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BackgroundPost-viral syndromes (PVS), including Long COVID, are symptoms sustained from weeks to years following an acute viral infection. Non-pharmacological treatments for these symptoms are poorly understood. This review summarises evidence for the effectiveness of non-pharmacological treatments for symptoms of PVS. It also summarises the symptoms and health impacts of PVS in individuals recruited to studies evaluating treatments. Methods and findingsWe conducted a systematic review to evaluate the effectiveness of non-pharmacological interventions for PVS, as compared to either standard care, alternative non-pharmacological therapy, or placebo. The outcomes of interest were changes in symptoms, exercise capacity, quality of life (including mental health and wellbeing), and work capability. We searched five databases (Embase, MEDLINE, PsycINFO, CINAHL, MedRxiv) for randomised controlled trials (RCTs) published between 1st January 2001 to 29th October 2021. We anticipated that there would be few RCTs specifically pertaining to Long COVID, so we also included observational studies only if they assessed interventions in individuals where the viral pathogen was SARS-COV-2. Relevant outcome data were extracted, study quality appraised using the Cochrane Risk of Bias tool, and the findings were synthesised narratively. Quantitative synthesis was not planned due to substantial heterogeneity between the studies. Overall, five studies of five different interventions (Pilates, music therapy, telerehabilitation, resistance exercise, neuromodulation) met the inclusion criteria. Aside from music-based intervention, all other selected interventions demonstrated some support in the management of PVS in some patients. ConclusionsIn this study, we observed a lack of robust evidence evaluating non-pharmacological treatments for PVS, including Long COVID. Considering the prevalence of prolonged symptoms following acute viral infections, there is an urgent need for clinical trials evaluating the effectiveness and cost-effectiveness of non-pharmacological treatments for patients with PVS as well as what may work for certain sub-groups of patients with differential symptom presentation. RegistrationThe study protocol was registered with PROSPERO [CRD42021282074] in October 2021 and published in BMJ Open in 2022. Author summaryWhy was this study done? O_LIThe prevalence of Long COVID following exposure to SARS CoV-2 is substantial, and the current guidance provides few evidence-based treatment options for clinicians to suggest to their patients. C_LIO_LIDue to the similarities in presentation of other post-viral syndromes (PVS), and the lack of consensus in management approaches, there is a need to synthesise the available data on PVS to both support patients with PVS predating the pandemic, and those with Long COVID. C_LI What did the researchers do and find? O_LIThis is the first comprehensive systematic review of the effectiveness of non-pharmacological treatments for patients with PVS, including Long COVID. C_LIO_LIWe identified four non-pharmacological treatments (Pilates, telerehabilitation, resistance exercises and neuromodulation) which have shown promise in those who have experienced signs and symptoms related to PVS. C_LI What do these findings mean? O_LIIn this study, we identified few trials assessing the effectiveness of non-pharmacological therapies to support the management of symptoms of PVS. Considering the prevalence of PVS, including Long COVID, there is an urgent need for clinical trials evaluating the effectiveness and cost-effectiveness of non-pharmacological therapies to support these patients. C_LI
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IntroductionIndividuals with COVID-19 frequently experience symptoms and impaired quality of life beyond 4-12 weeks, commonly referred to as Long COVID. Whether Long COVID is one or several distinct syndromes is unknown. Establishing the evidence base for appropriate therapies is needed. We aim to evaluate the symptom burden and underlying pathophysiology of Long COVID syndromes in non-hospitalised individuals and evaluate potential therapies. Methods and analysisA cohort of 4000 non-hospitalised individuals with a past COVID-19 diagnosis and 1000 matched controls will be selected from anonymised primary care records from the Clinical Practice Research Datalink (CPRD) and invited by their general practitioners to participate on a digital platform (Atom5). Individuals will report symptoms, quality of life, work capability, and patient reported outcome measures. Data will be collected monthly for one year. Statistical clustering methods will be used to identify distinct Long COVID symptom clusters. Individuals from the four most prevalent clusters and two control groups will be invited to participate in the BioWear sub-study which will further phenotype Long COVID symptom clusters by measurement of immunological parameters and actigraphy. We will review existing evidence on interventions for post-viral syndromes and Long COVID to map and prioritise interventions for each newly characterised Long COVID syndrome. Recommendations will be made using the cumulated evidence in an expert consensus workshop. A virtual supportive intervention will be coproduced with patients and health service providers for future evaluation. Individuals with lived experience of Long COVID will be involved throughout this programme through a patient and public involvement group. Ethics and disseminationEthical approval was obtained from the Solihull Research Ethics Committee, West Midlands (21/WM/0203). The study is registered on the ISRCTN Registry (1567490). Research findings will be presented at international conferences, in peer-reviewed journals, to Long COVID patient support groups and to policymakers. Article SummaryO_ST_ABSStrengths and limitations of the studyC_ST_ABSO_LIThe study will generate a nationally representative cohort of individuals with Long COVID recruited from primary care. C_LIO_LIWe will recruit controls matched on a wide range of demographic and clinical factors to assess differences in symptoms between people with Long COVID and similar individuals without a history of COVID-19. C_LIO_LIWe will use a newly developed electronic patient reported outcome measure (Symptom Burden Questionnaire) for Long COVID to comprehensively assess a wide range of symptoms highlighted by existing literature, patients, and clinicians. C_LIO_LIImmunological, proteomic, genetic, and wearable data captured in the study will allow deep phenotyping of Long COVID syndromes to help better target therapies. C_LIO_LIA limitation is that a significant proportion of non-hospitalised individuals affected by COVID-19 in the first wave of the pandemic will lack confirmatory testing and will be excluded from recruitment to the study. C_LI
