Infectious viral shedding of SARS-CoV-2 Delta following vaccination: A longitudinal cohort study

Abstract

The impact of vaccination on SARS-CoV-2 infectiousness is not well understood. We compared longitudinal viral shedding dynamics in unvaccinated and fully vaccinated adults. SARS-CoV-2-infected adults were enrolled within 5 days of symptom onset and nasal specimens were self-collected daily for two weeks and intermittently for an additional two weeks. SARS-CoV-2 RNA load and infectious virus were analyzed relative to symptom onset stratified by vaccination status. We tested 1080 nasal specimens from 52 unvaccinated adults enrolled in the pre-Delta period and 32 fully vaccinated adults with predominantly Delta infections. While we observed no differences by vaccination status in maximum RNA levels, maximum infectious titers and the median duration of viral RNA shedding, the rate of decay from the maximum RNA load was faster among vaccinated; maximum infectious titers and maximum RNA levels were highly correlated. Furthermore, amongst participants with infectious virus, median duration of infectious virus detection was reduced from 7.5 days (IQR: 6.0–9.0) in unvaccinated participants to 6 days (IQR: 5.0–8.0) in those vaccinated (P = 0.02). Accordingly, the odds of shedding infectious virus from days 6 to 12 post-onset were lower among vaccinated participants than unvaccinated participants (OR 0.42 95% CI 0.19–0.89). These results indicate that vaccination had reduced the probability of shedding infectious virus after 5 days from symptom onset.

SARS-CoV-2 viral load and shedding kinetics

“…Vaccination was also found to influence infectious virus isolation. Viable virus in cell culture was detected for significantly longer median time periods in unvaccinated patients infected with Delta than in vaccinated patients infected with Delta 155,158 . However, no significant differences in RNA viral loads were found between unvaccinated, fully vaccinated or boosted patients infected with Omicron BA.1 or BA.2 (refs.…”

“…Immunization with ChAdOx1 vaccine also led to a reduction of RNA viral load in breakthrough infections with Alpha VOC 153 . Faster clearance of RNA viral loads was detected in the group of vaccinated patients who mostly received mRNA vaccines 154,155 , and lower probability of isolation of infectious virus from patients vaccinated with mRNA or adenoviral vector vaccines was observed 156,157 . Even though not all studies could demonstrate a reduction of RNA viral loads in Delta breakthrough infections 150,154 , infectious virus titres were reported to be lower in individuals vaccinated with mRNA or adenoviral vector vaccines despite similar levels of viral RNA 25,93,157 .…”

Intranasal self-amplifying RNA SARS-CoV-2 vaccine produces protective respiratory and systemic immunity and prevents viral transmission

“…Since their introduction in late 2020, two now FDA-approved mRNA vaccines (Comirnaty and Spikevax) have had a remarkable impact on the trajectory of the pandemic and were developed at unprecedented speeds 1 . However, while these vaccines have displayed remarkable efficacy at preventing severe COVID-19 and slowing the worldwide pandemic, the lack of vaccine-induced local immunity in the respiratory tract allows for mild infection despite vaccination, resulting in transmission by vaccinated people [2][3][4] . Between lack of vaccine .…”

“…Since their introduction in late 2020, two now FDA-approved mRNA vaccines (Comirnaty and Spikevax) have had a remarkable impact on the trajectory of the pandemic and were developed at unprecedented speeds 1 . However, while these vaccines have displayed remarkable efficacy at preventing severe COVID-19 and slowing the worldwide pandemic, the lack of vaccine-induced local immunity in the respiratory tract allows for mild infection despite vaccination, resulting in transmission by vaccinated people [2][3][4] . Between lack of vaccine induction of mucosal immunity, newly emerging variants 5 , waning efficacy of currently-approved mRNA vaccines 6 , need for frequent booster doses 7 , vaccine hesitancy in part fueled by a fear of needles 8 , and limited access to cold chain storage 9 , global susceptibility to SARS-CoV-2 remains high.…”

Rapid recall andde novoT cell responses during SARS-CoV-2 breakthrough infection

“…In particular, it has been proposed that CD4 + and CD8 + T cell memory are important mediators of vaccine-associated protection from severe outcomes (Bertoletti et al, 2022b; Scurr et al, 2022; Wherry and Barouch, 2022). Interestingly, although unvaccinated and vaccinated cohorts show similar peak viral load after infection, vaccinated individuals exhibit accelerated viral clearance in the upper respiratory tract (URT) beginning four to six days after symptom onset(Chia et al, 2022; Garcia-Knight et al, 2022; Puhach et al, 2022; Singanayagam et al, 2022). While the mechanisms of vaccine-associated viral decline are yet to be defined, a role is plausible for both CD8 + T cells, which may induce cytolysis or produce antiviral cytokines (Rha et al, 2021; Sekine et al, 2020) as well as CD4 + T cells, which may support the recall of humoral immunity or potentially exert cytotoxic activity (Kaneko et al, 2022; Meckiff et al, 2020).…”