Multicentre study on the accuracy of lung ultrasound in the diagnosis and monitoring of respiratory sequelae in the medium and long term in patients with COVID-19.

Introduction: Lung ultrasound (LUS) has proven to be a more sensitive tool than radiography (X-ray) to detect alveolar-interstitial involvement in COVID-19 pneumonia. However, its usefulness in the detection of possible pulmonary alterations after overcoming the acute phase of COVID-19 is unknown. In this study we proposed studying the utility of LUS in the medium- and long-term follow-up of a cohort of patients hospitalized with COVID-19 pneumonia. Materials and methods: This was a prospective, multicentre study that included patients, aged over 18 years, at 3 ± 1 and 12 ± 1 months after discharge after treatment for COVID-19 pneumonia. Demographic variables, the disease severity, and analytical, radiographic, and functional clinical details were collected. LUS was performed at each visit and 14 areas were evaluated and classified with a scoring system whose global sum was referred to as the "lung score." Two-dimensional shear wave elastography (2D-SWE) was performed in 2 anterior areas and in 2 posterior areas in a subgroup of patients. The results were compared with high-resolution computed tomography (CT) images reported by an expert radiologist. Results: A total of 233 patients were included, of whom 76 (32.6%) required Intensive Care Unit (ICU) admission; 58 (24.9%) of them were intubated and non-invasive respiratory support was also necessary in 58 cases (24.9%). Compared with the results from CT images, when performed in the medium term, LUS showed a sensitivity (S) of 89.7%, specificity (E) 50%, and an area under the curve (AUC) of 78.8%, while the diagnostic usefulness of X-ray showed an S of 78% and E of 47%. Most of the patients improved in the long-term evaluation, with LUS showing an efficacy with an S of 76% and E of 74%, while the X-ray presented an S of 71% and E of 50%. 2D-SWE data were available in 108 (61.7%) patients, in whom we found a non-significant tendency toward the presentation of a higher shear wave velocity among those who developed interstitial alterations, with a median kPa of 22.76 ± 15.49) versus 19.45 ± 11.39; p = 0.1). Conclusion: Lung ultrasound could be implemented as a first-line procedure in the evaluation of interstitial lung sequelae after COVID-19 pneumonia.

Association of Kinesiophobia with Catastrophism and Sensitization-Associated Symptoms in COVID-19 Survivors with Post-COVID Pain

Pain symptoms after the acute phase of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are present in almost 50% of COVID-19 survivors. The presence of kinesiophobia is a risk factor which may promote and perpetuate pain. This study aimed to investigate variables associated with the presence of kinesiophobia in a sample of previously hospitalized COVID-19 survivors exhibiting post-COVID pain. An observational study was conducted in three urban hospitals in Spain, including one hundred and forty-six COVID-19 survivors with post-COVID pain. Demographic (age, weight, height), clinical (intensity and duration of pain), psychological (anxiety level, depressive level, sleep quality), cognitive (catastrophizing), sensitization-associated symptoms, and health-related quality of life variables were collected in 146 survivors with post-COVID pain, as well as whether they exhibited kinesiophobia. Stepwise multiple linear regression models were conducted to identify variables significantly associated with kinesiophobia. Patients were assessed a mean of 18.8 (SD 1.8) months after hospital discharge. Kinesiophobia levels were positively associated with anxiety levels (r: 0.356, p < 0.001), depression levels (r: 0.306, p < 0.001), sleep quality (r: 0.288, p < 0.001), catastrophism (r: 0.578, p < 0.001), and sensitization-associated symptoms (r: 0.450, p < 0.001). The stepwise regression analysis revealed that 38.1% of kinesiophobia variance was explained by catastrophism (r2 adj: 0.329, B = 0.416, t = 8.377, p < 0.001) and sensitization-associated symptoms (r2 adj: 0.381, B = 0.130, t = 3.585, p < 0.001). Kinesiophobia levels were associated with catastrophism and sensitization-associated symptoms in previously hospitalized COVID-19 survivors with post-COVID pain. Identification of patients at a higher risk of developing a higher level of kinesiophobia, associated with post-COVID pain symptoms, could lead to better therapeutic strategies.

Association of Kinesiophobia with Catastrophism and Sensitization-Associated Symptoms in COVID-19 Survivors with Post-COVID Pain.

Pain symptoms after the acute phase of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are present in almost 50% of COVID-19 survivors. The presence of kinesiophobia is a risk factor which may promote and perpetuate pain. This study aimed to investigate variables associated with the presence of kinesiophobia in a sample of previously hospitalized COVID-19 survivors exhibiting post-COVID pain. An observational study was conducted in three urban hospitals in Spain, including one hundred and forty-six COVID-19 survivors with post-COVID pain. Demographic (age, weight, height), clinical (intensity and duration of pain), psychological (anxiety level, depressive level, sleep quality), cognitive (catastrophizing), sensitization-associated symptoms, and health-related quality of life variables were collected in 146 survivors with post-COVID pain, as well as whether they exhibited kinesiophobia. Stepwise multiple linear regression models were conducted to identify variables significantly associated with kinesiophobia. Patients were assessed a mean of 18.8 (SD 1.8) months after hospital discharge. Kinesiophobia levels were positively associated with anxiety levels (r: 0.356, p < 0.001), depression levels (r: 0.306, p < 0.001), sleep quality (r: 0.288, p < 0.001), catastrophism (r: 0.578, p < 0.001), and sensitization-associated symptoms (r: 0.450, p < 0.001). The stepwise regression analysis revealed that 38.1% of kinesiophobia variance was explained by catastrophism (r2 adj: 0.329, B = 0.416, t = 8.377, p < 0.001) and sensitization-associated symptoms (r2 adj: 0.381, B = 0.130, t = 3.585, p < 0.001). Kinesiophobia levels were associated with catastrophism and sensitization-associated symptoms in previously hospitalized COVID-19 survivors with post-COVID pain. Identification of patients at a higher risk of developing a higher level of kinesiophobia, associated with post-COVID pain symptoms, could lead to better therapeutic strategies.

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.

Data-Driven Path Analytic Modeling to Understand Underlying Mechanisms in COVID-19 Survivors Suffering from Long-Term Post-COVID Pain: A Spanish Cohort Study.

Pain can be present in up to 50% of people with post-COVID-19 condition. Understanding the complexity of post-COVID pain can help with better phenotyping of this post-COVID symptom. The aim of this study is to describe the complex associations between sensory-related, psychological, and cognitive variables in previously hospitalized COVID-19 survivors with post-COVID pain, recruited from three hospitals in Madrid (Spain) by using data-driven path analytic modeling. Demographic (i.e., age, height, and weight), sensory-related (intensity or duration of pain, central sensitization-associated symptoms, and neuropathic pain features), psychological (anxiety and depressive levels, and sleep quality), and cognitive (catastrophizing and kinesiophobia) variables were collected in a sample of 149 subjects with post-COVID pain. A Bayesian network was used for structural learning, and the structural model was fitted using structural equation modeling (SEM). The SEM model fit was excellent: RMSEA < 0.001, CFI = 1.000, SRMR = 0.063, and NNFI = 1.008. The only significant predictor of post-COVID pain was the level of depressive symptoms (ß=0.241, p = 0.001). Higher levels of anxiety were associated with greater central sensitization-associated symptoms by a magnitude of ß=0.406 (p = 0.008). Males reported less severe neuropathic pain symptoms (-1.50 SD S-LANSS score, p < 0.001) than females. A higher level of depressive symptoms was associated with worse sleep quality (ß=0.406, p < 0.001), and greater levels of catastrophizing (ß=0.345, p < 0.001). This study presents a model for post-COVID pain where psychological factors were related to central sensitization-associated symptoms and sleep quality. Further, maladaptive cognitions, such as catastrophizing, were also associated with depression. Finally, females reported more neuropathic pain features than males. Our data-driven model could be leveraged in clinical trials investigating treatment approaches in COVID-19 survivors with post-COVID pain and can represent a first step for the development of a theoretical/conceptual framework for post-COVID pain.

Sensitization-Associated Post-COVID-19 Symptoms at 6 Months Are Not Associated with Serological Biomarkers at Hospital Admission in COVID-19 Survivors: A Secondary Analysis of a Cohort Study.

Individuals who survived coronavirus disease, 2019 (COVID-19), often have symptoms of sensitization, but the extent to which these symptoms relate to serological biomarkers remains unclear. Therefore, this secondary analysis evaluated the association between serological biomarkers at hospital admission with sensitization-associated post-COVID-19 symptoms in a sample of previously hospitalized COVID-19 survivors. Sixty-seven individuals hospitalized due to SARS-CoV-2 infection in one urban hospital of Madrid (Spain) during the first wave of the pandemic were assessed a mean of 6.0 (SD 0.8) months after hospital discharge. The Central Sensitization Inventory (CSI) was used as rough tool to estimate the presence of sensitization-associated post-COVID-19 symptoms (≥40/100 points). Levels of 16 serological biomarkers collected at hospital admission were obtained from medical records. Twenty-four (35.8%) patients reported sensitization-associated post-COVID-19 symptoms (CSI ≥ 40 points). Subjects reporting sensitization-associated symptoms had lower ferritin and hemoglobin levels than those not reporting sensitization-associated post-COVID-19 symptoms; however, these differences were small. We observed significant but small negative associations of the CSI score with ferritin (r: -0.251, p = 0.04) and hemoglobin (r: -0.292, p = 0.017) levels. No other significant difference was found. In conclusion, this secondary analysis did not find significant associations between the investigated serological biomarkers at hospital admission and sensitization-associated post-COVID-19 symptoms at 6 months after hospitalization in COVID-19 survivors.

The Self-Reported Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) and PainDETECT Questionnaires in COVID-19 Survivors with Post-COVID Pain.

This study aimed to analyze correlations between Self-Report Leeds Assessment of Neuropathic Symptoms (S-LANSS) and PainDETECT with proxies of sensitization, pain-related, or psychological/cognitive variables in coronavirus disease, 2019 (COVID-19) survivors exhibiting post-COVID pain. Demographic, clinical, psychological, cognitive, sensitization-associated symptoms, and health-related quality of life were collected in 146 survivors with post-COVID pain. The PainDETECT and S-LANSS questionnaires were used for assessing neuropathic pain-related symptoms. Patients were assessed with a mean of 18.8 (SD 1.8) months after hospitalization. Both questionnaires were positively associated with pain intensity (p < 0.05), anxiety (PainDETECT p < 0.05; S-LANSS p < 0.01), sensitization-associated symptoms (p < 0.01), catastrophism (p < 0.01), and kinesiophobia (p < 0.01) and negatively associated with quality of life (PainDETECT p < 0.05; S-LANSS p < 0.01). Depressive levels were associated with S-LANSS (p < 0.05) but not with PainDETECT. The stepwise regression analyses revealed that 47.2% of S-LANSS was explained by PainDETECT (44.6%), post-COVID pain symptoms duration (1.7%), and weight (1.1%), whereas 51.2% of PainDETECT was explained by S-LANSS (44.6%), sensitization-associated symptoms (5.4%), and anxiety levels (1.2%). A good convergent association between S-LANSS and PainDETECT was found. Additionally, S-LANSS was associated with symptom duration and weight whereas PainDETECT was associated with sensitization-associated symptoms and anxiety levels, suggesting that the two questionnaires evaluate different aspects of the neuropathic pain spectrum in post-COVID pain patients.

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.

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.

Pulmonary long-term consequences of COVID-19 infections after hospital discharge.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) survivors are reporting residual abnormalities after discharge from hospital. Limited information is available about this stage of recovery or the lingering effects of the virus on pulmonary function and inflammation. This study aimed to describe lung function in patients recovering from COVID-19 hospitalization and to identify biomarkers in serum and induced sputum samples from these patients. METHODS: Patients admitted to Spanish hospitals with laboratory-confirmed COVID-19 infection by a real-time PCR (RT-PCR) assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were recruited for this study. Each hospital screened their lists of discharged patients at least 45 days after symptom onset. SARS-CoV-2-infected patients were divided into mild/moderate and severe disease groups according to the severity of their symptoms during hospitalization. Patients' epidemiological and medical histories, comorbidities, chronic treatments, and laboratory parameters were evaluated. Pulmonary function tests, the standardized 6-minute walk test (6MWT) and chest computed tomography (CT) were also performed. The levels of proteases, their inhibitors, and shed receptors were measured in serum and induced sputum samples. RESULTS: A total of 100 patients with respiratory function tests were included in this study. The median number of days after the onset of symptoms was 104 (IQR 89.25, 126.75). COVID-19 was severe in 47% of patients (47/100). CT was normal in 48% of patients (48/100). Lung function was normal forced expiratory volume in one second (FEV1) ≥80%, forced vital capacity (FVC) ≥80%, FEV1/FVC ≥0.7, and diffusing capacity for carbon monoxide (DLCO) ≥80% in 92% (92/100), 94% (94/100), 100% (100/100) and 48% (48/100) of patients, respectively. Multivariate analysis showed that a DLCO <80% (OR 5.92; 95%CI 2.28-15.37; p < 0.0001) and a lower serum lactate dehydrogenase level (OR 0.98; 95%CI 0.97-0.99) were associated with the severe disease group of SARS-CoV-2 cases during hospital stay. CONCLUSIONS: A diffusion deficit (DLCO <80%) was still present after hospital discharge and was associated with the most severe SARS-CoV-2 cases.