Dataset Information

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.

SUBMITTER: Ke R

PROVIDER: S-EPMC9047214 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Ke Ruian R Martinez Pamela P PP Smith Rebecca L RL Gibson Laura L LL Achenbach Chad J CJ McFall Sally S Qi Chao C Jacob Joshua J Dembele Etienne E Bundy Camille C Simons Lacy M LM Ozer Egon A EA Hultquist Judd F JF Lorenzo-Redondo Ramon R Opdycke Anita K AK Hawkins Claudia C Murphy Robert L RL Mirza Agha A Conte Madison M Gallagher Nicholas N Luo Chun Huai CH Jarrett Junko J Conte Abigail A Zhou Ruifeng R Farjo Mireille M Rendon Gloria G Fields Christopher J CJ Wang Leyi L Fredrickson Richard R Baughman Melinda E ME Chiu Karen K KK Choi Hannah H Scardina Kevin R KR Owens Alyssa N AN Broach John J Barton Bruce B Lazar Peter P Robinson Matthew L ML Mostafa Heba H HH Manabe Yukari C YC Pekosz Andrew A McManus David D DD Brooke Christopher B CB

Open forum infectious diseases 20220413 7

<h4>Background</h4>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.<h4>Methods</h4>We examined viral dynamics and infectious virus shedding through daily longitudinal sampling in 23 adults infected with SARS-CoV-2 at varyin ...[more]

PMID: 35791353

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Project description:Breakthrough SARS-CoV-2 infections have been reported in fully vaccinated individuals, in spite of the high efficacy of the currently available vaccines, proven in trials and real-world studies. Several variants of concern (VOC) have been proffered to be associated with breakthrough infections following immunization. In this study, we investigated 378 breakthrough infections recorded between January and July 2021 and compared the distribution of SARS-CoV-2 genotypes identified in 225 fully vaccinated individuals to the frequency of circulating community lineages in the region of South Limburg (The Netherlands) in a week-by-week comparison. Although the proportion of breakthrough infections was relatively low and stable when the Alpha variant was predominant, the rapid emergence of the Delta variant lead to a strong increase in breakthrough infections, with a higher relative proportion of individuals vaccinated with Vaxzevria or Jcovden being infected compared to those immunized with mRNA-based vaccines. A significant difference in median age was observed when comparing fully vaccinated individuals with severe symptoms (83 years) to asymptomatic cases (46.5 years) or individuals with mild-to-moderate symptoms (42 years). There was no association between SARS-CoV-2 genotype or vaccine type and disease symptoms. Furthermore, the majority of adaptive mutations were concentrated in the N-terminal domain of the Spike protein, highlighting its role in immune evasion. Interestingly, symptomatic individuals harbored significantly higher SARS-CoV-2 loads than asymptomatic vaccinated individuals and breakthrough infections caused by the Delta variant were associated with increased viral loads compared to those caused by the Alpha variant. In addition, we investigated the role of the Omicron variant in causing breakthrough infections by analyzing 135 samples that were randomly selected for genomic surveillance during the transition period from Delta to Omicron. We found that the proportion of Omicron vs. Delta infections was significantly higher in individuals who received a booster vaccine compared to both unvaccinated and fully vaccinated individuals. Altogether, these results indicate that the emergence of the Delta variant and in particular Omicron has lowered the efficiency of particular vaccine types to prevent SARS-CoV-2 infections and that, although rare, the elderly are particularly at risk of becoming severely infected as the consequence of a breakthrough infection.

Project description:ImportanceLittle is known about COVID vaccine breakthrough infections and their risk factors.ObjectiveTo identify risk factors associated with COVID-19 breakthrough infections among vaccinated individuals and to reassess the effectiveness of COVID-19 vaccination against severe outcomes using real-world data.Design setting and participantsWe conducted a series of observational retrospective analyses using the electronic health records (EHRs) of Columbia University Irving Medical Center/New York Presbyterian (CUIMC/NYP) up to September 21, 2021. New York adult residence with PCR test records were included in this analysis.Main outcomes and measuresPoisson regression was used to assess the association between breakthrough infection rate in vaccinated individuals and multiple risk factors - including vaccine brand, demographics, and underlying conditions - while adjusting for calendar month, prior number of visits and observational days. Logistic regression was used to assess the association between vaccine administration and infection rate by comparing a vaccinated cohort to a historically matched cohort in the pre-vaccinated period. Infection incident rate was also compared between vaccinated individuals and longitudinally matched unvaccinated individuals. Cox regression was used to estimate the association of the vaccine and COVID-19 associated severe outcomes by comparing breakthrough cohort and two matched unvaccinated infection cohorts.ResultsIndividuals vaccinated with Pfizer/BNT162b2 (IRR against Moderna/mRNA-1273 [95% CI]: 1.66 [1.17 - 2.35]); were male (1.47 [1.11 - 1.94%]); and had compromised immune systems (1.48 [1.09 - 2.00]) were at the highest risk for breakthrough infections. Vaccinated individuals had a significant lower infection rate among all subgroups. An increased incidence rate was found in both vaccines over the time. Among individuals infected with COVID-19, vaccination significantly reduced the risk of death (adj. HR: 0.20 [0.08 - 0.49]).Conclusion and relevanceWhile we found both mRNA vaccines were effective, Moderna/mRNA-1273 had a lower incidence rate of breakthrough infections. Both vaccines had increased incidence rates over the time. Immunocompromised individuals were among the highest risk groups experiencing breakthrough infections. Given the rapidly changing nature of the SARS-CoV-2, continued monitoring and a generalizable analysis pipeline are warranted to inform quick updates on vaccine effectiveness in real time.Key pointsQuestion: What risk factors contribute to COVID-19 breakthrough infections among mRNA vaccinated individuals? How do clinical outcomes differ between vaccinated but still SARS-CoV-2 infected individuals and non-vaccinated, infected individuals?Findings: This retrospective study uses CUIMC/NYP EHR data up to September 21, 2021. Individuals who were vaccinated with Pfizer/BNT162b2, male, and had compromised immune systems had significantly higher incidence rate ratios of breakthrough infections. Comparing demographically matched pre-vaccinated and unvaccinated individuals, vaccinated individuals had a lower incidence rate of SARS-CoV-2 infection among all subgroups.Meaning: Leveraging real-world EHR data provides insight on who may optimally benefit from a booster COVID-19 vaccination.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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