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Long COVID, a term used to describe ongoing symptoms after COVID-19 infection, parallels the course of other postviral syndromes. Neuropsychiatric symptoms of long COVID can be persistent and interfere with quality of life and functioning. Within the biopsychosocial framework of chronic illness, rehabilitation professionals can address the neuropsychiatric sequelae of long COVID. However, current practice models are not designed to address concurrent psychiatric and cognitive symptoms in adults living with long COVID. Thus, we present a biopsychosocial framework for long COVID and provide treatment strategies based on evidence from current literature of postviral chronic illness. These recommendations will guide rehabilitation professionals in identifying common neuropsychiatric symptoms in long COVID that can be targeted for intervention and addressing these symptoms via integrative interventions taking into account the biopsychosocial presentation of long COVID symptoms.
The constellation of prolonged vascular, pulmonary, musculoskeletal, sensory, and/or neurologic challenges after SARS-CoV-2 infection have been designated in the International Classification of Diseases
World Health Organization World Health Organization. (2004). ICD-10 : international statistical classification of diseases and related health problems : tenth revision, 2nd ed. World Health Organization.
, 10th Edition as “Post COVID-19 condition,” also commonly referred to as “post-acute sequalae of SARS-CoV-2” (PASC) or “long COVID,” among other terms.
Although long COVID describes a heterogenous range of presentations, the scope of this commentary will focus on neuropsychiatric symptoms. Long COVID has a similar presentation and course as other postviral syndromes.
Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)—a systemic review and comparison of clinical presentation and symptomatology.
Moreover, Black, Indigenous, Latinx, and other marginalized groups who have been disproportionately affected by COVID-19 may be particularly vulnerable to chronic sequelae that are amplified by ongoing health care inequities.
Although there is an emerging literature to characterize the prolonged recovery process among individuals who experience severe infection and to provide recommendations for discrete facets of long COVID,
Multi-disciplinary collaborative consensus guidance statement on the assessment and treatment of cognitive symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC).
Multidisciplinary collaborative consensus guidance statement on the assessment and treatment of fatigue in postacute sequelae of SARS-CoV-2 infection (PASC) patients.
its interdependence of physical, psychological, and cognitive issues benefits from the contribution of methodology for a holistic approach to treatment.
In this communication, the neuropsychiatric sequelae of long COVID are contextualized within the framework of the biopsychosocial model (see fig 1) to include the complex interplay of somatic, cognitive, and emotional symptoms.
Further, we examine the parallels between long COVID and other postviral infections and chronic medical illnesses to provide a theoretical framework for multidisciplinary, evidence-based management of neuropsychiatric symptoms. We propose that central tenets for treatment of long COVID include assessment, identification of neuropsychiatric symptoms, and multidisciplinary intervention that simultaneously targets both psychiatric and cognitive sequelae.
Human coronaviruses, including SARS-CoV-2, are known to be neurovirulent, neurotropic, and neuro-invasive and may target the brain through multiple pathways, thus contributing to neuropsychiatric sequelae.
Editorial: the pathogenesis of long-term neuropsychiatric COVID-19 and the role of microglia, mitochondria, and persistent neuroinflammation: a hypothesis.
persistent inflammation and hypercoagulability, and respiratory and cardiovascular insufficiency are hypothesized mechanisms of acute and chronic neuropsychiatric symptoms of COVID-19.
Editorial: the pathogenesis of long-term neuropsychiatric COVID-19 and the role of microglia, mitochondria, and persistent neuroinflammation: a hypothesis.
Pathogenic apoptosis, disruption of neuronal integrity, secretion of neurotoxins, and excess release of glutamate may also contribute to neurologic dysfunction.
a model of central nervous system plasticity in which adaptation to prolonged nociception maintains somatic symptoms like those described in myalgic encephalopathy, fibromyalgia, and other pain syndromes.
Central sensitization is a useful construct for explaining persistent neuropsychiatric sequelae of long COVID, in which nociception reinforces the ongoing occurrence of other neuropsychiatric symptoms, thus creating maintenance of chronicity.
Postinfection factors that are relatively specific to COVID-19 may contribute to symptom maintenance as well. For example, grieving the loss of loved ones who died of this virus, limited medical treatments and access to medical resources, uncertainty of long-term prognosis, stigma, discrimination, and ongoing health care disparities all exacerbate experienced distress and prolong neuropsychiatric symptoms.
Psychological interventions on the front lines: a roadmap for the development of a behavioral treatment program to mitigate the mental health burden faced by COVID-19 survivors.
Further, COVID-19 illness is a traumatic experience for many, and patients hospitalized with COVID may develop delirium putting them at risk for posttraumatic stress disorder (PTSD). However, COVID infection may contribute to PTSD regardless of severity and/or hospitalization status.
Ongoing stressors specific to the pandemic (eg, long-term social isolation, diminished activity, financial uncertainty, unstable housing) compound neuropsychiatric consequences in long COVID.
Psychological interventions on the front lines: a roadmap for the development of a behavioral treatment program to mitigate the mental health burden faced by COVID-19 survivors.
Psychological interventions on the front lines: a roadmap for the development of a behavioral treatment program to mitigate the mental health burden faced by COVID-19 survivors.
COVID-19 is one of many viral illnesses to instigate chronic symptoms. Postviral neuropsychiatric symptomatology, including fatigue, is commonly reported after a diverse range of infections, including Epstein-Barr, herpes viruses, human immunodeficiency virus, rubella, and West Nile infections.
Long COVID has neuropsychiatric symptoms akin to the effects of other chronic medical conditions. Continuous fatigue, “brain fog,” mood dysfunction, diminished engagement in daily tasks, and emotional distress are common among patients living with prolonged medical challenges, such as cancer and its treatment, trauma secondary to intensive care procedures, myalgic encephalomyelitis/chronic fatigue syndrome, or postconcussive syndrome,
Diagnostic and interventional approaches to long COVID can be gleaned from parallels with myalgic encephalomyelitis/chronic fatigue syndrome, postconcussive syndrome, herpes simplex encephalopathy, rubella, West Nile, and human immunodeficiency virus.
Psychological interventions in chronic medical illness
Complex postviral physical, psychological, and cognitive challenges require an integrated and multidisciplinary treatment approach. The goals of neuropsychological intervention for long COVID are similar to those for all chronic illness and include reducing emotional distress, mitigating cognitive and physical dysfunction, and ultimately improving quality of life.
Interventions initiated early in recovery and that focus on ameliorating psychiatric symptoms, bolstering adherence to other treatments, and promoting psychological adjustment can reduce depression and disability, and improve the quality of life in patients with chronic illness.
For example, among patients with fibromyalgia, cognitive behavioral therapy (CBT) effectively treats symptoms of pain, fatigue, depression, sleep disturbance, and improves coping skills, enhancing quality of life.
In patients with chronic back pain, one randomized-controlled trial found that participants assigned to pain reprocessing therapy (a form of CBT) had significantly improved sleep, as well as reduced disability, pain, depression, and anger, in comparison with matched controls assigned to a placebo condition.
Further, pain reprocessing therapy–related symptom improvements were associated with decreased evoked pain-related activity on functional magnetic resonance imaging.
Similarly, psychological interventions that provide psychoeducation and strategies for behavioral activation can improve mood and disability in adults with comorbid chronic obstructive pulmonary disease and depression
when initiated early in the recovery process (ie, inpatient rehabilitation settings). Poststroke survivors diagnosed with major depressive disorder exhibited reduced depressive symptoms when treated with ecosystem-focused therapy. Ecosystem-focused therapy engages caregivers in ameliorating poststroke functional limitations and role changes and may improve physical and cognitive functioning in patients relative to controls.
Further, evidence-based treatments such as CBT and cognitive rehabilitation (CR) have been used in tandem to effectively to treat neuropsychiatric symptoms in a wide variety of medical populations with symptom chronicity including postconcussive syndrome,
can be applied to treat similar cognitive symptoms in persons with long COVID.
Proposed treatment for individuals with long COVID within a biopsychosocial model
By applying evidence-based CR/CBT practices used in other chronic medical conditions, we may expect comparable efficacy in the long COVID population. In the Stanford Hall Consensus Statement, derived from an interdisciplinary rehabilitation specialist meeting in response to the current global pandemic, Barker-Davies et al concluded that “for patients with COVID-19, rehabilitation should be aimed at relieving symptoms of psychological distress and improving participation in rehabilitation, physical function and quality of life.”
The integration of CR/CBT follows the biopsychosocial model by addressing symptom chronicity maintenance, incorporating methods of behavioral activation, implementing emotional coping skills, and using cognitive remediation strategies that support goal-directed behavior. Although CR/CBT can be thought of as a foundational aspect of treatment for emotional and cognitive symptoms of PASC, we propose an integrated treatment that also incorporates techniques from other evidence-based treatments, such as acceptance and commitment therapy and mindfulness-based approaches,
as outlined below in the proposed sequence of components. Goals of treatment within an integrated CR/CBT approach include increasing attentional control, developing compensatory strategies for self-management of cognitive dysfunction, diminishing affective distress and negative self-perception, and reducing the influence of fatigue on behavioral engagement. CR/CBT aims to diminish avoidance and withdrawal, which help maintain low mood and persistent disability. CR/CBT integrated with an interdisciplinary and multidisciplinary service delivery network of rehabilitation specialists complements and supplements the expertise and co-occurring treatment modalities to promote optimal outcomes.
Long COVID intervention to address neuropsychiatric difficulties
Guided by the expertise of those who have been at the fore of research on the neuropsychiatric effects of long COVID,
Psychological interventions on the front lines: a roadmap for the development of a behavioral treatment program to mitigate the mental health burden faced by COVID-19 survivors.
the goal here is to develop a flexible intervention protocol that can be utilized in a variety of modalities and platforms to increase accessibility of treatment. Currently, members on the COVID-19 Taskforce of the American Congress of Rehabilitation Medicine, drawing from their clinical experience with integrated CR/CBT techniques across varied institutions, are collaborating on an ordinal sequence of rehabilitative treatments for individuals with long COVID.
In caring for patients with long COVID, concurrently addressing both neuropsychiatric symptoms and barriers to treatment engagement is paramount. Three basic tenets are essential: first, psychoeducation regarding the biopsychosocial model can help patients understand the interaction and maintenance of their symptoms, thereby providing a framework for intervention. Neuropsychological treatment adherence can be emphasized in terms of longer-term physical and cognitive gains, thus diminishing disability. Second, psychoeducation on the hierarchy of cognitive domains, specifically the effect of fatigue on arousal, alertness, and autonomic regulation of the sleep-wake cycle, can help patients understand the interaction between their fatigue and cognitive dysfunction. Third, functionality, rather than causality, needs to be emphasized throughout treatment. Such functional orientation bolsters patients’ adjustment and promotes their adherence to other treatments. Elements of acceptance and commitment therapy are utilized throughout treatment. For example, tenets that can be applied to long COVID include acknowledging and validating the ambiguous nature of long COVID, tolerating the unknowns of causality and long-term prognosis, accepting functional challenges, making daily commitments to a gradual process of recovery, engaging with tasks of daily living despite ongoing symptoms, coping with stigma, and maintaining symptom management.
Development of standardized intervention modules, conceptualized as an evidence-based, flexible toolbox for use in a variety of settings, would serve as a catalyst for clinical research on treatment efficacy in long COVID and promote translational research to optimize intervention effectiveness. The exposure and response prevention aspects of this treatment may also target symptoms related to trauma.
The following sequence with treatment components of CR/CBT is proposed: (1) emotion regulation strategies are essential to introduce in the beginning of treatment to reduce anxiety and negative self-talk that may interfere with engagement in treatment protocol. Emotional strategies will be used throughout treatment to modify maladaptive self-messaging about cognitive dysfunction, increase tolerance of emotional distress, and diminish task and treatment avoidance; (2) attentional control strategies, memory encoding/retrieval skills, and metacognitive strategies, including goal management training and problem solving are all foundational to the treatment. These skills are consistent with mindfulness practice that emphasizes filtering out distraction while being fully present to utilize cognitive resources; (3) behavioral activation strategies support cognitive functioning in the context of fatigue, increasing engagement and self-efficacy through techniques like pacing, introduction of aerobic exercise, and activity scheduling. As these cognitive and behavioral strategies are internalized and used during everyday activities, increased efficiency of mental resources will contribute to diminished fatigue.
Moreover, neuropsychological intervention can foster patients’ momentum in other rehabilitation therapies and reintroduction of role functions (e.g., work/school) that may not have been resumed since their acute COVID infection. For example, activity pacing can help patients arrange their expenditures of energy to optimize physical engagement in physical therapy, attentional control can help patients master sequencing of everyday functional activities in occupational therapy, and metacognitive strategies can help patients attenuate the downstream effect of cognitive dysfunction on language to maximize their progress in speech-language pathology.
Conclusion
Long COVID occurs in a significant proportion of the population, many of whom will experience debilitating functional decline. Although the techniques described here are a synthesis of evidence-based approaches that have shown efficacy in similar patient populations, it is important to note that the research literature on neurorehabilitation specific to long COVID is nascent and still rapidly evolving; as such, the reader is cautioned against interpreting this writing as an assertion that the clinical utility of CR/CBT exceeds other treatment modalities. Nonetheless, integrating and expanding existent evidence-based interventions will be vital for improving outcomes of people affected by long COVID.
World Health Organization. (2004). ICD-10 : international statistical classification of diseases and related health problems : tenth revision, 2nd ed. World Health Organization.
Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)—a systemic review and comparison of clinical presentation and symptomatology.
Multi-disciplinary collaborative consensus guidance statement on the assessment and treatment of cognitive symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC).
Multidisciplinary collaborative consensus guidance statement on the assessment and treatment of fatigue in postacute sequelae of SARS-CoV-2 infection (PASC) patients.
Editorial: the pathogenesis of long-term neuropsychiatric COVID-19 and the role of microglia, mitochondria, and persistent neuroinflammation: a hypothesis.
Psychological interventions on the front lines: a roadmap for the development of a behavioral treatment program to mitigate the mental health burden faced by COVID-19 survivors.
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