Results of important study on COVID-19 vaccine effectiveness published in Hungary
A nationwide observational study (HUN-VE: Hungarian Vaccine Effectiveness) conducted between 22 January and 10 June 2021 examined the effectiveness of five Covid-19 vaccines against SARS-CoV-2 infection and Covid-19 related death among 3.7 million individuals that were vaccinated with two doses of any of the five vaccines examined.
All investigated vaccines showed overall high (>50%) or very high (>80%) effectiveness against SARS-CoV-2 infection and very high effectiveness against Covid-19 related mortality.
“The emergency approval of five different vaccines led to the prevention of more than 9,500 deaths,” the authors said in their report.
The official government portal (koronavirus.gov.hu) boasts in a statement that 40% of these lives saved were linked to vaccines Hungary procured from Russia (Sputnik V) and China (Sinopharm) without authorisation for emergency use by the European Medicines Agency (EMA) or the World Health Organisation (WHO). While the government’s alacrity and maverick approach in such purchases is absolutely laudable, it is unclear where this 40% comes from.
The portal also says these vaccines "helped ease the load on hospitals, reduce losses (of human lives?), and ensured a greater effectiveness at beating the [third] wave. This was particularly important during times of scarce vaccine supply capacities."
Note that at that time it was not the availability or shortage of vaccines that influenced the number of Covid deaths, rather than the restriction measures governments put in place to stem the spread of the virus. Hungary did not excel in that respect to say the least. It implemented restrictions only when daily fatalities were already numerous, and hospitals were at capacity. High mortality was in fact linked to the belated nature of lockdown measures rather than to anything else, including vaccine abundance or shortage.
In the study period 371,212 SARS-CoV-2 infections occurred in the unvaccinated and 6,912 in the fully vaccinated study populations, the authors said.
In total, 13,533 Covid-19 related deaths were found, including 553 deaths in the fully vaccinated cohorts, they added.
Data provided by the Coronavirus Task Force, however, show 18,093 deaths in the study period (in Portfolio database). Applying the above ratio to this figure would result in 739 deaths in the fully vaccinated cohorts.
The authors also claim that more 9,500 lives were saved by vaccines. This implies that without them there would have been 23,033 deaths in the study period, which would correspond to a 70% (!) higher death toll. Applying the Coronavirus Task Force’s mortality data (18,093 deaths), the growth would be ‘only’ 53% to 27,593 deaths. Or if we calculate with 70% more deaths, the death toll would have been 30,758.
Incidence rates of SARS-CoV2 infection and Covid-19 related death were 1.73–9.3/100,000 person-days and 0.04–0.65/100.000 person-days in the fully vaccinated population, respectively. (Person-days for each partially and fully vaccinated group were calculated by adding up the number of persons in each group for each day.)
Estimated adjusted effectiveness varied between 68.7% (95% CI 67.2–70.1%) and 88.7% (95% CI: 86.6–90.4%) against SARS-CoV-2 infection, and between 87.8% (95% CI: 86.1–89.5%) and 97.5% (95% CI: 95.6–98.6%) against Covid-19 related death, with 100% effectiveness in individuals aged 16–44 years for all vaccines.
This is just an excerpt of the data created for demonstrative purposes. The full table can be reached here.
The authors emphasised that clinical trials assessing vaccine effectiveness were mostly conducted against the original Wuhan strain, which may explain some differences between their results and clinical trials as several studies showed reduced neutralisation activity and effectiveness against the B.1.1.7 variant compared with a non-B.1.1.7 variant.
Importantly, vaccine effectiveness was demonstrated when the SARS-CoV-2 variant B.1.1.7 was the dominant strain in Hungary, therefore,
the results do not represent the effectiveness of vaccines investigated against the delta-variant (B.1.617.2) or against new, upcoming variants.
The results are largely consistent with phase III trial data and the limited number of available real-world studies.
Strengths and weaknesses
“The strengths of our study include its nationwide nature, the effectiveness analysis of five different SARS-CoV-2 vaccines during a powerful pandemic wave, the robust number of more than 3.7 million vaccinated individuals, and the almost 5-month study period,” the authors said.
At the same time, they highlighted that their results have important limitations, some inherent in surveillance-based vaccine effectiveness studies.
- The study period was different for each vaccine, so the analysis implicitly assumes that the effect of each covariate, including vaccination is constant during the follow-up.
- Despite adjustments for age, sex, and calendar day, further important covariates such as comorbidities, medications, or socio-economic status were not included. For chronic diseases, for example, the validity issue is the extent to which the likelihood of receiving each vaccine differs for a given day, age and sex depending on whether or not a person has a chronic disease, and the extent to which the risk of infection and death and the likelihood of detection differ. Given that some vaccines were specifically indicated for use in elderly and chronically ill patients, the bias due to chronic disease (which may occur in addition to the age effect) may have been a fundamental cause of underestimation of the effectiveness of some vaccines in middle-aged people. However, among the elderly there was no differential indication for people with and without chronic disease.
- Cases could be diagnosed based on clinical symptoms, too, which might have resulted in differential misclassification, somewhat overestimating vaccine efficacy because a physician could have been less likely to diagnose Covid-19 knowing a person is vaccinated. Differences in the likelihood of seeking SARS-CoV-2 testing, uptake of vaccines, site of vaccination, prognosis of Covid-19, and chance of detection may also have resulted in residual confounding.
Cover photo: Getty Images
