Risk Factors Associated With SARS-CoV-2 Breakthrough Infections in Fully mRNA-Vaccinated Individuals: Retrospective Analysis

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

COVID-19 messenger RNA (mRNA) vaccines have demonstrated efficacy and effectiveness in preventing symptomatic COVID-19, while being relatively safe in trial studies. However, vaccine breakthrough infections have been reported.

Objective

This study aims to identify risk factors associated with COVID-19 breakthrough infections among fully mRNA-vaccinated individuals.

Methods

We conducted a series of observational retrospective analyses using the electronic health records (EHRs) of the Columbia University Irving Medical Center/New York Presbyterian (CUIMC/NYP) up to September 21, 2021. New York City (NYC) adult residences with at least 1 polymerase chain reaction (PCR) record were included in this analysis. Poisson regression was performed to assess the association between the 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 in the EHR.

Results

The overall estimated breakthrough infection rate was 0.16 (95% CI 0.14-0.18). Individuals who were vaccinated with Pfizer/BNT162b2 (incidence rate ratio [IRR] against Moderna/mRNA-1273=1.66, 95% CI 1.17-2.35) were male (IRR against female=1.47, 95% CI 1.11-1.94) and had compromised immune systems (IRR=1.48, 95% CI 1.09-2.00) were at the highest risk for breakthrough infections. Among all underlying conditions, those with primary immunodeficiency, a history of organ transplant, an active tumor, use of immunosuppressant medications, or Alzheimer disease were at the highest risk.

Conclusions

Although we found both mRNA vaccines were effective, Moderna/mRNA-1273 had a lower incidence rate of breakthrough infections. Immunocompromised and male individuals were among the highest risk groups experiencing breakthrough infections. Given the rapidly changing nature of the SARS-CoV-2 pandemic, continued monitoring and a generalizable analysis pipeline are warranted to inform quick updates on vaccine effectiveness in real time.

Related collections

Most cited references 53

Record: found
Abstract: found
Article: not found

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Fernando P Polack, Stephen J. Thomas, Nicholas R.E. Kitchin … (2023)

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)

0 comments Cited 6931 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

Lindsey Baden, Hana El Sahly, Brandon Essink … (2020)

Abstract Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. Methods This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. Results The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups. Conclusions The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.)

0 comments Cited 4757 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant

Jamie Lopez Bernal, Nick Andrews, Charlotte Gower … (2021)

Background The B.1.617.2 (delta) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), has contributed to a surge in cases in India and has now been detected across the globe, including a notable increase in cases in the United Kingdom. The effectiveness of the BNT162b2 and ChAdOx1 nCoV-19 vaccines against this variant has been unclear. Methods We used a test-negative case–control design to estimate the effectiveness of vaccination against symptomatic disease caused by the delta variant or the predominant strain (B.1.1.7, or alpha variant) over the period that the delta variant began circulating. Variants were identified with the use of sequencing and on the basis of the spike ( S ) gene status. Data on all symptomatic sequenced cases of Covid-19 in England were used to estimate the proportion of cases with either variant according to the patients’ vaccination status. Results Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) was notably lower among persons with the delta variant (30.7%; 95% confidence interval [CI], 25.2 to 35.7) than among those with the alpha variant (48.7%; 95% CI, 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among persons with the alpha variant and 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among persons with the alpha variant and 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Conclusions Only modest differences in vaccine effectiveness were noted with the delta variant as compared with the alpha variant after the receipt of two vaccine doses. Absolute differences in vaccine effectiveness were more marked after the receipt of the first dose. This finding would support efforts to maximize vaccine uptake with two doses among vulnerable populations. (Funded by Public Health England.)

0 comments Cited 1379 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Chunhua Weng:

ORCID: https://orcid.org/0000-0002-9624-0214

Department of Biomedical InformaticsColumbia University Irving Medical CenterPH-20622 W 168 StreetNew York, NY, 10032United States1 212 304 7907cw2384@cumc.columbia.edu

Journal

Journal ID (nlm-ta): JMIR Public Health Surveill

Journal ID (iso-abbrev): JMIR Public Health Surveill

Journal ID (publisher-id): JPH

Title: JMIR Public Health and Surveillance

Publisher: JMIR Publications (Toronto, Canada )

ISSN (Electronic): 2369-2960

Publication date Collection: May 2022

Publication date (Electronic): 24 May 2022

Publication date PMC-release: 24 May 2022

Volume: 8

Issue: 5

Electronic Location Identifier: e35311

Affiliations

[1 ] Department of Biomedical Informatics Columbia University Irving Medical Center New York, NY United States

[2 ] School of Pharmacy Jeonbuk National University Jeonju Republic of Korea

[3 ] Department of Medicine Columbia University Irving Medical Center New York, NY United States

[4 ] Department of Computer Science New Jersey Institute of Technology Newark, NJ United States

Author notes

Corresponding Author: Chunhua Weng cw2384@ 123456cumc.columbia.edu

Author information

Cong Liu https://orcid.org/0000-0001-6024-3037

Junghwan Lee https://orcid.org/0000-0002-1240-7655

Casey Ta https://orcid.org/0000-0002-4679-805X

Ali Soroush https://orcid.org/0000-0001-6900-5596

James R Rogers https://orcid.org/0000-0001-7329-3535

Jae Hyun Kim https://orcid.org/0000-0002-8609-7135

Karthik Natarajan https://orcid.org/0000-0002-9066-9431

Jason Zucker https://orcid.org/0000-0001-6987-6412

Yehoshua Perl https://orcid.org/0000-0003-1940-9386

Chunhua Weng https://orcid.org/0000-0002-9624-0214

Article

Publisher ID: v8i5e35311

DOI: 10.2196/35311

PMC ID: 9132195

PubMed ID: 35486806

SO-VID: 6e17f9f2-d99c-49ca-b35b-e6af70abab8a

Copyright © ©Cong Liu, Junghwan Lee, Casey Ta, Ali Soroush, James R Rogers, Jae Hyun Kim, Karthik Natarajan, Jason Zucker, Yehoshua Perl, Chunhua Weng. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 24.05.2022.

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Public Health and Surveillance, is properly cited. The complete bibliographic information, a link to the original publication on https://publichealth.jmir.org, as well as this copyright and license information must be included.

History

Date received : 2 December 2021

Date revision requested : 18 March 2022

Date revision received : 29 March 2022

Date accepted : 27 April 2022

Comments

Comment on this article

scite_

Cited by 8

See all cited by

Most referenced authors 1,680

See all reference authors

Submit your digital health research with an established publisher
- celebrating 25 years of open access