ABSTRACT
BackgroundThe clinical sequelae (Long Covid) of acute Covid-19 are recognised globally, yet the risk of developing them is unknown. MethodsA 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. ResultsTwenty-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). ConclusionSARS-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. Systematic review registrationThe protocol was prospectively registered on the PROSPERO database (CRD42020211131). O_TEXTBOXO_TEXTBOXNOSection 1:C_TEXTBOXNO What is already known?O_LIPublished evidence indicates a high prevalence of people affected by post-acute SARS-CoV-2 sequelae often referred to as Long Covid; yet these estimates are impacted by heterogeneity in study design and a lack of controlled studies and core outcome sets. C_LIO_LIOur first version of this review, looking at studies till March 2021, identified a breadth of reported symptoms of Long Covid affecting both those who were hospitalised during the acute phase and those managed in the community. We also identified a lack of studies including children and set in low-middle income countries. C_LIO_LIThe most commonly reported symptoms identified were weakness, general malaise, fatigue, concentration difficulties, and breathlessness, suggesting Long Covid is a complex, heterogeneous condition. C_LI O_TEXTBOXNOSection 2:C_TEXTBOXNO What are the new findings?O_LITo address the limitations identified, this first update of our living systematic review provides a comprehensive summary of peer-reviewed published studies with a control group (till 22nd February 2022) on the risk of experiencing Covid-19 sequelae. C_LIO_LIDespite study limitations identifying control groups, our findings suggest that people with a confirmed previous SARS-CoV-2 infection are 1.5 times more likely to experience new or persisting symptoms at 12 or more weeks post-onset when compared to a control group. C_LIO_LIMapped to the new Core Outcome set for Post-Covid-19 Condition, a framework for standardised assessment, our review identifies cardiovascular functioning, cognitive functioning, and physical functioning as the outcomes with highest increased risk for people post-SARS-CoV-2 infection compared to controls. C_LI O_TEXTBOXNOSection 3:C_TEXTBOXNO What do the new findings imply?O_LIOur findings point to a clear association between exposure to SARS-CoV-2 and the risk of developing new or persistent symptoms, for some lasting longer than 12 months after the initial infection. C_LIO_LIControlled studies on Long Covid should focus on improving quality to enable multisite metaanalysis by using standardised research protocols and by evaluating participants with multiple standardised diagnostic tests at various time points to capture transitory and intermittent symptoms and complications. C_LIO_LITo help inform health system planning and rehabilitation to improve outcomes for those affected, Long Covid research should focus on estimating the burden of post-acute SARS-CoV-2 in lower resourced settings, investigating the impact of vaccination and variants on Long Covid, and investigating therapeutic strategies. C_LI C_TEXTBOX
ABSTRACT
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.
ABSTRACT
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
ABSTRACT
BackgroundWhile 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. MethodsA 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). ResultsThirty-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. ConclusionLong 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 registrationThe protocol was prospectively registered on the PROSPERO database (CRD42020211131). Section 1: What is already known?O_LIA significant number of people continue to describe ongoing symptoms long after the acute phase of Covid-19, often referred to as Long Covid. C_LIO_LILong Covid is a heterogeneous condition with an uncertain prevalence, for which there is currently no precise case definition. C_LI Section 2: What are the new findings?O_LIThis living systematic review provides a comprehensive summary of peer-reviewed published evidence on persistent symptoms of Covid-19 and will be regularly updated as new evidence emerges. C_LIO_LIThe breadth of reported symptoms suggests a complex, heterogeneous condition affecting both those who were hospitalised and those managed in the community. C_LIO_LIOur review identifies weakness (41%; 95% CI 25% to 59%), general malaise (33%; 95% confidence interval 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%) as the most common symptoms. C_LI Section 3: What do the new findings imply?O_LIThe current evidence base of the clinical spectrum of Long Covid is limited, based on heterogenous data, and vulnerable to biases, hence caution should be used when interpreting or generalising the results. C_LIO_LIOur review identifies areas where further Long Covid research is critically needed to help characterise Long Covid in different populations and define its aetiology, risk factors, and biomarkers, as well as the impact on variants of concern and vaccination on long term outcomes. C_LI
