Characterising Long Covid: a living systematic review update with controlled studies (preprint)

Background: The clinical sequelae (Long Covid) of acute Covid-19 are recognised globally, yet the risk of developing them is unknown. Methods: A living systematic review (second version). Bibliographical records from the C19 Living Map Long Covid segment (22nd February 2022), Medline, CINAHL, Global Health, WHO Covid-19 database, LitCOVID, and Google Scholar (18th November 2021). We included studies with at least 100 people at 12 weeks or more post-Covid-19 onset and with a control group without confirmed Covid-19. Risk of bias was assessed using the Newcastle-Ottawa scale. Symptoms are aligned with the Post Covid-19 Condition Core Outcome Set. We present descriptive statistics and use meta-analysis to estimate the relative risk of experiencing Long Covid. Results Twenty-eight studies were included: 20 cohort, five case-controls, three cross-sectional. Studies reported on 242,715 people with Covid-19 (55.6% female) and 276,317 controls (55.7% female) in 16 countries. Most were of moderate quality (71%). Only two were set in low-middle-income countries and few included children (18%). The longest mean follow-up time was 419.8 (standard deviation 49.4) days post-diagnosis. The relative risk (RR) of experiencing persistent or new symptoms in cases compared with controls was 1.53 (95% CI: 1.50 to 1.56). The core outcomes with the highest increased risk were cardiovascular (RR 2.53 95% CI: 2.16 to 2.96), cognitive (RR 1.99; 95% CI: 1.82 to 2.17), and physical functioning (RR 1.85; 95% CI: 1.75 to 1.96). Conclusion: SARS-CoV-2 infection is associated with a higher risk of new or persistent symptoms when compared with controls that can last over a year following acute Covid-19. There is still a lack of robust studies set in lower resourced settings and current studies have high heterogeneity and potential misclassifications of cases and controls. Future research should explore the role of vaccination and different variants on the risk of developing Long Covid.

Accessibility, inclusivity, and implementation of COVID-19 clinical management guidelines early in the pandemic: a global survey (preprint)

BackgroundWith a rapidly changing evidence base, high-quality clinical management guidelines (CMGs) are key tools for aiding clinical decision making and increasing access to best available evidence-based care. A rapid review of COVID-19 CMGs found that most lacked methodological rigour, overlooked many at-risk populations, and had variations in treatment recommendations. Furthermore, social science literature highlights the complexity of implementing guidelines in local contexts where they were not developed and the resulting potential to compound health inequities. The aim of this study was to evaluate access to, inclusivity of, and implementation of Covid-19 CMGs in different settings. MethodsA cross-sectional survey of clinicians worldwide from 15 June to 20 July 2020, to explore access to and implementation of Covid-19 CMGs and treatment and supportive care recommendations provided. Data on accessibility, inclusivity, and implementation of CMGs. were analyzed by geographic location. ResultsSeventy-six clinicians, from 27 countries responded, 82% from high-income countries, 17% from low-middle income countries. Most respondents reported access to Covid-19 CMG and confidence in implementation of these. However, many respondents, particularly from LMICs reported barriers to implementation, including limited access to treatments and equipment. Only 20% of respondents reported having access to CMGs covering care for children, 25% for pregnant women and 50% for older adults (>65 years). Themes emerging were for CMGs to include recommendations for different at-risk populations, and settings, include supportive care guidance, be readily updated as evidence emerges, and CMG implementation supported by training, and access to treatments recommended. ConclusionOur findings highlight important gaps in Covid-19 CMG development and implementation challenges during a pandemic, particularly affecting different at-risk populations and lower resourced settings. The findings highlight a need for a new, harmonized evidence-based, that is inclusive and adaptable for different context, incorporating implementation support, to improve access in evidence-based care recommendations during an emergency.

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