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Supplemental digital content is available in the text., Objective This report describes persistent symptoms associated with post-acute COVID-19 syndrome (PACS) and the impact of these symptoms on physical function, cognitive function, health-related quality of life, and participation. Design This study used a cross-sectional observational study design. Patients attending Mount Sinai’s post-acute COVID-19 syndrome clinic completed surveys containing patient-reported outcomes. Results A total of 156 patients completed the survey, at a median (range) time of 351 days (82–457 days) after COVID-19 infection. All patients were prevaccination. The most common persistent symptoms reported were fatigue (n = 128, 82%), brain fog (n = 105, 67%), and headache (n = 94, 60%). The most common triggers of symptom exacerbation were physical exertion (n = 134, 86%), stress (n = 107, 69%), and dehydration (n = 77, 49%). Increased levels of fatigue (Fatigue Severity Scale) and dyspnea (Medical Research Council) were reported, alongside reductions in levels of regularly completed physical activity. Ninety-eight patients (63%) scored for at least mild cognitive impairment (Neuro-Qol), and the domain of the EuroQol: 5 dimension, 5 level most impacted was Self-care, Anxiety/Depression and Usual Activities. Conclusions Persistent symptoms associated with post-acute COVID-19 syndrome seem to impact physical and cognitive function, health-related quality of life, and participation in society. More research is needed to further clarify the relationship between COVID-19 infection and post-acute COVID-19 syndrome symptoms, the underlying mechanisms, and treatment options.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative virus for the pandemic coronavirus disease 2019 (COVID-19). After more than one year it becomes apparent that for some patients the acute symptoms can persist for several months. Post-acute COVID-19 is defined as the persistence of symptoms and/or long-term complications beyond 4 weeks from the onset of the acute symptoms. Even though the evidence is preliminary, the prevalence in the general population is reported to range from 15 to 30%. The symptoms can be assigned to numerous organ systems and are described as very heterogenous with regards to their number, duration and severity. To this day it is not exactly known what causes the subacute and chronic manifestation of acute COVID-19. The treatment should be guided by the individual symptoms of the patients. To prevent setbacks, it is recommended to plan and monitor physical activity carefully. Athletes returning to sports with or recovered from post-acute COVID-19 require a thorough physical examination and a stepwise increase of training load to prevent long-term organ damage and a reduction in physical capacity. The aim of the scoping review is to summarize ongoing symptoms and possible causes for post-acute COVID-19 (“long-COVID”) and to classify essential aspects for post-acute COVID-19 management to regain physical fitness on the basis of current evidence. © 2021 Das schwere akute respiratorische Syndrom Coronavirus 2 (SARS-CoV-2) ist der Erreger der pandemischen Erkrankung COVID-19, fur die nach mehr als einem Jahr erkennbar ist, dass nach einer uberstandenen akuten Erkrankung andauernde Symptome existieren konnen. Als post-akutes COVID-19 werden das Anhalten klinischer Symptome und/oder das Auftreten langfristiger Komplikationen uber 4 Wochen nach der akut symptomatischen Krankheitsphase hinaus definiert. Aussagen uber die Pravalenz sind vorlaufig und abhangig vom Betrachtungszeitraum und untersuchter Bevolkerungsgruppe. In der Allgemeinbevolkerung wird das Auftreten derzeit mit einem Anteil von 15-30% der Infizierten angegeben. Die angegebenen Symptome lassen sich einer Vielzahl von Organsystemen zuordnen und weisen, was Anzahl, Dauer und Schweregrad anbelangt, teilweise grose, interindividuelle Unterschiede auf. Die Ursachen fur die subakute und chronische Manifestation der Symptome sind noch ungeklart und verschiedene Mechanismen, wie funktionelle Einschrankungen multipler Organsysteme durch Gewebeschadigung sowie eine postivirale Autoimmunitat werden diskutiert. Cluster aus moglichen individuellen Risikofaktoren, wie Alter und Geschlecht, kombiniert mit den Symptomen in der Akutphase zeigen sich am vielversprechendsten, um die Entwicklung von post-akutem COVID-19 zu prognostizieren. Ziel des Scoping Reviews ist es, andauernde Symptome und mogliche Ursachen fur post-akutes COVID-19 (”long-COVID“) zusammenzufassen und wesentliche Aspekte fur ein post-akutes COVID-19-Management zur Wiedererlangung der korperlichen Leistungsfahigkeit evidenzbasiert einzuordnen. © 2021

Altered smell is one of the most prevalent symptoms in acute COVID-19 infection. Although most patients recover normal neurosensory function in a few weeks, approximately one-tenth of patients report long-term smell dysfunction, including anosmia, hyposmia, parosmia and phantosmia, with a particularly notable impact on quality of life. In this complex scenario, inflammation and cellular damage may play a key role in the pathogenesis of olfactory dysfunctions and may affect olfactory signaling from the peripheral to the central nervous system. Appropriate management of smell disturbances in COVID-19 patients must focus on the underlying mechanisms and the assessment of neurosensorial pathways. This article aims to review the aspects of olfactory impairment, including its pathophysiology, epidemiology, and clinical management in post-acute COVID-19 syndrome (PACS).

Objectives: Various symptoms and considerable organ dysfunction persist following infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Uncertainty remains about the potential mid- and long-term health sequelae. This prospective study of patients hospitalized with coronavirus disease 2019 (COVID-19) in Liège University Hospital, Belgium aimed to determine the persistent consequences of COVID-19. Methods: Patients admitted to the University Hospital of Liège with moderate-to-severe confirmed COVID-19, discharged between 2 March and 1 October 2020, were recruited prospectively. Follow-up at 3 and 6 months after hospital discharge included demographic and clinical data, biological data, pulmonary function tests (PFTs) and high-resolution computed tomography (CT) scans of the chest. Results: In total, 199 individuals were included in the analysis. Most patients received oxygen supplementation (80.4%). Six months after discharge, 47% and 32% of patients still had exertional dyspnoea and fatigue. PFTs at 3-month follow-up revealed a reduced diffusion capacity of carbon monoxide (mean 71.6 ± 18.6%), and this increased significantly at 6-month follow-up (P

Introduction: Despite more than one year passed since the first cases of SARS-CoV-2 were reported, there is still no consensus on the definition and clinical management of post-acute-COVID-19. The condition has heterogeneously been named as Chronic COVID syndrome, Post COVID-19 Syndrome, post-acute sequela of SARS-CoV-2 (PASC), and the more familiar long COVID. Method: In order to capture all relevant published studies, we undertook a multi-step search with no language restriction. The following four-step search strategy was utilized: First, a preliminary (limited) search was conducted on January 20, 2021, in Google Scholar and PubMed to identify the appropriate keywords. Then, on January 30, 2021, we adopted a search strategy of electronic databases from Cochrane Library, PsycINFO, PubMed, Embase, Scopus, and Web of sciences, using those keywords. Then, after duplicate removal, we screened all titles, abstracts, and full texts. This resulted in 66 eligible studies. Subsequently, after a forward and backward search of their references and citations an additional 54 publications were found, resulting in a total of 120 publications that formed the basis of the present analysis. The titles, abstracts, and full-texts of non-English articles were translated using Google Translate for further evaluation. We conducted our scoping review based on the PRISMA-ScR Checklist.Results: We found only one randomized clinical trial in our search. Of the 67 original studies, 22 were cohort and 28 were cross-sectional studies totaling 74.6% of the original studies. Of the total of 120 publications, 59 (49.1%) focused on signs and symptoms, 28 (23.3%) were focused on management, and 13 (10.8%) focused on pathophysiology. Ten (9%) publications focused on imaging studies. Ninety-one percent of the original investigations came from high and upper-middle-income countries, highlighting the scarcity of reports originating from low-income and lower-middle-income countries.Conclusion: The predominant symptoms among those with the so-called “Long COVID” were: fatigue, breathlessness, arthralgia, sleep difficulties, and chest pain. Recent reports also point to the risk of long-term sequela with cutaneous, respiratory, cardiovascular, musculoskeletal, mental health, neurologic, and renal involvement in those who survive the acute phase of the illness. The ambiguity and controversies in its definition have impaired proper recognition and management of those requiring additional support following the resolution of the acute phase of this infection. This has resulted in long-standing distress for the patients and their families. Our findings highlight the need for a multidisciplinary approach, support, and rehabilitation for these patients in terms of long-term mental and physical health.

Background Approximately 10% of patients with Covid-19 experience symptoms beyond 3–4 weeks. Patients call this “long Covid”. We sought to document such patients’ lived experience, including accessing and receiving healthcare and ideas for improving services. Methods We held 55 individual interviews and 8 focus groups (n = 59) with people recruited from UK-based long Covid patient support groups, social media and snowballing. We restricted some focus groups to health professionals since they had already self-organised into online communities. Participants were invited to tell their stories and comment on others’ stories. Data were audiotaped, transcribed, anonymised and coded using NVIVO. Analysis incorporated sociological theories of illness, healing, peer support, clinical relationships, access, and service redesign. Results Of 114 participants aged 27–73 years, 80 were female. Eighty-four were White British, 13 Asian, 8 White Other, 5 Black, and 4 mixed ethnicity. Thirty-two were doctors and 19 other health professionals. Thirty-one had attended hospital, of whom 8 had been admitted. Analysis revealed a confusing illness with many, varied and often relapsing-remitting symptoms and uncertain prognosis; a heavy sense of loss and stigma; difficulty accessing and navigating services; difficulty being taken seriously and achieving a diagnosis; disjointed and siloed care (including inability to access specialist services); variation in standards (e.g. inconsistent criteria for seeing, investigating and referring patients); variable quality of the therapeutic relationship (some participants felt well supported while others felt “fobbed off”); and possible critical events (e.g. deterioration after being unable to access services). Emotionally significant aspects of participants’ experiences informed ideas for improving services. Conclusion Suggested quality principles for a long Covid service include ensuring access to care, reducing burden of illness, taking clinical responsibility and providing continuity of care, multi-disciplinary rehabilitation, evidence-based investigation and management, and further development of the knowledge base and clinical services. Trial registration NCT04435041.

Background It is expected that GPs are increasingly confronted with a large group of patients with symptoms persisting three weeks after initial symptoms of a mild (managed in the outpatient setting) COVID-19 infection. Currently, research on these persistent symptoms mainly focuses on patients with severe infections (managed in an inpatient setting) whereas patients with mild disease are rarely studied. Objective The main objective of this systematic review was to create an overview of the nature and frequency of persistent symptoms experienced by patients after mild COVID-19 infection. Methods Systematic literature searches were performed in Pubmed, Embase and PsychINFO on 2 February 2021. Quantitative studies, qualitative studies, clinical lessons and case reports were considered eligible designs. Results In total, nine articles were included in this literature review. The frequency of persistent symptoms in patients after mild COVID-19 infection ranged between 10% and 35%. Symptoms persisting after a mild COVID-19 infection can be distinguished into physical, mental and social symptoms. Fatigue was the most frequently described persistent symptom. Other frequently occurring persistent symptoms were dyspnoea, cough, chest pain, headache, decreased mental and cognitive status and olfactory dysfunction. In addition, it was found that persisting symptoms after a mild COVID-19 infection can have major consequences for work and daily functioning. Conclusion There is already some evidence that symptoms of mild COVID-19 persist after 3 weeks in a third of patients. However, there is a lack of data about symptoms persisting after 3 months (long-COVID). More research is needed to help GPs in managing long-COVID.

More than 87% of patients report the persistence of at least one symptom after recovery from Coronavirus disease 2019 (COVID-19). Dyspnea is one of the most frequently reported symptoms following severe acute respiratory syndrome coronavirus-2 infection (SARS CoV-2) with persistent chest radiological abnormalities up to three months after symptom onset. These radiological abnormalities are variable and most commonly include ground-glass opacities, reticulations, mosaic attenuation, parenchymal bands, interlobular septal thickening, bronchiectasis, and fibrotic like changes. However, in this case report, we describe findings of bullous lung disease as a complication of severe acute respiratory syndrome coronavirus-2 infection. As the pandemic continues there is a need to understand the multiple respiratory manifestations of post-acute sequelae of COVID-19. We, therefore, present this case to add to the current body of literature describing pulmonary disease as a consequence of SARS CoV-2 infection.

Resumen La infeccion por el nuevo coronavirus SARS-CoV-2 ha alcanzado proporciones de pandemia, con un numero de muertes muy elevado en todo el mundo. A pesar del esfuerzo improbo desarrollado por la comunidad cientifica para abordar esta enfermedad en su fase aguda, asi como en la prevencion mediante la creacion de vacunas en tiempo record, aun queda otro caballo de batalla importante: comprender y tratar la persistencia de sintomas mas alla de la fase aguda, el llamado Sindrome COVID-19 prolongado o COVID persistente. Estas manifestaciones persistentes afectan a varios organos y sistemas y podrian depender tanto de los mecanismos patogenicos del virus como de la respuesta fisiopatologica del paciente. Un ano despues del inicio de esta pandemia, es una necesidad urgente abordar esta situacion desde un enfoque integral

The cardiovascular system is significantly affected in coronavirus disease-19 (COVID-19). Microvascular injury, endothelial dysfunction, and thrombosis resulting from viral infection or indirectly related to the intense systemic inflammatory and immune responses are characteristic features of severe COVID-19. Pre-existing cardiovascular disease and viral load are linked to myocardial injury and worse outcomes. The vascular response to cytokine production and the interaction between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and angiotensin-converting enzyme 2 receptor may lead to a significant reduction in cardiac contractility and subsequent myocardial dysfunction. In addition, a considerable proportion of patients who have been infected with SARS-CoV-2 do not fully recover and continue to experience a large number of symptoms and post-acute complications in the absence of a detectable viral infection. This conditions often referred to as ‘post-acute COVID-19’ may have multiple causes. Viral reservoirs or lingering fragments of viral RNA or proteins contribute to the condition. Systemic inflammatory response to COVID-19 has the potential to increase myocardial fibrosis which in turn may impair cardiac remodelling. Here, we summarize the current knowledge of cardiovascular injury and post-acute sequelae of COVID-19. As the pandemic continues and new variants emerge, we can advance our knowledge of the underlying mechanisms only by integrating our understanding of the pathophysiology with the corresponding clinical findings. Identification of new biomarkers of cardiovascular complications, and development of effective treatments for COVID-19 infection are of crucial importance., Graphical Abstract Graphical Abstract

Ersin Sar&inodot;çam,1,2 Ali Do&gbreve;an Dursun,3,4 Gülçin Türkmen Sar&inodot;y&inodot;ld&inodot;z,5,6 Nalan Can,7 Engin Bozkurt,1 U&gbreve;ur Gönüllü,8 Nihal Basay,9 Meral Türkmen,10 Abdülaziz Denli,11 Mustafa Ünlü12 1Department of Cardiology, Medicana International Ankara Hospital, Ankara, Turkey; 2Department of Cardiology, At&inodot;l&inodot;m University Medical School, Ankara, Turkey; 3Department of Physiology, At&inodot;l&inodot;m University Medical School, Ankara, Turkey; 4Check-up Center, Home Care Services, Medicana International Ankara Hospital, Ankara, Turkey; 5Department of General Surgery, Medicana International Ankara Hospital, Ankara, Turkey; 6Operating Room Services, Vocational School of Health Services, At&inodot;l&inodot;m University, Ankara, Turkey; 7Department of Nuclear Medicine, Medicana International Ankara Hospital, Ankara, Turkey; 8Department of Pulmonary Medicine, At&inodot;l&inodot;m University Medical School, Ankara, Turkey; 9Department of Pulmonary Medicine, Medicana International Ankara Hospital, Ankara, Turkey; 10Department of Internal Medicine, Medicana International Ankara Hospital, Ankara, Turkey; 11Department of Physical Medicine and Rehabilitation, Medicana International Ankara Hospital, Ankara, Turkey; 12Department of Nuclear Medicine, Gazi University Medical School, Ankara, TurkeyCorrespondence: Ersin Sar&inodot;çamDepartment of Cardiology, Medicana International Ankara Hospital, Sö&gbreve;ütözü Cd. 2165. Sokak No: 6, Sö&gbreve;ütözü, Ankara, 06520, TurkeyTel +90 5324066440Fax +90 3122203170Email saricamersin@yahoo.comBackground: In the post-acute COVID-19 syndrome, many patients suffer from palpitations, effort-associated fatigue, and even sudden death. The mechanism of heart involvement in this syndrome is uncertain. The main purpose of the study was to identify possible cardiac involvement causes in patients with post-acute COVID-19 by using biomarkers such as NT-proBNP and nitric oxide (NO) and cardiac imaging modalities.Methods: In this cross-sectional study, a total of 105 participants were included according to the existence of symptoms, and 40 of these participants were asymptomatic patients. The ages of the participants ranged from 20 to 50 years. All patients were healthy before COVID-19. The symptoms were defined as palpitations and/or fatigue association with exercise in post-acute COVID-19 term. The comparison of the two groups was made by using biochemical parameters (NT-proBNP, Troponin I, NO) and imaging techniques (echocardiography, cardiovascular magnetic resonance (CMR) and cardiac positron emission tomography (PET)).Results: The symptomatic patients had higher NT-proBNP levels compared with asymptomatic patients (132.30± 35.15; 76.86± 16.79, respectively; p < 0.001). Interestingly, the symptomatic patients had lower NO levels than asymptomatic patients (9.20± 3.08; 16.15± 6.02, respectively; p < 0.001). Echocardiography and CMR were normal. However, we found regional increased 18F-FDG uptake on cardiac PET to be compatible with myocardial fatigue.Conclusion: We found elevated NT-proNBP levels, low serum NO levels, and increased 18F-FDG uptake on cardiac PET in post-acute COVID syndrome. Cardiac PET could replace or be added to CMR for detecting subtle subacute/chronic myocarditis. The follow-up of patients with post-acute COVID-19 could target the possibility of risk of heart failure.Keywords: post-acute COVID-19, cardiac involvement, laboratory tests, imaging

Dalia Tohamy,1 Mohamed Sharaf,1 Khaled Abdelazeem,1 Mohamed GA Saleh,1 Mahmoud F Rateb,1 Wael Soliman,1 Salma M Kedwany,1 Mohamed Omar Abdelmalek,2 Mohammed A Medhat,2 Amal M Tohamy,3 Hany Mahmoud4 1Ophthalmology Department, Assiut University, Assiut, Egypt; 2Tropical Medicine and Gastroenterology Department, Assiut University, Assiut, Egypt; 3Neuology Department, Assiut University, Assiut, Egypt; 4Ophthalmology Department, Sohag University, Sohag, EgyptCorrespondence: Hany MahmoudOphthalmology Department, Sohag University, Almohafza Street, Sohag, 82511, EgyptTel +20 1024368111Email drhanymahmoud@gmail.comPurpose: To evaluate the ocular manifestations of post-acute COVID-19 syndrome.Methods: A retrospective, comparative study included 100 patients who had recovered from COVID-19 and 100 controls who were recruited by stratified randomization from hospital registration system and analyzed regarding history, full ophthalmological examination, general examination including internal medicine and neurological evaluation. Laboratory tests were done.Results: Mean±SD of age were 55.5 ± 6.2 in COVID group vs 56.5 ± 5.8 in control group; P value = 0.7. In COVID group, 57 patients (57%) were males vs 51 patients (51%) in control group (P value = 0.39), the other compared parameters including history and risk factors showed non-significant difference except for ESR and D-dimer which were elevated in COVID group. In COVID group, 5 patients (5%) were having retinal vascular occlusion, 2 patients (2%) were having anterior ischemic optic neuropathy AION, 3 patients (3%) were having uveitis and 2 patients (2%) were having central serous chorioretinopathy CSCR. While in control group, 2 patients (2%) were having retinal vascular occlusion, and none had AION, uveitis or CSCR (P value = 0.006).Conclusion: Post-acute COVID-19 syndrome could affect the eyes in the form of coagulation problems, neurological morbidities, and other manifestations. This necessitates meticulous follow-up of recovered patients from COVID-19.Keywords: eye, post-acute COVID-19, Upper Egypt, coagulation, follow-up

Background: Coronavirus disease 2019 (COVID-19) has been implicated in a wide spectrum of cardiac manifestations following the acute phase of the disease. Objectives: To assess the range of cardiac sequelae after COVID-19 recovery. Data sources: PubMed, Embase, Scopus (inception through 17 February 2021) and Google scholar (2019 through 17 February 2021). Study eligibility criteria: Prospective and retrospective studies, case reports and case series. Participants: Adult patients assessed for cardiac manifestations after COVID-19 recovery. Exposure: Severe acute respiratory syndrome coronavirus 2 infection diagnosed by PCR. Methods: Systematic review. Results: Thirty-five studies (fifteen prospective cohort, seven case reports, five cross-sectional, four case series, three retrospective cohort and one ambidirectional cohort) evaluating cardiac sequelae in 52 609 patients were included. Twenty-nine studies used objective cardiac assessments, mostly cardiac magnetic resonance imaging (CMR) in 16 studies, echocardiography in 15, electrocardiography (ECG) in 16 and cardiac biomarkers in 18. Most studies had a fair risk of bias. The median time from diagnosis/recovery to cardiac assessment was 48 days (1–180 days). Common short-term cardiac abnormalities (

Evidence before this studyIt is emerging that long-term symptoms are often present in people who have had acute COVID-19 disease. These symptoms affect a range of organ systems including respiratory, cardiovascular and neurological systems. It is not clear how many patients who required hospitalisation develop these symptoms and the impact they have on quality of life. We searched PubMed on 24th March 2021 using the terms ‘COVID-19’, ‘long-Covid’, ‘long-term’ and ‘outcomes’. This was supplemented by hand searching relevant references and news reports. We identified several small studies focussing on specific symptoms or diseases, studies of patients in community settings and studies of patients who were hospitalised for acute COVID-19 in Italy, Russia and China. There were no peer-reviewed published data at the time of searching which captured outcomes of patients within the United Kingdom.Added Value of this studyWe found that over half of patients reported not feeling fully recovered several months after onset of Covid-19 symptoms. The most common symptoms reported were fatigue, followed by breathlessness. Patients reported significant increases in new or worse disability, increases in MRC dyspnoea scale and worse quality of life as measured by EQ5D-5L summary index at the time of follow-up compared to before onset of acute COVID-19 symptoms. Our study found that women, in particular women under the age of 50 were significantly more likely to not feel fully recovered, were more breathless, more fatigued and had higher rates of new or worsened disability, even after taking severity of acute disease into account when compared to men of the same age.Implications of all available evidenceLong-term symptoms following hospitalisation for COVID-19 are very common and have significant impacts on quality of life. Women under 50 were most likely to have the worst outcomes. Policy makers need to ensure there is long-term support for people experiencing long-Covid and should plan for lasting long-term population morbidity. Funding for research to understand mechanisms underlying long-Covid and identify potential interventions for testing in randomised trials is urgently required.Structured AbstractBackgroundThis study sought to establish the long-term effects of Covid-19 following hospitalisation.Methods327 hospitalised participants, with SARS-CoV-2 infection were recruited into a prospective multicentre cohort study at least 3 months post-discharge. The primary outcome was self-reported recovery at least ninety days after initial Covid-19 symptom onset. Secondary outcomes included new symptoms, disability (Washington group short scale), breathlessness (MRC Dyspnoea scale) and quality of life (EQ5D-5L).Findings55% of participants reported not feeling fully recovered. 93% reported persistent symptoms, with fatigue the most common (83%), followed by breathlessness (54%). 47% reported an increase in MRC dyspnoea scale of at least one grade. New or worse disability was reported by 24% of participants. The EQ5D-5L summary index was significantly worse at 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.InterpretationSurvivors of Covid-19 experienced long-term symptoms, new disability, increased breathlessness, and reduced quality of life. These findings were present in young, previously healthy working age adults, and were most common in younger females.Role of the funder: The study sponsors and funders had no role in the study design, collection, analysis, interpretation of data, writing of the report, or the decision to submit the article for publication. Investigators were independent from funders and the authors have full access to all of the data, including any statistical analysis and tables.

Background. COVID-19, caused by SARS-CoV-2, can involve sequelae and other medical complications that last weeks to months after initial recovery, which has come to be called Long-COVID or COVID long-haulers. This systematic review and meta-analysis aims to identify studies assessing long-term effects of COVID-19 and estimates the prevalence of each symptom, sign, or laboratory parameter of patients at a post-COVID-19 stage. Methods. LitCOVID (PubMed and Medline) and Embase were searched by two independent researchers. All articles with original data for detecting long-term COVID-19 published before 1st of January 2021 and with a minimum of 100 patients were included. For effects reported in two or more studies, meta-analyses using a random-effects model were performed using the MetaXL software to estimate the pooled prevalence with 95% CI. Heterogeneity was assessed using I2 statistics. This systematic review followed Preferred Reporting Items for Systematic Reviewers and Meta-analysis (PRISMA) guidelines, although the study protocol was not registered. Results. A total of 18,251 publications were identified, of which 15 met the inclusion criteria. The prevalence of 55 long-term effects was estimated, 21 meta-analyses were performed, and 47,910 patients were included. The follow-up time ranged from 14 to 110 days post-viral infection. The age of the study participants ranged between 17 and 87 years. It was estimated that 80% (95% CI 65-92) of the patients that were infected with SARS-CoV-2 developed one or more long-term symptoms. The five most common symptoms were fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and dyspnea (24%). All meta-analyses showed medium (n=2) to high heterogeneity (n=13). Conclusions. In order to have a better understanding, future studies need to stratify by sex, age, previous comorbidities, the severity of COVID-19 (ranging from asymptomatic to severe), and duration of each symptom. From the clinical perspective, multi-disciplinary teams are crucial to developing preventive measures, rehabilitation techniques, and clinical management strategies with whole-patient perspectives designed to address long COVID-19 care.

To date, information on COVID-19 long-term post-recovery sequelae in children and adolescents remains scarce. A retrospective descriptive cohort study was performed by collecting data on 92 patients (age ≤ 18 years). All were evaluated during a face-to-face visit following a specially designed post-COVID-19 symptom assessment protocol at the following stage: 1–3 months after COVID-19 onset. Among the 92 children, 45 (49%) were completely free of any COVID-19-related symptoms, while 47 (51%) reported persistence of at least one symptom, in particular tiredness, loss of taste and/or smell and headaches. The most common post-acute COVID-19 clinical features were noted in children aged between 10 and 18 years. A detailed multidisciplinary follow-up of patients with COVID-19 seems relevant, whatever the severity of the symptoms.

Central and peripheral nervous system involvement during acute COVID-19 is well known. Although many patients report some subjective symptoms months after the infection, the exact incidence of neurological and cognitive sequelae of COVID-19 remains to be determined. The aim of this study is to investigate if objective neurological or cognitive impairment is detectable four months after SARS-CoV-2 infection, in a group of patients who had mild-moderate COVID-19. A cohort of 120 health care workers previously affected by COVID-19 was examined 4 months after the diagnosis by means of neurological and extensive cognitive evaluation and compared to a group of 30 health care workers who did not have COVID-19 and were similar for age and co morbidities. At 4 month follow-up, 118/120 COVID-19 cases had normal neurological examination, two patients had neurological deficits. COVID-19 patients did not show general cognitive impairment at MMSE. In COVID-19 cases the number of impaired neuropsychological tests was not significantly different from non COVID-19 cases (mean 1.69 and 1 respectively, Mann-Whitney p = n.s.), as well as all the mean tests' scores. Anxiety, stress and depression scores resulted to be significantly higher in COVID-19 than in non COVID-19 cases. The results do not support the presence of neurological deficits or cognitive impairment in this selected population of mild-moderate COVID-19 patients four months after the diagnosis. Severe emotional disorders in patients who had COVID-19 in the past are confirmed.

Objective To study long term consequences of hospitalization for COVID-19 in patients with chronic inflammatory diseases. We studied the risk of subsequent hospitalizations in patients with chronic inflammatory diseases, who survived a hospitalization for COVID-19, compared to other patients who had been hospitalized for COVID-19. Design and Setting Population based cohort study based on Danish nationwide health registers. The study population included all adult patients in Denmark who had been discharged alive after a hospitalization with COVID-19 from March 1, 2020 to July 31, 2021. Population From the study population, the exposed cohort constituted patients who had inflammatory bowel diseases (IBD), rheumatoid arthritis (RA), spondyloarthropathy (SpA), or psoriatic arthritis (PsA) prior to hospitalization for COVID-19, and the unexposed cohort constituted those without these diseases. Main outcome measures We estimated the adjusted Hazard Rate (aHR) for the following outcomes: overall risk of hospitalization, cardiovascular diseases, respiratory diseases, blood and blood-forming organs, nervous system diseases, infections, sequelae of COVID-19, and death. Results A total of 417 patients with IBD/RA/SpA/PsA were discharged alive after COVID-19, and 9,248 patients without these diseases. Across the different outcomes examined, the median length of follow up was 6.50 months in the exposed cohort (25–75% percentiles: 4.38–8.12), and among the unexposed the median time of follow up was 6.59 months (25–75% percentiles: 4.17–8.49). Across different analyses, we consistently found a significantly increased risk of hospitalizations due to respiratory diseases (aHR 1.27 (95% CI 1.02–1.58)) and infections (aHR 1.55 (95% CI 1.26–1.92)). In sensitivity analyses, the overall risk of hospitalization was aHR 1.15 (95% CI 0.96–1.38) and the risk of hospitalization due to cardiovascular diagnoses was aHR 1.14 (95% CI 0.91–1.42). During the time of follow up, the risk of nervous system diagnoses or death was not increased in patients with IBD/RA/SpA/PsA. Conclusions After hospitalization with COVID-19, patients with IBD/RA/SpA/PsA had an increased risk of subsequent hospitalizations for a number of categories of diseases, compared to other patients who have been hospitalized with COVID-19. These results are disturbing and need to be examined further. The implication of our results is that clinicians should be particularly alert for post COVID-19 symptoms from several organ systems in patients with IBD/RA/SpA/PsA., Graphical abstract Image 1

(1) Background: Post-acute COVID-19 syndrome, characterized by persisting symptoms up to 12 weeks after the acute illness, impairs numerous people’s physical and mental health. (2) Methods: 64 inpatients and 79 outpatients, aged under 55 years, with post-acute COVID-19, were evaluated by a transthoracic echocardiography (TTE), mental health examination, Quality of Life (QoL) questionnaire, post-COVID-19 functional status scale (PCFS) and Hospital Anxiety and Depression Scale (HADS). (3) Results: all inpatients had mild/moderate pulmonary injury during acute COVID-19, in contrast to 37.97% of outpatients. Inpatients who reported an average of 5 persisting symptoms, had, predominantly, level 3 PCFS and a median QoL of 62, compared to outpatients, who reported an average of 3 symptoms, level 1 PCFS and a median QoL score of 70. Increased pulmonary artery pressure was detected in 28.11% of inpatients, compared to 17.72% of outpatients, while diastolic dysfunction was diagnosed in 28.12% of inpatients, in comparison with 20.25% of outpatients (p = 0.02). Abnormal systolic function was assessed in 9.37% of inpatients, and 7.58% of outpatients. According to the HADS depression subscale, 46.87% of inpatients and 27.84% of outpatients had clinical depression. Concomitantly, anxiety was detected in 34.37% of inpatients and 40.5% of outpatients (4) Conclusions: cardiovascular and mental health difficulties were frequently detected in patients with post-acute symptoms of COVID-19, which correlated with the number and intensity of persisting symptoms and reduced QoL scores.

The existence of a variety of symptoms with a duration beyond the acute phase of COVID-19, is referred to as post-COVID syndrome (PCS). We aimed to report a series of patients with PCS attending a Post-COVID Unit and offer a comprehensive review on the topic. Adult patients with previously confirmed SARS-CoV-2 infection were systematically assessed through a semi-structured and validated survey. Total IgG, IgA and IgM serum antibodies to SARS-CoV-2 were evaluated by an electrochemiluminescence immunoassay. A systematic review of the literature and meta-analysis were conducted, following PRISMA guidelines. Univariate and multivariate methods were used to analyze data. Out of a total of 100 consecutive patients, 53 were women, the median of age was 49 years (IQR: 37.8 to 55.3), the median of post-COVID time after the first symptoms was 219 days (IQR: 143 to 258), and 65 patients were hospitalized during acute COVID-19. Musculoskeletal, digestive (i.e., diarrhea) and neurological symptoms including depression (by Zung scale) were the most frequent observed in PCS patients. A previous hospitalization was not associated with PCS manifestation. Arthralgia and diarrhea persisted in more than 40% of PCS patients. The median of anti-SARS-CoV-2 antibodies was 866.2 U/mL (IQR: 238.2 to 1681). Despite this variability, 98 patients were seropositive. Based on autonomic symptoms (by COMPASS 31) two clusters were obtained with different clinical characteristics. Levels of anti-SARS-CoV-2 antibodies were not different between clusters. A total of 40 articles (11,196 patients) were included in the meta-analysis. Fatigue/muscle weakness, dyspnea, pain and discomfort, anxiety/depression and impaired concentration were presented in more than 20% of patients reported. In conclusion, PCS is mainly characterized by musculoskeletal, pulmonary, digestive and neurological involvement including depression. PCS is independent of severity of acute illness and humoral response. Long-term antibody responses to SARS-CoV-2 infection and a high inter-individual variability were confirmed. Future studies should evaluate the mechanisms by which SARS-CoV-2 may cause PCS and the best therapeutic options.HighlightsPCS is mainly characterized by musculoskeletal, pulmonary, digestive and neurological involvement including depression.PCS is independent of severity of acute illness and humoral immune response.Autonomic symptoms may help to classify patients with PCS.Long-term antibody responses to SARS-CoV-2 infection and a high inter-individual variability were confirmed.