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, ?<?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.Acknowledgments: This work was supported by Fundación Instituto de Investigación Marqués de Valdecilla (IDIVAL) (NVAL21/26)

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.</p

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

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

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.</p

Effects of Adding a Neurodynamic Mobilization to Motor Control Training in Patients with Lumbar Radiculopathy Due to Disc Herniation: A Randomized Clinical Trial

Objective The aim of the study was to investigate the effects of the inclusion of neural mobilization into a motor control exercise program on pain, related disability, neuropathic symptoms, straight leg raise, and pressure pain threshold in lumbar radiculopathy. Design This is a randomized clinical trial. Methods Individuals with low back pain, with confirmed disc herniation, and lumbar radiculopathy were randomly assigned to receive eight sessions of either neurodynamic mobilization plus motor control exercises (n = 16) or motor control exercises alone (n = 16). Outcomes included pain, disability, neuropathic symptoms, straight leg raise, and pressure pain threshold at baseline, after four visits, after eight visits, and after 2 mos. Results There were no between-groups differences for pain, related disability, or pressure pain threshold at any follow-up period because both groups get similar and large improvements. Patients assigned to the neurodynamic program group experienced better improvements in neuropathic symptoms and the straight leg raise compared with the motor control exercise group (P \u3c 0.01). Conclusions The addition of neurodynamic mobilization to a motor control exercise program leads to reductions in neuropathic symptoms and mechanical sensitivity (straight leg raise) but did not result in greater changes of pain, related disability, or pressure pain threshold over motor control exercises program alone in subjects with lumbar radiculopathy. Future trials are needed to further confirm these findings because between-groups differences did not reach clinically relevance

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

Abstract 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

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.Funding: Proyecto financiado por la convocatoria Next-Val 2021 de la Fundación Instituto de Investigación Marqués de Valdecilla (IDIVAL) and by a grant from the Novo Nordisk Foundation 0067235. Acknowledgements: The Center for Neuroplasticity and Pain (CNAP) is supported by the Danish National Research Foundation (DNRF121) and Novo Nordisk Foundation (NNF21OC0067235)

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 (?: 0.388) and CSI (?: 0.207). Further, CSI was associated with HADS-A (?: 0.269), TSK-11 (?: 0.165) and female gender (?: 0.413). As expected, HADS-A was associated with HADS-D (?: 0.598) and TSK-11 with PCS (?: 0.405). The only negative association was between sleep quality and EQ-5D-5L (?: ?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.Funding: Proyecto financiado por la convocatoria Next-Val 2021 de la Fundación Instituto de Investigación Marqués de Valdecilla (IDIVAL) and by a grant from the Novo Nordisk Foundation 0067235. The sponsors had no role in the design, collection, management, analysis, or interpretation of the data, draft, review, or approval of the manuscript or its content. The authors were responsible for the decision to submit the manuscript for publication, and the sponsor did not participate in this decision.Acknowledgments: The Center for Neuroplasticity and Pain (CNAP) is supported by the Danish National Research Foundation (DNRF121) and Novo Nordisk Foundation (NNF21OC0067235)