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Mindfulness Meditation Interventions for Long COVID: Biobehavioral Gene Expression and Neuroimmune Functioning

Authors Porter N, Jason LA 

Received 13 August 2022

Accepted for publication 26 October 2022

Published 8 November 2022 Volume 2022:18 Pages 2599—2626

DOI https://doi.org/10.2147/NDT.S379653

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Roger Pinder



Nicole Porter *, Leonard A Jason *

Center for Community Research, DePaul University, Chicago, IL, USA

*These authors contributed equally to this work

Correspondence: Leonard A Jason, Center for Community Research, DePaul University, 990 W. Fullerton Ave, Chicago, IL, 60614, USA, Tel +1 773 325 2018, Email [email protected]

Abstract: Some individuals infected with SARS CoV-2 have developed Post-Acute Sequelae of SARS CoV-2 infection (PASC) or what has been referred to as Long COVID. Efforts are underway to find effective treatment strategies for those with Long COVID. One possible approach involves alternative medical interventions, which have been widely used to treat and manage symptoms of a variety of medical problems including post-viral infections. Meditation has been found to reduce fatigue and unrefreshing sleep, and for those with post-viral infections, it has enhanced immunity, and reduced inflammatory-driven pathogenesis. Our article summarizes the literature on what is known about mindfulness meditation interventions, and reviews evidence on how it may apply to those with Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Evidence is reviewed suggesting effective and sustainable outcomes may be achieved for symptomatology and underlying pathology of post-viral fatigue (PASC and ME/CFS).

Keywords: long COVID, meditation, Myalgic Encephalomyelitis

Mindfulness Meditation Interventions for Long COVID

Biobehavioral Gene Expression and Neuroimmune Functioning

Although studies have shown that meditation can improve self-reported measures of disease symptomatology, the effect that meditation has on biological mechanisms underlying disease is less clear. The focus of this paper is to summarize the literature on mindfulness meditation interventions, and review evidence on its applicability to those with Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Evidence is reviewed suggesting effective and sustainable outcomes may be achieved for symptomatology and underlying pathology of post-viral fatigue (PASC and ME/CFS).1–9 In a literature review, Islam, Cotler, and Jason10 found some of patients affected by bacterial and viral epidemics developed persisting health complications. These types of post viral symptoms have also occurred with patients with Post-Acute Sequelae of SARS CoV-2 (PASC), which is also known as “Long-COVID”.11 Davis et al12 found that six months following infection with SARS CoV-2, patients continued to have fatigue, post-exertional malaise, and cognitive dysfunction. Patients following infection with SARS CoV-2 have also developed Guillain-Barré syndrome,13 lung scarring,14 and heart damage,15 including a higher risk of cardiac inflammation, especially in young males.16

Early on in the pandemic, the Body Politic COVID-19 support group17 found 40 days after SARS CoV-2 infection, 91% of respondents had not recovered. In another study,18 a longitudinal prospective cohort study involving individuals with confirmed SARS-Cov-2 infection, after 9 months, 30% of patients had recurring symptoms. Some have suggested that up 50–80% of PASC patients will continue to have symptoms 3 months post infection with SARS CoV-2,19 and up to 10% might have more serious symptoms.20

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) shares some features of Long COVID including fatigue, cognitive difficulty, unrefreshing sleep, and post-exertional malaise.21 These most commonly reported protracted symptoms overlap with PASC17,22–24 with neurocognitive symptoms being among the most disabling for both illnesses.

The National Health Service Long COVID Clinics25 are attempting to help patients with Long COVID.26 The World Health Organization has recommended more treatment to help patients with post-viral illness manage this illness.27 In addition, the National Institutes of Health created the RECOVER initiative to better understand the pathophysiology of this illness and ultimately find treatment options for individuals with PASC.28

To deal with PASC, we can learn from research conducted in other areas, such as the effects of psychosocial factors on various components of the immune system.29–31 Reviews of this research have shown that positive well-being boosts the human body’s immune response, improving its resistance to infection.32 One promising form of treatment for those with PASC involves meditation.

Mindfulness meditation involves sitting still and focusing exclusively on one’s breath, to hone one’s attention and maximize unmediated direct experience. According to Kabat-Zinn, “Mindfulness is awareness that arises through paying attention, on purpose, in the present moment, non-judgementally”.33 Mindfulness meditation is the basis of stress reduction programs operationalized by Kabat-Zinn et al33 and Richard Davidson.34 The effects of meditation may rely on the brain shifting to an alpha state during meditation, helping slow brain rhythms. As meditation practice is stabilized, these parasympathetic responses may be habituated and translated to daily life.35 Meditation might be an effective treatment for those with PASC. Below we first review what is known about how PASC and other post-viral illnesses such as ME/CFS affect the immune system.

Immune Functioning

There is some evidence that ME/CFS causes the immune system to overreact following infection36 causing oxidative stress.37 Immune dysregulation is thought to be related to COVID-19 pathophysiology after infection by SARS-CoV-2.38 In PASC, immunological symptoms may develop after the acute infection when the viral load is decreasing.39 A key driver of PASC might be continuing inflammation.40,41

Examination of the aberrant activation of innate immune signaling pathways has led to an examination of interleukin-6 (IL-6) as a prime candidate for mediating inflammation in Long COVID-19. IL-6 might be a potential biomarker,42 and a meta-analysis has found IL-6 is related to the development of hypoxemia.43 Those who at initial assessment evidence high IL-6 might be at increased risk of respiratory failure. IL-6 might be related to inflammation in patients with COVID-19 as it induces a pro-inflammatory response.44

Increases in other pro-inflammatory lymphocyte markers have also been proposed as a biomarker for post-viral fatigue, specifically related to ME/CFS in the case of interleukin-8 (IL-8).45,46 This might be similar to what occurs in a number of inflammatory conditions (eg, lupus).47 Recent research suggests that patients with PASC have elevated inflammatory proteins48,49 perhaps indicating an unbalanced inflammatory/anti-inflammatory cytokine response in PASC.

One cause of systemic inflammation is infectious agents.50 While there are multiple causes of systemic inflammation, many of which have been defined in establishing the Systemic Inflammatory Response Syndrome criteria, they are considered a subset of all “cytokine storm” syndromes. According to Fajgenbaum and June,51 they have inflammatory etiologies and can result in systemic inflammation and multiple organ dysfunction. More recently, cytokine storm syndrome is now thought to include all inflammatory conditions with elevated cytokines,35,52 including PASC.53,54

Helper thymus cells include T-helper (Th) 1 or Th2 effector cells.55 When polarized toward Th2 dominance, there is a Th2/Th1 imbalance. This imbalance is related to inflammation and diseases,56 including pyelonephritis, and systemic lupus erythematosus.57,58

A systemic Th2/Th1 imbalance might occur in patients with PASC, with variable duration and severity of disease related to systemic inflammation as indicated by differential cytokine expression. For example, Pavel et al59 suggest a Th2/Th1 imbalance may be related to higher mortality in COVID-19 patients. A similar pattern of these cytokine profiles with very high levels of mixed Th1/Th2 affinity occur in some patients with COVID-19 infection.60 These findings suggest a Th1 to a Th2 shift in cytokine response with superantigen-associated progression for the duration, perhaps as an adaptive process by the immune system in an attempt to down-regulate abnormal inflammatory Th1 immune responses.38

Individuals with COVID-19 display a pattern of immunologic association reflective of a more global pattern of activation, characterized by increased interrelationship among proteins with a differential grouping of proteins.61,62 Taken together, this research suggests that a pro-inflammatory cytokine profile occurs with PASC,63 as is the case in patients with other types of post-viral infections (eg, ME/CFS).64 These mechanisms have been hypothesized as causing oxidative stress,36 and the patient’s immune system overreacts following infection,45 which may be due to an underlying post-viral infection in general.36,65

Anti-Inflammatory Effects Associated with Meditation

Meditative practices have been related to anti-inflammatory cytokine activity in a variety of studies,66–71 and has been reported in systematic reviews.72,73 For example, after 6 weeks of daily meditation, each lasting only 20 minutes, Bower et al66 found a downregulation of pro-inflammatory genes in cancer survivors.65

Meta-analyses of immunological and psychological efficacy of mindfulness meditation interventions indicate effectiveness with an 8-week intervention as measured by improvement in immune markers for people with AIDS.74 Creswell et al5 and Naoroibam75 found that after an 8-week intervention, CD4+ T lymphocytes changes in AIDS evidenced significant improvements. In Creswell et al5 study, the decline in CD4 levels was halted after a meditation course lasting 8 weeks.5 These immunological findings were also validated and generalized in other short-term random control trials (6–12 weeks) for relatively inactive college students,76 for breast cancer patients awaiting surgery or after treatment.77 Other meditation studies have shown reductions in pro-inflammatory cytokine interleukin-12 (IL12) and anti-inflammatory cytokine IL-10 increases.66–70 Among those who are obese, meditation studies found reductions in C-reactive protein and IL-6,66–69 but other investigators were not able to replicate such findings.67

Concerning inflammatory cytokines, Sanada et al78 in a meta-analysis found mindfulness-based interventions yielded significant positive effects on cytokine blood levels related to low-grade inflammation. Another meta-analysis found that meditation outcomes of reduced C-reactive protein and blood pressure.73 They concluded that meditation practice leads to the moderation of important physiological markers in a range of populations. From these studies, it is clear that mindfulness meditation has been associated with a number of healthy inflammatory process changes.2

Seated meditation has been related to sympathetic nervous system reductions in activation.48,69,73 The studies that have been reviewed have also found positive meditation on immune cell subsets related to the immune systems.79,80

It had also been found that meditation has led to increasing vagal tone,81,82 as well as inflammatory-based diseases.68,71,83,84 The benefits of meditation practice have also occurred with 90 minutes of yogic practice over a 2-week period, which found increased expression of important antimicrobial peptides,85 which is of interest for work with COVID patients as they are expressed in respiratory epithelial cells.8 A mind-body intervention down-regulated cytokine receptors and C-reactive protein.86 Epel et al87 (2016) found that combined meditation/yoga regulated levels of the proinflammatory tumor necrosis factor alpha. In a study by Jang et al,69 in contrast to healthy controls, patients in a meditation arm demonstrated a significantly decreased expression of pro-inflammatory cytokines, with a shift towards anti-inflammatory cytokine secretion (Th2 response).

Bushell et al88 summarized this extensive literature by indicating that meditation can be effective as an adjunctive intervention for a range of infectious diseases. In summary, common features of the inflammatory-driven pathogenesis of virulent infectious diseases can be modified by the anti-stress and anti-inflammatory properties of meditation practice (see Table 1).89–91

Table 1 Summary of findings on biomarkers associated with meditation practices

Epigenetics and DNA Methylation

Developmental epigenetics also has implications for what occurs with Long COVID and meditation,92 as we will review below. DNA methylation is one molecular epigenetic phenomenon that corresponds to emergent structural states and modified gene activity.93,94 Epigenetic factors such as movements in mindful activities are important means of environmental enrichment.95

As an example of this literature, differential methylation at genes occurred when comparing patients with and without sepsis.96

In one bioinformatics study of COVID-19, Balnis et al97 activation associated was associated with a predominance of autoimmune disorders. For those patients that were COVID-19-positive, those with a hyper-methylated status had worse outcomes, and COVID-19 severity was related to seventy-seven differentially methylated positions. Another study of COVID-19 severity identified differentially methylated genes, such as those related to interferon response to viral infections.98 These candidate biomarkers may be useful in the identification of those infected by SARS-CoV-2.

Epigenetic and DNA Methylation Effects of Meditation

As indicated earlier in this article, it is possible meditation may help patients by re-regulating pro-inflammatory to anti-inflammatory processes and by reducing sympathetic nervous system over-activation through the relaxation response.68,99 However, research on DNA methylation may indicate more profound biological mechanisms, such as telomere stability, the hypothalamic-pituitary-adrenal axis100 and inflammatory pathways.101,102 Le Nguyen et al103 found that mindfulness meditation was related to increased telomerase activity. In a meta-analysis, Schutte and Malouff104 found the effect size across all telomere studies including both novice and long-term meditators to be 0.46. Research by Dasanayaka et al105 with long-term meditators found telomerase changes, and comparable results with meditation on telomeres length, also with strong effect sizes (0.66-0.88) for relatively small sample sizes (n < 20).106,107

A few epigenetic studies have been conducted with meditators involving DNA methylation.90 Black and Slavich’s72 meta-analysis reported that meditation led to increases in telomerase activity. Subsequent longitudinal observations revealed that meditation can bring about gene expression changes.108 Profiling at CpG sites, research by Harkess et al109 focused on tumor necrosis factor alpha (TNF-α), IL-6, and C-reactive protein. Chaix et al110 also used peripheral blood mononuclear cells and methylation levels of 353 CpG sites were highly correlated with chronological age, which is a measure of epigenetic age (DNAm age).111,112 For those involved in mindfulness and compassion meditation, Chaix et al110 found decreased epigenetic aging rate. For genes associated with immune metabolism aging, Chaix et al113 found meditation to influence the methylome. In a Smartphone mindfulness meditation training, researchers81,82 found reduced pro-inflammatory gene expression. One thousand twenty-seven gene transcripts differed by greater than 50% between groups from baseline to post-intervention.114 We conclude from this literature that meditation can improve the immune response for those with persistent inflammation (see Table 1).

Neurocognitive Functioning and Central Autonomic Network

The neurocognitive problems that intensify over time in some patients with PASC seem similar to those seen in patients with ME/CFS.23,115 Regarding patients with PASC, Jason et al23 found over approximately 6 months, the one group of symptoms that got worse were from the neurocognitive domain,23 findings similar to that reported by the Body Politic COVID-19 support group.17

It has been suggested that some viral infections or parts of the contribute to the prolonged neurocognitive impairment, with some theorizing that the post-viral fatigue patient’s immune system overreacts following infection-causing oxidative stress.37 The literature cited above suggests that the immune state may affect the central nervous system of those with PASC and ME/CFS.36,61,64,116 These causal reactivations may be similar to cerebral toxoplasmosis.117,118 In post-viral infections, such as ME/CFS, there is evidence of aberrant low natural killer cell cytotoxicity, cortisol deficiency, and sympathetic nervous system hyperactivity.37

The central autonomic network is critically involved in homeostatic situational control and bi-directional signaling of visceral function,119 and it operates at different levels throughout the central nervous system, including the lower/upper brainstem and forebrain levels, integrating visceral sensation with autonomic and neuroendocrine responses.120 SARS-Cov-2 may cause long-term changes to central autonomic network structure (eg, brainstem-forebrain connections) and damage to ascending-descending visceral pathways involved in interoceptive awareness (perception of senses and autonomic functioning).121 Furthermore, interoceptive signals could be disrupted by perfusion abnormalities, microvascular injury, and increased inflammation,122 which can be seen with acute SARS- Cov-2 infection, leading to worsening function following initial infection.

Central Nervous System

The Central Nervous System is highly integrated,123 sending dynamic signals that promote physiologic stability in response to internal and external demands.124 Post-infectious, chronic inflammatory processes within the central nervous system can lead to disease states, which are known to disrupt the body’s homeostatic regulatory mechanisms and create an imbalance that favors sympathetic nervous system dominance.125 In addition, the neuroendocrine system regulates a cascade of chemical biological mediators between health and disease.126 Biological and behavioral features of PASC might be linked to the central nervous system.127,128 Neurologic manifestations (eg, encephalopathy) in hospitalized patients have been associated with a poorer prognosis, independent of respiratory disease severity.129 There is growing evidence that adaptive mechanisms underlying symptom maintenance and magnification in post-viral illnesses crucially involve the cortico-limbic-brainstem circuits.130–135 A neuroimaging study found that alterations in brain activity in the parietal lobe and cingulate gyrus were related to worsening post-viral symptoms.136 Lu et al122 found increased registered fractional anisotropy (directionality) and decreased mean and axial diffusivity in the corona radiata, external capsule, and superior frontal-occipital fasciculus in recovered SARS Cov-2 patients.

Structural, functional, cerebrovascular, and electrical CNS abnormalities have been identified in post-viral fatigue. Regarding structural brain abnormalities, using T1-weighted spin echo MR imaging, Barnden et al130 detected decreased signal intensity in the brainstem and increased signal intensity in the sensorimotor white matter of subjects with post-viral fatigue compared to healthy controls. Stüber137 postulated that these sensorimotor findings may reflect altered myelin levels, given that 90% of T1 contrast in white matter is due to myelin, but were cautious to apply the same interpretation for the brainstem results due to its more complex tissue composition. Further support for myelin alterations in white matter tracts of patients with post-viral fatigue was shown in a study by Thapaliya et al.138 Tracts within these structures carry motor signals between primary motor areas of the cortex, brainstem, pons, and lower motor areas in the spinal cord. In a separate longitudinal study using T1w/T2w imaging, Shan et al139 found progressive atrophy in the left inferior fronto-occipital fasciculus in a sample of patients with post-viral fatigue measured 6 years apart. The connection fibers of the IFOF are widespread, connecting the ipsilateral frontal lobe to the superior parietal lobe, inferior occipital lobe, and basal surface of the temporal lobe. These fibers assume a critical role in the transport of information between regions of large-scale networks (eg, fronto-parietal, default-mode, dorsal attention) for the integration of auditory and visual association cortices with the prefrontal cortex.

White matter volume reduction has also been found in the midbrain and pons of patients with post-viral fatigue using volumetric analysis.139 Diffusion tensor imaging is another MRI technique that uses microstructure (eg, myelin integrity). Diffusion tensor imaging provides a quantitative analysis of the magnitude and directionality of molecules. A Diffusion tensor imaging-based prospective study with patients who recovered from COVID-19 found changes in fractional anisotropy, mean diffusivity, axial diffusivity, indicating a possible disruption in tissue and functional brain integrity.122

In addition to abnormal structural integrity mainly of white matter, MRI has also detected functional alterations in post-viral fatigue. Functional MRI (fMRI) has detected abnormal activity in patients with post-viral fatigue related to the ventral anterior cingulate during the erroneous performance of a motor imagery task,134 increasing task load,140 and fatigue-inducing cognitive tasks.141,142 Compensatory mechanisms may also explain the association of higher gray matter volume in the supplementary motor area with worse neurological symptom scores in a longitudinal MRI study of patients with post-viral fatigue.139

A growing number of studies also use functional connectivity methods to investigate changes in brain networks in post-viral fatigue. Convergent findings of these studies have pointed to the salience network which handles functional properties of many brain systems.143 For example, significantly decreased connectivity was found by Gay et al.144 Using arterial spin labeling based functional connectivity, patients with post-viral fatigue had reduced functional connectivity within the salience network between the anterior cingulate cortex and right insula.145 In an adolescent patient sample with post-viral fatigue who underwent resting-state fMRI, Wortinger et al146 found that decreased connectivity to the right posterior insula of the salience network was related to post-viral fatigue severity. Investigating resting-state fMRI in female patients with post-viral fatigue, Kim et al114 reported aberrant connectivity between the posterior and anterior cingulate cortex. These studies all reported abnormalities consistent with central autonomic regions (left posterior cingulate, anterior cingulate, right insula), suggesting a need for research that assesses the integrity of the central autonomic network114 in patients with post-viral fatigue.

Although fMRI provides useful insight into brain function, it is a semi-quantitative measure dependent on many variables, one of which is cerebral blood flow. Early studies suggested that hypoperfusion may underlie abnormalities in patients with post-viral fatigue leading to deficiencies in energy metabolism.147,148 Using MRI-based Arterial spin labeling, these findings were later extended.149,150 Finally, using positron emission tomography, Tirelli et al151 patients with post viral fatigue were differentiated from those with Major Depressive Disorder due to hypo-metabolism as did Helms et al152 and Chougar et al.153 There is also emerging evidence for disruption of central nervous system vascular health in acute COVID-19 infection. Koralnik and Tyler154 an increased risk for stroke for COVID-19 patients, even in younger individuals and those with milder COVID-19 infections.

Neurological Effects of Meditation

Among the different effects of meditation, one involves increased blood flow to the frontal cortex, parietal and temporal lobes,155 as well as increase glucose metabolism156 and improve global functioning.34 Meditation has also been demonstrated to cause neural reorganization and re-regulation in practitioners.34 Mind-body techniques have been used by individuals as a remedy for symptoms related to the brain and cognitive dysfunctions.157–159

Meditation has been demonstrated to cause neural reorganization and re-regulation in both novices and long-term practitioners.34,160 These studies on the neurochemical effects of meditation on neurotransmitters, coupled with the established research on salutogenic immune profiles of meditators,72 indicate several wide-ranging neuroimmune benefits of a regular practice of meditation. Meditation may help patients by re-regulating pro-inflammatory to anti-inflammatory processes and/or by reducing sympathetic nervous system over-activation through the relaxation response.68 As meditation practice is stabilized, these parasympathetic responses may be habituated and translated to daily life (see Table 1).35

Meditation Effect Sizes

A recent meta-analysis on meditation by Whitfield et al161 examined 180 pooled, effect sizes from 46 studies of meditation with small to moderate effect sizes (0.27-0.36). Another recent study by Zhang162 found large effect sizes for improved sleep, depression and anxiety, as well as large neurophysiological changes (0.59). In the largest meta-analysis of meditation to date, Goldberg et al163 found overall effect size ranged from small (0.21, for well-being) to moderate (0.55, for psychiatric symptoms). Another meta-analysis concluded that mind-body interventions effects endured at 3 months post-intervention.164 In Morgan et al7 and Black’s et al72 meditation reviews, overall significant weighted effect sizes were moderate (0.34-0.58) on specific markers, suggesting a sound effect size relative to biomedical interventions. Similarly, a meta-analysis by Leucht et al165 found somewhat higher effect sizes. Interestingly, meta-analyses from meditation interventions report the average standardized effect size (0.30), which is similar to effect sizes from mainstream medical interventions across a variety of health domains (0.30).

In Schutte et al's104 meditation study, changes in telomere length also had a promising, moderate effect size (0.40). In a meditation review by Dasanayaka et al,105 DNA methylation research found telomere length had a moderate effect size (0.40) for novice meditators (0.40). These findings outperformed the majority of reviewed biomedical interventions.166 In summary, given comparable effects and the absence of adverse side effects in alternative non-pharmacological interventions in biomedical populations,167 meditation appears to be a promising intervention for those with post-viral complications (see Table 2).

Table 2 Meta and Reviews

Intervention Duration Parameters

It has long been suggested that longevity and intensity of practice is an important aspect of the efficacy of practice.168–171 There is some positive studies with briefer meditation interventions, such as 20-minute meditation that helped depression and anger in a college sample.172 A study by Zeidan et al173 found that only three sessions of meditation could also improve cardiovascular variables related to anxiety reactivity. However, these studies and others174 involved healthy populations, and did not include individuals with underlying disease pathology.

Dobkin and Zhao9 have argued that short-term interventions of less than 8 weeks of practice may not be enough to support significant clinical changes or physiological effects in chronically ill populations. Similarly, a recent review of meditation for post-viral fatigue (eg, ME/CFS) did not find significant differences at follow-up for any interventions lasting less than 8 weeks.175 Interventions shorter than 8 weeks did not find changes in underlying biomarkers, immune markers, or neurocognitive functioning. The research appears to support bringing about positive biological processes in 8–12 weeks of meditation (see Tables 1 and 2).

There is one recent study reporting positive biological outcomes after short-term intervention, and this involved 8 days of intensive practice during a full-time on-site retreat.175 The retreat was also tightly controlled: participants meditated more than 10 hours a day, remained silent for 8 days, ate vegan meals prepared for them, did not work, and followed a regular sleep schedule. This suggests that short-term interventions may compensate for a small duration of practice, by intensifying the amount of time spent in meditation.

Situ versus eMobile Interventions

An important question is the use of meditation with virtual and mobile implementation.176 It has been claimed by meditation teachers that watching videos or just reading about meditation may be less effective.177 However, there is some evidence that guided, smartphone-based meditation apps alone can be used to facilitate mindfulness practice and promote feelings of well-being and social connectedness.178 For example, one group meditation intervention included a smartphone-based meditation app - the Breath Counting Task from MindFi. This intervention was effective in facilitating mindfulness practice,179–182 as well as reducing stress,178 and increasing well-being.183 However, there are limitations to the research available, as the above findings are restricted to positive responses on self-report questionnaires of perceived well-being in relatively healthy samples.

Meditation for PASC and ME/CFS

Meditation and several other mind-body practices are being used to treat COVID-19 symptoms.184,185 Studies in this area are beginning to appear in the literature, but there is a larger body of work with other post-viral illnesses. For example, Porter, Jason, Boulton, Bothne, and Coleman3 reviewed mind-body trials for patients with ME/CFS; the most effective intervention was meditation. In addition, a recent review of meditation for post-viral fatigue (eg, ME/CFS) concluded that the basic symptoms were shown to be improved in patients receiving mind-body interventions.175

Mahendru4 found that those provided meditation after SARS-CoV-2 infection reported improvement in multiple sleep indicators. Bushell et al8 review suggested that meditation interventions were of importance to moderating immune function, specifically for SARS-CoV-2 infection and Long COVID. If COVID-19 has a runaway hyperinflammatory response to a viral infection,53 this pathway is moderated by both short-term acute meditation intervention and long-term practice. The review also asserted that meditation may be effective at reducing future sequelae to negative inflammatory factors, and acknowledges additional, rigorous research is needed on therapeutic efficacy.8

Patients with PASC who regularly practice meditation also evidence more dominant wave frequency due to a reorganization of specific cortical areas such as a hemispheric slowing and multifocal epileptiform discharges from the frontotemporal and temporoparietal head regions as well as decreased self-reported fatigue, sleeplessness, pain, and cognitive and motor dysfunction.186,187

In one study168 mentioned earlier in this article, participants with COVID-19 were provided a retreat and they reported positive immune-modulatory effects after 80 hours of meditation practice. The researchers concluded that findings support discrete benefits to those with COVID-19.

Conclusions

Our review suggests that there are immunological problems in patients with post-viral infections that may also lead to abnormal epinephrine and norepinephrine levels.188 In addition, patients with post-viral fatigue exhibit similar patterns as those with post-viral encephalopathy, including a generalized and focal slowing in the frontal cortex.189 This review suggests immunological mechanisms that may underly the effects of meditation on the physiological functioning of multiple related systems for individuals with PASC and ME/CFS. Studies reviewed indicate the wide-ranging neurophysiological consequences of a regular practice of meditation. The studies also suggest a neurophysiological basis for the health benefits that are attributed to meditation (see Table 1).

What occurs with PASC has been characterized by some as a Th2/Th1 cytokine imbalance, which is associated with a higher risk of mortality.59 Meditation may help patients with PASC by balancing pro-inflammatory to anti-inflammatory processes and by reducing sympathetic nervous system over-activation through the relaxation response.67 Increased blood oxygen level-dependent responses to an attentional measure due to a reorganization of specific cortical areas such as dorsolateral prefrontal cortex activation, and deactivation of Default network and medial prefrontal cortex, as well as decreased self-reported fatigue, sleeplessness, pain, and cognitive and motor dysfunction.

Mind-body techniques have been used by individuals as a treatment many of the symptoms experienced by those with PASC157–159 and have the potential to bring about structural and functional changes to the brain.3,155 Investigators and practitioners are beginning to explore the use of meditation for those with PASC.4,190 This was mentioned by a meta-analysis by Khanpour Ardestani et al,175 where mind-body practices were effective at reducing symptom severity in post-viral fatigue (eg, ME/CFS), including fatigue, anxiety, and depression, and improved physical and mental functioning.

Another meta-analysis recommends the use of mobile health meditation for COVID, given its overall effectiveness and availability of sessions in situ.191 A retrospective of mindfulness meditation using app-based interventions for those dealing with the COVID-19 pandemic found they reduced mental health worsening.192 Another recent review by Schlechta Portella et al99 found meditation research was the most comprehensive intervention, showing a substantial number of positive mental and physical health outcomes. They concluded mindfulness meditation can promote neural plasticity, has important physical and metabolic impacts, and improves the immune system.

Meditation research indicates that short-term interventions (<6–8 weeks) can moderate responses on self-reports of quality of life, elevate mood and decrease stress for both mobile app-based and real-time group practices in relatively healthy participants. However, there is also evidence that moving underlying biomarkers in a population with disease pathology only achieves effects during longer interventions (>8–12 weeks).194–196 Taken together, these studies of meditation suggest that effective and sustainable outcomes may be achieved for symptomatology and underlying pathology of post-viral fatigue (PASC and ME/CFS) (see Tables 1 and 2).

There are several limitations to the conclusions of meditation studies involving patients with PASC. First, there are few investigations that have been implemented and evaluated. Second, data are not available on intervention effects for patients with PASC over extended time. Thirdly, the exact cause of the Long COVID symptoms is still unknown, and in a recent study after extensive diagnostic evaluations of patients with PASC, Seller et al193 did not find persistent viral infection or abnormal immune activation.

There is a need for more high-quality studies assessing the frequency and duration required for the efficacy of meditation interventions for those with post-viral fatigue, using measures of the types of biological measures that were reviewed in this article. Meditation interventions that are at least 8 weeks in duration appear to have the most promise, but there is a need to investigate how such interventions might best be implemented, such as through new internet possibilities.

Disclosure

The authors report no conflicts of interest in this work.

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