Detection of SARS-COV-2 variants and their proportions in wastewater samples using next-generation sequencing in Finland.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants may have different characteristics, e.g., in transmission, mortality, and the effectiveness of vaccines, indicating the importance of variant detection at the population level. Wastewater-based surveillance of SARS-CoV-2 RNA fragments has been shown to be an effective way to monitor the COVID-19 pandemic at the population level. Wastewater is a complex sample matrix affected by environmental factors and PCR inhibitors, causing insufficient coverage in sequencing, for example. Subsequently, results where part of the genome does not have sufficient coverage are not uncommon. To identify variants and their proportions in wastewater over time, we utilized next-generation sequencing with the ARTIC Network's primer set and bioinformatics pipeline to evaluate the presence of variants in partial genome data. Based on the wastewater data from November 2021 to February 2022, the Delta variant was dominant until mid-December in Helsinki, Finland's capital, and thereafter in late December 2022 Omicron became the most common variant. At the same time, the Omicron variant of SARS-CoV-2 outcompeted the previous Delta variant in Finland in new COVID-19 cases. The SARS-CoV-2 variant findings from wastewater are in agreement with the variant information obtained from the patient samples when visually comparing trends in the sewerage network area. This indicates that the sequencing of wastewater is an effective way to monitor temporal and spatial trends of SARS-CoV-2 variants at the population level.

Hybrid Immunity Improves the Immune Response after the Fourth COVID-19 Vaccine Dose in Individuals with Medical Conditions Predisposing to Severe COVID-19.

Data on immune responses following COVID-19 booster vaccinations and subsequent infections in the immunocompromised are limited. We studied antibody responses after the fourth dose and subsequent infections to define patient groups benefiting most from boosters. Fourth vaccine (booster) doses were, in Finland, first recommended for severely immunocompromised individuals, whom we invited to participate in our study in 2022. We assessed spike protein-specific IgG and neutralizing antibodies (NAb) against the ancestral and Omicron BA.1 strains one month after the fourth dose from 488 adult participants and compared them to the levels of 35 healthy controls after three doses. We used Bayesian generalized linear modeling to assess factors explaining antibody levels and assessed vaccine-induced and hybrid immunity six months after the last vaccine dose. Chronic kidney disease (CKD) and immunosuppressive therapy (IT) were identified as factors explaining sub-optimal antibody responses. The proportion of participants with a normal antibody response and NAbs was significantly lower regarding CKD patients compared to the controls. By the 6-month sampling point, one-third of the participants became infected (documented by serology and/or molecular tests), which notably enhanced antibody levels in most immunocompromised participants. Impaired antibody responses, especially NAbs against the Omicron lineage, suggest limited protection in individuals with CKD and highlight the need for alternative pharmaceutical preventive strategies. Vaccination strategies should take into account the development of robust hybrid immunity responses also among the immunocompromised.

Face mask recommendations in schools did not impact COVID-19 incidence among 10-12-year-olds in Finland - joinpoint regression analysis.

BACKGROUND: In autumn 2021 in Finland, a recommendation to use face masks was implemented nationwide in schools for pupils ages 12 years and above. While national guidelines were in form of recommendations, cities implemented mandatory masking in schools. Some cities extended this mandate for younger pupils as well. Our aim was to compare COVID-19 incidence among 10-12-year-olds between cities with different recommendations on the use of face masks in schools. METHODS: COVID-19 case numbers, defined as positive laboratory verified SARS-CoV-2 test results, were obtained from the National Infectious Disease Registry (NIDR) of the Finnish Institute for Health and Welfare. Helsinki, Turku and Tampere were selected for comparison since the baseline COVID-19 incidence in the cities had been similar in August and September 2021. Helsinki and Tampere implemented the national recommendation on face mask use at schools, while Turku extended this to include those 10 years old and above, starting from the beginning of semester in early August. Age groups of 7-9-year-olds, 10-12-year-olds and 30-49-year-olds were included in the statistical analysis and moving averages of 14-day incidences per 100 000 inhabitants were used as a dependent variable. Joinpoint regression was used to estimate average percent changes (APC) and average daily percent changes (ADPC) in the 14-day incidences. Differences in the ADPC values between the cities were compared in one-month periods. We also calculated cumulative incidences from the beginning of August to the end of November in the cities by age group. RESULTS: In August, the ADPC was highest in Turku (3.9) and lowest in Tampere (2.0), while in September, the ADPC was highest in Turku (-0.3) and lowest in Helsinki (-3.2) among 10-12-year-olds. In October, the ADPC was highest in Helsinki (2.1) and lowest in Turku (-0.2) and in November, the ADPC was highest in Turku (4.1) and lowest in Tampere (-0.5) among 10-12-year-olds. We also calculated cumulative incidences from the beginning of August to the end of November in the cities by age groups of 7-9 years, 10-12 years, and 30-49 years. The cumulative incidence was highest in Turku in all age groups and lowest in Tampere. CONCLUSIONS: According to our analysis, no additional effect was gained from mandating face masks, based on comparisons between the cities and between the age groups of the unvaccinated children (10-12 years versus 7-9 years).

Online searches of children's oseltamivir in public primary and specialized care: Detecting influenza outbreaks in Finland using dedicated databases for health care professionals.

INTRODUCTION: Health care professionals working in primary and specialized care typically search for medical information from Internet sources. In Finland, Physician's Databases are online portals aimed at professionals seeking medical information. As dosage errors may occur when prescribing medication to children, professionals' need for reliable medical information has increased in public health care centers and hospitals. Influenza continues to be a public health threat, with young children at risk of developing severe illness and easily transmitting the virus. Oseltamivir is used to treat children with influenza. The objective of this study was to compare searches for children's oseltamivir and influenza diagnoses in primary and specialized care, and to determine if the searches could aid detection of influenza outbreaks. METHODS: We compared searches in Physician's Databases for children's oral suspension of oseltamivir (6 mg/mL) for influenza diagnoses of children under 7 years and laboratory findings of influenza A and B from the National Infectious Disease Register. Searches and diagnoses were assessed in primary and specialized care across Finland by season from 2012-2016. The Moving Epidemic Method (MEM) calculated seasonal starts and ends, and paired differences in the mean compared two indicators. Correlation was tested to compare seasons. RESULTS: We found that searches and diagnoses in primary and specialized care showed visually similar patterns annually. The MEM-calculated starting weeks in searches appeared mainly in the same week. Oseltamivir searches in primary care preceded diagnoses by -1.0 weeks (95% CI: -3.0, -0.3; p = 0.132) with very high correlation (τ = 0.913). Specialized care oseltamivir searches and diagnoses correlated moderately (τ = 0.667). CONCLUSION: Health care professionals' searches for children's oseltamivir in online databases linked with the registers of children's influenza diagnoses in primary and specialized care. Therefore, database searches should be considered as supplementary information in disease surveillance when detecting influenza epidemics.

Rationale and Description of Implementation of Regional Collaborative Service Model for Enhancing Psychosocial Wellbeing of Children and Families-Oulu Collective Impact Study.

Background: The psychosocial wellbeing of children and adolescents is an ongoing global concern. Despite positive outcomes of child- and family-focused programs, the fragmentation of services presents challenges. To enhance harmonization and diminish fragmentation of service policies, we implement a preventive collaborative service model for children and families. The rationale for our study is based on analyses of national and local data before implementing the service model in the pilot area. Methods: The need for a preventive service model for children and families was demonstrated using national and local data sources. First, a national school health survey was utilized to screen adolescents' perceptions of their depressive symptoms and support. Second, time trends in child and adolescent psychiatric and child protection service use were investigated. For these aims, epidemiological data of the study area (city of Oulu) were compared with data from the whole country (Finland). Third, local usage data of the preventive stand-alone Let's Talk About Children (LT) intervention before the service model implementation were evaluated. After these analyses, Let's Talk About Children Service Model (LT-SM) implementation in the pilot area is described in detail. Results: The background data showed that 17% of the adolescents in the study area had reported depressive symptoms, and almost half of them had not received professional help. Child and adolescent psychiatric outpatient visits had increased during the last decade, but the number of visits remains lower in the study area compared with the country as a whole. The number of adolescent psychiatric inpatient days had increased contrary to a decreasing national trend. The number of urgent child welfare placements was also higher compared with the whole country. The local LT intervention data revealed very low utilization rates. These results indicated a necessity to enhance preventive and collaborative support for children and their families. This article describes the implementation of the LT-SM. Discussion: We demonstrated excessive use of curative services in social and health care and insufficient usage of the stand-alone preventive intervention. The LT-SM is now piloted in one regional service area of the city of Oulu. Its effectiveness will be evaluated when enough data have been accumulated for statistical analyses.

Detection and quantification of SARS-CoV-2 RNA in wastewater influent in relation to reported COVID-19 incidence in Finland.

Wastewater-based surveillance is a cost-effective concept for monitoring COVID-19 pandemics at a population level. Here, SARS-CoV-2 RNA was monitored from a total of 693 wastewater (WW) influent samples from 28 wastewater treatment plants (WWTP, N = 21-42 samples per WWTP) in Finland from August 2020 to May 2021, covering WW of ca. 3.3 million inhabitants (∼ 60% of the Finnish population). Quantity of SARS-CoV-2 RNA fragments in 24 h-composite samples was determined by using the ultrafiltration method followed by nucleic acid extraction and CDC N2 RT-qPCR assay. SARS-CoV-2 RNA signals at each WWTP were compared over time to the numbers of confirmed COVID-19 cases (14-day case incidence rate) in the sewer network area. Over the 10-month surveillance period with an extensive total number of samples, the detection rate of SARS-CoV-2 RNA in WW was 79% (including 6% uncertain results, i.e., amplified only in one out of four, two original and two ten-fold diluted replicates), while only 24% of all samples exhibited gene copy numbers above the quantification limit. The range of the SARS-CoV-2 detection rate in WW varied from 33% (including 10% uncertain results) in Pietarsaari to 100% in Espoo. Only six out of 693 WW samples were positive with SARS-COV-2 RNA when the reported COVID-19 case number from the preceding 14 days was zero. Overall, the 14-day COVID-19 incidence was 7.0, 18, and 36 cases per 100 000 persons within the sewer network area when the probability to detect SARS-CoV-2 RNA in wastewater samples was 50%, 75% and 95%, respectively. The quantification of SARS-CoV-2 RNA required significantly more COVID-19 cases: the quantification rate was 50%, 75%, and 95% when the 14-day incidence was 110, 152, and 223 COVID-19 cases, respectively, per 100 000 persons. Multiple linear regression confirmed the relationship between the COVID-19 incidence and the SARS-CoV-2 RNA quantified in WW at 15 out of 28 WWTPs (overall R2 = 0.36, p < 0.001). At four of the 13 WWTPs where a significant relationship was not found, the SARS-CoV-2 RNA remained below the quantification limit during the whole study period. In the five other WWTPs, the sewer coverage was less than 80% of the total population in the area and thus the COVID-19 cases may have been inhabitants from the areas not covered. Based on the results obtained, WW-based surveillance of SARS-CoV-2 could be used as an indicator for local and national COVID-19 incidence trends. Importantly, the determination of SARS-CoV-2 RNA fragments from WW is a powerful and non-invasive public health surveillance measure, independent of possible changes in the clinical testing strategies or in the willingness of individuals to be tested for COVID-19.

Predicting the stability of early employment with its timing and childhood social and health-related predictors: a mixture Markov model approach.

To extend work careers, it is important to focus on all working-aged people including young adults. The aim of this study was to identify typical patterns of work participation among young adults after their first entry into the labour market and to examine whether the timing of entry together with parental and own socio-economic position and health predict early work participation. More in-depth understanding of early careers and their early determinants is important to plan targeted interventions and to promote more stable work participation among young adults. We used the Finnish Birth Cohort 1987 including data from several registers from all 59,476 children born in 1987 as well as their parents, followed until 2015. We estimated a mixture Markov model that allowed for joint identification of latent classes of labour-market attachment, estimation of labour-market transitions within classes, and prediction of class membership using childhood social and health-related determinants. We observed that the first entry into the labour market as measured by six months in continuous employment was not a permanent entry for many, not only due to negative reasons such as unemployment and ill health but also due to more voluntary reasons such as studies. Individuals entering the labour market at a later age were more likely to be in continuous employment thereafter. More advantaged background predicted exits due to studies or - when following a late entry - stable employment, while disadvantaged background factors predicted more unstable work and long-term exits from the labour market.

Closing lower secondary schools had no impact on COVID-19 incidence in 13-15-year-olds in Finland.

School lockdowns have been widely used to control the COVID-19 pandemic. However, these lockdowns may have a significant negative impact on the lives of young people. In this study, we have evaluated the impact of closing lower secondary schools for COVID-19 incidence in 13-15-year-olds in Finland, in a situation where restrictions and recommendation of social distancing were implemented uniformly in the entire country. COVID-19 case numbers were obtained from the National Infectious Disease Registry (NIDR) of the Finnish Institute for Health and Welfare, in which clinical microbiology laboratories report all positive SARS-CoV-2 tests with unique identifiers in a timely manner. The NIDR is linked to population data registry, enabling calculation of incidences. We estimated the differences in trends between areas with both restaurant and lower secondary school closures and areas with only restaurant closures in different age groups by using joinpoint regression. We also estimated the differences in trends between age groups. Based on our analysis, closing lower secondary schools had no impact on COVID-19 incidence among 13-15-year-olds. No significant changes on COVID-19 incidence were observed in other age groups either.