Risk factor assessment for the development of severe SARS-CoV-2 breakthrough infections

By Pooja Toshniwal PahariaReviewed by Aimee MolineuxDec 1 2022

In a recent study published in BMC Scientific Diseases, researchers evaluated the severity of breakthrough SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infections and the risk factors associated with severity among individuals vaccinated for coronavirus disease 2019 (COVID-19) in Sousse, Tunisia.

Background

Vaccination has been regarded as the key tool for coronavirus disease 2019 (COVID-19) mitigation and the prevention of severe outcomes such as hospitalizations and deaths. However, breakthrough infections have been reported among vaccinated individuals. With the expansion of COVID-19 vaccination programs, vaccine efficacy in preventing COVID-19 severity needs to be evaluated.

The Tunisian Ministry of Health’s regional office affiliated with the national strategy for SARS-CoV-2 infection surveillance to implement a prevention campaign for motivating individuals to undergo symptomatic individuals to undergo SARS-CoV-2 testing and health professionals to perform testing. Active and passive types of screening were performed for COVID-19 case identification. The active screening included contact tracing, individual screening clusters, and those at border points.

The passive screening was conducted at primary health centers, hospitals, private laboratories, medical offices, pharmacies, and during emergencies. COVID-19 was confirmed via a well-coded system. Authorized health offices or institutions declared COVID-19 cases to the Tunisian Ministry of Health’s regional office, and the cases were verified by a trained government agent and laboratory test reports. Post-verification, the infected individual was registered in the database.

About the study

In the present observational longitudinal study, researchers evaluated the severity and risk factors associated with COVID-19 breakthrough infections among SARS-CoV-2 vaccinees residing in Sousse between March and August 2021.

Individual-level data of post-vaccinated real-time reverse transcription-polymerase chain reaction (RT-PCR)-confirmed COVID-19 case individuals residing in Sousse, documented in the daily SARS-CoV-2 infection database maintained at the Tunisian Ministry of Health’s regional office, were analyzed. The database included data for variables such as sex, age, reporting date, symptom onset date, and status of vaccination.

In addition, sociodemographic (sex, age, occupation, district) and clinical data (tobacco consumption habits, medical history, symptoms, self-estimated compliance with COVID-19 prevention measures, oxygenation requirements, hospitalizations, and deaths) were obtained by the epidemiology department through 15.0-minute telephone interviews.

COVID-19 SIR (specific incidence rates) by vaccination type for every 100,000 individuals were estimated. Logistic regression modeling was performed, and adjusted odds ratios were calculated to identify risk factors associated with severe or critical SARS-CoV-2 infections. Individuals exposed to SARS-CoV-2 before vaccination were excluded from the analysis. Breakthrough infections were described as SARS-CoV-2 infections occurring ≥2.0 weeks after full COVID-19 vaccination.

SARS-CoV-2 infections were considered severe if they required oxygen supplementation, and the infections were considered critical if they led to intensive care unit (ICU) admissions or deaths. Confirmed and suspected COVID-19 cases were described based on the COVID-19 diagnosis and treatment scheme, and close contacts were identified by the COVID-19 prevention and control scheme published by Tunisia’s national health commission.

Results

By July 31, 2021, 1,07,545 individuals aged >19.0 years were vaccinated with ≥1.0 COVID-19 vaccine doses. Among Sousse residents, 74,503 individuals, 15,305 individuals, 13,944 individuals, 1,943 individuals, 967 individuals, and 883 individuals were vaccinated with Pfizer, AstraZeneca, CORONAVAC, SINOPHARM, SPUTNIK V, and other COVID-19 vaccines, respectively.

Among the vaccinees, 765 COVID-19 breakthrough infections were detected, with an incidence rate of 711. Most of the vaccinees were women, and the mean individual age was 56.0 years. The odds of severe or critical COVID-19 were two-fold higher among males than females (OR 2.1). Additionally, advancing age, cardiovascular disorders, and single-dose vaccinations were associated with greater odds of severe COVID-19. Contrastingly, higher scores for self-estimated compliance with COVID-19 prevention measures were linked to lower odds of severe or critical COVID-19.

The prevalence of severe or critical COVID-19 among the vaccinees was 11.0%, and the observed global cumulative incidence for COVID-19 was 3484. Of the 765 cases of breakthrough infections identified, 123 cases were excluded due to participation unwillingness or missed telephonic calls, and thus, data from 618 individuals were analyzed. Almost half (49%, n=399) of the individuals had comorbidities, 20% were health professionals, and 18% smoked. Most of the case individuals were vaccinated with ≥1.0 doses of Pfizer (n=424, 70%) and CORONAVAC (n=96, 16%) vaccines.

COVID-19 incidence rates were higher among SPUTNIK V vaccinees and SINOPHARM vaccinees, with SIR values of 1551, and 824, respectively. COVID-19 led to oxygen requirements, hospitalization, ICU admissions, and deaths in seven percent, eight percent, two percent, and two percent of cases, respectively. The percentage of critical or severe COVID-19 cases was the highest among individuals aged ≥75 years (25%) and the least for those aged between 40 and 49 years.

Overall, the study findings showed a relatively low prevalence of critical or severe COVID-19 breakthrough infections among Sousse residents. The findings indicated that having cardiovascular disorders, poor self-estimated compliance to COVID-19 prevention measures, and single-dose vaccinations increased the risk of COVID-19 severity.