Long-term Follow up (> 1 year) of Plasma Donors and Patients treated with COVID-19 Convalescent Plasma within the CAPSID trial

Background: COVID-19-Convalescent Plasma (CCP) showed beneficial effects when given early in the treatment course or when it contains high-titre of neutralizing antibodies. Here we present a long-term follow up of patients of the multicentric national randomized CAPSID trial that investigated the effect of CCP in hospitalized COVID-19 patients. CCP donors were also included in the follow up and severed as a control group of patients with mild to moderate disease. Method(s): Patients and donors were invited to participate in the long-term follow up. Data on long-term overall survival (OS) were available for n=52 patients (control group: n=22, high titre CCP: n=16, low-titre CCP: n=14) and n=113 donors. Structured interview and a quality of life (QoL) assessment by questionnaires (FACIT fatigue, FACIT dyspnea and EQ-ED- 5DL) were performed. Visits took place online or on site. Laboratory tests included neutralizing antibody testing by PRNT and inflammation markers. Data are given as median with IQR. Medical events were assessed and graded according to CTCAE. For donors the median follow up time was 517 (483-553) days after the first plasmapheresis and for patients 395 (371-417) days after randomization. Result(s): Medical events during follow up were reported in 27% of donors and 16% of patients (p=0.164) with grade 3 or higher in 9% of donors and 22% of patients. More patients than donors reported a decrease in their socioeconomic status and reported more frequently about GI, pulmonal, pain symptoms or alopecia (p<0.02), but no difference in neurologic symptoms including anosmia was observed. Post COVID-Scale was worse in patients with a trend for better outcome in the CCP group (p=0.089). The trend for better OS in the CCP group became more pronounced during the long-term follow up (p=0.08) and OS remained significantly better in the high dose CCP group (p=0.01). All QoL scores showed a consistent trend towards better outcomes of the CCP group. Conclusion(s): To our knowledge, this is the first long-term follow up from a randomized trial of CCP. CCP-donors with mild to moderate COVID- 19 had a significant smaller long-term disease burden than patients with severe disease. The addition of CCP added to standard treatment in severe COVID-19 showed a trend to better OS and QoL. We had previously reported significant better outcomes in the high-titre CCP subgroup (until day 60). This was even more pronounced during the long-term follow up (> 1 year).

The results of cardiac surgery during the COVID-19 pandemic compared with previous years: a propensity weighted study of outcomes at six months.

OBJECTIVES: In addition to excess mortality due to COVID-19, the pandemic has been characterised by excess mortality due to non-COVID diagnoses and consistent reports of patients delaying seeking medical treatment. This study seeks to compare the outcomes of cardiac surgery during and before the COVID-19 pandemic. DESIGN: Our institutional database was interrogated retrospectively to identify all patients undergoing one of three index procedures during the first six months of the pandemic and the corresponding epochs of the previous five years. SETTING: A regional cardiothoracic centre. PARTICIPANTS: All patients undergoing surgery during weeks #13-37, 2015-2020. MAIN OUTCOME MEASURES: Propensity score weighted analysis was employed to compare the incidence of major complications (stroke, renal failure, re-ventilation), 30-day mortality, six month survival and length of hospital stay between the two groups. RESULTS: There was no difference in 30-day mortality (HR = 0.76 [95% CI 0.27-2.20], p = 0.6211), 6-month survival (HR = 0.94 [95% CI 0.44-2.01], p = 0.8809) and duration of stay (SHR = 1.00 (95% CI 0.90-1.12), p = 0.959) between the two eras. There were no differences in the incidence of major complications (weighted chi-square test: renal failure: p = 0.923, stroke: p = 0.991, new respiratory failure: p = 0.856). CONCLUSIONS: Cardiac surgery is as safe now as in the previous five years. Concerns over the transmission of COVID-19 in hospital are understandable but patients should be encouraged not to delay seeking medical attention. All involved in healthcare and the wider public should be reassured by these findings.

Antiviral drug screen identifies DNA-damage response inhibitor as potent blocker of SARS-CoV-2 replication.

SARS-CoV-2 has currently precipitated the COVID-19 global health crisis. We developed a medium-throughput drug-screening system and identified a small-molecule library of 34 of 430 protein kinase inhibitors that were capable of inhibiting the SARS-CoV-2 cytopathic effect in human epithelial cells. These drug inhibitors are in various stages of clinical trials. We detected key proteins involved in cellular signaling pathways mTOR-PI3K-AKT, ABL-BCR/MAPK, and DNA-damage response that are critical for SARS-CoV-2 infection. A drug-protein interaction-based secondary screen confirmed compounds, such as the ATR kinase inhibitor berzosertib and torin2 with anti-SARS-CoV-2 activity. Berzosertib exhibited potent antiviral activity against SARS-CoV-2 in multiple cell types and blocked replication at the post-entry step. Berzosertib inhibited replication of SARS-CoV-1 and the Middle East respiratory syndrome coronavirus (MERS-CoV) as well. Our study highlights key promising kinase inhibitors to constrain coronavirus replication as a host-directed therapy in the treatment of COVID-19 and beyond as well as provides an important mechanism of host-pathogen interactions.

Work team identification associated with less stress and burnout among front-line emergency department staff amid the COVID-19 pandemic

Background: The COVID-19 pandemic has exposed front-line healthcare workers to unprecedented risks and stressors threatening both physical and mental health. Prior work in the military has found that team identification, or the sense that one was a part of a team, can help reduce stress and prevent burnout during prolonged stress. Methods: We conducted repeated cross-sectional surveys embedded within emergency department workflow to understand whether team identification was associated with reduced reports of stress and burnout among front-line workers. Results: During the 10-week study which spanned the first wave of COVID-19, 327 of 431 (76%) front-line healthcare workers responded to at least one round of the survey. Higher team identification was associated with significantly less work stress (B=-0.60, 95% CI -0.84 to to -0.40, p<0.001) and burnout (B=-12.87, 95% CI -17.73 to -8.02, p<0.001) in cross-sectional analyses. Further evidence of the protective effect of team identification for work stress (B=-0.36, 95% CI -0.76 to 0.05, p=0.09) and burnout (B=-13.25, 95% CI -17.77 to -8.73, p<0.001) was also found in prospective longitudinal evidence. Conclusion: This work suggests work team identification is a key buffering factor against feelings of stress and burnout. Efforts to promote team identification may offer a promising way for leaders to support front-line healthcare workers' well-being during the COVID-19 pandemic. These results can inform ongoing COVID-19 operational and quality improvement initiatives. © 2020 Author(s) (or their employer(s)). No commercial re-use. See rights and permissions. Published by BMJ.