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Lakshmi Manoharan

Bio: Lakshmi Manoharan is an academic researcher from University of Oxford. The author has contributed to research in topics: Critical appraisal & Newcastle–Ottawa scale. The author has an hindex of 4, co-authored 8 publications receiving 48 citations.

Papers
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Journal ArticleDOI
TL;DR: In this article, a living systematic review was conducted to synthesize evidence on Long Covid characteristics, to inform clinical management, rehabilitation, and interventional studies to improve long term outcomes.
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).

352 citations

Posted ContentDOI
09 Dec 2020-medRxiv
TL;DR: The 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.
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).

50 citations

Journal ArticleDOI
TL;DR: A protocol for a living systematic review that aims to synthesize the evidence on the prevalence and duration of symptoms and clinical features of post-acute CO VID-19 and its long-term complications to support the work of policy makers, practitioners, and patients when planning rehabilitation for those recovering from COVID-19.
Abstract: Although the majority of people with Covid-19 will experience mild to moderate symptoms and will recover fully, there is now increasing evidence that a significant proportion will experience persistent symptoms for months after the acute phase of the illness. These symptoms include, among others, fatigue, problems breathing, lack of smell and taste, headaches, and depression and anxiety. It is also clear the virus has lasting fluctuating multiorgan sequelae, including affecting not only the respiratory system but also the heart, liver, and nervous system. We present a protocol for a living systematic review that aims to synthesize the evidence on the prevalence and characteristics of post-acute COVID-19. The living systematic review will be updated regularly, approximately every 6 months, as new evidence emerges. We will include studies that follow up at least 100 people with Covid-19 at 12 or more weeks post Covid-19 onset, with no restrictions regarding country, setting, or language. We will use descriptive statistics and, for outcomes reported in two or more studies, we will use meta-analyses to estimate prevalence with 95% confidence intervals (CIs) using the exact method. Heterogeneity between estimates will be assessed using the I2 statistic. Our findings will also be presented as infographics to facilitate transcription to lay audiences. Ultimately, we aim to support the work of policy makers, practitioners, and patients when planning rehabilitation for those recovering from Covid-19. The protocol has been registered with PROSPERO ( CRD42020211131, 25/09/2020).

8 citations

Journal ArticleDOI
02 Jul 2021
TL;DR: The quality of most CMGs produced in coronaviridae outbreaks is poor and limited evidence of improvement over time is found, highlighting that current development frameworks must be improved.
Abstract: Background : Clinical management guidelines (CMGs) can be useful tools to guide clinician’s decision making and enable consistent evidence-based high-quality care. Here, we assessed whether their objective quality has improved over time by considering CMGs for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and from different timepoints for coronavirus disease 2019 (COVID-19). Methods: We performed a rapid literature review, quality assessment and focus group consultation. The Appraisal of Guidelines for Research and Evaluation (AGREE-II) tool was used to evaluate the quality of the CMGs. In total, six COVID-19 treatments were selected to assess the responsiveness of a subset of guidelines and their updates to 20 th November 2020. We ran two sessions of focus groups with patient advocates to elicit their views on guideline development. Results: We 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 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. 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. Conclusions: The quality of most CMGs produced in coronaviridae outbreaks is poor and we have found limited evidence of improvement over time, highlighting that current development frameworks must be improved. PROSPERO registration: CRD42020167361 (17/02/2020)

6 citations

Posted ContentDOI
15 Jan 2021-medRxiv
TL;DR: The quality of most CMGs produced in coronaviridae outbreaks is poor and there is no evidence of improvement over time, highlighting that current development frameworks must be improved.
Abstract: Objective: To assess the responsiveness and quality of clinical management guidelines (CMGs) in SARS, MERS and COVID-19 and determine whether this has improved over time. Design: Rapid 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 Criteria- CMGs for the treatment of COVID-19/SARS/MERS providing recommendations on supportive care and/or specific treatment. Methods: Data 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. Results: We 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 rigor 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. Conclusion: The 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 registration- PROSPERO CRD42020167361

5 citations


Cited by
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01 Jan 2020
TL;DR: Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
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.

4,408 citations

Journal ArticleDOI
TL;DR: In this paper, the authors conducted an online survey of people with confirmed and confirmed COVID-19, distributed via COVID19 support groups and social media (e.g. Body Politic, Long COVID Support Group, Long Haul COVID Fighters).

996 citations

Posted Content
TL;DR: Nearly 50% COVID-19 patients could not reach obvious clinical and radiological remission within 10 days after hospitalization, and the patients with male sex, anorexia and no fever on admission predicted poor efficacy.
Abstract: South Australia is presently in the throes of major changes to its regulatory system governing land use, development of land and the development of planning policy against which development assessment decisions are to be made. Eventually the planning and development control system established under the Development Act 1993 (SA) will be replaced by a new system implemented by the Planning, Development and Infrastructure Act 2016 (SA) (the new Act).

568 citations

Posted ContentDOI
27 Dec 2020-medRxiv
TL;DR: The symptom profile and time course in patients with Long COVID, along with the impact on daily life, work, and return to baseline health are characterized, to report prolonged multisystem involvement and significant disability.
Abstract: Objective To characterize the symptom profile and time course in patients with Long COVID, along with the impact on daily life, work, and return to baseline health. Design International web-based survey of suspected and confirmed COVID-19 cases with illness lasting over 28 days and onset prior to June 2020. Setting Survey distribution via online COVID-19 support groups and social media Participants 3,762 respondents from 56 countries completed the survey. 1166 (33.7%) were 40-49 years old, 937 (27.1%) were 50-59 years old, and 905 (26.1%) were 30-39 years old. 2961 (78.9%) were women, 718 (19.1%) were men, and 63 (1.7%) were nonbinary. 8.4% reported being hospitalized. 27% reported receiving a laboratory-confirmed diagnosis of COVID-19. 96% reported symptoms beyond 90 days. Results Prevalence of 205 symptoms in 10 organ systems was estimated in this cohort, with 66 symptoms traced over seven months. Respondents experienced symptoms in an average of 9.08 (95% confidence interval 9.04 to 9.13) organ systems. The most frequent symptoms reported after month 6 were: fatigue (77.7%, 74.9% to 80.3%), post-exertional malaise (72.2%, 69.3% to 75.0%), and cognitive dysfunction (55.4%, 52.4% to 58.8%). These three symptoms were also the three most commonly reported overall. In those who recovered in less than 90 days, the average number of symptoms peaked at week 2 (11.4, 9.4 to 13.6), and in those who did not recover in 90 days, the average number of symptoms peaked at month 2 (17.2, 16.5 to 17.8). Respondents with symptoms over 6 months experienced an average of 13.8 (12.7 to 14.9) symptoms in month 7. 85.9% (84.8% to 87.0%) experienced relapses, with exercise, physical or mental activity, and stress as the main triggers. 86.7% (85.6% to 92.5%) of unrecovered respondents were experiencing fatigue at the time of survey, compared to 44.7% (38.5% to 50.5%) of recovered respondents. 45.2% (42.9% to 47.2%) reported requiring a reduced work schedule compared to pre-illness and 22.3% (20.5% to 24.3%) were not working at the time of survey due to their health conditions. Conclusions Patients with Long COVID report prolonged multisystem involvement and significant disability. Most had not returned to previous levels of work by 6 months. Many patients are not recovered by 7 months, and continue to experience significant symptom burden.

542 citations

Journal ArticleDOI
31 Mar 2021-BMJ
TL;DR: The authors in this article found that individuals discharged from hospital after acute covid-19 had increased rates of multiorgan dysfunction compared with the expected risk in the general population, and the increase in risk was not confined to the elderly and was not uniform across ethnicities.
Abstract: Objective To quantify rates of organ specific dysfunction in individuals with covid-19 after discharge from hospital compared with a matched control group from the general population. Design Retrospective cohort study. Setting NHS hospitals in England. Participants 47 780 individuals (mean age 65, 55% men) in hospital with covid-19 and discharged alive by 31 August 2020, exactly matched to controls from a pool of about 50 million people in England for personal and clinical characteristics from 10 years of electronic health records. Main outcome measures Rates of hospital readmission (or any admission for controls), all cause mortality, and diagnoses of respiratory, cardiovascular, metabolic, kidney, and liver diseases until 30 September 2020. Variations in rate ratios by age, sex, and ethnicity. Results Over a mean follow-up of 140 days, nearly a third of individuals who were discharged from hospital after acute covid-19 were readmitted (14 060 of 47 780) and more than 1 in 10 (5875) died after discharge, with these events occurring at rates four and eight times greater, respectively, than in the matched control group. Rates of respiratory disease (P Conclusions Individuals discharged from hospital after covid-19 had increased rates of multiorgan dysfunction compared with the expected risk in the general population. The increase in risk was not confined to the elderly and was not uniform across ethnicities. The diagnosis, treatment, and prevention of post-covid syndrome requires integrated rather than organ or disease specific approaches, and urgent research is needed to establish the risk factors.

404 citations