SAFETY of REMDESIVIR VS PLACEBO in NONHOSPITALIZED PATIENTS with COVID-19

Background: Remdesivir (RDV), a potent nucleotide inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase, effectively reduces COVID-19 related hospitalization in outpatients at high risk for progression to severe disease. However, limited data exist on the safety profile of RDV in this population. Methods: We conducted a Phase III placebo-controlled study evaluating a 3-day regimen of RDV in non-hospitalized patients who are at risk for disease progression (age>60 years or underlying comorbid condition). Patients were randomly assigned 1:1 to receive intravenous RDV (200 mg on day 1, 100 mg on days 2 to 3) or placebo (PBO). The primary safety endpoint was the proportion of patients with treatment-emergent adverse events (AEs). AEs were evaluated through day 28 and lab abnormalities were evaluated through day 14. Results: 562 patients were randomized and initiated treatment (279, RDV;283, placebo). Baseline characteristics were balanced between groups. Thirty percent were ≥60 years old and most common comorbidities were diabetes mellitus (62%), obesity (56%;median BMI, 30.7 kg/m2), and hypertension (48%). RDV was well tolerated with a similar rate of any AEs between groups (Table). Patients treated with RDV had fewer Grade ≥3 and serious AEs (SAEs) compared to PBO, but had more study-drug related AEs, with the most common one being nausea (18 [6.5%] in RDV vs. 10 [3.5%] in PBO). Grade 3 or higher ALT elevation was reported in 1 (0.4%) RDV vs. 2 (0.7%) PBO treated patients. Median change from baseline in AST, ALT, and bilirubin was similar between groups (Table). Grade 3 or higher decrease in creatinine clearance (CrCl) occurred more often in RDV vs. to PBO treated patients (5.6% vs 1.9% respectively). Most decreases in creatinine clearance occurred within the normal serum creatinine range, occurred after completion of RDV therapy, and resolved on follow-up. Median changes in CrCl from baseline were similar between groups and no renal AEs were reported (Table). Incidence of cardiac-related AEs was similar between RDV and PBO groups. All bradycardia events occurred in the PBO group. No patient experienced a serious AE or drug discontinuation due to hypersensitivity. Conclusion: Treatment with RDV was safe and well tolerated in non-hospitalized patients with risk factors for COVID-19 disease progression. Patients in the RDV group had similar type, incidence, and severity of AEs and lab abnormalities as those receiving PBO.

Percentage of Children and/or Adolescents of All COVID-19 Cases: A Meta-analysis

Since the first report of COVID-19 in Wuhan, China, the disease has rapidly spread to many countries worldwide. The initial reports showed that the incidence rate in adults was higher, while children and adolescents had fewer cases of infection. However, the number of COVID-19 cases has gradually increased in children and adolescents. Therefore, this study aimed to assess the percentage of children and/or adolescents of the total patients diagnosed with COVID-19. PubMed, Embase, Web of Science and the Cochrane Library were searched to find relevant studies. All statistical analyses were conducted using StataMP 14 software. A total of 12 studies met the inclusion criteria. The final results showed that the percentage of children and/or adolescents of all COVID-19 cases was 0.06 [95% confidence interval (CI), 0.04-0.07], which meant an average of 6 cases in children per 10,000 COVID-19 cases. The percentage of children and/or adolescents with COVID-19 was 0.03 (95% CI, 0.01-0.05), 0.09 (95% CI, 0.08-0.09), 0.09 (95% CI, 0.03-0.16) and 0.04 (95% CI, 0.00-0.10) in Asia, South America, North America and Europe, respectively. The present study showed a low percentage of COVID-19 cases of children and/or adolescents, but not without infection risk. Therefore, we should pay attention to the cases of children and/or adolescents during the COVID-19 period and raise our vigilance. © 2022, Medcom Limited. All rights reserved.

Coordinated Mobilization Matters: How DidTaiwan Do It During the Covid-19 Pandemic?

The Covid-19 pandemic hit the world hard. Ensnared by a large-scale emergency unprecedented in recent history, mobilization, the classic issue of emergency management, is under stress and test. Yet Taiwan stands out in its rather limited cases of infections despite its frequent contact with mainland China and high population density. Could its mobilization have made the difference? This article traces the steps and strategies that Taiwan took to implement a coordinated mobilization. Three strategies were highlighted: awareness mobilization by declaring emergency early on, resource mobilization by preemptively controlling, boldly incentivizing and surgically distributing resources, and agility mobilization via big data and technology to optimize the response system.

Review Article In vitro diagnostics of coronavirus disease 2019: Technologies and application

Laboratory-based diagnostic measures including virological and serological tests are essential for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Real-time reverse transcription-polymerase chain reactions (rRT-PCR) can detect SARS-COV-2 by targeting open reading frame-1 antibodies (ORF1ab), envelope protein, nucleocapsid protein, RNA-dependent RNA polymerase genes, and the N1, N2, and N3 (3N) target genes. Therefore, rRT-PCR remains the primary method of diagnosing SARS-CoV-2 despite being limited by false-negative results, long turnaround, complex protocols, and a need for skilled personnel. Serological diagnosis of coronavirus disease 2019 (COVID-19) is simple and does not require complex techniques and equipment, rendering it suitable for rapid detection and massive screening. However, serological tests cannot confirm SARS-CoV-2, and results will be false negative when antibody concentrations fall below detection limits. Balancing the increased use of laboratory tests, risk of testing errors, need for tests, burden on healthcare systems, benefits of early diagnosis, and risk of unnecessary exposure is a significant and persistent challenge in diagnosing COVID-19. Copyright (c) 2020, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).

Gilead sciences' commitment to the COVID-19 pandemic

Background: COVID-19 has spread rapidly: from the first case in Dec 2019, the declaration of a global pandemic in Mar 2020, to Jun 18, 2020 with >8 M confirmed cases and >400,000 deaths worldwide. Throughout this rapid spread, Gilead has focused on contributing antiviral expertise and resources to help patients (pts) and communities fighting COVID-19 Methods: Gilead is supporting the efforts of governments, partnering with professionals, and community-based org., and collaborating with healthcare providers to accelerate research and access to remdesivir (RDV), the first medicine with demonstrated efficacy in treatment of COVID-19. This is a review of the programs initiated in RDV research, access, research grants and collaborative education Results: In Jan 2020 Gilead began working with government and regulatory authorities to make RDV accessible to pts globally through the compassionate use and expanded access programs. These programs has treated >2000 COVID-19 pts. By Feb 2020, several phase 3 randomized trials on RDV were initiated. Based on trials completed and published data (n= >2000), RDV was granted emergency use authorization in the US on May 1, 2020 with full approval in 5 countries thereafter and several under review elsewhere. Collectively there will be >12,000 pts enrolled in RDV clinical programs by Dec 2020. Increasing manufacturing of RDV began at-risk in Jan 2020. By May 2020 Gilead has decreased production time, increased supply and committed to donating all its 1.5 M doses. Under the licensing agreements with generic drug manufacturers, RDV will be available in 127 countries upon approval. Gilead has committed to supporting research grants to enhance the understanding of the clinical course and outcomes in vulnerable population, long-term sequelae, and evaluate real world safety and effectiveness of COVID-19 therapies. Finally, Gilead has provided corporate grants to support the efforts of community-based orgs and public health entities to expand education on COVID-19 Conclusion: Gilead has initiated a global, multifaceted rapid response that reflects the unprecedented emergency posed by SARS-COV-2. This includes increasing RDV production, access, timely initiation of phase 3 RDV trials, and establishment of grants programs for community projects, research and education.

A human monoclonal antibody blocking SARS-CoV-2 infection (vol 11, 2251, 2020)

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Using regulatory focus to encourage physical distancing in services: when fear helps to deal with Mr. Deadly COVID-19

Although physical distancing is the key to reducing the risk of virus infection, the commonly used signs to spur physical distancing in services seem ineffective as many customers still refrain from practicing physical distancing. This research therefore suggests using regulatory focus (prevention vs. promotion) to improve the persuasiveness of these appeals. Study 1 creates and validates one multiple-item scale for measuring physical distancing in services, which is then adopted in two subsequent scenario-based experiments. Study 2 proves the superior effect of prevention-focused message to both promotion-focused message and conventional message in encouraging physical distancing compliance, which is explained by perceived fear as the underlying psychological mechanism. Study 3 further unveils the boundary condition of anthropomorphism in strengthening this superiority (i.e. Mr. Deadly COVID-19, scary face). Given a great deal of uncertain future caused by this epidemic, this research provides relevant implications for fostering the engagement in physical distancing in services. © 2020 Informa UK Limited, trading as Taylor & Francis Group.

[Discussion on early warning, prevention and control of emerging infectious diseases from a macroscopic perspective based on big data and effective distance model: enlightenment of COVID-19 epidemic data in China].

Objective: To provide a system for warning, preventing and controlling emerging infectious diseases from a macroscopic perspective, using the COVID-19 epidemic data and effective distance model. Methods: The dates of hospitalization/isolation treatment of the first confirmed cases of COVID-19 and the cumulative numbers of confirmed cases in different provinces in China reported as of 23 February, 2020 were collected. The Location Based Service (LBS) big data platform of "Baidu Migration" was employed to obtain the data of the proportion of the floating population from Wuhan to all parts of the country. Effective distance models and linear regression models were established to analyze the relationship between the effective distance and the arrival time of the epidemic as well as the number of cumulative confirmed cases at provincial and municipal levels. Results: The arrival time of the epidemic and the cumulative number of confirmed cases of COVID-19 had significant linear relationship at both provincial and municipal levels in China, and the regression coefficients of each linear model were significant (P<0.001). At the provincial level, the effective distance could explain about 71% of the variation of the model with arrival time along with around 90% of the variation for the model in the cumulative confirmed case magnitude; at the municipal level, the effective distance could explain about 66% of the variation for the model in arrival time, and about 85% of the variation of the model with the cumulative confirmed case magnitude. Conclusions: The fitting degree of the models are good. The LBS big data and effective distance model can be used to estimate the track, time and extent of epidemic spread to provide useful reference for early warning, prevention and control of emerging infectious diseases.