Researchers explore viral emissions in a phase 1, open label, first-in-human SARS-CoV-2 experimental infection study

In a recent study posted to The Lancet Microbe, researchers explored the release of viral particles into the environment and air after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) human challenge.

Background

Understanding the contagiousness and the timing of infection is crucial for implementing effective strategies to reduce the transmission of SARS-CoV-2. Measuring viral emissions could be an accurate technique to determine the likelihood of onward transmission and discover potential routes, rather than relying solely on viral load from upper respiratory swabs. The present study aimed to observe the correlation between viral emissions, symptoms noted over time, and viral load in the upper respiratory tract in individuals challenged with SARS-CoV-2.

About the study

The team recruited healthy adults aged between 18 and 30 years who were unvaccinated and had no history of SARS-CoV-2 infection. The study was conducted at a single center in London and was a first-in-human experimental infection study. Participants were screened for seronegativity and were quarantined at the Royal Free London NHS Foundation Trust. The QCOVID tool was utilized to offer a personalized estimation of the absolute risk of hospitalization and death. It identified participants who exceeded a predetermined risk threshold. Before inoculation, the individual underwent echocardiography and a chest X-ray.

The participants were placed in individual negative pressure rooms. The study involved administering 10 50% tissue culture infectious doses (TCID50) of pre-alpha wild-type SARS-CoV-2 to participants via nasal drops. The participants were kept in quarantine for at least 14 days after being inoculated until they met the criteria for discharge. Daily collection of nasal and throat swabs was conducted. The study also collected air samples from a distance of one meter from the participant's head.

Daily collection of environmental surfaces and hand swabs was conducted. The study conducted virological analyses on all samples, including nose and throat samples, masks, air, and environmental samples. Polymerase chain reaction (PCR) was used to quantify human housekeeping gene 18S ribosomal ribonucleic acid (rRNA) in all samples to determine the impact of sampling efficiency or estimate total particle emissions on the observation. Self-reported symptom diaries were used to collect symptom scores three times a day.

The study's primary outcome was to investigate environmental and air contamination in healthy adults participating in the SARS-CoV-2 human challenge model. The methods used for this exploration included exhaled breath sampling, air sampling, and surface swabbing. The study also described SARS-CoV-2 transmission pathways and the associations between host factors and viral emissions as a secondary outcome.

Results

The study enrolled 36 participants between 6 March and 8 July 2021. Out of 34 seronegative participants, 18 reported SARS-CoV-2 infection after the challenge. The infected participants experienced mild-to-moderate symptoms and had high viral loads in their nose and throat for a long time after a short incubation period. The air, breath, and rooms of uninfected persons were free of viral contamination. The study also showed that all 18 infected participants released virus-laden particles into the air.

Viral contamination was found to be consistent among the five surfaces that were swabbed. The study found that viable SARS-CoV-2 was detected on 16 masks and 13 surface swabs but not on any hand samples or Coriolis air samples.

The study conducted a correlation analysis on all samples from participants to determine the association between viral load in emitted virus and swabs, as well as symptoms. Surface and air viral load measurements were found to be clustered together. The hand and mask viral load were clustered with nasal viral load. Hand swabs showed stronger associations with television remote controls and bathroom handles. Nasal viral load showed a stronger correlation with mask, hand, air, and surface viral loads than throat viral load. Notably, emissions and symptom scores showed minimal correlation.

Consistent levels of human housekeeping gene 18S rRNA were found in daily air specimens from the same individual, suggesting that the amount of expelled airborne particles did not change during infection and that particles detected in the air sample remained stable. The differences in 18S rRNA from masks were more significant, indicating that this type of sampling is more variable and could be influenced by various factors such as individual activity levels, expiratory events, or mask alignment during the one-hour sampling period.

Viral RNA was identified in mask, air, and surface swabs before any reported symptoms appeared. Viral RNA emissions accounted for 2%, 8%, 9%, and 10% of total area under the curve (AUC) for hand swabs, surface swabs, air, and mask emissions, respectively. The study also showed that the majority of contagiousness was detected after the participant was first reported to be unwell, as only 7% of emissions into the environment and air occurred prior to the first reported symptom.

Conclusion

The study discovered that after infecting healthy individuals with SARS-CoV-2, there was a significant amount of viral contamination in the surrounding environment and air. The contamination was found to be extensive but varied and likely originated from the nasal epithelium. Early symptoms initiating self-testing could detect a large proportion of infectiousness, as viral emissions were incident after participants reported early symptoms and tested positive by lateral flow antigen test (LFT).

Correlation between viral emissions and viral load was found to be stronger in the nose as compared to the throat, suggesting that the infected nasal mucosa is a significant source of virus for viral transmission.

The team noted that LFT has the potential to be a more effective method for identifying infectious individuals compared to fever screening due to its quick results. The study concludes that hand hygiene, along with surface cleaning, play important roles in decreasing the risk of transmission.

Written by

Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.