SARS-CoV-2 mutations in MHC-I-restricted epitopes evade CD8+ T cell responses.

CD8+ T cell immunity to SARS-CoV-2 has been implicated in COVID-19 severity and virus control. Here, we identified nonsynonymous mutations in MHC-I-restricted CD8+ T cell epitopes after deep sequencing of 747 SARS-CoV-2 virus isolates. Mutant peptides exhibited diminished or abrogated MHC-I binding in a cell-free in vitro assay. Reduced MHC-I binding of mutant peptides was associated with decreased proliferation, IFN-γ production and cytotoxic activity of CD8+ T cells isolated from HLA-matched COVID-19 patients. Single cell RNA sequencing of ex vivo expanded, tetramer-sorted CD8+ T cells from COVID-19 patients further revealed qualitative differences in the transcriptional response to mutant peptides. Our findings highlight the capacity of SARS-CoV-2 to subvert CD8+ T cell surveillance through point mutations in MHC-I-restricted viral epitopes.

Occupational swine exposure and Hepatitis E virus, Leptospira, Ascaris suum seropositivity and MRSA colonization in Austrian veterinarians, 2017-2018-A cross-sectional study.

We investigated the prevalence of Hepatitis E Virus (HEV), Leptospira and Ascaris suum (A. suum) seropositivity, and of nasal methicillin-resistant Staphylococcus aureus (MRSA) colonization among Austrian practising veterinarians, and assessed the association with occupational swine livestock exposure. The 261 participants completed a questionnaire on demographics, intensity of occupational swine livestock contact and glove use during handling animals and their secretions. Participants' blood samples were tested for HEV, Leptospira and A. suum seropositivity and nasal swabs cultured for MRSA. We compared swine veterinarians (defined as >3 swine livestock visits/week) to non-swine veterinarians (≤3 swine livestock visits/week) with regard to the outcomes through calculating prevalence ratio (PR) and 95% confidence interval (CI). Furthermore, the relationship between occupational swine livestock contact and the study outcomes was examined by age (3 occupational swine livestock visits per week is associated with HEV and A. suum seropositivity and nasal MRSA colonization and that glove use may play a putative preventive role in acquiring HEV and A. suum. Further analytical epidemiological studies have to prove the causality of these associations.

Detection of the mcr-1 Gene in a Multidrug-Resistant Escherichia coli Isolate from an Austrian Patient.

Since colistin resistance based on the plasmid-encoded mcr-1 gene was first described, this resistance gene in Enterobacteriaceae has been found worldwide. These organisms are typically of heterogeneous genetic background and show exceptional clonal diversity. We describe the first confirmation of mcr-1 in a human Escherichia coli strain cultured from a surveillance stool sample of an Austrian oncology patient.

West Nile virus positive blood donation and subsequent entomological investigation, Austria, 2014.

The detection of West Nile virus (WNV) nucleic acid in a blood donation from Vienna, Austria, as well as in Culex pipiens pupae and egg rafts, sampled close to the donor's residence, is reported. Complete genomic sequences of the human- and mosquito-derived viruses were established, genetically compared and phylogenetically analyzed. The viruses were not identical, but closely related to each other and to recent Czech and Italian isolates, indicating co-circulation of related WNV strains within a confined geographic area. The detection of WNV in a blood donation originating from an area with low WNV prevalence in humans (only three serologically diagnosed cases between 2008 and 2014) is surprising and emphasizes the importance of WNV nucleic acid testing of blood donations even in such areas, along with active mosquito surveillance programs.

Epidemiology of listeriosis in Austria.

A total of 150 human cases of listeriosis (case definition based on isolation of Listeria monocytogenes from normally sterile material) were reported in Austria between 1997 and 2007. Of these, 14 cases (9.3%) were pregnancy-associated (mother/child illness considered as a single case) with a mean age of 29.3 years (median: 26.5; range 24-36). Among the non-pregnancy-associated cases (n = 136), 75 were male (55.2%) and 61 female (44.9%); patients in this group had a mean age of 64.3 years (median: 66.2; range 1-93). The average incidence of listeriosis in Austria in the period studied was 0.168 cases per 100,000 population. The majority of cases (90.7%) were caused by systemic infection, only 9.3% of cases were local infections. Among non-pregnancy-associated cases the fatality rate was 28.7% (39/136) and among the pregnancy-associated cases 35.7% (5/14: miscarriage x3, stillbirth x1, and one death in a newborn within 15 days of birth). Serotyping results for the 150 isolates revealed serovar (SV) 4b: 54%, SV 1/2a: 31.3%, SV 1/2b: 10%, SV 1/2c: 2.7%, 4d: 1.3% and SV 3a: 0.7%. Predisposing risk factors were determined for 131 of the 150 cases: age > or = 65 years (n = 73), pregnancy (n = 14) and 44 cases of carcinoma, blood malignancies, autoimmune diseases and status post solid organ transplants (7 patients had more than one underlying illness). During the period studied, the incidence of listeriosis doubled, despite a drastic reduction in the frequency of pregnancy-associated cases.

Epidemiology of enterovirus types causing neurological disease in Austria 1999-2007: detection of clusters of echovirus 30 and enterovirus 71 and analysis of prevalent genotypes.

Between 1999 and 2007 1,388 stool specimens from patients with acute flaccid paralysis or aseptic meningitis were submitted to the Austrian reference laboratory for poliomyelitis. Samples (201) yielded non-poliovirus enterovirus in culture. One hundred eighty-one viruses were available for typing and 78 isolates which remained serologically untyped were further analyzed by CODEHOP-PCR and sequencing of the VP1 gene and the 5'-untranslated region (5'-UTR). Typing revealed an Echovirus 30 outbreak in northwestern Austria in 2000, which was in accordance with the situation in Europe, and no dramatic seasonal changes of Coxsackie viruses were observed. In 2002/2003 a small outbreak of enterovirus 71 (EV71), affected 12 patients in the province of Styria. This virus was identified as genotype C1 and appeared to be genetically distinct from the isolates observed in 2001/2002 in Vienna. In 2004 two unrelated cases occurred in Lower Austria, which were identified as genotype C4, which has been described associated with high mortality most recently in China. In contrast to the situation in Asia the detected EV71 cases were not associated with hand-foot-mouth disease, but with serous meningitis only. This was surprising as a recent publication suggested a reduced neurovirulence of C1 genotype in children in Norway, presumably due to alterations in 5'-UTR and polymerase gene. However, comparing the 5'-UTR of the Austrian isolates and established virulent reference strains to the Norwegian isolate and an attenuated EV71 laboratory strain we did not find an indication that the genotype C1 possesses a RNA structure in its 5'-UTR leading to reduced neurovirulence.

Occurrence of Vibrio cholerae serogroups other than O1 and O139 in Austria.

From 2000 to 2005, 13 infections due to non-O1/non-O139 Vibrio cholerae were documented in Austria. Twelve patients (8 years to 65 years old; 7 male) had symptomatic infections: diarrhea x 5, otitis x 6, septicemia once. All 5 patients who acquired their infections abroad, suffered from diarrhea. The 8 persons without travel history outside of Austria had otitis media (n = 4) or otitis externa (n = 2); the lethal case of septicemia affected a fisherman with underlying malignancy. One isolate was from an asymptomatic child. Detailed data on travel history inside Austria was available for 5 of these 8 patients: all 5 had visited or lived near Austria's largest lake. The concentration of salt in this westernmost steppe lake in Europe is approximately one-twentieth of that of sea water. Why otitis and not diarrhea is the dominating manifestation of non-O1/non-O139 infection acquired in Austria remains to be elucidated. We hypothesize that diarrhea due to Vibrio cholerae serogroups other than O1 and O139 acquired in Austria may simply be unrecognized by the standard operating procedures employed in clinical microbiology laboratories. Testing for Vibrio cholerae is not considered necessary for domestically acquired diarrhea. Only in patients who acquired diarrhea abroad, do physicians sometimes consider cholera as a differential diagnosis, thereby prompting the laboratory to use thiosulfate citrate bile salt sucrose (TCBS) agar plates.

Listeria meningitis in transplant recipients.

INTRODUCTION: Meningitis is a rare complication following organ and stem-cell transplantation and can be caused by a variety of microorganisms. AIM: To retrospectively review the clinical course and outcome of five cases of listeriosis in four organ recipients and one stem-cell recipient during a seven-year period. PATIENTS AND METHODS: Patient records for more than 3500 patients undergoing organ or stem-cell transplantation at the university hospital of Innsbruck during a 27-year period were evaluated. Standard immunosuppression consisted of calcineurin inhibitor-based triple drug therapy with or without ATG or IL2 receptor antagonist induction. RESULTS: The first case affected a 35-year-old woman who received an allogenic bone marrow transplant for advanced breast cancer. Cases two and three related to two male heart recipients. Cases four and five were diagnosed in one male and one female renal recipient. Listeria monocytogenes was isolated from blood in two cases and from cerebrospinal fluid in three. Treatment consisted of ampicillin in all cases with the addition of tobramycin (1), TMPS (1), meropenem (2) or imipenem/cilastatin (1). The deaths of two patients were directly related to L. monocytogenes. CONCLUSIONS: Although listeriosis is a rare complication following transplantation, this infection should be ruled out in individuals presenting with neurological symptoms and fever.