[Attitudes toward digital tools in pain medicine : Survey of German Pain Society health professional members and members of self-help groups]. / Einstellung zur digitalen Medizin im Schmerzbereich : Eine Umfrage unter Ärzten und Patienten der Deutschen Schmerzgesellschaft und Patientenorganisationen.

Digital medicine has increasing influence on the German healthcare system. In times of social distancing during the ongoing coronavirus disease 2019 (COVID-19) pandemic, digital tools enable health professionals to maintain medical care. Furthermore, digital elements have potential to provide effective guideline-oriented treatment to a broad range of patients independently from location and time. This survey was used to assess the attitudes of members of the German Pain Society (health professionals) and of associated self-help groups (patients) towards digital medicine. It was sent out as an online survey to health professionals in September 2020 and to patients in February 2021. The survey referred especially to present usage, attitude and potential concerns regarding particular digital elements. Furthermore, technical affinity was assessed. In total, 250 health professionals and 154 patients participated in the survey. The results show that-although digital elements are already known-a substantial proportion of health professionals still lack broad transfer to regular treatment. The potential of digital tools seems to be recognized by both groups; interestingly, patients consider digital medicine as more useful than health professionals. Nevertheless, concerns about for example data security or digital competence remain in both groups. Taken together, our results indicate that disruptive changes, as the implementation of digital medicine in the healthcare system, have to be guided by intense education and channeled by political policies in order to successfully integrate digital elements into medicine on a long-term basis. This would be in favor for all involved parties and is demanded especially by patients.

Targeted escape of SARS-CoV-2 in vitro from monoclonal antibody S309, the precursor of sotrovimab.

Class 1 and 2 monoclonal antibodies inhibit SARS-CoV-2 entry by blocking the interaction of the viral receptor-binding domain with angiotensin-converting enzyme 2 (ACE2), while class 3 antibodies target a highly conserved epitope outside the ACE2 binding site. We aimed to investigate the plasticity of the spike protein by propagating wild-type SARS-CoV-2 in the presence of class 3 antibody S309. After 12 weeks, we obtained a viral strain that was completely resistant to inhibition by S309, due to successively evolving amino acid exchanges R346S and P337L located in the paratope of S309. The antibody lost affinity to receptor-binding domains carrying P337L or both amino acid exchanges, while ACE2 binding was not affected. The resistant strain replicated efficiently in human CaCo-2 cells and was more susceptible to inhibition of fusion than the original strain. Overall, SARS-CoV-2 escaped inhibition by class 3 antibody S309 through a slow, but targeted evolution enabling immune escape and altering cell entry. This immune-driven enhancement of infectivity and pathogenicity could play an important role in the future evolution of SARS-CoV-2, which is under increasing immunological pressure from vaccination and previous infections.

Influenza vaccination coverage among emergency department personnel is associated with perception of vaccination and side effects, vaccination availability on site and the COVID-19 pandemic.

INTRODUCTION: Influenza is a major concern in hospitals, including the emergency department (ED), mainly because of a high risk for ED personnel to acquire and transmit the disease. Although influenza vaccination is recommended for health care workers, vaccination coverage is low. METHODS: This survey was conducted in the 2016/2017 and 2020/2021 influenza seasons. Questionnaires were sent to ED personnel in 12 hospitals in Bavaria, South-Eastern Germany. The response rates were 62% and 38% in 2016/2017 and 2020/2021, respectively. Data were compared between the two seasons as well as between vaccinated and not vaccinated respondents in 2020/2021. RESULTS: Significantly more ED personnel reported having been vaccinated in the 2020/2021 season. Factors associated with vaccination coverage (or the intention to get vaccinated) were profession (physician / medical student), having been vaccinated at least twice, the availability of an influenza vaccination on site (in the ED) as well as the COVID-19 pandemic. Additionally, significant differences in the assessment and evaluation of influenza, its vaccination side effects and ethical aspects were found between vaccinated and not vaccinated ED personnel in 2020/2021. Unvaccinated respondents estimated higher frequencies of almost all potential vaccination side effects, were less likely to accept lay-offs if employees would not come to work during an influenza pandemic and more likely to agree that work attendance should be an employee´s decision. Vaccinated participants instead, rather agreed that vaccination should be mandatory and were less likely to consider job changes in case of a mandatory vaccination policy. CONCLUSION: The COVID-19 pandemic might have contributed to a higher influenza vaccination rate among ED workers. Vaccination on site and interventions targeting the perception of influenza vaccination and its side effects may be most promising to increase the vaccination coverage among ED personnel.

Lack of antibodies against seasonal coronavirus OC43 nucleocapsid protein identifies patients at risk of critical COVID-19.

BACKGROUND: The vast majority of COVID-19 patients experience a mild disease. However, a minority suffers from critical disease with substantial morbidity and mortality. OBJECTIVES: To identify individuals at risk of critical COVID-19, the relevance of a seroreactivity against seasonal human coronaviruses was analyzed. METHODS: We conducted a multi-center non-interventional study comprising 296 patients with confirmed SARS-CoV-2 infections from four tertiary care referral centers in Germany and France. The ICU group comprised more males, whereas the outpatient group contained a higher percentage of females. For each patient, the serum or plasma sample obtained closest after symptom onset was examined by immunoblot regarding IgG antibodies against the nucleocapsid protein (NP) of HCoV 229E, NL63, OC43 and HKU1. RESULTS: Median age was 60 years (range 18-96). Patients with critical disease (n=106) had significantly lower levels of anti-HCoV OC43 nucleocapsid protein (NP)-specific antibodies compared to other COVID-19 inpatients (p=0.007). In multivariate analysis (adjusted for age, sex and BMI), OC43 negative inpatients had an increased risk of critical disease (adjusted odds ratio (AOR) 2.68 [95% CI 1.09 - 7.05]), higher than the risk by increased age or BMI, and lower than the risk by male sex. A risk stratification based on sex and OC43 serostatus was derived from this analysis. CONCLUSIONS: Our results suggest that prior infections with seasonal human coronaviruses can protect against a severe course of COVID-19. Therefore, anti-OC43 antibodies should be measured for COVID-19 inpatients and considered as part of the risk assessment for each patient. Hence, we expect individuals tested negative for anti-OC43 antibodies to particularly benefit from vaccination against SARS-CoV-2, especially with other risk factors prevailing.

The potential of herbal extracts to inhibit SARS-CoV-2: a pilot study

BackgroundHerbal medicinal products have a long-standing history of use in the therapy of common respiratory infections. We sought to assess the potential of five validated herbal extracts regarding their ability to restrict SARS-CoV-2 replication in vitro: Bronchipret thyme-ivy (BRO TI), Bronchipret thyme-primrose (BRO TP), Imupret (IMU), Sinupret extract (SINx) and Tonsipret (TOP).MethodsVero cells were incubated with different concentrations of herbal extracts and infected with SARS-CoV-2 for 48 hours. The inhibition of viral replication was assessed by determination of the viral RNA load in the cell culture supernatant using quantitative polymerase chain reaction (qPCR).ResultsSARS-CoV-2 RNA load was reduced by non-cytotoxic concentrations of BRO-TP (up to approximately 1,000-fold) and, to a lesser extent, IMU and TOP (approximately 10-fold).ConclusionsSome herbal extracts showed a promising in vitro effectiveness against SARS-CoV-2, suggesting an antiviral potential of herbal medicinal products. The potential of herbal medicines to restrict SARS-CoV-2 and to treat COVID-19 should be investigated further in a clinical setting.

Secondary hemophagocytic lymphohistiocytosis and severe liver injury induced by hepatic SARS-CoV-2 infection unmasking Wilson's disease: Balancing immunosuppression.

A 21-year-old woman was hospitalized due to coronavirus disease 2019 (COVID-19)-associated respiratory and hepatic impairment concomitant with severe hemolytic anemia. Upon diagnosis of secondary hemophagocytic lymphohistiocytosis, immunosuppression with anakinra and steroids was started, leading to a hepatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and viremia. Subsequent liver biopsy revealed virus particles in hepatocytes by electron microscopy and SARS-CoV-2 virus could be isolated and cultured. Immunosuppression was stopped and convalescent donor plasma given. In the differential diagnosis, an acute crisis of Wilson's disease was raised by laboratory and genetic testing. This case highlights the complexity of balancing immunosuppression to control hyperinflammation versus systemic SARS-CoV-2 dissemination.

A highly specific and sensitive serological assay detects SARS-CoV-2 antibody levels in COVID-19 patients that correlate with neutralization.

OBJECTIVE: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic challenges national health systems and the global economy. Monitoring of infection rates and seroprevalence can guide public health measures to combat the pandemic. This depends on reliable tests on active and former infections. Here, we set out to develop and validate a specific and sensitive enzyme linked immunosorbent assay (ELISA) for detection of anti-SARS-CoV-2 antibody levels. METHODS: In our ELISA, we used SARS-CoV-2 receptor-binding domain (RBD) and a stabilized version of the spike (S) ectodomain as antigens. We assessed sera from patients infected with seasonal coronaviruses, SARS-CoV-2 and controls. We determined and monitored IgM-, IgA- and IgG-antibody responses towards these antigens. In addition, for a panel of 22 sera, virus neutralization and ELISA parameters were measured and correlated. RESULTS: The RBD-based ELISA detected SARS-CoV-2-directed antibodies, did not cross-react with seasonal coronavirus antibodies and correlated with virus neutralization (R2 = 0.89). Seroconversion started at 5 days after symptom onset and led to robust antibody levels at 10 days after symptom onset. We demonstrate high specificity (99.3%; N = 1000) and sensitivity (92% for IgA, 96% for IgG and 98% for IgM; > 10 days after PCR-proven infection; N = 53) in serum. CONCLUSIONS: With the described RBD-based ELISA protocol, we provide a reliable test for seroepidemiological surveys. Due to high specificity and strong correlation with virus neutralization, the RBD ELISA holds great potential to become a preferred tool to assess thresholds of protective immunity after infection and vaccination.