At the long-term follow-up, the patients scored significantly lower in a diversity of neurocognitive and motor symptoms, in comparison with controls. These sequelae and their pathogenesis should be further explored and specific neurocognitive assessment tests are needed.

Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematological diseases are at risk of severe disease and death from COVID-19. To determine the safety and immunogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines, samples from 50 infection-naïve allo-HSCT recipients (median 92 months from transplantation, range 7-340 months) and 39 healthy controls were analyzed for serum IgG against the receptor-binding-domain (RBD) within spike 1 (S1) of SARS-CoV-2 (anti-RBD-S1 IgG) and for SARS-CoV-2-specific T-cell immunity, reflected by induction of T-cell-derived interferon-γ in whole blood stimulated ex vivo with fifteen 11-mer S1-spanning peptides. The rate of seroconversion was not significantly lower in allo-transplanted patients than controls with 24% (12/50) and 6% (3/50) of patients remaining seronegative after the first and second vaccination, respectively. However, 58% of transplanted patients lacked T-cell responses against S1 peptides after 1 vaccination compared with 19% of controls (OR 0.17; P=0.009, Fisher's exact test) with a similar trend after the second vaccination where 28% of patients were devoid of detectable specific T-cell immunity, compared with 6% of controls (OR 0.18, P=0.02, Fisher's exact test). Importantly, lack of T-cell reactivity to S1 peptides after vaccination heralded substandard levels (<100 BAU/ml) of anti-RBD-S1 IgG 5-6 months after the second vaccine dose (OR 8.2, P=0.007, Fisher's exact test). We conclude that while allo-HSCT recipients achieve serum anti-RBD-S1 IgG against SARS-CoV-2 after 2 vaccinations, a deficiency of SARS-CoV-2-specific T-cell immunity may subsequently translate into insufficient humoral responses. This trial is registered at EudraCT as 2021-000349-42.

We set out to investigate the serological response of TBE virus (TBEV)-specific IgM and IgG antibodies in stored serum and cerebrospinal fluid (CSF) in notified TBE patients, in order to confirm or reject the diagnosis. We applied the ELISA methods used in clinical practice, Enzygnost and Immunozym, and assessed RT-PCR as a diagnostic tool. A total of 173 TBE cases were notified to the Public Health Agency. Samples from 129 patients were eligible for the study. Stored serum samples were found for 111 patients and CSF samples for 88 patients. All serum samples were analyzed with both Enzygnost and Immunozym, as well as an additional 140 control samples. CSF samples, including samples from ten controls, were analyzed with Immunozym. RT-PCR for TBEV was performed on 126 serum, two whole blood, 96 CSF, two feces and four nasopharynx samples. Only two of 111 notified patients lacked detectable TBEV IgM in serum, from whom one sample was RT-PCR positive. According to the ECDC definition, 117/129 (90.7%) of the reported TBE cases were confirmed. Positive RT-PCR results were obtained in eight patients, one from whole blood and eight from serum samples. Four out of eight of the RT-PCR positive patients were TBEV-IgM positive and none had detectable TBEV-specific IgG. All of the tested CSF, feces and nasopharynx samples were RT-PCR-negative. TBEV-specific IgG was detected in 88.4% and IgM in 31.6% of the CSF samples. RT-PCR on serum samples and CSF IgG antibodies can be used as complementary methods in TBE diagnostics, not least early in the disease course.Electronic supplementary materialThe online version of this article (10.1007/s10096-017-3139-9) contains supplementary material, which is available to authorized users.

b T ick-borne encephalitis (TBE) is a viral zoonosis of increasing incidence in Eurasia, and diagnosis relies mainly on the detection of IgM antibodies in serum. We here present two cases of TBE, of four patients tested, in which we have detected TBE virus (TBEV) RNA in urine with real-time PCR during the encephalitic phase. This observation suggests a new diagnostic opportunity that could be evaluated in a larger cohort of patients.In the first case we report here, 1 week after a tick bite, a 61-yearold woman had high fever, nausea, and fatigue lasting for 5 to 6 days. She was asymptomatic for a week, after which the fever returned along with vomiting and severe headache. After admission, her condition worsened. She was unable to follow instructions, became somnolent and disoriented, and had signs of dysphasia. A cerebrospinal fluid (CSF) sample showed a leukocyte count of 69 ϫ 10 6 /liter (41% polymorphonuclear and 59% mononuclear) and elevated albumin. Specific TBE virus (TBEV) IgM antibodies were detected in serum drawn on day 2 after admission, and the patient seroconverted as regards IgG during the hospital stay. Before nucleic acid extraction using the EasyMag instrument (bioMérieux, Marcy l=Etoile, France), 250-l amounts of serum, CSF, and urine samples were added to 2 ml of lysis buffer and incubated for 10 min at room temperature. TBEV RNA was detected from urine by TaqMan PCR performed as described previously (1) on day 19 after fever onset (Fig. 1). The patient's condition improved, and she was discharged after 10 days of hospitalization.The second case was a 70-year-old woman who reported several tick bites during the preceding weeks and was admitted 2 days after the onset of high fever, nausea, and fatigue. She was on treatment with immunosuppressive drugs (mycophenolate, tacrolimus, and prednisolone) due to kidney transplantation. She developed paresis of the lower extremities and lost the strength in her hands. A CSF sample showed 488 ϫ 10 6 leukocytes/liter (28% polymorphonuclear and 72% mononuclear), elevated albumin and lactate, and a slightly decreased glucose quotient. TBEV IgM antibodies (but not IgG) were detected in serum. On day 8 after admission, the patient became deeply unconscious, had a generalized status epilepticus, and was intubated. Magnetic resonance imaging (MRI) demonstrated high signals in the amygdala and hippocampus. Her neurological condition deteriorated, and she died 11 weeks after admission. TBEV RNA was detected from urine on day 7 and day 16 after onset ( Fig. 1). The RNA quantities allowed sequencing of 10,432 nt from TBEV RNA amplicons, as

Tick-borne encephalitis (TBE) is a widespread viral infection of the central nervous system with increasing incidence in Europe and northern Asia. Post-infectious sequelae are frequent, and patients with TBE commonly experience long-term fatigue and subjective sleep disturbances. Obstructive sleep apnea (OSA) may be a contributing factor, and objective sleep studies with polysomnography (PSG) are lacking. Forty-two adults, 22 TBE patients (cases), diagnosed in Region Västra Götaland, Sweden, between 2012 and 2015, and 20 controls without a known TBE history, underwent an overnight PSG, respectively. All participants responded to questionnaires. The cases and controls were similar regarding age, sex, obesity, concomitant diseases, smoking, and alcohol habits. Despite similar PSG characteristics such as total sleep time and OSA severity indices, the TBE cases reported statistically more sleep-related functional impairment on the Functional Outcome of Sleep Questionnaire (FOSQ) compared with the controls (median scores 18.1 vs. 19.9; p<0.05). In a multivariate analysis, TBE correlated significantly with the lower FOSQ scores (unstandardized β −1.80 [%95 confidence interval −3.02 - −0.58]; p = 0.005) independent of age, sex, total sleep time and apnea-hypopnea-index. TBE cases with OSA reported the lowest scores on the FOSQ compared with the other subgroups with TBE or OSA alone, and the ones with neither TBE nor OSA. TBE is associated with impaired functional outcomes, in which concomitant OSA may worsen the subjective symptoms. Further studies are warranted to determine the effect of treatment of concomitant OSA on functional outcomes with regard to optimal rehabilitation of TBE.

Background To outline how the training program and work situation of residents in Obstetrics and Gynecology (OB-GYN) was affected by the pandemic and to illuminate how residents experienced these changes. Methods As part of the COVID-19 in Pregnancy and Early Childhood Staff (COPE Staff) cohort study, between January and May 2021, all participating residents were invited to answer a 28-question online Resident Survey focusing on their specialist education, work situation and experiences during the COVID-19 pandemic. Descriptive statistics were given in percentages for categorical variables and means and standard deviations (SD) for continuous variables. Univariate comparative analyses were performed with the use of the Pearson’s Chi-2-test for dichotomous data. The association between residents’ worry about the quality and length of their specialist training, with extra clinical hours and transfer to other healthcare institutions were assessed by multivariate logistic regression. Free text responses were analyzed by content analysis. Results Of the 162 participating OB-GYN residents, 69% expressed concern that the pandemic would have a negative impact on their training. Ninety-five (95%) reported cancellation/postponement of educational activities, 70% performed fewer surgeries and 27% had been transferred to other healthcare institutions where about half reported having gained more general knowledge as a physician. Working extra clinical hours was reported by 69% (7.4 ± 5.3 hours per week) and 14% had considered changing their profession due to the pandemic. Senior residents, compared to junior residents, more often experienced cancelled/postponed clinical rotations (30% vs 15%, P=0.02) and reported performing fewer surgeries (P=0.02). The qualitative analysis highlighted the lack of surgical procedural training as a major concern for residents. Conclusion The COVID-19 pandemic has strongly impacted the training program and work situation of OB-GYN residents in Sweden. Residents were concerned over the negative impact of the pandemic on their training program and senior residents reported more missed educational opportunities as compared to junior residents. Program directors, head of institutions and clinical supervisors can use the problem areas pinpointed by this study to support residents and compensate for missed educational opportunities. While hands-on-training and operating time cannot be compensated for, the authors hope that the findings of the study can help develop new strategies to minimize the negative impact of the current and future pandemics on resident education and work situation.

No abstract

No abstract