Changes in SARS-CoV-2 seroprevalence and population immunity in Finland, 2020-2022.

Studying the prevalence of SARS-CoV-2 specific antibodies (seroprevalence) allows for assessing the impact of epidemic containment measures and vaccinations and estimating the number of infections regardless of viral testing. We assessed antibody-mediated immunity to SARS-CoV-2 induced by infections and vaccinations from April 2020 to December 2022 in Finland by measuring serum IgG to SARS-CoV-2 nucleoprotein (N-IgG) and spike glycoprotein from randomly selected 18-85-year-old subjects (n = 9794). N-IgG seroprevalence remained at <7% until the last quartile (Q) of 2021. After the emergence of the Omicron variant, N-IgG seroprevalence increased rapidly and was 31% in Q1/2022 and 54% in Q4/2022. Seroprevalence was highest in the youngest age groups from Q2/2022 onwards. We did not observe regional differences in seroprevalence in 2022. We estimated that 51% of the Finnish 18-85-year-old population had antibody-mediated hybrid immunity induced by a combination of vaccinations and infections by the end of 2022. In conclusion, major shifts in the COVID-19 pandemic and resulting population immunity could be observed by serological testing.

Incidence of SARS-CoV-2 Infection and Factors Associated With Complete COVID-19 Vaccine Uptake Among Migrant Origin Persons in Finland.

Objective: We examined incidence of SARS-CoV-2 infection, COVID-19 vaccine uptake and factors associated with complete COVID-19 vaccine uptake among persons of migrant origin in Finland. Methods: Data on laboratory-confirmed SARS-CoV-2 infection and COVID-19 vaccine doses between March 2020 and November 2021 were linked to FinMonik register sample (n = 13,223) and MigCOVID (n = 3,668) survey data using unique personal identifier. Logistic regression was the main method of analyses. Results: Among FinMonik sample, complete COVID-19 vaccine uptake was lower among persons of Russia/former Soviet Union, Estonia, and rest of Africa and higher among persons of Southeast Asia, rest of Asia, and the Middle East/North Africa than among persons originating from Europe/North America/Oceania. Male sex, younger age, migration age (<18 years) and shorter length of residence were associated with lower vaccine uptake among FinMonik sample, whereas younger age, being economically inactive, poorer language skills, experiences of discrimination and psychological distress were associated with lower vaccine uptake among MigCOVID sub-sample. Conclusion: Our Findings point to a further need of tailored and targeted communication and community outreach strategies to increase vaccine uptake among persons of migrant origin.

Nationwide health, socio-economic and genetic predictors of COVID-19 vaccination status in Finland.

Understanding factors associated with COVID-19 vaccination can highlight issues in public health systems. Using machine learning, we considered the effects of 2,890 health, socio-economic and demographic factors in the entire Finnish population aged 30-80 and genome-wide information from 273,765 individuals. The strongest predictors of vaccination status were labour income and medication purchase history. Mental health conditions and having unvaccinated first-degree relatives were associated with reduced vaccination. A prediction model combining all predictors achieved good discrimination (area under the receiver operating characteristic curve, 0.801; 95% confidence interval, 0.799-0.803). The 1% of individuals with the highest predicted risk of not vaccinating had an observed vaccination rate of 18.8%, compared with 90.3% in the study population. We identified eight genetic loci associated with vaccination uptake and derived a polygenic score, which was a weak predictor in an independent subset. Our results suggest that individuals at higher risk of suffering the worst consequences of COVID-19 are also less likely to vaccinate.

Incidence of sinus thrombosis with thrombocytopenia-A nation-wide register study.

Safe vaccination is essential for mitigation of the COVID-19 pandemic. Two adenoviral vector vaccines, ChAdOx1 nCov-19 (AstraZeneca) and Ad26.COV2.S (Johnson&Johnson/Janssen) have shown to be effective and they are distributed globally, but reports on serious cerebral venous sinus thrombosis (CVST) associated with thrombocytopenia, have emerged. Our objective was to evaluate the background incidence of CVST with thrombocytopenia and to compare it to incidences following COVID-19 vaccines. We conducted a register-based nation-wide cohort study in Finland, including all 5.5 million individuals alive in Finland, 1 Jan 2020. COVID-19 vaccinations registered in the National Vaccination Register served as the exposure. We detected CVST admissions or hospital visits recorded in the hospital discharge register from Jan 1, 2020 through April 2, 2021. We confirmed the diagnosis of CVST and thrombocytopenia (platelet count <150,000 per cubic millimeter) using radiology reports and laboratory data. By Poisson regression, we compared the baseline incidences to the risks within four weeks after COVID-19 vaccinations. Out of the 167 CVST episodes identified in the registers, 117 were confirmed as CVST, 18 of which coincided with thrombocytopenia (baseline incidence 0.18 per 28 days per million persons). We found 2 episodes of CVST with thrombocytopenia within 28 days of the first ChAdOx1 nCov-19 vaccination (among 200,397 vaccinated, aged 16 or above). No cases were found following the first mRNA vaccine dose among 782,604 vaccinated. The background incidence of CVST combined with thrombocytopenia was minuscule compared to the incidence during the weeks following the ChAdOx1 nCov-19 vaccination. Accurate estimation of the baseline incidence is essential in the critical appraisal of the benefit-risk of any vaccination program.

Qualitative Insights into Vaccine Uptake of Nursing Staff in Long-Term Care Facilities in Finland.

Vaccine hesitancy and refusal have undermined COVID-19 vaccination efforts of nursing staff. This study aimed to identify behavioral factors associated with COVID-19 vaccine uptake among unvaccinated nursing staff in long-term care facilities (LTCF) in Finland. Methodology: The study was based on the Theoretical Domains Framework. Data were collected through qualitative in-depth interviews among nursing staff and managers of LTCFs. The analysis was based on thematic analysis. We identified seven behavioral domains, with several themes, that reduced the staff's intention to get vaccinated: knowledge (information overload, inability to identify trustworthy information sources, lack of vaccine-specific and understandable scientific information), beliefs about consequences (incorrect perceptions about the vaccine effectiveness, and lack of trust in the safety of the vaccine), social influences (influence of family and friends), reinforcement (limited abilities of the management to encourage vaccination), beliefs about capabilities (pregnancy or desire to get pregnant), psychological factors (coping with changing opinion), and emotions (confusion, suspicion, disappointment, and fatigue). We also identified three behavioral domains that encouraged vaccine uptake: social influences (trust in health authorities), environmental context and resources (vaccination logistics), and work and professional role (professional pride). The study findings can help authorities to develop tailored vaccine promotion strategies for healthcare workers in LTCFs.

Sudden Hearing Loss Following Vaccination Against COVID-19.

Importance: Spontaneous adverse reaction reports of sudden hearing loss have been observed, and a population-based cohort study conducted in Israel showed an increase in the incidence of sudden sensorineural hearing loss (SSNHL) following vaccination with messenger RNA COVID-19 vaccine BNT162b2 (Pfizer-BioNTech). However, in this setting, the possibility of confounding remained. Objective: To assess a potential association between COVID-19 vaccinations and SSNHL. Design, Setting, and Participants: This register-based country-wide retrospective cohort study of 5.5 million Finnish residents was conducted from January 1, 2019, to April 20, 2022, and included all individuals who were identified from the population information system who were alive or born during the study period except individuals who had SSNHL during 2015 to 2018 according to specialized care derived diagnosis codes for SSNHL (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] code H91.2) as a primary or secondary diagnosis. Exposures: The a priori primary risk period was 0 to 54 days following each COVID-19 vaccination. The risk periods for different vaccine doses did not overlap so that a later vaccine exposure ended the previous risk period. The secondary risk period was from 55 days following each COVID-19 vaccination until a subsequent COVID-19 vaccination. A secondary analysis included a risk time from 0 to 54 days following a positive polymerase chain reaction test result for SARS-CoV-2. Main Outcomes and Measures: The incidences of SSNHL following COVID-19 vaccination were compared with the incidences before the COVID-19 epidemic in Finland. The Poisson regression model included calendar time, age, sex, diabetes, cardiovascular disease, other chronic diseases, and the number of visits in primary health care. Results: For the 5.5 million Finnish residents included in the study, the comparison time comprised 6.5 million person-years, the primary risk time of 1.7 million person-years, and the secondary risk time of 2.1 million person-years. Before the COVID-19 epidemic in Finland, 18.7/100 000 people received a diagnosis of SSNHL annually. The study data suggested no increased risk for SSNHL following any COVID-19 vaccination. In particular, adjusted incidence rate ratios with 95% confidence intervals for the BNT162b2 vaccine's 3 doses were 0.8 (95% CI, 0.6-1.0), 0.9 (95% CI, 0.6-1.2), and 1.0 (95% CI, 0.7-1.4), respectively. There was no association between SARS-CoV-2 infection and an increased incidence of SSNHL. Conclusions and Relevance: The results of this cohort study show no evidence of an increased risk of SSNHL following COVID-19 vaccination. The study accounted for previous disease and other potential confounding factors. These results are based on diagnosis codes in specialized care but still need to be verified in settings that are capable of evaluating the degree of hearing loss.

Strong Neutralizing Antibody Responses to SARS-CoV-2 Variants Following a Single Vaccine Dose in Subjects With Previous SARS-CoV-2 Infection.

Background: Previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection primes the immune system; thus individuals who have recovered from infection have enhanced immune responses to subsequent vaccination (hybrid immunity). However, it remains unclear how well hybrid immunity induced by severe or mild infection can cross-neutralize emerging variants. We aimed to compare the strength and breadth of antibody responses in vaccinated recovered and uninfected subjects. Methods: We measured spike-specific immunoglobulin (Ig)G and neutralizing antibodies (NAbs) from vaccinated subjects including 320 with hybrid immunity and 20 without previous infection. From 29 subjects with a previous severe or mild infection, we also measured NAb responses against Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529/BA.1) variants following vaccination. Results: A single vaccine dose induced 2-fold higher anti-spike IgG concentrations and up to 4-fold higher neutralizing potency of antibodies in subjects with a previous infection compared with vaccinated subjects without a previous infection. Hybrid immunity was more enhanced after a severe than a mild infection, with sequentially decreasing NAb titers against Alpha, Beta, Delta, and Omicron variants. We found similar IgG concentrations in subjects with a previous infection after 1 or 2 vaccine doses. Conclusions: Hybrid immunity induced strong IgG responses, particularly after severe infection. However, the NAb titers were low against heterologous variants, especially against Omicron.

High vaccine effectiveness against severe COVID-19 in the elderly in Finland before and after the emergence of Omicron.

BACKGROUND: The elderly are highly vulnerable to severe COVID-19. Waning immunity and emergence of Omicron have caused concerns about reduced effectiveness of COVID-19 vaccines. The objective was to estimate vaccine effectiveness (VE) against severe COVID-19 among the elderly. METHODS: This nationwide, register-based cohort analysis included all residents aged 70 years and over in Finland. The follow-up started on December 27, 2020, and ended on March 31, 2022. The outcomes of interest were COVID-19-related hospitalization and intensive care unit (ICU) admission timely associated with SARS-CoV-2 infection. VE was estimated as one minus the hazard ratio comparing the vaccinated and unvaccinated and taking into account time since vaccination. Omicron-specific VE was evaluated as the effectiveness observed since January 1, 2022. RESULTS: The cohort included 896,220 individuals. Comirnaty (BioNTech/Pfizer) VE against COVID-19-related hospitalization was 93% (95% CI 89-95%) and 85% (95% CI 82-87%) 14-90 and 91-180 days after the second dose; VE increased to 95% (95% CI 94-96%) 14-60 days after the third dose. VE of other homologous and heterologous three dose series was similar. Protection against severe COVID-19 requiring ICU treatment was even better. Since January 1, 2022, Comirnaty VE was 98% (95% CI 92-99%) and 92% (95% CI 87-95%) 14-90 and 91-180 days after the second and 98% (95% CI 95-99%) 14-60 days after the third dose. CONCLUSIONS: VE against severe COVID-19 is high among the elderly. It waned slightly after two doses, but a third restored the protection. VE against severe COVID-19 remained high even after the emergence of Omicron.

Report of the 2nd workshop of the International Collaboration on advanced vaccinology training.

At a workshop on 22-24 March 2022, leaders of 33 advanced vaccinology courses were invited to meet with partners to further the aims of the International Collaboration on Advanced Vaccinology Training (ICAVT) initiated in 2018 to assist courses in addressing challenges in priority areas and facilitate interactions and exchange of information. This included: an update to the landscape analysis of advanced vaccinology courses conducted in 2018, sharing experiences and good practices in the implementation of virtual training, reviewing the training needs of target audiences, informing courses of the principles, challenges, and added value of accreditation, discussing course evaluations and measurement of course impact, reviewing principles and support needed for quality cascade training, reviewing COVID-19 impact on training and identifying remaining related training needs, and identifying solutions to facilitate refresher courses and ways to facilitate networking of courses' alumni (particularly for virtual courses). The aims were to identify needs and impediments and implement necessary actions to facilitate sharing of information and resources between courses, to identify need for further developments of the e-Portal of the Collaboration (icavt.org) established to facilitate communication between the different courses and assist future course participants identify the most suitable course for them, and to discuss the formalization of the Collaboration. During the workshop, participants looked at several reports of surveys completed by courses and courses' alumni or partners. The COVID-19 pandemic impacted the delivery of some vaccinology courses leading to postponement, delivery online or hybrid training events. Lack of sustainable funding remained a major constraint for advanced vaccinology training and needs to be addressed. The Collaboration was consolidated with responsibilities and benefits for the members better defined. There was strong support for the Collaboration to continue with the organization of educational sessions at future workshops. The meeting re-enforced the view that there was much enthusiasm and commitment for the Global Collaboration and its core values.

The value of public-private collaborative real-world evidence platforms to monitor vaccine performance post authorization: DRIVE - a European initiative.

INTRODUCTION: Fighting pandemics requires an established infrastructure for pandemic preparedness, with existing, sustainable platforms ready to be activated. This includes platforms for disease surveillance, virus circulation, and vaccine performance monitoring based on Real-World data, to complement clinical trial evidence. AREAS COVERED: Because of its complexity, this can best be done by combining efforts between public and private sectors, developing a multi-stakeholder approach. Public-Private-Partnerships increasingly play a critical role in combating infectious diseases but are still looked at with hesitancy. The Development of Robust and Innovative Vaccine Effectiveness (DRIVE) project, which established a platform for measuring brand-specific influenza vaccine effectiveness in Europe, exemplifies how to build a collaborative platform with transparent governance, state-of-the-art methodology, and a large network of participating sites. Lessons learned from DRIVE have been cardinal to set up COVIDRIVE, a platform for brand-specific COVID-19 vaccine effectiveness monitoring. EXPERT OPINION: The DRIVE partners propose that a debate on the benefits of Public-Private-Partnership-generated real-world evidence for vaccine effectiveness monitoring should be pursued to clarify roles and responsibilities, set up expectations, and decide the future environment for vaccine monitoring in Europe. In parallel, the driving factors behind PPP hesitancy should be studied.

Age-Specific Estimates of Respiratory Syncytial Virus-Associated Hospitalizations in 6 European Countries: A Time Series Analysis.

BACKGROUND: Knowledge on age-specific hospitalizations associated with RSV infection is limited due to limited testing, especially in older children and adults in whom RSV infections are not expected to be severe. Burden estimates based on RSV coding of hospital admissions are known to underestimate the burden of RSV. We aimed to provide robust and reliable age-specific burden estimates of RSV-associated hospital admissions based on data on respiratory infections from national health registers and laboratory-confirmed cases of RSV. METHODS: We conducted multiseason regression analysis of weekly hospitalizations with respiratory infection and weekly laboratory-confirmed cases of RSV and influenza as covariates, based on national health registers and laboratory databases across 6 European countries. The burden of RSV-associated hospitalizations was estimated by age group, clinical diagnosis, and presence of underlying medical conditions. RESULTS: Across the 6 European countries, hospitalizations of children with respiratory infections were clearly associated with RSV, with associated proportions ranging from 28% to 60% in children younger than 3 months and we found substantial proportions of admissions to hospital with respiratory infections associated with RSV in children younger than 3 years. Associated proportions were highest among hospitalizations with ICD-10 codes of "bronchitis and bronchiolitis." In all 6 countries, annual incidence of RSV-associated hospitalizations was >40 per 1000 persons in the age group 0-2 months. In age group 1-2 years the incidence rate ranged from 1.3 to 10.5 hospitalizations per 1000. Adults older than 85 years had hospitalizations with respiratory infection associated to RSV in all 6 countries although incidence rates were low. CONCLUSIONS: Our findings highlight the substantial proportion of RSV infections among hospital admissions across different ages and may help public health professionals and policy makers when planning prevention and control strategies. In addition, our findings provide valuable insights for health care professionals attending to both children and adults presenting with symptoms of viral respiratory infections.

High secondary attack rate and persistence of SARS-CoV-2 antibodies in household transmission study participants, Finland 2020-2021.

Background: Household transmission studies offer the opportunity to assess both secondary attack rate (SAR) and persistence of SARS-CoV-2 antibodies over time. Methods: In Spring 2020, we invited confirmed COVID-19 cases and their household members to four visits, where we collected nasopharyngeal and serum samples over 28 days after index case onset. We calculated SAR based on the presence of SARS-CoV-2 neutralizing antibodies (NAb) and assessed the persistence of NAb and IgG antibodies (Ab) against SARS-CoV-2 spike glycoprotein and nucleoprotein. Results: SAR was 45% (39/87), including 35 symptomatic secondary cases. During the initial 28-day follow-up, 62% (80/129) of participants developed NAb. Of those that seroconverted, 90% (63/70), 85% (63/74), and 78% (45/58) still had NAb to early B-lineage SARS-CoV-2 3, 6, and 12 months after the onset of the index case. Anti-spike IgG Ab persisted in 100% (69/69), 97% (72/74), and 93% (55/59) of seroconverted participants after 3, 6, and 12 months, while anti-nucleoprotein IgG Ab levels waned faster, persisting in 99% (68/69), 78% (58/74), and 55% (39/71) of participants, respectively. Conclusion: Following detection of a COVID-19 case in a household, other members had a high risk of becoming infected. NAb to early B-lineage SARS-CoV-2 persisted for at least a year in most cases.

Access to Vaccination among Disadvantaged, Isolated and Difficult-to-Reach Communities in the WHO European Region: A Systematic Review.

Vaccination has a significant impact on morbidity and mortality. High vaccination coverage rates are required to achieve herd protection against vaccine-preventable diseases. However, limited vaccine access and hesitancy among specific communities represent significant obstacles to this goal. This review provides an overview of critical factors associated with vaccination among disadvantaged groups in World Health Organisation European countries. Initial searches yielded 18,109 publications from four databases, and 104 studies from 19 out of 53 countries reporting 22 vaccine-preventable diseases were included. Nine groups representing the populations of interest were identified, and most of the studies focused on asylum seekers, refugees, migrants and deprived communities. Recall of previous vaccinations received was poor, and serology was conducted in some cases to confirm protection for those who received prior vaccinations. Vaccination coverage was lower among study populations compared to the general population or national average. Factors that influenced uptake, which presented differently at different population levels, included health service accessibility, language and vaccine literacy, including risk perception, disease severity and vaccination benefits. Strategies that could be implemented in vaccination policy and programs were also identified. Overall, interventions specific to target communities are vital to improving uptake. More innovative strategies need to be deployed to improve vaccination coverage among disadvantaged groups.

Neutralizing antibodies to SARS-CoV-2 Omicron variant after third mRNA vaccination in health care workers and elderly subjects.

The emergence of SARS-CoV-2 Omicron variant (B.1.1.529) with major spike protein mutations has raised concern over potential neutralization escape and breakthrough infections among vaccinated and previously SARS-CoV-2-infected subjects. We measured cross-protective antibodies against variants in health care workers (HCW, n = 20) and nursing home residents (n = 9) from samples collected at 1-2 months, following the booster (3rd) dose. We also assessed the antibody responses in subjects infected before the Omicron era (n = 38) with subsequent administration of a single mRNA vaccine dose. Following booster vaccination, HCWs had high IgG antibody concentrations to the spike protein and neutralizing antibodies (NAb) were detectable against all variants. IgG concentrations among the elderly remained lower, and some lacked NAbs against the Beta and Omicron variants. NAb titers were significantly reduced against Delta, Beta, and Omicron compared to WT virus regardless of age. Vaccination induced high IgG concentrations and variable titers of cross-reactive NAbs in previously infected subjects, whereas NAb titers against Omicron were barely detectable 1 month postinfection. High IgG concentrations with cross-protective neutralizing activity were detected after three Coronavirus Disease 2019 (COVID-19) vaccine doses in HCWs. However, lower NAb titers seen in the frail elderly suggest inadequate protection against Omicron breakthrough infections, yet protection against severe COVID-19 is expected.

SARS-CoV-2 Vaccination and Myocarditis in a Nordic Cohort Study of 23 Million Residents.

Importance: Reports of myocarditis after SARS-CoV-2 messenger RNA (mRNA) vaccination have emerged. Objective: To evaluate the risks of myocarditis and pericarditis following SARS-CoV-2 vaccination by vaccine product, vaccination dose number, sex, and age. Design, Setting, and Participants: Four cohort studies were conducted according to a common protocol, and the results were combined using meta-analysis. Participants were 23 122 522 residents aged 12 years or older. They were followed up from December 27, 2020, until incident myocarditis or pericarditis, censoring, or study end (October 5, 2021). Data on SARS-CoV-2 vaccinations, hospital diagnoses of myocarditis or pericarditis, and covariates for the participants were obtained from linked nationwide health registers in Denmark, Finland, Norway, and Sweden. Exposures: The 28-day risk periods after administration date of the first and second doses of a SARS-CoV-2 vaccine, including BNT162b2, mRNA-1273, and AZD1222 or combinations thereof. A homologous schedule was defined as receiving the same vaccine type for doses 1 and 2. Main Outcomes and Measures: Incident outcome events were defined as the date of first inpatient hospital admission based on primary or secondary discharge diagnosis for myocarditis or pericarditis from December 27, 2020, onward. Secondary outcome was myocarditis or pericarditis combined from either inpatient or outpatient hospital care. Poisson regression yielded adjusted incidence rate ratios (IRRs) and excess rates with 95% CIs, comparing rates of myocarditis or pericarditis in the 28-day period following vaccination with rates among unvaccinated individuals. Results: Among 23 122 522 Nordic residents (81% vaccinated by study end; 50.2% female), 1077 incident myocarditis events and 1149 incident pericarditis events were identified. Within the 28-day period, for males and females 12 years or older combined who received a homologous schedule, the second dose was associated with higher risk of myocarditis, with adjusted IRRs of 1.75 (95% CI, 1.43-2.14) for BNT162b2 and 6.57 (95% CI, 4.64-9.28) for mRNA-1273. Among males 16 to 24 years of age, adjusted IRRs were 5.31 (95% CI, 3.68-7.68) for a second dose of BNT162b2 and 13.83 (95% CI, 8.08-23.68) for a second dose of mRNA-1273, and numbers of excess events were 5.55 (95% CI, 3.70-7.39) events per 100 000 vaccinees after the second dose of BNT162b2 and 18.39 (9.05-27.72) events per 100 000 vaccinees after the second dose of mRNA-1273. Estimates for pericarditis were similar. Conclusions and Relevance: Results of this large cohort study indicated that both first and second doses of mRNA vaccines were associated with increased risk of myocarditis and pericarditis. For individuals receiving 2 doses of the same vaccine, risk of myocarditis was highest among young males (aged 16-24 years) after the second dose. These findings are compatible with between 4 and 7 excess events in 28 days per 100 000 vaccinees after BNT162b2, and between 9 and 28 excess events per 100 000 vaccinees after mRNA-1273. This risk should be balanced against the benefits of protecting against severe COVID-19 disease.

Information nudges for influenza vaccination: Evidence from a large-scale cluster-randomized controlled trial in Finland.

BACKGROUND: Vaccination is the most effective means of preventing the spread of infectious diseases. Despite the proven benefits of vaccination, vaccine hesitancy keeps many people from getting vaccinated. METHODS AND FINDINGS: We conducted a large-scale cluster randomized controlled trial in Finland to test the effectiveness of centralized written reminders (distributed via mail) on influenza vaccination coverage. The study included the entire older adult population (aged 65 years and above) in 2 culturally and geographically distinct regions with historically low (31.8%, n = 7,398, mean age 75.5 years) and high (57.7%, n = 40,727, mean age 74.0 years) influenza vaccination coverage. The study population was randomized into 3 treatments: (i) no reminder (only in the region with low vaccination coverage); (ii) an individual-benefits reminder, informing recipients about the individual benefits of vaccination; and (iii) an individual- and social-benefits reminder, informing recipients about the additional social benefits of vaccination in the form of herd immunity. There was no control treatment group in the region with high vaccination coverage as general reminders had been sent in previous years. The primary endpoint was a record of influenza vaccination in the Finnish National Vaccination Register during a 5-month follow-up period (from October 18, 2018 to March 18, 2019). Vaccination coverage after the intervention in the region with historically low coverage was 41.8% in the individual-benefits treatment, 38.9% in the individual- and social-benefits treatment and 34.0% in the control treatment group. Vaccination coverage after the intervention in the region with historically high coverage was 59.0% in the individual-benefits treatment and 59.2% in the individual- and social-benefits treatment. The effect of receiving any type of reminder letter in comparison to control treatment group (no reminder) was 6.4 percentage points (95% CI: 3.6 to 9.1, p < 0.001). The effect of reminders was particularly large among individuals with no prior influenza vaccination (8.8 pp, 95% CI: 6.5 to 11.1, p < 0.001). There was a substantial positive effect (5.3 pp, 95% CI: 2.8 to 7.8, p < 0.001) among the most consistently unvaccinated individuals who had not received any type of vaccine during the 9 years prior to the study. There was no difference in influenza vaccination coverage between the individual-benefit reminder and the individual- and social-benefit reminder (region with low vaccination coverage: 2.9 pp, 95% CI: -0.4 to 6.1, p = 0.087, region with high vaccination coverage: 0.2 pp, 95% CI: -1.0 to 1.3, p = 0.724). Study limitations included potential contamination between the treatments due to information spillovers and the lack of control treatment group in the region with high vaccination coverage. CONCLUSIONS: In this study, we found that sending reminders was an effective and scalable intervention strategy to increase vaccination coverage in an older adult population with low vaccination coverage. Communicating the social benefits of vaccinations, in addition to individual benefits, did not enhance vaccination coverage. The effectiveness of letter reminders about the benefits of vaccination to improve influenza vaccination coverage may depend on the prior vaccination history of the population. TRIAL REGISTRATION: AEA RCT registry AEARCTR-0003520 and ClinicalTrials.gov NCT03748160.