Effectiveness of SARS-CoV-2 primary vaccines and boosters in patients with type 2 diabetes mellitus in Hungary (HUN-VE 4 Study).

INTRODUCTION: Type 2 diabetes mellitus is a risk factor for severe COVID-19 infection and is associated with increased risk of complications. The present study aimed to investigate effectiveness and persistence of different COVID vaccines in persons with or without diabetes during the Delta wave in Hungary. RESEARCH DESIGN AND METHODS: Data sources were the national COVID-19 registry data from the National Public Health Center and the National Health Insurance Fund on the total Hungarian population. The adjusted incidence rate ratios and corresponding 95% CIs were derived from a mixed-effect negative binomial regression model. RESULTS: A population of 672 240 cases with type 2 diabetes and a control group of 2 974 102 non-diabetic persons free from chronic diseases participated. Unvaccinated elderly persons with diabetes had 2.68 (95% CI 2.47 to 2.91) times higher COVID-19-related mortality rate as the 'healthy' controls. Primary immunization effectively equalized the risk of COVID-19 mortality between the two groups. Vaccine effectiveness declined over time, but the booster restored the effectiveness against mortality to over 90%. The adjusted vaccine effectiveness of the primary Pfizer-BioNTech against infection in the 14-120 days of postvaccination period was 71.6 (95% CI 66.3 to 76.1)% in patients aged 65-100 years with type 2 diabetes and 64.52 (95% CI 59.2 to 69.2)% in the controls. Overall, the effectiveness tended to be higher in individuals with diabetes than in controls. The booster vaccines could restore vaccine effectiveness to over 80% concerning risk of infection (eg, patients with diabetes aged 65-100 years: 89.1 (88.1-89.9)% with Pfizer-on-Pfizer, controls 65-100 years old: 86.9 (85.8-88.0)% with Pfizer-on-Pfizer, or patients with diabetes aged 65-100 years: 88.3 (87.2-89.2)% with Pfizer-on-Sinopharm, controls 65-100 years old: 87.8 (86.8-88.7)% with Pfizer-on-Sinopharm). CONCLUSIONS: Our data suggest that people with type 2 diabetes may have even higher health gain when getting vaccinated as compared with non-diabetic persons, eliminating the marked, COVID-19-related excess risk of this population. Boosters could restore protection.

Waning of SARS-CoV-2 Vaccine Effectiveness in COPD Patients: Lessons from the Delta Variant.

Although the COVID-19 pandemic is profoundly changing, data on the effect of vaccination and duration of protection against infection and severe disease can still be advantageous, especially for patients with COPD, who are more vulnerable to respiratory infections. The Hungarian COVID-19 registry was retrospectively investigated for risk of infection and hospitalization by time since the last vaccination, and vaccine effectiveness (VE) was calculated in adults with COPD diagnosis and an exact-matched control group during the Delta variant of concern (VOC) wave in Hungary (September-December 2021). For the matching, sex, age, major co-morbidities, vaccination status, and prior infection data were obtained on 23 August 2021. The study population included 373,962 cases divided into COPD patients (age: 66.67 ± 12.66) and a 1:1 matched group (age: 66.73 ± 12.67). In both groups, the female/male ratio was 52.2:47.7, respectively. Among the unvaccinated, there was no difference between groups in risk for infection or hospitalization. Regarding vaccinated cases, in the COPD group, a slightly faster decline in effectiveness was noted for hospitalization prevention, although in both groups, the vaccine lost its significant effect between 215 and 240 days after the last dose of vaccination. Based on a time-stratified multivariate Cox analysis of the vaccinated cases, the hazard was constantly higher in the COPD group, with an HR of 1.09 (95%: 1.05-1.14) for infection and 1.87 (95% CI: 1.59-2.19) for hospitalization. In our study, COPD patients displayed lower vaccine effectiveness against SARS-CoV-2 infection and hospitalization but a similar waning trajectory, as vaccines lost their preventive effect after 215 days. These data emphasize revaccination measures in the COPD patient population.

Effectiveness and waning of protection with the BNT162b2 vaccine against the SARS-CoV-2 Delta variant in immunocompromised individuals.

Introduction: In Hungary, the HUN-VE 3 study determined the comparative effectiveness of various primary and booster vaccination strategies during the Delta COVID-19 wave. That study included more than 8 million 18-100-year-old individuals from the beginning of the pandemic. Immunocompromised (IC) individuals have increased risk for COVID-19 and disease course might be more severe in them. In this study, we wished to estimate the risk of SARS-CoV-2 infection and COVID-19 related death in IC individuals compared to healthy ones and the effectiveness of the BNT162b2 vaccine by reassessing HUN-VE 3 data. Patients and methods: Among the 8,087,988 individuals undergoing follow-up from the onset of the pandemic in the HUN-VE 3 cohort, we selected all the 263,116 patients with a diagnosis corresponding with IC and 6,128,518 controls from the second wave, before vaccinations started. The IC state was defined as two occurrences of corresponding ICD-10 codes in outpatient or inpatient claims data since 1 January, 2013. The control group included patients without chronic diseases. The data about vaccination, SARS-CoV-2 infection and COVID-19 related death were obtained from the National Public Health Center (NPHC) during the Delta wave. Cases of SARS-CoV-2 infection were reported on a daily basis using a centralized system via the National Public Health Center (NPHC). Results: Out of the 263,116 IC patients 12,055 patients (4.58%) and out of the 6,128,518 healthy controls 202,163 (3.30%) acquired SARS-CoV-2 infection. Altogether 436 IC patients and 2141 healthy controls died in relation to COVID-19. The crude incidence rate ratio (IRR) of SARS-CoV-2 infection was 1.40 (95%CI: 1.37-1.42) comparing IC patients to healthy controls. The crude mortality rate ratio was 4.75 (95%CI: 4.28-5.27). With respect to SARS-CoV-2 infection, interestingly, the BNT162b2 vaccine was more effective in IC patients compared to controls. Primary vaccine effectiveness (VE) was higher in IC patients compared to controls and the booster restored VE after waning. VE regarding COVID-19 related death was less in IC patients compared to healthy individuals. Booster vaccination increased VE against COVID-19-related death in both IC patients and healthy controls. Conclusion: There is increased risk of SARS-CoV-2 infection and COVID-19 related mortality in IC patient. Moreover, booster vaccination using BNT162b2 might restore impaired VE in these individuals.

Opposite trends in incidence of breast cancer in young and old female cohorts in Hungary and the impact of the Covid-19 pandemic: a nationwide study between 2011-2020.

Background: This nationwide study examined breast cancer (BC) incidence and mortality rates in Hungary between 2011-2019, and the impact of the Covid-19 pandemic on the incidence and mortality rates in 2020 using the databases of the National Health Insurance Fund (NHIF) and Central Statistical Office (CSO) of Hungary. Methods: Our nationwide, retrospective study included patients who were newly diagnosed with breast cancer (International Codes of Diseases ICD)-10 C50) between Jan 1, 2011 and Dec 31, 2020. Age-standardized incidence and mortality rates (ASRs) were calculated using European Standard Populations (ESP). Results: 7,729 to 8,233 new breast cancer cases were recorded in the NHIF database annually, and 3,550 to 4,909 all-cause deaths occurred within BC population per year during 2011-2019 period, while 2,096 to 2,223 breast cancer cause-specific death was recorded (CSO). Age-standardized incidence rates varied between 116.73 and 106.16/100,000 PYs, showing a mean annual change of -0.7% (95% CI: -1.21%-0.16%) and a total change of -5.41% (95% CI: -9.24 to -1.32). Age-standardized mortality rates varied between 26.65-24.97/100,000 PYs (mean annual change: -0.58%; 95% CI: -1.31-0.27%; p=0.101; total change: -5.98%; 95% CI: -13.36-2.66). Age-specific incidence rates significantly decreased between 2011 and 2019 in women aged 50-59, 60-69, 80-89, and ≥90 years (-8.22%, -14.28%, -9.14%, and -36.22%, respectively), while it increased in young females by 30.02% (95%CI 17,01%- 51,97%) during the same period. From 2019 to 2020 (in first COVID-19 pandemic year), breast cancer incidence nominally decreased by 12% (incidence rate ratio [RR]: 0.88; 95% CI: 0.69-1.13; 2020 vs. 2019), all-cause mortality nominally increased by 6% (RR: 1.06; 95% CI: 0.79-1.43) among breast cancer patients, and cause-specific mortality did not change (RR: 1.00; 95%CI: 0.86-1.15). Conclusion: The incidence of breast cancer significantly decreased in older age groups (≥50 years), oppositely increased among young females between 2011 and 2019, while cause-specific mortality in breast cancer patients showed a non-significant decrease. In 2020, the Covid-19 pandemic resulted in a nominal, but not statistically significant, 12% decrease in breast cancer incidence, with no significant increase in cause-specific breast cancer mortality observed during 2020.

[Summary of the Hungarian Mobile Health Screening Program data for 2021]. / A "Helybe visszük a szurovizsgálatokat" program 2021. évi adatainak összegzése.

INTRODUCTION: In Hungary, significant regional and social inequalities in health status exist. In addition, this is exacerbated by health care inequalities between West and East Hungary. OBJECTIVE: The aim of our study was to summarize the results of the 2021 Hungarian Mobile Health Screening Program, in order to determine the rates of detected cases and to assess the health status differences between different regions. METHOD: A cross-sectional retrospective study was executed to analyze the screening results (n = 5185) of the Hungarian Mobile Health Screening Program. RESULTS: 9% of screening attendees had higher than normal blood glucose level, 25% had abnormal cholesterol levels and 20% had elevated blood pressure. Of those screened, 35% had a not-negative result at the neurological examination, 44% at the dermatological examination, 42% at the cardiological examination, 20% at the spirometry function test, and 4% at the ankle-brachial index measurement. Newly detected gynaecological problems affected 1 in 5 women (21%) and 3 women were diagnosed with malignant tumors. Of those attending oral screening (n = 1836), 90% were directed to different levels of the health care system. CONCLUSION: The results of the Hungarian Mobile Health Screening Program have also demonstrated the health inequalities in our country. The data confirmed the need for the continuation of the Program under the current structure. The aim for the future screening period is to increase the attendance of several examinations and preventive/health promotion advices. Orv Hetil. 2023; 164(27): 1070-1076.

Effectiveness and Waning of Protection With Different SARS-CoV-2 Primary and Booster Vaccines During the Delta Pandemic Wave in 2021 in Hungary (HUN-VE 3 Study).

Background: In late 2021, the pandemic wave was dominated by the Delta SARS-CoV-2 variant in Hungary. Booster vaccines were offered for the vulnerable population starting from August 2021. Methods: The nationwide HUN-VE 3 study examined the effectiveness and durability of primary immunization and single booster vaccinations in the prevention of SARS-CoV-2 infection, Covid-19 related hospitalization and mortality during the Delta wave, compared to an unvaccinated control population without prior SARS-CoV-2 infection. Results: The study population included 8,087,988 individuals who were 18-100 years old at the beginning of the pandemic. During the Delta wave, after adjusting for age, sex, calendar day, and chronic diseases, vaccine effectiveness (VE) of primary vaccination against registered SARS-CoV-2 infection was between 11% to 77% and 18% to 79% 14-120 days after primary immunization in the 16-64 and 65-100 years age cohort respectively, while it decreased to close to zero in the younger age group and around 40% or somewhat less in the elderly after 6 months for almost all vaccine types. In the population aged 65-100 years, we found high, 88.1%-92.5% adjusted effectiveness against Covid-19 infection after the Pfizer-BioNTech, and 92.2%-95.6% after the Moderna booster dose, while Sinopharm and Janssen booster doses provided 26.5%-75.3% and 72.9%-100.0% adjusted VE, respectively. Adjusted VE against Covid-19 related hospitalization was high within 14-120 days for Pfizer-BioNTech: 76.6%, Moderna: 83.8%, Sputnik-V: 78.3%, AstraZeneca: 73.8%, while modest for Sinopharm: 45.7% and Janssen: 26.4%. The waning of protection against Covid-19 related hospitalization was modest and booster vaccination with mRNA vaccines or the Janssen vaccine increased adjusted VE up to almost 100%, while the Sinopharm booster dose proved to be less effective. VE against Covid-19 related death after primary immunization was high or moderate: for Pfizer-BioNTech: 81.5%, Moderna: 93.2%, Sputnik-V: 100.0%, AstraZeneca: 84.8%, Sinopharm: 58.6%, Janssen: 53.3%). VE against this outcome also showed a moderate decline over time, while booster vaccine types restored effectiveness up to almost 100%, except for the Sinopharm booster. Conclusions: The HUN-VE 3 study demonstrated waning VE with all vaccine types for all examined outcomes during the Delta wave and confirmed the outstanding benefit of booster vaccination with the mRNA or Janssen vaccines, and this is the first study to provide clear and comparable effectiveness results for six different vaccine types after primary immunization against severe during the Delta pandemic wave.

Booster Vaccination Decreases 28-Day All-Cause Mortality of the Elderly Hospitalized Due to SARS-CoV-2 Delta Variant.

(1) Background: SARS-CoV-2 infections are associated with an increased risk of hospital admissions especially in the elderly (age ≥ 65 years) and people with multiple comorbid conditions. (2) Methods: We investigated the effect of additional booster vaccinations following the primary vaccination series of mRNA, inactivated whole virus, or vector vaccines on infections with the SARS-CoV-2 delta variant in the total Hungarian elderly population. The infection, hospital admission, and 28-day all-cause mortality of elderly population was assessed. (3) Results: A total of 1,984,176 people fulfilled the criteria of elderly including 299,216 unvaccinated individuals, while 1,037,069 had completed primary vaccination and 587,150 had obtained an additional booster. The primary vaccination series reduced the risk of infection by 48.88%, the risk of hospital admission by 71.55%, and mortality by 79.87%. The booster vaccination had an additional benefit, as the risk of infection, hospital admission, and all-cause mortality were even lower (82.95%; 92.71%; and 94.24%, respectively). Vaccinated patients needing hospitalization suffered significantly more comorbid conditions, indicating a more vulnerable population. (4) Conclusions: Our data confirmed that the primary vaccination series and especially the booster vaccination significantly reduced the risk of the SARS-CoV-2 delta-variant-associated hospital admission and 28-day all-cause mortality in the elderly despite significantly more severe comorbid conditions.

Nationwide Effectiveness of First and Second SARS-CoV2 Booster Vaccines During the Delta and Omicron Pandemic Waves in Hungary (HUN-VE 2 Study).

Background: In Hungary, the pandemic waves in late 2021 and early 2022 were dominated by the Delta and Omicron SARS-CoV-2 variants, respectively. Booster vaccines were offered with one or two doses for the vulnerable population during these periods. Methods and Findings: The nationwide HUN-VE 2 study examined the effectiveness of primary immunization, single booster, and double booster vaccination in the prevention of Covid-19 related mortality during the Delta and Omicron waves, compared to an unvaccinated control population without prior SARS-CoV-2 infection during the same study periods. The risk of Covid-19 related death was 55% lower during the Omicron vs. Delta wave in the whole study population (n=9,569,648 and n=9,581,927, respectively; rate ratio [RR]: 0.45, 95% confidence interval [CI]: 0.44-0.48). During the Delta wave, the risk of Covid-19 related death was 74% lower in the primary immunized population (RR: 0.26; 95% CI: 0.25-0.28) and 96% lower in the booster immunized population (RR: 0.04; 95% CI: 0.04-0.05), vs. the unvaccinated control group. During the Omicron wave, the risk of Covid-19 related death was 40% lower in the primary immunized population (RR: 0.60; 95% CI: 0.55-0.65) and 82% lower in the booster immunized population (RR: 0.18; 95% CI: 0.16-0.2) vs. the unvaccinated control group. The double booster immunized population had a 93% lower risk of Covid-19 related death compared to those with only one booster dose (RR: 0.07; 95% CI. 0.01-0.46). The benefit of the second booster was slightly more pronounced in older age groups. Conclusions: The HUN-VE 2 study demonstrated the significantly lower risk of Covid-19 related mortality associated with the Omicron vs. Delta variant and confirmed the benefit of single and double booster vaccination against Covid-19 related death. Furthermore, the results showed the additional benefit of a second booster dose in terms of SARS-CoV-2 infection and Covid-19 related mortality.

Nationwide effectiveness of five SARS-CoV-2 vaccines in Hungary-the HUN-VE study.

OBJECTIVES: The Hungarian vaccination campaign was conducted with five different vaccines during the third wave of the coronavirus disease 2019 (COVID-19) pandemic in 2021. This observational study (HUN-VE: Hungarian Vaccine Effectiveness) estimated vaccine effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19-related mortality in 3.7 million vaccinated individuals. METHODS: Incidence rates of SARS-CoV-2 infection and COVID-19-related mortality were calculated using data from the National Public Health Centre surveillance database. Estimated vaccine effectiveness was calculated as 1 - incidence rate ratio ≥7 days after the second dose for each available vaccine versus an unvaccinated control group using mixed-effect negative binomial regression controlling for age, sex and calendar day. RESULTS: Between 22 January 2021 and 10 June 2021, 3 740 066 Hungarian individuals received two doses of the BNT162b2 (Pfizer-BioNTech), HB02 (Sinopharm), Gam-COVID-Vac (Sputnik-V), AZD1222 (AstraZeneca), or mRNA-1273 (Moderna) vaccines. Incidence rates of SARS-CoV-2 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. 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%-89.4%) 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. CONCLUSIONS: Our observational study demonstrated the high or very high effectiveness of five different vaccines in the prevention SARS-CoV-2 infection and COVID-19-related death.