From SARS and MERS to COVID-19: a review of the quality and responsiveness of clinical management guidelines in outbreak settings (preprint)

ObjectiveTo assess the responsiveness and quality of clinical management guidelines (CMGs) in SARS, MERS and COVID-19 and determine whether this has improved over time. DesignRapid literature review, quality assessment and focus group consultation. Data Sources- Google and Google Scholar were systematically searched from inception to 6th June 2020.This was supplemented with hand searches of national and international public health agency and infectious disease society websites as well as directly approaching clinical networks in regions where few CMGs had been identified via the primary search. Eligibility CriteriaCMGs for the treatment of COVID-19/SARS/MERS providing recommendations on supportive care and/or specific treatment. MethodsData extraction was performed using a standardised form. The Appraisal of Guidelines for Research and Evaluation (AGREE-II) tool was used to evaluate the quality of the CMGs. Six COVID-19 treatments were selected to assess the responsiveness of a subset of guidelines and their updates to 20th November 2020. We ran two sessions of focus groups with patient advocates to elicit their views on guideline development. ResultsWe included 37 COVID-19, six SARS, and four MERS CMGs. Evidence appraisals in CMGs generally focused on novel drugs rather than basic supportive care; where evidence for the latter was provided it was generally of a low quality. Most CMGs had major methodological flaws (only two MERS-CoV and four COVID-19 CMGs were recommended for use by both reviewers without modification) and there was no evidence of improvement in quality over time. CMGs scored lowest in the following AGREE-II domains: scope and purpose, editorial independence, stakeholder engagement, and rigour of development. Of the COVID-19 CMGs, only eight included specific guidance for the management of elderly patients and only ten for high-risk groups; a further eight did not specify the target patient group at all. Early in the pandemic, multiple guidelines recommended unproven treatments and whilst in general findings of major clinical trials were eventually adopted, this was not universally the case. Eight guidelines recommended that use of unproven agents should be considered on a case-by-case basis. Patient representatives expressed concern about the lack of engagement with them in CMG development and that these documents are not accessible to non-experts. ConclusionThe quality of most CMGs produced in coronaviridae outbreaks is poor and we have found no evidence of improvement over time, highlighting that current development frameworks must be improved. There is an need to strengthen the evidence base surrounding basic supportive care and develop methods to engage patients in CMG development from the beginning in outbreak settings. Systematic review registrationPROSPERO CRD42020167361

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

ObjectiveTo understand the frequency, profile, and duration of persistent symptoms of covid-19 and to update this understanding as new evidence emerges. DesignA living systematic review produced in response to the rapidly evolving evidence base for long covid. Data sourcesMedline and CINAHL (EBSCO), Global Health (Ovid), WHO Global Research Database on covid-19, LitCOVID, and Google Scholar to 28th September 2020. Study selectionStudies reporting long-term symptoms and complications among people with confirmed or suspected covid-19, both in those previously hospitalised and those never hospitalised. Only studies incorporating over 100 participants qualified for data extraction and were assessed for risk of bias. Results were analysed using descriptive statistics. Quality assessmentRisk of bias was assessed using a quality assessment checklist for prevalence studies. ResultsTwenty-eight studies qualified for data extraction; 16 of these were cohort studies, ten cross-sectional, and two large case series. The analysis included 9,442 adults with covid-19 from 13 countries. The longest mean follow-up period was 111 (SD: 11) days post-hospital discharge. A wide range of systemic, cardiopulmonary, gastrointestinal, neurological, and psychosocial symptoms was reported, of which the most common were breathlessness, fatigue, smell and taste disturbance, and anxiety. Persistent symptoms were described across both previously hospitalised and non-hospitalised populations. The quality of evidence was low, with a high risk of bias and heterogeneity in prevalence. The incorporated studies demonstrated limited external validity, a lack of control subjects, and inconsistent data collection methods. Few studies were conducted in primary care, no studies focused solely on children, and no studies were set in low- and middle-income countries. ConclusionOur findings suggest that long covid is a complex, heterogeneous condition; however, the limited evidence base currently precludes a precise definition of its symptoms and prevalence. There is a clear need for robust, controlled, prospective cohort studies, including different at-risk populations and settings, incorporating appropriate investigations, collected and recorded in a standardised way. Systematic review registrationThe protocol was prospectively registered on the PROSPERO database (CRD42020211131). Readers noteThis living systematic review will be updated regularly as new evidence emerges. The search terms and inclusion criteria will be updated in line with new evidence, research priorities and policy needs. This version is the original publication. Updates may occur for up to two years from the date of original publication. When citing this paper please consider adding the version number and date of access for clarity. O_TEXTBOXSection 1: What is already known on this topic? O_LIA significant number of people continue to describe symptoms long after the acute phase of covid-19 is over, so called long covid. C_LIO_LIThere is no case definition for long covid, which appears to be a heterogeneous condition with an uncertain prevalence. C_LI Section 2: What this study adds O_LIThis living systematic review provides a comprehensive summary of the published evidence on persistent symptoms of covid-19 and will be regularly updated. C_LIO_LIThe breadth of reported symptoms suggests a complex, heterogeneous condition affecting both hospitalised patients and those managed in the community. C_LIO_LIHowever, the current evidence base of the clinical spectrum of long covid is of limited quality and is vulnerable to biases. C_LIO_LIOur review identifies those areas where further long covid research is critically needed. C_LI C_TEXTBOX

Early clinical characteristics of Covid-19: scoping review (preprint)

ABSTRACT Background: The Coronavirus disease 2019 (covid-19) pandemic has spread rapidly across the globe. Accurate clinical characterisation studies are essential to informing research, diagnosis and clinical management efforts, particularly early in a pandemic. In this scoping review we identify the clinical characteristics of patients admitted to hospital in the early months of the pandemic, focusing on symptoms, laboratory and imaging findings, and clinical outcomes. Methods: A scoping review. MEDLINE, EMBASE and Global Health databases were searched studies published from January 1st 2020 to April 28th 2020. Studies which reported on at least 100 hospitalised patients with covid-19 of any age were included. Results: Of 1,249 studies identified through the search 78 studies were eligible for inclusion; one randomized control trial and 77 observational studies presenting data on 77,443 patients admitted with covid-19. Most studies were conducted in China (82%), 9% in the US and 10% in Europe and two studies were set in more than one country. No studies included patients from low and middle income countries. Coagulopathy was underrecognised as a complication in the early months of the pandemic. Use of corticosteroids varied widely, and the use of anticoagulants was reported in only one study. Fever, cough and dyspnoea are less common in older adults; gastrointestinal symptoms, as the only presenting feature may be underrecognised. The most common laboratory finding was lymphocytopenia. Inflammatory biomarkers were commonly elevated, including C-reactive protein and interleukin-6. Typical computed tomography findings include bilateral infiltrates however imaging may be normal in early disease. Data on clinical characteristics in children and vulnerable populations were limited. Conclusions: Clinical characterisation studies from early in the pandemic indicated that covid-19 is a multisystem disease, with biomarkers indicating inflammation and coagulopathy. However, early data collection on symptoms and clinical outcomes did not consistently reflect this wide spectrum. Corticosteroid use varied widely, and anticoagulants were rarely used. Clinicians should remain vigilant to the possibility of covid-19 in patients presenting without fever, cough and dyspnoea, particularly in older adults. Further characterisation studies in different at-risk populations is needed. Review registration: Available at https://osf.io/r2ch9 Keywords: Covid-19, clinical characteristics, symptoms, biochemical parameters, imaging, outcomes, pandemic research