ABSTRACT
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.
Subject(s)
COVID-19ABSTRACT
ImportanceWhile much of the attention on the COVID-19 pandemic was directed at the daily counts of cases and those with serious disease overwhelming health services, increasingly, reports have appeared of people who experience debilitating symptoms after the initial infection. This is popularly known as long COVID. ObjectiveTo estimate by country and territory of the number of patients affected by long COVID in 2020 and 2021, the severity of their symptoms and expected pattern of recovery DesignWe jointly analyzed ten ongoing cohort studies in ten countries for the occurrence of three major symptom clusters of long COVID among representative COVID cases. The defining symptoms of the three clusters (fatigue, cognitive problems, and shortness of breath) are explicitly mentioned in the WHO clinical case definition. For incidence of long COVID, we adopted the minimum duration after infection of three months from the WHO case definition. We pooled data from the contributing studies, two large medical record databases in the United States, and findings from 44 published studies using a Bayesian meta-regression tool. We separately estimated occurrence and pattern of recovery in patients with milder acute infections and those hospitalized. We estimated the incidence and prevalence of long COVID globally and by country in 2020 and 2021 as well as the severity-weighted prevalence using disability weights from the Global Burden of Disease study. ResultsAnalyses are based on detailed information for 1906 community infections and 10526 hospitalized patients from the ten collaborating cohorts, three of which included children. We added published data on 37262 community infections and 9540 hospitalized patients as well as ICD-coded medical record data concerning 1.3 million infections. Globally, in 2020 and 2021, 144.7 million (95% uncertainty interval [UI] 54.8-312.9) people suffered from any of the three symptom clusters of long COVID. This corresponds to 3.69% (1.38-7.96) of all infections. The fatigue, respiratory, and cognitive clusters occurred in 51.0% (16.9-92.4), 60.4% (18.9-89.1), and 35.4% (9.4-75.1) of long COVID cases, respectively. Those with milder acute COVID-19 cases had a quicker estimated recovery (median duration 3.99 months [IQR 3.84-4.20]) than those admitted for the acute infection (median duration 8.84 months [IQR 8.10-9.78]). At twelve months, 15.1% (10.3-21.1) continued to experience long COVID symptoms. Conclusions and relevanceThe occurrence of debilitating ongoing symptoms of COVID-19 is common. Knowing how many people are affected, and for how long, is important to plan for rehabilitative services and support to return to social activities, places of learning, and the workplace when symptoms start to wane. Key PointsO_ST_ABSQuestionC_ST_ABSWhat are the extent and nature of the most common long COVID symptoms by country in 2020 and 2021? FindingsGlobally, 144.7 million people experienced one or more of three symptom clusters (fatigue; cognitive problems; and ongoing respiratory problems) of long COVID three months after infection, in 2020 and 2021. Most cases arose from milder infections. At 12 months after infection, 15.1% of these cases had not yet recovered. MeaningThe substantial number of people with long COVID are in need of rehabilitative care and support to transition back into the workplace or education when symptoms start to wane.
Subject(s)
Acute Disease , Dyspnea , COVID-19 , Fatigue , Cognition Disorders , DiseaseABSTRACT
BackgroundThe long-term sequelae of coronavirus disease 2019 (Covid-19) in children remain poorly characterised. This study aimed to assess long-term outcomes in children previously hospitalised with Covid-19 and associated risk factors. MethodsThis is a prospective cohort study of children ([≤]18 years old) admitted with confirmed Covid-19 to Z.A. Bashlyaeva Childrens Municipal Clinical Hospital in Moscow, Russia. Children admitted to the hospital during the first wave of the pandemic, between April 2, 2020 and August 26, 2020, were included. Telephone interview using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) Covid-19 Health and Wellbeing paediatric follow up survey. Persistent symptoms (>5 months) were further categorised by system(s) involved. FindingsOverall, 518 of 853 (61%) of eligible children were available for the follow-up assessment and included in the study. Median age was 10.4 years (IQR, 3-15.2) and 270 (52.1%) were girls; median follow-up since hospital discharge was 256 (223-271) days. At the time of the follow-up interview 126 (24.3%) participants reported persistent symptoms among which fatigue (53, 10.7%), sleep disturbance (36, 6.9%,) and sensory problems (29, 5.6%) were the most common. Multiple symptoms were experienced by 44 (8.4%) participants. Risk factors for persistent symptoms were: age "6-11 years" (odds ratio 2.74 (95% confidence interval 1.37 to 5.75) and "12-18 years" (2.68, 1.41 to 5.4), and a history of allergic diseases (1.67, 1.04 to 2.67). InterpretationA quarter of children experienced persistent symptoms months after hospitalization with acute covid-19 infection, with almost one in ten experiencing multi-system involvement. Older age and allergic diseases were associated with higher risk of persistent symptoms at follow-up. Our findings highlight the need for replication and further investigation of potential mechanisms as well as clinical support to improve long term outcomes in children. FundingNone. O_TEXTBOXResearch in contextO_ST_ABSEvidence before this studyC_ST_ABSEvidence suggests that Covid-19 may result in short- and long-term consequences to health. Studies in children and adolescents are limited and available evidence is scarce. We searched Embase for publications from inception to April, 25, 2021, using the following phrases or combinations of phrases "post-covid condition" or "post-covid syndrome" or "covid sequalae" or "post-acute covid" or "long covid" or "long hauler" with "pediatric*" or "paediatric*" or "child*" or "infant*" or "newborn*" or "toddler*" or "neonate*" or "neonatal" or "adolescent*" or "teen*". We found small case series and small cohort studies looking at Covid-19 consequences in children. No large cohort studies of previously hospitalised children, assessing symptom duration, categorisation or attempting multivariable analyses to identify independent risk factors for long Covid development were identified. Added value of this studyTo our knowledge, this is the largest cohort study with the longest follow-up since hospital discharge of previously hospitalised children. We found that even months after discharge from the hospital, approximately a quarter of children experience persistent symptoms with one in ten having multi-system involvement. Older age and allergic diseases are associated with Covid-19 consequences. Parents of some children report emotional and behavioural changes in their children after Covid-19. Implications of all the available evidenceOur findings highlight the need for continued global research of Covid-19 consequences in the paediatric population. Older children admitted to the hospital should be carefully monitored upon discharge. Large, controlled studies aiming to identify risk groups and potential intervention strategies are required to fill knowledge gaps. C_TEXTBOX
Subject(s)
COVID-19ABSTRACT
Structured Abstract Objectives: The long-term consequences of severe Covid-19 requiring hospital admission are not well characterised. The objective of this study was to establish the long-term effects of Covid-19 following hospitalisation and the impact these may have on patient reported outcome measures. Design: A multicentre, prospective cohort study with at least 3 months follow-up of participants admitted to hospital between 5th February 2020 and 5th October 2020. Setting: 31 hospitals in the United Kingdom. Participants: 327 hospitalised participants discharged alive from hospital with confirmed/high likelihood SARS-CoV-2 infection. Main outcome measures and comparisons: The primary outcome was self-reported recovery at least ninety days after initial Covid-19 symptom onset. Secondary outcomes included new symptoms, new or increased disability (Washington group short scale), breathlessness (MRC Dyspnoea scale) and quality of life (EQ5D-5L). We compared these outcome measures across age, comorbidity status and in-hospital Covid-19 severity to identify groups at highest risk of developing long-term difficulties. Multilevel logistic and linear regression models were built to adjust for the effects of patient and centre level risk factors on these outcomes. Results: In total 53.7% (443/824) contacted participants responded, yielding 73.8% (327/443) responses with follow-up of 90 days or more from symptom onset. The median time between symptom onset of initial illness and completing the participant questionnaire was 222 days (Interquartile range (IQR) 189 to 269 days). In total, 54.7% (179/327) of participants reported they did not feel fully recovered. Persistent symptoms were reported by 93.3% (305/325) of participants, with fatigue the most common (82.8%, 255/308), followed by breathlessness (53.5%, 175/327). 46.8% (153/327) reported an increase in MRC dyspnoea scale of at least one grade. New or worse disability was reported by 24.2% (79/327) of participants. Overall (EQ5D-5L) summary index was significantly worse at the time of follow-up (median difference 0.1 points on a scale of 0 to 1, IQR: -0.2 to 0.0). Females under the age of 50 years were five times less likely to report feeling recovered (adjusted OR 5.09, 95% CI 1.64 to 15.74), were more likely to have greater disability (adjusted OR 4.22, 95% CI 1.12 to 15.94), twice as likely to report worse fatigue (adjusted OR 2.06, 95% CI 0.81 to 3.31) and seven times more likely to become more breathless (adjusted OR 7.15, 95% CI 2.24 to 22.83) than men of the same age. Conclusions: Survivors of Covid-19 experienced long-term symptoms, new disability, increased breathlessness, and reduced quality of life. These findings were present even in young, previously healthy working age adults, and were most common in younger females. Policymakers should fund further research to identify effective treatments for long-Covid and ensure healthcare, social care and welfare support is available for individuals with long-Covid.
Subject(s)
COVID-19 , Dyspnea , FatigueABSTRACT
Background The World Health Organization has recently recognized Long COVID, calling the international medical community to strengthen research and comprehensive care of patients with this condition. However, if Long COVID pertains to children as well is not yet clear. Methods An anonymous, online survey was developed by an organization of parents of children suffering from persisting symptoms since initial infection. Parents were asked to report signs and symptoms, physical activity and mental health issues. Only children with symptoms persisting for more than four weeks were included. Results 510 children were included (56.3% females) infected between January 2020 and January 2021. At their initial COVID-19 infection, 22 (4.3%) children were hospitalized. Overall, children had persisting COVID-19 for a mean of 8.2 months (SD 3.9). Most frequent symptoms were: Tiredness and weakness (444 patients, 87.1% of sample), Fatigue (410, 80.4%), Headache (401, 78.6%), Abdominal pain (387, 75.9%), Muscle and joint pain (309, 60.6%), Post-exertional malaise (274, 53.7%), rash (267, 52.4%). 484 (94.9%) children had had at least four symptoms. 129 (25.3%) children have suffered constant COVID-19 infection symptoms, 252 (49.4%) have had periods of apparent recovery and then symptoms returning, and 97 (19.0%) had a prolonged period of wellness followed by symptoms. Only 51 (10.0%) children have returned to previous levels of physical activity. Parents reported a significant prevalence of Neuropsychiatric symptoms. Conclusions Our study provides further evidence on Long COVID in children. Symptoms like fatigue, headache, muscle and joint pain, rashes and heart palpitations, and mental health issues like lack of concentration and short memory problems, were particularly frequent and confirm previous observations, suggesting that they may characterize this condition. A better comprehension of Long COVID is urgently needed..
Subject(s)
Abdominal Pain , Exanthema , Memory Disorders , Headache , Mental Disorders , Arthralgia , Muscle Weakness , Nystagmus, Pathologic , Myalgia , COVID-19 , FatigueABSTRACT
BackgroundThe long-term sequalae of COVID-19 remain poorly characterised. In this study, we aimed to assess long-standing symptoms (LS) (symptoms lasting from the time of discharge) in previously hospitalised patients with COVID-19 and assess associated risk factors. MethodsThis is a longitudinal cohort study of adults ([≥]18 years of age) with clinically diagnosed or laboratory-confirmed COVID-19 admitted to Sechenov University Hospital Network in Moscow, Russia. Data were collected from patients discharged between April 8 and July 10, 2020. Participants were interviewed via telephone using Tier 1 ISARIC Long-term Follow-up Study CRF and the WHO CRF for Post COVID conditions. Reported symptoms were further categorised based on the system(s) involved. Additional information on dyspnoea, quality of life and fatigue was collected using validated instruments. Multivariable logistic regressions were performed to investigate risk factors for development of LS categories. FindingsOverall, 2,649 of 4,755 patients discharged from the hospitals were available for the follow-up and included in the study. The median age of the patients was 56 years (IQR, 46-66) and 1,353 (51.1%) were women. The median follow-up time since hospital discharge was 217.5 (200.4-235.5) days. At the time of the follow-up interview 1247 (47.1%) participants reported LS. Fatigue (21.2%, 551/2599), shortness of breath (14.5%, 378/2614) and forgetfulness (9.1%, 237/2597) were the most common LS reported. Chronic fatigue (25%, 658/2593) and respiratory (17.2% 451/2616) were the most common LS categories. with reporting of multi-system involvement (MSI) less common (11.3%; 299). Female sex was associated with LS categories of chronic fatigue with an odds ratio of 1.67 (95% confidence interval 1.39 to 2.02), neurological (2.03, 1.60 to 2.58), mood and behaviour (1.83, 1.41 to 2.40), dermatological (3.26, 2.36 to 4.57), gastrointestinal (2.50, 1.64 to 3.89), sensory (1.73, 2.06 to 2.89) and respiratory (1.31, 1.06 to 1.62). Pre-existing asthma was associated with neurological (1.95, 1.25 to 2.98) and mood and behavioural changes (2.02, 1.24 to 3.18) and chronic pulmonary disease was associated with chronic fatigue (1.68, 1.21 to 2.32). Interpretation6 to 8 months after acute infection episode almost a half of patients experience symptoms lasting since hospital discharge. One in ten individuals experiences MSI. Female sex is the main risk factor for majority of the LS categories. chronic pulmonary disease is associated with a higher risk of chronic fatigue development, and asthma with neurological and mood and behaviour changes. Individuals with LS and MSI should be the main target for future research and intervention strategies. FundingThis study is supported by Russian Fund for Basic Research and UK Embassy in Moscow. The ISARIC work is supported by grants from: the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford [award 200907], Wellcome Trust and Department for International Development [215091/Z/18/Z], and the Bill and Melinda Gates Foundation [OPP1209135], EU Platform for European Preparedness Against (Re-) emerging Epidemics (PREPARE) [FP7 project 602525] This research was funded in part, by the Wellcome Trust. The views expressed are those of the authors and not necessarily those of the DID, NIHR, Wellcome Trust or PHE. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSEvidence suggests that COVID-19 may result in short- and long-term consequences to health. Most studies do not provide definitive answers due to a combination of short follow-up (2-3 months), small sample size, and use of non-standardised tools. There is a need to study the longer-term health consequences of previously hospitalised patients with COVID-19 infection and to identify risk factors for sequalae. Added value of this studyTo our knowledge, this is the largest cohort study (n=2,649) with the longest follow-up since hospital discharge (6-8 months) of previously hospitalised adult patients. We found that 6-8 months after discharge from the hospital, around a half (47.1%) of patients reported at least one long-standing symptom since discharge. Once categories of symptoms were assessed, chronic fatigue and respiratory problems were the most frequent clusters of long-standing symptoms in our patients. Of those patients having long-term symptoms, a smaller proportion (11.3%) had multisystem involvement, with three or more categories of long-standing symptoms present. Although most patients developed symptoms since discharge, a smaller number of individuals experienced symptom beginning symptom appearing weeks or months after the acute phase. Female sex was a predictor for most of the symptom categories at the time of the follow-up interview, with chronic pulmonary disease associated with chronic fatigue-related symptoms, and asthma with a higher risk of neurological symptoms, mood and behaviour problems. Implications of all the available evidenceThe majority of patients experienced long-lasting symptoms 6 to 8 months after hospital discharge and almost half reported at least one long-standing symptom, with chronic fatigue and respiratory problems being the most frequent. A smaller number reported multisystem impacts with three or more long-standing categories present at follow-up. A higher risk was found for women, for chronic pulmonary disease with chronic fatigue, and neurological symptoms and mood and behaviour problems with asthma. Patterns of the symptom development following COVID-19 should be further investigated in future research.
Subject(s)
COVID-19ABSTRACT
There is increasing evidence that adult patients diagnosed with acute COVID-19 suffer from Long COVID initially described in Italy. To date, data on Long COVID in children are lacking. We assessed persistent symptoms in pediatric patients previously diagnosed with COVID-19. More than a half reported at least one persisting symptom even after 120 days since COVID-19, with 42.6% being impaired by these symptoms during daily activities. Symptoms like fatigue, muscle and joint pain, headache, insomnia, respiratory problems and palpitations were particularly frequent, as also described in adults. The evidence that COVID-19 can have long-term impact children as well, including those with asymptomatic/paucisymptomatic COVID-19, highlight the need for pediatricians, mental health experts and policy makers of implementing measures to reduce impact of the pandemic on child’s health.
Subject(s)
COVID-19ABSTRACT
Introduction Very little is known about possible clinical sequelae that may persist after resolution of the acute Coronavirus Disease 2019 (COVID-19). A recent longitudinal cohort from Italy including 143 patients recovered after hospitalisation with COVID-19 reported that 87% had at least one ongoing symptom at 60 day follow-up. Early indications suggest that patients with COVID-19 may need even more psychological support than typical ICU patients. The assessment of risk factors for longer term consequences requires a longitudinal study linked to data on pre-existing conditions and care received during the acute phase of illness. Methods and analysis This is an international open-access prospective, observational multi-site study. It will enrol patients following a diagnosis of COVID-19. Tier 1 is developed for following up patients day 28 post-discharge, additionally at 3 to 6 months intervals. This module can be used to identify sub-sets of patients experiencing specific symptomatology or syndromes for further follow up. A Tier 2 module will be developed for in-clinic, in-depth follow up. The primary aim is to characterise physical consequences in patients post-COVID-19. Secondary aim includes estimating the frequency of and risk factors for post-COVID- 19 medical sequalae, psychosocial consequences and post-COVID-19 mortality. A subset of patients will have sampling to characterize longer term antibody, innate and cell-mediated immune responses to SARS-CoV-2. Ethics and dissemination This collaborative, open-access study aims to characterize the frequency of and risk factors for long-term consequences and characterise the immune response over time in patients following a diagnosis of COVID-19 and facilitate standardized and longitudinal data collection globally. The outcomes of this study will inform strategies to prevent long term consequences; inform clinical management, direct rehabilitation, and inform public health management to reduce overall morbidity and improve outcomes of COVID-19.