High titers of neutralizing SARS-CoV-2 antibodies six months after symptom onset are associated with increased severity in COVID-19 hospitalized patients.

BACKGROUND: Viral shedding and neutralizing antibody (NAb) dynamics among patients hospitalized with severe coronavirus disease 2019 (COVID-19) and immune correlates of protection have been key questions throughout the pandemic. We investigated the duration of reverse transcriptase-polymerase chain reaction (RT-PCR) positivity, infectious viral shedding and NAb titers as well as the association between NAb titers and disease severity in hospitalized COVID-19 patients in Denmark 2020-2021. MATERIALS AND METHODS: Prospective single-center observational cohort study of 47 hospitalized COVID-19 patients. Oropharyngeal swabs were collected at eight time points during the initial 30 days of inclusion. Serum samples were collected after a median time of 7 (IQR 5 - 10), 37 (IQR 35 - 38), 97 (IQR 95 - 100), and 187 (IQR 185 - 190) days after symptom onset. NAb titers were determined by an in-house live virus microneutralization assay. Viral culturing was performed in Vero E6 cells. RESULTS: Patients with high disease severity had higher mean log2 NAb titers at day 37 (1.58, 95% CI [0.34 -2.81]), 97 (2.07, 95% CI [0.53-3.62]) and 187 (2.49, 95% CI [0.20- 4.78]) after symptom onset, compared to patients with low disease severity. Peak viral load (0.072, 95% CI [- 0.627 - 0.728]), expressed as log10 SARS-CoV-2 copies/ml, was not associated with disease severity. Virus cultivation attempts were unsuccessful in almost all (60/61) oropharyngeal samples collected shortly after hospital admission. CONCLUSIONS: We document an association between high disease severity and high mean NAb titers at days 37, 97 and 187 after symptom onset. However, peak viral load during admission was not associated with disease severity. TRIAL REGISTRATION: The study is registered at https://clinicaltrials.gov/ (NCT05274373).

Early and intense epidemic of respiratory syncytial virus (RSV) in Denmark, August to December 2022.

In the autumn of 2022, Denmark witnessed the second out-of-season epidemic of respiratory syncytial virus (RSV) following widespread societal preventive measures implemented against the coronavirus disease (COVID-19) pandemic during 2020 and 2021. Admissions peaked at twice the level of pre-pandemic seasons. Especially infants below 6 months of age were affected, but also adults over 45 years of age. The current epidemic is dominated by RSV subtype B, unlike the major RSV summer epidemic in 2021 dominated by RSV subtype A.

A late sharp increase in influenza detections and low interim vaccine effectiveness against the circulating A(H3N2) strain, Denmark, 2021/22 influenza season up to 25 March 2022.

We estimated interim influenza A vaccine effectiveness (VE) following a late sharp rise in cases during an influenza A(H3N2)-dominated 2021/22 season, after lifting COVID-19 restrictions. In children aged 2-6 years offered a live attenuated influenza vaccine, adjusted VE was 62.7% (95% CI: 10.9-84.4) in hospitalised and 64.2% (95% CI: 50.5-74.1) in non-hospitalised children. In non-hospitalised patients aged 7-44 years, VE was 24.8% (95% CI: 12.8-35.2); VE was non-significant in remaining age groups and hospital/non-hospital settings.

A Novel Prophylaxis Strategy Using Liposomal Vaccine Adjuvant CAF09b Protects against Influenza Virus Disease.

The SARS-CoV-2 pandemic caused a massive health and societal crisis, although the fast development of effective vaccines reduced some of the impact. To prepare for future respiratory virus pandemics, a pan-viral prophylaxis could be used to control the initial virus outbreak in the period prior to vaccine approval. The liposomal vaccine adjuvant CAF®09b contains the TLR3 agonist polyinosinic:polycytidylic acid, which induces a type I interferon (IFN-I) response and an antiviral state in the affected tissues. When testing CAF09b liposomes as a potential pan-viral prophylaxis, we observed that intranasal administration of CAF09b liposomes to mice resulted in an influx of innate immune cells into the nose and lungs and upregulation of IFN-I-related gene expression. When CAF09b liposomes were administered prior to challenge with mouse-adapted influenza A/Puerto Rico/8/1934 virus, it protected from severe disease, although the virus was still detectable in the lungs. However, when CAF09b liposomes were administered after influenza challenge, the mice had a similar disease course to controls. In conclusion, CAF09b may be a suitable candidate as a pan-viral prophylactic treatment for epidemic viruses, but must be administered prior to virus exposure to be effective.

Reassortant Influenza A(H1N1)pdm09 Virus in Elderly Woman, Denmark, January 2021.

A case of human infection with influenza A(H1N1)pdm09 virus containing a nonstructural gene highly similar to Eurasian avian-like H1Nx swine influenza virus was detected in Denmark in January 2021. We describe the clinical case and report testing results of the genetic and antigenic characterizations of the virus.

Abrupt termination of the 2019/20 influenza season following preventive measures against COVID-19 in Denmark, Norway and Sweden.

BackgroundIn mid-March 2020, a range of public health and social measures (PHSM) against the then new coronavirus disease (COVID-19) were implemented in Denmark, Norway and Sweden.AimWe analysed the development of influenza cases during the implementation of PHSM against SARS-CoV-2 in the Scandinavian countries.MethodBased on the established national laboratory surveillance of influenza, we compared the number of human influenza cases in the weeks immediately before and after the implementation of SARS-CoV-2 PHSM by country. The 2019/20 influenza season was compared with the five previous seasons.ResultsA dramatic reduction in influenza cases was seen in all three countries, with only a 3- to 6-week duration from the peak of weekly influenza cases until the percentage dropped below 1%. In contrast, in the previous nine influenza seasons, the decline from the seasonal peak to below 1% of influenza-positive samples took more than 10 weeks.ConclusionsThe PHSM against SARS-CoV-2 were followed by a dramatic reduction in influenza cases, indicating a wider public health effect of the implemented measures.

Commercially available rapid diagnostic tests for the detection of high priority pathogens: status and challenges.

The ongoing COVID-19 pandemic has shown the importance of having analytical devices that allow a simple, fast, and robust detection of pathogens which cause epidemics and pandemics. The information these devices can collect is crucial for health authorities to make effective decisions to contain the disease's advance. The World Health Organization published a list of primary pathogens that have raised concern as potential causes of future pandemics. Unfortunately, there are no rapid diagnostic tests commercially available and approved by the regulatory bodies to detect most of the pathogens listed by the WHO. This report describes these pathogens, the available detection methods, and highlights areas where more attention is needed to produce rapid diagnostic tests for future pandemic surveillance.

Point-of-care tests for influenza A and B viruses and RSV in emergency departments - indications, impact on patient management and possible gains by syndromic respiratory testing, Capital Region, Denmark, 2018.

BackgroundPoint-of-care tests (POCT) for influenza A and B viruses and respiratory syncytial virus (RSV) were implemented in emergency departments of all hospitals in the Capital Region of Denmark in 2018.AimTo establish whether POC testing for influenza viruses or RSV is based on a valid respiratory symptom indication, whether changes in patient management based on a positive result are safe and whether syndromic POC testing may benefit patients with influenza or RSV.MethodsSamples from 180 children (< 18 years) and 375 adults tested using POCT between February and July 2018 were retested for 26 respiratory pathogens. Diagnosis, indication for POC testing, hospitalisation time, antimicrobial therapy and readmission or death within one month of testing were obtained from patient records.ResultsA valid indication for POC testing was established in 168 (93.3%) of children and 334 (89.1%) of adults. A positive POCT result significantly reduced antibiotic prescription and median hospitalisation time by 44.3 hours for adults and 14.2 hours for children, and significantly increased antiviral treatment in adults. Risk of readmission or death was not significantly altered by a positive result. Testing for 26 respiratory pathogens established that risk of coinfection is lower with increasing age and that POCT for adults should be restricted to the influenza and RSV season.ConclusionPositive POCT resulted in changed patient management for both children and adults, and was deemed safe. POCT for additional pathogens may be beneficial in children below 5 years of age and outside the influenza and RSV season.

Effectiveness of Adding a Mask Recommendation to Other Public Health Measures to Prevent SARS-CoV-2 Infection in Danish Mask Wearers : A Randomized Controlled Trial.

BACKGROUND: Observational evidence suggests that mask wearing mitigates transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is uncertain if this observed association arises through protection of uninfected wearers (protective effect), via reduced transmission from infected mask wearers (source control), or both. OBJECTIVE: To assess whether recommending surgical mask use outside the home reduces wearers' risk for SARS-CoV-2 infection in a setting where masks were uncommon and not among recommended public health measures. DESIGN: Randomized controlled trial (DANMASK-19 [Danish Study to Assess Face Masks for the Protection Against COVID-19 Infection]). (ClinicalTrials.gov: NCT04337541). SETTING: Denmark, April and May 2020. PARTICIPANTS: Adults spending more than 3 hours per day outside the home without occupational mask use. INTERVENTION: Encouragement to follow social distancing measures for coronavirus disease 2019, plus either no mask recommendation or a recommendation to wear a mask when outside the home among other persons together with a supply of 50 surgical masks and instructions for proper use. MEASUREMENTS: The primary outcome was SARS-CoV-2 infection in the mask wearer at 1 month by antibody testing, polymerase chain reaction (PCR), or hospital diagnosis. The secondary outcome was PCR positivity for other respiratory viruses. RESULTS: A total of 3030 participants were randomly assigned to the recommendation to wear masks, and 2994 were assigned to control; 4862 completed the study. Infection with SARS-CoV-2 occurred in 42 participants recommended masks (1.8%) and 53 control participants (2.1%). The between-group difference was -0.3 percentage point (95% CI, -1.2 to 0.4 percentage point; P = 0.38) (odds ratio, 0.82 [CI, 0.54 to 1.23]; P = 0.33). Multiple imputation accounting for loss to follow-up yielded similar results. Although the difference observed was not statistically significant, the 95% CIs are compatible with a 46% reduction to a 23% increase in infection. LIMITATION: Inconclusive results, missing data, variable adherence, patient-reported findings on home tests, no blinding, and no assessment of whether masks could decrease disease transmission from mask wearers to others. CONCLUSION: The recommendation to wear surgical masks to supplement other public health measures did not reduce the SARS-CoV-2 infection rate among wearers by more than 50% in a community with modest infection rates, some degree of social distancing, and uncommon general mask use. The data were compatible with lesser degrees of self-protection. PRIMARY FUNDING SOURCE: The Salling Foundations.