Covid protocol
220056670
Randomized Controlled Study Evaluating Efficiency of Low Intensity Transcranial Direct Current Stimulation (tDCS) for Dyspnea Relief in Mechanically Ventilated COVID 19 Patients in ICU: The tDCS DYSP COVID Protocol
The severe respiratory distress syndrome linked to the new coronavirus disease (COVID 19) includes unbearable dyspneic suffering which contributes to the deterioration of the prognosis of patients in intensive care unit (ICU) Patients are put on mechanical ventilation to reduce respiratory suffering and preserve life. Despite this mechanical ventilation, most patients continue to suffer from dyspnea. Dyspnea is a major source of suffering in intensive care and one of the main factors that affect the prognosis of patients. The development of innovative methods for its management, especially non drug management is more than necessary. In recent years, numerous studies have shown that transcranial direct current stimulation (tDCS) could modulate the perception of acute or chronic pain. In the other hand, it has been shown that the brain zones activated during pain and dyspnea are close and/or superimposed, suggesting that brain structures involved in the integration of aversive emotional component are shared by these two complex sensory experiences. Therefore, it can be hypothesized that stimulation by tDCS with regard to the areas which, in the case of pain have activated one or more of these brain structures, may also have an effect on dyspnea. In addition, our team recently demonstrated that the application of tDCS on the primary cortical motor area can modulate the excitability of the respiratory neurological pathways. Indeed, tDCS in anodal or cathodal modality reduced the excitability of the diaphragmatic cortico spinal pathways in healthy subjects. We therefore hypothesized that tDCS could relieve dyspnea in COVID 19 patients under mechanical ventilation in ICU. This study was designed to evaluate effects of two modalities of tDCS (anodal and cathodal) vs. placebo, on the relief of dyspnea in COVID 19 patients requiring mechanical ventilation in ICU. Trial Registration: This protocol is derived from the tDCS DYSP REA project registered on ClinicalTrials.gov NCT03640455. It will however be registered under its own NCT number.
Frontiers in Medicine
Eric Azabou Guillaume Bao Nicholas Heming Rania Bounab Pierre Moine Sylvain Chevallier Sylvie Chevret Matthieu Resche-Rigon Shidaps Siami Tarek Sharshar Frederic Lofaso Djillali Annane
229012532
Dawatek COVID protocol v1 (protocols.io.bk24kygw)
Leela Raavi Davina G Moossazadeh Isaac Chadri
218859765
Features of 20 133 UK patients in hospital with covid 19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study
Abstract Objective To characterise the clinical features of patients admitted to hospital with coronavirus disease 2019 (covid 19) in the United Kingdom during the growth phase of the first wave of this outbreak who were enrolled in the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP UK) study, and to explore risk factors associated with mortality in hospital. Design Prospective observational cohort study with rapid data gathering and near real time analysis. Setting 208 acute care hospitals in England, Wales, and Scotland between 6 February and 19 April 2020. A case report form developed by ISARIC and WHO was used to collect clinical data. A minimal follow up time of two weeks (to 3 May 2020) allowed most patients to complete their hospital admission. Participants 20 133 hospital inpatients with covid 19. Main outcome measures Admission to critical care (high dependency unit or intensive care unit) and mortality in hospital. Results The median age of patients admitted to hospital with covid 19, or with a diagnosis of covid 19 made in hospital, was 73 years (interquartile range 58 82, range 0 104) More men were admitted than women (men 60% n=12 068; women 40% n=8065) The median duration of symptoms before admission was 4 days (interquartile range 1 8) The commonest comorbidities were chronic cardiac disease (31% 5469/17 702) uncomplicated diabetes (21% 3650/17 599) non asthmatic chronic pulmonary disease (18% 3128/17 634) and chronic kidney disease (16% 2830/17 506) 23% (4161/18 525) had no reported major comorbidity. Overall, 41% (8199/20 133) of patients were discharged alive, 26% (5165/20 133) died, and 34% (6769/20 133) continued to receive care at the reporting date. 17% (3001/18 183) required admission to high dependency or intensive care units; of these, 28% (826/3001) were discharged alive, 32% (958/3001) died, and 41% (1217/3001) continued to receive care at the reporting date. Of those receiving mechanical ventilation, 17% (276/1658) were discharged alive, 37% (618/1658) died, and 46% (764/1658) remained in hospital. Increasing age, male sex, and comorbidities including chronic cardiac disease, non asthmatic chronic pulmonary disease, chronic kidney disease, liver disease and obesity were associated with higher mortality in hospital. Conclusions ISARIC WHO CCP UK is a large prospective cohort study of patients in hospital with covid 19. The study continues to enrol at the time of this report. In study participants, mortality was high, independent risk factors were increasing age, male sex, and chronic comorbidity, including obesity. This study has shown the importance of pandemic preparedness and the need to maintain readiness to launch research studies in response to outbreaks. Study registration ISRCTN66726260.
BMJ
Annemarie B Docherty Ewen M Harrison Christopher A Green Hayley E Hardwick Riinu Pius Lisa Norman Karl A Holden Jonathan M Read Frank Dondelinger Gail Carson Laura Merson James Lee Daniel Plotkin Louise Sigfrid Sophie Halpin Clare Jackson Carrol Gamble Peter W Horby Jonathan S Nguyen-Van-Tam Antonia YW Ho Clark D Russell Jake Dunning Peter J M Openshaw John Kenneth Baillie Malcolm G Semple
214627660
Hydroxychloroquine and azithromycin as a treatment of COVID 19: results of an open label non randomized clinical trial
Abstract Background Chloroquine and hydroxychloroquine have been found to be efficient on SARS CoV 2, and reported to be efficient in Chinese COV 19 patients. We evaluate the role of hydroxychloroquine on respiratory viral loads. Patients and methods French Confirmed COVID 19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6 post inclusion was considered the end point. Results Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6 post inclusion compared to controls, and much lower average carrying duration than reported of untreated patients in the literature. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination. Conclusion Despite its small sample size our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID 19 patients and its effect is reinforced by azithromycin.
International Journal of Antimicrobial Agents
Philippe Gautret Jean-Christophe Lagier Philippe Parola Van Thuan Hoang Line Meddeb Morgane Mailhe Barbara Doudier Johan Courjon Valerie Giordanengo Vera Esteves Vieira Herve Tissot Dupont Stephane Honore Philippe Colson Eric Chabriere Bernard La Scola J M Rolain Philippe Brouqui Didier Raoult
215751082
Early nutritional supplementation in non critically ill patients hospitalized for the 2019 novel coronavirus disease (COVID 19) Rationale and feasibility of a shared pragmatic protocol
Abstract Objectives Beginning in December 2019, the 2019 novel coronavirus disease (COVID 19) has caused a pneumonia epidemic that began in Wuhan, China, and is rapidly spreading throughout the whole world. Italy is the hardest hit country after China. Considering the deleterious consequences of malnutrition, which certainly can affect patients with COVID 19, the aim of this article is to present a pragmatic protocol for early nutritional supplementation of non critically ill patients hospitalized for COVID 19 disease. It is based on the observation that most patients present at admission with severe inflammation and anorexia leading to a drastic reduction of food intake, and that a substantial percentage develops respiratory failure requiring non invasive ventilation or even continuous positive airway pressure. Methods High calorie dense diets in a variety of different consistencies with highly digestible foods and snacks are available for all patients. Oral supplementation of whey proteins as well as intravenous infusion of multivitamin, multimineral trace elements solutions are implemented at admission. In the presence of 25 hydroxyvitamin D deficit, cholecalciferol is promptly supplied. If nutritional risk is detected, two to three bottles of protein calorie oral nutritional supplements (ONS) are provided. If <2 bottles/d of ONS are consumed for 2 consecutive days and/or respiratory conditions are worsening, supplemental/total parenteral nutrition is prescribed. Conclusion We are aware that our straight approach may be debatable. However, to cope with the current emergency crisis, its aim is to promptly and pragmatically implement nutritional care in patients with COVID 19, which might be overlooked despite being potentially beneficial to clinical outcomes and effective in preventing the consequences of malnutrition in this patient population.
Nutrition
Riccardo Caccialanza Alessandro Laviano Federica Lobascio Elisabetta Sara Montagna Raffaele Bruno Serena Ludovisi Angelo Guido Corsico Antonio Di Sabatino Mirko Belliato Monica Calvi Isabella Iacona Giuseppina Grugnetti Elisa Bonadeo Alba Muzzi Emanuele Cereda
216588732
Features of 16,749 hospitalised UK patients with COVID 19 using the ISARIC WHO Clinical Characterisation Protocol
Objective: To characterize the clinical features of patients with severe COVID 19 in the UK. Design: Prospective observational cohort study with rapid data gathering and near real time analysis, using a pre approved questionnaire adopted by the WHO. Setting: 166 UK hospitals between 6th February and 18th April 2020. Participants: 16,749 people with COVID 19. Interventions: No interventions were performed, but with consent samples were taken for research purposes. Many participants were co enrolled in other interventional studies and clinical trials. Results: The median age was 72 years [IQR 57, 82; range 0, 104] the median duration of symptoms before admission was 4 days [IQR 1,8] and the median duration of hospital stay was 7 days [IQR 4,12] The commonest comorbidities were chronic cardiac disease (29% uncomplicated diabetes (19% non asthmatic chronic pulmonary disease (19% and asthma (14% 47% had no documented reported comorbidity. Increased age and comorbidities including obesity were associated with a higher probability of mortality. Distinct clusters of symptoms were found: 1. respiratory (cough, sputum, sore throat, runny nose, ear pain, wheeze, and chest pain) 2. systemic (myalgia, joint pain and fatigue) 3. enteric (abdominal pain, vomiting and diarrhoea) Overall, 49% of patients were discharged alive, 33% have died and 17% continued to receive care at date of reporting. 17% required admission to High Dependency or Intensive Care Units; of these, 31% were discharged alive, 45% died and 24% continued to receive care at the reporting date. Of those receiving mechanical ventilation, 20% were discharged alive, 53% died and 27% remained in hospital. Conclusions: We present the largest detailed description of COVID 19 in Europe, demonstrating the importance of pandemic preparedness and the need to maintain readiness to launch research studies in response to outbreaks. Trial documentation: Available at https:/isaric4c.net/protocols Ethical approval in England and Wales (13/SC/0149) and Scotland (20/SS/0028) ISRCTN (pending)
medRxiv
Annemarie B Docherty Ewen M Harrison Christopher A Green Hayley E Hardwick Riinu Pius Lisa Norman Karl A Holden Jonathan M Read Frank Dondelinger Gail Carson Laura Merson J Lee Daniel Plotkin Louise Sigfrid Sophie Halpin Clare Jackson Carrol Gamble Peter W Horby Jonathan S Nguyen-Van-Tam Jake Dunning Peter J M Openshaw John Kenneth Baillie Malcolm G Semple
220907181
Risk stratification of patients admitted to hospital with covid 19 using the ISARIC WHO Clinical Characterisation Protocol: development and validation of the 4C Mortality Score
Objectives To develop and validate a pragmatic risk score to predict mortality for patients admitted to hospital with covid 19. Design Prospective observational cohort study: ISARIC WHO CCP UK study (ISARIC Coronavirus Clinical Characterisation Consortium [4C] Model training was performed on a cohort of patients recruited between 6 February and 20 May 2020, with validation conducted on a second cohort of patients recruited between 21 May and 29 June 2020. Setting 260 hospitals across England, Scotland, and Wales. Participants Adult patients ]18 years) admitted to hospital with covid 19 admitted at least four weeks before final data extraction. Main outcome measures In hospital mortality. Results There were 34 692 patients included in the derivation dataset (mortality rate 31.7% and 22 454 in the validation dataset (mortality 31.5% The final 4C Mortality Score included eight variables readily available at initial hospital assessment: age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea, and C reactive protein (score range 0 21 points) The 4C risk stratification score demonstrated high discrimination for mortality (derivation cohort: AUROC 0.79; 95% CI 0.78 0.79; validation cohort 0.78, 0.77 0.79) with excellent calibration (slope 1.0) Patients with a score ]15 (n 2310, 17.4% had a 67% mortality (i.e. positive predictive value 67% compared with 1.0% mortality for those with a score ]3 (n 918, 7% negative predictive value 99% Discriminatory performance was higher than 15 pre existing risk stratification scores (AUROC range 0.60 0.76) with scores developed in other covid 19 cohorts often performing poorly (range 0.63 0.73) Conclusions We have developed and validated an easy to use risk stratification score based on commonly available parameters at hospital presentation. This outperformed existing scores, demonstrated utility to directly inform clinical decision making, and can be used to stratify inpatients with covid 19 into different management groups. The 4C Mortality Score may help clinicians identify patients with covid 19 at high risk of dying during current and subsequent waves of the pandemic. Study registration ISRCTN66726260
medRxiv
Stephen R Knight Antonia YW Ho Riinu Pius Iain E Buchan Gail Carson Thomas M Drake Jake Dunning Cameron J Fairfield Carrol Gamble Christopher A Green R K Gupta Sophie Halpin Hayley E Hardwick Karl A Holden Peter W Horby Clare Jackson Kenneth A McLean Laura Merson Jonathan S Nguyen-Van-Tam Lisa Norman Mahdad Noursadeghi Piero L Olliaro Mark G Pritchard Clark D Russell Catherine A Shaw Aziz Sheikh Tom Solomon Cathie L M Sudlow Olivia V Swann Lance C W Turtle Peter J M Openshaw John Kenneth Baillie Malcolm G Semple Annemarie B Docherty Ewen M Harrison
212667080
Development of a Laboratory safe and Low cost Detection Protocol for SARS CoV 2 of the Coronavirus Disease 2019 (COVID 19)
The severe acute respiratory coronavirus 2 (SARS CoV 2) which emerged in December 2019 in Wuhan, China, has spread rapidly to over a dozen countries. Especially, the spike of case numbers in South Korea sparks pandemic worries. This virus is reported to spread mainly through person to person contact via respiratory droplets generated by coughing and sneezing, or possibly through surface contaminated by people coughing or sneezing on them. More critically, there have been reports about the possibility of this virus to transmit even before a virus carrying person to show symptoms. Therefore, a low cost, easy access protocol for early detection of this virus is desperately needed. Here, we have established a real time reverse transcription PCR (rtPCR) based assay protocol composed of easy specimen self collection from a subject via pharyngeal swab, Trizol based RNA purification, and SYBR Green based rtPCR. This protocol shows an accuracy and sensitivity limit of 1 10 virus particles as we tested with a known lentivirus. The cost for each sample is estimated to be less than 15 US dollars. Overall time it takes for an entire protocol is estimated to be less than 4 hours. We propose a cost effective, quick and easy method for early detection of SARS CoV 2 at any conventional Biosafety Level II laboratories that are equipped with a rtPCR machine. Our newly developed protocol should be helpful for a first hand screening of the asymptomatic virus carriers for further prevention of transmission and early intervention and treatment for the rapidly propagating virus.
Experimental neurobiology
Joungha Won Solji Lee V Narry Kim
218520704
Cardiac safety of off label COVID 19 drug therapy: a review and proposed monitoring protocol
More than 2,000,000 individuals worldwide have had coronavirus 2019 disease infection (COVID 19) yet there is no effective medical therapy. Multiple off label and investigational drugs, such as chloroquine and hydroxychloroquine, have gained broad interest due to positive pre clinical data and are currently used for treatment of COVID 19. However, some of these medications have potential cardiac adverse effects. This is important because up to one third of patients with COVID 19 have cardiac injury, which can further increase the risk of cardiomyopathy and arrhythmias. Adverse effects of chloroquine and hydroxychloroquine on cardiac function and conduction are broad and can be fatal. Both drugs have an anti arrhythmic property and are proarrhythmic. The American Heart Association has listed chloroquine and hydroxychloroquine as agents which can cause direct myocardial toxicity. Similarly, other investigational drugs such as favipiravir and lopinavir/ritonavir can prolong QT interval and cause Torsade de Pointes. Many antibiotics commonly used for the treatment of patients with COVID 19, for instance azithromycin, can also prolong QT interval. This review summarizes evidenced based data regarding potential cardiac adverse effects due to off label and investigational drugs including chloroquine and hydroxychloroquine, antiviral therapy, monoclonal antibodies, as well as common antibiotics used for the treatment of COVID 19. The article focuses on practical points and offers a point of care protocol for providers who are taking care of patients with COVID 19 in an inpatient and outpatient setting. The proposed protocol is taking into consideration that resources during the pandemic are limited.
European heart journal. Acute cardiovascular care
Niyada Naksuk Sorin Lazar Thoetchai (Bee) Peeraphatdit
215411279
Traditional Chinese herbal medicine for treating novel coronavirus (COVID 19) pneumonia: protocol for a systematic review and meta analysis
Background A new type of coronavirus, novel coronavirus (COVID 19) is causing an increasing number of cases of pneumonia and was declared a Public Health Emergency of International Concern by the World Health Organization on 30 January 2020. The virus first appeared in Wuhan, China, in late December 2019, and traditional Chinese herbal medicine is being used for its treatment. This systematic review and meta analysis will assess studies of the effects of traditional Chinese herbal medicine in COVID 19 pneumonia. Methods We will search electronic databases including PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) Chinese Biomedical Literature Database (CBM) China National Knowledge Infrastructure (CNKI) Chinese Science and Technology Periodical Database (VIP) and Wanfang database using keywords related to COVID 19 and traditional Chinese herbal medicine. Reference lists of relevant trials and reviews will be searched. We will manually search gray literature, such as conference proceedings and academic degree dissertations, and trial registries. Two independent reviewers will screen studies (XL and DZ) extract data (YL and LG) and evaluate risk of bias (YL and DZ) Data analysis will be conducted using the Review Manager software (version 5.3.5) and R software (version 3.6.1) Statistical heterogeneity will be assessed using a standard chi square test with a significance level of P 0.10. Biases associated with study size (e.g. publication bias) will be investigated using funnel plots, Egger's test and Begg's test, and Trim and Fill analysis. Discussion This study will provide a high quality synthesis of the effects of traditional Chinese herbal medicine for COVID 19. The use of traditional Chinese herbal medicine for treatment or prevention of these novel viral infections affecting the pneumonia will be investigated. Systematic review registration PROSPERO registration number: CRD42020168004
Systematic Reviews
Yuxi Li Xiaobo Liu Liuxue Guo Juan Li Dongling Zhong Yonggang Zhang Mike Clarke Rongjiang Jin