|
 
 |
| PERSPECTIVE |
|
| Year : 2022 | Volume
: 6
| Issue : 3 | Page : 195-202 |
|
COVID-19, Long COVID, and Psychosomatic Manifestations: A Possible Burden on Existing Rheumatology Facilities
Md Abu Bakar Siddiq1, Johannes Jacobus Rasker2
1 Department of Physical Medicine and Rheumatology, Brahmanbaria Medical College, Brahmanbaria, Bangladesh; Department of Rheumatology, University of South Wales, Pontypridd, United Kingdom
2 Department of Psychology, Health and Technology, Faculty of Behavioral, Management and Social Sciences, University of Twente, Enschede, The Netherlands
| Date of Submission | 05-Oct-2021 |
| Date of Acceptance | 27-May-2022 |
| Date of Web Publication | 30-Sep-2022 |
Correspondence Address:
Prof. Johannes Jacobus Rasker
University of Twente, P. O. Box: 217, 7500 AE, Enschede
The Netherlands
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/hm.hm_63_21
COVID-19 mainly affects the respiratory system; however, other body parts can also be involved. After resolving the acute stage, long-standing COVID effects can continue to trouble COVID survivors; a term used to describe them is “long COVID” or post-COVID syndrome. Long COVID phenotypes are physical and functional: physical symptoms include persistent dyspnea, chest pain, myalgia, impaired mobility, and arthralgia, whereas fatigue, depression, cognitive impairment, anxiety, posttraumatic stress disorder, insomnia, and somatization are considered the functional aspects. Growing evidence suggests inflammatory rheumatic conditions may develop in COVID-19. COVID-19 further impact patients significantly with inflammatory arthritis (IA), their physical, psychological and social relationships, and their quality of life. Psychiatric COVID long-haulers could overload the existing rheumatology facilities globally, especially in the simultaneous presence of IA and COVID-19. This perspective addresses how psychosomatic manifestations of COVID-19 and “long COVID” burden the present rheumatology facility. We further address treatment options of “long COVID” and future research direction regarding its pathophysiology and “long COVID” psychosomatic illness, especially in the setting of chronic rheumatic diseases.
Keywords: Burden, COVID-19, long COVID, psychosomatic, quality of life, rheumatology
How to cite this article:
Bakar Siddiq MA, Rasker JJ. COVID-19, Long COVID, and Psychosomatic Manifestations: A Possible Burden on Existing Rheumatology Facilities. Heart Mind 2022;6:195-202 |
| Introduction | |  |
When someone has recovered from COVID-19 illness and still experiences some symptoms, he or she may have a post-COVID condition called long COVID.[1] Once the COVID-19 pandemic has ended, “long COVID” will likely continue to trouble society. Ongoing, sustained inflammatory response with highly activated innate immune cells, lacking naive T- and B-cells, and elevated expression of type I interferon (IFN-β) and type III IFN (IFN-λ1) could contribute in “long COVID” features for months or longer.[1] Most COVID-19 patients recover without much consequence, although pulmonary sequelae may require pulmonary rehabilitation.[2] Neurological symptoms may also have a protracted course, even in children.[3] About one in five patients may have long-standing physical and functional impairments and complaints collectively termed “long COVID.”[4],[5],[6]
| What is Long Covid? | | |
The terms “long COVID” or “COVID long-haulers” describe those with COVID-19 experiencing symptoms beyond 4 weeks from the onset of the disease when testing for replication-competent SARS-CoV-2 has been negative for at least 1 week.[6] It signifies biochemical, but not clinical recovery.[4] Long COVID symptoms may include dyspnea, muscle pain, chest pain, headache, insomnia, diarrhea and also anxiety, depression, posttrauma stress disorder (PTSD), and fatigue are comprised in the functional symptom complex.[6] In a meta-analysis, the five-most common symptoms of long COVID were fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and dyspnea (24%).[7] These nonspecific clinical features are also seen in inflammatory arthritis (IA), connective tissue diseases (CTDs), and noninflammatory soft-tissue rheumatisms, like fibromyalgia (FMS) and chronic fatigue syndrome (CFS).[8],[9],[10] Systemic rheumatic disorders further may have aggravated clinical manifestations if patients get COVID-19, or new chronic rheumatic disorders may develop in COVID-19 milieu.[11]
In the SARS-CoV2 pandemic, there is a surge in psychological stressors irrespective of people getting infected or not, geographic location, religion, socioeconomic status, and cultural association.[6],[7] The question remains how much of the long COVID is caused directly by the viral infection itself[1] and how much by stressors on the general population like the lock down, the fear of getting infected, the economic consequences and death often being so near. As rheumatic disorders flare up and the COVID-19 pandemic, including “long COVID” are associated with psychological stressors,[10] it is believed that COVID-19 may produce substantial burden on current rheumatology facilities globally, especially, when COVID-19 coexists in patients with established chronic rheumatic conditions.
The aim of this perspective is to explore the psychosomatic aspects of COVID and long COVID, and to review how they link with causation of new rheumatic diseases or aggravation of existing systemic rheumatic conditions.
| ”Long Covid” and Psychosomatic Symptoms | | |
”Long COVID” may be seen in patients who had a mild disease course as well as in those who had been severely affected.[4] The symptoms of long COVID are not limited to respiratory, cardiovascular, neurological, gastrointestinal, and musculoskeletal systems; impairments may also include psychological status, cognitive, and higher mental functioning.[12] In a retrospective cohort study, among COVID-19 survivors, 57% had one or more long COVID features during the whole 6-month period, and 36.55% between 3 and 6 months at follow-up.[13] The incidence of each feature was: abnormal breathing (18.71% in the 1- to 180-day period; 7.94% in the 90- to 180-day period), fatigue/malaise (12.82%; 5.87%), chest/throat pain (12.60%; 5.71%), headache (8.67%; 4.63%), other pain (11.60%; 7.19%), abdominal symptoms (15.58%; 8.29%), myalgia (3.24%; 1.54%), cognitive symptoms (7.88%; 3.95%), and anxiety/depression (22.82%; 15.49%).[13] “Long COVID” is more common in women than in men; patients with older age and the presence of more than five symptoms during the acute stage are at increased risk of developing “long COVID.”[4] Post-COVID complications, including psychological manifestations are reported to be higher in hospitalized patients.[12] In a hospital-based study, 384 COVID patients who were followed after discharge, reported with fatigue (69%), persistent breathlessness (53%), cough (34%), and depression (14.6%).[14] Huang et al. studied 1,733 COVID-19 cases 6 months after discharge; fatigue or muscle weakness (63%), sleep difficulties (26%), and anxiety or depression were the three most commonly reported symptoms.[15] Age was positively associated with lung diffusion impairment, fatigue and negatively related to the computed tomography (CT) score change.[15] Per 10-year increase of age, the risk of diffusion impairment was 27% higher and fatigue or muscle weakness was 17% higher and the CT score 4% lower.[15] No significant association of age with anxiety or depression was observed.[15]
In an online survey of 180 COVID-19 nonhospitalized patients, “long COVID” symptoms were reported: 53.1% of individuals had at least one, 33.3% had one or two, and 19.4% had three or more symptoms even after 125 days of disease onset.[16] The youngest patients' (0–17 years) reported fewer symptoms, and persistent symptoms increase significantly with age.[16] The most prevalent persistent symptoms were fatigue, loss of smell and taste, and arthralgias.[16] All patients had fatigue in the acute stage and at follow-up, only <1% had newly developed fatigue at follow-up.[16] A longitudinal cohort study was done in 312 Norwegian COVID-19 cases – 247 home-isolated and 65 hospitalized; at 6 months, persistent symptoms were documented in 61% of the patients, the most common symptom was persistent fatigue (Chalder fatigue score). In patients 16 years or older fatigue was present in 7% of home-isolated patients and in 24% of hospitalized patients.[17] In home-isolated patients, the most frequent symptoms of physical fatigue were tiredness (35%), increased need for rest (30%), and lack of energy (29%); the most common symptoms of mental fatigue were difficulties with finding words (23%), problems with concentrating (19%), and memory problems (18%).[17] In patients, fever during acute illness, the severity of initial illness, female gender, preexisting pulmonary disease, and increased convalescent antibody (SARS-CoV-2 spike protein specific Immunoglobulin G (IgG) and microneutralizing) titers were independently associated with increasing fatigue score at 6 months.[17] Increased fatigue may be associated with existing breathlessness and with poor recovery of respiratory function even a few months after discharge.[4] A study among Egyptian post-COVID cases revealed that only 10.8% of all patients had no manifestation after recovery from the disease, 67.6% had post-COVID-19 manifestations, and 32.4% had persistent manifestations; a significant number of patients had fatigue (72.8%), anxiety (38%), dementia (28.6%), and depression (28.6%).[18] However, 83.3% of the moderate–severe cases were related to comorbid conditions, such as diabetes, bronchial asthma, hypertension, and pregnancy.[18]
| Covid-19 and Psychosomatic Illness | | |
A recent study in an Australian adult community found a marked increase of depression and anxiety during the pandemic among individuals without COVID diagnosis.[19] However, in a recent retrospective study, a substantial psychiatric morbidity has been reported to be highest among COVID-19 survivors, but this was not limited to only severe COVID-19 cases.[20] Higher levels of depression and anxiety and lower psychological well-being were associated with job loss, financial distress, and overall work-related and social impairments.[19] A population-based study estimated the prevalence of sleep disturbance, loneliness, anxiety, and depression at 73%, 71%, 64%, and 38%, respectively, among 672 Bangladeshi surveyed online during the pandemic.[21] Female gender, unemployment, being a student, obesity, and living without a family were considered poor mental health risks in the country.[21] Working from home during the pandemic was not associated with any mental illness, and could be a solution for the problem during the pandemic.[19]
During a COVID 19 outbreak, depression and anxiety among surgical teams were significantly higher than in nonoutbreak periods.[22] Health-care teams had higher levels of anxiety, somatization, and insomnia in comparison with administrative teams and nonhealth professionals.[22] In another meta-analysis, the same authors concluded that the psychiatric repercussions, including PTSD among COVID health fighters was significant both in European and non-European countries:[23] Doctors experienced a higher prevalence of insomnia, anxiety, depression, somatization, and obsessive-compulsive symptoms in comparison with nondoctor health workers.[23] In health professionals worried of infection of coworkers and family members, PPE availability, medical violence and so on could trigger their psychological suffering.[23]
An online survey in 606 health professionals revealed that anxiety, insomnia, and somatic symptoms were frequent among them using the Chinese version of the 7-item Generalized Anxiety Disorder scale, 7-item Insomnia Severity Index, and the somatization subscale of Symptom Checklist 90 (SCL-90). Insomnia and anxiety were independently associated with somatic symptoms during COVID-19, and was seen in 22.9% of patients.[24] In a cross-sectional study in China, the mental health was studied in 450 health-care workers (178 were doctors) who had been working for more than a year in community hospitals during the COVID-19 outbreak in Sichuan Province, using the SCL-90 online. Doctors experienced psychological problems with the highest scores on most SCL-90 factors except for obsessive compulsiveness, hostility, phobic anxiety, and psychoticism.[25]
A longitudinal single-center study in 2020 assessed the mental health impact of COVID-19 on nurses working in Belgium.[26] Based on the Four-Dimensional Symptom Questionnaire scale, low rates were found of depression, somatization, anxiety declining over time, but distress scores were high throughout the study. The Impact of Event Scale-Revised (IES-R) and Brief-COPE questionnaires were used to assess the psychological impact and coping strategies, respectively.[26] A history of stress symptoms was significantly associated with higher distress scores at the inclusion and 1-month follow-up. As a significant psychological impact, more participants experienced “intrusion” than “avoidance” specifically among nurses working in intensive care unit (ICU).[26] IES-R scores were predictive for PTSD.[23] A pooled analysis of 20 studies by Hao et al. revealed that depression and anxiety were higher among females and among nurses.[27] Frontline health-care workers had a higher prevalence of anxiety, though a lower prevalence of depression than those in the second line.[27] In a retrospective study with Malaysian health-care providers, depressive symptoms (Hospital Anxiety and Depression Scale, score >8) were found higher in the nonfront line than frontline health-care providers.[28] In another online survey in China, hospital staff was shown to have severely negative psychological distress, requiring early diagnosis and treatment.[29] In a survey of 652 medical staff in China, psychological stress was seen to improve following psychological intervention.[30]
A substantial number of COVID-19 patients may subsequently develop rheumatic diseases or clinical features of rheumatic diseases may aggravate; on the other hand, some patients with IA may also get COVID-19. Both conditions share some psychological manifestations. We wonder whether COVID-19 frontline health-care providers with rheumatic diseases develop any psychosomatic illness. Until today, we do not find any publication describing the incidence of psychosomatic problems among rheumatoid-specific healthcare providers treating COVID-19 patients or getting COVID-19 infections.
| Covid-19, “Long Covid” and Rheumatology Facility Burden | | |
The incidence of IA in COVID is inconsistent; it varies throughout the studies.[31] It is uncertain how many COVID patients will develop features of IA or whether COVID aggravates the IA features. In a cohort study, the risk of severe COVID-19 was seen higher in rheumatic patients than in nonrheumatic patients.[32] Hospitalized chronic inflammatory rheumatic patients with CTD had severe COVID-19.[32] Sometimes, chest CT images in COVID-19 can resemble and obscure new-onset rheumatologic conditions with pulmonary involvement, such as mixed CTD (MCTD), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA); hence, in patients with progressive pulmonary conditions the diagnosis and adequate treatment may be delayed.[33]
Systemic sclerosis
Three weeks after a mild COVID-19 infection, a 47-year-old male developed systemic sclerosis (SSc) (clinical, biochemistry, immunological, and radiological pictures satisfied the ACR/EULAR classification criteria).[34] SSc patients from the European Scleroderma Trial and Research database with COVID-19 were followed prospectively.[35] In total, 178 European SSc patients with COVID-19 were registered; 38% were hospitalized (84% due to COVID-19), and 24% had a severe outcome (required noninvasive ventilation, mechanical ventilation/extracorporeal membrane oxygenation, or death).[35] Age, non-SSc comorbidities, interstitial lung disease, pulmonary artery hypertension, and SSc-associated renal or cardiac diseases were numerically associated with hospitalization and death.[35]
Rheumatoid arthritis
There is an increased risk of COVID-19 incidence and COVID severity in RA patients compared to those without RA.[36] The US Department of veterans affairs (VA) studied a cohort of patients with and without RA. It was found that a higher incidence of COVID-19 and higher COVID-19 severity lead more often to hospitalization and death among RA patients than in non-RA controls. The use of disease-modifying anti-rheumatic drugs (DMARDs) and prednisolone, self-reported ethnic difference, and the presence of several chronic conditions, but not seropositivity for rheumatoid factor (RF), were associated with risk of COVID-19 and of severe COVID-19.[36] Recurrences of COVID-19 were observed in RA patients with long-term usage of hydroxychloroquine, and leflunomide.[37] Tocilizumab further complicated the COVID features with superimposed Pneumocystis jirovecii and Aspergillus fumigatus infections.[37] Autoimmune phenomena were demonstrated to be aggravated during COVID-19 infection, and discontinuation of glucocorticoid (GC) therapy could promote recovery of their immunity and limit the occurrence of opportunistic infections.[38]
Systemic lupus erythematosus
Even though the mortality of individuals with SLE due to COVID is comparable to that in the general population, higher risks of hospitalization, ICU admission, mechanical ventilation, stroke, thromboembolism, and sepsis are documented. For that reason, identifying and vaccinating against COVID of the high-risk group SLE cases should be and ensured.[39] According to Colombia Lupus Cohort, there was a higher risk of symptomatic COVID among lupus patients than in the community in New York City. Severe COVID-19 manifestations were associated with elevated serum interleukin-6 (IL-6) and multifocal pulmonary radio-opacities.[40] In a hospital-based survey in France, death due to acute organ failure (AOF) was higher in SLE-COVID-19-AOF cases than in non-SLE-COVID-19-AOF cases.[41]
Myositis
COVID-19-associated myositis has also been reported.[31],[42] In a case–control study, severe COVID-19 had myositis ranging from mild to severe.[43] Inflammatory myositis was associated with COVID duration and was more pronounced than cardiac inflammation.[43] Although viral load in the affected muscle was low, circulating viral RNA could contribute to postinfectious, immune-mediated myopathy.[43] COVID myositis involves the proximal limb, bulbar, and facial muscles. Myositis and myasthenia gravis (MG) may coexist.[44]
| How are Covid, Long Covid Symptoms, and Inflammatory Rheumatic Disorders Connected? | | |
It is believed that “cytokine storm” affecting hypothalamic pituitary adrenal (HPA) axis contributes to COVID-19 psychosomatic illness with aggravation of features mimicking rheumatic disorders.[5],[11],[12],[45] HPA axis dysfunction is also seen in IA and can explain better the aspects of psychological involvement in IA.[10] However, SARS-CoV2 invading various body tissues, resulting in neuroinflammation, muscle inflammation also contributes in fatigue, arthralgia, myalgia and so on, that are common both in COVID survivors and in patients with systemic rheumatic diseases (SRDs).[5],[12] COVID-19-associated psychological impairments can also be explained by central sensitization (CS) theory [Figure 1].[5],[31] | Figure 1: Triad of psychosomatic aspects of long COVID. *cytokine storm hyper- and or hypo-activating hypothalamic pituitary adrenal (HPA) axis; **direct invasion of body tissue causing tissue damage and functional impairment; ***persistent peripheral stimuli or stressors cause altered neurotransmitter metabolism and level at the synapsis
Click here to view |
Cytokine storm and hypothalamic pituitary adrenal axis
Chronic IA may disrupt the HPA axis. However, GC can restore the deranged HPA axis circadian rhythms. Iatrogenic adrenal suppression following GC can happen, if patients do not follow circadian rhythm.[46] Subtle HPA axis dysfunction in RA mainly happens at the adrenal level, especially in a subset of premenopausal-onset women with lower levels of adrenal androgens.[47] In an original research in GC-naïve patients with systemic autoimmune diseases (RA, SLE, MCTD, SSc, IIM, adult Still's disease, IgG4-related disease, and vasculitis), increased serum concentration of pro-inflammatory cytokines, mostly IL-6 causes increased production of cortisol through ACTH stimulation, though GC therapy can reverse that.[48]
In a clinical trial, an increased prevalence of subclinical GC deficiency in AS patients has also been documented.[49] Anti-tumor necrosis factor (TNF) treatment appeared not have influenced the HPA axis. Inadequate cortisol responses following low-dose ACTH were significantly correlated with basal and peak cortisol concentrations and increased Bath Ankylosing Spondylitis Disease Activity Index scores.[49]
Critical illness-related GC insufficiency was defined as a dynamic condition characterized by inappropriate cellular activity of GC for the severity of the disease, manifested by persistently elevated pro-inflammatory mediators (TNF-alpha, IL-1, 6).[50] In the acute COVID stage, cytokine storm (increased serum IL-1β, 6, TNF-α) is believed to activate the HPA axis with increased GC levels mitigating cytokine-mediated inflammation.[3] In long-standing cases, HPA-axis dysfunction can lead to hypocortisolism.[3] Hypocortisolism is also found in patients with depression and PTSD; hence, it is believed that the neuroimmune axis further links depression and COVID pathophysiology.[5] In a recent systematic review, social isolation, and loneliness were shown to be linked with systemic inflammation (raised C-reactive protein and IL-6) in the general population.[45] Anxiety, depression, insomnia, social isolation, PTSD aggravates symptoms of IA, regardless of active synovitis; all these feature are seen with “long COVID” at variable frequencies and could be explained by “HPA axis dysfunction and hypocortisolism” theory.[5],[10]
Virus-induced (neuro)-inflammation, relation to pain and psychosomatic symptoms
SARS-CoV-2-induced neuro-inflammation disrupts the blood-brain barrier (BBB) with increased IL-1, 6, and free radicals in the cerebrospinal fluid and brain tissue. BBB disruption further leads to inflammatory cell infiltration into the central nervous system (CNS), activating microglia and astrocytes, and neuronal death. SARS-CoV-2-induced inflammation and hypoxia affect human brain areas essential for fine motor function, learning, memory, and emotional responses, resulting in the loss of adult life hippocampal neurogenesis with persisting effects as “long COVID.”[51],[52] Consequently, COVID-19 patients may present with memory deficit, poor attention, impaired movement coordination and cognition, and altered mood).[52] SARS-CoV-2-induced defective synthesis of angiotensin-converting enzyme 2 (ACE2) receptors, and Dopa decarboxylase (DDC) in nonneuronal cells lead to reduced synthesis of serotonin, dopamine, and histamine could further contribute in confusion, delirium, agitation, and sleep-wake disorders.[53]
Severe respiratory infection with low oxygen saturation and breathlessness and myocardial injury may require mechanical ventilation; recovery from prolonged ventilation is also associated with seizure, delirium, cognitive impairment.[12] SARS-CoV-2-mediated myocarditis through the high density of ACE2 receptors expressed in cardiomyocytes may recover with lower left ventricular ejection fraction, higher left ventricular volumes, higher left ventricular mass, biopsy revealed endomyocardial tissue lymphocyte infiltration, and magnetic resonance imaging (MRI)-pericardial enhancement.[54] Severe COVID-19 with cardiac involvement with ongoing myocardial inflammation is seen in 25% of the cases, 3 months post discharge.[54] Long COVID cardiovascular effects include CFS, dyspnea, chest pain, exercise-induced arrythmia, dysautonomia, and postural orthostatic tachycardia syndrome-like syndrome.[55] Besides, viral invasion to muscle may lead to myonecrosis, impaired neurotransmitter metabolism, and neuromuscular junction impairments also lead to fatigue.[12] Fatigue is a common nonspecific manifestation in RA, SLE, FMS, myositis, and MCTD.
Long COVID fatigue could mislead the physicians as of those rheumatic diseases in coexistence or whether the post-COVID manifestations signify the flaring up of existing chronic inflammatory and noninflammatory rheumatic disorders.
Central sensitization theory
CS implies amplifying the sensory input from various organs to the CNS.[56] This enhanced sensory response causes neuronal plasticity with heightened sensitivity to pain perception from nonpainful stimuli (allodynia) and increased pain feeling disproportionate to the painful stimuli (hyperalgesia).[56] It is due to nociceptive neuron membrane excitability, facilitation of synaptic strength, and decreases in inhibitory transmission.[56] Affected neurons display spontaneous activity, reduced activation threshold, and enlarged receptive fields.[56] Perceptions may be irrespective of the intensity, duration, or the presence of any noxious peripheral stimuli.[56] In the CS, changes in brain activity can be detected by functional MRI or positron-emission tomographic imaging, and electrophysiology studies.[56]
COVID and non-COVID individuals develop some stressors during the pandemic, such as loneliness, the unknown natural history of COVID, worries about family, loss of income and so on could impair the offset of neurotransmitters at the synapsis (reduced serotonin and norepinephrine, and increased substance P), leading to the development of generalized body aches, joint pain, morning stiffness, fatigue, features of FMS, an example of CS.[31]
It may be expected that long COVID will give an increase in workload for cardiology and pulmonary facilities worldwide. Based on literature, also rheumatology facilities across the world are going to face a huge burden due to long COVID. The existing rheumatology sub-specialty may face troubles to handle it, for sure.[57] To document rheumatic manifestations of COVID long haulers, rheumatologists should work with other health-care facilities. Hence, “long COVID” does not only make anxious COVID survivors but also treating physicians including rheumatologists to find the ways to respond to the post-COVID syndrome.
| Long Covid, Psychological Factors, and Quality of Life among Rheumatic Diseases | | |
Quality-of-life (QoL) of patients with rheumatic diseases has a strong biomedical focus. [5,8-10,58] Recently, the impact of COVID-19-related-health care interruption (HCI) on the physical, psychological, social relationships, and environment QoL-dimensions in rheumatic diseases, mainly in RA and SLE, was evaluated at the outpatient door and at 6-month follow-up.[58] Psycho-emotional factors (primarily feeling confused, depression, and anxiety), sociodemographic factors (age, COVID-19-negative economic impact, years of scholarship, HCI, and having a job), and biomedical factors (routine assessment of patient index data-3, RAPID-3 score and GC use) were associated with baseline QoL dimensions scores.[58] Psycho-emotional factors had the strongest influence on the dimensions scores.[58] The most consistent predictor of QoL dimensions scores at 6-month follow-up was each corresponding baseline dimension score.[58]
Besides, in a web-based study among 26,045 US patients with SRDs statistically significant worse pain, depression, fatigue, and anxiety were found compared with the mean values in the US population and in those without SRDs.[59] Patients with SRDs had a higher incidence of contact with COVID-19 cases, more COVID-19-like symptoms, and spent >95% of their time homebound compared with those without SRDs. This might differently have impact on the QoL of SRD patients. However, further research is required to depict whether the difference will continue in the post-COVID period.[59]
| Treatment of Long Covid | | |
There is no specific treatment yet available for all patients, and that cannot be expected as the psychosomatic and other symptoms and complaints are probably multi-causal in origin. All patients developing a post COVID-19 condition should be looked after carefully. This care should be multidisciplinary, including the primary care provider as well as relevant specialists like rehabilitation professionals, social workers, psychologists and other, mental health professionals.[60] COVID lockdown reportedly caused a mental health deterioration (PTSD, anger, and anxiety) that improved with exposure to nature, as tested in a cross-sectional study among 3,157 participants in Europe (1,638 from Portugal, 1,519 from Spain).[61] Viewing nature from home, including contact with private green space and greenery, significantly reduced psychological distress, somatization, and stress levels.[61] COVID-19 patients may develop psychiatric symptoms after treatment with antiviral drugs, and some psychiatric patients have been infected with COVID-19. However, antidepressants, antipsychotics, and valproate are considered safe when taken together with antiviral drugs.[62] Severe anxiety with intrusive thoughts could develop in young males recovered from COVID-19 infection and could respond with group therapy and psychotropic medications.[63] Besides, melatonin, an intracellular transcription factor activator (NRF2, nuclear factor erythroid-derived 2-like 2), could increase the expression of enzymes required to synthesize intracellular antioxidant, glutathione quenching free radicals causing oxidative stress and could improve insomnia, depression, fatigue, and brain fog in long COVID.[64] It is believed that SARS-CoV2 associated ACE2 and DDC dysfunction may lead to defective synthesis of serotonin, melatonin, dopamine, and histamine synthesis at nonneuronal cells with psychosomatic features; hence, melatonin or dopamine agonists is believed to improve the symptoms; however, further research is warranted.[64]
Patients treated with biologic and conventional DMARDs (except rituximab, TNF inhibitors, mycophenolate mofetil) and infected with SARS-CoV2 are considered safe during COVID infections, as seen on clinical trials.[11] After the recovery from COVID-19, maintenance of DMARDs therapy should be decided jointly by the treating rheumatology and infectious disease physicians. Distinct combinations of IFN-α, IFN-β, IL-10, and TNF-α are better predictors of mortality in different severity groups. In the low-IL-6 group of COVID-19 patients, mortality is significantly lower; tocilizumab therapy showed a considerable reduction in mortality in patients with high-baseline IL-6, but no reduction in mortality in low-baseline IL-6 patients.[65] IL-17 is related to the hyper-inflammatory state in SARS-CoV-2 infection; however, the clinical course of COVID-19 among patients with IA treated with secukinumab (anti-IL-17) is mild, in general.[66] The potential role of IL-17 inhibition in the clinical course of COVID-19 still needs further research. As IL-1, 6, TNF-alpha mediated neuro-inflammation explain COVID psychosomatic features, ant-IL-1, 6, TNF-alpha might have improved them, but further research is warranted. Fatigue associated with myositis and MG in COVID-19 could be successfully treated with tocilizumab.[44] In the latest longitudinal study, “long COVID” was seen associated with combinations of the inflammatory mediators, like IFN-γ, IFN-λ2/3), IFN-β, long-pentraxin 3 (PTX3), IL-6, suggesting future opportunities for prevention and treatment of the post-COVID syndrome.[1]
Future research direction
Psychosomatic COVID long-haulers have widely been reported. However, we are yet to learn more about the post-COVID syndrome. We need to explore COVID psychiatric features and compare them between treating health-care facilities or between COVID severity grades. The pathophysiology of COVID somatization deserves further research. Further research on the HPA axis, hypocortisolism, neuro-inflammation, and altered neurotransmission can increase our understanding of COVID and “long COVID” psychosomatic illness, especially in the setting of chronic rheumatic diseases. Longitudinal follow-up of “long COVID” further could estimate the incidence of IA, FMS, and CFS among COVID survivors. How psychosomatic illness affects QoL of COVID survivors those having rheumatic diseases could be investigated.
| Conclusion | | |
Long COVID psychosomatic presentations may adversely affect patients' survival and QoL. COVID psychiatric manifestations could aggravate preexisting inflammatory and noninflammatory rheumatic disorders; hence, it is essential to manage them accordingly. COVID psychiatric illnesses, including fatigue, malaise, anxiety, depression, and somatization, are also seen as nonspecific features of rheumatic disorders, identifying them in the milieu of the post-COVID syndrome helps physicians to diagnose and treat the respective diseases.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Phetsouphanh C, Darley DR, Wilson DB, Howe A, Munier CM, Patel SK, et al. Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection. Nat Immunol 2022;23:210-6.  |
| 2. | Siddiq MA, Rathore FA, Clegg D, Rasker JJ. Pulmonary Rehabilitation in COVID-19 patients: A scoping review of current practice and its application during the pandemic. Turk J Phys Med Rehabil 2020;66:480-94. |
| 3. | Khalifa M, Zakaria F, Ragab Y, Saad A, Bamaga A, Emad Y, et al. Guillain-barre syndrome associated with SARS-CoV-2 detection and a COVID-19 infection in a child. J Pediatr Infect Dis Soc 2020;9:510-3. |
| 4. | Raveendran AV, Jayadevan R, Sashidharan S. Long COVID: An overview. Diabetes Metab Syndr 2021;15:869-75. |
| 5. | Raony Á de Figueiredo CS, Pandolfo P, Giestal-de-Araujo E, Oliveira-Silva Bomfim P, Savino W. Psycho-neuroendocrine-immune interactions in COVID-19: Potential impacts on mental health. Front Immunol 2020;11:1170. |
| 6. | Naeije R, Caravita S. Phenotyping long COVID. Eur Respir J 2021;58:2101763. |
| 7. | Lopez-Leon S, Wegman-Ostrosky T, Perelman C, Sepulveda R, Rebolledo PA, Cuapio A, et al. More than 50 long-term effects of COVID-19: A systematic review and meta-analysis. Sci Rep 2021;11:16144. |
| 8. | Bradley LA. Pathophysiology of fibromyalgia. Am J Med 2009;122:S22-30. |
| 9. | Rowe PC, Underhill RA, Friedman KJ, Gurwitt A, Medow MS, Schwartz MS, et al. Myalgic encephalomyelitis/chronic fatigue syndrome diagnosis and management in young people: A primer. Front Pediatr 2017;5:121. |
| 10. | Yılmaz V, Umay E, Gündoğdu İ, Karaahmet ZÖ, Öztürk AE. Rheumatoid Arthritis: Are psychological factors effective in disease flare? Eur J Rheumatol 2017;4:127-32. |
| 11. | Stradner MH, Dejaco C, Zwerina J, Fritsch-Stork RD. Rheumatic musculoskeletal diseases and COVID-19 A review of the first 6 months of the pandemic. Front Med (Lausanne) 2020;7:562142. |
| 12. | Crook H, Raza S, Nowell J, Young M, Edison P. Long COVID-mechanisms, risk factors, and management. BMJ 2021;374:n1648. |
| 13. | Taquet M, Dercon Q, Luciano S, Geddes JR, Husain M, Harrison PJ. Incidence, co-occurrence, and evolution of long-COVID features: A 6-month retrospective cohort study of 273,618 survivors of COVID-19. PLoS Med 2021;18:e1003773. |
| 14. | Mandal S, Barnett J, Brill SE, Brown JS, Denneny EK, Hare SS, et al. 'Long-COVID': A cross-sectional study of persisting symptoms, biomarker and imaging abnormalities following hospitalisation for COVID-19. Thorax 2021;76:396-8. |
| 15. | Huang C, Huang L, Wang Y, Li X, Ren L, Gu X, et al. 6-month consequences of COVID-19 in patients discharged from hospital: A cohort study. Lancet 2021;397:220-32. |
| 16. | Petersen MS, Kristiansen MF, Hanusson KD, Danielsen ME, Á Steig B, et al. Long COVID in the Faroe Islands – A longitudinal study among non-hospitalized patients. Clin Infect Dis 2021;73:e4058-63. |
| 17. | Blomberg B, Mohn KG, Brokstad KA, Zhou F, Linchausen DW, Hansen BA, et al. Long COVID in a prospective cohort of home-isolated patients. Nat Med 2021;27:1607-13. |
| 18. | Kamal M, Abo Omirah M, Hussein A, Saeed H. Assessment and characterisation of post-COVID-19 manifestations. Int J Clin Pract 2021;75:e13746. |
| 19. | Dawel A, Shou Y, Smithson M, Cherbuin N, Banfield M, Calear AL, et al. The effect of COVID-19 on mental health and wellbeing in a representative sample of Australian adults. Front Psychiatry 2020;11:579985. |
| 20. | Taquet M, Geddes JR, Husain M, Luciano S, Harrison PJ. 6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: A retrospective cohort study using electronic health records. Lancet Psychiatry 2021;8:416-27. |
| 21. | Das R, Hasan MR, Daria S, Islam MR. Impact of COVID-19 pandemic on mental health among general Bangladeshi population: A cross-sectional study. BMJ Open 2021;11:e045727. |
| 22. | da Silva Neto RM, Benjamim CJ, de Medeiros Carvalho PM, Neto ML. Psychological effects caused by the COVID-19 pandemic in health professionals: A systematic review with meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry 2021;104:110062. |
| 23. | da Silva FC, Neto ML. Psychiatric symptomatology associated with depression, anxiety, distress, and insomnia in health professionals working in patients affected by COVID-19: A systematic review with meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry 2021;104:110057. |
| 24. | Li H, Zhang Y, Wang H, Liang J, Zhou Y, Huang Y, et al. The relationship between symptoms of anxiety and somatic symptoms in health professionals during the coronavirus disease 2019 pandemic. Neuropsychiatr Dis Treat 2020;16:3153-61. |
| 25. | Zhang J, Deng X, Liu H, Xu X, Fang R. Evaluation of the mental health status of community healthcare workers during the COVID-19 outbreak. Medicine (Baltimore) 2021;100:e24739. |
| 26. | Van Steenkiste E, Schoofs J, Gilis S, Messiaen P. Mental health impact of COVID-19 in frontline healthcare workers in a Belgian Tertiary care hospital: A prospective longitudinal study. Acta Clin Belg 2022;77:533-40. |
| 27. | Hao Q, Wang D, Xie M, Tang Y, Dou Y, Zhu L, et al. Prevalence and risk factors of mental health problems among healthcare workers during the COVID-19 pandemic: A systematic review and meta-analysis. Front Psychiatry 2021;12:567381. |
| 28. | Norhayati MN, Che Yusof R, Azman MY. Depressive symptoms among frontline and non-frontline healthcare providers in response to the COVID-19 pandemic in Kelantan, Malaysia: A cross sectional study. PLoS One 2021;16:e0256932. |
| 29. | Juan Y, Yuanyuan C, Qiuxiang Y, Cong L, Xiaofeng L, Yundong Z, et al. Psychological distress surveillance and related impact analysis of hospital staff during the COVID-19 epidemic in Chongqing, China. Compr Psychiatry 2020;103:152198. |
| 30. | Xu J, Liu X, Xiao Y, Fang X, Cheng Y, Zhang J. Effect of EAP psychological intervention on improving the mental health of medical workers under the novel coronavirus epidemic in China. Front Public Health 2021;9:649157. |
| 31. | Khasru M, Siddiq M, Marzen T, Rahman M, Islam I, Refaie S, et al. Musculoskeletal Manifestations of COVID-19: A Systematic Search and Review. Rheum Res 2021;6:59-80. |
| 32. | Pablos JL, Galindo M, Carmona L, Lledó A, Retuerto M, Blanco R, et al. Clinical outcomes of hospitalised patients with COVID-19 and chronic inflammatory and autoimmune rheumatic diseases: A multicentric matched cohort study. Ann Rheum Dis 2020;79:1544-9. |
| 33. | Patel M, Willoughby J, Kousha M. Determining new-onset pulmonary involvement of connective tissue disease in a patient with recently diagnosed coronavirus disease 2019. Am J Resp Crit Care Med 2021;203;1. |
| 34. | Fineschi S. Case report: Systemic sclerosis after COVID-19 infection. Front Immunol 2021;12:686699. |
| 35. | Hoffmann-Vold AM, Brunborg C, Tirelli F, Carreira P, Papa ND, Mekinian A, et al. The impact and outcome of COVID-19 on systemic sclerosis patients from the European scleroderma trial and research group (EUSTAR). Ann Rheum Dis 2021;80 Suppl 1:232-33. |
| 36. | England BR, Roul P, Yang Y, Kalil AC, Michaud K, Thiele GM, et al. Risk of COVID-19 in rheumatoid arthritis: A national veterans affairs matched cohort study in at-risk individuals. Arthritis Rheumatol 2021;73:2179-88. |
| 37. | Cai S, Sun W, Li M, Dong L. A complex COVID-19 case with rheumatoid arthritis treated with tocilizumab. Clin Rheumatol 2020;39:2797-802. |
| 38. | Condé K, Atakla HG, Garba MS, Garba I. COVID-19 infection during autoimmune disease: Study of 2 cases in Republic of Guinea. Pan Afr Med J 2020;35:96. |
| 39. | Raiker R, Pakhchanian H, DeYoung C, Gupta L, Kardeş S, Ahmed S, et al. Short term outcomes of COVID-19 in lupus: Propensity score-matched analysis from a nationwide multi-centric research network. J Autoimmun 2021;125:102730. |
| 40. | Gartshteyn Y, Askanase AD, Schmidt NM, Bernstein EJ, Khalili L, Drolet R, et al. COVID-19 and systemic lupus erythematosus: A case series. Lancet Rheumatol 2020;2:e452-4. |
| 41. | Mageau A, Papo T, Ruckly S, Strukov A, van Gysel D, Sacre K, et al. Survival after COVID-19-associated organ failure among inpatients with systemic lupus erythematosus in France: A nationwide study. Ann Rheum Dis 2022;81:569-74. |
| 42. | Uslu S. Myositis due to COVID-19. Postgrad Med J 2021;97:399. |
| 43. | Aschman T, Schneider J, Greuel S, Meinhardt J, Streit S, Goebel HH, et al. Association between SARS-CoV-2 infection and immune-mediated myopathy in patients who have died. JAMA Neurol 2021;78:948-60. |
| 44. | Zhang H, Charmchi Z, Seidman RJ, Anziska Y, Velayudhan V, Perk J. COVID-19-associated myositis with severe proximal and bulbar weakness. Muscle Nerve 2020;62:E57-60. |
| 45. | Smith KJ, Gavey S, RIddell NE, Kontari P, Victor C. The association between loneliness, social isolation and inflammation: A systematic review and meta-analysis. Neurosci Biobehav Rev 2020;112:519-41. |
| 46. | Spies CM, Straub RH, Cutolo M, Buttgereit F. Circadian rhythms in rheumatology--a glucocorticoid perspective. Arthritis Res Ther 2014;16 Suppl 2:S3. |
| 47. | Imrich R, Rovenský J. Hypothalamic-pituitary-adrenal axis in rheumatoid arthritis. Rheum Dis Clin North Am 2010;36:721-7. |
| 48. | Fujio N, Masuoka S, Shikano K, Kusunoki N, Nanki T, Kawai S. Apparent hypothalamic-pituitary-adrenal axis suppression via reduction of interleukin-6 by glucocorticoid therapy in systemic autoimmune diseases. PLoS One 2016;11:e0167854. |
| 49. | Kebapcilar L, Bilgir O, Alacacioglu A, Yildiz Y, Taylan A, Gunaydin R, et al. Impaired hypothalamo-pituitary-adrenal axis in patients with ankylosing spondylitis. J Endocrinol Invest 2010;33:42-7. |
| 50. | Marino LO, Souza HP. Dysfunction of the hypothalamic-pituitary-adrenal axis in critical illness: A narrative review for emergency physicians. Eur J Emerg Med 2020;27:406-13. |
| 51. | Klein R, Soung A, Sissoko C, Nordvig A, Canoll P, Mariani M, et al. COVID-19 induces neuroinflammation and loss of hippocampal neurogenesis. Res Sq 2021:s3-1031824. |
| 52. | Almutairi MM, Sivandzade F, Albekairi TH, Alqahtani F, Cucullo L. Neuroinflammation and its impact on the pathogenesis of COVID-19. Front Med (Lausanne) 2021;8:745789. |
| 53. | Attademo L, Bernardini F. Are dopamine and serotonin involved in COVID-19 pathophysiology? Eur J Psychiatry 2021;35:62-3. |
| 54. | Becker RC. Anticipating the long-term cardiovascular effects of COVID-19. J Thromb Thrombolysis 2020;50:512-24. |
| 55. | |
| 56. | Fleming KC, Volcheck MM. Central sensitization syndrome and the initial evaluation of a patient with fibromyalgia: A review. Rambam Maimonides Med J 2015;6:e0020. |
| 57. | Al Maini M, Adelowo F, Al Saleh J, Al Weshahi Y, Burmester GR, Cutolo M, et al. The global challenges and opportunities in the practice of rheumatology: White paper by the World Forum on Rheumatic and Musculoskeletal Diseases. Clin Rheumatol 2015;34:819-29. |
| 58. | Guaracha-Basáñez GA, Contreras-Yáñez I, Hernández-Molina G, Estrada-González VA, Pacheco-Santiago LD, Valverde-Hernández SS, et al. Quality of life of patients with rheumatic diseases during the COVID-19 pandemic: The biopsychosocial path. PLoS One 2022;17:e0262756. |
| 59. | |
| 60. | Yue L, Wang J, Ju M, Zhu Y, Chen L, Shi L, et al. How psychiatrists coordinate treatment for COVID-19: A retrospective study and experience from China. Gen Psychiatr 2020;33:e100272. |
| 61. | Ribeiro AI, Triguero-Mas M, Jardim Santos C, Gómez-Nieto A, Cole H, Anguelovski I, et al. Exposure to nature and mental health outcomes during COVID-19 lockdown. A comparison between Portugal and Spain. Environ Int 2021;154:106664. |
| 62. | Zhang K, Zhou X, Liu H, Hashimoto K. Treatment concerns for psychiatric symptoms in patients with COVID-19 with or without psychiatric disorders. Br J Psychiatry 2020;217:351. |
| 63. | Driscoll M, Gu J. Severe anxiety post-COVID-19 infection. Case Rep Psychiatry 2021;2021:9922508. |
| 64. | Jarrott B, Head R, Pringle KG, Lumbers ER, Martin JH. “LONG COVID” – A hypothesis for understanding the biological basis and pharmacological treatment strategy. Pharmacol Res Perspect 2022;10:e00911. |
| 65. | Neumann AU, Goekkaya M, Dorgham K, Traidl-Hoffmann C, Gorochov G. Tocilizumab in COVID-19 therapy: Who benefits, and how? Lancet 2021;398:299-300. |
| 66. | Coskun Benlidayi I, Kurtaran B, Tirasci E, Guzel R. Coronavirus disease 2019 (COVID-19) in a patient with ankylosing spondylitis treated with secukinumab: A case-based review. Rheumatol Int 2020;40:1707-16. |
[Figure 1]
|
Search Pubmed for