No association between disease severity and respiratory syncytial virus subtypes RSV-A and RSV-B in hospitalized young children in Norway.

OBJECTIVE: There is conflicting evidence whether subtypes of Respiratory syncytial virus have different seasonality or are differentially associated with clinical severity. We aimed to explore the associations between disease severity and RSV subtypes RSV-A and RSV-B and to describe the circulation of RSV subtypes pattern by season and age. METHODS: Active prospective hospital surveillance for RSV-A and RSV-B in children <59 months of age was conducted during 2015-2018. All febrile children 12-59 months of age were enrolled, whereas children <12 months were eligible if presenting with fever or respiratory symptoms. Risk factors and upper and lower respiratory tract infection was identified by linkage to national registry data and analyzed using penalized maximum likelihood logistic regression. RESULTS: Both RSV-A and B were found to co-circulate throughout all three study seasons, and no clear seasonal pattern was identified. Likewise, we found no association between sex or measures of severity with RSV-A or RSV-B. There was significantly more RSV-A than RSV-B among children with comorbidities. CONCLUSIONS: No association was found between disease severity or sex and RSV subtypes RSV-A and RSV-B in hospitalized young children in Norway.

Risk factors for SARS-CoV-2 infection: a test-negative case-control study with additional population controls in Norway.

OBJECTIVES: This study aims to assess risk factors for SARS-CoV-2 infection by combined design; first comparing positive cases to negative controls as determined by PCR testing and then comparing these two groups to an additional prepandemic population control group. DESIGN AND SETTING: Test-negative design (TND), multicentre case-control study with additional population controls in South-Eastern Norway. PARTICIPANTS: Adults who underwent SARS-CoV-2 PCR testing between February and December 2020. PCR-positive cases, PCR-negative controls and additional age-matched population controls. PRIMARY OUTCOME MEASURES: The associations between various risk factors based on self- reported questionnaire and SARS-CoV-2 infection comparing PCR-positive cases and PCR-negative controls. Using subgroup analysis, the risk factors for both PCR-positive and PCR-negative participants were compared with a population control group. RESULTS: In total, 400 PCR-positive cases, 719 PCR-negative controls and 14 509 population controls were included. Male sex was associated with the risk of SARS-CoV-2 infection only in the TND study (OR 1.9, 95% CI 1.4 to 2.6), but not when PCR-positive cases were compared with population controls (OR 1.2, 95% CI 0.9. to 1.5). Some factors were positively (asthma, wood heating) or negatively (hypertension) associated with SARS-CoV-2 infection when PCR-positive cases were compared with population controls, but lacked convincing association in the TND study. Smoking was negatively associated with the risk of SARS-CoV-2 infection in both analyses (OR 0.5, 95% CI 0.3 to 0.8 and OR 0.6, 95% CI 0.4 to 0.8). CONCLUSIONS: Male sex was a possible risk factor for SARS-CoV-2 infection only in the TND study, whereas smoking was negatively associated with SARS-CoV-2 infection in both the TND study and when using population controls. Several factors were associated with SARS-CoV-2 infection when PCR-positive cases were compared with population controls, but not in the TND study, highlighting the strength of combining case-control study designs during the pandemic.

Boosted production of antibodies that neutralized different SARS-CoV-2 variants in a COVID-19 convalescent following messenger RNA vaccination - a case study.

Vaccinated convalescents do not develop severe COVID-19 after infection with new SARS-CoV-2 variants. We questioned how messenger RNA (mRNA) vaccination of convalescents provides protection from emerging virus variants. From the cohort of 71 convalescent plasma donors, we identified a patient who developed immune response to infection with SARS-CoV-2 variant of 20A clade and who subsequently received mRNA vaccine encoding spike (S) protein of strain of 19A clade. We showed that vaccination increased the production of immune cells and anti-S antibodies in the serum. Serum antibodies neutralized not only 19A and 20A, but also 20B, 20H, 21J, and 21K virus variants. One of the serum antibodies (100F8) completely neutralized 20A, 21J, and partially 21K strains. 100F8 was structurally similar to published Ab188 antibody, which recognized non-conserved epitope on the S protein. We proposed that 100F8 and other serum antibodies of the patient which recognized non- and conserved epitopes of the S protein, could have additive or synergistic effects to neutralize various virus variants. Thus, mRNA vaccination could be beneficial for convalescents because it boosts production of neutralizing antibodies with broad-spectrum activity.

The Burden of Human Bocavirus 1 in Hospitalized Children With Respiratory Tract Infections.

BACKGROUND: Human bocavirus 1 (HBoV1) is frequently codetected with other viruses, and detected in asymptomatic children. Thus, the burden of HBoV1 respiratory tract infections (RTI) has been unknown. Using HBoV1-mRNA to indicate true HBoV1 RTI, we assessed the burden of HBoV1 in hospitalized children and the impact of viral codetections, compared with respiratory syncytial virus (RSV). METHODS: Over 11 years, we enrolled 4879 children <16 years old admitted with RTI. Nasopharyngeal aspirates were analyzed with polymerase chain reaction for HBoV1-DNA, HBoV1-mRNA, and 19 other pathogens. RESULTS: HBoV1-mRNA was detected in 2.7% (130/4850) samples, modestly peaking in autumn and winter. Forty-three percent with HBoV1 mRNA were 12-17 months old, and only 5% were <6 months old. A total of 73.8% had viral codetections. It was more likely to detect HBoV1-mRNA if HBoV1-DNA was detected alone (odds ratio [OR]: 3.9, 95% confidence interval [CI]: 1.7-8.9) or with 1 viral codetection (OR: 1.9, 95% CI: 1.1-3.3), compared to ≥2 codetections. Codetection of severe viruses like RSV had lower odds for HBoV1-mRNA (OR: 0.34, 95% CI: 0.19-0.61). The yearly lower RTI hospitalization rate per 1000 children <5 years was 0.7 for HBoV1-mRNA and 8.7 for RSV. CONCLUSIONS: True HBoV1 RTI is most likely when HBoV1-DNA is detected alone, or with 1 codetected virus. Hospitalization due to HBoV1 LRTI is 10-12 times less common than RSV.

The Contribution of Viruses and Bacteria to Childhood Community-acquired Pneumonia: 11-Year Observational Study From Norway.

BACKGROUND: Viruses are associated with pediatric community-acquired pneumonia (CAP) but are also common in the upper airways of healthy children. We have determined the contribution of respiratory viruses and bacteria by comparing children with CAP and hospital controls. METHODS: Children less than 16 years old with radiologically confirmed CAP (n = 715) were enrolled over an 11-year period. Children admitted for elective surgery during the same period served as controls (n = 673). Nasopharyngeal aspirates were tested for 20 respiratory pathogens by semiquantitative polymerase chain reaction tests and cultivated for bacteria and viruses. We used logistic regression to calculate adjusted odds ratios [aOR; 95% confidence intervals (CIs)], and estimated population-attributable fractions (95% CI). RESULTS: At least 1 virus was detected in 85% of cases and 76% of controls, and greater than or equal to 1 bacterium was detected in 70% of cases and controls. The presence of respiratory syncytial virus (RSV) (aOR, 16.6; 95% CI: 9.81-28.2), human metapneumovirus (HMPV) (13.0; 6.17-27.5) and Mycoplasma pneumoniae (27.7; 8.37-91.6) were most strongly associated with CAP. For RSV and HMPV, there were significant trends between lower cycle-threshold values indicating higher viral genomic loads, and higher aORs for CAP. The population-attributable fraction estimates of RSV, HMPV, human parainfluenza virus, influenza virus and M. pneumoniae were 33.3% (32.2-34.5), 11.2% (10.5-11.9), 3.7% (1.0-6.3), 2.3% (1.0-3.6) and 4.2% (4.1-4.4), respectively. CONCLUSIONS: RSV, HMPV and M. pneumoniae were most strongly related to pediatric CAP and accounted for half of all cases. There were positive trends between increasing viral genomic loads of RSV and HMPV, and higher odds for CAP.

Risk factors associated with severe disease in respiratory syncytial virus infected children under 5 years of age.

Objective: To evaluate risk factors for severe disease in children under 59 months of age hospitalized with respiratory syncytial virus (RSV) infection. Study design: We prospectively enrolled 1,096 cases of laboratory confirmed RSV infection during three consecutive RSV seasons in 2015-2018. Potential risk factors for severe disease were retrieved through patient questionnaires and linkage to national health registries. Need for respiratory support (invasive ventilation, bi-level positive airway pressure, or continuous positive airway pressure), and length of stay exceeding 72 h were used as measures of disease severity. Associations were investigated using multivariable logistic regression analyses. Multiple imputation was used to avoid bias and inference induced by missing data. Results: Risk factors associated with a need for respiratory support included age younger than 3 months of age [aOR: 6.73 (95% CI 2.71-16.7)], having siblings [aOR: 1.65 (95% CI 1.05-2.59)] and comorbidity [aOR: 2.40 (95% CI 1.35-4.24)]. The length of hospital stay >72 h was significantly associated with being younger than 3 months of age [aOR: 3.52 (95% CI 1.65-7.54)], having siblings [aOR: 1.45 (95% CI 1.01-2.08)], and comorbidity [aOR: 2.18 (95% CI 1.31-3.61)]. Sub-group analysis of children younger than 6 months of age confirmed the association between both young age and having siblings and the need for respiratory support. Conclusion: In a large cohort of children <59 months hospitalized with RSV infection, young age, comorbidity, and having siblings were associated with more severe disease.

The burden of hospital-attended influenza in Norwegian children.

Background: Norwegian health authorities do not recommend universal pediatric vaccination against seasonal influenza. We aimed to estimate the incidence of influenza by age and underlying medical conditions in hospitalized Norwegian children aged <18 years. Methods: Active surveillance for influenza in children <18 years was implemented in five hospitals during 2015-18. Children with respiratory symptoms and/or fever were prospectively enrolled and tested for influenza. Surveillance data were linked to health registry data to estimate the national burden of influenza in hospitals. Results: In 309 (10%) out of 3,010 hospital contacts, the child tested positive for influenza, corresponding to an average incidence of 0.96 hospital-attended influenza cases per 1,000 children <18 years of age. Children <1 year of age (3.8 per 1,000 children) and children with underlying medical conditions (17 per 1,000 children with bronchopulmonary dysplasia) had the highest average incidence. Among <1 year old children, 3% tested positive for influenza, compared to 25% for children aged 6-17. Few children were vaccinated against influenza. Conclusions: Children <1 year of age and children with underlying medical conditions had a higher incidence of influenza requiring hospital treatment compared to the general population. Effective interventions against seasonal influenza for children in Norway should be considered.

SARS-CoV-2 antibody persistence after five and twelve months: A cohort study from South-Eastern Norway.

OBJECTIVES: To assess total antibody levels against Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS CoV-2) spike protein up to 12 months after Coronavirus Disease (COVID-19) infection in non-vaccinated individuals and the possible predictors of antibody persistence. METHODS: This is the first part of a prospective multi-centre cohort study. PARTICIPANTS: The study included SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) positive and negative participants in South-Eastern Norway from February to December 2020. Possible predictors of SARS-CoV-2 total antibody persistence was assessed. The SARS-CoV-2 total antibody levels against spike protein were measured three to five months after PCR in 391 PCR-positive and 703 PCR-negative participants; 212 PCR-positive participants were included in follow-up measurements at 10 to 12 months. The participants completed a questionnaire including information about symptoms, comorbidities, allergies, body mass index (BMI), and hospitalisation. PRIMARY OUTCOME: The SARS-CoV-2 total antibody levels against spike protein three to five and 10 to 12 months after PCR positive tests. RESULTS: SARS-CoV-2 total antibodies against spike protein were present in 366 (94%) non-vaccinated PCR-positive participants after three to five months, compared with nine (1%) PCR-negative participants. After 10 to 12 months, antibodies were present in 204 (96%) non-vaccinated PCR-positive participants. Of the PCR-positive participants, 369 (94%) were not hospitalised. The mean age of the PCR-positive participants was 48 years (SD 15, range 20-85) and 50% of them were male. BMI ≥ 25 kg/m2 was positively associated with decreased antibody levels (OR 2.34, 95% CI 1.06 to 5.42). Participants with higher age and self-reported initial fever with chills or sweating were less likely to have decreased antibody levels (age: OR 0.97, 95% CI 0.94 to 0.99; fever: OR 0.33, 95% CI 0.13 to 0.75). CONCLUSION: Our results indicate that the level of SARS-CoV-2 total antibodies against spike protein persists for the vast majority of non-vaccinated PCR-positive persons at least 10 to 12 months after mild COVID-19.

Detection of subgenomic mRNA from endemic human coronavirus OC43 and NL63 compared to viral genomic loads, single virus detection and clinical manifestations in children with respiratory tract infections.

BACKGROUND: The importance of endemic human coronavirus (HCoV) in children has been insufficiently elucidated upon. Our aims were to develop subgenomic (sg) mRNA tests for HCoV species OC43 and NL63, and to evaluate the relationships to HCoV genomic loads, single HCoV detections and clinical manifestations. METHODS: We have used an 11-yearlong cohort study of children admitted with respiratory tract infection (RTI) and hospital controls. Nasopharyngeal aspirates were analyzed for HCoV subtypes OC43 and NL63 with in-house diagnostic PCR. Positive samples were tested with newly developed real-time PCRs targeting sg mRNA coding for the nucleocapsid protein. RESULTS: OC43 sg mRNA was detected in 86% (105/122) of available OC43-positive samples in the RTI group, and in 63% (12/19) of control samples. NL63 sg mRNA was detected in 72% (71/98) and 71% (12/17) of available NL63-positive patient and control samples, respectively. In RTI samples, sg mRNA detection was strongly associated with a Ct value <32 in both diagnostic PCR tests (OC43: OR = 54, 95% CI [6.8-428]; NL63: OR = 42, 95% CI [9.0-198]) and single NL63 detections (OR = 6.9, 95% CI [1.5-32]). Comparing RTI and controls, only OC43 was associated with RTI when adjusted for age (aOR = 3.2, 95% CI [1.1-9.4]). CONCLUSION: We found strong associations between OC43 and NL63 sg mRNA and high viral genomic loads. sg mRNA for OC43 was associated with RTI. The association between sg mRNA and clinical manifestations needs further evaluation.

Rapid elimination of SARS-CoV-2 in a fully vaccinated patient. / Rask eliminasjon av SARS-CoV-2 hos fullvaksinert pasient.

High SARS-CoV-2 viral loads in respiratory secretions detected by PCR technique are usually an indicator of high transmission risk, but not always. In this article, we present the case of a fully-vaccinated patient with rapid clearance of the alpha variant of the virus.

Hospitalized Children With Common Human Coronavirus Clinical Impact of Codetected Respiratory Syncytial Virus and Rhinovirus.

BACKGROUND: The clinical impact of common human coronavirus (cHCoV) remains unclear. We studied the clinical manifestations of pediatric cHCoV infections and the possible modifying effects of codetected human rhinovirus (RV) and respiratory syncytial virus (RSV). METHODS: We used data from an 11-year-long prospective study of hospitalized children with community-acquired respiratory tract infections. Nasopharyngeal aspirates were analyzed with real-time polymerase chain reaction assay for cHCoV OC43, NL63, HKU1 and 229E, and 15 other respiratory viruses. We assessed disease severity based on the clinical factors hospitalization length, oxygen requirement, other respiratory support and supplementary fluids. RESULTS: cHCoV was detected in 341 (8%) of 4312 children. Among 104 children with single cHCoV detections, 58 (56%) had lower respiratory tract infection (LRTI) and 20 (19%) developed severe disease. The proportion with severe disease was lower among single cHCoV detections compared with single RSV detections (338 of 870; 39%), but similar to single RV detections (136 of 987; 14%). Compared with single cHCoV, codetected cHCoV-RSV was more often associated with LRTI (86 of 89; 97%) and severe disease (adjusted odds ratio, 3.3; 95% confidence interval: 1.6-6.7). LRTI was more frequent in codetected cHCoV-RV (52 of 68; 76%) than single cHCoV, but the risk of severe disease was lower (adjusted odds ratios, 0.3; 95% confidence interval: 0.1-1.0). CONCLUSIONS: cHCoV was associated with severe LRTI in hospitalized children. Viral codetections were present in two-thirds. Codetections of cHCoV-RV were associated with lower proportions of severe disease, suggesting a modifying effect of RV on HCoV.

Genetic diversity of rotavirus strains circulating in Norway before and after the introduction of rotavirus vaccination in children.

Globally, rotavirus (RV) is the leading cause of acute gastroenteritis (AGE) in young children under 5 years of age. Implementation of RV vaccination is expected to result in fewer cases of RV in the target population, but it is unknown if this also results in vaccine-induced virus strain replacement. Rotarix, a monovalent vaccine based on G1P[8] RV, was introduced in Norway in the children's immunization program in September 2014. The main aim of this study was to describe the diversity of RV circulating pre and post introduction of the RV vaccine in Norway and investigate changes in genotype distribution during the first 4 years after implementation. A total of 1108 samples were collected from children under 5 years enrolled with AGE from five large hospitals in Norway and were analyzed for RV by enzyme immunoassay (EIA). All positive results were genotyped by multiplex semi-nested reverse transcription PCR for identification of G and P types. In total, 487 of the 1108 (44%) samples, collected from the enrolled children, were positive for RV by EIA method which were further genotyped. G1P[8] was found to be the most common type of RV pre and post RV vaccine implementation followed by G9P[8]. There were neither geographical nor temporal differences in genotype dominance. Also, no apparent changes were shown in the genotype distribution in the postvaccine era for years from 2015 to 2018. In 21.4% of the cases, vaccine strains were detected. Continuous RV genotype surveillance is vital for assessing the effectiveness of a vaccine program and monitoring for any emergence of vaccine-escape strains. Genotyping is also necessary to detect vaccine strains to avoid reporting false-positive cases of active RV infection in newly vaccinated cases.

The burden of respiratory syncytial virus in children under 5 years of age in Norway.

OBJECTIVES: To estimate age-specific incidence of medically attended respiratory syncytial virus (RSV) infections in hospitalised Norwegian children and describe disease epidemiology. METHODS: Active prospective hospital surveillance for RSV in children <59 months of age was conducted during 2015-2018. All febrile children 12-59 months of age were enrolled, whereas children <12 months were enrolled based on respiratory symptoms regardless of fever. Surveillance data were linked to national registry data to estimate the clinical burden of RSV. RESULTS: Of the children enrolled, 1096 (40%) were infected with RSV. The highest incidence rates were found in children 1 month of age, with a peak incidence of 43 per 1000 during the 2016-2017 season. In comparison, children 24-59 months of age had an infection rate of 1.4 per 1000 during the same winter season. The peak season was during the 2016-2017 winter, with an incidence rate of 6.0 per 1000 children 0-59 months of age. In the study population a total of 168 (15%) of the infected children had pre-existing medical conditions predisposing for more severe disease. High infection rates were found in this population. CONCLUSIONS: Children with comorbidities showed high hospital contact rates, but the majority of children in need of medical attention associated with RSV infection were previously healthy.

Synergistic Interferon-Alpha-Based Combinations for Treatment of SARS-CoV-2 and Other Viral Infections.

BACKGROUND: There is an urgent need for new antivirals with powerful therapeutic potential and tolerable side effects. METHODS: Here, we tested the antiviral properties of interferons (IFNs), alone and with other drugs in vitro. RESULTS: While IFNs alone were insufficient to completely abolish replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), IFNα, in combination with remdesivir, EIDD-2801, camostat, cycloheximide, or convalescent serum, proved to be more effective. Transcriptome and metabolomic analyses revealed that the IFNα-remdesivir combination suppressed SARS-CoV-2-mediated changes in Calu-3 cells and lung organoids, although it altered the homeostasis of uninfected cells and organoids. We also demonstrated that IFNα combinations with sofosbuvir, telaprevir, NITD008, ribavirin, pimodivir, or lamivudine were effective against HCV, HEV, FLuAV, or HIV at lower concentrations, compared to monotherapies. CONCLUSIONS: Altogether, our results indicated that IFNα can be combined with drugs that affect viral RNA transcription, protein synthesis, and processing to make synergistic combinations that can be attractive targets for further pre-clinical and clinical development against emerging and re-emerging viral infections.

Hepatitis C outreach project and cross-sectional epidemiology in high-risk populations in Trondheim, Norway.

BACKGROUND: Hepatitis C is highly prevalent among people who use drugs (PWUD), and the hepatitis C virus (HCV) epidemic is less characterised in Norway. The aims of the study were to assess the prevalence and treatment willingness in high-risk populations by reaching out to frequently visited sites for high-risk populations. METHODS: Individuals from high-risk populations were included from September 2015 to March 2017. Two dedicated study nurses frequently visited the local opioid substitution clinic, outpatient clinics, PWUD day centres, local prison, and refugee centre in Trondheim, Norway. Demographic data, risk behaviour, and clinical symptoms were obtained by study questionnaire. Subjects with anti-HCV+ rapid test were subsequently tested for HCV RNA and genotyped. Viraemic patients were offered referral for HCV treatment evaluation. RESULTS: A total of 381 participants were included in the study: 52 immigrants, 62 prisoners, and 267 PWUD. The anti-HCV prevalence rates were 0% (n = 0) in immigrants, 40% (n = 25) in prisoners, and 61% (n = 164) in PWUD, with 24% (n = 15) of prisoners and 42% (n = 108) of PWUD being viraemic. Of those qualifying for treatment (n = 31), 30 wished to be evaluated. CONCLUSION: This study showed high HCV prevalence in prisoners and PWUD and that infected high-risk patients were interested in treatment evaluation.

Molecular Epidemiology and Evolutionary Trajectory of Emerging Echovirus 30, Europe.

In 2018, an upsurge in echovirus 30 (E30) infections was reported in Europe. We conducted a large-scale epidemiologic and evolutionary study of 1,329 E30 strains collected in 22 countries in Europe during 2016-2018. Most E30 cases affected persons 0-4 years of age (29%) and 25-34 years of age (27%). Sequences were divided into 6 genetic clades (G1-G6). Most (53%) sequences belonged to G1, followed by G6 (23%), G2 (17%), G4 (4%), G3 (0.3%), and G5 (0.2%). Each clade encompassed unique individual recombinant forms; G1 and G4 displayed >2 unique recombinant forms. Rapid turnover of new clades and recombinant forms occurred over time. Clades G1 and G6 dominated in 2018, suggesting the E30 upsurge was caused by emergence of 2 distinct clades circulating in Europe. Investigation into the mechanisms behind the rapid turnover of E30 is crucial for clarifying the epidemiology and evolution of these enterovirus infections.

Parechovirus A in Hospitalized Children With Respiratory Tract Infections: A 10-Year-Long Study From Norway.

BACKGROUND: The role of Parechovirus A (PeV-A) in hospitalized children with respiratory tract infections (RTIs) is unclear. We studied the occurrence and impact of PeV-A over 10 years. METHODS: Children from Sør-Trøndelag County, Norway, hospitalized with RTI and a comparison group of asymptomatic children admitted to elective surgery, were prospectively enrolled from 2006 to 2016. Nasopharyngeal aspirates were cultured and analyzed with polymerase chain reaction tests for PeV-A and 19 other pathogens. The cycle threshold levels of PeV-A were reported as measures of viral genomic loads. Parechovirus A-positive samples were genotyped by amplification and sequencing of the VP3/VP1 junction. RESULTS: Parechovirus A was detected in 8.8% (323/3689) patients with RTI and in 10.1% (45/444) of the children in the comparison group (P = .34). Parechovirus A genotyping (n = 188) revealed PeV-A1 (n = 121), PeV-A3 (n = 15), PeV-A5 (n = 6), and PeV-A6 (n = 46). Viral codetections occurred in 95% of patients and in 84% of the children in the comparison group (P = .016). In multivariable logistic regression analysis, RTI was unrelated to PeV-A genomic loads, adjusted for other viruses and covariates. Similar results were found for PeV-A1 and PeV-A6. CONCLUSIONS: Parechovirus A and viral codetections were common in hospitalized children with RTI and asymptomatic children in a comparison group. Our findings suggest that PeV-A has a limited role in hospitalized children with RTI.

Impact of the Rotavirus Vaccination Program in Norway After Four Years With High Coverage.

BACKGROUND: Use of rotavirus vaccines worldwide since 2006 has led to a significant impact on the burden of rotavirus disease. However, only a third of European countries have introduced rotavirus vaccination in their immunization programs. In October 2014, rotavirus vaccination was introduced for Norwegian infants under strict age restrictions. Exclusive use of the monovalent rotavirus vaccine (RV1) and high vaccination coverage from the beginning enabled evaluation of the impact of this vaccine during the first 4 years after introduction. METHODS: Prospective laboratory-based surveillance among children <5 years of age hospitalized for acute gastroenteritis at 5 Norwegian hospitals was used to assess the vaccine effectiveness of 2 vaccine doses against rotavirus hospitalization in a case-control study. We used community controls selected from the national population-based immunization registry, and test-negative controls recruited through hospital surveillance. We also assessed the vaccine impact by using time-series analysis of retrospectively collected registry data on acute gastroenteritis in primary and hospital care during 2009-2018. RESULTS: Vaccine effectiveness against rotavirus-confirmed hospitalization was 76% (95% confidence interval [CI]: 34%-91%) using test-negative controls, and 75% (95% CI: 44%-88%) using community controls. In the postvaccine period, acute gastroenteritis hospitalizations in children <5 years were reduced by 45% compared with the prevaccine years (adjusted incidence rate ratios 0.55; 95% CI: 0.49-0.61). Reduction in hospitalizations was also seen in cohorts not eligible for vaccination. Rates in primary care decreased to a lesser degree. CONCLUSIONS: Four years after introduction of rotavirus vaccination in the national childhood immunization program, we recorded a substantial reduction in the number of children hospitalized for acute gastroenteritis in Norway, attributable to a high vaccine effectiveness.

Epitope-resolved profiling of the SARS-CoV-2 antibody response identifies cross-reactivity with endemic human coronaviruses.

The SARS-CoV-2 proteome shares regions of conservation with endemic human coronaviruses (CoVs), but it remains unknown to what extent these may be cross-recognized by the antibody response. Here, we study cross-reactivity using a highly multiplexed peptide assay (PepSeq) to generate an epitope-resolved view of IgG reactivity across all human CoVs in both COVID-19 convalescent and negative donors. PepSeq resolves epitopes across the SARS-CoV-2 Spike and Nucleocapsid proteins that are commonly targeted in convalescent donors, including several sites also recognized in some uninfected controls. By comparing patterns of homologous reactivity between CoVs and using targeted antibody-depletion experiments, we demonstrate that SARS-CoV-2 elicits antibodies that cross-recognize pandemic and endemic CoV antigens at two Spike S2 subunit epitopes. We further show that these cross-reactive antibodies preferentially bind endemic homologs. Our findings highlight sites at which the SARS-CoV-2 response appears to be shaped by previous CoV exposures and which have the potential to raise broadly neutralizing responses.