Plasma with high titers of anti-SARS-Cov2 antibodies improves outcome of COVID-19 in patients with hematological malignancy and cancer in a randomized controlled trial

Background. Patients with hematological malignancy or other cancers as well as immunosuppression bear a high risk for severe COVID-19. Monoclonal antibodies (mAb) are efficient at early stages of the disease but may lose potency with new variants. Trials on plasma from convalescent donors in unselected patients have not shown clinical benefit. No randomized trials focussing on patients with underlying disease have been published. Methods. We conducted an open-label, multicenter, randomized controlled trial to evaluate efficacy of plasma (CVP - convalescent or after vaccination) in patients with COVID-19 at high risk for adverse outcome in Germany. We assessed the effect of high-titer CVP (2 units from different donors, 238-337 ml each, on subsequent days). Patients with hematological or other malignancy (group 1), immunosuppression (group 2), age >50 and <=75 years and lymphopenia and/or high D-dimers (group 3) or age >75 years (group 4) who were hospitalized with confirmed SARS-CoV-2 infection and with an oxygen saturation <=94% were included. Primary outcome measure was time to clinical improvement on a seven-point ordinal scale, secondary outcome was mortality (Janssen et al. Trials 2020 Oct 6;21(1):828). Results. Overall, 133 patients were randomized, 68 received CVP with an additional 10 patients as a crossover on day 10. Median age (range) was 68 years (39-95) in the CVP group and 70 (38-90) in controls. For the entire cohort, no significant difference was seen in time to improvement (median days: CVP 12.5 vs. control 18;HR 1.24 (95% confidence interval (CI) 0.83-1.85), p=0.29). Subgroup analysis (group 1+2) revealed shortened time to improvement (median days CVP 13 vs. control 32;HR 2.03 (95%CI 1.17-3.6), p=0.01) and mortality was reduced (mortality CVP n=6 (18%) vs. control n=10 (29%). No significant differences in time to improvement were observed in group 3 or 4 (HR 0.72 (95%CI 0.41-1.28), p=0.26). No relevant adverse events were observed. Conclusion. CVP improves time to clinical improvement and mortality for COVID-19 patients with underlying hematological disease/cancer or other reasons of impaired immune response. Even with new variants, high-titer CVP may offer a widely available and inexpensive therapy option in high-risk groups. Funding. BMBF FKZ 01KI20152;EudraCT 2020-001632-10.

A RANDOMIZED CONTROLLED CLINICAL TRIAL DEMONSTRATES THAT PLASMA FROM CONVALESCENT AND VACCINATED DONORS IMPROVES OUTCOME OF COVID-19 IN PATIENTS WITH HEMATOLOGICAL DISEASE, CANCER OR IMMUNOSUPPRESSION

Background: Therapy options are limited for COVID-19 patients with hematological disease, cancer, immunosuppression or adanced age. Een though no benefit was obsered for conalescent plasma in unselected patients with COVID-19, retrospectie data suggest that it could be effectie in patients unable to mount a sufficient immune response upon SARS-CoV-2 infection. Plasma from accinated donors has not been systematically assessed for COVID-19 treatment. Aims: We conducted a randomized clinical trial to address plasma efficacy in patients at high risk for an aderse outcome. Methods: COVID-19 patients with confirmed SARS-CoV-2 infections and oxygen saturation <=94% were randomized (NCT05200754). Patients receied conalescent or accinated SARS-CoV-2 plasma in two bags (238 - 337 ml plasma each) from different donors on day 1 and 2 (PLASMA) or standard of care (CONTROL). Randomization was stratified according to four clinical patient groups, hematological/solid cancer (group-1), treatment or disease associated immunosuppression (group 2), high risk disease by standard parameters (group-3) or age >=75 years (group-4). Mechanically entilated patients were not eligible. Plasma was obtained from donors with high leel neutralizing actiity (titer >=1:80) either after SARS-CoV-2 infection (conalescent) or after accination with at least two doses of mRNA accines (accinated). Crossoer for the control group was allowed at day 10. The primary endpoint was time to improement as two points on a seen-point ordinal scale or lie discharge from the Hospital (IMPROVEMENT) with prespecified analyses of subgroups (Janssen M, et al. Trials 2020 Oct 6;21(1):828). Results: A total of 133 patients were randomized with 68 receiing PLASMA with a median age of 68 years (range 36-95) or CONTROL (n=65, of which n=10 (15.4%) crossed oer at day 10) with a median age of 70 years (range 38-90). The distribution of the four predefined groups was group-1, n=53;group-2, n=18;group-3, n=35;and group-4, n=27. The intention to treat analysis reealed a non-significant shorter time to IMPROVEMENT for patients in PLASMA (median 12.5 days, 95%-CI [10;16]) compared to patients in CONTROL (median 18 days, 95%-CI [11;28] ), hazard ratio 1.24, 95% confidence interal [0.83;1.85], p=0.29). Oerall, 27 patients died (PLASMA, n=12;CONTROL, n=15;p=0.80). Predefined subgroup analysis reealed a clinically significant benefit in patients with hematological malignancies, other cancers or immunosuppression (group-1, group-2, n=71). With a median time to improement of 13 days (95%-CI [9;19]) for PLASMA and 32 days (95%-CI [17;57]) for CONTROL(HR 2.03, 95%-CI [1.17;3.6], p=0.01). A sensitiity analysis reealed that IMPROVEMENT appeared to be seen een earlier with accinated (median 10 days, 95%-CI [8;14]) compared to conalescent SARS-CoV-2 plasma (median 13 days, 95%-CI [6;38]) and CONTROL. Within group-1 and group-2, six patients in PLASMA (18.2%) and 10 in CONTROL (28.6%) died. No significant differences in improement were obsered in group-3 and group-4 with a HR of 0.72 (95%-CI [0.41;1.28], p=0.26). Within group-3 and group-4, six patients in PLASMA (18.8%) and fie in CONTROL (16.7%) died. No preiously unknown side effects of plasma therapy emerged within the trial. Summary/Conclusion: Plasma from conalescent and particularly accinated donors improed outcome of COVID-19 patients with an underlying hematological disease /cancer or other reasons of impaired immune response. Plasma did not improe outcome in immune-competent patients with other risk factors and/or older age. (Figure Presented).

Are our children engaged with school in the era of covid-19?

During 2020 the health situation linked to the COVID-19 has led to the suspension of face-to-face classes in almost all of the Argentine territory. Different distance-learning resources were developed to replace traditional classes. The aim of this study was to assess the school engagement (SE) of Argentinian children and adolescents aged 3 to 18 in the distance schooling context due to the COVID-19 pandemic, and to analyze its variability based on socioeconomic status, gender, educational level and movement restriction measures. Caregivers of 1205 children and adolescents (47,5% females, 51,8% males, 0,7% trans/non-binary) answered an online survey between June 5 and June 28, 2020. The survey included an SE questionnaire which was adapted to the virtual schooling context and showed adequate psychometric properties. The results showed higher values of behavioral SE in comparison to emotional SE, and differences according to the variables measured. Less general SE in students attending second cycle of primary school (9 to 12 years), higher behavioral SE in secondary school students, and higher emotional SE in preschool children was found. Girls and students of the upper-middle and upper classes who attend private schools reported higher levels of SE in both dimensions. Also, lower SE was found in students under isolation measures, comparing to those under distancing measures. The contribution of the results for the analysis of the current situation is discussed, and the importance of school engagement as a central variable to assess the effectiveness of the educational practices in a pandemic context is highlighted. © 2021, Universitatea din Oradea. All rights reserved.

Institutional Provision of Destination Management in the Most Important and in the Crisis Period the Most Vulnerable Regions of Tourism in Slovakia

The aim of the presented paper is to examine the specific situation in the institutional provision of tourism in Slovakia with special regard to the most important and in the crisis period the most vulnerable tourism regions, their identification is a partial goal of the paper. With regard to the current crisis period, the survey is supplemented by identifying factors of employment change, focusing mainly on the region's competitiveness in tourism. The importance of regions is assessed in the article on the basis of potential for tourism development, further in terms of their importance for tourism in Slovakia based on tourism performance expressed by the number of overnight stays and on the basis of industry concentration of tourism measured by employment in tourism. We consider the most vulnerable regions to be those that reach the level of specialization in tourism (based on the localization coefficient) and it has a growing tendency. The research results show that the importance of regional competitiveness in tourism for employment change (which is a regional component) is very different despite the established destination management, it is even negative, and in the case of positive figures, it is without an obvious advantage over other factors analyzed in the shift-share analysis. Also, it is possible that the current crisis period caused by measures in connection with the COVID-19 pandemic will help to find endogenous solutions to fragmented destination management in the most important and vulnerable tourism regions, or legislative solutions related to the amendment to the Tourism Promotion Act. © 2021 Anna Michálková et al., published by Sciendo 2021.