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First Human COVID19 Challenge Study

Investigators at the Royal Free Hospital in London recently published the results of the first COVID19 human challenge study in Nature Portfolio, a preprint server. Thirty-six healthy volunteers with no previous immunity to SARS-CoV-2, ranging in age from 18 to 30, were inoculated with the lowest possible infectious dose of SARS-CoV-2 into their nose. The study used the original strain of SARS-CoV-2 prior to the emergence of the Alpha variant. The participants were carefully monitored by clinical staff in a controlled environment for two weeks

Eighteen of the 36 became infected. Two participants were excluded from the final analysis after developing antibodies between initial screening and inoculation. Sixteen of the 18 developed mild to moderate symptoms such as runny nose, sneezing and a sore throat. Some experienced headaches, muscle and joint aches, fatigue, and fever. Thirteen infected volunteers reported loss of their sense of smell for up to 90 days. None of participants developed severe illness.

The average time from exposure to viral detection and onset of symptoms was 42 hours. This incubation period was much shorter than previous estimates of 5 to 6 days. SARS-CoV-2 was first detected in the throat at 40 hours and later in the nose at 58 hours.

Viral levels peaked at an average of 5 days after exposure. Peak levels were significantly higher in the nose than in the throat, indicating a potentially greater risk of virus being shed from the nose than the mouth. This finding supported the importance of properly wearing a facemask to cover both the mouth and nose.

High levels of viable virus remained detectable for an average of 9 days and up to a maximum of 12 days. These findings supported an isolation period of two weeks for infected individuals.

Lateral flow rapid antigen tests were less sensitive than PCR early after exposure and later in the course of infection but were shown to be a good indicator of whether someone was harboring infectious virus. The investigators concluded that rapid antigen tests can reliably predict when someone is unlikely to infect others and can leave isolation.

This was the first study that has been able to provide detailed data during the early phase of infection, before and during the appearance of symptoms. All participants are being followed for up to 12 months to detect any long-term effects. Future studies will seek to determine why half of the volunteers did not become infected.

The limitations of this study were its small sample size, lack of diversity of infected volunteers and limited follow up period.


Killingley B et al. Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge, Nature portfolio, posted February 1, 2022, DOI: 10.21203/

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