Inpatient forensic psychiatry in the time of COVID-19: a survey study of perceived mental health implications on people with schizophrenia spectrum disorder

Background: The aim of our study was to assess the perceived mental health impact of the COVID-19 pandemic on people with schizophrenia spectrum disorder (SSD) in an inpatient forensic psychiatric institution and to identify personal networks most crucial for the patient during the pandemic. Method(s): In this cross-sectional survey study, 44 patients with SSD took part in a COVID-19-specific interview. The data was correlated with the Positive and Negative Syndrome Scale (PANSS) to evaluate the patients' psychopathology. In addition, we investigated subgroups of vaccinated and unvaccinated patients to analyze possible differences in psychopathology. Result(s): Less contact with family members was associated with significantly higher PANSS scores (p < 0.05). Patients who reported to feel less relaxed and more stressed during the pandemic than they had been before the outbreak of the virus showed significantly higher PANSS scores (p < 0.05). Unvaccinated patients demonstrated significantly higher PANSS scores than their vaccinated controls (p < 0.05). Conclusion(s): Social support from family members played an important role for people with SSD in inpatient forensic psychiatric institutions during the pandemic. Moreover, individuals with SSD seemed to be more emotionally vulnerable during the pandemic. A more pronounced symptomatology in patients with SSD might be a potential barrier to immunization against COVID-19.Copyright © 2022 Informa UK Limited, trading as Taylor & Francis Group.

Severity score-based study of predictors and clinical correlates of Post-COVID Syndrome (PCS)in Germany

Background: Post-COVID Syndrome (PCS) is an important sequela of COVID-19, characterised by symptom persistence >3 months, subacute symptom onset, and worsening of pre-existing comorbidities. The causes and public health impact of PCS are still unclear, not least for the lack of efficient means to assess the presence and severity of PCS. Method(s): COVIDOM is a population-based cohort study of PCR-confirmed cases of SARS-CoV-2 infection, recruited through local public health authorities in three German regions. Standardised interviews and in-depth onsite examinations were scheduled 6-12 months post infection. Based upon 12 long-term symptom complexes, we developed a comprehensive PCS severity score in a training cohort and validated the score in two independent subcohorts. Result(s): In the training sub-cohort (n=667, 56% female), 90% of participants were treated as outpatients for acute COVID-19. Neurological ailments (61.5%) and fatigue (57.1%) persisted most frequently. Across all sub-cohorts, higher PCS scores were associated with lower health-related quality of life (EQ-5D-5L-VAS/-index, all p<0.001). Similarly, participants with a higher PCS score consistently showed increased blood inflammatory markers and Ddimer as well as lower diffusing capacity in lung function (all p<0.01). Significant early predictors of the PCS score included the number and intensity of acute symptoms, resilience, and general anxiousness. Conclusion(s): PCS severity can be quantified by an easy-to-use score summarising individual disease burden and reflecting pathological processes. The PCS score promises to facilitate diagnosis of PCS, studies of its natural course, and of therapeutic interventions.

Persisting chemosensory dysfunction in COVID-19 - a cross-sectional population-based survey.

BACKGROUND: Chemosensory dysfunction (CD) has been reported as a common symptom of SARS-CoV-2 infection, but it is not well understood whether and for how long changes of smell, taste and chemesthesis persist in infected individuals. METHODOLOGY: Unselected adult residents of the German federal state of Schleswig-Holstein with Polymerase Chain Reaction (PCR)-test-confirmed SARS-CoV-2 infection were invited to participate in this large cross-sectional study. Data on the medical history and subjective chemosensory function of participants were obtained through questionnaires and visual analogue scales (VAS). Olfactory function (OF) was objectified with the Sniffin' Sticks test (SST), including threshold (T), discrimination (D) and identification (I) test as well as summarized TDI score, and compared to that in healthy controls. Gustatory function (GF) was evaluated with the suprathreshold taste strips (TS) test, and trigeminal function was tested with an ampoule containing ammonia. RESULTS: Between November 2020 and June 2021, 667 infected individuals (mean age: 48.2 years) were examined 9.1 months, on average, after positive PCR testing. Of these, 45.6% had persisting subjective olfactory dysfunction (OD), 36.2% had subjective gustatory dysfunction (GD). Tested OD, tested GD and impaired trigeminal function were observed in 34.6%, 7.3% and 1.8% of participants, respectively. The mean TDI score of participants was significantly lower compared to healthy subjects. Significant associations were observed between subjective OD and GD, and between tested OD and GD. CONCLUSION: Nine months after SARS-CoV-2 infection, OD prevalence is significantly increased among infected members of the general population. Therefore, OD should be included in the list of symptoms collectively defining Long-COVID.

Etrasimod 2mg Once Daily as Treatment for Moderately to Severely Active Ulcerative Colitis: Results from the Phase 3 Elevate Uc 52 and Elevate Uc 12 Trials

Introduction: Etrasimod (APD334), an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 modulator, demonstrated efficacy in adults with moderately to severely active ulcerative colitis (UC) in the Phase 2 OASIS trial (NCT02447302). Here, we report data from 2 trials, ELEVATE UC 52 and ELEVATE UC 12, that evaluated the efficacy and safety of etrasimod 2mg for induction and maintenance in adults with UC. Aims & Methods: ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) were global, randomized, double-blind, placebo-controlled trials. In both trials, adults (16-80 years) with moderately to severely active UC (based on modified Mayo Score [MMS] of 4-9 with centrally read endoscopic subscore >=2 and rectal bleeding subscore >=1) and documented history of inadequate response, loss of response, or intolerance to >=1 treatment for UC were randomized 2:1 to once-daily treatment with etrasimod 2mg or placebo. Patients (pts) were stratified by previous exposure to biologic/Janus kinase inhibitor (JAKi) therapy, baseline corticosteroid use, and baseline disease activity (MMS 4-6 or 7-9). ELEVATE UC 52 utilized a treat-through design comprising a 12-week induction period followed by a 40-week maintenance period. Beginning at Week (Wk) 12, all pts could continue their randomized treatment;pts whose disease had not improved or had worsened compared to baseline (based on investigator judgement) could discontinue and enroll in an open-label extension study (NCT03950232). ELEVATE UC 12 comprised a 12-week induction period only. The primary efficacy endpoints were the proportion of pts achieving clinical remission (using the MMS) at Wk 12 and Wk 52 in ELEVATE UC 52, and at Wk 12 in ELEVATE UC 12. Safety was evaluated throughout the trials. Result(s): In ELEVATE UC 52, 433 pts were randomized (etrasimod, n=289;placebo, n=144) and 207 completed Wk 52. In ELEVATE UC 12, 354 pts were randomized (etrasimod, n=238;placebo, n=116) and 316 completed Wk 12. 62.6% of etrasimod-treated pts in both trials and 61.8% and 62.9% of placebo-treated pts in ELEVATE UC 52 and ELEVATE UC 12, respectively, were naive to biologic/JAKi therapy. All primary and key secondary efficacy endpoints were achieved with etrasimod vs placebo at both Wks 12 and 52 in ELEVATE UC 52 and Wk 12 in ELEVATE UC 12 (Table). Most commonly reported TEAEs (>=3% of etrasimod-treated pts and greater than placebo in either trial) were headache, nausea, COVID-19 infection, dizziness, pyrexia, arthralgia, abdominal pain and worsening of UC. Serious AEs were similar between treatment groups in both trials. The overall safety profile was consistent with previous studies. Conclusion(s): Treatment with etrasimod 2mg resulted in statistically significant and clinically meaningful improvements based on clinical, endoscopic, symptomatic, and endo-histologic endpoints at Wks 12 and 52 in adults with moderately to severely active UC. No new safety findings were observed with etrasimod 2mg treatment for up to 52 weeks.

INCREASED PROTEASE-ACTIVATED RECEPTOR 1 AUTOANTIBODIES ARE ASSOCIATED with SEVERE COVID-19

Background: In acute COVID-19 infection, growing evidence hints towards a broad activation of plasma cells and the presence of pathologic autoantibodies (abs). A systematic screening for abs confrmed induction of diverse functional abs by SARS-CoV-2 infection (1, 2). Immune-mediated thrombosis, involving platelet activation, has been identifed as one of the key pathogenic mechanisms in COVID-19 and is linked to morbidity and mortality (3). As natural abs against G protein-coupled receptors, functional abs against the thrombin receptor type-1 (PAR-1) might predispose for increased activation of the coagulation system present in COVID-19 infection. Objectives: The aim of this study is to identify the diagnostic value of anti-PAR1 antibodies and their capacity to predict the outcome of COVID-19 infection. Methods: 82 serum samples from 55 individuals with COVID-19 derived from three different hospitals in Schleswig-Holstein, Germany, and 88 single time point samples from healthy controls were subjected to ELISA-based quantifcation of anti-PAR-1 abs (CellTrend GmbH Luckenwalde, Germany). The levels of anti-AT1R abs were compared with clinical and laboratory parameters. Results: COVID-19 patients revealed markedly increased levels of circulating anti-PAR1 abs in hospitalized patients particularly in those required intensive care treatment in comparison to controls (p < 0.0001, Figure 1a). Anti-PAR1 ab levels were highest in patients with fatal outcome (p = 0.006, Figure 1a). Receiver operating characteristic (ROC) analysis of PAR1 abs levels in COVID-19 patients revealed a sensitivity of 84.00% and a specifcity 79.25% for patients requiring intensive care unit (ICU) treatment and a sensitivity of 87.50 % and a specifcity 84.51 % to distinguish fatal vs. non-fatal disease outcome (Figure 1b). We found correlation of circulating anti-PAR1 abs with D dimers. Conclusion: The increased anti-PAR1 abs, their prediction to identify patients requiring ICU and fatal outcome, and the correlation with markers for blood clotting suggest a role for antibodies against PAR1 in the disease development of blood clotting in COVID-19.

Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/ TAF) for the Treatment of People Living with HIV (PLWH): 12-month (12M) Effectiveness, Persistence, and Safety in a Multi-country Cohort Study

Introduction: BICSTaR (GS-EU-380-4472/GS-CA-380-4574/GS-IL-380- 5335) is an ongoing, multinational, observational cohort study evaluating real-world effectiveness and safety of B/F/TAF in ART naïve (TN) and ARTexperienced (TE) PLWH. Materials and Methods: This 12M pooled analysis included PLWH starting B/F/TAF in clinical practice from June 2018 to September 2020 (latterly during the COVID-19 pandemic) in Europe/Israel/Canada. Outcomes included virological effectiveness (HIV-1 RNA <50 copies/ml [missing=excluded]), persistence, drug-related adverse events (DRAEs), and laboratory parameters. Results: One-thousand one hundred thirty-five PLWH were included (Table 1). The TE group had older median age than TN. Of TE participants, 65%/20%/16% switched from INSTI/NNRTI/PI-based regimens (36% TDF/46% TAF/13% ABC);12% had prior virologic failure. Baseline resistance was documented in 124/535 participants (NRTI/NNRTI/PI/ INSTI=6%/6%/3%/0.2%). Prevalence of comorbidities (47%/72% TN/TE) and concomitant medication usage was high. At 12M, 97% (149/154) of TN and 96% (771/800) of TE participants had HIV-1 RNA <50 copies/ml, and persistence on B/F/TAF was high [91% (1032/1135)]. In a multivariable analysis, TE participants with neuropsychiatric disorder ongoing at baseline had lower odds for viral suppression (odds ratio=0.45, 95% CI: 0.21-0.96). There was no emergence of resistance to the components of B/F/TAF. DRAEs occurred in 13% (148/1135) of participants;gastrointestinal and neuropsychiatric DRAEs were the most common (3% each). Discontinuations due to DRAEs were low (TN 4%;TE 6%). Serious DRAEs were rare (0.2%;2 TE participants with depression). Lipidchanges are shown (Figure 1). Conclusion: B/F/TAF was associated with high levels of effectiveness and persistence after 12M in this large real-world cohort of TN and TE PLWH with a high comorbidity burden. Effectiveness was demonstrated across key subgroups (females, older participants, late presenters). Importantly, there were no new or unexpected safety findings. Collectively, these real-world data continue to support the use of B/F/TAF in clinical practice.

Switching from intravenous to subcutaneous infliximab in patients with active inflammatory bowel disease: post-hoc analysis of pre/post switch outcomes from a multicentre, randomised controlled pivotal

Introduction: A subcutaneous (SC) infliximab (IFX), CT-P13 SC, has received regulatory approval from the European Medicines Agency for indications including inflammatory bowel disease.1 In response to the coronavirus disease 2019 (COVID-19) pandemic, clinical guidance has recommended considering switching from intravenous (IV) treatment to SC alternatives to minimise hospital visits.2 Aims & Methods: In this analysis, data from the pivotal randomised controlled trial (NCT02883452) of CT-P13 SC in patients with active Crohn's disease (CD) and ulcerative colitis (UC) were analysed to investigate the clinical impact of switching from IV to SC IFX.3 Patients in the CT-P13 IV arm of the pivotal trial received CT-P13 5 mg/kg IV every 8 weeks from Week (W) 6 until W22. At W30, patients switched to receive CT-P13 SC every 2 weeks up to W54 (dose 120 mg or 240 mg for patients <80 kg or ≥80 kg, respectively).3 This post hoc analysis compared per-patient pairwise data at W30 (pre-switch) and W54 (post-switch) from the CT-P13 IV arm for the following outcomes: trough serum concentration (Ctrough;5 μg/mL was considered to be the target exposure level), clinical response (for CD patients, ≥100-point decrease in Crohn's Disease Activity Index score;for UC patients, ≥2-point decrease in partial Mayo score with accompanying ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding subscore of 0 or 1) and immunogenicity (anti-drug antibody [ADA] and neutralising antibody [NAb] positivity;as measured by a drug tolerant assay;ADA negative was regarded as NAb negative). For pairwise comparisons, patients with missing data at either W30 or W54 were excluded from the analysis. Statistical comparisons used Fisher's exact test. The differences are reported in a descriptive manner. Results: Overall, 65 patients (25 CD;40 UC) were included in the CT-P13 IV arm. The proportion of patients with a Ctrough level exceeding target exposure was significantly higher post-switch (36/41, 87.8%) than pre-switch (8/41, 19.5%;p<0.00001) (Table). Clinical response rates were comparable at both pre- and post-switch timepoints (40/49 [81.6%] vs 44/49 [89.8%], respectively;p=0.3873). Positive ADA and NAb rates at pre-switch and post-switch were also comparable, in which some changes were regarded from patients with marginal value (Table). Conclusion: Switching from IV to SC IFX did not detrimentally affect the clinical outcomes of patients with active CD or UC. Further, switching from IV to SC IFX might confer more favourable pharmacokinetic outcomes, although larger comparative studies are warranted. (Table Presented).

Long-term health sequelae and quality of life at least 6 months after infection with SARS-CoV-2: design and rationale of the COVIDOM-study as part of the NAPKON population-based cohort platform (POP).

PURPOSE: Over the course of COVID-19 pandemic, evidence has accumulated that SARS-CoV-2 infections may affect multiple organs and have serious clinical sequelae, but on-site clinical examinations with non-hospitalized samples are rare. We, therefore, aimed to systematically assess the long-term health status of samples of hospitalized and non-hospitalized SARS-CoV-2 infected individuals from three regions in Germany. METHODS: The present paper describes the COVIDOM-study within the population-based cohort platform (POP) which has been established under the auspices of the NAPKON infrastructure (German National Pandemic Cohort Network) of the national Network University Medicine (NUM). Comprehensive health assessments among SARS-CoV-2 infected individuals are conducted at least 6 months after the acute infection at the study sites Kiel, Würzburg and Berlin. Potential participants were identified and contacted via the local public health authorities, irrespective of the severity of the initial infection. A harmonized examination protocol has been implemented, consisting of detailed assessments of medical history, physical examinations, and the collection of multiple biosamples (e.g., serum, plasma, saliva, urine) for future analyses. In addition, patient-reported perception of the impact of local pandemic-related measures and infection on quality-of-life are obtained. RESULTS: As of July 2021, in total 6813 individuals infected in 2020 have been invited into the COVIDOM-study. Of these, about 36% wished to participate and 1295 have already been examined at least once. CONCLUSION: NAPKON-POP COVIDOM-study complements other Long COVID studies assessing the long-term consequences of an infection with SARS-CoV-2 by providing detailed health data of population-based samples, including individuals with various degrees of disease severity. TRIAL REGISTRATION: Registered at the German registry for clinical studies (DRKS00023742).

Circulating sDPP-4 is increased in human subjects with obesity and related metabolic abnormalities and is altered in subjects hospitalized for severe COVID-19 infection

Aims Dipeptidylpeptidase is a key regulator of the incretin system. Initially, it's soluble form (sDPP-4) was described as an adipokine mediating metabolic inflammation. This is recently questioned in mechanistic rodent studies. To further clarify sDPP-4's role in physiology and metabolic diseases, we examined sDPP-4 in a large human cohort and during weight-loss interventions. Like ACE2, sDPP-4 serves as a binding partner for certain corona-like viruses enabling virus entry. As metabolic diseases are major risk factors for the COVID-19 pandemic, we additionally examined sDPP-4 in patients suffering severe Sars-CoV-2 infection. Methods sDPP-4 serum concentrations were measured using ELISA and related to various metabolic variables. Using a case-control-design, sDPP-4 was assessed in acute COVID-19 and sepsis infection. Results sDPP-4 increased with body weight, insulin resistance and hypertriglyceridemia but reduced in type 2 diabetes and arterial hypertension. Altered serum concentrations appeared with impaired liver and kidney but not cardiac function. No association to systemic inflammation was observed. Having found increased sDPP-4 in obesity, surgical (gastric bypass/sleeve gastrectomy) and non-surgical weight-loss interventions revealed a significant association of sDPP-4 with the improvement of liver function but neither with changes in body weight nor fat mass. Complementary, the case control study revealed reduced sDPP-4 concentrations specific for COVID-19 infection. Conclusions We suggest that sDPP-4 is rather related to hepatic abnormalities in obesity than primarily functioning as an adipokine. sDPP-4 is implicated in glucose and lipid metabolism, but not fundamentally in systemic inflammation. Additional to ACE-2, sDPP-4 might also have a regulatory role in COVID-19 infection.

Impact of concomitant hydroxychloroquine use on safety and efficacy of remdesivir in moderate COVID-19 patients

Background: Remdesivir (RDV) has been shown to shorten recovery time and was well tolerated in patients with severe COVID-19. Hydroxychloroquine (HQN) is an experimental treatment for COVID-19. Effects of coadministration of HQN with RDV have not been studied and are relevant given the long half-life (∼22 days) of HQN. We report the impact of concomitant HQN and RDV use on clinical outcomes and safety in patients with moderate COVID-19. Methods: We enrolled hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation >94% on room air, and radiological evidence of pneumonia. Patients were randomized 1:1:1 to receive 5d or 10d of intravenous RDV once daily plus standard of care (SoC), or SoC only. We compared patients on concomitant HQN (HQNpos) vs not (HQNneg). Clinical recovery was evaluated using Cox proportional hazards. Covariate adjustment included age, sex, race, region, symptom duration, oxygen support status and obesity. Recovery and adverse events (AEs) were assessed through death, discharge, or d14. Results: Of 584 patients, 199 (34%) received HQN (5d RDV: n=57 [30%];10d RDV, n=49 [25%];SoC: n=93 [47%]). Through median follow-up of 13d (range 1-41d), HQNpos patients on 5d or 10d RDV had a lower recovery rate (adjusted HR [95% CI] 0.78 [0.59, 1.03], p=0.09) with longer median time to recovery (8 vs 6 days) compared to HQNneg. HQNpos compared to HQNneg patients in 5d RDV showed a trend of reduced recovery rate (HR: 0.69 [0.45,1.04], p=0.080);such an effect was not observed in 10d RDV or SoC (Table 1). More HQNpos than HQNneg patients had AEs in RDV (5/10d) or SoC arms evaluated separately, and all arms combined. This difference was significant for AEs and SAEs for all arms combined after covariate adjustment (Table 2). Conclusion: In moderate COVID-19 patients, concomitant HQN may delay recovery on RDV and showed no impact on recovery with SoC alone. The AE profile of HQNpos patients was worse than that observed for HQNneg patients, regardless of RDV treatment.