Researchers have deliberately infected humans with coronavirus. Here is what happened | Science

Researchers in the United Kingdom published yesterday results of a first of its kind study where healthy young volunteers were deliberately infected with an early strain of the pandemic coronavirus. As hoped, none of the participants became seriously ill, and the researchers were able to closely track their symptoms and gain a unique insight into how both SARS-CoV-2 levels and symptoms vary from start to finish during an infection.

The success of this initial “human challenge” study provides a strategy to test COVID-19 treatments, vaccines and viral variants going forward, the researchers say. The study may also help scientists understand why the pandemic coronavirus can break the immune system in some people, but not others.

In the study, 34 healthy volunteers aged 18 to 29 received nasal drops with a small amount of the virus. Eighteen, or 53%, were infected by polymerase chain reaction (PCR) test. Most volunteers developed mild to moderate symptoms, but no one needed hospitalization or treatment, indicating that the study could be performed safely, according to the investigators who ran it. The study also found that after the first 1 to 2 days of infection, rapid antigen tests reliably indicated the presence of virus.

The results posted on a preprint server have not yet been peer-reviewed, but are being reviewed in a Nature journal.

“It’s a very important piece of work,” said David Dowdy, an infectious disease epidemiologist at the Johns Hopkins School of Public Health. “None of the other research out there is capable of tracking … both the symptoms and the immunology from a known time of infection.”

“It really is a first glimpse of what’s happening right from the beginning of the infection,” adds Akiko Iwasaki, an immunologist at Yale University. “Fortunately, all of these people who were infected had mild illness. That’s a good thing. Because these challenge experiments always carry a risk of developing serious illness.”

Researchers have long conducted human challenge studies for various pathogens, including influenza viruses, but ethical questions arise if there are no established treatments for an infection that becomes serious.

Human challenge studies for SARS-CoV-2 aroused interest early in the pandemic, but when successful COVID-19 vaccines were developed, various groups abandoned their plans, including a team at the U.S. National Institutes of Health (NIH), which had developed a detailed trial protocol. A large British consortium funded by more than £ 33 million from the British government pressed on.

They launched their trial in early 2021 with a viral strain that had been circulating in the UK by July 2020, early in the pandemic. None of the 26 male and eight female volunteers had been vaccinated or had a natural SARS-CoV-2 infection. Volunteers were infected with a low dose – roughly equivalent to the amount of virus in a drop of nasal fluid when they were most contagious – in a high-inclusion quarantine unit at the Royal Free Hospital in London. Researchers monitored their symptoms and tested them intensively with rapid antigen, PCR and antibody tests.

Whether it was due to the low dose, the volunteers’ strong immune system or both, the virus did not quite succeed in establishing an infection in 16 people who got the nasal drops. Because volunteers all got the same virus in the same way with the same small dose, the results open a door to study why and how some people manage to resist infection.

The results also painted a clear time course of viral travel in the body. On average, 2 days after the nasal drops were delivered, the symptoms began and viruses were precipitated in the throat. The symptoms peaked after about 5 days. It was also when the active virus level peaked in the nose where the amount of virus was much greater than in the throat. Infectious virus ceased to be isolated from the noses of volunteers on average 10 days after infection.

Only two volunteers with confirmed infection were completely asymptomatic. The other 16 developed mild to moderate symptoms such as nasal congestion, sore throat, muscle aches and fever. A little later, 12 volunteers developed olfactory disorders, nine of which temporarily lost their sense of smell completely. One still had minor odor abnormalities 6 months later.

In particular, the viral load of the two volunteers who became infected but did not have symptoms was not lower than that of their sick colleagues. “Even though people had no symptoms at all … they all generated extremely large amounts of virus, which really speaks to the risk of infection. [of the virus] and explains how the pandemic has spread so rapidly, ”says Chris Chiu, an immunologist at Imperial College London (ICL), who was the study’s lead researcher; he spoke at a press briefing at the Science Media Center today.

However, some scientists note – and the researchers acknowledge – that the early virus strain used in the study is likely to work differently from newer variants such as Delta and Omicron, which are more transmissible. “Different variants would require different experiments,” Iwasaki says. “The extent of [virus] replication as well as duration [of symptoms] may differ somewhat. And potentially even location [of viral load] may differ. “

Future multi-variant human challenge studies could be used to test vaccines designed to be broadly protective against various strains of SARS-CoV-2 or even other coronaviruses, says Matthew Memoli, a physician and virologist at the US National Institute of Allergy and Infectious Diseases. who had developed the planned NIH challenge experiment. “The problem is right now, when we make these vaccines, we fly a little blind,” he says.

Memoli also says the UK study is pulling back a curtain on basic biology. For example, it found that uninfected volunteers did not develop SARS-CoV-2 antibodies in their blood. This is in contrast to studies of the flu challenge – which Memoli has been running for 10 years – where vulnerable but uninfected people develop antibodies. Memoli suspects the difference may be due to specialized mucosal antibodies closing SARS-CoV-2 in the nose of the uninfected volunteers of the current study.

Some critics have pushed back against studies of human challenges, arguing that their risks to volunteers outweigh the benefits to society as a whole.

But the study’s co-researcher Peter Openshaw, a respiratory physician and immunologist at ICL, dismissed it at today’s press briefing: “Is it ethical not to do these studies if they can be done?… We get unique insights. We just have to acknowledge and thank the altruism of those volunteers who came forward. “

He and his colleagues are planning their next move: In the spring, they hope to launch a Wellcome Trust-funded human challenge study using a standardized Delta variant in vaccinated volunteers.

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