Vincent Cheng

Bio: Vincent Cheng is an academic researcher from University of Bristol. The author has contributed to research in topics: Medicine & Guideline. The author has an hindex of 4, co-authored 7 publications receiving 119 citations.

Characterising long COVID: a living systematic review.

Abstract: Background: While it is now apparent clinical sequelae (often called Long Covid) may persist after acute Covid-19, their nature, frequency, and aetiology are poorly characterised. This study aims to regularly synthesise evidence on Long Covid characteristics, to inform clinical management, rehabilitation, and interventional studies to improve long term outcomes. Methods: A living systematic review. Medline, CINAHL (EBSCO), Global Health (Ovid), WHO Global Research Database on Covid-19, LitCOVID, and Google Scholar were searched up to 17th March 2021. Published studies including at least 100 people with confirmed or clinically suspected Covid-19 at 12 weeks or more post-onset were included. Results were analysed using descriptive statistics and meta-analyses to estimate prevalence with 95% confidence intervals (CIs). Results: Thirty-nine studies were included: 32 cohort, six cross-sectional, and one case-control. Most showed high or moderate risk of bias. None were set in low-income countries, limited studies included children. Studies reported on 10,951 people (48% female) in 12 countries. Most followed-up post hospital discharge (78%, 8520/10951). The longest mean follow-up was 221.7 (SD: 10.9) days post Covid-19 onset. An extensive range of symptoms with wide prevalence was reported, most commonly weakness (41%; 95% CI 25% to 59%), malaise (33%; 95% CI 15% to 57%), fatigue (31%; 95% CI 24% to 39%), concentration impairment (26%; 95% CI 21% to 32%), and breathlessness (25%; 95% CI 18% to 34%). Other frequent symptoms included musculoskeletal, neurological, and psychological. 37% (95% CI 18% to 60%) of people reported reduced quality of life. Conclusion: Long Covid is a complex condition with heterogeneous symptoms. The nature of the studies precludes a precise case definition or evaluation of risk factors. There is an urgent need for prospective, robust, standardised controlled studies into aetiology, risk factors, and biomarkers to characterise Long Covid in different at-risk populations and settings. Systematic review registration: The protocol was prospectively registered on the PROSPERO database (CRD42020211131).

Scope, quality, and inclusivity of clinical guidelines produced early in the covid-19 pandemic: rapid review.

Abstract: Objective To appraise the availability, quality, and inclusivity of clinical guidelines produced in the early stage of the coronavirus disease 2019 (covid-19) pandemic. Design Rapid review. Data sources Ovid Medline, Ovid Embase, Ovid Global Health, Scopus, Web of Science Core Collection, and WHO Global Index Medicus, searched from inception to 14 Mar 2020. Search strategies applied the CADTH database guidelines search filter, with no limits applied to search results. Further studies were identified through searches of grey literature using the ISARIC network. Inclusion criteria Clinical guidelines for the management of covid-19, Middle East respiratory syndrome (MERS), and severe acute respiratory syndrome (SARS) produced by international and national scientific organisations and government and non-governmental organisations relating to global health were included, with no exclusions for language. Regional/hospital guidelines were excluded. Only the earliest version of any guideline was included. Quality assessment Quality was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool. The quality and contents of early covid-19 guidelines were also compared with recent clinical guidelines for MERS and SARS. Results 2836 studies were identified, of which 2794 were excluded after screening. Forty two guidelines were considered eligible for inclusion, with 18 being specific to covid-19. Overall, the clinical guidelines lacked detail and covered a narrow range of topics. Recommendations varied in relation to, for example, the use of antiviral drugs. The overall quality was poor, particularly in the domains of stakeholder involvement, applicability, and editorial independence. Links between evidence and recommendations were limited. Minimal provision was made for vulnerable groups such as pregnant women, children, and older people. Conclusions Guidelines available early in the covid-19 pandemic had methodological weaknesses and neglected vulnerable groups such as older people. A framework for development of clinical guidelines during public health emergencies is needed to ensure rigorous methods and the inclusion of vulnerable populations. Systematic review registration PROSPERO CRD42020167361.

Characterising long-term covid-19: a rapid living systematic review

Abstract: Background: While it is now apparent clinical sequelae (often called Long Covid) may persist after acute Covid-19, their nature, frequency, and aetiology are poorly characterised. This study aims to regularly synthesise evidence on Long Covid characteristics, to inform clinical management, rehabilitation, and interventional studies to improve long term outcomes. Methods: A living systematic review. Medline, CINAHL (EBSCO), Global Health (Ovid), WHO Global Research Database on Covid-19, LitCOVID, and Google Scholar were searched up to 17th March 2021. Published studies including at least 100 people with confirmed or clinically suspected Covid-19 at 12 weeks or more post-onset were included. Results were analysed using descriptive statistics and meta-analyses to estimate prevalence with 95% confidence intervals (CIs). Results: Thirty-nine studies were included: 32 cohort, six cross-sectional, and one case-control. Most showed high or moderate risk of bias. None were set in low-income countries, limited studies included children. Studies reported on 10,951 people (48% female) in 12 countries. Most followed-up post hospital discharge (78%, 8520/10951). The longest mean follow-up was 221.7 (SD: 10.9) days post Covid-19 onset. An extensive range of symptoms with wide prevalence was reported, most commonly weakness (41%; 95% CI 25% to 59%), malaise (33%; 95% CI 15% to 57%), fatigue (31%; 95% CI 24% to 39%), concentration impairment (26%; 95% CI 21% to 32%), and breathlessness (25%; 95% CI 18% to 34%). Other frequent symptoms included musculoskeletal, neurological, and psychological. 37% (95% CI 18% to 60%) of people reported reduced quality of life. Conclusion: Long Covid is a complex condition with heterogeneous symptoms. The nature of the studies precludes a precise case definition or evaluation of risk factors. There is an urgent need for prospective, robust, standardised controlled studies into aetiology, risk factors, and biomarkers to characterise Long Covid in different at-risk populations and settings. Systematic review registration: The protocol was prospectively registered on the PROSPERO database (CRD42020211131).

Availability, scope and quality of monkeypox clinical management guidelines globally: a systematic review

Abstract: Background Monkeypox (MPX) is an important human Orthopoxvirus infection. There has been an increase in MPX cases and outbreaks in endemic and non-endemic regions in recent decades. We appraised the availability, scope, quality and inclusivity of clinical management guidelines for MPX globally. Methods For this systematic review, we searched six databases from inception until 14 October 2021, augmented by a grey literature search until 17 May 2022. MPX guidelines providing treatment and supportive care recommendations were included, with no exclusions for language. Two reviewers assessed the guidelines. Quality was assessed using the Appraisal of Guidelines for Research and Evaluation II tool. Results Of 2026 records screened, 14 guidelines were included. Overall, most guidelines were of low-quality with a median score of 2 out of 7 (range: 1–7), lacked detail and covered a narrow range of topics. Most guidelines focused on adults, five (36%) provided some advice for children, three (21%) for pregnant women and three (21%) for people living with HIV. Treatment guidance was mostly limited to advice on antivirals; seven guidelines advised cidofovir (four specified for severe MPX only); 29% (4/14) tecovirimat, and 7% (1/14) brincidofovir. Only one guideline provided recommendations on supportive care and treatment of complications. All guidelines recommended vaccination as post-exposure prophylaxis (PEP). Three guidelines advised on vaccinia immune globulin as PEP for severe cases in people with immunosuppression. Conclusion Our results highlight a lack of evidence-based clinical management guidelines for MPX globally. There is a clear and urgent need for research into treatment and prophylaxis including for different risk populations. The current outbreak provides an opportunity to accelerate this research through coordinated high-quality studies. New evidence should be incorporated into globally accessible guidelines, to benefit patient and epidemic outcomes. A ‘living guideline’ framework is recommended. PROSPERO registration number CRD42020167361.

Time to reconsider the role of ribavirin in Lassa fever.

Abstract: Ribavirin is the only available Lassa fever treatment. The rationale for using ribavirin is based on one clinical study conducted in the early 1980s. However, reanalysis of previous unpublished data reveals that ribavirin may actually be harmful in some Lassa fever patients. An urgent reevaluation of ribavirin is therefore needed.

Dexamethasone in Hospitalized Patients with Covid-19

Abstract: BackgroundCoronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death.MethodsIn this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the final results of this assessment.ResultsA total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.92 to 1.55).ConclusionsIn patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936. opens in new tab; ISRCTN number, 50189673. opens in new tab.)

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

Abstract: 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.

Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19

Abstract: BackgroundHydroxychloroquine and chloroquine have been proposed as treatments for coronavirus disease 2019 (Covid-19) on the basis of in vitro activity and data from uncontrolled studies and small, randomized trials.MethodsIn this randomized, controlled, open-label platform trial comparing a range of possible treatments with usual care in patients hospitalized with Covid-19, we randomly assigned 1561 patients to receive hydroxychloroquine and 3155 to receive usual care. The primary outcome was 28-day mortality.ResultsThe enrollment of patients in the hydroxychloroquine group was closed on June 5, 2020, after an interim analysis determined that there was a lack of efficacy. Death within 28 days occurred in 421 patients (27.0%) in the hydroxychloroquine group and in 790 (25.0%) in the usual-care group (rate ratio, 1.09; 95% confidence interval [CI], 0.97 to 1.23; P=0.15). Consistent results were seen in all prespecified subgroups of patients. The results suggest that patients in the hydroxychloroquine group were less likely to be discharged from the hospital alive within 28 days than those in the usual-care group (59.6% vs. 62.9%; rate ratio, 0.90; 95% CI, 0.83 to 0.98). Among the patients who were not undergoing mechanical ventilation at baseline, those in the hydroxychloroquine group had a higher frequency of invasive mechanical ventilation or death (30.7% vs. 26.9%; risk ratio, 1.14; 95% CI, 1.03 to 1.27). There was a small numerical excess of cardiac deaths (0.4 percentage points) but no difference in the incidence of new major cardiac arrhythmia among the patients who received hydroxychloroquine.ConclusionsAmong patients hospitalized with Covid-19, those who received hydroxychloroquine did not have a lower incidence of death at 28 days than those who received usual care. (Funded by UK Research and Innovation and National Institute for Health Research and others; RECOVERY ISRCTN number, ISRCTN50189673. opens in new tab; ClinicalTrials.gov number, NCT04381936. opens in new tab.)

Effect of Dexamethasone in Hospitalized Patients with COVID-19: Preliminary Report

Abstract: Background: Coronavirus disease 2019 (COVID-19) is associated with diffuse lung damage Corticosteroids may modulate immune-mediated lung injury and reducing progression to respiratory failure and death Methods: The Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, adaptive, platform trial comparing a range of possible treatments with usual care in patients hospitalized with COVID-19 We report the preliminary results for the comparison of dexamethasone 6 mg given once daily for up to ten days vs usual care alone The primary outcome was 28-day mortality Results: 2104 patients randomly allocated to receive dexamethasone were compared with 4321 patients concurrently allocated to usual care Overall, 454 (216%) patients allocated dexamethasone and 1065 (246%) patients allocated usual care died within 28 days (age-adjusted rate ratio [RR] 083; 95% confidence interval [CI] 074 to 092; P<0001) The proportional and absolute mortality rate reductions varied significantly depending on level of respiratory support at randomization (test for trend p<0001): Dexamethasone reduced deaths by one-third in patients receiving invasive mechanical ventilation (290% vs 407%, RR 065 [95% CI 051 to 082]; p<0001), by one-fifth in patients receiving oxygen without invasive mechanical ventilation (215% vs 250%, RR 080 [95% CI 070 to 092]; p=0002), but did not reduce mortality in patients not receiving respiratory support at randomization (170% vs 132%, RR 122 [95% CI 093 to 161]; p=014) Conclusions: In patients hospitalized with COVID-19, dexamethasone reduced 28-day mortality among those receiving invasive mechanical ventilation or oxygen at randomization, but not among patients not receiving respiratory support