Longitudinal Analysis of SARS-CoV-2 Vaccine Breakthrough Infections Reveals Limited Infectious Virus Shedding and Restricted Tissue Distribution

Abstract

Background: The global effort to vaccinate people against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during an ongoing pandemic has raised questions about how vaccine breakthrough infections compare with infections in immunologically naive individuals and the potential for vaccinated individuals to transmit the virus.

Methods: We examined viral dynamics and infectious virus shedding through daily longitudinal sampling in 23 adults infected with SARS-CoV-2 at varying stages of vaccination, including 6 fully vaccinated individuals.

Results: The durations of both infectious virus shedding and symptoms were significantly reduced in vaccinated individuals compared with unvaccinated individuals. We also observed that breakthrough infections are associated with strong tissue compartmentalization and are only detectable in saliva in some cases.

Conclusions: Vaccination shortens the duration of time of high transmission potential, minimizes symptom duration, and may restrict tissue dissemination.

Keywords: SARS-CoV-2; breakthrough infections; vaccines; viral dynamics.

Figure 1.

Viral dynamics in vaccinated individuals. A, Temporal trends for the saliva RTqPCR (light blue squares), nasal swab RTqPCR (dark blue dots), and positive nasal swab viral culture results (tan bars) in fully vaccinated individuals who enrolled ≥14 days after the second mRNA vaccine dose or first J&J vaccine dose. The x-axis shows days since the first positive PCR result. The y-axis indicates Ct values for saliva RTqPCR assay (covidSHIELD) and CN values for nasal swab RTqPCR assay (Abbott Alinity). The horizontal dashed line indicates the limit of detection of RTqPCR assays. For individuals at the NU study site, saliva samples were not collected; thus only nasal swab data are shown. B, Same data as in (A) but for partially vaccinated individuals who enrolled ≥14 days after first mRNA vaccine dose but were not yet fully vaccinated. C, Same data as in (A) but for newly vaccinated individuals who enrolled <14 days after first mRNA or J&J vaccine dose. D, Numbers of days that vaccinated (combined fully and partially vaccinated individuals), newly vaccinated individuals, and unvaccinated individuals (from Ke et al. [7]) tested viral culture positive. ns, P > .05; *P < .05; **P < .01; ***P < .001. E, Association between the nasal CN values and the probability of the sample being viral culture positive summarized across the vaccinated individuals, newly vaccinated individuals, and unvaccinated individuals (from Ke et al. [7]). Dots indicate individual viral culture results, 1 being a positive result and 0 a negative result. The solid line and the shaded area are the mean and CI, respectively, of a logistic regression fit. F, Proportion of days postenrollment (up to 14 days) that vaccinated, newly vaccinated, and unvaccinated individuals reported no symptoms. ns, P > .05; *P < .05; **P < .01; ***P < .001. G, Plot showing antigen FIA results from days where participants tested either positive or negative by viral culture. The text inside the bars indicates the percentage of antigen FIA results that were positive when the concurrent viral culture sample was positive or negative. Abbreviations: CN, cycle number; Ct, cycle threshold; FIA, fluorescence Immunoassay; NU, Northwestern University; PCR, polymerase chain reaction; RTqPCR, reverse transcription quantitative polymerase chain reaction; UIUC, University of Illinois at Urbana-Champaign.