When schools were open for in-person teaching during the COVID-19 pandemic - the nordic experience on control measures and transmission in schools during the delta wave.

BACKGROUND: Extensive measures to control spread of SARS-CoV-2 have led to limited access to education for millions of children and adolescents during the COVID-19 pandemic. Education and access to schools is vital for children and adolescents' learning, health, and wellbeing. Based on high vaccine uptake and low incidence levels, the Nordic countries (Denmark, Finland, Iceland, Norway and Sweden) decided to start the academic year 2021/22 with schools open for in-person teaching and moderate mitigation measures. We describe trends in SARS-CoV-2 infections and vaccination coverage among students during the first 12 weeks of the fall semester. METHODS: In this multinational, retrospective, observational study, we have used surveillance and registry data from each of the Nordic countries to describe vaccine uptake (≥12 years), infection incidence (whole population) and transmission of SARS-CoV-2 among students. The study period, week 30 to 41 (Jul 26th - Oct 17th), represents the autumn semester from immediately before school started until fall break. In addition, we collected information on mitigation measures applied by the respective countries. RESULTS: There were slight variations between the countries regarding existing infection prevention and control (IPC) measures, testing strategies and vaccination start-up among adolescents. All countries had high vaccine uptake in the adult population, while uptake varied more in the younger age groups. Incidence in the school-aged population differed between countries and seemed to be influenced by both vaccine uptake and test activity. Infection clusters among school-aged children were described for Denmark and Norway, and the number of clusters per week reflected the incidence trend of the country. Most events consisted of only 1-2 cases. Larger clusters appeared more frequently in the higher grades in Norway and in lower grades in Denmark. CONCLUSION: Data from the Nordic countries indicate that vaccination of adults and adolescents, in addition to mitigation measures, enabled full in-person learning. As SARS-CoV-2 infection does not represent a severe medical risk for most children as previously thought, measures targeting this group should be carefully adjusted and kept at a minimum. Our data add to the evidence on incidence and transmission of SARS-CoV-2 among students in schools open for in-person teaching, and may be valuable for decision makers worldwide.

Evolution of Bordetella pertussis in the acellular vaccine era in Norway, 1996 to 2019.

We described the population structure of Bordetella pertussis (B. pertussis) in Norway from 1996 to 2019 and determined if there were evolutionary shifts and whether these correlated with changes in the childhood immunization program. We selected 180 B. pertussis isolates, 22 from the whole cell vaccine (WCV) era (1996-1997) and 158 from the acellular vaccine (ACV) era (1998-2019). We conducted whole genome sequencing and determined the distribution and frequency of allelic variants and temporal changes of ACV genes. Norwegian B. pertussis isolates were evenly distributed across a phylogenetic tree that included global strains. We identified seven different allelic profiles of ACV genes (A-F), in which profiles A1, A2, and B dominated (89%), all having pertussis toxin (ptxA) allele 1, pertussis toxin promoter (ptxP) allele 3, and pertactin (prn) allele 2 present. Isolates with ptxP1 and prn1 were not detected after 2007, whereas the prn2 allele likely emerged prior to 1972, and ptxP3 before the early 1980s. Allele conversions of ACV genes all occurred prior to the introduction of ACV. Sixteen percent of our isolates showed mutations within the prn gene. ACV and its booster doses (implemented for children in 2007 and adolescents in 2013) might have contributed to evolvement of a more uniform B. pertussis population, with recent circulating strains having ptxA1, ptxP3, and prn2 present, and an increasing number of prn mutations. These strains clearly deviate from ACV strains (ptxA1, ptxP1, prn1), and this could have implications for vaccine efficiency and, therefore, prevention and control of pertussis.

Experience with open schools and preschools in periods of high community transmission of COVID-19 in Norway during the academic year of 2020/2021.

BACKGROUND: Schools and preschools have largely remained open in Norway throughout the pandemic, with flexible mitigation measures in place. This contrasts with many other high-income countries that closed schools for long periods of time. Here we describe cases and outbreaks of COVID-19 in schools and preschools during the academic year 2020/2021, to evaluate the strategy of keeping these open with infection prevention control measures in place. METHODS: In this descriptive study, the Norwegian Institute of Public Health initiated systematic surveillance for COVID-19 cases and outbreaks in schools and preschools in October 2020. Data was compiled from the national outbreak alert system VESUV, municipality websites, and media scanning combined with the national emergency preparedness register Beredt C-19. An outbreak was defined as ≥ 2 cases among pupils or staff within 14 days at the same educational setting. Settings were categorized as preschool (1-5-years), primary school (6-12-years), lower secondary school (13-15-years) and upper secondary school (16-18- years). We reported the incidence rate among preschool and school-aged pupils and gave a descriptive overview of outbreaks and included cases per educational setting. RESULTS: During the whole academic year, a total of 1203 outbreaks in preschools and school settings were identified, out of a total of 8311 preschools and schools nationwide. The incidence of COVID-19 in preschool- and school-aged children and the rates of outbreaks in these settings largely followed the community trend. Most of the outbreaks occurred in primary schools (40%) and preschools (25%). Outbreaks across all settings were mostly small (median 3 cases, range 2 to 72), however, 40 outbreaks (3% of total) included 20 or more cases. The larger outbreaks were predominantly seen in primary schools (43%). CONCLUSIONS: We observed few large outbreaks in open schools and preschools in Norway during the academic year of 2020/2021, also when the Alpha variant was predominant. This illustrates that it is possible to keep schools and preschools open even during periods of high community transmission of COVID-19. Adherence to targeted IPC measures adaptable to the local situation has been essential to keep educational settings open, and thus reduce the total burden on children and adolescents.

Secondary attack rates of COVID-19 in Norwegian families: a nation-wide register-based study.

To characterize the family index case for detected SARS-CoV-2 and describe testing and secondary attack rates in the family, we used individual-level administrative data of all families and all PCR tests for SARS-CoV-2 in Norway in 2020. All families with at least one parent and one child below the age of 20 who lived at the same address (N = 662,582), where at least one member, i.e. the index case, tested positive for SARS-CoV-2 in 2020, were included. Secondary attack rates (SAR7) were defined as the share of non-index family members with a positive PCR test within 7 days after the date when the index case tested positive. SARs were calculated separately for parent- and child-index cases, and for parent- and child-secondary cases. We identified 7548 families with an index case, comprising 26,991 individuals (12,184 parents, 14,808 children). The index was a parent in 66% of the cases. Among index children, 42% were in the age group 17-20 and only 8% in the age group 0-6. When the index was a parent, SAR7 was 24% (95% CI 24-25), whilst SAR7 was 14% (95% CI 13-15) when the index was a child. However, SAR7 was 24% (95% CI 20-28) when the index was a child aged 0-6 years and declined with increasing age of the index child. SAR7 from index parent to other parent was 35% (95% CI 33-36), and from index child to other children 12% (95% CI 11-13). SAR7 from index child aged 0-6 to parents was 27% (95% CI 22-33). The percent of non-index family members tested within 7 days after the index case, increased from about 20% in April to 80% in December, however, SAR7 stabilized at about 20% from May. We conclude that parents and older children are most often index cases for SARS-CoV-2 in families in Norway, while parents and young children more often transmit the virus within the family. This study suggests that whilst the absolute infection numbers are low for young children because of their low introduction rate, when infected, young children and parents transmit the virus to the same extent within the family.

Minimal transmission of SARS-CoV-2 from paediatric COVID-19 cases in primary schools, Norway, August to November 2020.

An intense debate on school closures to control the COVID-19 pandemic is ongoing in Europe. We prospectively examined transmission of SARS-CoV-2 from confirmed paediatric cases in Norwegian primary schools between August and November 2020. All in-school contacts were systematically tested twice during their quarantine period. With preventive measures implemented in schools, we found minimal child-to-child (0.9%, 2/234) and child-to-adult (1.7%, 1/58) transmission, supporting that under 14 year olds are not the drivers of SARS-CoV-2 transmission.

Infection prevention guidelines and considerations for paediatric risk groups when reopening primary schools during COVID-19 pandemic, Norway, April 2020.

In response to the coronavirus disease (COVID-19) pandemic, most countries implemented school closures. In Norway, schools closed on 13 March 2020. The evidence of effect on disease transmission was limited, while negative consequences were evident. Before reopening, risk-assessment for paediatric risk groups was performed, concluding that most children can attend school with few conditions requiring preventative homeschooling. We here present infection prevention and control guidelines for primary schools and recommendations for paediatric risk groups.

SARS-CoV-2 in children and adolescents in Norway: confirmed infection, hospitalisations and underlying conditions. / Sars-CoV-2 hos barn og ungdom i Norge: påvist smitte, sykehusinnleggelser og underliggende tilstander.

BACKGROUND: Children and adolescents are at lower risk of disease caused by SARS-CoV-2. We describe the incidence of confirmed infection and hospitalisation of children and adolescents under the age of 20 in Norway, and specifically among those with underlying conditions. MATERIAL AND METHOD: The Norwegian Directorate of Health has collaborated with the Norwegian Institute of Public Health on the establishment of a data extraction system to monitor the coronavirus outbreak. Data from the specialist health service (Norwegian Patient Registry, NPR), and the primary health service (Norwegian Registry for Primary Health Care, NRPHC) are linked to data on positive SARS-CoV-2 tests from the Surveillance System for Communicable Diseases (MSIS). This covers all persons living in Norway as of 1 March 2020, with data on confirmed infection up to and including 13 May 2020 and on hospitalisations up to and including 30 April 2020. RESULTS: Of 8 125 persons with confirmed SARS-CoV-2 in the whole population, 493 (6.1 %) were under 20 years old. The median age of the under-20s was 15 years, and 252 (51 %) were girls. 3 % were hospitalised. No deaths were registered among patients aged under 20 in Norway. We found a somewhat larger share with confirmed SARS-CoV-2 in the group with diseases of the neuromuscular system. INTERPRETATION: Few children and adolescents have had SARS-CoV-2 confirmed, and only a very few have been hospitalised. Underlying conditions may result in a lower threshold for testing, and hence a higher incidence of confirmed infection in this group, although higher risk cannot be excluded.

Pertactin-deficient Bordetella pertussis isolates: evidence of increased circulation in Europe, 1998 to 2015.

IntroductionPertussis outbreaks have occurred in several industrialised countries using acellular pertussis vaccines (ACVs) since the 1990s. High prevalence of pertactin (PRN)-deficient Bordetella pertussis isolates has been found in these countries.AimsTo evaluate in Europe: (i) whether proportions of PRN-deficient strains increased in consecutive collections of B. pertussis clinical isolates; (ii) if the frequency of PRN-deficient strains in countries correlated with the time since ACV introduction; (iii) the presence of pertussis toxin (PT)-, filamentous haemagglutinin (FHA)- or fimbriae (Fim)-deficient isolates.MethodsB. pertussis clinical isolates were obtained from different European countries during four periods (EUpert I-IV studies): 1998 to 2001 (n = 102), 2004 to 2005 (n = 154), 2007 to 2009 (n = 140) and 2012 to 2015 (n = 265). The isolates' selection criteria remained unchanged in all periods. PRN, PT, FHA and Fim2 and Fim3 expression were assessed by ELISA.ResultsIn each period 1.0% (1/102), 1.9% (3/154), 6.4% (9/140) and 24.9% (66/265) of isolates were PRN-deficient. In EUpert IV, PRN-deficient isolates occurred in all countries sampled and in six countries their frequency was higher than in EUpert III (for Sweden and the United Kingdom, p < 0.0001 and p = 0.0155, respectively). Sweden and Italy which used ACVs since the mid 1990s had the highest frequencies (69%; 20/29 and 55%; 11/20, respectively) while Finland, where primary immunisations with ACV containing PRN dated from 2009 had the lowest (3.6%). Throughout the study, no PT- or FHA-deficient isolate and one Fim2/3-deficient was detected.ConclusionResults suggest that the longer the period since the introduction of ACVs containing PRN, the higher the frequency of circulating PRN-deficient isolates.

Surveillance of Circulating Bordetella pertussis Strains in Europe during 1998 to 2015.

One reason for increased pertussis incidence is the adaptation of Bordetella pertussis to vaccine-induced immunity by modulating its genomic structure. This study, EUpert IV, includes 265 isolates collected from nine European countries during 2012 to 2015 (n = 265) and compares the results to previous EUpert I to III studies (1998 to 2009). The analyses included genotyping, serotyping, pulsed-field gel electrophoresis (PFGE), and multilocus variable-number tandem-repeat analysis (MLVA). Genotyping results showed only small variations among the common virulence genes of B. pertussis The frequencies of serotypes Fim2 and Fim3 varied among the four collections. Genomic analyses showed that MLVA type 27 increased to 80% between the periods of 1998 to 2001 and 2012 to 2015. Two PFGE profiles, BpSR3 (29.4%) and BpSR10 (27.2%), constituted more than 50% of the circulating isolates in the present collection. Our study indicates that the European B. pertussis population is changing and became more homogenous after the introduction of acellular pertussis vaccines.

Large outbreak of mumps virus genotype G among vaccinated students in Norway, 2015 to 2016.

From 6 September 2015-May 2016, a large mumps outbreak occurred among vaccinated students in Norway. A case was defined as a person presenting with a clinical mumps infection, notified between 1 September 2015 and 30 June 2016. Confirmed cases had positive laboratory confirmation and probable cases had an epidemiological link; PCR-positive specimens were genotyped. A total of 232 cases were notified (230 confirmed) with median age of 23 years (range 4-81) and 61% were male. Of 68 (30%) confirmed cases that were genotyped, 66 were genotype G and associated with the outbreak. Cases that had received two doses of the measles-mumps-rubella (MMR) vaccine had reduced risk of hospitalisation (adjusted relative risk (aRR): 0.14; 95%CI: 0.03-0.57), mumps-related orchitis (aRR: 0.21; 95% CI: 0.08-0.55) and severe outcome (aRR: 0.25; 95% CI: 0.10-0.62) compared with those unvaccinated. A third dose of the vaccine was offered to approximately 1,300 fully vaccinated close contacts and subsequently reported cases decreased. This large outbreak, occurring among predominately vaccinated students, suggests the current genotype A vaccine offers suboptimal protection against mumps genotype G. We recommend maintaining high vaccination coverage and offering the vaccine to all unvaccinated individuals.

When the restrictions are worse than the pandemic. / Når tiltaket er verre enn pandemien.

Stricter infection controls and school closures to tackle COVID-19 are regularly called for in the public discourse on the pandemic. However, restrictions on schooling and leisure activities can have negative consequences. Norwegian and international data appear to support the argument to keep schools and day-care centres open, with good infection control measures, and that closing them should be a last resort.

Predictors of maternal pertussis vaccination acceptance among pregnant women in Norway.

Maternal vaccination against pertussis is safe and provides effective protection against pertussis for the newborn, but the vaccine coverage rate remains generally low. Norway is currently planning for introduction of routine maternal pertussis vaccination. To assess maternal pertussis vaccination acceptance among pregnant Norwegian women, we surveyed women at 20-40 weeks gestation in 2019. Among the 1,148 pregnant women participating in this cross-sectional study, 73.8% reported they would accept pertussis vaccination during pregnancy if it was recommended, 6.9% would not accept and 19.2% were undecided. Predictors for low likelihood of accepting pertussis vaccination during pregnancy included low confidence in health authorities and in maternal pertussis vaccination safety and effectiveness, low awareness and adherence to influenza vaccination during pregnancy, and low awareness of pertussis vaccination. The major reasons reported for not accepting or being undecided about maternal pertussis vaccination were lack of information on vaccine safety for both mother and child. Most women reported that they would consult their general practitioner or a midwife for information if they were offered maternal pertussis vaccination. General practitioners and midwives were also regarded as the most trustworthy sources of information if the women were in doubt about accepting vaccination. We conclude that information addressing safety concerns and raising awareness about maternal pertussis vaccination could increase acceptance of maternal pertussis vaccination. Our findings highlight the pivotal role of the antenatal and primary health care services in providing such information to pregnant women.

Effectiveness of BNT162b2 vaccine against SARS-CoV-2 Delta and Omicron infection in adolescents, Norway, August 2021 to January 2022.

OBJECTIVES: We estimated the BNT162b2 vaccine effectiveness (VE) against any (symptomatic or not) SARS-CoV-2 Delta and Omicron infection among adolescents (aged 12-17 years) in Norway from August 2021 to January 2022. METHODS: We used Cox proportional hazard models, where vaccine status was included as a time-varying covariate and models were adjusted for age, sex, comorbidities, residence county, birth country, and living conditions. RESULTS: The VE against Delta infection peaked at 68% (95% confidence interval [CI]: 64-71%) and 62% (95% CI: 57-66%) in days 21-48 after the first dose among those aged 12-15 years and 16-17 years, respectively. Among those aged 16-17 years who received two doses, the VE against Delta infection peaked at 93% (95% CI: 90-95%) in days 35-62 and decreased to 84% (95% CI: 76-89%) in ≥63 days after vaccination. We did not observe a protective effect against Omicron infection after receiving one dose. Among those aged 16-17 years, the VE against Omicron infection peaked at 53% (95% CI: 43-62%) in 7-34 days after the second dose and decreased to 23% (95% CI: 3-40%) in ≥63 days after vaccination. CONCLUSION: We found a reduced protection after two BNT162b2 vaccine doses against any Omicron infection compared to Delta. Effectiveness decreased with time from vaccination for both variants. The impact of vaccination among adolescents on reducing infection and thus transmission is limited during the Omicron dominance.

T cells raised against allogeneic HLA-A2/CD20 kill primary follicular lymphoma and acute lymphoblastic leukemia cells.

T cells mediating a graft-versus-leukemia/lymphoma effects without causing graft-versus-host disease would greatly improve the safety and applicability of hematopoietic stem cell transplantation. We recently demonstrated that highly peptide- and HLA-specific T cells can readily be generated against allogeneic HLA-A*02:01 in complex with a peptide from the B cell-restricted protein CD20. Here, we show that such CD20-specific T cells can easily be induced from naïve precursors in cord blood, demonstrating that they do not represent cross-reactive memory cells. The cells displayed high avidity and mediated potent cytotoxic effects on cells from patients with the CD20(pos) B cell malignancies follicular lymphoma (FL) and acute lymphoblastic leukemia (ALL). However, the cytotoxicity was consistently lower for cells from two of the ALL patients. The ALL cells that were less efficiently killed did not display lower surface expression of CD20 or HLA-A*02:01, or mutations in the CD20 sequence. Peptide pulsing fully restored the levels of cytotoxicity, indicating that they are indeed susceptible to T cell-mediated killing. Adoptive transfer of CD20-specific T cells to an HLA-A*02:01(pos) patient requires an HLA-A*02:01(neg) , but otherwise HLA identical, donor. A search clarified that donors meeting these criteria can be readily identified even for patients with rare haplotypes. The results bear further promise for the clinical utility of CD20-specific T cells in B cell malignancies.