Exercise Training in Post-COVID-19 Patients: The Need for a Multifactorial Protocol for a Multifactorial Pathophysiology

Cattadori, Gaia; Marco, Silvia Di; Baravelli, Massimo; Picozzi, Anna; Ambrosio, Giuseppe

doi:10.3390/jcm11082228

Cited by 43 publications

(43 citation statements)

References 58 publications

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“…Our data can be useful also for the management and treatment of long COVID; in fact, the so-called "Long COVID-19 Syndrome", indicating the set of disorders and clinical manifestations that remain long after COVID-19 infection, is emerging as the next challenge in biomedical research (Yan et al, 2021;Antoniou et al, 2022;Cattadori et al, 2022;Desai et al, 2022;Martinez-Salazar et al, 2022;Murray et al, 2022;Oikonomou et al, 2022;Thye et al, 2022). Henceforward, the deep understanding of the molecular mechanisms underlying the major complications of COVID-19 will allow us to intervene and tackle Long-COVID.…”

Section: Discussionmentioning

confidence: 91%

Exosomal miR-145 and miR-885 Regulate Thrombosis in COVID-19

Gambardella

Kansakar

Sardu³

et al. 2022

J Pharmacol Exp Ther

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We hypothesized that exosomal microRNAs (miRNAs) could be implied in the pathogenesis of thromboembolic complications in COVID-19. We isolated circulating exosomes from COVID-19 patients and then we divided our population in two arms based on the D-dimer level on hospital admission. We observed that exosomal miR-145 and miR-885 significantly correlate with D-Dimer levels. Moreover, we demonstrate that human endothelial cells express the main cofactors needed for SARS-CoV-2 internalization, including ACE2, TMPRSS2, and CD-147. Interestingly, human endothelial cells treated with serum from COVID-19 patients release significantly less miR-145 and miR-885, exhibit increased apoptosis, and display significantly impaired angiogenetic properties compared to cells treated with non-COVID-19 serum. Taken together, our data indicate that exosomal miR-145 and miR-885 are essential in modulating thromboembolic events in COVID-19.

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Section: Discussionmentioning

confidence: 91%

Exosomal miR-145 and miR-885 Regulate Thrombosis in COVID-19

Gambardella

Kansakar

Sardu³

et al. 2022

J Pharmacol Exp Ther

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“…The associations identified in the current network have several implications for clinical practice. For instance, the presence of sensitization-associated symptoms would support why exercise, which effects are mainly mediated by the central nervous system, could be a therapeutic strategy to be applied in people with long COVI D [ 39 ]. Nevertheless, it is important to consider that sensitization is associated with poor clinical outcomes to conservative treatment in musculoskeletal pain conditions [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

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

Fernández‐de‐las‐Peñas

Herrero-Montes

Cancela-Cilleruelo

et al. 2022

Diagnostics

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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.

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“…Second, the association between weight (e.g., obesity) and neuropathic pain is also discussed in the literature [ 33 ]. Accordingly, this association would explain why exercise programs should be implemented into a multimodal therapeutic approach of long-COVID [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

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

Fernández‐de‐las‐Peñas

Valera‐Calero

Herrero-Montes

et al. 2022

Viruses

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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.

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Exercise Training in Post-COVID-19 Patients: The Need for a Multifactorial Protocol for a Multifactorial Pathophysiology

Cited by 43 publications

References 58 publications

Exosomal miR-145 and miR-885 Regulate Thrombosis in COVID-19

Exosomal miR-145 and miR-885 Regulate Thrombosis in COVID-19

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

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

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