Safety and Efficacy of Vidofludimus Calcium in Patients Hospitalized with COVID-19: A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial.

INTRODUCTION: Vidofludimus calcium has shown anti-inflammatory effects in clinical trials of autoimmune diseases and recently demonstrated antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We performed a double-blind, randomized, placebo-controlled, phase 2 trial to evaluate the safety and efficacy of vidofludimus calcium in patients hospitalized for coronavirus disease 2019 (COVID-19) in Europe and the USA. METHODS: Patients aged 18 years or older who positive for COVID-19 were randomized (1:1) to receive placebo or 45 mg vidofludimus calcium for 14 days with both groups receiving standard-of-care treatment. The primary endpoint was the need for invasive ventilation after 28 days (ClinicalTrials.gov NCT04379271; EudraCT 2020-001264-28). RESULTS: Between June 12, 2020 and December 10, 2020, a total of 223 were randomized to receive either placebo (n = 112) or vidofludimus calcium (n = 111); three patients withdrew consent and were not treated. Eight (9%) patients in the placebo group and 12 (11%) patients in the vidofludimus calcium group needed invasive ventilation during the 28-day study period, which was lower than the assumed rate of 40%. Time to clinical improvement was shorter by approximately 1 day in the vidofludimus calcium group (15.0 days [90% CI 14.8-15.9]) compared to the placebo group (15.9 days [90% CI 14.9-19.9]). This effect was greatest in patients who initiated therapy within 9 days of symptom onset (3.8 days shorter in the vidofludimus calcium group). Higher trough concentrations of vidofludimus calcium were associated with quicker time to clinical recovery. The rate and timing of appearance of anti-SARS-CoV-2 antibodies were not different between groups. Serious adverse events occurred in 4 (4%) patients in the placebo group and 2 (2%) patients in the vidofludimus calcium group; treatment-emergent adverse events of increased severity related to COVID-19 occurred in 13 (12%) patients in the placebo group and 8 (7%) patients in the vidofludimus calcium group. Overall mortality was low (2%). CONCLUSIONS: These findings support vidofludimus calcium being safe and well tolerated in patients with COVID-19.

On the Concept of RISK, UNCERTAINTY & BLACK SWANS

[...]within financial risk, there are many forms such as investment risk, market risk, inflation risk, credit risk, business risk, liquidity risk and others (Sraders, 2019). In occupational safety, health and environmental standards, risk has generally been defined as the probability or likelihood of an occurrence, and its resulting severity of consequences. A third variation on the definition of risk is found among management systems standards including ISO 45001, Occupational Health and Safety Management Systems (OHSMS);ISO 14001, Environmental Management Systems;and ISO 9000, Quality Management Systems. An organization considering locating a new facility in such areas would likely assess the degree of risk for wind and flood damage based on a location's weather patterns, flooding and wind damage history, elevation, proximity to coastal waters, and other risk factors. The accepted proposal will involve a high-level committee of global experts with the goal of developing a consensus on meta-definitions (universal or base definitions) for risk and associated terms that would standardize their use in standards and reduce confusion to end users.

Development and application of a modified procedure for quantitative fit testing of disposable masks and respirators.

In this study, a modified procedure for quantitative fit testing of disposable masks and respirators using condensation nuclei counting was developed and applied. The procedure permits disposable masks and respirators to be initially tested and retested multiple times after use. Different types of masks and respirators were tested over time and quantitative results were obtained. It was found that after multiple testing that the N95 respirator passed the testing requirements with a fit factor above 100, the KN95 respirator did not perform satisfactorily in the tests, and the disposable masks did not reach fit factors above 4 or 7. The results in this study provided relevant information toward use, reuse, and testing of disposable masks and respirators, particularly relevant during the COVID pandemic when access to N95 respirators was limited.

Induction of humoral and cellular immune responses to COVID-19 mRNA and vector vaccines: A prospective cohort study in Bulgarian healthcare workers.

Installing efficient protective immunity by anti-SARS-CoV-2 vaccines is the only current means to overcome coronavirus disease 2019 pandemics. The cellular and humoral immune responses induced with an messenger RNA (mRNA) (BNT162b2) or with a vector (ChAdOx1nCoV-19) vaccine among Bulgarian healthcare workers (n = 123, aged 23-71 years) were studied in the course of 16 weeks after priming. Receptor-binding domain (RBD)-blocking Abs and SARS-CoV-2 RBD immunoglobulin A  (IgA) were evaluated in parallel with interferon gamma (IFNγ)-producing virus-specific T cells. Both vaccines induced RBD-blocking Abs in 100% of the participants after complete immunization while the levels of protection after a single dose largely varied (22%-98%). Advanced age had a negative impact on the level and longevity of virus-neutralizing activity induced by one dose mRNA, but not by the vector vaccine. RBD-binding IgA was detected in 100% of tested donors from the mRNA vaccine cohort, and in 67% of tested from the vector vaccine cohort, at least 1 month after completed immunization. One month after completing mRNA immunization, the number of IFNγ-producing T cells correlated significantly with the levels of RBD-specific IgA and virus-neutralizing activity induced after priming. Enumeration of circulating virus-specific IFNγ+ T cells is not recommended for evaluation of protective immunity as their detection may require longer stimulation beyond the firstmonth postimmunization. In conclusion, BNT162B2 and ChAdOx1nCoV-19 induced potent and comparable humoral and cellular anti-SARS-CoV-2 immune responses, peaking between 10 and 30 days after complete immunization. A single dose of any vaccine did not induce adequate protection in a great part of donors, making the shorter interval between mRNA vaccine doses preferable in the settings of increased risk of infection.

THE ROLE OF RISK MANAGEMENT With COVID-19 & Its Impact on Pandemics

[...]the company considered outsourcing 50% of its production to a manufacturer in China. Considering the complexity and nature of the risks, the team reviewed the methods found in ISO 31010 and ASSP's TR-31010-2020 technical report, "Risk Management-Techniques for Safety Practitioners" (Figure 5) and decided upon a modified what-if method called structured what-if risk assessment (SWIFRA). Because of its low cost and ready availability, bleach was initially suggested by the purchasing department as the disinfectant solution. According to an OSHA (2003) interpretation letter, "office temperature and humidity conditions are generally a matter of human comfort rather than hazards that could cause death or serious physical harm.

Clinical Characteristics of Hospitalized Patients with COVID-19 in Sofia, Bulgaria.

Introduction: SARS-CoV-2 infection is spreading around the world, including countries from Southeastern Europe. The purpose of the study was to present the clinical manifestations of COVID-19 patients admitted to the Military Medical Academy, Sofia, Bulgaria. Materials and Methods: A retrospective study was conducted for a period of 3 months from March 2020 to June 2020 on this infection in our hospital. All participants were laboratory confirmed cases of COVID-19. RT-PCR was performed for etiological diagnosis. The hospitalized patients were divided into two groups on admission, that is, nonsevere and severe. Results: One hundred thirty-eight COVID-19 patients were hospitalized and analyzed during the study period. The mean age was 52.9 years. Male was the dominant sex (sex ratio: male/female = 1/0.6). The leading clinical signs were fever, fatigue, cough, and headache. On comparative analysis of both groups (nonsevere and severe) was measured significant elevation of white blood cells (odds ratio [OR] = 1.238; p value = 0.006), C-reactive protein (OR = 1.021; p < 0.001), creatinine (OR = 1.037; p < 0.001), aspartate aminotransferase (OR = 1.014; p = 0.040), lactate dehydrogenase (OR = 1.004; p < 0.001), ferritin (OR = 1.002; p < 0.001), fibrinogen (OR = 2.028; p < 0.001), and d-dimer (OR = 2.162; p = 0.002) in severe group than in nonsevere group. Interleukin 6 was tested in 17.4% of patients and high value was found-38.6 pg/mL (95% confidence interval: 16.5-60.7). Conclusion: The first Bulgarian retrospective study of COVID-19 hospitalized patients was presented. Older age, male sex, comorbidity, and signs of dyspnea and nausea were estimated as higher risk factors for severe form. Abnormality in inflammatory markers was associated with poor progression of the illness.