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COVID mRNA Vaccines Appear to Protect
Against Infection Transmission
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2022 CROI, February 12-16 and 22-24, 2022
Mark Mascolini
SARS-CoV-2 proved most infectious (transmissible) in primary infection of unvaccinated people, followed by people with Pfizer vaccine breakthrough infection, Moderna vaccine breakthroughs, then reinfection of unvaccinated people, according to analysis of the Qatar national COVID-19 database [1]. "Public health benefits of vaccination may have been underestimated," researchers from Weill Cornell Medicine-Qatar proposed, "as COVID-19 vaccines not only protect against acquisition of infection, but also appear to protect against transmission of infection."
Breakthrough COVID-19 infections after vaccination or a first infection are familiar phenomena of the pandemic, but no one gauged the infectiousness of breakthrough infections until this study. To assess infectiousness, Weill Cornell-Qatar researchers used real-time (quantitative) reverse transcription PCR (RT-qPCR) cycle threshold, which measures the inverse of viral load and correlates strongly with the amount of virus that can be cultured. A higher RT-qPCR cycle threshold value indicates less infectious (less transmissible) virus.
The investigators estimated the effect of vaccination and of prior infection on SARS-CoV-2 infectiousness in Qatar's national COVID-19 database from February 28, 2020 to July 11, 2021 by making pairwise comparisons of RT-qPCR cycle threshold values in four cohorts:
Group 1. Primary infection in unvaccinated people
Group 2. Reinfection in unvaccinated people
Group 3. Breakthrough infection after Pfizer-BioNTech vaccination
Group 4. Breakthrough infection after Moderna vaccination
SARS-CoV-2 incidence had two peaks in Qatar during the study period-wild-type virus in May/June 2020, and Beta variant-dominated virus around March/April 2021.
The researchers could make 6 pairwise comparisons matching on sex, 10-year age group, reason for RT-qPCR, and calendar week of RT-qPCR:
Study 1: Group 1 (n = 4035) paired with Group 3
Study 2: Group 1 (n = 265) paired with Group 4
Study 3:Group 3 (n = 227) paired with Group 4
Study 4: Group 2 (n = 1686) paired with Group 1
Study 5: Group 2 (n = 761) paired with Group 3
Study 6: Group 2 (n = 85) paired with Group 4
Average RT-qPCR cycle threshold values in randomly diagnosed asymptomatic infections differed significantly in 5 of the 6 comparisons and nearly significantly in the sixth:
Study 1: mean 25.5 in Group 1 (primary infection in unvaccinated) vs 26.8 in Group 3 (breakthrough after Pfizer vaccination); difference in means 1.3 (95% confidence interval [CI] 0.9 to 1.8, P < 0.001)
Study 2: mean 28.0 in Group 1 (primary infection of unvaccinated) vs 31.2 in Group 4 (breakthrough after Moderna vaccination): difference in means 3.2 (95% CI 1.9 to 4.5, P < 0.001
Study 3: mean 28.7 in Group 3 (breakthrough after Pfizer vaccination) vs 31.0 in Group 4 (breakthrough after Moderna vaccination): difference in means 2.2 (95% CI 0.9 to 3.6, P = 0.003)
Study 4: mean 24.8 in Group 1 (primary infection in unvaccinated) vs 28.8 in Group 2 (reinfection in unvaccinated): difference in means 4.0 (95% CI 3.5 to 4.5, P < 0.001)
Study 5: mean 27.0 in Group 3 (breakthrough after Pfizer vaccination) vs 28.9 in Group 2 (reinfection in unvaccinated): difference in means 2.0 (95% CI 1.2 to 2.8, P < 0.001)
Study 6: mean 30.0 in Group 4 (breakthrough after Moderna vaccination) vs 31.7 in Group 2 (reinfection in unvaccinated): difference in means 1.7 (95% CI -0.3 to 3.7, P = 0.096)
Average RT-qPCR cycle threshold values in symptomatic infections differed significantly in 4 of the 6 comparisons (and virtually significantly, P = 0.051, in one):
Study 1: mean 22.5 in Group 1 (primary infection of unvaccinated) vs 22.7 in Group 3 (breakthrough after Pfizer vaccination); difference in means 0.2 (95% CI -0.2 to 0.6, P = 0.332)
Study 2: mean 21.7 in Group 1 (primary infection of unvaccinated) vs 26.6 in Group 4 (breakthrough after Moderna vaccination): difference in means 4.9 (95% CI 2.3 to 7.4, P < 0.001)
Study 3: mean 21.3 in Group 3 (breakthrough after Pfizer vaccination) vs 26.6 in Group 4 (breakthrough after Moderna vaccination): difference in means 5.3 (95% CI 2.6 to 8.1, P < 0.001)
Study 4: mean 22.7 in Group 1 (primary infection of unvaccinated) vs 26.5 in Group 2 (reinfection in unvaccinated): difference in means 3.8 (95% CI 2.9 to 4.7, P < 0.001)
Study 5: mean 23.7 Group 3 (breakthrough after Pfizer vaccination) vs 25.6 in Group 2 (reinfection in unvaccinated): difference in means 1.8 (95% CI 0.6 to 3.0, P = 0.003)
Study 6: mean 23.5 in Group 4 (breakthrough after Moderna vaccination) vs 30.0 in Group 2 (reinfection in unvaccinated): difference in means 6.4 (95% CI -0.04 to 12.9, P = 0.051)
Adjusting for age, sex, nationality, reason for RT-qPCR, and calendar week of RT-qPCR, linear regression analysis for RT-qPCR cycle threshold value found significantly higher values (denoting less infectious virus) in:
- Reinfection of unvaccinated people (vs primary infection in unvaccinated people): beta 3.67 (95% CI 3.38 to 3.96, P < 0.001)
- Pfizer breakthroughs (vs primary infection in unvaccinated people): beta 0.82 (95% CI 0.63 to 1.01, P < 0.001)
- Moderna breakthroughs (vs primary infection in unvaccinated people): beta 3.29 (95% CI 2.58 to 4.00, P < 0.001)
The Weill Cornell-Qatar researchers believe their findings indicate a "hierarchy of infectiousness of SARS-CoV-2" with the most infectious virus found in unvaccinated people with primary infection, followed by Pfizer breakthrough infections, Moderna breakthrough infections, and reinfections of unvaccinated people.
"Strikingly," the investigators noted, "this hierarchy is the mirror image of the hierarchy observed in the efficacy against" acquiring SARS-CoV-2 infection. Therefore the investigators suggested the "public health benefits of vaccination may have been underestimated" because the Pfizer and Moderna vaccines not only protect against primary infection, but also seem to protect against transmission of the acquired virus.
Reference
1. Abu-Raddad LJ, Chemaitelly H, for the National Study Group for COVID-19 Epidemiology in Qatar. Infectiousness of breakthrough infections after vaccination and natural infection. 2022 CROI, February 12-16 and 22-24, 2022. Abstract 49.
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