Background Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. Methods We conducte...

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Remdesivir for the Treatment of Covid-19 - Final Report.

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Background Hydroxychloroquine has been widely administered to patients with Covid-19 without robust evidence supporting its use. Methods We examined the association between hydroxychloroqu...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2012410?articleTools=true

Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19.

Immunology of COVID-19: Current State of the Science.

Key Clinical Points Evaluation and Management of Severe Covid-19 Patients with severe coronavirus disease 2019 (Covid-19) may become critically ill with acute respiratory distress syndrome that typ...

https://www.nejm.org/doi/pdf/10.1056/NEJMcp2009575?articleTools=true

Severe Covid-19

Importance There is no specific antiviral therapy recommended for coronavirus disease 2019 (COVID-19). In vitro studies indicate that the antiviral effect of chloroquine diphosphate (CQ) requires a high concentration of the drug. Objective To evaluate the safety and efficacy of 2 CQ dosages in patients with severe COVID-19. Design, Setting, and Participants This parallel, double-masked, randomized, phase IIb clinical trial with 81 adult patients who were hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted from March 23 to April 5, 2020, at a tertiary care facility in Manaus, Brazilian Amazon. Interventions Patients were allocated to receive high-dosage CQ (ie, 600 mg CQ twice daily for 10 days) or low-dosage CQ (ie, 450 mg twice daily on day 1 and once daily for 4 days). Main Outcomes and Measures Primary outcome was reduction in lethality by at least 50% in the high-dosage group compared with the low-dosage group. Data presented here refer primarily to safety and lethality outcomes during treatment on day 13. Secondary end points included participant clinical status, laboratory examinations, and electrocardiogram results. Outcomes will be presented to day 28. Viral respiratory secretion RNA detection was performed on days 0 and 4. Results Out of a predefined sample size of 440 patients, 81 were enrolled (41 [50.6%] to high-dosage group and 40 [49.4%] to low-dosage group). Enrolled patients had a mean (SD) age of 51.1 (13.9) years, and most (60 [75.3%]) were men. Older age (mean [SD] age, 54.7 [13.7] years vs 47.4 [13.3] years) and more heart disease (5 of 28 [17.9%] vs 0) were seen in the high-dose group. Viral RNA was detected in 31 of 40 (77.5%) and 31 of 41 (75.6%) patients in the low-dosage and high-dosage groups, respectively. Lethality until day 13 was 39.0% in the high-dosage group (16 of 41) and 15.0% in the low-dosage group (6 of 40). The high-dosage group presented more instance of QTc interval greater than 500 milliseconds (7 of 37 [18.9%]) compared with the low-dosage group (4 of 36 [11.1%]). Respiratory secretion at day 4 was negative in only 6 of 27 patients (22.2%). Conclusions and Relevance The preliminary findings of this study suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir. These findings cannot be extrapolated to patients with nonsevere COVID-19. Trial Registration ClinicalTrials.gov Identifier:NCT04323527

/pdf/effect-of-high-vs-low-doses-of-chloroquine-diphosphate-as-1z7uohmsgw.pdf

Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial.

There are several arthropods that can transmit disease to humans. To make inferences about the rate of infection of these arthropods, it is common to collect a large sample of vectors, divide them into groups (called pools), and apply a test to detect infection. This paper presents an approximate likelihood point estimator to rate of infection for pools of different sizes, when the variability of these sizes is small and the infection rate is low. The performance of this estimator was evaluated in four simulated scenarios, created from real experiments selected in the literature. The new estimator performed well in three of these scenarios. As expected, the new estimator performed poorly in the scenario with great variability in the size of the pools for some values of the parameter space.

An approximate likelihood estimator for the prevalence of infections in vectors using pools of varying sizes

Conditional tests are constructed by conditioning a fit measure to a minimal sufficient statistic. To calculate the p-value of these tests, Monte Carlo methods with co-sufficient samples ca...

A Metropolis algorithm to obtain co-sufficient samples with applications in conditional tests

The elicitation of hyperparameters at time t in dynamic Bayesian models for proportions is performed by solving a nonlinear system. This paper presents an algorithm to solve this system when the logit function is used. If the initial conditions are satisfied, it is guaranteed that the algorithm converges to the solution. The performance of some dynamic models was compared using the standard method and the new method presented here, using simulated data and the monthly series of deaths from tuberculosis sequelae in the state of Sao Paulo, Brazil.

James D. Santos

Papers

Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial.

An approximate likelihood estimator for the prevalence of infections in vectors using pools of varying sizes

A Metropolis algorithm to obtain co-sufficient samples with applications in conditional tests

An Algorithm for Prior Elicitation in Dynamic Bayesian Models for Proportions with the Logit Link Function