Test-negative case-control analysis during a Delta variant-dominant period in California’s prisons

A new study published in the medRxiv* preprint server studies the waning of vaccine-conferred protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, specifically the Delta variant, in two high-risk populations. 

Study: Waning of Vaccine-Conferred Protection against SARS-CoV-2 Infection: Matched Case-Control Test-Negative Design Study in Two High-Risk Populations. Image Credit: As Good As Possible/Shutterstock

Vaccine waning study

Coronavirus disease 2019 (COVID-19) vaccines provide sufficient immune protection. Vaccine-conferred immunity also protects against the severe outcomes of COVID-19. In the U.S., over 144 million people were fully vaccinated against SARS-CoV-2 by June 2021.

However, vaccine waning or reducing immune protection over time is a serious concern, especially for high-risk individuals since they were the first to be vaccinated. 

Decisions regarding booster vaccinations need to be made based on evidence of protection against severe disease. Also, with time, vaccine effectiveness may vary against different variants. Thus, the reduction in vaccine effectiveness will also vary against some variants. The temporal waning of vaccine effectiveness should be distinguished from differential vaccine effectiveness against variants. Therefore, this study is restricted to vaccine effectiveness against the Delta variant.

Study population

The study population included residents of California state prisons and staff who worked in roles involving direct contact with residents. All individuals included in the study were fully vaccinated without any history of prior infection. These populations were vaccinated from December 2020. There was an extensive uptake of vaccines before April 2021.

Individuals who tested positive during the study period and those who received a booster dose were excluded. According to the dosing protocol, fully vaccinated individuals received either two doses of Moderna, two doses of Pfizer, or one dose of Janssen. They were considered fully vaccinated 14 days after the final dose.

This study ensured that all individuals included had sufficient contact with the prison system.

Study data

In this study, de-identified person-day-level data was taken from the California Department of Corrections and Rehabilitation (CDCR). It included data from January 1, 2020, through November 5, 2021. The data included information on RT-PCR and antigen testing and vaccination status for prison staff and incarcerated residents from 35 prisons. To ensure vaccine effectiveness against a single variant, data was collected from June 1, 2021, through November 5, 2021. During this study period, the Delta variant accounted for 95% of infections, according to CDCR data. According to the California Department of Public Health, the Delta variant accounted for 90% of infections in the general non-prison population.

Study design

This study uses a matched case-control test-negative study design. In a case-control study, two groups of people are compared – the cases and the controls. The cases include individuals with disease, and controls are individuals without the disease. The individuals in the control group are matched with or are very similar in characteristics to those in the case group. In a test-negative study design, the individuals in the case group show symptoms and are tested positive for the disease, in this instance, COVID-19. The individuals in the control group show symptoms but are tested negative for the disease.

The test-positive cases were matched and analyzed with four controls separately for staff and residents. Individuals were matched according to the type of vaccine taken, prison, and sociodemographic characteristics.

The sociodemographic characteristics included age, gender, ethnicity, and COVID Risk Score. COVID Risk Score was developed and used by CDCR to capture the risk of severe outcomes for the infected individuals based on risk factors known for these outcomes. For the prison staff, the sociodemographic characteristics included age, gender, ethnicity, and staff type (Custody or Healthcare).

Statistical analyses were employed to estimate the odds of infection among the fully vaccinated individuals. An increase in the odds of infection indicates a decrease in vaccine effectiveness.

Study results

A total of 9,858 staff and 25,970 residents were included in the study. More than 75% of individuals were administered the Moderna vaccine in both groups. Three hundred and eighty-six or 3.9% of the staff and 419 or 1.6% of the residents tested COVID-19 positive between June 1 and November 5, 2021. Controls were matched for 317 or 82% of staff cases and 411 or 98% of resident cases.

Over 70% of individuals were in the 18-49 years age group. Among the staff, 77% were male, and among the residents, 94% were male. Fifty-two percent of the staff and 77% of the residents were Black or Hispanic. Within the staff, 75% were in custody, and 25% were in healthcare. The odds of infection increased by 25% among the staff and 21% among the residents in each 28-day-period post-vaccination. After 181 days since full vaccination, the odds of infection were over fourfold greater for staff and nearly threefold greater for residents.

Despite the waning in vaccine effectiveness observed, disease incidence was low during the Delta wave.

Limitations of the study

It is possible that individuals at higher risk of infection may have been vaccinated earlier. Also, those vaccinated later may have had undiagnosed SARS-CoV-2 infection conferring additional protection. This will confound the results.

Implications of the study

In this study, the odds of infection increased each 28-day-period post-vaccination. It was 3.4-fold for residents and 4.7-fold for staff after 180 days post-vaccination.

Waning protection highlights the importance of booster vaccination doses since they protect against severe COVID-19 outcomes, especially in high-risk populations.

*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.