The test negative case control study conducted in several Eastern European countries (n = 5,165) was missing data on previous infections for nearly half of participants and only enrolled patients hospitalized for severe acute respiratory infections including those unrelated to COVID19. Unsurprisingly, the median age for participants in this study is 64 and 63% have at least one chronic medical condition (i.e. are sick prior to infection) which establishes a clear cohort bias towards older and immunocompromised persons who do not reflect the general demographics of people who have contracted SARS-COV-2 over the past four years (i.e. everyone). Another bias not mentioned until the very end is that test negative controls were about 2.5x more likely to have prior documented infections than patients with COVID19. The seroprevalence of anti-nucleocapsid antibodies and lymphocytes is also extremely low (only 17% have documented prior infections) compared to today. Thus, the study wouldn’t be very informative of estimating the clinical benefit of the shots for young healthy children, adolescents and young adults or immunocompetent persons in general with prior infections. Despite pulling out all the stops to find high mean VE they could not find it past 6 months after the last dose and at 6 months post administration mean VE was already in negligible single digit territory. Averaged over a year, mean VE against hospitalization with severe acute respiratory infection was a measly 15% with a lower limit of -5% (a 5% higher relative risk of infection).
Annual VE was 60% (95% Confidence Interval (CI) 12–82) for a last dose received up to 89 days months prior, 59% (95% CI 31–76) for last dose received 90–179 days prior, 7% (95% CI -29–33) for 180–269 days, and -6% (95% CI -44–22) for 270–364 days. Overall annual VE for last vaccine dose received in the entire previous 365-day period was 15% (95% CI -5–32) (Table 3 and Figure 4). In secondary analyses, both absolute VE and rVE had similar point estimates and trends.
Annualized mean VE against hospitalization was pretty much negligible for the most at risk population: patients over 60 years of age. It is especially concerning for this population because during the course of the study COVID19 cases peaked in the Summer of 2022, more than 6 months after the first booster doses were released in September 2021.
When we limited our analysis to SARI patients ≥ 60 years old, annual VE was 44% (95% CI -33–77) for last dose received up to 89 days prior to onset, 50% (95% CI 7–73) at 90–179 days, -3% (95% CI -51–30) at 180–179 days, and -14% (95% CI -67–22) for those with a last dose 270–364 days before symptom onset. Annual VE for last vaccine received in the previous 365 days was 5% (95% CI - 23–27). Results in sensitivity analyses for absolute VE and rVE were similar (Table 3, Figure 4)
A mean 5% lower relative risk of hospitalization is something that could happen randomly. 5% lower risk is not meaningful. The authors only refer to “waning VE” after 6 months but do not explain the findings of negative VE that they likely obtained from outbreaks in the Summer of 2022 and fall of 2023. Negative VE is immune tolerance found in observational data. The modRNA shot isn’t what is waning in protection; the recipients’ immune system is waning and becoming tolerant of the spike protein. As I explained in a prior answer this coincides with an antibody subclass switch from the promulgation of IgGE, IgG1 and IgG3 anti-spike nabs to IgG4 antibodies that block the former from binding to antigens and stimulating other complement immune processes such as interferon signaling and phagocytosis resulting in disease enhancement in immunocompromised individuals which can also occur as a result of IgG4 antibodies binding to viral surfaces and incorporating them into white blood cells that effectively become hosts for replication. The subclass shift takes at least a few months to occur which may explain why we observe initially high VE against infection and symptoms in the first two months that rapidly declines between months 3-4 post administration, becomes negligible between months 4-6 and results in an observation of negative VE against infection after 6 months (well before the next annual booster rollout).