SMYD2 Inhibition Downregulates TMPRSS2 and Decreases SARS-CoV-2 Infection in Human Intestinal and Airway Epithelial Cells.

The COVID-19 pandemic caused by SARS-CoV-2 has lasted for more than two years. Despite the presence of very effective vaccines, the number of virus variants that escape neutralizing antibodies is growing. Thus, there is still a need for effective antiviral treatments that target virus replication independently of the circulating variant. Here, we show for the first time that deficiency or pharmacological inhibition of the cellular lysine-methyltransferase SMYD2 decreases TMPRSS2 expression on both mRNA and protein levels. SARS-CoV-2 uses TMPRSS2 for priming its spike protein to infect target cells. Treatment of cultured cells with the SMYD2 inhibitors AZ505 or BAY598 significantly inhibited viral replication. In contrast, treatment of Vero E6 cells, which do not express detectable amounts of TMPRSS2, had no effect on SARS-CoV-2 infection. Moreover, by generating a recombinant reporter virus that expresses the spike protein of the Delta variant of SARS-CoV-2, we demonstrate that BAY598 exhibits similar antiviral activity against this variant of concern. In summary, SMYD2 inhibition downregulates TMPRSS2 and blocks viral replication. Targeting cellular SMYD2 represents a promising tool to curtail SARS-CoV-2 infection.

Long COVID 1 year after hospitalisation for COVID-19: a prospective bicentric cohort study.

AIMS OF THE STUDY: There is increasing interest in better understanding of long COVID, a condition characterised by long-term sequelae ­ appearing or persisting after the typical convalescence period ­ of coronavirus disease 2019 (COVID-19). Herein, we describe long-term outcomes regarding residual symptoms and psychological distress in hospitalised patients 1 year after COVID-19. METHODS: This prospective cohort study included consecutive adult patients hospitalised for confirmed COVID-19 in two Swiss tertiary-care hospitals between March and June 2020. The primary endpoint was evidence of long COVID 1 year after discharge, defined as ≥1 persisting or new symptom related to COVID-19, from a predefined list of symptoms. Secondary endpoints included psychological distress and symptoms of post-traumatic stress disorder (PTSD). RESULTS: Among 90 patients included in the study, 63 (70%) had symptoms of long COVID 1 year after hospitalisation, particularly fatigue (46%), concentration difficulties (31%), shortness of breath (21%) and post-exertion malaise (20%). Three predictors, namely duration of hospitalisation (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.00­1.22; p = 0.041), severity of illness (OR 1.19, 95% CI 1.04­1.37; p = 0.013), and self-perceived overall health status 30 days after hospitalisation (OR 0.97, 95% CI 0.94­1.00; p = 0.027) were associated with long COVID. Regarding secondary endpoints, 16 (18%) experienced psychological distress and 3 (3.3%) patients had symptoms of PTSD. CONCLUSION: A high proportion of COVID-19 patients report symptoms of long COVID 1 year after hospitalisation, which negatively affects their quality of life. The most important risk factors were severe initial presentation of COVID-19 with long hospital stays.

Doctor-patient communication during the Corona crisis - web-based interactions and structured feedback from standardized patients at the University of Basel and the LMU Munich.

Background: Due to the pandemic-related restrictions in classroom teaching at the medical faculties of the LMU Munich and the University of Basel, teaching methods with standardized patients (SPs), were shifted to a digital, web-based format at short notice as of April 2020. We report on our experiences with the WebEncounter program, which was used for the first time in German-speaking countries. The program enables one-to-one encounters between SPs and students. Students receive an invitational email with brief instructions and background information on the case. SPs use case-specific criteria that are compliant with the learning objectives for digital evaluation during the encounter. A feedback session takes place immediately following the encounter. The SPs address the didactically relevant sections and can illustrate them with the corresponding video sequences. Finally, the students receive the links to the video recordings of the encounter and the feedback unit by email. Project description: The aim of this pilot study was to analyze the practicability of the program and its acceptance by students and SPs. In addition, we examined whether the operationalization of the learning objectives in the form of assessment items has an impact on the content and thematic development of courses in the area of doctor-patient communication. Methods: To implement the program, patient cases previously tested in communication seminars in Munich and Basel were rewritten and case-specific evaluation criteria were developed. SPs were trained to use the program, to present their patient figure online and to give feedback. The experience of those involved (faculty, SPs and SP trainers, students) in implementing the program was documented at various levels. The frequency and causes of technical problems were described. Student results on the patient cases and on the feedback items were collected quantitatively and, where possible, supplemented by free-text statements. Results: Data from 218/220 students in Basel and 120/127 students in Munich were collected and evaluated. Students were very satisfied with the patient cases, the encounter with the SPs and their feedback: 3.81±0.42. SPs experienced the training as an increase in their competence and the structured feedback as particularly positive. The training effort per SP was between 2.5 and 4 hours. The results show predominantly normally-distributed, case-specific sum scores of the evaluation criteria. The analysis of the individual assessment items refers to learning objectives that students find difficult to achieve (e.g. explicitly structuring the conversation). Problems in the technical implementation (<10 percent of the encounters) were due mainly to the use of insufficient hardware or internet connection problems. The need to define case-specific evaluation criteria triggered a discussion in the group of study directors about learning objectives and their operationalization. Summary: Web-based encounters can be built into the ongoing communication curriculum with reasonable effort. Training the SPs and heeding the technical requirements are of central importance. Practicing the virtual consultation was evaluated very positively by the students - in particular, the immediate feedback in the protected dialogue was appreciated by all involved.

Psychological burden in patients with COVID-19 and their relatives 90 days after hospitalization: A prospective observational cohort study.

OBJECTIVE: COVID-19 causes psychological distress for patients and their relatives at short term. However, little research addressed the longer-term psychological outcomes in this population. Therefore, we aimed to prospectively assess clinically relevant psychological distress in hospitalized patients with COVID-19 and their relatives 90 days after hospital discharge. METHODS: This exploratory, prospective, observational cohort study included consecutive adult patients hospitalized in two Swiss tertiary-care hospitals between March and June 2020 for confirmed COVID-19 and their relatives. The primary outcome was psychological distress defined as clinically relevant symptoms of anxiety and/or depression measured with the Hospital Anxiety and Depression Scale (HADS) 90 days after discharge. RESULTS: Clinically relevant psychological distress 90 days after hospital discharge was present in 23/108 patients (21.3%) and 22/120 relatives (18.3%). For patients, risk and protective factors associated with clinically relevant psychological distress included sociodemographic, illness-related, psychosocial, and hospital-related factors. A model including these factors showed good discrimination, with an area under the receiver-operating characteristic curve (AUC) of 0.84. For relatives, relevant risk factors were illness-related, psychosocial, and hospital-related factors. Resilience was negatively associated with anxiety and depression in both patients and relatives and regarding PTSD in relatives only. CONCLUSION: COVID-19 is linked to clinically relevant psychological distress in a subgroup of patients and their relatives 90 days after hospitalization. If confirmed in an independent and larger patient cohort, knowledge about these potential risk and protective factors might help to develop preventive strategies.

Prevalence and factors associated with psychological burden in COVID-19 patients and their relatives: A prospective observational cohort study.

BACKGROUND: Due to the dramatic measures accompanying isolation and the general uncertainty and fear associated with COVID-19, patients and relatives may be at high risk for adverse psychological outcomes. Until now there has been limited research focusing on the prevalence of psychological distress and associated factors in COVID-19 patients and their relatives. The objective of our study was to assess psychological distress in COVID-19 patients and their relatives 30 days after hospital discharge. METHODS: In this prospective observational cohort study at two Swiss tertiary-care hospitals we included consecutive adult patients hospitalized between March and June 2020 for a proven COVID-19 and their relatives. Psychological distress was defined as symptoms of anxiety and/or depression measured with the Hospital Anxiety and Depression Scale (HADS), i.e., a score of ≥8 on the depression and/or anxiety subscale. We further evaluated symptoms of post-traumatic stress disorder (PTSD), defined as a score of ≥1.5 on the Impact of Event Scale-Revised (IES-R). RESULTS: Among 126 included patients, 24 (19.1%) had psychological distress and 10 (8.7%) had symptoms of PTSD 30 days after hospital discharge. In multivariate logistic regression analyses three factors were independently associated with psychological distress in patients: resilience (OR 0.82; 95%CI 0.71 to 0.94; p = 0.005), high levels of perceived stress (OR 1.21; 95%CI 1.06 to 1.38; p = 0.006) and low frequency of contact with relatives (OR 7.67; 95%CI 1.42 to 41.58; p = 0.018). The model showed good discrimination, with an area under the receiver-operating characteristic curve (AUC) of 0.92. Among 153 relatives, 35 (22.9%) showed symptoms of psychological distress, and 3 (2%) of PTSD. For relatives, resilience was negatively associated (OR 0.85; 95%CI 0.75 to 0.96; p = 0.007), whereas perceived overall burden caused by COVID-19 was positively associated with psychological distress (OR 1.72; 95%CI 1.31 to 2.25; p<0.001). The overall model also had good discrimination, with an AUC of 0.87. CONCLUSION: A relevant number of COVID-19 patients as well as their relatives exhibited psychological distress 30 days after hospital discharge. These results might aid in development of strategies to prevent psychological distress in COVID-19 patients and their relatives.

Collateral damage of the COVID-19 pandemic: an alarming decline in critical procedures in otorhinolaryngology in a German university hospital.

PURPOSE: The COVID-19 pandemic has a major impact on the diagnosis and treatment of ENT patients. The aim of this study was to analyze the influence of the pandemic on the number of otolaryngological procedures, particularly for critical diagnoses with potential negative effects due to prolonged symptom duration. METHODS: We evaluated 10,716 surgical procedures between January 1, 2018 and May 31, 2020, focusing on the 16-week period around March 16, 2020, which includes 1080 observations. We further analyzed subsets of critical procedures. RESULTS: We found a decline in critical procedures by 43% although no critical procedures were postponed by the hospital. Meanwhile, the share of critical procedures increased up to 90% caused by the cancellation of elective surgery. Especially worrisome was that diagnostic procedures for suspected malignancies decreased by 41% during the pandemic. CONCLUSION: The decline in critical procedures in otorhinolaryngology as collateral damage of the COVID-19 pandemic is considerable and therefore alarming.