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Prevalence estimates of a post-COVID-19 condition, long COVID, or post-acute sequelae of SARS-CoV-2 vary according to definition, methodology, and population. A recent systematic review reported persistent symptoms at 3–6 months in a median of 57% (range 13–92) of hospitalised patients (six studies) and 26% (2–62) of non-hospitalised patients (ten studies).
This study and other reviews identified few studies from low-income settings,
but with more than 245 million SARS-CoV-2 infections reported globally,
millions of people are likely to already be experiencing long-term illness. While COVID-19 vaccines have reduced the risk of severe COVID-19 and death, continued high rates of SARS-CoV-2 infection will lead to further disability, having a huge impact on individuals, their families, health services, and society.
but there is not yet a health professional consensus definition or nomenclature. In October, 2021, WHO used a Delphi method to develop a clinical definition of post-COVID-19 condition as a range of symptoms occurring 3 or more months after probable or confirmed SARS-CoV-2 infection that last for at least 2 months, cannot be explained by an alternative diagnosis, generally have an impact on daily functioning, and may fluctuate or relapse over time.
A separate definition is recommended for children.
Other definitions use different time frames and terminology,
but remain difficult to apply in research and clinical management.
However, the absence of specific diagnostic criteria means that clinicians and patients must live with substantial uncertainty, with the risk that people will be either overinvestigated and overtreated or not receive adequate support.
Patients report not being taken seriously by medical practitioners or refused referral to long COVID services.
These services remain limited and where they exist vary in scope, quality, and access to some therapeutic options. In the absence of diagnostic tests, long COVID is partly a diagnosis of exclusion, creating challenges for patients and carers. Previous diagnoses of exclusion, such as chronic fatigue syndrome, fibromyalgia, and irritable bowel syndrome, are now better defined than in the past, meaning patients are more able to obtain acknowledgment, treatment, sick pay, or insurance.
although the latter might also reflect post-intensive care syndrome.
However, the pathophysiology of long COVID remains poorly understood with different mechanisms probably explaining the heterogeneous symptoms, including viral persistence, autoimmunity due to molecular mimicry, aberrant T-cell and humoral responses, and micro-thrombi.
Understanding the mechanisms and natural history of long COVID will inform diagnostic and therapeutic strategies, building on experience of other post-viral syndromes—eg, careful pacing in rehabilitation to avoid post-exertional symptom exacerbation. To date no antiviral or immunomodulatory drug has proven effective for the treatment of long COVID in trials. Some preliminary reports suggest COVID-19 vaccination might improve symptoms in some people,
supporting the notion of a possible role for persistent viral reservoirs, circulating virus fragments, or both in long COVID.
As with most chronic disease, a holistic approach and individualised rehabilitation plan will be crucial. Reliable online and other resources are needed to ensure that clinicians, researchers, and patients can keep up to date with the latest evidence on long COVID in a rapidly evolving field. Yet these resources will be beyond what is available in many health systems, particularly in low-income and middle-income countries (LMICs).
Countries with limited resources and already overwhelmed health systems are unlikely to be able to provide specific services for long COVID, which will therefore remain hidden. Surveillance of this emerging public health threat must be a priority globally, and we support the need for national registers, with chronic cases reported alongside infections, hospitalisations, and deaths. Large-scale multinational partnerships, including LMIC researchers, patients, and funding, are needed to evaluate evidence-based diagnostics and therapeutics and assure affordability, applicability, and adaptability to different health-care systems, including in resource-limited contexts.
Such collaborative efforts should lead to greater understanding of disease mechanisms and treatments for long COVID, improving lived experience of the millions of people with this condition around the world.
HW reports grants from the UK Department of Health and Social Care (DHSC) for the REACT study, grants from DHSC/National Institute for Health Research (NIHR) for the REACT Long COVID study, and grants from the NIHR Imperial Biomedical Research Centre for the Patient Experience Research Centre. PE reports grants from UK Research and Innovation (UKRI)/NIHR for REACT-Genomics England and REACT Long COVID studies. GC reports funding from NIHR, DHSC, and UKRI for REACT-Genomics England and REACT Long COVID studies. BF, PJG, SWXO, DMA, BD, and NS declare no competing interests.
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Published: November 10, 2021
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