Correction: Broadly directed SARS-CoV-2-specific CD4+ T cell response includes frequently detected peptide specificities within the membrane and nucleoprotein in patients with acute and resolved COVID-19.

[This corrects the article DOI: 10.1371/journal.ppat.1009842.].

Gentamicin combination treatment is associated with lower mortality in patients with invasive listeriosis: a retrospective analysis.

PURPOSE: Listeria monocytogenes causes severe bacterial infections with the highest mortality rate among foodborne pathogens in Europe. Combination treatment with ampicillin and gentamicin is recommended for invasive manifestations. However, evidence to support this treatment approach remains limited due to a lack of randomised controlled trials. To explore this critical issue further, we conducted this retrospective, single-center study. METHODS: We identified all patients hospitalized with invasive listeriosis at the University Medical Center Hamburg-Eppendorf between 2009 and 2020 and analyzed the effect of gentamicin combination treatment versus monotherapy on 90-day mortality. RESULTS: In total, 36 patients with invasive listeriosis were included, of which 21 patients received gentamicin combination treatment and 15 received monotherapy. The mean age-adjusted Charlson Comorbidity Index (aaCCI) value was lower in the gentamicin combination treatment group (5.4 vs. 7.4). Neurolisteriosis was more common in the gentamicin group (81% vs. 20%). The 90-day mortality was with significantly lower in the gentamicin combination treatment group (10%) compared to the monotherapy group (60%). Multivariable cox regression analysis, adjusted for a propensity score computed based on neurolisteriosis, aaCCI and sex, revealed a significantly reduced hazard ratio of 0.07 (95% CI: 0.01-0.53, p = 0.01) for 90-day mortality for the gentamicin combination treatment. CONCLUSION: This retrospective study highlights the benefit of gentamicin combination treatment in reducing the 90-day mortality rate among patients with invasive listeriosis. The high prevalence of monotherapy in this study cohort raises concerns about the adequacy of antibiotic therapy in clinical practice.

Broadly directed SARS-CoV-2-specific CD4+ T cell response includes frequently detected peptide specificities within the membrane and nucleoprotein in patients with acute and resolved COVID-19.

The aim of this study was to define the breadth and specificity of dominant SARS-CoV-2-specific T cell epitopes using a comprehensive set of 135 overlapping 15-mer peptides covering the SARS-CoV-2 envelope (E), membrane (M) and nucleoprotein (N) in a cohort of 34 individuals with acute (n = 10) and resolved (n = 24) COVID-19. Following short-term virus-specific in vitro cultivation, the single peptide-specific CD4+ T cell response of each patient was screened using enzyme linked immuno spot assay (ELISpot) and confirmed by single-peptide intracellular cytokine staining (ICS) for interferon-γ (IFN-γ) production. 97% (n = 33) of patients elicited one or more N, M or E-specific CD4+ T cell responses and each patient targeted on average 21.7 (range 0-79) peptide specificities. Overall, we identified 10 N, M or E-specific peptides that showed a response frequency of more than 36% and five of them showed high binding affinity to multiple HLA class II binders in subsequent in vitro HLA binding assays. Three peptides elicited CD4+ T cell responses in more than 55% of all patients, namely Mem_P30 (aa146-160), Mem_P36 (aa176-190), both located within the M protein, and Ncl_P18 (aa86-100) located within the N protein. These peptides were further defined in terms of length and HLA restriction. Based on this epitope and restriction data we developed a novel DRB*11 tetramer (Mem_aa145-164) and examined the ex vivo phenotype of SARS-CoV-2-specific CD4+ T cells in one patient. This detailed characterization of single T cell peptide responses demonstrates that SARS-CoV-2 infection universally primes a broad T cell response directed against multiple specificities located within the N, M and E structural protein.

Vagus nerve inflammation contributes to dysautonomia in COVID-19.

Dysautonomia has substantially impacted acute COVID-19 severity as well as symptom burden after recovery from COVID-19 (long COVID), yet the underlying causes remain unknown. Here, we hypothesized that vagus nerves are affected in COVID-19 which might contribute to autonomic dysfunction. We performed a histopathological characterization of postmortem vagus nerves from COVID-19 patients and controls, and detected SARS-CoV-2 RNA together with inflammatory cell infiltration composed primarily of monocytes. Furthermore, we performed RNA sequencing which revealed a strong inflammatory response of neurons, endothelial cells, and Schwann cells which correlated with SARS-CoV-2 RNA load. Lastly, we screened a clinical cohort of 323 patients to detect a clinical phenotype of vagus nerve affection and found a decreased respiratory rate in non-survivors of critical COVID-19. Our data suggest that SARS-CoV-2 induces vagus nerve inflammation followed by autonomic dysfunction which contributes to critical disease courses and might contribute to dysautonomia observed in long COVID.

Analysis of the humoral and cellular response after the third COVID-19 vaccination in patients with autoimmune hepatitis.

BACKGROUND & AIMS: To explore the humoral and T-cell response to the third COVID-19 vaccination in autoimmune hepatitis (AIH). METHODS: Anti-SARS-CoV-2 antibody titers were prospectively determined in 81 AIH patients and 53 healthy age- and sex-matched controls >7 days (median 35) after the first COVID-19 booster vaccination. The spike-specific T-cell response was assessed using an activation-induced marker assay (AIM) in a subset of patients. RESULTS: Median antibody levels were significantly lower in AIH compared to controls (10 908 vs. 25 000 AU/ml, p < .001), especially in AIH patients treated with MMF (N = 14, 4542 AU/ml, p = .004) or steroids (N = 27, 7326 AU/ml, p = .020). Also, 48% of AIH patients had antibody titers below the 10% percentile of the healthy controls (9194 AU/ml, p < .001). AIH patients had a high risk of failing to develop a spike-specific T-cell response (15/34 (44%) vs. 2/16 (12%), p = .05) and showed overall lower frequencies of spike-specific CD4 + T cells (median: 0.074% vs 0.283; p = .01) after the booster vaccination compared to healthy individuals. In 34/81 patients, antibody titers before and after booster vaccination were available. In this subgroup, all patients but especially those without detectable/low antibodies titers (<100 AU/ml) after the second vaccination (N = 11/34) showed a strong, 148-fold increase. CONCLUSION: A third COVID-19 vaccination efficiently boosts antibody levels and T-cell responses in AIH patients and even seroconversion in patients with the absent immune response after two vaccinations, but to a lower level compared to controls. Therefore, we suggest routinely assessing antibody levels in AIH patients and offering additional booster vaccinations to those with suboptimal responses.

History of cerebrovascular disease but not dementia increases the risk for secondary vascular events during SARS-CoV-2 infection with presumed Omicron variant: a retrospective observational study.

BACKGROUND AND PURPOSE: This study aimed to investigate if pre-existing neurological conditions, such as dementia and a history of cerebrovascular disease, increase the risk of severe outcomes including death, intensive care unit (ICU) admission and vascular events in patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in 2022, when Omicron was the predominant variant. METHODS: A retrospective analysis was conducted of all patients with SARS-CoV-2 infection, confirmed by polymerase chain reaction test, admitted to the University Medical Center Hamburg-Eppendorf from 20 December 2021 until 15 August 2022. In all, 1249 patients were included in the study. In-hospital mortality was 3.8% and the ICU admission rate was 9.9%. Ninety-three patients with chronic cerebrovascular disease and 36 patients with pre-existing all-cause dementia were identified and propensity score matching by age, sex, comorbidities, vaccination status and dexamethasone treatment was performed in a 1:4 ratio with patients without the respective precondition using nearest neighbor matching. RESULTS: Analysis revealed that neither pre-existing cerebrovascular disease nor all-cause dementia increased mortality or the risk for ICU admission. All-cause dementia in the medical history also had no effect on vascular complications under investigation. In contrast, an increased odds ratio for both pulmonary artery embolism and secondary cerebrovascular events was observed in patients with pre-existing chronic cerebrovascular disease and myocardial infarction in the medical history. CONCLUSION: These findings suggest that patients with pre-existing cerebrovascular disease and myocardial infarction in their medical history may be particularly susceptible to vascular complications following SARS-CoV-2 infection with presumed Omicron variant.

Tecovirimat for the treatment of severe Mpox in Germany.

BACKGROUND: In May 2022, a multi-national mpox outbreak was reported in several non-endemic countries. The only licensed treatment for mpox in the European Union is the orally available small molecule tecovirimat, which in Orthopox viruses inhibits the function of a major envelope protein required for the production of extracellular virus. METHODS: We identified presumably all patients with mpox that were treated with tecovirimat in Germany between the onset of the outbreak in May 2022 and March 2023 and obtained demographic and clinical characteristics by standardized case report forms. RESULTS: A total of twelve patients with mpox were treated with tecovirimat in Germany in the study period. All but one patient identified as men who have sex with men (MSM) who were most likely infected with mpox virus (MPXV) through sexual contact. Eight of them were people living with HIV (PLWH), one of whom was newly diagnosed with HIV at the time of mpox, and four had CD4+ counts below 200/µl. Criteria for treatment with tecovirimat included severe immunosuppression, severe generalized and/or protracted symptoms, a high or increasing number of lesions, and the type and location of lesions (e.g., facial or oral soft tissue involvement, imminent epiglottitis, or tonsillar swelling). Patients were treated with tecovirimat for between six and 28 days. Therapy was generally well-tolerated, and all patients showed clinical resolution. CONCLUSIONS: In this cohort of twelve patients with severe mpox, treatment with tecovirimat was well tolerated and all individuals showed clinical improvement.

Mini-laparoscopy as a diagnostic tool for abdominal tuberculosis: a retrospective series of 29 cases.

OBJECTIVES: Abdominal tuberculosis (TB) is a "great mimic," and diagnosis remains challenging even for experienced clinicians. While mini-laparoscopy has already been demonstrated to be an efficient diagnostic tool for a variety of diseases, we aimed to demonstrate the feasibility of this technique in diagnosing abdominal TB. METHODS: We retrospectively included patients who underwent mini-laparoscopy at the University Medical Center Hamburg-Eppendorf between April 2010 and January 2022 for suspected abdominal TB. Demographic, clinical, and laboratory data, radiological findings as well as macroscopic, histopathologic, and microbiologic results were analyzed by chart review. RESULTS: Out of 49 consecutive patients who underwent mini-laparoscopy for suspected abdominal TB, the diagnosis was subsequently confirmed in 29 patients (59%). Among those, the median age was 30 years (range 18-86 years) and the majority were male (n = 22, 76%). Microbiological diagnosis was established in a total of 16 patients. The remaining patients were diagnosed with abdominal TB either by histopathological detection of caseating granulomas (n = 3), or clinically by a combination of typical presentation, mini-laparoscopic findings, and good response to anti-tuberculous treatment (n = 10). Bleeding from the respective puncture site occurred in 19 patients (66%) and either resolved spontaneously or was arrested with argon plasma coagulation alone (n = 10) or in combination with fibrin glue (n = 1). Minor intestinal perforation occurred in 2 patients and was treated conservatively. CONCLUSIONS: Mini-laparoscopy is a useful and safe modality for the diagnosis of abdominal TB.

Predictors of somatic symptom burden in healthcare professionals during the COVID-19 pandemic: an 8-week follow-up study.

BACKGROUND: Literature investigating the impact of COVID-19 on healthcare professionals barely addresses predictors of somatic symptom burden during the COVID-19 pandemic. AIMS: As biopsychosocial models propose that not only the disease but also sociodemographic and psychosocial factors contribute to the development and maintenance of symptoms, this study investigates the predictive value of these factors for bothersome somatic symptoms in SARS-CoV-2 negative healthcare professionals. METHODS: German healthcare professionals were assessed with self-rating questionnaires and underwent SARS-CoV-2 IgG antibody tests at baseline and 8 weeks later between April and August 2020. Differences in psychosocial variables between the time points were analyzed and regression analyses were performed to predict somatic symptoms at follow-up. RESULTS: 1185 seronegative healthcare professionals completed both assessments. Previous somatic symptom burden, higher levels of anxiety, being a nurse, younger age, higher psychological symptom burden, lower efficiency, and higher fatigability at baseline predicted somatic symptom burden at follow-up. Comparisons between baseline and follow-up showed a significant improvement in psychological impairment and deterioration of physical exhaustion. CONCLUSIONS: Our study applies a biopsychosocial perspective to bothersome somatic symptoms during the COVID-19 pandemic and contributes to the identification of potential risk factors as a starting point for future interventions that could support the handling of symptoms.

Clinical efficacy and in vitro neutralization capacity of monoclonal antibodies for severe acute respiratory syndrome coronavirus 2 delta and omicron variants.

We aimed to provide in vitro data on the neutralization capacity of different monoclonal antibody (mAb) preparations against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delta and omicron variant, respectively, and describe the in vivo RNA kinetics of coronavirus disease 2019 (COVID-19) patients treated with the respective mAbs. Virus neutralization assays were performed to assess the neutralizing effect of the mAb formulations casirivimab/imdevimab and sotrovimab on the SARS-CoV-2 delta and omicron variant. Additionally, respiratory tract SARS-CoV-2 RNA kinetics are provided for 25 COVID-19 patients infected with either delta variant (n = 18) or omicron variant (n = 7) treated with the respective mAb formulations during their hospital stay. In the virus neutralization assay, sotrovimab exhibits neutralizing capacity at therapeutically achievable concentrations against the SARS-CoV-2 delta and omicron variant. In contrast, casivirimab/imdevimab had neutralizing capacity against the delta variant but failed neutralization against the omicron variant except for a very high concentration above the currently recommended therapeutic dosage. In patients with delta variant infections treated with casivirimab/imdevimab, we observed a rapid decrease of respiratory viral RNA at day 3 after mAb therapy. In contrast, no such prompt decline was observed in patients with delta variant or omicron variant infections receiving sotrovimab.

[Attitudes Towards COVID-19 Vaccination Compared to Influenza Vaccination Among Hospital Staff]. / Einstellungen gegenüber der COVID-19-Impfung im Vergleich zur Grippeschutzimpfung bei Krankenhauspersonal.

This cross-sectional study compared hospital staff who had received influenza or COVID-19 vaccination or who had refused COVID-19 vaccination in terms of attitudes towards each vaccination, uptake of influenza vaccination and reasons for refusing COVID-19 vaccination. COVID-19 vaccine refusers rated the risk of infection for themselves and in general and the effectiveness of the vaccination lowest and the vaccination risk highest compared to the other two groups. They also reported the lowest past uptake of influenza vaccination. Perceived pressure to vaccinate proved to be a relevant barrier. Future vaccination campaigns should maintain a balance between information on vaccines, the need for vaccination, and voluntary uptake.

Heatwave-associated Vibrio infections in Germany, 2018 and 2019.

BackgroundVibrio spp. are aquatic bacteria that prefer warm seawater with moderate salinity. In humans, they can cause gastroenteritis, wound infections, and ear infections. During the summers of 2018 and 2019, unprecedented high sea surface temperatures were recorded in the German Baltic Sea.AimWe aimed to describe the clinical course and microbiological characteristics of Vibrio infections in Germany in 2018 and 2019.MethodsWe performed an observational retrospective multi-centre cohort study of patients diagnosed with domestically-acquired Vibrio infections in Germany in 2018 and 2019. Demographic, clinical, and microbiological data were assessed, and isolates were subjected to whole genome sequencing and antimicrobial susceptibility testing.ResultsOf the 63 patients with Vibrio infections, most contracted the virus between June and September, primarily in the Baltic Sea: 44 (70%) were male and the median age was 65 years (range: 2-93 years). Thirty-eight patients presented with wound infections, 16 with ear infections, six with gastroenteritis, two with pneumonia (after seawater aspiration) and one with primary septicaemia. The majority of infections were attributed to V. cholerae (non-O1/non-O139) (n = 30; 48%) or V. vulnificus (n = 22; 38%). Phylogenetic analyses of 12 available isolates showed clusters of three identical strains of V. vulnificus, which caused wound infections, suggesting that some clonal lines can spread across the Baltic Sea.ConclusionsDuring the summers of 2018 and 2019, severe heatwaves facilitated increased numbers of Vibrio infections in Germany. Since climate change is likely to favour the proliferation of these bacteria, a further increase in Vibrio-associated diseases is expected.

[Mild COVID-19 disease in healthcare workers at a German university clinic : The "first wave" at the University Medical Center Hamburg-Eppendorf]. / Milde COVID-19-Verläufe bei Mitarbeitenden einer Universitätsklinik : Die "erste Welle" am Universitätsklinikum Hamburg-Eppendorf.

BACKGROUND: Healthcare workers are among the most exposed and potentially most threatened populations of the ongoing COVID-19 pandemic. Despite some reports on numbers of infections with SARS-CoV­2 in German healthcare workers, the courses of their clinical presentation when affected by COVID-19 are not well described. OBJECTIVE: In this contribution, characteristics and progressions of infected cases among healthcare workers at the University Medical Center Hamburg-Eppendorf during the first wave of the COVID-19 pandemic will be presented. METHODS: Between 1 July and 28 July 2020, 67 healthcare workers, who previously tested positive for SARS-CoV­2 via PCR, were invited via E­mail to participate in an anonymous online questionnaire; 39 persons participated. RESULTS: Participants (58%) were mostly ≤ 39 years old (64%) and female (70%). Most healthcare workers were involved in direct patient management (85%), including contact with SARS-CoV­2 positive patients (62%). All participants reported acute symptoms with a median duration of 19 days. The most frequent symptoms were fatigue (85%), anosmia (67%), cough (64%), headache (62%), and shortness of breath (51%). The disease course was mostly mild with low admission rates (5%). Ongoing symptoms lasting more than four weeks post-symptom-onset, particularly anosmia, fatigue, and shortness of breath, were reported by 38%. This group more frequently had pre-existing conditions (53% vs. 12%, p = 0.010), specifically hypertension (27% vs. 4%, p = 0.062). DISCUSSION: Healthcare workers reported mostly mild courses of COVID-19 despite increased contact with SARS-CoV-2 patients. However, some reported persistent symptoms months after infection.

[Non-cholera Vibrio species - currently still rare but growing danger of infection in the North Sea and the Baltic Sea]. / Nicht-Cholera-Vibrionen ­ derzeit noch seltene, aber wachsende Infektionsgefahr in Nord- und Ostsee.

BACKGROUND: The abundance of non-cholera Vibrio spp. in the aquatic environment shows a positive correlation with water temperatures. Therefore, climate change has an important impact on the epidemiology of human infections with these pathogens. In recent years large outbreaks have been repeatedly observed during the summer months in temperate climate zones. OBJECTIVE: To inform medical professionals about the potentially life-threatening diseases caused by non-cholera Vibrio spp. MATERIAL AND METHODS: Review of the current literature on infections with non-cholera Vibrio spp. in general and on the epidemiological situation in Germany in particular. RESULTS: Non-cholera Vibrio spp. predominantly cause wound and ear infections after contact with contaminated seawater and gastroenteritis after consumption of undercooked seafood. As there have not been mandatory notification systems for these pathogens in Germany up to March 2020, a high number of unreported cases must be assumed. Immunosuppressed and chronically ill patients have a much higher risk for severe courses of diseases. If an infection with non-cholera Vibrio spp. is suspected anti-infective treatment should be promptly initiated and surgical cleansing is often necessary for wound and soft tissue infections. CONCLUSION: Due to the ongoing global warming an increased incidence of human infections with non-cholera Vibrio spp. must be expected in the future. Medical professionals should be aware of these bacterial pathogens and the potentially life-threatening infections in order to enable timely diagnostics and treatment.

Wound infection with Vibrio harveyi following a traumatic leg amputation after a motorboat propeller injury in Mallorca, Spain: a case report and review of literature.

BACKGROUND: Vibrio spp. are aquatic bacteria that are ubiquitous in warm estuarine and marine environments, of which 12 species are currently known to cause infections in humans. So far, only five human infections with V. harveyi have been reported. CASE PRESENTATION: A 26-year old patient was transferred to our center by inter-hospital air transfer from Mallorca, Spain. Seven days before, he had suffered a complete amputation injury of his left lower leg combined with an open, multi-fragment, distal femur fracture after he had been struck by the propeller of a passing motorboat while snorkeling in the Mediterranean Sea. On admission he was febrile; laboratory studies showed markedly elevated inflammatory parameters and antibiotic treatment with ampicillin/sulbactam was initiated. Physical examination showed a tender and erythematous amputation stump, so surgical revision was performed and confirmed a putrid infection with necrosis of the subcutaneous tissue and the muscles. Tissue cultures subsequently grew V. harveyi with a minimal inhibitory concentration (MIC) of 16 mg/L for ampicillin, and antibiotic treatment was switched to ceftriaxone and ciprofloxacin. Throughout the following days, the patient repeatedly had to undergo surgical debridement but eventually the infection could be controlled, and he was discharged. CONCLUSIONS: We report the first human infection with V. harveyi acquired in Spain and the second infection acquired in the Mediterranean Sea. This case suggests that physicians and microbiologists should be aware of the possibility of wound infections caused by Vibrio spp. acquired in the ocean environment, especially during hot summer months. Since Vibrio spp. preferentially grow at water temperatures above 18 °C, global warming is responsible for an abundance of these bacteria in coastal waters. This will likely lead to a worldwide increase in reports of Vibrio-associated diseases in the future.

Epidemiology, clinical and laboratory features of 24 consecutive cases of leptospirosis at a German infectious disease center.

To determine epidemiological, clinical and laboratory characteristics of leptospirosis, 24 consecutive patients diagnosed with the infection between 2011 and 2017 at the University Medical Center Hamburg-Eppendorf were retrospectively analyzed. The majority of patients were male travelers who returned from Southeast Asia and had a history of freshwater-associated activities. Considering the lack of discriminatory clinical or clinical chemistry parameters, leptospirosis should be regarded as differential diagnosis in any patient with acute febrile illness, especially with a history of travel to tropical and subtropical regions or freshwater exposure.