Related Experiment Video
Updated: Sep 25, 2025

Author Spotlight: Studying Host-Virus Interactions with Pseudotyped Viruses
Published on: November 21, 2023
Risk Factors Associated With SARS-CoV-2 Breakthrough Infections in Fully mRNA-Vaccinated Individuals: Retrospective
Cong Liu1, Junghwan Lee1, Casey Ta1
1Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY, United States.
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.
More Related Videos
Related Concept Videos
Factors Affecting the Risk of Infection
The integrity and count of the white blood cells help the body resist pathogens and fight infection. When impaired, it reduces the body's resistance to pathogens. The acidic pH levels of the gastrointestinal, genitourinary tracts, and skin...
Single Nucleotide Polymorphisms-SNPs
Rous Sarcoma Virus (RSV) and Cancer
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
Bias in Epidemiological Studies
Viral Mutations
Confounding in Epidemiological Studies

