In a recent study published in PLOS Medicine, investigators determined the vaccine effectiveness (VE) of the primary vaccination series against coronavirus disease 2019 (COVID-19). They determined the VE against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection, COVID-19-related hospitalization, and mortality. In this way, the researchers evaluated the effect of the time elapsed since vaccination during the periods of prevalence of different variants of SARS-CoV-2, namely Alpha, Delta and Omicron.
In Denmark, the government provides free COVID-19 tests, vaccinations and medical care to all its residents. They launched the COVID-19 vaccination program in December 2020, prioritizing the elderly and people at high risk of severe illness. They also started a booster vaccination program in September 2021.
Scientific data points to reduced efficacy of COVID-19 vaccines against the Omicron variant (B.1.1.529). Studies have also shown that natural immunity protects more effectively against SARS-CoV-2 reinfections than vaccination. Therefore, it is in the public health interest to examine the additional benefits of vaccination (if any) among people previously infected with SARS-CoV-2.
About the study
In the present study, the researchers collected data from four national resources, the Danish Civil Registration System (CRS), the Danish Microbiology Database (MiBa), the Danish Vaccination Registry (DVR), and the Danish National Patient Registry. (DNPR).
Combined with a unique personal registration number of a Danish citizen, this data helped them identify people with a confirmed SARS-CoV-2 infection between January 1, 2020 and January 31, 2022. They also obtained the periods of dominance of each SARS-CoV-2 variant using CSR data, defined as the period in which a variant accounted for 75% or more of all reverse transcription polymerase chain reaction (RT-P) tests. PCR) sequenced from the whole genome. Additionally, the team investigated COVID-19-related hospitalization up to 14 days after or 48 hours before SARS-CoV-2 reinfection and death within 30 days of reinfection.
In statistical analyses, they included gender, comorbidity, and country of origin as categorical variables, while age and length of hospital stay as time-varying covariates. The team used a quasi-Poisson regression model to estimate crude incidence rates (IRRs) and a Cox proportional hazards regression model to estimate adjusted hazard ratios (HRs) for all variables before and in the respective periods. after vaccination. Finally, they calculated the crude VE (VEraw) and adjusted (VEbalanced) as a percentage using the IRR and HR values.
The study population comprised 209,814, 292,978, and 245,530 people infected before or during the Alpha, Delta, and Omicron eras of dominance, respectively. Of these, 19.2%, 64.9% and 64.6% of people had received primary vaccination against COVID-19 during the Alpha, Delta and Omicron periods, respectively. The main finding of the study was that previously infected people also benefited from vaccination against COVID-19 during all three variant periods, crucial data to inform policymakers on future vaccination strategies.
In the period dominated by Alpha, VE was not statistically significant. It peaked at 71% at 104 days or more after vaccination with any type of COVID-19 vaccine. However, VE against reinfection was highest between 14 and 43 days after the primary vaccination series in the Delta (94%) and Omicron (60%) periods. Although lower than for other variants, the researchers observed an initial VE of 60% against reinfections, even during the Omicron period. These results are consistent with the findings of a study from Qatar showing a 55.1% VE against reinfection with Omicron after two doses of a COVID-19 mRNA vaccine.
Since the elderly and most vulnerable people received vaccination against SARS-CoV-2 as a priority. These individuals developed a slower immune response after vaccination, which explains why the VE observed was statistically insignificant during the Alpha period. In addition, all people 65 years and older experienced more severe outcomes than SARS-CoV-2 reinfections in other age groups, overall and within the same variation period.
Another intriguing finding was that the risk of COVID-19-related hospital admission during the Alpha period was higher for vaccinated versus unvaccinated individuals (RI: 0.002 vs. 0.001). Perhaps even before the release of vaccines, several long-term care facility (LTCF) residents had already contracted SARS-CoV-2 infections. Because the events of hospitalization and death due to complications induced by COVID-19 were very few in the present study, the investigators were unable to estimate the VE for these.
The data integrity of the Danish registry likely removed any unmeasured biases that could have affected the study results. However, studies with longer follow-up times could assess VE against severe COVID-19 outcomes in people with prior infection.
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