Introduction
The COVID-19 pandemic has revealed an unexpected medical reality: beyond the acute phase of the infection, many people continue to suffer from persistent and debilitating symptoms for months, or even years. Among these manifestations of long COVID, neuropsychological and behavioral disorders play a prominent role, profoundly affecting the quality of life, professional capabilities, and social relationships of those affected.
"Brain fog," a term that has become emblematic of these post-COVID disorders, describes a constellation of cognitive symptoms: difficulties in concentration, memory problems, slowed thinking, and a sense of mental confusion. These difficulties, often fluctuating and exacerbated by mental effort, can persist for months after the resolution of the initial infection, even in individuals who had mild forms of COVID-19.
Irritability, mood disorders, anxiety, and emotional fatigue are other common manifestations of neuropsychological long COVID. These behavioral and emotional disorders are not mere psychological reactions to the illness but result from complex neurobiological mechanisms involving inflammation, vascular dysfunction, and immune dysregulation affecting the central nervous system.
In France and around the world, millions of people are affected by long COVID. Estimates suggest that 10 to 30% of individuals who had COVID-19 develop persistent symptoms beyond 12 weeks, with a particularly high prevalence of neurocognitive and behavioral disorders. This silent epidemic of post-infectious neurological disorders poses a major public health challenge requiring recognition, understanding, and appropriate management.
Understanding Long COVID and Its Neurological Manifestations
Definition and Epidemiology of Long COVID
Long COVID, also known as post-COVID-19 syndrome or long-haul COVID, refers to the persistence or emergence of symptoms beyond 4 weeks after the initial infection with SARS-CoV-2, without any other identifiable medical explanation. The WHO more precisely defines post-COVID condition as persistent symptoms 3 months after the initial infection lasting for at least 2 months.
The exact prevalence of long COVID remains debated due to variable definitions and diagnostic challenges, but studies suggest that about 10 to 30% of infected individuals develop persistent symptoms. Risk factors include the severity of the initial infection, female sex, middle age (30-50 years), the presence of comorbidities, and the number of symptoms during the acute phase.
Paradoxically, long COVID can occur after initially mild or even asymptomatic infections. The absence of severe initial forms does not protect against the development of chronic debilitating symptoms. This reality has surprised many patients and healthcare professionals.
Pathophysiological Mechanisms
The mechanisms explaining the persistence of post-COVID neurological symptoms are multiple and likely intertwined, creating a complex pathophysiological picture that is still imperfectly understood.
Chronic inflammation and aberrant immune response appear to play a central role. Infection with SARS-CoV-2 triggers an intense inflammatory response that, in some patients, does not completely resolve after the virus is eliminated. This chronic low-grade inflammation affects the central nervous system, creating persistent "neuroinflammation" that disrupts neuronal functioning.
Cerebral vascular impairment by the SARS-CoV-2 virus infects the endothelial cells of blood vessels, creating dysfunctions in cerebral microcirculation. These vascular alterations can induce chronic cerebral hypoperfusion, particularly in the frontal and temporal regions, explaining some cognitive and behavioral disorders.
Direct viral infection of the nervous system has been documented in some cases, with the presence of the virus or viral components in cerebrospinal fluid or brain tissue. This direct viral invasion can cause persistent neuronal damage even after the virus has been eliminated from the body.
Autoimmune phenomena with the production of autoantibodies directed against structures of the central nervous system have been identified in some long COVID patients. These autoantibodies can disrupt neuronal functioning long-term even in the absence of active virus.
Mitochondrial dysfunction and chronic oxidative stress resulting from the infection affect cellular energy production, particularly in neurons that are highly dependent on energy metabolism. This energy dysfunction could explain cognitive fatigue and the worsening of symptoms during mental efforts.
Dysregulation of the autonomic nervous system (dysautonomia) with impaired cardiovascular, respiratory, and thermoregulatory regulation contributes to fatigue, concentration difficulties, and the symptomatic fluctuations characteristic of long COVID.
Brain Fog: An Emblematic Symptom
Clinical Manifestations
Brain fog, although its name is figurative and not medical, describes a very specific clinical reality experienced by patients as a "fog in the head," "mental cotton," or a "feeling of slowed brain."
Difficulties in concentration are the main complaint. Patients describe an inability to maintain their attention on a task, significant distractibility, and a feeling of "fluttering" mentally without being able to focus their attention. Reading a book, following a conversation, or watching a movie becomes difficult as attention is constantly lost.
Memory problems primarily affect working memory (short-term memory) and prospective memory (remembering what one needs to do). Patients forget what they were going to do when changing rooms, lose the thread of a conversation, and cannot recall information that was recently read. Memory of old facts is generally preserved, distinguishing brain fog from dementias.
Cognitive slowing manifests as an increased time required to process information, answer questions, and make decisions. Patients feel "mentally slow," as if their thoughts are moving through a viscous medium. This slowing affects all cognitive tasks, particularly the more complex ones.
Difficulties in lexical access ("finding words") are common and frustrating. Familiar words suddenly seem inaccessible, replaced by circumlocutions or approximations. This difficulty, usually subtle in daily life, becomes evident in demanding professional or social situations.
The sensation of confusion or "empty head," difficulty thinking clearly, and feeling mentally foggy are described by many patients. These sensations fluctuate throughout the day, generally worsening with fatigue, stress, or cognitive effort.
Worsening with cognitive effort is an important characteristic. Sustained mental effort (intellectual work, meetings, complex conversations) exacerbates all cognitive symptoms and can trigger a "crash" (sudden collapse) with deep exhaustion requiring several hours to several days of recovery.
Functional Impact
The impact of brain fog on daily functioning is often underestimated by those around because the deficits are subtle, fluctuating, and "invisible." However, the consequences are significant.
Professionally, brain fog severely compromises performance, particularly in intellectual professions. The difficulty in maintaining concentration, the slowing of information processing, and memory problems make many professional tasks difficult or even impossible. Many patients are forced into prolonged work stoppages or therapeutic part-time work, with some losing their jobs permanently.
In daily life, usual activities become exhausting. Grocery shopping requires detailed lists, administrative management becomes complex, and cooking elaborate meals is difficult. These difficulties, combined with physical fatigue, significantly reduce autonomy.
Socially, brain fog creates isolation and misunderstanding. Group conversations become impossible to follow, and social outings are exhausting. Loved ones do not always understand these "invisible" difficulties, creating tension and a sense of loneliness.
The psychological impact is significant. The loss of cognitive abilities, even partial, profoundly affects identity and self-esteem. The fear that these disorders may be permanent, uncertainty about progression, and confronting the limitations imposed by brain fog generate anxiety and reactive depression.
Irritability and Emotional Disorders
Manifestations of Post-COVID Irritability
Irritability is a frequent and disturbing symptom of long COVID, often described by patients as "not recognizing themselves" emotionally.
This irritability is characterized by a marked decrease in the threshold of tolerance to frustration. Minor annoyances that would have been easily managed before now trigger disproportionate emotional reactions. Patients describe "getting angry over nothing," "getting upset over trivial matters," and being "on edge."
Noise intolerance is particularly common. Sounds that were previously tolerable become unbearable: conversations, background noise, music, television. This hyperacusis or misophonia exacerbates irritability and can lead to social isolation.
Intolerance to stimulation in general (visual, social, emotional) leads to a need for calm and solitude to "recharge." Social interactions, even enjoyable ones, become exhausting and generate irritability.
Excessive emotional reactions can occur: easy crying, disproportionate anger, emotions that are difficult to control. This emotional lability is experienced as a destabilizing loss of control for the person and their surroundings.
Impatience and difficulty tolerating delays, complications, and unforeseen events are heightened. Cognitive and physical fatigue leaves fewer resources to manage daily frustrations.
Anxiety and Mood Disorders
Anxiety disorders are very common in long COVID, affecting about 30 to 40% of patients.
Generalized anxiety with persistent worries about health, symptom progression, and future capabilities is understandable in this context of medical uncertainty. This anxiety is often exacerbated by the absence of effective treatment and the medical misunderstanding sometimes encountered.
Panicking attacks may occur, sometimes for the first time in the person's life. They can be triggered by physical symptoms (palpitations, breathing difficulties) or occur spontaneously.
Social anxiety develops in some patients, fearing they will not be able to keep up with social interactions due to brain fog, or anticipating the exhaustion that will follow social efforts.
Depression affects about 20 to 30% of long COVID patients. It results from multiple factors: reaction to disability and losses (job, activities, relationships), neurobiology of chronic inflammation affecting neurotransmitters, social isolation, and medical and social misunderstanding.
Depressive symptoms include persistent sadness, loss of interest and pleasure, emotional fatigue (adding to physical fatigue), sleep disturbances, feelings of devaluation, and sometimes dark thoughts. The risk of suicide should not be overlooked, particularly among young active individuals suddenly confronted with an invisible and debilitating disability.
Fatigue and Emotional Exhaustion
Fatigue in long COVID far exceeds simple physical fatigue. It is a global fatigue affecting physical, cognitive, and emotional dimensions.
Emotional fatigue manifests as an inability to manage emotions, a feeling of being "emotionally drained," and a lack of resources to cope with daily stress. Social interactions, even brief ones, are emotionally exhausting.
Post-exertional malaise (PEM) is a characteristic symptom. Physical or cognitive effort, even modest, triggers a collapse of symptoms (worsening brain fog, fatigue, irritability) occurring with a delay of 12 to 48 hours and requiring several days of recovery. This PEM makes it very difficult to gradually return to activity.
Sleep disturbances are almost constant: difficulties falling asleep, frequent night awakenings, non-restorative sleep. This sleep disruption exacerbates all other symptoms, creating a vicious cycle that is hard to break.
Impact on Loved Ones and Family Life
Transformation of Relationships
Long COVID profoundly transforms family and marital dynamics, creating tensions and requiring continuous adaptations.
Misunderstanding from loved ones is a major source of suffering for patients. Cognitive and behavioral disorders being "invisible," loved ones sometimes minimize the difficulties or attribute behavioral changes to a lack of will rather than the illness.
Guilt is omnipresent, both on the patient's side (guilt for no longer fulfilling responsibilities, for being a burden on others) and on the caregiver's side (guilt for feeling frustration or impatience in the face of the loved one's limitations).
The caregiver partner often finds themselves in a role they did not choose, having to assume additional responsibilities (managing daily life, income if the patient can no longer work, emotional support) while facing the behavioral transformation of their partner. The patient's irritability, fatigue, and cognitive limitations transform the relationship.
Children are affected by a parent's illness, especially when that parent was previously active and present. They must adapt to a tired, less available, sometimes irritable parent, without always understanding what is happening.
The DYNSEO training "Behavioral Changes Related to Illness: A Practical Guide for Loved Ones" can help families facing long COVID understand behavioral disorders, develop appropriate communication strategies, and preserve their own balance in the face of the challenges of caregiving.
Social Isolation
Social isolation is a major and aggravating consequence of long COVID.
The gradual withdrawal from social activities results from multiple factors: fatigue making outings impossible, brain fog preventing following conversations, fear of post-exertional malaise, and misunderstanding from those around. This withdrawal, although understandable, exacerbates isolation and depression.
Friends gradually drift away, not always understanding the invisibility and chronicity of symptoms. Repeatedly declining invitations and the inability to maintain commitments lead to a crumbling of social ties.
The professional world can also prove unsympathetic. The absence of recognition of long COVID as a chronic disabling illness in many professional contexts, difficulties in obtaining workplace accommodations, and sometimes dismissal create isolation and a sense of injustice.
Patient groups (associations, online support groups) often become the only community where individuals feel understood and validated in their experience. These peer support spaces are valuable but do not replace usual social ties.
Diagnosis and Evaluation
Diagnostic Approach
The diagnosis of long COVID remains primarily clinical, based on the patient's history, the chronology of symptoms, and the exclusion of other pathologies.
A detailed medical history must establish the temporal link with the COVID-19 infection (even if it was mild or not confirmed by a test), the evolving profile of symptoms, their functional impact, and the absence of other medical explanations.
The evaluation of symptoms must be systematic and multidimensional, covering physical dimensions (fatigue, pain, dyspnea), cognitive (brain fog), behavioral (irritability, mood disorders), and functional (impact on daily life and work).
Complementary examinations have a limited role as they are often normal in long COVID. They mainly serve to rule out other pathologies: standard biological assessment, imaging if neurological symptoms are present, cardio-pulmonary explorations if organ symptoms are present.
Formal neuropsychological evaluation can objectify cognitive disorders, quantify their severity, and guide rehabilitation strategies. It is particularly useful in cases of professional difficulties or for disability recognition processes.
Scales and Questionnaires
Several tools allow for quantifying and tracking long COVID symptoms.
The fatigue questionnaire (Chalder scale, Piper fatigue scale) assesses the intensity and impact of fatigue. The quality of life questionnaire (SF-36, EQ-5D) measures the overall impact on functioning. Specific long COVID scales are under development and validation.
Cognitive evaluation can use standardized tests (MoCA for brief assessment or more comprehensive batteries) to objectify attention, memory, and executive disorders reported by patients.
Differential Diagnosis
Several pathologies must be ruled out before confirming the diagnosis of long COVID:
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) pre-existing may be reactivated or worsened by COVID-19. The diagnostic criteria are similar to those of long COVID, making distinction sometimes difficult.
Primary anxiety or depressive disorders can mimic or worsen long COVID symptoms. However, the presence of psychiatric disorders does not exclude long COVID, as both can coexist.
Neurological pathologies (MS, early dementia, brain tumor) must be ruled out through appropriate imaging and neurological evaluation.
Thyroid disorders, vitamin deficiencies, sleep apnea are common causes of fatigue and cognitive disorders that must be systematically investigated.
Management and Adaptation Strategies
Global and Multidisciplinary Approach
The management of long COVID requires a global, personalized, and multidisciplinary approach, as no curative treatment currently exists.
The general practitioner or internist coordinates overall management, ensures regular follow-up, adjusts symptomatic treatments, and refers to specialists if necessary.
Specialized consultations may include neurologists (for cognitive disorders), psychiatrists or psychologists (for mood disorders and adaptation), pulmonologists (respiratory disorders), cardiologists (palpitations, dysautonomia), and physical medicine and rehabilitation doctors (coordination of rehabilitation).
The rehabilitation team (physiotherapist, occupational therapist, neuropsychologist, speech therapist) offers targeted interventions for specific deficits.
Energy Management and Pacing
Pacing (adapted energy management) is the central strategy for managing long COVID, particularly in the presence of post-exertional malaise.
The principle of pacing consists of:
- Identifying one's energy envelope: recognizing the level of activity (physical and cognitive) that can be sustained without triggering a crash
- Staying below this threshold even on days when feeling better, to avoid relapses
- Breaking activities into segments: alternating short periods of activity with recovery breaks
- Planning and prioritizing: identifying essential activities, delegating or eliminating non-essential ones
- Accepting temporary limitations to promote long-term recovery
- Very short sessions (5-10 minutes maximum initially) to avoid cognitive fatigue
- Use at times of best energy during the day
- Immediate stop if fatigue or headaches occur
- Very gradual progression in duration and difficulty
- Acceptance of performance fluctuations without discouragement
- Mindfulness helps observe emotions without reacting impulsively
- Breathing techniques (heart coherence, abdominal breathing) reduce physiological activation
- Psychoeducation helps understand that irritability results from the illness and fatigue, reducing guilt
- Calm environment: reduce auditory, visual, and social stimuli
- Planned recovery times throughout the day
- Communication with loved ones about the need for calm and solitude
- Manage anxiety and reactive depression
- Mourn lost abilities (even temporarily)
- Adapt identity to the new reality
- Maintain hope despite uncertainty
- Antidepressants if significant depression (SSRIs are generally well tolerated)
- Anxiolytics for short durations for anxiety attacks (avoid chronic use)
- Sleep treatment (melatonin, sleep hygiene rules, rarely hypnotics)
- Gradual therapeutic part-time work
- Remote work reducing travel fatigue
- Workplace adjustments: calm environment, frequent breaks, reduction of multitasking
- Task adaptation: prioritizing less cognitively demanding tasks
This approach, counterintuitive for usually active individuals, requires learning and support. It opposes the classic gradual reconditioning to effort, which can exacerbate symptoms in cases of long COVID with PEM.
Cognitive Rehabilitation
Cognitive rehabilitation, led by specialized neuropsychologists, can help partially compensate for cognitive disorders.
Compensatory strategies include: systematic use of planners, alarms, and lists, memorization techniques, adapted work environment (calm, distraction-free), breaking down cognitive tasks.
Cognitive stimulation exercises aim to maintain and improve attention, memory, and executive functions. These exercises should be progressive, adapted to the level of fatigue, and practiced regularly but without excess.
SCARLETT, developed by DYNSEO, can serve as a complementary cognitive stimulation tool at home for long COVID patients. Short, progressive, and varied exercises allow for regular training adapted to fatigue levels.
The use of SCARLETT in the context of long COVID must adhere to certain principles:
For younger individuals with mild to moderate long COVID, CLINT, the brain coach from DYNSEO, can offer more varied and stimulating cognitive exercises, always respecting energy limits and avoiding cognitive overexertion.
Managing Irritability and Emotional Disorders
Emotional regulation techniques include:
Environmental adjustments reduce sources of irritation:
Psychological support from a therapist trained in long COVID helps to:
Pharmacological treatments may be necessary:
Professional Adaptation
Returning to work after long COVID poses a major challenge requiring adaptations and support.
Assessment of capabilities by occupational medicine helps identify compatible tasks and those requiring adjustments.
Possible adjustments include:
Recognition as a long-term illness (ALD) or occupational disease for long COVID is still challenging but progressing, allowing for better management and social protection.
Prognosis and Evolution
Temporal Evolution
The evolution of long COVID is highly variable among individuals, making individual prognoses difficult.
The first months (3-6 months) are often the most challenging, with intense and fluctuating symptoms. It is during this period that the diagnosis is generally made and adaptations put in place.
Between 6 months and 1 year, about 50% of patients report partial improvement of symptoms. This improvement is often slow, nonlinear, with relapses during overexertion or intercurrent infections.
Beyond 1 year, the majority of patients (60-70%) report gradual improvement, but many retain residual symptoms limiting their activities. About 20-30% of patients do not observe significant improvement, developing chronic disability.
Factors indicating a good prognosis include: initially mild form, early initiation of appropriate management, strict adherence to pacing, absence of overexertion, good social and family support, recognition by the employer, and professional adjustments.
Factors indicating a poor prognosis include: initially severe form, comorbidities, non-adherence to pacing with repeated relapses, chronic stress, lack of support, denial or misunderstanding from those around.
Long-Term Sequelae
For some patients, lasting sequelae may persist, constituting chronic disability:
Residual cognitive disorders may permanently limit professional capabilities, particularly for demanding intellectual professions.
Persistent chronic fatigue with intolerance to effort may require permanent lifestyle adjustments.
Heightened sensitivity of the nervous system with persistent hypersensitivity to stimuli (noise, light, stress) may last for years.
Chronic mood disorders (anxiety, depression) may persist even after improvement of physical symptoms.
Research and Perspectives
Advances in Understanding
Research on long COVID is progressing rapidly, with many international teams working to better understand its mechanisms.
Immunological studies identify persistent anomalies in the immune response: chronic inflammation, autoantibodies, dysregulation of T lymphocytes.
Brain imaging (functional MRI, PET scan) objectifies anomalies in perfusion and brain metabolism in some patients, validating the biological reality of brain fog.
Longitudinal studies following cohorts of long COVID patients over the long term will help better understand the natural evolution and prognostic factors.
Therapeutic Avenues
Several therapeutic avenues are currently being evaluated:
Anti-inflammatory treatments targeting chronic inflammation are being tested: low-dose corticosteroids, synthetic antimalarials, monoclonal antibodies.
Intravenous immunoglobulins could modulate the aberrant immune response in forms with documented autoimmunity.
Anticoagulants at preventive doses are being evaluated to improve cerebral microcirculation.
Intensive cognitive stimulation and neuropsychological rehabilitation are being evaluated for their effectiveness on brain fog.
Integrative medicine approaches (acupuncture, nutritional supplements, mind-body techniques) are being studied, although evidence remains limited.
Prevention
Vaccination
Vaccination against COVID-19 significantly reduces the risk of developing long COVID, even in cases of breakthrough infection. Vaccinated individuals who develop long COVID generally have less severe symptoms and a better outcome.
For individuals already experiencing long COVID, vaccination may have variable effects: improvement in about 30%, no change in 50%, temporary worsening in 20%. The decision to vaccinate should be individualized and discussed with a physician.
Management of Acute Infection
Optimal management of the acute phase of the infection could reduce the risk of long COVID:
Conclusion
Long COVID, with its neuropsychological and behavioral manifestations centered on brain fog and irritability, represents a major medical challenge of this decade. Millions of people worldwide, often young and active, find themselves facing an invisible yet debilitating disability, profoundly transforming their professional, social, and family lives.
Brain fog, an emblematic symptom, describes a complex clinical reality of fluctuating and debilitating cognitive disorders. Irritability, mood disorders, and emotional fatigue complete this behavioral picture, creating a significant burden for patients and their loved ones.
Medical and social recognition of long COVID is progressing but remains insufficient. Too many patients face misunderstanding, denial, or minimization of their symptoms, adding psychological suffering to the physical burden of the illness.
Current management relies primarily on symptomatic and adaptive approaches, with pacing being the cornerstone of management. The training offered by DYNSEO and cognitive stimulation tools like SCARLETT and CLINT can provide complementary support for patients and their families.
Current research holds promise for a better understanding of the mechanisms and the development of specific treatments in the coming years. In the meantime, recognizing the reality and severity of long COVID, supporting patients, adapting health and social protection systems, and prevention through vaccination remain priorities in addressing this new silent epidemic.
DYNSEO Resources for Supporting Long COVID:
Keywords: long COVID, brain fog, cognitive disorders post-COVID, irritability, chronic fatigue, post-exertional malaise, behavioral disorders, cognitive stimulation, cognitive rehabilitation, pacing
