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Cognitive and mental health outcomes in Long COVID



On July 16, 2025, a comprehensive review article was published in the British Medical Journal (BMJ) on the functional and economic impact, nature and severity, and course of post-COVID neuropsychiatric sequelae. This article discusses risk factors, potential mechanisms, and provides guidance for treatment strategies and future research. This article can be considered a supplement to previous review articles on the current state of the art, for which C-support previously published extensive summaries. We are sharing this article because it is one of the few articles that cites significant numbers and offers information that appears to be useful for this type of complaint.

As C-support, we believe it's important to consider this in a broader context, and we've included our own disclaimer below regarding CBT and psychologization, which are discussed in the article. We also refer to additional existing research.

Below you can read the summary of this article by E. Aretouli, et al. Cognitive and mental health outcomes in long covid.

Post-COVID neuropsychiatric complaints

Post-COVID-19 refers to a range of chronic and often disabling health problems that arise after an acute illness (COVID-19). Physical symptoms such as debilitating fatigue, respiratory problems, muscle and joint pain, and cardiac problems occur, possibly due to damage to organs and systems. In addition, many patients also report cognitive and psychological symptoms. These are also called neuropsychiatric symptoms. These include brain fog, difficulty concentrating and remembering, depression, anxiety, and post-traumatic stress. Approximately 20% of people with post-COVID-19 experience neuropsychiatric symptoms, which often persist longer than other physical symptoms. These have a significant impact on daily functioning, quality of life, and participation in society.

How often does it occur?

Research shows that 1 in 5 adults experiences long-term cognitive or psychological symptoms that persist for ≥12 weeks after the acute infection. It is estimated that globally, approximately 6% of adults who have had COVID-19 develop long-term symptoms. This is often grouped into clusters:

  • Fatigue with pain or mood swings.
  • Cognitive problems.
  • Breathing problems.

Definitions and figures on the number of sick people vary widely due to different definitions, research methods and population characteristics.

Consequences for functioning and the economy

The consequences for functioning and economic well-being are significant. Between 28% and 38% of patients experience cognitive or psychological complaints that cause functional limitations in work and daily activities. This leads to reduced productivity, adjustments to work, long-term absenteeism, and a substantial economic burden. The economic impact is estimated at billions of dollars worldwide in lost work time, medical costs, and reduced quality of life. Post-COVID-19 risk groups include the elderly, women, people with severe acute COVID-19 infection, and people with neurological complications.

Possible mechanisms and the risk of neuropsychiatric complaints

The causes of neuropsychiatric sequelae are multifactorial. A single-factor approach to post-COVID-19 can lead to missing crucial risk factors and mechanisms. Little attention has been paid to the mechanisms behind persistent cognitive impairment and psychological complaints. Biological research has focused more on neurological complications, mechanisms related to the acute infection, and its consequences:

  • Infection of the brain by SARS-CoV-2.
  • Immune response and inflammatory reactions (including of the blood-brain barrier).
  • Endothelial and vascular dysfunction (damage to vessel walls and inflammation in small blood vessels).
  • Hypoxia (lack of oxygen) or metabolic disturbances.

In addition, (pre-existing) biopsychosocial factors play a role in the risk of persistent post-COVID neuropsychiatric symptoms. These include fatigue, pain, sleep problems, autonomic disruption, prior trauma, and stress. Research suggests that this is due to immune system dysregulation and increased inflammation. Research into biomarkers and brain imaging has not yet yielded conclusive results explaining the neuropsychiatric symptoms.

Cognitive and mental health in post-COVID

Cognitive complaints are among the most common symptoms of post-COVID-19, but the exact numbers are difficult to determine. This is due to limitations in diagnostic methods and overlap with other complaints such as depression and fatigue. Self-reports often show high rates of illness, up to 58%, while objective cognitive tests find lower percentages around 15–20%. The main areas of cognitive impairment described in post-COVID-19 are attention, memory, processing speed, and executive functions. These impairments are mild in most patients but still cause significant functional limitations.

In post-COVID-19 cases, mental health problems such as depression, anxiety, and PTSD appear to be common and are considered a significant cause of disability. Research shows that people with post-COVID-19 infections report depressive and anxiety symptoms twice as often as controls after a COVID-19 infection without post-COVID-19 infections. Although hospitalization for acute infections increases the risk of cognitive problems, the figures appear comparable to those of other serious illnesses (not related to COVID-19). The risk of dementia appears to be higher in older adults after COVID-19, but this is comparable to other respiratory infections.

Variation in cognitive and psychological complaints arises from factors such as the course of the acute infection, the degree of recovery, the severity of long-term complaints, relapse or fluctuation of complaints.

Treatment perspective and symptom management

The treatment of neuropsychiatric complaints in post-COVID-19 requires a tailored, multidisciplinary approach involving physicians, psychologists, speech therapists, occupational therapists, and physiotherapists. For treatment and support, it is important to recognize both physical and psychological aspects, without stigmatizing patients. Prior to treatment, a thorough diagnosis is necessary, including medical history, comorbidities (having multiple illnesses simultaneously), and the exclusion of other causes (e.g., thyroid or vitamin B12 problems).

Standardized assessment tools for neuropsychiatric symptoms and functions are recommended for diagnosis. Recommended interventions are often non-medication-based;

  • Cognitive rehabilitation and self-management.
  • Compensation techniques.
  • Cognitive behavioral therapy (CBT), mindfulness, exercise.
  • Peer support and psycho-education.

Extensive evidence is lacking, but several randomized controlled trials (RCTs) show that CBT and structured group programs may be effective in improving fatigue, depression, and subjective cognitive functioning.* New techniques such as neuromodulation (brain stimulation) are still being investigated.

Regarding medication, there is still little evidence. SSRIs appear to alleviate depressive symptoms, possibly through anti-inflammatory effects. Low-dose naltrexone (LDN) has shown improvements in cognitive symptoms, fatigue, and mood in early studies.

Guidelines aimed at functioning

An evidence-based treatment pathway is still lacking, but international organizations (WHO, NICE, CDC, AAPMR) have developed guidelines since February 2025 aimed at reducing mental health problems, improving functioning, and improving quality of life. The focus is not on finding an explanation for the cause, but on maintaining/improving functioning. Consider these guidelines:

  • Patient-centered and multidisciplinary care.
  • Use of standardized measurement instruments for cognitive and mental health.
  • Attention to other factors such as fatigue, comorbidity, multi-medication.
  • Use of proven psychological and behavioural interventions.

Where are we standing right now?

Five years after the start of the COVID-19 pandemic, there are still no reliable biomarkers, diagnostic criteria, or agreed-upon definitions for post-COVID-19. Neuropsychiatric complaints remain common and cause substantial disability and economic burden. Objective cognitive complaints are generally mild, but their impact on daily functioning and work is significant. Older adults with severe acute illness and those with pre-existing mental health problems are at greater risk for neuropsychiatric complaints.

Further research into biological, disease-related, and psychosocial mechanisms is necessary to develop effective treatments.

Recommendations for further research

  • Establishing optimal diagnostic criteria.
  • Role of existing psychological complaints and risk factors.
  • Development of phenotypic profiles, in which certain manifestations of post-COVID can be distinguished.
  • Biomarkers for personalized care.
  • Research into the most effective drug therapies and psychological, behavioural and neuromodulatory treatments.
  • Determining the optimal time for intervention in the recovery process.
  • Strategies to reduce stigma surrounding cognitive and mental health issues.

Disclaimer C-support about Dutch summary Review article Neuropsychiatric complaints of post-COVID

* Historically, CBT (cognitive behavioral therapy) has been recommended as a treatment for people with post-infectious conditions. It is important that CBT is not used for post-COVID-19 with the assumption that the illness is a mental health problem, but solely as support for coping with the consequences of the illness. It is crucial that the therapy is not aimed at ignoring or exceeding physical limits, as this can actually lead to (severe) worsening of symptoms in patients with post-exertional malaise (PEM). Because of these considerations, we advise professionals to use CBT only in close consultation with the patient, discussing together what the therapy can entail and what limits are important. Pacing is often a better option.

Research shows that Post-COVID is a multisystem disease, and no Mental illness, social phenomenon, or behavioral problem. Disruptions have been found, including in the immune system, blood vessels, cellular energy supply, and the functioning of the autonomic nervous system. These are biological processes. Psychological and social factors (such as stress and loneliness) can influence the course of the disease (both negatively and positively). Patients may experience psychological complaints due to their long-term illness. These complaints are a consequence, not the cause, of post-COVID-19. If patients already had psychological problems before developing post-COVID-19, these can also be exacerbated.

Additional literature and other studies on psychological and social factors surrounding chronic illness

Post-COVID

COVID-19 pandemic research on quality of life

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