The largest clinical research funder in the United Kingdom, the National Institute for Health Research (NIHR)’s Health Protection Research Unit in Respiratory Infections, the National Heart and Lung Institute, and Imperial College of London recently had results from an important study published in the prominent peer-reviewed medical journal The Lancet. Titled ‘Community transmission and viral load kinetics of the SARS-CoV-2 delta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: a prospective, longitudinal, cohort study,’ the group sought to study transmission and viral load kinetics in both individuals that are vaccinated as well as unvaccinated in the community. While the study team made a point of declaring that vaccination does help with not only risk reduction of infection but also expedited viral clearance, nonetheless they came to a disturbing conclusion. Fully vaccinated people with breakthrough infections, and those who are accelerating, experience peak viral load comparable to unvaccinated people. Vaccinated people can efficiently transmit SARS-CoV-2 in household settings too, meaning the vaccinated serve as vectors of the disease just like the unvaccinated. This finding has serious implications for the premise that mass vaccination leads to pathogen eradication.
The study team was able to leverage a robust contract tracing system established by the UK between Sept. 13, 2020, and Sept 15, 2020. The study authors identified 602 community contacts and ultimately recruited 471 UK COVID-19 index cases to the Assessment of Transmission and Contagiousness of COVID-19 in Contacts study leading to 8145 upper respiratory tract samples via the intensive study program.
The participants included household and non-household exposed contacts from 5 years and up based on adequate informed consent and agreement to engage with self-swabbing of the upper respiratory tract. Thereafter the team probed risk levels by vaccination status for 231 contacts exposed to 162 epidemiologically linked delta variant cases. Looking at the delta of viral load trajectories of both vaccinated and unvaccinated participants the team probed for primary outcomes of secondary attack rate (SAR) in household contacts stratified by contact vaccination status and the index cases’ vaccination status.
Identifying primary outcomes associated with viral load kinetics they sought differences in peak viral load, viral growth rate, and viral decline rates between the different cohorts.
- Household contracts exposed to the delta variant equaled 25% 95% CI 18–33) for fully vaccinated individuals compared with 38% (24–53) in unvaccinated individuals. The study team found the following:
- Median time between second vaccine dose and study recruitment in fully vaccinated contacts was longer for infected participants (median 101 days [IQR 74–120]) than for uninfected individuals (64 days [32–97], p=0·001).
- SAR among household contacts exposed to fully vaccinated index cases was like household contacts exposed to unvaccinated index cases (25% [95% CI 15–35] for vaccinated vs 23% [15–31] for unvaccinated)
- 12 (39%) of 31 infections in fully vaccinated household contacts arose from fully vaccinated epidemiologically linked index cases, further confirmed by genomic and virological analysis in three index case–contact pairs
- Although peak viral load did not differ by vaccination status or variant type, it increased modestly with age (difference of 0·39 [95% credible interval – 0·03 to 0·79] in peak log10 viral load per mL between those aged 10 years and 50 years).
- Fully vaccinated individuals with delta variant infection had a faster (posterior probability >0·84) mean rate of viral load decline (0·95 log10 copies per mL per day) than did unvaccinated individuals with pre-alpha (0·69), alpha (0·82), or delta (0·79) variant infections.
- Within individuals, faster viral load growth was correlated with higher peak viral load (correlation 0·42 [95% credible interval 0·13 to 0·65]) and slower decline (–0·44 [–0·67 to –0·18]).
What do these points mean?
While vaccination reduces the risk of delta variant infection while also expediting viral clearance, fully vaccinated individuals that succumbed to breakthrough infections have similar peak viral loads to unvaccinated individuals and “…can efficiently transmit infection in household settings, including to fully vaccinated contacts.” The authors suggest “Host-virus interactions early in infection may shape the entire viral trajectory.”
A few limitations are associated with this case study, including:
- Recruited only symptomatic index cases
- Index cases were defined as the first household member to have a PCR-positive swab, but we cannot exclude the possibility that another household member might already have been infected and transmitted to the index case.
- recording of viral load trajectories is subject to left censoring, where the growth phase in prevalent contacts (already PCR-positive at enrolment) was missed for a proportion of participants. However, we captured 29 incident cases and 15 additional cases on the upslope of the viral trajectory, providing valuable, informative data on viral growth rates and peak viral load in a subset of participants
- Owing to the age-stratified rollout of the UK vaccination program, the age of the unvaccinated, delta variant-infected participants was lower than that of vaccinated participants. Thus, age might be a confounding factor in our results and, as discussed, peak viral load was associated with age. However, it is unlikely that the higher SAR observed in the unvaccinated contacts would have been driven by younger age rather than the absence of vaccination and, to our knowledge, there is no published evidence showing increased susceptibility to SARS-CoV-2 infection with decreasing age.
- While they study team didn’t undertake viral culture in the study (a better proxy for infectiousness over RT-PCR) two other studies evidenced cultivable virus from around 67% of vaccinated people infected with delta variant. This represents a consistent data point with the authors’ conclusions that vaccinated persons can infected others, especially early on in the infection lifecyle when viral loads are high
Ajit Lalvani, Professor NIHR Health Projection Research Unit in Respiratory Infections, National Heart and Lung Institute, Imperial College London, Corresponding Author, Chair Infectious Disease