Transmissibility of SARS-CoV-2 among fully vaccinated individuals

The important analysis by Anika Singanayagam and colleagues¹ demonstrated that individuals fully vaccinated against SARS-CoV-2 with breakthrough infections have similar peak viral loads to unvaccinated people and might infect other fully vaccinated individuals within the same household. Of particular concern, vaccines that permit transmission do not confer sterilising immunity, thus potentially resulting in accumulation of large viral loads and increased risk of immune escape.² By mainly targeting the SARS-CoV-2 spike protein, vaccines can favour propagation of variants with immune-escape mutations.³ Single point mutations in the receptor-binding domain of the viral spike protein are sufficient to facilitate the immune escape and transmission of resistant viruses.² By further examining the unpublished whole-genome sequencing data of vaccinated and unvaccinated participants in the study by Singanayagam and colleagues,¹ invaluable information could be gleaned about whether the current first-generation COVID-19 vaccines potentially exerted selective pressure for resistant SARS-CoV-2 variants.

Tracing the whole-genome sequencing data of all unvaccinated participants chronologically from the pre-alpha-variant (B.1.1.7) phase (September–November, 2020), to the alpha-variant phase (December, 2020, to March, 2021), and to the delta-variant (B.1.617.2) period (May 25–Sept 15, 2021) would likely reveal a trend of increasing number of mutations that converge towards the resultant whole-genome sequence aligned with delta lineage-defining mutations presented in figure 2 of the Article.¹ To determine if vaccines possibly contributed to this genetic drift, the whole-genome sequencing data from patients who tested PCR positive (vaccinated and unvaccinated) can be compared with data from their respective contacts over time from the pre-alpha to the delta phases.

Identical whole-genome sequences between PCR-positive participants and their respective contacts demonstrates direct viral transmission without mutation. Clearly distinct whole-genome sequences between both groups indicate cross-infection of contacts by a different viral lineage. Slight variations in whole-genome sequences between both groups show mutation has occurred, in which case the vaccination status of the contact should be examined. If mutation occurred predominantly among vaccinated contacts but not within unvaccinated contacts, it suggests vaccine-induced mutation has developed. Because the sample size in the research by Singanayagam and colleagues¹ is relatively small, it will be worrisome if a fair number of vaccinated contacts of PCR-positive participants are identified with mutations, especially with the amino acid mutations summarised in the appendix.

The earliest detection of the delta variant was in India on Oct 14, 2020,⁴ before India's vaccination commencement on Jan 16, 2021.⁵ However, with fastidious propagation of these variants over time by non-sterilising vaccines targeting the spike protein, it is still reasonably plausible that selective pressure could have contributed to the current dominance of the delta variant.

It would be much appreciated if Singanayagam and colleagues would consider analysing their unpublished whole-genome sequencing data as suggested above. If theoretical risk of evolutionary escape from the existing COVID-19 vaccines² translates into real-life evidence, which could be verified via whole-genome sequencing data from this study,¹ then it will be prudent to expedite resources towards second-generation COVID-19 vaccines that exert sterilising immunity, in addition to non-pharmacological interventions.