Widespread Pressure Pain Hyperalgesia Is Not Associated with Morphological Changes of the Wrist Extensor Tendon in Unilateral Lateral Epicondylalgia: A Case-Control Study.

OBJECTIVE: The aims of the current study were to investigate the presence of widespread pressure hyperalgesia, the presence of structural changes in the wrist extensor tendon and muscle, and their association in people with lateral epicondylalgia (LE). METHODS: Thirty-seven patients with LE (43% women; mean age = 45.5 [SD = 9.5] years) and 37 controls matched for age and sex and free of pain participated in this study. Pressure pain thresholds (PPTs) were assessed bilaterally over the symptomatic area (elbow), 2 segment-related areas (C5-C6 joint, second intermetacarpal space), and 1 remote area (tibialis anterior) in a blinded design. Ultrasound measurements (eg, cross-sectional area, thickness, width) of the common wrist extensor tendon and extensor carpi radials brevis muscle as well as thickness of supinator muscle were assessed. RESULTS: Patients with LE exhibited lower PPTs bilaterally at all points and lower PPTs at the lateral epicondyle and second intermetacarpal space at the symptomatic side as compared to the nonsymptomatic side (η2 from 0.123-0.369; large effects). Patients exhibited higher cross-sectional area and width of the common wrist extensor tendon (η2 from 0.268-0.311; large effects) than controls bilaterally, whereas tendon thickness was also higher (η2 = 0.039; small effects) on the painful side than on the nonpainful side. CONCLUSIONS: This study reported bilateral widespread pressure pain hyperalgesia and morphological changes in the tendon, but not the muscle, in LE. Pressure pain sensitivity and morphological changes were not associated in individuals with LE. IMPACT STATEMENT: Management of LE should consider altered nociceptive pain processing and structural tendon changes as 2 different phenomena in patients with LE.

Effects of Adding Four Sessions of Ultrasound-Guided Percutaneous Electrical Nerve Stimulation to an Exercise Program in Patients with Shoulder Pain: A Randomized Controlled Trial.

Objective: Percutaneous electrical nerve stimulation (PENS) appears to be effective for the treatment of musculoskeletal pain. The aim of this trial was to investigate the effects on disability and pain, as well as on the psychological aspects of adding PENS into an exercise program in patients with subacromial pain syndrome. Methods: A randomized, parallel-group clinical trial was conducted. Sixty patients with subacromial pain were allocated into exercise alone (n = 20), exercise plus PENS (n = 20), or exercise plus placebo PENS (n = 20) groups. Patients in all groups performed an exercise program twice daily for 3 weeks. Patients allocated to the PENS group also received four sessions of ultrasound-guided PENS targeting the axillar and suprascapular nerves. Patients allocated to the exercise plus placebo PENS received a sham PENS application. The primary outcome was related disability (Disabilities of the Arm, Shoulder, and Hand, DASH). Secondary outcomes included mean pain, anxiety levels, depressive symptoms, and sleep quality. They were assessed at baseline, one week after, and one and three months after. An analysis was performed using intention-to-treat with mixed-models ANCOVAs. Results: The results revealed no between-group differences for most outcomes (related disability: F = 0.292, p = 0.748, n2p = 0.011; anxiety: F = 0.780, p = 0.463, n2p = 0.027; depressive symptoms: F = 0.559, p = 0.575, n2p = 0.02; or sleep quality: F = 0.294, p = 0.747, n2p = 0.01); both groups experienced similar changes throughout the course of this study. Patients receiving exercise plus PENS exhibited greater improvement in shoulder pain at one month than those in the exercise (Δ -1.2, 95%CI -2.3 to -0.1) or the placebo (Δ -1.3, 95%CI -2.5 to -0.1) groups. Conclusions: The inclusion of four sessions of ultrasound-guided PENS targeting the axillar and suprascapular nerves into an exercise program did not result in better outcomes in our sample of patients with subacromial pain syndrome at one and three months after treatment.

Trajectory of post-COVID brain fog, memory loss, and concentration loss in previously hospitalized COVID-19 survivors: the LONG-COVID-EXP multicenter study.

Objective: This study aimed to apply Sankey plots and exponential bar plots for visualizing the trajectory of post-COVID brain fog, memory loss, and concentration loss in a cohort of previously hospitalized COVID-19 survivors. Methods: A sample of 1,266 previously hospitalized patients due to COVID-19 during the first wave of the pandemic were assessed at 8.4 (T1), 13.2 (T2), and 18.3 (T3) months after hospital discharge. They were asked about the presence of the following self-reported cognitive symptoms: brain fog (defined as self-perception of sluggish or fuzzy thinking), memory loss (defined as self-perception of unusual forgetfulness), and concentration loss (defined as self-perception of not being able to maintain attention). We asked about symptoms that individuals had not experienced previously, and they attributed them to the acute infection. Clinical and hospitalization data were collected from hospital medical records. Results: The Sankey plots revealed that the prevalence of post-COVID brain fog was 8.37% (n = 106) at T1, 4.7% (n = 60) at T2, and 5.1% (n = 65) at T3, whereas the prevalence of post-COVID memory loss was 14.9% (n = 189) at T1, 11.4% (n = 145) at T2, and 12.12% (n = 154) at T3. Finally, the prevalence of post-COVID concentration loss decreased from 6.86% (n = 87) at T1, to 4.78% (n = 60) at T2, and to 2.63% (n = 33) at T3. The recovery exponential curves show a decreasing trend, indicating that these post-COVID cognitive symptoms recovered in the following years after discharge. The regression models did not reveal any medical record data associated with post-COVID brain fog, memory loss, or concentration loss in the long term. Conclusion: The use of Sankey plots shows a fluctuating evolution of post-COVID brain fog, memory loss, or concentration loss during the first years after the infection. In addition, exponential bar plots revealed a decrease in the prevalence of these symptoms during the first years after hospital discharge. No risk factors were identified in this cohort.

Sensitization-associated and neuropathic-associated symptoms in patients with unilateral lateral elbow tendinopathy: an exploratory study.

OBJECTIVES: We evaluate the presence of sensitization-associated symptoms and neuropathic pain features and identify if there is an association between these symptoms and pressure pain sensitivity, pain, and related-disability in lateral elbow tendinopathy. METHODS: Thirty-seven (43% women, age: 45.5 ± 9.5 years) patients with lateral elbow tendinopathy completed: demographic (i.e. age, height, and weight); clinical (i.e. pain history, pain intensity, and Disabilities of the Arm, Shoulder and Hand); and psychophysical (i.e. pressure pain thresholds at the elbow, cervical spine, hand, and leg) outcomes, and the Central Sensitization Inventory and Self-administered Leeds Assessment of Neuropathic Symptoms and Signs questionnaires. Step-wise multiple linear regression models were performed to identify predictors of sensitization- or neuropathic-associated symptoms. RESULTS: Six (16%) patients exhibited sensitization-associated symptoms (mean: 46.5, SD: 6.1), whereas 13 (35%) patients showed neuropathic-associated symptoms (mean: 13.5; SD: 1.4). Sensitization-associated symptoms were positively associated with neuropathic-associated symptoms (r = 0.538, P = .001) and negatively associated with pressure pain thresholds at the leg (r = -0.378, P = .021). Neuropathic-associated symptoms were positively associated with related-disability (r = 0.479, P = .003) and negatively associated with pressure pain threshold at the elbow (r = -0.394, P = .017). Stepwise regression analyses revealed that neuropathic-like symptoms explained 26.8% of the variance of sensitization symptoms (r2: 0.268), whereas pressure pain threshold at the elbow explained an additional 6.6% to neuropathic-like symptoms (r2: 0.334). CONCLUSION: This explorative study identified sensitization- and neuropathic-associated symptoms in 16% and 35% of the people with lateral elbow tendinopathy. Sensitization- and neuropathic-associated symptoms were associated. Pressure pain sensitivity at the elbow (peripheral sensitization) was associated with neuropathic -associated symptoms.

Pressure Pain Hypersensitivity and Ultrasound Changes in the Radial Nerve in Patients with Unilateral Lateral Epicondylalgia: A Case-Control Study.

Some authors have proposed the potential role of the radial nerve in lateral epicondylalgia. The aims of this study were to investigate the presence of pressure pain hyperalgesia and nerve swelling (increased cross-sectional area) assessed with ultrasound imaging on the radial nerve in people with lateral epicondylalgia, and to investigate if an association exists between pressure pain sensitivity and cross-sectional area. A total of 37 patients with lateral epicondylalgia (43% women, age: 45.5 ± 9.5 years) and 37 age- and sex-matched pain-free controls were recruited for participation. Pressure pain thresholds (PPTs) were assessed bilaterally on the radial nerve at the spiral groove, the arcade of Frohse, and the anatomic snuffbox in a blinded design. Further, the cross-sectional area of the radial nerve at the spiral groove and antecubital fossa was also assessed. The results demonstrated lower PPTs on the radial nerve of the affected side in individuals with lateral epicondylalgia as compared with the unaffected side (p < 0.01) and with both sides in healthy controls (p < 0.001). Additionally, the cross-sectional area of the radial nerve on the affected side in patients was higher compared with the unaffected side (p < 0.01) and both sides in healthy controls (p < 0.001). The cross-sectional area of the radial nerve at the spiral groove was negatively associated with PPTs over the radial nerve at the spiral groove (r = -0.496, p = 0.002) and positively associated with function (r = 0.325, p = 0.045). Our findings revealed generalized pressure pain hyperalgesia and also nerve swelling of the radial nerve in people with lateral epicondylalgia, suggesting the presence of a widespread sensitization of nerve tissues in this population. The radial nerve could represent a potential peripheral drive to initial and maintain altered pain processing in lateral epicondylalgia.

Trajectory of Post-COVID Self-Reported Fatigue and Dyspnoea in Individuals Who Had Been Hospitalized by COVID-19: The LONG-COVID-EXP Multicenter Study.

Fatigue and dyspnoea are common post-COVID symptoms. The aim of this study was to apply Sankey plots and exponential bar plots for visualizing the evolution and trajectory of post-COVID fatigue and dyspnoea symptoms in a cohort of previously hospitalized COVID-19 survivors. A total of 1266 previously hospitalized patients due to COVID-19 participated in this multicentre study. They were assessed at hospital admission (T0), 8.4 months (T1), 13.2 months (T2) and 18.3 months (T3) after hospital discharge and were asked about the presence of self-reported fatigue or dyspnoea symptoms. Fatigue was defined as a self-perceived feeling of constant tiredness and/or weakness whereas dyspnoea was defined as a self-perceived feeling of shortness of breath at rest. We specifically asked for fatigue and dyspnoea that participants attributed to the infection. Clinical/hospitalization data were collected from hospital medical records. The prevalence of post-COVID fatigue was 56.94% (n = 721) at T1, 52.31% (n = 662) at T2 and 42.66% (n = 540) at T3. The prevalence of dyspnoea at rest decreased from 28.71% (n = 363) at hospital admission (T0), to 21.29% (n = 270) at T1, to 13.96% (n = 177) at T2 and 12.04% (n = 153) at T3. The Sankey plots revealed that 469 (37.08%) and 153 (12.04%) patients exhibited fatigue and dyspnoea at all follow-up periods. The recovery exponential curves show a decreased prevalence trend, showing that fatigue and dyspnoea recover the following three years after hospitalization. The regression models revealed that the female sex and experiencing the symptoms (e.g., fatigue, dyspnoea) at T1 were factors associated with the presence of post-COVID fatigue or dyspnoea at T2 and T3. The use of Sankey plots shows a fluctuating evolution of post-COVID fatigue and dyspnoea during the first two years after infection. In addition, exponential bar plots revealed a decreased prevalence of these symptoms during the first years after. The female sex is a risk factor for the development of post-COVID fatigue and dyspnoea.

Prevalence of Self-Reported Anosmia and Ageusia in Elderly Patients Who Had Been Previously Hospitalized by SARS-CoV-2: The LONG-COVID-EXP Multicenter Study.

We explored two different graph methods for visualizing the prevalence of self-reported post-COVID anosmia and ageusia in a large sample of individuals who had been previously hospitalized in five different hospitals. A cohort of 1266 previously hospitalized COVID-19 survivors participated. Participants were assessed at hospitalization (T0) and at three different follow-up periods: 8.4 (T1), 13.2 (T2), and 18.3 (T3) months after hospital discharge. They were asked about the presence of self-reported anosmia and ageusia that they attributed to infection. Anosmia was defined as a self-perceived feeling of complete loss of smell. Ageusia was defined as a self-perceived feeling of complete loss of taste. Data about hospitalization were recorded from medical records. The results revealed that the prevalence of anosmia decreased from 8.29% (n = 105) at hospitalization (T0), to 4.47% (n = 56) at T1, to 3.27% (n = 41) at T2, and 3.35% (n = 42) at T3. Similarly, the prevalence of ageusia was 7.10% (n = 89) at the onset of SARS-CoV-2 infection (T0), but decreased to 3.03% (n = 38) at T1, to 1.99% (n = 25) at T2, and 1.36% (n = 17) at T3. The Sankey plots showed that only 10 (0.8%) and 11 (0.88%) patients exhibited anosmia and ageusia throughout all the follow-ups. The exponential curves revealed a progressive decrease in prevalence, demonstrating that self-reported anosmia and ageusia improved in the years following hospitalization. The female sex (OR4.254, 95% CI 1.184-15.294) and sufferers of asthma (OR7.086, 95% CI 1.359-36.936) were factors associated with the development of anosmia at T2, whereas internal care unit admission was a protective factor (OR0.891, 95% CI 0.819-0.970) for developing anosmia at T2. The use of a graphical method, such as a Sankey plot, shows that post-COVID self-reported anosmia and ageusia exhibit fluctuations during the first years after SARS-CoV-2 infection. Additionally, self-reported anosmia and ageusia also show a decrease in prevalence during the first years after infection, as expressed by exponential bar plots. The female sex was associated with the development of post-COVID anosmia, but not ageusia, in our cohort of elderly patients previously hospitalized due to COVID-19.

Clustering analysis reveals different profiles associating long-term post-COVID symptoms, COVID-19 symptoms at hospital admission and previous medical co-morbidities in previously hospitalized COVID-19 survivors.

PURPOSE: To identify subgroups of COVID-19 survivors exhibiting long-term post-COVID symptoms according to clinical/hospitalization data by using cluster analysis in order to foresee the illness progress and facilitate subsequent prognosis. METHODS: Age, gender, height, weight, pre-existing medical comorbidities, Internal Care Unit (ICU) admission, days at hospital, and presence of COVID-19 symptoms at hospital admission were collected from hospital records in a sample of patients recovered from COVID-19 at five hospitals in Madrid (Spain). A predefined list of post-COVID symptoms was systematically assessed a mean of 8.4 months (SD 15.5) after hospital discharge. Anxiety/depressive levels and sleep quality were assessed with the Hospital Anxiety and Depression Scale and Pittsburgh Sleep Quality Index, respectively. Cluster analysis was used to identify groupings of COVID-19 patients without introducing any previous assumptions, yielding three different clusters associating post-COVID symptoms with acute COVID-19 symptoms at hospital admission. RESULTS: Cluster 2 grouped subjects with lower prevalence of medical co-morbidities, lower number of COVID-19 symptoms at hospital admission, lower number of post-COVID symptoms, and almost no limitations with daily living activities when compared to the others. In contrast, individuals in cluster 0 and 1 exhibited higher number of pre-existing medical co-morbidities, higher number of COVID-19 symptoms at hospital admission, higher number of long-term post-COVID symptoms (particularly fatigue, dyspnea and pain), more limitations on daily living activities, higher anxiety and depressive levels, and worse sleep quality than those in cluster 2. CONCLUSIONS: The identified subgrouping may reflect different mechanisms which should be considered in therapeutic interventions.

Sensitization symptoms are associated with psychological and cognitive variables in COVID-19 survivors exhibiting post-COVID pain.

OBJECTIVE: To investigate the association between demographic, clinical, psychological, cognitive, and health-related variables and the Central Sensitization Inventory (CSI) in previously hospitalized COVID-19 survivors exhibiting "de novo" post-COVID pain. METHODS: Seventy-seven (n = 77) COVID-19 survivors with "de novo" post-COVID pain completed demographic (age, height, and weight), clinical (duration and intensity of the pain), psychological (depressive/anxiety levels and sleep quality), cognitive (catastrophizing and kinesiophobia levels), and health-related quality of life variables as well as the CSI. A multivariable correlation analysis was conducted to determine the association between variables, and a stepwise multiple linear regression model was performed to identify CSI predictors. RESULTS: Patients were assessed a mean of 6.0 (SD 0.8) months after hospital discharge. Twenty-six (33.7%) individuals showed indications of sensitization-associated symptoms (CSI score ≥40 points). The CSI score was positively associated with pain intensity (r: 0.371), anxiety (r: 0.784), depressive (r: 0.709), catastrophizing (r: 0.620), and kinesiophobia (r: 0.359) levels (all, p < 0.001). The stepwise regression analysis revealed that 60.2% of CSI was explained by anxiety levels and pain intensity. CONCLUSION: This study found that psychological and cognitive variables were associated with the CSI score in previously hospitalized COVID-19 survivors with "de novo" post-COVID pain. Anxiety levels and the intensity of pain symptoms were independently associated with CSI score suggesting a significant overlap with psychological construct. The "de novo" post-COVID pain association with CSI may indicate changes in the pain processing important for managing the pain.

Exploring the trajectory curve of long-term musculoskeletal post-COVID pain symptoms in hospitalized COVID-19 survivors: a multicenter study.

ABSTRACT: This multicenter cohort study investigated the prevalence of musculoskeletal post-COVID pain during the first year after the infection with mosaic plots and an exponential bar plot model and its associated risk factors. Patients hospitalized because of COVID-19 in 5 hospitals of Madrid (Spain) were scheduled for a telephone interview at 2 follow-up periods after hospitalization for collecting data about musculoskeletal post-COVID pain. Hospitalization and clinical data were collected from hospital medical records. From 2000 patients initially recruited, 1593 (44.6% women, age: 61 ± 15 years) were assessed at T0 (hospital admission), T1 (mean: 8.0 ± 1.5 months after discharge), and T2 (mean: 13.2 ± 1.5 months after discharge). The prevalence of musculoskeletal pain (myalgia) was 30.3% (n = 483) at T0, increased to 43.4% (n = 692) at T1, and decreased to 37.8% (n = 603) at T2. The trajectory curve revealed a decreasing prevalence trend of musculoskeletal post-COVID pain the following years after hospitalization. According to the presence of pre-existing pain symptoms, the prevalence of new-onset post-COVID pain was 75.9%. Female sex (odds ratio [OR] 1.593, 95% confidence interval [CI] 1.148-2.211), history of musculoskeletal pain (OR 1.591, 95% CI 1.211-2.07), the presence of myalgia (OR 1.371, 95% CI 1.032-1.821) or headache (OR 2.278, 95% CI 1.622-3.199) at hospitalization, the days of hospitalization (OR 1.013, 95% CI 1.000-1.025), and the presence of post-COVID pain at T1 (OR 11.02, 95% CI 8.493-14.305) were factors associated with musculoskeletal post-COVID pain 1 year after hospitalization. In conclusion, musculoskeletal post-COVID pain remains highly prevalent 1 year after hospitalization. Female sex, previous history of pain symptoms, pain symptoms at onset, and days at hospital were factors associated with musculoskeletal post-COVID pain 1 year after hospitalization.

Post-COVID-19 Symptoms 2 Years After SARS-CoV-2 Infection Among Hospitalized vs Nonhospitalized Patients.

Importance: Identification of long-term post-COVID-19 symptoms among hospitalized and nonhospitalized patients is needed. Objective: To compare the presence of post-COVID-19 symptoms 2 years after acute SARS-CoV-2 infection between hospitalized and nonhospitalized patients. Design, Setting, and Participants: A cross-sectional cohort study was conducted at 2 urban hospitals and general practitioner centers from March 20 to April 30, 2020, among 360 hospitalized patients and 308 nonhospitalized patients with acute SARS-CoV-2 infection during the first wave of the pandemic. Follow-up was conducted 2 years later. Main Outcomes and Measures: Participants were scheduled for a telephone interview 2 years after acute infection. The presence of post-COVID-19 symptoms was systematically assessed, with particular attention to symptoms starting after infection. Hospitalization and clinical data were collected from medical records. Between-group comparisons and multivariate logistic regressions were conducted. Results: A total of 360 hospitalized patients (162 women [45.0%]; mean [SD] age, 60.7 [16.1] years) and 308 nonhospitalized patients (183 women [59.4%]; mean [SD] age, 56.7 [14.7] years) were included. Dyspnea was more prevalent at the onset of illness among hospitalized than among nonhospitalized patients (112 [31.1%] vs 36 [11.7%]; P < .001), whereas anosmia was more prevalent among nonhospitalized than among hospitalized patients (66 [21.4%] vs 36 [10.0%]; P = .003). Hospitalized patients were assessed at a mean (SD) of 23.8 (0.6) months after hospital discharge, and nonhospitalized patients were assessed at a mean (SD) of 23.4 (0.7) months after the onset of symptoms. The number of patients who exhibited at least 1 post-COVID-19 symptom 2 years after infection was 215 (59.7%) among hospitalized patients and 208 (67.5%) among nonhospitalized patients (P = .01). Among hospitalized and nonhospitalized patients, fatigue (161 [44.7%] vs 147 [47.7%]), pain (129 [35.8%] vs 92 [29.9%]), and memory loss (72 [20.0%] vs 49 [15.9%]) were the most prevalent post-COVID-19 symptoms 2 years after SARS-CoV-2 infection. No significant differences in post-COVID-19 symptoms were observed between hospitalized and nonhospitalized patients. The number of preexisting medical comorbidities was associated with post-COVID-19 fatigue (odds ratio [OR], 1.93; 95% CI, 1.09-3.42; P = .02) and dyspnea (OR, 1.91; 95% CI, 1.04-3.48; P = .03) among hospitalized patients. The number of preexisting medical comorbidities (OR, 3.75; 95% CI, 1.67-8.42; P = .001) and the number of symptoms at the onset of illness (OR, 3.84; 95% CI, 1.33-11.05; P = .01) were associated with post-COVID-19 fatigue among nonhospitalized patients. Conclusions and Relevance: This cross-sectional study suggested the presence of at least 1 post-COVID-19 symptom in 59.7% of hospitalized patients and 67.5% of nonhospitalized patients 2 years after infection. Small differences in symptoms at onset of COVID-19 were identified between hospitalized and nonhospitalized patients. Post-COVID-19 symptoms were similar between hospitalized and nonhospitalized patients; however, lack of inclusion of uninfected controls limits the ability to assess the association of SARS-CoV-2 infection with overall and specific post-COVID-19 symptoms 2 years after acute infection. Future studies should include uninfected control populations.

Psychometric Properties of the Functional Impairment Checklist (FIC) as a Disease-Specific Patient-Reported Outcome Measure (PROM) in Previously Hospitalized COVID-19 Survivors with Long-COVID.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is associated with a plethora of long-lasting symptoms (long-COVID). The presence of long-COVID symptoms causes decreased functionality. This study described the psychometric properties of the Functional Impairment Checklist (FIC), a disease-specific patient-reported outcome measure (PROM) used for evaluating the functional consequences of SARS in previously hospitalized COVID-19 survivors with long-COVID symptoms. The LONG-COVID-EXP-CM is a multicenter cohort study including patients hospitalized with COVID-19 during the first wave of the pandemic in five hospitals in Madrid. A total of 1969 (age: 61 ± 16 years, 46.4% women) COVID-19 survivors with long-COVID completed the FIC at a long-term follow-up after hospitalization (mean: 8.4 ± 1.5 months). Internal consistency (Cronbach alpha value), reliability (item-internal consistency, item-discriminant validity), construct validity (exploratory factor analysis), floor effect and ceiling effect were calculated. The mean time for fulfilling the FIC was 62 ± 11 s. The Cronbach's alpha values reflecting the internal consistency reliability were 0.864 for FIC-symptoms and 0.845 for FIC-disability. The correlation coefficient between the FIC-symptoms and FIC-disability scale was good (r: 0.676). The ceiling effect ranged from 2.29% to 9.02%, whereas the floor effect ranged from 38.56% to 80.19%. The exploratory factor analysis showed factor loadings from 0.514 to 0.866, supporting good construct validity. Women exhibited greater limitations in all physical symptoms and disability-related domains of the FIC compared with men (all, p < 0.001). Further, younger patients (those aged <45 years) self-reported lower physical symptoms and disability-related domains than older patients. In conclusion, this study indicates that the FIC has good psychometric properties to be used as a specific-disease PROM to measure function and disability in COVID-19 survivors with long-COVID.

Prevalence of Musculoskeletal Post-COVID Pain in Hospitalized COVID-19 Survivors Depending on Infection with the Historical, Alpha or Delta SARS-CoV-2 Variant.

We compared the prevalence of musculoskeletal post-COVID pain between previously hospitalized COVID-19 survivors infected with the historical, Alpha or Delta SARS-CoV-2 variant. Data about musculoskeletal post-COVID pain were systematically collected through a telephone interview involving 201 patients who had survived the historical variant, 211 who had survived the Alpha variant and 202 who had survived the Delta variant six months after hospital discharge. Participants were recruited from non-vaccinated individuals hospitalized due to SARS-CoV-2 infection in one hospital of Madrid (Spain) during three different waves of the pandemic (historical, Alpha or Delta variant). Hospitalization and clinical data were collected from hospital medical records. In addition, anxiety/depressive levels and sleep quality were also assessed. The prevalence of musculoskeletal post-COVID pain was higher (p = 0.003) in patients infected with the historical variant (47.7%) than in those infected with the Alpha (38.3%) or Delta (41%) variants. A significantly (p = 0.002) higher proportion of individuals infected with the historical variant reported generalized pain (20.5%) when compared with those infected with the other variants. The prevalence of new-onset post-COVID musculoskeletal pain reached 80.1%, 75.2% and 79.5% of patients infected with the historical, Alpha or Delta variants, respectively. No specific risk factors for developing post-COVID pain were identified depending on the SARS-CoV-2 variant. In conclusion, this study found that musculoskeletal post-COVID pain is highly prevalent in COVID-19 survivors six months after hospital discharge, with the highest prevalence and most generalized pain symptoms in individuals infected with the historical variant. Approximately 50% developed "de novo" post-COVID musculoskeletal pain symptoms.

Psychometric Properties of the Hospital Anxiety and Depression Scale (HADS) in Previously Hospitalized COVID-19 Patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is associated with psychological/emotional disturbances. This study aimed to assess internal consistency, reliability, and construct validity of the Hospital Anxiety and Depressive Scale (HADS), as a patient-reported outcome measure (PROM) for evaluating emotional consequences of SARS-CoV-2 in hospitalized COVID-19 survivors with long COVID. The LONG-COVID-EXP-CM is a multicenter cohort study including patients hospitalized by COVID-19 during the first wave of the pandemic in five hospitals in Madrid. A total of 1969 (age: 61 ± 16 years, 46.5% women) COVID-19 survivors experiencing post-COVID symptoms a mean of 8.4 ± 1.5 months after hospital discharge completed HADS. Internal consistency (Cronbach α), reliability (item-internal consistency, item-discriminant validity), construct validity (confirmatory factor analysis), and floor effect and ceiling effect were calculated. The mean time for fulfilling HADS was 65 ± 12 s. A ceiling effect ranging from 1.99% to 13.74% and a floor effect ranging from 43.05% to 77.77% was observed. Based on the item-scale correlation coefficients, the Cronbach's alpha values reflecting the internal consistency reliability were 0.890 for the anxiety scale (HADS-A) and 0.856 for the depressive scale (HADS-D) The correlation coefficient between HADS-A and HADS-D scores was excellent (r: 0.878). The confirmatory factor analysis revealed that five out of the seven fitness indexes were excellent: CFI = 0.969, NNFI = 0.963; TLI = 0.963; AGFI = 0.951; GFI = 0.972), supporting good construct validity. In conclusion, this study indicates that both anxiety and depressive symptoms scales of HADS had overall good psychometric properties to be used for assessing psychological and emotional stress in COVID-19 survivors with long COVID.

Associated-Onset Symptoms and Post-COVID-19 Symptoms in Hospitalized COVID-19 Survivors Infected with Wuhan, Alpha or Delta SARS-CoV-2 Variant.

This study compared associated-symptoms at the acute phase of infection and post-COVID-19 symptoms between individuals hospitalized with the Wuhan, Alpha or Delta SARS-CoV-2 variant. Non-vaccinated individuals hospitalized because of SARS-CoV-2 infection in one hospital during three different waves of the pandemic (Wuhan, Alpha or Delta) were scheduled for a telephone interview. The presence of post-COVID-19 symptoms was systematically assessed. Hospitalization and clinical data were collected from medical records. A total of 201 patients infected with the Wuhan variant, 211 with the Alpha variant and 202 with Delta variant were assessed six months after hospitalization. Patients infected with the Wuhan variant had a greater number of symptoms at hospital admission (higher prevalence of fever, dyspnea or gastrointestinal problems) than those infected with Alpha or Delta variant (p < 0.01). A greater proportion of patients infected with the Delta variant reported headache, anosmia or ageusia as onset symptoms (p < 0.01). The mean number of post-COVID-19 symptoms was higher (p < 0.001) in individuals infected with the Wuhan variant (mean: 2.7 ± 1.3) than in those infected with the Alpha (mean: 1.8 ± 1.1) or Delta (mean: 2.1 ± 1.5) variant. Post-COVID-19 dyspnea was more prevalent (p < 0.001) in people infected with the Wuhan variant, whereas hair loss was higher in those infected with the Delta variant (p = 0.002). No differences in post-COVID-19 fatigue by SARS-CoV-2 variant were found (p = 0.594). Differences in COVID-19 associated onset symptoms and post-COVID-19 dyspnea were observed depending on the SARS-CoV-2 variant. The presence of fatigue was a common post-COVID-19 symptom to all SARS-CoV-2 variants.

Understanding Sensitization, Cognitive and Neuropathic Associated Mechanisms behind Post-COVID Pain: A Network Analysis.

This study aimed to describe a network including demographic, sensory-related, psychological/cognitive and other variables in individuals with post-COVID pain after hospitalization. Demographic (i.e., age, height, weight, months with symptoms), sensory-related (Central Sensitization Inventory -CSI-, Self-Report Leeds Assessment of Neuropathic Symptoms -S-LANSS-, PainDETECT), psychological/cognitive (Hospital Anxiety and Depression Scale -HADS-A/HADS-D-, Pain Catastrophizing Scale -PCS-, Tampa Scale for Kinesiophobia -TSK-11-) and other (sleep quality and health-related quality of life -EQ/5D/5L) variables were collected in 146 COVID-19 survivors with post-COVID pain. A network analysis was conducted to quantify the adjusted correlations between the modelled variables, and to assess their centrality indices (i.e., the connectivity with other symptoms in the network and the importance in the system modelled as network). The network revealed associations between sensory-related and psychological/cognitive variables. PainDETECT was associated with S-LANSS (ρ: 0.388) and CSI (ρ: 0.207). Further, CSI was associated with HADS-A (ρ: 0.269), TSK-11 (ρ: 0.165) and female gender (ρ: 0.413). As expected, HADS-A was associated with HADS-D (ρ: 0.598) and TSK-11 with PCS (ρ: 0.405). The only negative association was between sleep quality and EQ-5D-5L (ρ: -0.162). Gender was the node showing the highest strength, closeness, and betweenness centralities. In addition, CSI was the node with the second highest closeness and betweenness centralities, whereas HADS-D was the node with the second highest strength centrality. This is the first study applying a network analysis for phenotyping post-COVID pain. Our findings support a model where sensitization-associated symptoms, neuropathic phenotype, and psychological aspects are connected, reflecting post-COVID pain as a nociplastic pain condition. In addition, post-COVID pain is gender dependent since female sex plays a relevant role. Clinical implications of current findings, e.g., developing treatments targeting these mechanisms, are discussed.

Psychometric properties of the Spanish version of the EuroQol-5D-5L in previously hospitalized COVID-19 survivors with long COVID.

The EuroQol 5-dimensions 5-levels (EQ-5D-5L) is a generic patient-reported outcome measures (PROM) used for evaluating health-related quality of life (HRQoL). No data on its psychometric properties in COVID-19 survivors is available. We aimed to describe internal consistency, test-retest reliability, and construct validity of the EQ-5D-5L in people with long-COVID. Ninety-three (n = 93) individuals previously hospitalized due to COVID-19 with post-COVID symptoms completed the EQ-5D-5L questionnaire twice one year after hospital discharge in a three-week interval. Internal consistency (Cronbach alpha and Omega value), test-retest reliability (kappa and ICC2,1) and construct validity (factor analysis), and floor/ceiling effects were calculated. No ceiling effect was observed in any dimension whereas the floor effect ranged from 53.76 to 94.62%. The overall Cronbach's α value was 0.75 (95%CI 0.64-0.83) and the Omega ω value was 0.77 (95%CI 0.66-0.84), showing good internal consistency of the questionnaire. Further, Cronbach's alpha values the of each dimension ranged from 0.63 to 0.77 whereas those for Omega values ranged from 0.70 to 0.79. The test-retest reliability of the total score was excellent (ICC2,1 0.86, 95%CI 0.798-0.911). The agreement percentage ranged from 85.13 to 96.77%; but kappa coefficients ranged from fair (κ: 0.37) to good (κ: 0.61). The factor analysis showed factor loadings from 0.585 to 0.813 supporting good construct validity. The EQ-5D-5L has good psychometric properties to be used as a PROM to assess HRQoL in hospitalized COVID-19 survivors with long-COVID.

Prevalence of Neuropathic Component in Post-COVID Pain Symptoms in Previously Hospitalized COVID-19 Survivors.

Objectives: To investigate the prevalence of neuropathic pain symptoms and to analyze the correlation between neuropathic symptoms with pain-related, psychological, and cognitive variables in COVID-19 survivors exhibiting "de novo" post-COVID pain. Methods: Seventy-seven (n = 77) previously hospitalized COVID-19 survivors presenting with post-COVID pain completed demographic (such as age, height, and weight), pain-related (the duration and intensity of pain), psychological (depressive/anxiety levels), and cognitive (catastrophizing and kinesiophobia) variables. The Self-Report Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) questionnaire was also assessed. After conducting multivariable correlation analyses, a stepwise multiple linear regression model was performed to identify S-LANSS predictors. Results: Participants were assessed a mean of 6.0 (SD 0.8) months after hospital discharge. Nineteen (24.6%) exhibited neuropathic pain symptoms (S-LANSS score≥12 points). The S-LANSS score was positively associated with the duration of post-COVID pain (r: 0.262), anxiety levels (r: 0.275), and kinesiophobia level (r: 0.291) (all, P < 0.05). The stepwise regression analysis revealed that 12.8% of the S-LANSS variance was just explained by kinesiophobia. Conclusion: This study found that almost 25% of previously hospitalized COVID-19 survivors with "de novo" post-COVID pain reported a neuropathic pain component. The presence of neuropathic pain symptomatology was associated with more anxiety and kinesiophobia, but only kinesiophobia level was significantly associated explaining 12.8% of the variance of the S-LANSS score.