says Lennart Svensson.

Scientists believe that the virus that causes MERS jumped from bats to camels and then to humans. The number of confirmed infections since then is fewer than 3,000, but the death rate is high – around one third of those infected have died from MERS.

“MERS-CoV has not spread outside of the Middle East, but we don’t know why this is the case. The MERS-CoV virus is still active, but the number of cases is extremely low.” 

The outbreak of SARS in the early years of the new millennium started, just as the current pandemic, in China. The virus spread rapidly, and around 10,000 people became infected.

“In contrast with the two previous coronavirus outbreaks, the current one is truly a pandemic, and has affected the whole world. It spreads at a remarkable rate, and has an enormous ability to infect and continue to spread”, says Lennart Svensson.

The figures for the numbers of infections and deaths from COVID-19 are continuously being updated, and when this article was written had reached considerably more than 2 million global infections and 170,000 deaths. The pandemic affects humans on several levels.

“I suggest that this is the first time in history that a pandemic has affected the whole world economy to such an extreme extent. One reason for this, of course, is that the economy is now global, and that we fly here and there across continents. The plague and the Spanish flu took much longer to spread, whereas today we can fly from Beijing to New York in ten hours, enabling the virus to spread to a new continent”, says Lennart Svensson.

Research in the thick of things

For virologists such as Lennart Svensson, the pandemic has led many who previously worked on other human viruses to focus on SARS-CoV-2. Many clinically relevant questions need to be answered.Marie Hagbom, forskningsingenjör och expert på stamceller, Lennart Svensson, professor i molekylär virologi vid Linköpings universitet. Foto - Ulrik Svedin - LiU Photo credit Ulrik Svedin

“Initially, we knew nothing about this virus. In just four months we have generated a huge amount of information about it, in a way that we have never seen before. Each morning when I arrive at work, new information has become available for me to read and understand. It’s enormously dynamic and extremely exciting.”

Lennart Svensson believes that the most important question at the moment is whether we become immune to the virus after being infected once.

“In principle, there is no clear exception to the rule that you develop immunity against a virus that you have been infected with. And obviously, we have extremely high immunity against the four most common coronaviruses. There’s not much evidence for it at the moment, but I believe that we also gain immunity against the novel coronavirus. It’s not different in any way. It’s important that we start tests to determine whether we gain immunity.”

Lennart Svensson believes that SARS-CoV-2 will in the long run become the fifth coronavirus to infect mainly young children, who have not yet developed immunity against it.

Questions about the rapid spread

“We need to find out how infectious this virus is. I believe that we can infect other people even when we are not showing any symptoms of disease. This would explain the incredibly rapid spread in care homes, among other things”, says Lennart Svensson.

The scientists are now isolating the novel coronavirus from infected people, some of whom have felt completely healthy while others have been sick. One important question, of course, is whether many people are infected without knowing about it, and whether the virus can be transmitted from people who have mild symptoms or none at all. This research is being conducted in close collaboration with Uppsala University Hospital, Ryhov County Hospital in Jönköping and Vrinnevi Hospital in Norrköping. Another closely related question concerns infection pathways. Lennart Svensson suspects that the novel coronavirus can infect through the stools.

“Several new studies have shown that the virus is present in stools, and that in several cases it survives there longer than in the respiratory tract. The fact that the SARS-CoV-2 virus can also be found in wastewater shows that the presence of the virus is extremely high. We are planning to investigate in the near future whether the virus is present in wastewater in Östergötland”, says Lennart Svensson.

They are investigating this hypothesis by purifying stem cells from small tissue samples from the human intestine. The research group is one of few in the world that can grow small fragments of intestine from human stem cells in the laboratory. They will try to determine whether the intestine can become infected by SARS-CoV-2, and if so, whether the intestinal cells can also release viruses that can infect other cells.

“Not the last time”

Many viruses that have their origin among animal species have jumped to humans through bats. This is the case for MERS-CoV, SARS-CoV-1 and SARS-CoV-2, where it has been shown that bats are involved as a source. Photo credit Steve Bourne

“Bats are subject to extremely many viruses. What is interesting is that in many cases the bats do not themselves become sick. This may be a factor in them often spreading the virus onwards. For example, one of the most lethal virus infections, rabies, can be spread by bats that themselves do not become sick”, says Lennart Svensson.

Scientists are discussing intensively which species was the intermediate between bats and humans in the case of SARS-CoV-2, and it seems that a firm answer will have to wait. Since there are so many coronaviruses in animal species, one of the greatest challenges for the scientists is to decide which species they should examine in order to identify the origin of the virus that has now jumped to humans. Not all viruses that infect animals infect humans. Since viruses have become adapted during the process of evolution to infect certain species, they can seldom infect other species. In order for a virus to jump from one species to another, the receptor that the virus uses to gain access to the host cells must be present in both.

“You can think of it as a door – only if the virus knocks on the right door can the door open and the virus enter the cell. The receptor used by the novel coronavirus is known as ‘ACE-2’, and it is found in many other species. ACE-2 is present in several tissues in the body, and among other things plays a role in regulating blood pressure”, says Lennart Svensson.

Have you been surprised by anything about the novel coronavirus?

“I was surprised by its pandemic spread. I don’t think many people expected it to be so extensive. Another thing that surprised me is that high blood pressure is a risk factor. We haven’t seen such a coupling previously for any other virus. This may be a consequence of the virus target, ACE-2, being involved in regulating blood pressure. We don’t know yet whether this is the cause, but we do know that there is a link”, says Lennart Svensson.

Sooner or later the grip of the corona pandemic on the world will loosen. When the acute crisis is over, we will have time to reflect and see what we can learn from it.

“What we should by then have learnt, and this has until now been neglected, is how important virology is for society. WHO has a list of infections that the world must have a preparedness to deal with and that we must conduct research on. All of them are virus infections. This is not the last time we will see an outbreak of a coronavirus. I just want folk to be more alert and I want much better preparedness at all levels. Many people have been left standing helpless this time.”

Lennart Svensson was interviewed on 20 April 2020.

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