Development and validation of COVID-19 Radiological Risk Score (COVID-RRS): a multivariable radiological score to estimate the in-hospital mortality risk in COVID-19 patients.

OBJECTIVE: To develop and validate in-hospital mortality risk score comprising radiological aberrances in chest computed tomography (CT) performed on admission. PATIENTS AND METHODS: Single-center, longitudinal cohort study in adult patients admitted with Coronavirus Disease 2019 (COVID-19) to our ward. Patients were followed-up during hospitalization until discharge or death. Eligibility criteria for the study comprised positive real-time reverse transcription-polymerase chain reaction test (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and ground-glass opacities in chest CT. In-hospital death was the outcome of interest. Radiological, laboratory, and clinical data were analyzed. Radiological determinants of mortality were used as variables in multivariate logistic regression analysis, and results were used to build a radiological risk score. RESULTS: 371 patients were enrolled in development and validation cohorts (181 and 190 respectively), with a total of 47 non-survivors. Univariate analysis data determined 12 predictive factors (nine risk and three protective). In multivariate analysis, we developed COVID-RRS (COVID-19 Radiological Risk Score) - a radiological score predicting in-hospital COVID-19 mortality risk comprising estimated lung involvement percentage, pleural effusion, and domination of consolidation-type changes in chest CT. Our score was superior in the prediction of COVID-19 mortality to the percentage of lung involvement alone, Chest Computed Tomography Severity Score (CTSS), and Total Severity Score (TSS) in both groups with AUC of 0.910 and 0.902, respectively (p <0.001). CONCLUSIONS: Additional imaging features independently contribute to COVID-19 mortality risk. Our model comprising lung involvement estimation, pleural effusion, and domination of consolidations performed significantly better than scores based on the extent of the changes alone. COVID-RRS is a simple, reliable, and ready-to-use tool for clinical practice.

Attitude towards and experience with SARS-CoV-2 vaccination among German cancer patients

Background: Cancer patients (pts) were among the first to receive vaccination against SARS-CoV-2 (vac). However, their attitude towards as well as experience with vac remain unclear. Methods: Between 04-11/2021 cancer pts at our university cancer center completed a baseline (BL) and follow-up (FU) questionnaire (Q) containing multiple choice questions and ten eleven-level Likert items ranging from 1 (“totally disagree”) to 11 (“totally agree”). Data was analyzed using Student's t-test or Chi-square test. Results: 219 pts (43% female) completed BLQ (110 FUQ). Mean age was 64 (24-87) years. 82% had solid tumors, 93% were on active therapy (80% chemotherapy). 4% had history of COVID-19. 78% had already received at least one vac at BL, mainly BNT162b2 (91%) or ChAdOx1-S (8%). Only 1% refused vac. Most pts completely agreed to “definitely get vaccinated” (82%) and completely disagreed with “vac is dispensable due to COVID-19 being no serious threat” (82%;more dissent among men, p = 0.037) or “being against vaccination in general” (81%). Self-assessment as member of a risk group (p = 0.03) and fear of COVID-19 (p = 0.002) were more common among women. Every third patient (31%) completely agreed to “being afraid of COVID-19”, every second thinks “SARSCoV-2 infection would be very dangerous” (56%). Only 41% expressed “complete confidence in the vaccine being safe” and 37% “not being afraid of side effects”. Fear of side effects (SE) was more common among women (p = 0.0016), pts with solid tumors (p = 0.05), with GI tumors (p < 0.0001) and below mean age (p = 0.006). The latter expressed less “confidence in the vaccine being safe” (p = 0.0029). At FUQ, most pts (91%) reported their vac to be well tolerated, 44% reported no SE, especially men (p = 0.001) and pts above age average (p = 0.002). Most common SE was local pain at injection site (36%), which was more frequent among women (p = 0.002), younger pts (p = 0.024) and pts with solid tumors (p = 0.04). Other common SE included fatigue (18%) and myalgia (8%). No thromboembolic events occurred. Only 3 pts had their therapy postponed due to SE. Almost all pts felt retrospectively sufficiently informed about vac and possible SE (94%), would have it again (88%) and agree to get it yearly, if recommended (78%). After vac, pts felt safe meeting friends or family (91%) or shopping (62%). Vacation (32%), work (22%), public transport (21%) or sports (19%) were considered less safe (less frequent among men, p < 0.05). Most pts (70%) did not feel that the COVID-19 pandemic negatively influenced their treatment and regarded the hospitals protective measures as adequate (91%). Conclusions: Willingness to get vac is high among cancer pts and vac is well tolerated in this sensitive cohort. However, concerns about vac safety remain an issue. Those as well as gender differences need to be addressed to increase vac rates and tolerability. The present results may help identify pts that benefit from more detailed pre-vac consultation.

CLINICAL RESPONSE PREDICTORS of TOCILIZUMAB THERAPY in PATIENTS with SEVERE COVID-19

Background: Aberrant immune response is hallmark of severe COVID-19, irrespectively from viral replication. Immunomodulatory therapies such as interleukin-6 (IL-6) receptor inhibitors were proven to be benefcial in reducing in-hospital mor-tality1. Yet, it remains unclear which patients can beneft most from such therapy. Objectives: To identify predictors of clinical response to tocilizumab (TCZ) added to dexamethasone in patients hospitalized with severe COVID-19. Methods: We prospectively assessed clinical and laboratory details of 120 patients hospitalized due to severe COVID-19 treated with TCZ (two doses of 8 mg/kg 24h apart) in our ward between 1st Feb 2021 and 31st Dec 2021. Severe COVID-19 was defned as SpO2 <94% on room air with ground glass opacities in chest computed tomography (CT). Clinical response was defned as respiratory improvement on day 5 after TCZ infusion compared to day of treatment initiation, no further deterioration and survival. Decision of adding TCZ to dexamethasone as emergency therapy was made collectively by rheumatologists experienced in COVID-19 treatment. Laboratory and clinical parameters from hospital admission day and from TCZ institution day were analyzed. Statistical analysis was conducted with PQStat v.1.8.2 and predictors were identifed in univariate logistic regression. Results: We identifed 86 (71.7%) clinical responders and 34 (28.3%) non-re-sponders. 20 (58.8%) of the second group needed ICU admission, 18 (52.9%) died on ICU and 2 patients (5.9%) died on the ward. Responders were signif-cantly younger (mean age 56.1 vs. 63.5 years, p=0.006), had lesser comorbidity burden (median Charleson Comorbidity Index 2 vs. 3, p=0.005), lower median lung involvement (50 vs. 70%, p<0.001), higher median baseline PaO2/FiO2 index (203 vs. 106, p<0.001) and less of them needed high-fow oxygen therapy on TCZ initiation day (12.7% vs 32.4%, p=0.025). Identifed predictors of clinical response are shown in Table 1. Conclusion: Administration of TCZ early in severe disease, with moderate IL-6 concentration and low organ damage indices is most benefcial in patients with severe COVID-19, especially in younger patients without respiratory and cardiac comorbidities.

SARS-CoV-2 surveillance and usage of COVID-19 protection in hospital staff within clinical COVID-19 risk areas

Study design: Hospital personnel with contact to COVID-19 patients is regarded to be at risk for SARS-CoV-2 infections. So far, there is no longitudinal data on the incidence of SARS-CoV-2 infection in healthcare personnel working within clinical COVID-19 risk-areas compared to non-exposed personnel and considering the intensity of exposure, the use of personal protective equipment (PPE) and the regional infection rate of new infections. Therefore, a repetitive cross-sectional study of the incidence of SARS-CoV-2 infections in a risk and a control group within a German university hospital specialized in the care of COVID-19 patients was performed. Methods: From May to November 2020, healthcare personnel working within risk areas of a German university hospital and controls were regularly tested for SARS-CoV-2 RNA and anti-SARS-CoV-2 antibodies. Furthermore, participants were interviewed on COVID-19 exposure, symptoms, and the use of PPE. Results: In total, 199 persons (106 (53.3%) working in risk-areas and 93 (46.7%) controls) participated, corresponding to 77.4% of all healthcare- workers in risk-areas of the hospital. No participant in either group was tested positive for SARS-CoV-2 RNA in any of the 984 tests performed. Antibody incidence did not differ between the groups. Upon contact with COVID- 19 patients, FFP-2/KN95-masks or higher standard were always used, while other PPE (e.g., gloves) were used inconsistently. Symptoms did not differ between the groups. Conclusion: The incidence of SARSCoV- 2 infection in healthcare staff working in clinical COVID-19 risk areas using PPE, especially FFP-2/KN95- masks, is not increased compared to non-exposed controls. © 2021 mhp-Verlag GmbH. All rights reserved.

Medical Device Regulation and current challenges for the implementation of new technologies

The European Parliament and the European Council on May 26, 2017 decided to introduce the new regulatory framework for medical devices. The transitional period of the so called Medical Device Regulation (EU 2017/745, MDR) should end on May 26, 2020. Currently the European Commission is working on a proposal to postpone the application for one year to relieve pressure from all stakeholders allowing them to fully focus on priorities related to the coronavirus crisis. From this date or most likely from May 26, 2021, manufacturers must present a CE-certificate according to the new MDR requirements not only for novel medical devices, but also for approved medical devices which are already on the market. The MDR will significantly complicate the process of bringing medical devices into market due to the increased requirements for the CE-certification process, particularly concerning increased documentation effort. This involves a risk for the translation of innovative products due to an overload of the overall system (manufacturers, Notified Bodies, experts) and might lead to shrinkage of the product range of existing products. Thankfully, adaption of transitional periods, special regulations, extensions of deadlines and most probably postponement of the MDR application date will ensure that there will be no gaps in medical supply that endanger patients. Establishing and keeping the relevant regulatory expertise up to date and devoting the necessary financial, time and human resources that is the biggest immediate challenge the medium-sized medical technology sector is facing in the near future. The current article, written about one month before the initially expected end of the first transition period on May 26, 2020, summarized the main aspects of the current state of MDR implementation with respect to regulatory novelties, the current legal basis in Germany, transition periods and changes in the requirements of CE-certification relevant technical documentation. Furthermore, challenges for existing and innovative medical devices were shortly discussed using a new stent based therapy of the proximal Fallopian tubal stenosis and transcatheter aortic valve implantation as two examples. © 2020 by Walter de Gruyter Berlin/Boston 2020.