Infection with mpox virus via the genital mucosae increases shedding and transmission in the multimammate rat (Mastomys natalensis).

The 2022 mpox virus (MPXV) outbreak was sustained by human-to-human transmission; however, it is currently unclear which factors lead to sustained transmission of MPXV. Here we present Mastomys natalensis as a model for MPXV transmission after intraperitoneal, rectal, vaginal, aerosol and transdermal inoculation with an early 2022 human outbreak isolate (Clade IIb). Virus shedding and tissue replication were route dependent and occurred in the presence of self-resolving localized skin, lung, reproductive tract or rectal lesions. Mucosal inoculation via the rectal, vaginal and aerosol routes led to increased shedding, replication and a pro-inflammatory T cell profile compared with skin inoculation. Contact transmission was higher from rectally inoculated animals. This suggests that transmission might be sustained by increased susceptibility of the anal and genital mucosae for infection and subsequent virus release.

Filamentous fungus-produced human monoclonal antibody provides protection against SARS-CoV-2 in hamster and non-human primate models.

Monoclonal antibodies are an increasingly important tool for prophylaxis and treatment of acute virus infections like SARS-CoV-2 infection. However, their use is often restricted due to the time required for development, variable yields and high production costs, as well as the need for adaptation to newly emerging virus variants. Here we use the genetically modified filamentous fungus expression system Thermothelomyces heterothallica (C1), which has a naturally high biosynthesis capacity for secretory enzymes and other proteins, to produce a human monoclonal IgG1 antibody (HuMab 87G7) that neutralises the SARS-CoV-2 variants of concern (VOCs) Alpha, Beta, Gamma, Delta, and Omicron. Both the mammalian cell and C1 produced HuMab 87G7 broadly neutralise SARS-CoV-2 VOCs in vitro and also provide protection against VOC Omicron in hamsters. The C1 produced HuMab 87G7 is also able to protect against the Delta VOC in non-human primates. In summary, these findings show that the C1 expression system is a promising technology platform for the development of HuMabs in preventive and therapeutic medicine.

Concurrent Detection of a Papillomatous Lesion and Sequence Reads Corresponding to a Member of the Family Adintoviridae in a Bell's Hinge-Back Tortoise (Kinixys belliana).

An adult male Bell's hinge-back tortoise (Kinixys belliana) was admitted to a veterinary clinic due to a swelling in the oral cavity. Physical examination revealed an approximately 2.5 × 1.5 cm sized, irregularly shaped tissue mass with villiform projections extending from its surface located in the oropharyngeal cavity. An initial biopsy was performed, and the lesion was diagnosed as squamous papilloma. Swabs taken for virological examination tested negative with specific PCRs for papillomavirus and herpesvirus. Further analysis of the oropharyngeal mass via metagenomic sequencing revealed sequence reads corresponding to a member of the family Adintoviridae. The tissue mass was removed one week after the initial examination. The oral cavity remained unsuspicious in follow-up examinations performed after one, five and twenty weeks. However, a regrowth of the tissue was determined 23 months after the initial presentation. The resampled biopsy tested negative for sequence reads of Adintoviridae. Conclusively, this report presents the diagnostic testing and therapy of an oral cavity lesion of unknown origin. The significance of concurrent metagenomic determination of adintovirus sequence reads within the tissue lesion is discussed.

Pre-analytical properties of different respiratory viruses for PCR-based detection: Comparative analysis of sampling devices and sample stabilization solutions.

After the decline of the COVID-19 pandemic, health systems were challenged by the simultaneous prevalence of different respiratory viruses causing a wide overlap in symptoms. This increased the demand for multi-virus diagnostic tests which require suitable pre-analytical workflow solutions in order to receive valid diagnostic results. In this context, the effects of specimen storage duration and temperature on the RNA/DNA copy number stability of influenza A/B, RSV A/B, SARS-CoV-2 and adenovirus were examined for four commercially available transport swab systems and saliva collection devices. The respiratory viruses were more stable in the saliva collection devices than in the transport swab systems when stored at RT or 37 °C for up to 96 h. Moreover, no differences between viral nucleic acid stability of enveloped and non-enveloped viruses were observed. The infectivity of all enveloped viruses could be inactivated by the saliva collection device from PreAnalytiX. The Norgen saliva device completely inactivated influenza A/B, while RSV A/B were partially inactivated. The non-enveloped adenovirus was inactivated by a reduction factor of 10E+ 4 in both saliva collection devices. All respiratory viruses remained infectious in the transport swab systems. Two possible transport medium additives were tested which inactivated or strongly reduced viral replication of tested enveloped viruses but had no effect on the non-enveloped adenovirus. Finally the implementation of multi-target detection procedures involving a direct amplification approach was successfully tested by spike-in of all enveloped viruses simultaneously into transport swab systems. This fast and reproducible setup presents a valuable solution for future implementations in multi-virus testing strategies.

Empowerment group therapy for refugees with affective disorders: results of a multicenter randomized controlled trial.

BACKGROUND: Against the background of missing culturally sensitive mental health care services for refugees, we developed a group intervention (Empowerment) for refugees at level 3 within the stratified Stepped and Collaborative Care Model of the project Mental Health in Refugees and Asylum Seekers (MEHIRA). We aim to evaluate the effectiveness of the Empowerment group intervention with its focus on psychoeducation, stress management, and emotion regulation strategies in a culturally sensitive context for refugees with affective disorders compared to treatment-as-usual (TAU). METHOD: At level 3 of the MEHIRA project, 149 refugees and asylum seekers with clinically relevant depressive symptoms were randomized to the Empowerment group intervention or TAU. Treatment comprised 16 therapy sessions conducted over 12 weeks. Effects were measured with the Patient Health Questionnaire-9 (PHQ-9) and the Montgomery-Åsberg Depression Rating Scale (MÅDRS). Further scales included assessed emotional distress, self-efficacy, resilience, and quality of life. RESULTS: Intention-to-treat analyses show significant cross-level interactions on both self-rated depressive symptoms (PHQ-9; F(1,147) = 13.32, p < 0.001) and clinician-rated depressive symptoms (MÅDRS; F(1,147) = 6.91, p = 0.01), indicating an improvement in depressive symptoms from baseline to post-intervention in the treatment group compared to the control group. The effect sizes for both scales were moderate (d = 0.68, 95% CI 0.21-1.15 for PHQ-9 and d = 0.51, 95% CI 0.04-0.99 for MÅDRS). CONCLUSION: In the MEHIRA project comparing an SCCM approach versus TAU, the Empowerment group intervention at level 3 showed effectiveness for refugees with moderately severe depressive symptoms.

Shared sorrow, shared costs: cost-effectiveness analysis of the Empowerment group therapy approach to treat affective disorders in refugee populations.

BACKGROUND: Refugees and asylum seekers (RAS) in Germany need tailored and resource-oriented mental healthcare interventions. AIMS: To evaluate the cost-effectiveness of group psychotherapy for RAS with moderate depressive symptoms. METHOD: This is a post hoc cost-effectiveness analysis of Empowerment group psychotherapy that was embedded in a stratified stepped and collaborative care model (SCCM) from the multicentre randomised controlled MEHIRA trial. One hundred and forty-nine participants were randomly assigned to SCCM or treatment as usual (TAU) and underwent Empowerment (i.e. level 3 of the SCCM for adults) or TAU. Effects were measured with the nine-item Patient Health Questionnaire (PHQ-9) and quality adjusted life-years (QALY) post-intervention. Health service and intervention costs were measured. Incremental cost-effectiveness ratios (ICER) were estimated and net monetary benefit (NMB) regressions with 95% confidence intervals were performed. Cost-effectiveness was ascertained for different values of willingness to pay (WTP) using cost-effectiveness acceptability curves for probable scenarios. Trial registration number: NCT03109028 on ClinicalTrials.gov. RESULTS: Health service use costs were significantly lower for Empowerment than TAU after 1 year. Intervention costs were on average €409.6. Empowerment led to a significant change in PHQ-9 scores but not QALY. Bootstrapped mean ICER indicated cost-effectiveness according to PHQ-9 and varied considerably for QALY in the base case. NMB for a unit reduction in PHQ-9 score at WTP of €0 was €354.3 (€978.5 to -€269.9). Results were confirmed for different scenarios and varying WTP thresholds. CONCLUSIONS: The Empowerment intervention was cost-effective in refugees with moderate depressive symptoms regarding the clinical outcome and led to a reduction in direct healthcare consumption. Concerning QALYs, there was a lack of confidence that Empowerment differed from TAU.

Preclinical immunogenicity and protective efficacy of a SARS-CoV-2 RBD-based vaccine produced with the thermophilic filamentous fungal expression system Thermothelomyces heterothallica C1.

Introduction: The emergency use of vaccines has been the most efficient way to control the coronavirus disease 19 (COVID-19) pandemic. However, the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern has reduced the efficacy of currently used vaccines. The receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein is the main target for virus neutralizing (VN) antibodies. Methods: A SARS-CoV-2 RBD vaccine candidate was produced in the Thermothelomyces heterothallica (formerly, Myceliophthora thermophila) C1 protein expression system and coupled to a nanoparticle. Immunogenicity and efficacy of this vaccine candidate was tested using the Syrian golden hamster (Mesocricetus auratus) infection model. Results: One dose of 10-µg RBD vaccine based on SARS-CoV-2 Wuhan strain, coupled to a nanoparticle in combination with aluminum hydroxide as adjuvant, efficiently induced VN antibodies and reduced viral load and lung damage upon SARS-CoV-2 challenge infection. The VN antibodies neutralized SARS-CoV-2 variants of concern: D614G, Alpha, Beta, Gamma, and Delta. Discussion: Our results support the use of the Thermothelomyces heterothallica C1 protein expression system to produce recombinant vaccines against SARS-CoV-2 and other virus infections to help overcome limitations associated with the use of mammalian expression system.

First Report of Skunk Amdoparvovirus (Species Carnivore amdoparvovirus 4) in Europe in a Captive Striped Skunk (Mephitis mephitis).

Skunk amdoparvovirus (Carnivore amdoparvovirus 4, SKAV) is closely related to Aleutian mink disease virus (AMDV) and circulates primarily in striped skunks (Mephitis mephitis) in North America. SKAV poses a threat to mustelid species due to reported isolated infections of captive American mink (Neovison vison) in British Columbia, Canada. We detected SKAV in a captive striped skunk in a German zoo by metagenomic sequencing. The pathological findings are dominated by lymphoplasmacellular inflammation and reveal similarities to its relative Carnivore amdoparvovirus 1, the causative agent of Aleutian mink disease. Phylogenetic analysis of the whole genome demonstrated 94.80% nucleotide sequence identity to a sequence from Ontario, Canada. This study is the first case description of a SKAV infection outside of North America.

Evidence for a Novel Gammaherpesvirus as the Putative Agent of Malignant Catarrhal Fever Disease in Roan Antelopes (Hippotragus equinus).

Upon the sudden death of two captive roan antelopes (Hippotragus equinus) that had suffered from clinical signs reminiscent of malignant catarrhal fever (MCF) in a German zoo, next generation sequencing of organ samples provided evidence of the presence of a novel gammaherpesvirus species. It shares 82.40% nucleotide identity with its so far closest relative Alcelaphine herpesvirus 1 (AlHV-1) at the polymerase gene level. The main histopathological finding consisted of lympho-histiocytic vasculitis of the pituitary rete mirabile. The MCF-like clinical presentation and pathology, combined with the detection of a nucleotide sequence related to that of AlHV-1, indicates a spillover event of a novel member of the genus Macavirus of the Gammaherpesvirinae, probably from a contact species within the zoo. We propose the name Alcelaphine herpesvirus 3 (AlHV-3) for this newly identified virus.

Predicting treatment outcomes of the Empowerment group intervention for refugees with affective disorders: Findings from the MEHIRA project.

BACKGROUND: Research on outcome predictors in the field of transcultural treatment for refugees and asylum seekers (RAS) is scarce. We aimed to evaluate predictors of outcome of a group intervention (Empowerment) for RAS with affective disorders which was incorporated at level three of the stratified stepped-care model within the Mental Health in Refugees and Asylum Seekers (MEHIRA) project. METHODS: A predictor analysis was performed at level three of the MEHIRA project, where 149 refugees with moderate depressive symptoms were treated either with Empowerment or Treatment-as-usual (TAU). Outcome measures were depression severity as assessed by patient-rated Patient Health Questionnaire 9 (PHQ-9) and clinician-rated Montgomery Asberg Depression Rating Scale (MADRS). Regression models with change scores (T1-T0) of PHQ-9 and MADRS as dependent variables were fit. Predictor selection was a mixed-method approach combining testing of literature-based hypotheses and explorative hypothesis-generating analyses of multiple baseline variables. RESULTS: Intention-to-treat (ITT) analyses revealed significant linear relationships between change in PHQ-9 and baseline depression severity (ß = -0.35, t = -3.27, p = .002) and perceived self-efficacy (ß = -0.24, t = -2.26, p = .027) in the treatment (verum) condition. MADRS change scores were predicted by baseline depression severity (ß = -0.71, t = -8.65, p < .001) in the treatment (verum) condition. LIMITATIONS: Due to small cell numbers, single predictors could not be evaluated reliably. CONCLUSIONS: Severity of depression and self-efficacy at baseline were predictors of symptom improvement at level three (Empowerment) of the MEHIRA project. Comorbidity and trauma indicators did not predict outcomes in the treatment (verum) condition, pointing towards broad applicability of the Empowerment intervention in refugee populations.

Canine real-time detection of SARS-CoV-2 infections in the context of a mass screening event.

INTRODUCTION: Previous research demonstrated that medical scent detection dogs have the ability to distinguish SARS-CoV-2 positive from negative samples with high diagnostic accuracy. To deploy these dogs as a reliable screening method, it is mandatory to examine if canines maintain their high diagnostic accuracy in real-life screening settings. We conducted a study to evaluate the performance of medical scent detection dogs under real-life circumstances. METHODS: Eight dogs were trained to detect SARS-CoV-2 RT-qPCR-positive samples. Four concerts with a total of 2802 participants were held to evaluate canines' performance in screening individuals for SARS-CoV-2 infection. Sweat samples were taken from all participants and presented in a line-up setting. In addition, every participant had been tested with a SARS-CoV-2 specific rapid antigen test and a RT-qPCR and they provided information regarding age, sex, vaccination status and medical disease history. The participants' infection status was unknown at the time of canine testing. Safety measures such as mask wearing and distance keeping were ensured. RESULTS: The SARS-CoV-2 detection dogs achieved a diagnostic specificity of 99.93% (95% CI 99.74% to 99.99%) and a sensitivity of 81.58% (95% CI 66.58% to 90.78%), respectively. The overall rate of concordant results was 99.68%. The majority of the study population was vaccinated with varying vaccines and vaccination schemes, while several participants had chronic diseases and were under chronic medication. This did not influence dogs' decisions. CONCLUSION: Our results demonstrate that SARS-CoV-2 scent detection dogs achieved high diagnostic accuracy in a real-life scenario. The vaccination status, previous SARS-CoV-2 infection, chronic disease and medication of the participants did not influence the performance of the dogs in detecting the acute infection. This indicates that dogs provide a fast and reliable screening option for public events in which high-throughput screening is required.

Comparison of two antibody screening systems for SARS-CoV-2 antibody detection in recovered and vaccinated subjects - test performance and possible indicators for immunity.

BACKGROUND: Detection of seroconversion after SARS-CoV-2-infection or vaccination is relevant to discover subclinical cases and recognize patients with a possible immunity. OBJECTIVES: Test performance, effects of age, time-point of seroconversion and immune status regarding neutralizing antibodies (NAbs) and T-cell-reactivity were investigated. STUDY DESIGN: Two antibody assays (Viramed-Test for S/N-specific IgG, Roche-Test for N-specific IgA, -M, -G) were evaluated with classified samples. In total, 381 subjects aged 6-99 years, who had either recovered from the disease or had been vaccinated, were screened for SARS-CoV-2-specific antibodies. This screening was part of an open observational study with working adults. Additionally, children and adults were analyzed in a longitudinal COVID-19 study in schools. For immunity evaluation, virus neutralization tests and ELISpot tests were performed in a subgroup of subjects. RESULTS: Viramed revealed a slightly lower test performance than Roche, but test quality was equally well in samples from very young or very old donors. The time-point of seroconversion after the respective immunization detected by the two tests was not significantly different. N-specific antibodies, detected with Roche, highly correlated with NAbs in recovered subjects, whereas a positive Viramed-Test result was paralleled by a positive ELISpot result. CONCLUSION: Viramed-Test was not as sensitive as Roche-Test, but highly specific and beneficial to distinguish between recovered and vaccinated status. For both tests correlations with humoral and cellular immunity were found. Of note, the expected early detection of IgA and IgM by the Roche-Test did not prove to be an advantage over IgG testing by Viramed.

Effectiveness and cost-effectiveness for the treatment of depressive symptoms in refugees and asylum seekers: A multi-centred randomized controlled trial.

Background: Current evidence points towards a high prevalence of psychological distress in refugee populations, contrasting with a scarcity of resources and amplified by linguistic, institutional, financial, and cultural barriers. The objective of the study is to investigate the overall effectiveness and cost-effectiveness of a Stepped Care and Collaborative Model (SCCM) at reducing depressive symptoms in refugees, compared with the overall routine care practices within Germany's mental healthcare system (treatment-as-usual, TAU). Methods: A multicentre, clinician-blinded, randomised, controlled trial was conducted across seven university sites in Germany. Asylum seekers and refugees with relevant depressive symptoms with a Patient Health Questionnaires score of ≥ 5 and a Refugee Health Screener score of ≥ 12. Participants were randomly allocated to one of two treatment arms (SCCM or TAU) for an intervention period of three months between April 2018 and March 2020. In the SCCM, participants were allocated to interventions tailored to their symptom severity, including watchful waiting, peer-to-peer- or smartphone intervention, psychological group therapies or mental health expert treatment. The primary endpoint was defined as the change in depressive symptoms (Patient Health Questionnaire-9, PHQ-9) after 12 weeks. The secondary outcome was the change in Montgomery Åsberg Depression Rating Scale (MADRS) from baseline to post-intervention. Findings: The intention-to-treat sample included 584 participants who were randomized to the SCCM (n= 294) or TAU (n=290). Using a mixed-effects general linear model with time, and the interaction of time by randomisation group as fixed effects and study site as random effect, we found significant effects for time (p < .001) and time by group interaction (p < .05) for intention-to-treat and per-protocol analysis. Estimated marginal means of the PHQ-9 scores after 12 weeks were significantly lower in SCCM than in TAU (for intention-to-treat: PHQ-9 mean difference at T1 1.30, 95% CI 1.12 to 1.48, p < .001; Cohen's d=.23; baseline-adjusted PHQ-9 mean difference at T1 0.57, 95% CI 0.40 to 0.74, p < .001). Cost-effectiveness and net monetary benefit analyses provided evidence of cost-effectiveness for the primary outcome and quality-adjusted life years. Robustness of results were confirmed by sensitivity analyses. Interpretation: The SSCM resulted in a more effective and cost-effective reduction of depressive symptoms compared with TAU. Findings suggest a suitable model to provide mental health services in circumstances where resources are limited, particularly in the context of forced migration and pandemics. Funding: This project is funded by the Innovationsfond and German Ministry of Health [grant number 01VSF16061]. The present trial is registered under Clinical-Trials.gov under the registration number: NCT03109028. https://clinicaltrials.gov/ct2/show/NCT03109028.

SARS-CoV-2 Omicron variant causes mild pathology in the upper and lower respiratory tract of hamsters.

Since its discovery in 2019, multiple variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been identified. This study investigates virus spread and associated pathology in the upper and lower respiratory tracts of Syrian golden hamsters at 4 days post intranasal SARS-CoV-2 Omicron infection, in comparison to infection with variants of concern (VOCs) Gamma and Delta as well as ancestral strain 614 G. Pathological changes in the upper and lower respiratory tract of VOC Omicron infected hamsters are milder than those caused by other investigated strains. VOC Omicron infection causes a mild rhinitis with little involvement of the olfactory epithelium and minimal lesions in the lung, with frequent sparing of the alveolar compartment. Similarly, viral antigen, RNA and infectious virus titers are lower in respiratory tissues of VOC Omicron infected hamsters. These findings demonstrate that the variant has a decreased pathogenicity for the upper and lower respiratory tract of hamsters.

An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants of concern.

The ongoing evolution of SARS-CoV-2 has resulted in the emergence of Omicron, which displays notable immune escape potential through mutations at key antigenic sites on the spike protein. Many of these mutations localize to the spike protein ACE2 receptor binding domain, annulling the neutralizing activity of therapeutic antibodies that were effective against other variants of concern (VOCs) earlier in the pandemic. Here, we identified a receptor-blocking human monoclonal antibody, 87G7, that retained potent in vitro neutralizing activity against SARS-CoV-2 variants including the Alpha, Beta, Gamma, Delta, and Omicron (BA.1/BA.2) VOCs. Using cryo-electron microscopy and site-directed mutagenesis experiments, we showed that 87G7 targets a patch of hydrophobic residues in the ACE2-binding site that are highly conserved in SARS-CoV-2 variants, explaining its broad neutralization capacity. 87G7 protected mice and hamsters prophylactically against challenge with all current SARS-CoV-2 VOCs and showed therapeutic activity against SARS-CoV-2 challenge in both animal models. Our findings demonstrate that 87G7 holds promise as a prophylactic or therapeutic agent for COVID-19 that is more resilient to SARS-CoV-2 antigenic diversity.

Lifetime Prevalence of Victimization and Perpetration as Related to Men's Health: Clinical Insights.

Violence is a known risk factor for health problems. In this epidemiological study across 5,385 male patients, we investigate the prevalence of perpetrated violence, exposure to violence, their overlap and the relationship between violence, mental, and psychosomatic health, as well as adverse health behaviors, such as self-harming behavior and the consumption of drugs. Participants completed an anonymous questionnaire addressing violence experience (i.e., both expose and perpetration), age of victimization/perpetration, frequency, and perceived severity of violence exposure. We considered physical, psychological as well as sexual violence. Information on health status and adverse health behaviors complemented the data. Results showed that 48.4% of the sample reported having experienced violence (perpetration, victimization, or both). The victim-perpetrator overlap formed the largest group, in which the incidence of having experienced multiple types of violence was significantly higher compared to victims and perpetrators. The age-crime curve flattened more slowly with increasing age in this group. Although the perceived severity of exposure to violence is lower in the overlap group, its health status and adverse health behaviors were worse. Interventions should focus on this group since they constitute a burden for the healthcare system.

Combined Prospective Seroconversion and PCR Data of Selected Cohorts Indicate a High Rate of Subclinical SARS-CoV-2 Infections-an Open Observational Study in Lower Saxony, Germany.

Despite lockdown measures, intense symptom-based PCR, and antigen testing, the SARS-CoV-2 pandemic spread further. In this open observational study conducted in Lower Saxony, Germany, voluntary SARS-CoV-2 PCR tests were performed from April 2020 until June 2021, supported by serum antibody testing to prove whether PCR testing in subjects with none or few symptoms of COVID-19 is a suitable tool to manage the pandemic. In different mobile stations, 4,817 subjects from three different working fields participated in the PCR testing. Serum antibody screening using the SARS-CoV-2 ViraChip IgG (Viramed, Germany) and the Elecsys Anti-SARS-CoV-2 assay (Roche, Germany) was performed alongside virus neutralization testing. Subjects were questioned regarding comorbidities and COVID-19 symptoms. Fifty-one subjects with acute SARS-CoV-2 infection were detected of which 31 subjects did not show any symptoms possibly characteristic for COVID-19. An additional 37 subjects reported a previous SARS-CoV-2 infection (total prevalence 1.82%). Seroconversion was discovered in 58 subjects with known SARS-CoV-2 infection and in 58 subjects that never had a positive PCR test. The latter had a significantly lower Charlson Comorbidity Index, and one third of them were asymptomatic. In 50% of all seroconverted subjects, neutralizing serum antibodies (NAbs) were detectable in parallel to N/S1 (n = 16) or N/S1/S2 antigen specific antibodies (n = 40) against SARS-CoV-2. NAb titers decreased within 100 days after PCR-confirmed SARS-CoV-2 acute infection by at least 2.5-fold. A relatively high rate of subclinical SARS-CoV-2 infections may contribute to the spread of SARS-CoV-2, suggesting that in addition to other intervention strategies, systematic screening of asymptomatic persons by PCR testing may significantly enable better pandemic control. IMPORTANCE Within this open observational study, repeated PCR (n > 4,700) and antibody screening (n > 1,600) tests were offered in three different working fields. The study identified 51 subjects with acute SARS-CoV-2 infection and 37 subjects reported to have had a positive PCR test taken externally. Thirty-one of the 51 subjects did not display any symptoms prior to testing. In addition, 58 subjects without PCR-confirmed SARS-CoV-2 infection were identified by seroconversion. Subjects, that had undergone SARS-CoV-2 infection without having noticed, more often had a low grade of immunization with no NAbs, but may have relevantly contributed to the spread of the pandemic. Based on these results, we suggest that both regular PCR and rapid test screening of symptomatic and asymptomatic individuals, specifically within groups or workplaces identifiable as having close quarter contact, thus increased infection transference risk, is necessary to better assess and therefore reduce the spread of a pandemic virus.

Infections with highly pathogenic avian influenza A virus (HPAIV) H5N8 in harbor seals at the German North Sea coast, 2021.

In brain tissue of three harbor seals of the German North Sea coast, high virus loads of highly pathogenic avian influenza virus (HPAIV) H5N8 were detected. Identification of different virus variants indicates high exposure to HPAIV circulating in wild birds, but there is no evidence for H5 specific antibodies in healthy seals. Replication of avian viruses in seals may allow HPAIV to acquire mutations needed to adapt to mammalian hosts as shown by PB2 627K variants detected in these cases.

Signs of immunosenescence correlate with poor outcome of mRNA COVID-19 vaccination in older adults.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is effective in preventing COVID-19 hospitalization and fatal outcome. However, several studies indicated that there is reduced vaccine effectiveness among older individuals, which is correlated with their general health status1,2. How and to what extent age-related immunological defects are responsible for the suboptimal vaccine responses observed in older individuals receiving SARS-CoV-2 messenger RNA vaccine, is unclear and not fully investigated1,3-5. In this observational study, we investigated adaptive immune responses in adults of various ages (22-99 years old) receiving 2 doses of the BNT162b2 mRNA vaccine. Vaccine-induced Spike-specific antibody, and T and memory B cell responses decreased with increasing age. These responses positively correlated with the percentages of peripheral naïve CD4+ and CD8+ T cells and negatively with CD8+ T cells expressing signs of immunosenescence. Older adults displayed a preferred T cell response to the S2 region of the Spike protein, which is relatively conserved and a target for cross-reactive T cells induced by human 'common cold' coronaviruses. Memory T cell responses to influenza virus were not affected by age-related changes, nor the SARS-CoV-2-specific response induced by infection. Collectively, we identified signs of immunosenescence correlating with the outcome of vaccination against a new viral antigen to which older adults are immunologically naïve. This knowledge is important for the management of COVID-19 infections in older adults.