Factors associated with SARS-CoV-2 breakthrough infection in fully vaccinated individuals

In a recent study posted to the medRxiv* pre-print server, researchers conducted a retrospective case-control exploratory research to determine the demographic and clinical risk factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infections and their severity in fully vaccinated individuals.

Study: SARS-CoV-2 vaccine Alpha and Delta variant breakthrough infections are rare and mild, but happen relative early after vaccination. Image Credit: LookerStudio/Shutterstock

Coronavirus disease 2019 (COVID-19) vaccines effectively reduce SARS-CoV-2 infection-related hospitalizations and deaths and also show efficacy against different variants of SARS-CoV-2. However, many cases of breakthrough infections have been reported in fully vaccinated individuals. The factors compromising vaccine effectiveness and leading to breakthrough infections are still unknown and should be determined to develop an effective vaccination strategy against the new SARS-CoV-2 variants.

The study

The present study used the data of 1,26,586 residents of the Canton of Basel-City, who were fully vaccinated with any approved SARS-CoV-2 vaccine between 28 December 2020 to 25 December 2021. The study aimed to identify the risk factors associated with SARS-CoV-2 breakthrough infections and severity in individuals who had received both doses of vaccine. The researchers also compared the patient characteristics between breakthrough infections by Alpha and Delta variants. By the end of the study period, 1,26,586 individuals were fully vaccinated against SARS-COV-2 with either BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna), or Ad26.COV2.S (Janssen) vaccine, among which breakthrough infection was found in 492 individuals.

Methods and findings

The researchers analyzed the time distribution, in days, from being fully vaccinated to being positive for SARS-CoV-2 breakthrough infection and found that the majority of breakthrough infections occurred from a few days to 170 days post full vaccination (median of 78 days).

The analysis of patient characteristics showed that the median age of patients was 45 years (ranging between 32 – 64 years) and females (52.6%) comparatively had slightly more breakthrough infections than males. About 99.2% of the immunized population was vaccinated with mRNA-1273 (Moderna) or BNT162b2 mRNA (Pfizer/BioNTech).

Among the people with breakthrough infections, 26/492 (5.3%) suffered asymptomatic disease and 452/492 (91.9%) had a mild illness. The patients requiring hospitalization were very few (18/492; 2.8%) and were generally older in comparison to those who did not require hospitalization. The patients with moderate or severe illness displayed high predisposing risk factors as compared to those with mild or asymptomatic breakthrough infection.

The researchers compared the group of breakthrough infection patients (n=492) with the two control groups (control group 1, n=126,586; control group 2, n=109,382). The median age of patients in breakthrough infection cases was slightly lower at 45 years as compared to control group 1 (49 years) and control group 2 (52 years). The group with breakthrough infection cases (47%) were more frequently vaccinated with Pfizer/BioNTech vaccine than the control group 1 (33.5%) and the control group 2 (33.1%). Individuals with chronic disease conditions were at high risk of developing a breakthrough infection as compared to the control group and the same was evident from the study data.

Further, the researchers compared the patient clinical characteristics only found in breakthrough infections with the control group 2 and observed slightly higher breakthrough infections in patients with severe immunosuppression (5.3% vs. 3.0%) and fewer people with serious side-effects after vaccination (0.2% vs. 1.0%).

Between the Alpha and Delta variants, the majority of breakthrough infections were caused by the Delta variant as it was the dominant circulating strain in Switzerland during the study period.

Conclusion

Overall, the present study findings showed that the SARS-CoV-2 breakthrough infections are rare and show mild or asymptomatic profiles generally. The breakthrough infection occurs early after vaccination in almost 50% of the cases within 70 to 80 days post full vaccination. Breakthrough infections are common in people vaccinated with the Pfizer/BioNTech vaccine, individuals with chronic disease, or healthcare workers. The individuals with prior history of COVID-19 before vaccination are at low risk of having a breakthrough infection.

Taken together, these findings underline the significance of initiating booster vaccination as early as possible for populations at high risk of breakthrough infections such as healthcare workers and people in long-term care facilities.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Susha Cheriyedath

Susha has a Bachelor of Science (B.Sc.) degree in Chemistry and Master of Science (M.Sc) degree in Biochemistry from the University of Calicut, India. She always had a keen interest in medical and health science. As part of her masters degree, she specialized in Biochemistry, with an emphasis on Microbiology, Physiology, Biotechnology, and Nutrition. In her spare time, she loves to cook up a storm in the kitchen with her super-messy baking experiments.