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.

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.

[Immunological effectiveness of the nucleoside/nucleotide analog combinations, tenofovir + lamivudine, didanosine + lamivudine and tenofovir + didanosine, in patients with HIV infection and sustained viral suppression]. / Efectividad inmunológica de las combinaciones de análogos de nucleósidos/nucleótidos, tenofovir + lamivudina, didanosina + lamivudina y tenofovir + didanosina, en pacientes con infección por el VIH y supresión virológica mantenida.

BACKGROUND: Several recent studies have shown that the combination of ddI plus TDF can produce an unexpected drop in CD4 cell counts, even after correcting the ddI dose. OBJECTIVE: Comparative study of the immunological effectiveness of various once-daily NRTI backbones (ddI plus TDF, ddI plus 3TC or TDF plus 3TC) in antiretroviral-experienced HIV-infected patients achieving viral suppression (PCR, HIV-RNA < 50 copies/microl). METHODS: Prospective cohort study of 48 weeks' duration following viral load suppression with any of the NRTI combinations studied. The main outcome variable was the increase in CD4+ lymphocyte count from the time that viral load was undetectable or treatment was changed for simplification or toxicity (baseline) up to 48 weeks of follow-up. Differences between the assigned therapies were compared. The variables included in analysis were age, sex, risk group, HCV infection, clinical categories of HIV (CDC criteria), lowest CD4 cell count, reason for change of NRTI backbone, type of antiretroviral treatment (PI, NNRTI, or 3 NRTI) and duration of suppressed viral load. RESULTS. Regimens including ddI plus TDF showed significant decreases in CD4 cell counts with adjustments by type of HAART, reason for change, and duration of suppressed viral load. In patients treated with TDF + 3TC, CD4 count increased by 160 cel/microl (95% CI, 53-266) more than in patients treated with TDF + ddI; and in patients receiving ddI + 3TC, CD4+ count increased by 138 cel/microl (95% CI, 25-266) more than in patients receiving TDF + ddI. CONCLUSIONS: The ddI plus TDF backbone seems unadvisable because of the lower associated CD4 cell counts, and because it is poorer than the other options from the immunological standpoint.

Efectividad inmunologica de las combinaciones de analogos de nucleosidos / nucleotidos, tenofovir + lamivudina, didanosina + lamivudina y tenofovir + didanosina, en pacientes con infeccion por el VIH y supresion virologica mantenida / Immunological effectiveness of the nucleoside / nucleotide analog combinations, tenofovir + lamivudine, didanosine + lamivudine and tenofovir + didanosine, in patients with HIV infection and sustained viral suppression

Antecedentes. Recientemente, se ha comunicado en varios artículos que la combinación tenofovir (TDF) y didanosina (ddI) puede tener efecto paradójico en la respuesta inmunológica, incluso tras el ajuste de dosis de ddI. Objetivo. El objetivo de este trabajo es comparar en pacientes infectados por el virus de la inmunodeficiencia humana (VIH), con supresión virológica (reacción en cadena de la polimerasa [PCR] ARN-VIH < 50 copias/ìl), la efectividad inmunológica de ddI + TDF frente a ddI + lamivudina (3TC) o TDF + 3TC. Métodos. Estudio de cohortes prospectivo de 48 semanas de duración tras supresión virológica con cualquiera de las combinaciones de inhibidores de transcriptasa inversa nucleósidos (NRTI) del estudio. La variable principal de evaluación fue el incremento de la cifra de linfocitos CD4 desde el momento en que el paciente tiene una carga viral indetectable o desde el momento del cambio por simplificación o toxicidad (visita basal) hasta las 48 semanas. Introdujimos como variables de ajuste para dicho análisis la edad, el sexo, el grupo de riesgo, la infección por virus de la hepatitis C (VHC), el grupo de clasificación del Center for Disease Control and Prevention (CDC), recuento delinfocitos CD4+ nadir, motivos del cambio, el tipo de tratamiento antirretroviral (inhibidor de proteasa [IP], inhibidor de transcriptasa inversa no nucleósido [NNRTI] o combinación de inhibidores de transcriptasa inversa nucleósidos [3 NRTI]) y tiempo con carga viral indetectable. Resultados. Los regímenes que incluyeron TDF + ddI mostraron una reducción del recuento de CD4+. Ajustando por el tipo de tratamiento antirretroviral de gran actividad (TARGA), por los motivos del cambio, y por el tiempo con carga viral indetectable, en los pacientes que recibieron TDF + 3TC la cifra de linfocitos CD4 aumentó en 160 cél./ìl (intervalo de confianza del 95% [IC 95%]: 53-266) más que en los pacientes que recibieron TDF + ddI y que los pacientes que recibieron ddI + 3TC aumentaron 138 cél./ìl (IC 95%: 25-266) más que los que recibieron TDF + ddI. Conclusiones. La combinación ddI + TDF no es aconsejable, no sólo porque puede producir descenso del recuento de linfocitos CD4+, sino porque desde el punto de vista inmunológico es peor que las otras combinaciones (AU)

Background. Several recent studies have shown that the combination of ddI plus TDF can produce an unexpected drop in CD4 cell counts, even after correcting the ddI dose. Objective. Comparative study of the immunological effectiveness of various once-daily NRTI backbones (ddI plus TDF, ddI plus 3TC or TDF plus 3TC) in antiretroviral-experienced HIV-infected patients achieving viral suppression (PCR, HIV-RNA < 50 copies/ìl). Methods. Prospective cohort study of 48 weeks' duration following viral load suppression with any of the NRTI combinations studied. The main outcome variable was the increase in CD4+ lymphocyte count from the time that viral load was undetectable or treatment was changed for simplification or toxicity (baseline) up to 48 weeks of follow-up. Differences between the assigned therapies were compared. The variables included in analysis were age, sex, risk group, HCV infection, clinical categories of HIV (CDC criteria), lowest CD4 cell count, reason for change of NRTI backbone, type of antiretroviral treatment (PI, NNRTI, or 3 NRTI) and duration of suppressed viral load. Results. Regimens including ddI plus TDF showed significant decreases in CD4 cell counts with adjustments by type of HAART, reason for change, and duration of suppressed viral load. In patients treated with TDF + 3TC, CD4 count increased by 160 cel/ìl (95% CI, 53-266) more than in patients treated with TDF + ddI; and in patients receiving ddI + 3TC, CD4+ count increased by 138 cel/ìl (95% CI, 25-266) more than in patients receiving TDF + ddI. Conclusions. The ddI plus TDF backbone seems unadvisable because of the lower associated CD4 cell counts, and because it is poorer than the other options from the immunological standpoint (AU)