New Study: Vax Effectiveness - negligible at BEST. Not worth the cost or policy impacts

As the COVID-19 pandemic eases into the rear-view distance, understanding the effectiveness of vaccines in various populations remains crucial. One area of interest is the impact of vaccination on individuals who have already recovered from a prior SARS-CoV-2 infection. A recent nationwide retrospective cohort study based on data from Austria, led by Dr. Tracy Høeg and colleagues, sheds light on this topic by evaluating the effectiveness of the first and second doses of SARS-CoV-2 vaccines among previously infected adults during the Delta variant wave, with extended follow-up into the Omicron period.

Study Overview

Objectives

• To assess the effectiveness of the first and second doses of SARS-CoV-2 vaccines in preventing COVID-19 deaths and reinfections among previously infected adults.

• To evaluate the relative vaccine effectiveness (rVE) over time.

• To examine non-COVID-19 mortality rates to identify potential healthy vaccinee bias.

Methodology

• Study Design: Nationwide retrospective cohort study.

• Population: 494,646 previously infected Austrian adults.

  • Two Vaccine Doses: 169,543 individuals.

  • One Vaccine Dose: 133,567 individuals.

  • Unvaccinated: 190,275 individuals.

• Timeframes:

  • Primary Period: October 1 to December 31, 2021 (Delta variant predominant).

  • Extended Follow-Up: January 1 to June 30, 2022 (Omicron variant predominant).

• Data Analysis:

  • Adjusted for age, gender, and nursing home residency.

  • Calculated adjusted hazard ratios (HRs) for COVID-19 deaths, SARS-CoV-2 reinfections, and non-COVID-19 deaths.

  • Relative vaccine effectiveness (rVE) was determined using the formula: rVE = (1 - HR) × 100.

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A quick note about hazard ratios.… the rVE relative vaccine effectiveness in that last bullet point.

• HR < 1: The event is less likely in the vaccinated group compared to the unvaccinated group.

• HR = 1: No difference in risk between the two groups.

• HR > 1: The event is more likely in the vaccinated group.

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Key Findings

1. Extremely Low COVID-19 Mortality:

   • Primary Period Deaths: 17 COVID-19 deaths among previously infected individuals.

     • Vaccinated Deaths: 6 individuals.

     • Unvaccinated Deaths: 11 individuals.

   • Absolute Risk: 0.003% for COVID-19 deaths.

   • Implication: Suggests strong protection against COVID-19 mortality from prior infection, regardless of vaccination status.

2. Relative Vaccine Effectiveness (rVE):

   • Short-Term Effectiveness: rVE for preventing COVID-19 deaths and reinfections exceeded 75% during the primary period.

   • Diminishing Effectiveness Over Time:

     • rVE declined significantly during the extended follow-up in 2022.

     • Potential factors include waning immunity, emergence of the Omicron variant, and changing population dynamics.

3. SARS-CoV-2 Reinfections:

   • Total Reinfections: 8,209 during the study period.

   • Vaccine Impact: Vaccinated individuals had a lower risk of reinfection during the primary period, but effectiveness waned over time.

4. Non-COVID-19 Mortality and Healthy Vaccinee Bias:

   • Lower Non-COVID-19 Mortality in Vaccinated Individuals:

     • One Dose: 27% lower risk.

     • Two Doses: 36% lower risk compared to unvaccinated individuals.

   • Interpretation: Suggests that healthier individuals are more likely to get vaccinated.

   • Healthy Vaccinee Bias: This bias may lead to overestimating vaccine effectiveness in observational studies.

Discussion

The study provides valuable insights into the effectiveness of COVID-19 vaccines among previously infected individuals, highlighting several important considerations:

1. Protection from Prior Infection:

   • Strong Natural Immunity: The extremely low COVID-19 mortality rate suggests that prior infection confers significant protection against death from COVID-19.

   • Survivorship Bias: Some of the observed protection may be due to the most vulnerable individuals having succumbed during their initial infection.

2. Vaccine Effectiveness Over Time:

   • Waning Immunity: The decline in vaccine effectiveness over time underscores the challenges posed by emerging variants and waning immunity.

   • Variant Impact: The shift from the Delta to Omicron variant may have contributed to reduced vaccine effectiveness.

3. Healthy Vaccinee Bias:

   • Impact on Study Results: The lower non-COVID-19 mortality rates among vaccinated individuals indicate that healthier people are more likely to be vaccinated.

   • Overestimation of Effectiveness: This bias can lead to inflated estimates of vaccine effectiveness in observational studies.

   • Need for Adjustments: Recognizing and adjusting for this bias is crucial for accurate assessments.

4. Limitations of Observational Studies:

   • Data Constraints: Lack of information on comorbidities, socioeconomic status, medications, and testing behaviors limits the ability to fully adjust for confounding factors.

   • Residual Bias: The unexpected finding that one vaccine dose appeared more protective than two suggests residual confounding.

   • Testing Variability: Differences in access to and usage of PCR versus home antigen tests could introduce bias.

Implications for Public Health Policy

• Vaccination Strategies:

  • Cost-Effectiveness: The low absolute risk of COVID-19 mortality in previously infected individuals raises questions about the cost-effectiveness of vaccinating this population solely for preventing deaths.

  • Targeted Vaccination: Resources might be better allocated by focusing on high-risk populations or those without prior infection.

• Need for Robust Data:

  • Randomized Controlled Trials: There's a critical need for studies less prone to bias to accurately assess vaccine benefits and harms in previously infected individuals.

  • Comprehensive Analysis: Future research should include data on comorbidities, socioeconomic factors, and behavioral variables.

Conclusions

The Austrian nationwide study highlights that while vaccination offers short-term protection against SARS-CoV-2 reinfection among previously infected individuals, the absolute risk of COVID-19 mortality in this group is exceedingly low. The presence of healthy vaccinee bias suggests that observational studies may overestimate vaccine effectiveness due to underlying differences in health status between vaccinated and unvaccinated individuals.