In the UK, with lead researchers from Imperial College London helming, a human challenge trial was undertaken to better understand the course of the disease. Such human challenge trials are the subject of some controversy, an aspect I acknowledge but do not focus on here.
There has been sparse data emanating from the study, and some of the longer term follow-up studies and several related pieces of research will likely be reported upon in due course. Today marked the first pre-publication of data concerning the initial dose-rate related work from the onset of the trial.
The report is presently seen on a pre-print server and though there has been a significant internal review within the study group, this data as pre-published has not been subject to independent peer review.
What seems to have caught the attention of journalists is just how highly infectious COVID-19 actually is.
For context, all of this round of test work was conducted with the original “wild form” of COVD-19, before Delta (which is far more infectious and transmissible) or Omicron (which is also yet more transmissible and infectious yet than Delta) came onto the scene. Bear that in mind as you read the following. (Guardian UK).
Exposure to one nasal droplet enough for Covid infection – study
Trial in which volunteers were given dose of virus is first to monitor people during entire course of infection
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Exposure to a single nasal droplet is sufficient to become infected with Covid-19, according to a landmark trial in which healthy volunteers were intentionally given a dose of the virus.
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The trial’s chief investigator, Prof Christopher Chiu, of Imperial College London, said: “Our study reveals some very interesting clinical insights, particularly around the short incubation period of the virus, extremely high viral shedding from the nose, as well as the utility of lateral flow tests, with potential implications for public health.”
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“We found that overall, lateral flow tests correlate very well with the presence of infectious virus,” said Chiu. “Even though in the first day or two they may be less sensitive, if you use them correctly and repeatedly, and act on them if they read positive, this will have a major impact on interrupting viral spread.”
The full study is reported here in pre-print form.
From their Abstract
To establish a novel SARS-CoV-2 human challenge model, 36 volunteers aged 18-29 years without evidence of previous infection or vaccination were inoculated with 10 TCID50 of a wild-type virus (SARS-CoV-2/human/GBR/484861/2020) intranasally.
From their Discussion
We here report the virological and clinical results from the first SARS-CoV-2 human challenge study. With a low inoculum dose of 10 TCID50, robust viral replication was observed in 53% of seronegative participants. After an incubation period of <2 days, VLs escalated rapidly, peaking at high levels and continuing for over a week. Symptoms were present in 89% of infected individuals but, despite high VLs, were consistently mild-to-moderate, transient and predominantly confined to the upper respiratory tract. Anosmia/dysosmia was common, occurred later than other symptoms and resolved without treatment in most participants within 90 days. In those with residual smell disturbance, their sense of smell steadily improved during the follow-up period, consistent with the good long-term prognosis seen in community cases13. There was no evidence of pulmonary disease in infected participants based on clinical and radiological assessments.
The natural infectious dose of SARS-CoV-2 is unknown but based on in vitro and preclinical models, the virus is understood to be highly infectious14–16 and well-adapted to rapid and high-titre replication in human respiratory mucosa17. Early in the pandemic, a WHO Advisory Group published expert consensus guidelines recommending a starting dose of 10^2 TCID5010. Here, based on in vitro data of high viral replication in primary human airway epithelial cells, we started with a tenfold lower dose of 10 TCID50 (equivalent to 55 FFU) and found it sufficient to meet the 50-70% target infection rate. With prospective household contact studies having similarly shown high secondary attack rates of ~38%12, this suggests that the model can recapitulate higher exposure than naturally-acquired infection events. In contrast, experimental infections of non-human primates have used 1,000-10,000 times more virus, with intratracheal or combined upper/lower airway administration, which results in markedly different kinetics to those observed during human infection18,19. In human challenge studies with other respiratory viruses such as influenza viruses and RSV, inoculum doses are typically also much higher at 104-106 TCID50 since all volunteers have been exposed multiple times throughout life to those viruses, with pre-existing immunity reducing susceptibility and resulting in substantially lower peak viral loads at 103-104 copies/mL by PCR20,21. Thus, neither animal models nor human data from other viral infections were helpful in estimating the optimal SARS-CoV-2 inoculum dose.
I can only say that, no matter their relative youth, the volunteers in this trial should be given our thanks, and we should recognize their courage in taking part in what could easily have been a risky and life-changing experience.
I dashed this piece off during lunch and am now off back to the laboratory.
Looking forward to hearing everyone’s thoughts on what might be the first of several reports coming from the UK Human Challenge trials.