The first long-term follow-up data from the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) Clinical Characterisation Protocol study from the UK is available today as a pre-print, and shows that, in adults who were admitted to hospital, nearly all experienced ongoing symptoms 3 months or more after the onset of their COVID-19 infection.
This paper was tabled at a meeting of the Scientific Advisory Group for Emergencies (SAGE) on 25 February 2021.
The research finds that adult women under the age of 50 had higher odds of worse long-term health outcomes when compared with men and older study participants, even if they had no previous co-morbidity.
People with more severe acute disease in hospital also had worst long-term outcomes than those who did not require oxygen. Overall, more than half of all the participants reported not being fully recovered three months after the onset of COVID-19 symptoms.
This research, which is led by the University of Glasgow in collaboration with the Universities of Oxford, Liverpool, Edinburgh and Imperial College London, and working with ISARICs global COVID-19 follow up working group, is the first UK data on persistent symptoms—and impact on day to day functioning and quality of life—after three to nine months after COVID-19 onset.
Researchers followed 327 adults from 31 hospitals around the UK who had been admitted to hospital between 5th February 2020 and 5th October 2020. Participants were followed-up with for at least three months, and up to 11 months, in order to document their physical health, and impact on psychological health and quality of life.
Female participants under the age of 50 years-old were five times less likely to report feeling fully recovered. Moreover, they were twice as likely to report worse fatigue, were seven times more likely to be more breathless and were more likely to have worsening difficulties or a new disabilities, especially relating to memory, mobility and communication, and also vision, hearing and self-care than men of the same age after their acute COVID-19 illness.
Overall, 55% of participants reported that they did not feel fully recovered. In addition, ongoing symptoms were reported by 93% of participants, with fatigue the most common, reported by 83%, followed by breathlessness, which was reported by 54% of people, many also experienced muscular pain and discomfort.
Dr. Janet Scott, from the University of Glasgow-MRC Centre for Virus Research, lead author of the study, said: “Our research shows that survivors of COVID-19 experienced long-term symptoms, including a new disability, increased breathlessness, and a reduced quality of life. These findings were present even in young, previously healthy working age adults, and were most common in younger females.
“The fact that women under the age of 50 are the group with the worst outcomes could have profound implications for pandemic policy decision, as well as vaccination strategy.”
Margaret O’Hara, of the Long COVID patient group, Long COVID Support, said “This research is important because it shows that just because people have been discharged from hospital it doesn’t mean that they have recovered from COVID. Long COVID support have worked closely with the research team to develop the questionnaire for this study to make sure that the incidence of Long COVID is properly recorded.
“The tens of thousands of people using online support forums for long COVID are desperate for research which can help them get their lives back. Research such as this is crucial to understand the true incidence of Long COVID and the huge impact it has on people’s lives so that proper services can be developed to meet their needs.”
Louise Sigfrid of the ISARIC Global Support Centre, University of Oxford said: “This is an important first step and part of a wider harmonized international effort to better understand Long COVID. We have sister projects running in 15 countries in Europe, South America, Africa, Asia and the Middle East, to forward our understanding of Long COVID, including identifying people at increased risk for developing Long COVID, to inform preventative strategies, interventional studies and targeted support to improve outcomes.”
Professor Calum Semple, Professor of Child Health and Outbreak Medicine at the University of Liverpool and chief investigator of ISARIC 4C, said: “ISARIC uses prepared protocols and harmonized data tools to conduct timely research in outbreaks. This prospective cohort study of UK COVID survivors is an important first step in defining the spectrum of Long COVID.
We found that the most severely affected people are women of working age and the continued to experience a range of disabling problems long after discharge from hospital.”
Dr. Tom Drake, Clinical Research Fellow at the Usher Institute, University of Edinburgh, said: “It is becoming increasingly clear that COVID-19 has profound consequences for those who survive the disease.
In our study, we found that younger women were most likely to have worse long-term outcomes. It’s really important that people living with the consequences of COVID-19 get the right support they need. Governments, both in the UK and across the world, need to think about the impact this will have in the long-term and fund urgent research to find treatments for long-COVID.”
The paper, “Long COVID in adults discharged from UK hospitals after COVID-19: A prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol,” is available on MedRxiv.
The title and abstract of 18,251 publications were screened. Of these, 82 full publications were reviewed. Nineteen studies were excluded because they involved less than 100 persons. A total of 15 studies were selected to be analyzed (Table 1, Figure 1). Most of the studies assessed specific symptoms included in a previously applied questionnaire.
The process of study selection is presented in Figure 1. There were 9 studies from UK/ Europe, 3 from the US, 1 each from Australia, China, Egypt, and Mexico. The patient follow-up time ranged from 14 days to 110 days. Six out of the 11 studies included only patients hospitalized for COVID-19. The rest of the studies mixed mild, moderate, and severe COVID-19 patients. The number of patient cohorts that were followed up in the studies ranged from 102 to 44,799. Adults ranging from 17-87 years of age were included.
There were no studies with overlapping samples. A couple of studies reported that fatigue was more common in female, and one study reported that postactivity polypnoea and alopecia were more common in female 3,10. The rest of the studies did not stratify their results by age or sex.
Regarding the quality of the studies, all had a score of 8 or more. The general characteristics of the studies are shown in Table 1. Different authors have used the terms “Post-acute COVID-19”, “Long COVID-19”, “Persistent COVID-19 Symptoms”, “Chronic COVID-19”, “Post COVID-19 manifestations”, “Long-term COVID-19 effects”, “Post COVID-19 syndrome”, “Ongoing COVID-19,” “long term sequelae”, or “Long-haulers” as synonyms (Table 2).
We identified a total of 55 long-term effects associated with COVID-19 in the literature reviewed (Table 3). Most of the effects correspond to clinical symptoms such as fatigue, headache, joint pain, anosmia, ageusia, etc. Diseases such as stroke and diabetes mellitus were also present. Measurable parameters included 6 elevated laboratory parameters, i.e., interleukin-6 (IL-6), procalcitonin, serum ferritin, C-reactive protein (CRP), N-terminal (NT)-pro hormone BNP (NT-proBNP), and D-dimer. Abnormal chest XRay/computed tomography (CT) was also identified (Figure 2).
Table 2 presents the prevalence of all the effects that were reported. It was possible to perform 21 meta-analyses, for the rest the prevalence was estimated using 1 cohort. The meta-analysis of the studies (n=7) that included an estimate for one symptom or more reported that 80% (95% CI 65-92) of the patients with COVID-19 have long-term symptoms.
The 5 most common manifestations were fatigue (58%, 95% CI 42-73), headache (44%, 95% CI 13-78), attention disorder (27% 95% CI 19-36), hair loss (25%, 95% CI 17-34), dyspnea (24%, 95% CI 14-36) (Table 2, Figure 2). An abnormal chest XRay/CT was observed in 34% (95% CI 27-42) of the patients. Markers reported to be elevated were D-dimer (20%, 95% CI 6-39), NT-proBNP (11%, 95% CI 6-17) C-reactive protein (8%, 95% CI 5-12), serum ferritin (8% 95% CI 4-14), procalcitonin (4% 95% CI 2-9) and IL-6 (3% 95% CI% 1-7) (Table 2, Figure 2).
Other symptoms were related to lung disease (cough, chest discomfort, reduced pulmonary diffusing capacity, sleep apnea, and pulmonary fibrosis), cardiovascular (arrhythmias, myocarditis), neurological (dementia, depression, anxiety, attention disorder, obsessive-compulsive disorders), and others were unspecific such as hair loss, tinnitus, and night sweat (Table 2, Figure 2). Two meta-analyses showed low heterogeneity (I2<25%), two medium heterogeneity, and the high rest heterogeneity (I2>75%).
One study was excluded because it did not provide a denominator, and therefore it was not possible to estimate the prevalence11. In such a study, the authors performed a survey in a Facebook group of patients who previously had COVID-19 and compared the symptoms of those hospitalized with mild to moderate symptoms. They concluded that both groups had symptoms after three months of having COVID-19. Symptoms that were not mentioned in any of the articles we studied include sudden loss of body weight, ear pain, eye problems, sneezing, cold nose, burning feeling in the trachea, dizziness, heart palpitations, pain/ burning feeling in the lungs, pain between the shoulder blades, Sicca syndrome, vertigo, body aches, and confusion2,12.
reference link :https://www.medrxiv.org/content/10.1101/2021.01.27.21250617v2.full
More information: Louise Sigfrid et al. Long Covid in adults discharged from UK hospitals after Covid-19: A prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol., (2021). DOI: 10.1101/2021.03.18.21253888