Interventions for mental health, cognition, and psychological wellbeing in long COVID: a systematic review of registered trials

BACKGROUND: Among patients diagnosed with COVID-19, a substantial proportion are experiencing ongoing symptoms for months after infection, known as 'long COVID'. Long COVID is associated with a wide range of physical and neuropsychological symptoms, including impacts on mental health, cognition, and psychological wellbeing. However, intervention research is only beginning to emerge. This systematic review synthesizes currently registered trials examining interventions for mental health, cognition, and psychological wellbeing in patients with long COVID. METHODS: Standard systematic review guidelines were followed. Trials registered in two large trial registries in 2020 to May 2022 were reviewed. Included studies were narratively synthesized by type of intervention and a risk-of-bias assessment was conducted. RESULTS: Forty-two registered trials were included, with a total target sample size of 5814 participants. These include 11 psychological interventions, five pharmacological and other medical interventions, and five evaluating herbal, nutritional, or natural supplement interventions. An additional nine trials are examining cognitive and neurorehabilitation interventions and 12 are examining physiotherapy or physical rehabilitation. Most trials are randomized, but many are feasibility trials; trials are evaluating a wide spectrum of outcomes. CONCLUSIONS: While there is a newly emerging body of research testing interventions for mental health, cognition, and psychological wellbeing in long COVID, the breadth and scope of the research remains limited. It is urgently incumbent on researchers to expand upon the intervention research currently under way, in order to generate high-quality evidence on a wide range of candidate interventions for diverse long COVID patient populations.