The results of the very first human challenge study are in and reveal, among other things, that the period between infection and the first symptoms is much shorter than previously thought.

What exactly happens when someone is exposed to the coronavirus? That was unclear for a long time; most people don’t discover they have the virus until they start developing symptoms, leaving the early stages of infection shrouded in mystery. To gain more insight into this crucial phase, British researchers recently developed a human challengestudy set up. In this study, healthy young subjects who had not previously been exposed to SARS-CoV-2 were infected with the virus and then monitored closely. The first results of that research are now as preprint published (see box). This preprint states, among other things, that people develop symptoms remarkably quickly after infection, the infection first appears in the throat and the lateral flow tests are well able to indicate whether someone is carrying an infectious virus, i.e. is capable of to infect others with corona.

A preprint is a study that has not yet undergone peer review. Normally, studies are reviewed prior to publication by scientists who were not involved in these studies. In this way scientific journals can guarantee the quality of their articles. Sometimes, however, researchers decide to put their results online before that peer review. Researchers may, for example, opt for this, because the results have urgent implications and they therefore consider it permissible to release them before the time-consuming process of peer review. We’ve seen that happen a lot during this pandemic with studies on SARS-Cov-2.

The research

The researchers based their conclusions on a study of 36 subjects who were between 18 and 30 years old. None of the subjects had been exposed to SARS-CoV-2 or had been vaccinated against the virus prior to the study. The subjects were administered a low dose of the coronavirus by nasal drops and were subsequently monitored by the researchers in a controlled environment for two weeks in a row.

Eighteen infections

18 of the test subjects were actually infected by the coronavirus, of which 16 developed mild symptoms and 2 were not included in the final analysis because they had acquired antibodies between the first screening and administration of the virus (and therefore had to be exposed to the virus elsewhere). have been exposed). The 16 subjects with mild complaints mainly suffered from cold-like complaints, such as sore throat, sneezing and a runny nose. Some also developed headaches, muscle aches, fatigue and fever. 13 of the infected subjects reported a temporary loss of smell. None of the subjects developed serious complaints. There were also no changes in their lungs, the researchers concluded.

Incubation period

The research provides crucial, yet surprising information about what happens in the period between infections and the first symptoms. For example, the researchers established that the 18 infected subjects already developed the first symptoms on average 42 hours after being infected. This means that the incubation period is much shorter than expected; It was assumed that people developed the first symptoms on average 5-6 days after being infected.

Throat

In addition, the research shows that the virus is first found in the throat and only almost a day later in the nose. However, the amount of virus (the viral load) in the throat was found to be much lower and to reach a peak faster than in the nose. The fact that the viral load in the nose is much higher indicates that people are significantly more likely to transmit the virus from the nose to others. It shows once again how important it is to wear mouth masks not only over the mouth, but also over the nose, the researchers say.

Quarantine

The researchers saw that the total viral load peaked on average about five days after infection. But during lab tests, the infected subjects were found to still carry infectious (or contagious) virus on average nine days after being infected. And for some it was even 12 days after infection. It endorses the quarantine duration that is enforced in most countries, the researchers say.

In addition, the research shows that the lateral flow tests (which also include the self-tests) were generally able to indicate whether someone was carrying an infectious virus or not; positive lateral flow tests often coincided with lab tests that also revealed the presence of infectious virus (even when subjects were asymptomatic). It is true that the lateral flow tests at the very beginning and the end of the infection were less able to pick up the virus. And so the study endorses the idea that the self-tests can be used to determine whether someone is still contagious and can already come out of isolation or not. In addition, the study reveals that it should be possible to detect contamination before 70 to 80 percent of infectious virus particles are generated. Namely by simply testing preventatively twice a week. “Although they (the lateral flow tests, ed.) may be less sensitive in the first two days, if you use them correctly and repeatedly and act if they are positive, they can significantly disrupt the spread of the virus,” says researcher Christopher Chiu.

The virus strain
The test subjects were infected with a small dose of the coronavirus (roughly comparable to the amount of virus found in one droplet from the nose of a corona patient who is in the most contagious part of his infection). Use was made of a virus strain that was obtained early in the pandemic, even before the emergence of the Alpha variant. The virus used belongs to the so-called B1 line of the SARS-CoV-2 virus, which also includes the Alpha, Beta and Delta variants. Obviously, this raises the question to what extent the results apply to the dominant variant at the moment: Omikron. Although this variant is different – ​​for example much more contagious – than the early variant with which the researchers worked, according to Chiu this does not detract from the implications of the study, which mainly deal with the way in which we can best protect ourselves and others against the virus. (wearing masks correctly, testing regularly, maintaining the correct quarantine period, etc.). “Although the emergence of variants such as Delta and Omikron has caused differences in the transmission of the virus, it is in fact still the same disease and the factors that can protect us against it have not changed.”

Follow-up question

Although the research provides more insight into the early stages of a mild corona infection, many questions also remain unanswered. For example, it is still unclear why of the 36 people who all received the same dose of the virus, 18 were not infected. The researchers still want to find out.

Although the human challengestudy yields unique insights, it also has limitations, especially at this stage, the researchers acknowledge. For example, the number of test subjects and the diversity among infected subjects is limited. Also, not much time has passed since the intentional contamination, so that any long-term effects of the contamination have not yet been mapped out. But despite these limitations, the research is still very valuable, the researchers emphasize. First of all, because it endorses various corona measures – such as wearing a mouth cap correctly and maintaining a quarantine period. In addition, the researchers also find it very important that the study demonstrates that SARS-CoV-2 can be studied further in a safe and effective way through a human challenge study. And this clears the way for comparable follow-up studies in which new corona variants are investigated or new corona vaccines and antivirals can be tested (accelerated).