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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.

Coronavirus disease 2019 (COVID-19) which is caused by the novel SARS-CoV-2 virus is a severe flu-like illness which is associated with hyperinflammation and immune dysfunction. The virus induces a strong T and B cell response but little is known about the immune pathology of this viral infection. Acute malaria also causes acute clinical illness and is characterized by hyperinflammation due to the strong production of pro-inflammatory cytokines and a massive activation of T cells. In malaria, T cells express a variety of co-inhibitory receptors which might be a consequence of their activation but also might limit their overwhelming function. Thus, T cells are implicated in protection as well as in pathology. The outcome of malaria is thought to be a consequence of the balance between co-activation and co-inhibition of T cells. Following the hypothesis that T cells in COVID-19 might have a similar, dual function, we comprehensively characterized the differentiation (CCR7, CD45RO) and activation status (HLA-DR, CD38, CD69, CD226), the co-expression of co-inhibitory molecules (PD1, TIM-3, LAG-3, BTLA, TIGIT), as well as the expression pattern of the transcription factors T-bet and eomes of CD8 and CD4 T cells of PBMC of = 20 SARS-CoV-2 patients compared to = 10 infected patients and = 13 healthy controls. Overall, acute COVID-19 and malaria infection resulted in a comparably elevated activation and altered differentiation status of the CD8 and CD4 T cell populations. T effector cells of COVID-19 and malaria patients showed higher frequencies of the inhibitory receptors T-cell immunoglobulin mucin-3 (TIM-3) and Lymphocyte-activation gene-3 (LAG-3) which was linked to increased activation levels and an upregulation of the transcription factors T-bet and eomes. COVID-19 patients with a more severe disease course showed higher levels of LAG-3 and TIM-3 than patients with a mild disease course. During recovery, a rapid normalization of these inhibitory receptors could be observed. In summary, comparing the expression of different co-inhibitory molecules in CD8 and CD4 T cells in COVID-19 vs. malaria, there is a transient increase of the expression of certain inhibitory receptors like LAG-3 and TIM-3 in COVID-19 in the overall context of acute immune activation.

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.

While several studies have described the clinical course of patients with coronavirus disease 2019 (COVID-19), direct comparisons with patients with seasonal influenza are scarce. We compared 166 patients with COVID-19 diagnosed between February 27 and June 14, 2020, and 255 patients with seasonal influenza diagnosed during the 2017–18 season at the same hospital to describe common features and differences in clinical characteristics and course of disease. Patients with COVID-19 were younger (median age [IQR], 59 [45–71] vs 66 [52–77]; P < 0001) and had fewer comorbidities at baseline with a lower mean overall age-adjusted Charlson Comorbidity Index (mean [SD], 3.0 [2.6] vs 4.0 [2.7]; P < 0.001) than patients with seasonal influenza. COVID-19 patients had a longer duration of hospitalization (mean [SD], 25.9 days [26.6 days] vs 17.2 days [21.0 days]; P = 0.002), a more frequent need for oxygen therapy (101 [60.8%] vs 103 [40.4%]; P < 0.001) and invasive ventilation (52 [31.3%] vs 32 [12.5%]; P < 0.001) and were more frequently admitted to the intensive care unit (70 [42.2%] vs 51 [20.0%]; P < 0.001) than seasonal influenza patients. Among immunocompromised patients, those in the COVID-19 group had a higher hospital mortality compared to those in the seasonal influenza group (13 [33.3%] vs 8 [11.6%], P = 0.01). In conclusion, we show that COVID-19 patients were younger and had fewer baseline comorbidities than seasonal influenza patients but were at increased risk for severe illness. The high mortality observed in immunocompromised COVID-19 patients emphasizes the importance of protecting these patient groups from SARS-CoV-2 infection.

Background Influenza is the most common vaccine-preventable infection among travelers, affecting approximately one percent of those travelling to subtropical and tropical destinations. Methods We analysed demographic, travel-related and clinical information from travelers diagnosed with influenza at our travel clinic between January 2015 and March 2020 and influenza-negative controls. Results We included 68 travelers diagnosed with influenza and 207 controls. In total, 22.1% of influenza patients ( n  = 15) were older than 60 years and/or had comorbidities for which annual influenza vaccination is recommended, but only one had received an influenza vaccine. Patients with respiratory and musculoskeletal symptoms who presented during the German influenza season had the highest risk proportion of positive tests (54%, n  = 25/46). Overall, three (4.4%) influenza patients were hospitalised, two (2.9%) received antiviral treatment, and eight (11.8%) received antibiotic therapy. Conclusions Influenza occurs throughout the year in international travelers and can cause significant morbidity. Travelers with febrile illness should be tested for influenza, especially if they have respiratory or musculoskeletal symptoms, present during the local influenza season, or have travelled to South-East Asia. Influenza vaccination coverage among international travelers needs to be improved among high-risk individuals.

So far, only a few reports about reinfections with SARS-CoV-2 have been published, and they often lack detailed immunological and virological data. We report about a SARS-CoV-2 reinfection with a genetically distinct SARS-CoV-2 variant in an immunocompetent female healthcare worker that has led to a mild disease course. No obvious viral escape mutations were observed in the second virus variant. The infectious virus was shed from the patient during the second infection episode despite the presence of neutralizing antibodies in her blood. Our data indicate that a moderate immune response after the first infection, but not a viral escape, did allow for reinfection and live virus shedding.

The African visiting friends and relatives (VFR) community in the Global North is at high risk of contracting preventable travel-associated infections including malaria when travelling to sub-Saharan Africa. This study aimed to assess barriers to effective prevention and to develop tailored travel counselling. A questionnaire-based survey was conducted from January to August 2023 at the Hamburg Airport among adult sub-Saharan African VFR travellers returning from malaria-endemic destinations in Africa to assess malaria risk perceptions, attitudes towards prophylaxis and counselling and their experiences with travel medicine and malaria prophylaxis. A total of 389 participants completed the survey. Of these, 67 % (n = 261) demonstrated adequate knowledge of malaria transmission. Fifty-one percent (n = 198) perceived minimal risk of contracting malaria in the malaria-endemic country leading to lower uptake of prophylaxis. Ten percent (n = 37) mistakenly believed they were vaccinated against malaria. Approximately half of the respondents did not seek medical travel advice prior to departure or take antimalarial prophylaxis due to perceived minimal risk of disease. Of those who took antimalarial drugs, 77 % (n = 149) completed the full course. On return, 5 % (n = 20) of the respondents had malaria-like symptoms and of these, 55 % (n = 11) either self-medicated or did not seek medical treatment. VFR travellers mistakenly perceive a low risk of malaria, resulting in low uptake of travel medical advice and chemoprophylaxis. Mistrust of advice from healthcare providers was found. Insights from this survey are valuable for practitioners and travel medicine clinics to provide more tailored and culturally sensitive travel advice to VFR travellers.

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

The treatment of drug-resistant Mycobacterium tuberculosis relies on complex antibiotic therapy. Inadequate antibiotic exposure can lead to treatment failure, acquired drug resistance, and an increased risk of adverse events. Therapeutic drug monitoring (TDM) can be used to optimize the antibiotic exposure. Therefore, we aimed to develop a single-run multiplex assay using high-performance liquid chromatography–mass spectrometry (HPLC–MS) for TDM of patients with multidrug-resistant, pre-extensively drug-resistant and extensively drug-resistant tuberculosis. A target profile for sufficient performance, based on the intended clinical application, was established and the assay was developed accordingly. Antibiotics were analyzed on a zwitterionic hydrophilic interaction liquid chromatography column and a triple quadrupole mass spectrometer using stable isotope-labeled internal standards. The assay was sufficiently sensitive to monitor drug concentrations over five half-lives for rifampicin, rifabutin, levofloxacin, moxifloxacin, bedaquiline, linezolid, clofazimine, terizidone/cycloserine, ethambutol, delamanid, pyrazinamide, meropenem, prothionamide, and para-amino salicylic acid (PAS). Accuracy and precision were sufficient to support clinical decision making (≤±15% in clinical samples and ±20–25% in spiked samples, with 80% of future measured concentrations predicted to fall within ±40% of nominal concentrations). The method was applied in the TDM of two patients with complex drug-resistant tuberculosis. All relevant antibiotics from their regimens could be quantified and high-dose therapy was initiated, followed by microbiological conversion. In conclusion, we developed a multiplex assay that enables TDM of the relevant first- and second-line anti-tuberculosis medicines in a single run and was able to show its applicability in TDM of two drug-resistant tuberculosis patients.

In patients with hepatitis E virus (HEV) infections, extrahepatic, particularly renal and hematological manifestations, are increasingly reported in the medical literature but have never been studied compared to a control cohort. We retrospectively analyzed medical records of consecutive patients that were diagnosed with acute hepatitis E (AHE) (n = 69) or acute hepatitis A (AHA) (n = 46) at the University Medical Center Hamburg Eppendorf from January 2009 to August 2019 for demographical, clinical, and laboratory information. Patients with AHE had significantly lower median levels of ALAT (798 U/L) and total bilirubin (1.8 mg/dL) compared to patients with AHA (2326 U/L; p < 0.001 and 5.2 mg/dL; p < 0.001), suggesting a generally less severe hepatitis. In contrast, patients with AHE had significantly higher median serum creatinine levels (0.9 mg/dL vs. 0.8 mg/dL; p = 0.002) and lower median estimated glomerular filtration rate (eGFR) (91 mL/min/1.73 m2 vs. 109 mL/min/1.73 m2; p < 0.001) than patients with AHA. Leucocyte, neutrophil and lymphocyte count, hemoglobin, platelets, red cell distribution width (RDW), neutrophil to lymphocyte ratio (NLR), and RDW to lymphocyte ratio (RLR) did not differ between patients with AHE and those with AHA. Our observations indicate that renal but not hematological interference presents an underrecognized extrahepatic feature of AHE, while inflammation of the liver seems to be more severe in AHA.