Understanding Breakthrough Infections Following mRNA SARS-CoV-2 Vaccination

Abstract

The current surge in infections with the SARS-CoV-2 Delta variant has made it clear to health care workers and the public alike that fully vaccinated people remain at risk for SARS-CoV-2 infections. It is also apparent that breakthrough infections in fully vaccinated people can sometimes be serious. As of October 21, 2021, for example, 35% of the 519 patients hospitalized with COVID-19 in Massachusetts had been fully vaccinated. 1 Furthermore, multiple reports have documented that if fully vaccinated individuals do become infected, their viral loads may be as high as the levels seen in unvaccinated individuals. 2 In July 2021, these observations led the US Centers for Disease Control and Prevention to modify its guidance for fully vaccinated people, advising that those in communities with substantial or high SARS-CoV-2 transmission rates should wear masks indoors regardless of their vaccination status. 3,4 A wealth of new data has since emerged that is helping to deepen understanding of the frequency, severity, and importance of breakthrough infections in fully vaccinated individuals.New evidence shows that even though fully vaccinated people remain at risk for SARS-CoV-2 infection, they are substantially less prone to carry SARS-CoV-2 compared with unvaccinated people. A point-prevalence survey of almost 100 000 people conducted in England in June-July 2021 during the height of that country's spring Delta variant surge found that fully vaccinated people (n = 55 962) were two-thirds less likely to harbor SARS-CoV-2 compared with unvaccinated people (n = 15 135), with absolute rates of 0.40% vs 1.21%, respectively. 5 Likewise, in a randomized trial of the mRNA-1273 vaccine (Moderna) vs placebo, vaccinated participants (n = 14 287) were two-thirds less likely to be asymptomatic carriers than unvaccinated participants (n = 14 164), with absolute rates of 1.5% vs 3.5%, respectively (estimated vaccine effectiveness against asymptomatic infection, 63.0% [95% CI, 56.6%-68.5%]). 6 Studies of viral dynamics further suggest that while viral loads in breakthrough infections may be as high in vaccinated individuals as they are in unvaccinated individuals, viral loads in those who are vaccinated decline more rapidly, and the virus that they shed is less likely to be culturepositive than virus shed by unvaccinated individuals. 7,8 This suggests that people who are fully vaccinated are less likely to become infected and if infected, will be contagious for shorter periods than unvaccinated people. This is supported by transmission studies that confirm that vaccinated people are less likely to transmit SARS-CoV-2 to close contacts compared with unvaccinated people, including the

Characterization of the significant decline in humoral immune response six months post-SARS-CoV-2 mRNA vaccination: A systematic review

“…9 Such vulnerability is correlated to the significant decline in anti-SARS-CoV-2 antibodies (Abs) over time. [10][11][12] This waning humoral response could lead to breakthrough infections, thus highlighting the potential role of serologic testing to assess vaccine immunogenicity and protection efficacy. While the role of T cells and B memory cells from vaccine-induced immunity has yet to be fully elucidated, multiple studies showed that Ab levels directly correlate with risk of vaccine reinfection and breakthrough, with low levels of anti-SARS-CoV-2 IgG in patients with infections correlating with high viral load and duration of viral shedding.…”

Virological and Serological Characterisation of SARS-CoV-2 Infections Diagnosed After mRNA BNT162b2 Vaccination Between December 2020 and March 2021

“…Case-control and population-level studies widely demonstrated that vaccination substantially reduces both asymptomatic and symptomatic infections, and significantly prevents severe COVID-19 (2,(14)(15)(16)(17). However vaccines are not sterilising and SARS-CoV-2 infections in previously vaccinated individuals can occur, although more likely to have a favourable outcome (18)(19)(20), even for immunecompromised individuals who were reported among the highest risk groups in experiencing breakthrough infections (21). Notably, breakthrough infections after vaccination against SARS-CoV-2 are increasingly reported, possibly due to the combined effect of the waning of vaccine-induced antibody levels and the emergence of new variants (22).…”

Vaccination Hesitancy among Health-Care-Workers in Academic Hospitals Is Associated with a 12-Fold Increase in the Risk of COVID-19 Infection: A Nine-Month Greek Cohort Study

“…Especially among HCWs, apart from the individual benefit of preventing severe COVID-19 and death, reducing the risk of SARS-CoV-2 infection can further prevent secondary transmission especially from asymptomatic stage in the Hospital setting [4,24]. Moreover, vaccinated people with breakthrough infections, including the "delta" variant, are less likely to develop symptoms in particular severe symptoms, are more likely to recover from their illness quickly and much less likely to require hospitalization or to transmit the infection to others [25][26][27]. The implication of additional preventive measures, such as COVID-19 vaccine booster doses and continued masking in particular for individuals at highest risk for breakthrough infections, may facilitate control of COVID-19 [18].…”