Non-pharmacological therapies for post-viral syndromes, including Long COVID: A systematic review
Authors: Chandan Joht Singh , Brown Kirsty R , Simms-Williams Nikita , Bashir Nasir Z , Camaradou Jenny , Heining Dominic , Turner Grace M , Rivera Samantha Cruz , Hotham Richard , Minhas Sonica , Niratharakumar Krishnarajah , Sivan Manoj , Khunti Kamlesh , Raindi Devan , Marwaha Steven , Hughes Sarah E. , McMullan Christel , Marshall Tom , Calvert Melanie J , Haroon Shamil , Aiyegbusi Olalekan Lee 
Published: June 2022

Background

Post-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 findings

We 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.

Conclusions

In 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.

Registration

The study protocol was registered with PROSPERO [CRD42021282074] in October 2021 and published in BMJ Open in 2022.

Author summary

Why was this study done?

The 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.

Due 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.

What did the researchers do and find?

This is the first comprehensive systematic review of the effectiveness of non-pharmacological treatments for patients with PVS, including Long COVID.

We 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.

What do these findings mean?

In 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.