Between a quarter and three-quarters of people with long Covid struggle with memory, attention, and concentration — yet doctors have no clear picture of what this “cognitive Covid” looks like or how to treat it. This matters because the sheer number of people affected — millions globally — means lost productivity, reduced quality of life, and strain on families and health services. The problem is urgent, but the science is thin: standard cognitive tests may miss key deficits, and no rehabilitation programme has been rigorously tested for this condition. The CICERO study will first pin down the exact nature of the cognitive impairment. Researchers will use both standard tests and a phone-based app to probe memory processes in the medial temporal lobe — a brain region vulnerable to direct infection by SARS-CoV-2. They will also use MRI scans to see how brain structure and connectivity change. In a second phase, 118 people will receive a tailored cognitive rehabilitation programme, with success measured by whether they meet their own personal goals. If the intervention works, the team will produce a “Covid-19 Cognitive Recovery Guide” for patients and clinicians — a practical tool that could be rolled out across the NHS.
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Cognitive impairment is present in 25-75% of people with long Covid, but little is known about its nature, or treatment options. The loss of functional ability has major consequences for affected people, families and the wider economy and the huge number of people with long Covid makes this a top priority issue for health services worldwide. This study aims to phenotype “cognitive Covid” and deliver cognitive rehabilitation to help recovery. In Workstream 1 we will establish the phenotype of cognitive Covid. First, we will identify aspects of cognitive function that are most affected. The test battery will include traditional tests, encompassing all principal cognitive domains including memory, attention and executive function. Given that the medial temporal lobe (MTL) is vulnerable to direct infiltration by SARS-CoV-2, we will additionally use the Neotiv app-based tests to probe memory processes subserved by the MTL that are not examined with traditional tests. Second, we will determine how the cognitive impairment is modulated by other aspects of long Covid, namely fatigue, anxiety/depression and sleep disturbance. Third, we will identify the imaging correlates of cognitive Covid, using MRI to measure whole brain and MTL volume, functional and structural connectivity. Workstream 2 will use cognitive rehabilitation to help recovery from cognitive Covid. The rehabilitation programme will focus on those cognitive domains found in Workstream 1 to be most affected, including remediation, compensatory and adaptive strategies and co-produced with PPI input. We will deliver a “Covid-19 Cognitive Recovery Guide” for patients and clinicians. An RCT (n=118) will compare the intervention (rehabilitation) against standard of care, with the primary outcome being participant-set goals. Secondary outcomes will be measures of cognition, quality of life, MRI structure and connectivity. Health economic benefits of treatment will be assessed in terms of health resource utilisation, primary (cost per QALY) and secondary cost-effectiveness analyses.
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