Post-COVID-19 Ongoing Symptoms and Health-Related Quality of Life: Does Rehabilitation Matter?: Preliminary Evidence.

OBJECTIVE: Individuals with persisting symptoms after coronavirus disease 2019 have reported a decrease in health-related quality of life. This study explores the outcome of 50 subjects with post-coronavirus disease 2019 ongoing symptoms including "long COVID"(symptoms lasting over 3 mos), after a rehabilitation program focused on three symptoms: fatigue, breathlessness, and pain. The aims were as follows: to assess the feasibility of the program, to observe a possible change in symptoms and quality of life (null hypothesis: no differences in variables before and after treatment), and to investigate a possible relationship between symptoms and quality of life. DESIGN: This is a retrospective observational study. RESULTS: Symptoms intensity measured with numeric rating scale decreased. Mean differences are as follows: breathlessness, -2.91; fatigue, -2.05; and pain, -2.41 ( P > 0.001). Quality of life measured with Euroqol-5D improved. Mean differences are as follows: Euroqol-5D index, 0.104, and Euroqol-5D visual analog scale, 19.21 ( P < 0.001). Effect size of these changings is classifiable as large (Cohen d > 0.8 and <1.3) except for Euroqol-5D index (Cohen d = -0.575), resulting medium (>0.5 and <0.8). Correlation (Pearson r ) between symptoms and Euroqol-5D resulted moderate for pain and fatigue (-0.609 and -0.531, P < 0.001) and low for breathlessness (-0.533, P < 0.001). CONCLUSIONS: Rehabilitation can be feasible and may improve symptoms and quality of life. Further research is needed.

Rehabilitative treatment of patients with COVID-19 infection: the P.A.R.M.A. evidence based clinical practice protocol.

BACKGROUND: The impact of the SARS-CoV-2 on the National Health System (NHS) required a reorganization of the various levels of care, which also involved the rehabilitation reality. AIM OF THE WORK: A clinical practice review of the literature was conducted to provide operational-rehabilitation guidelines adapted to the local reality and to the recent corporate reorganization in the context of the COVID-19 emergency. METHODS: A practice review of the available scientific evidence was regularly conducted from the start of the COVID-19 pandemic to periodically update the clinical practice guidelines. Articles that met the following inclusion criteria were included: studies conducted on human adult subjects with COVID-19 infection, undergoing rehabilitation in any hospitalization setting. RESULTS: The results of this clinical practice update were periodically discussed with colleagues and collaborators in a multi-professional team, in order to guarantee a good clinical practice protocol, named P.A.R.M.A. CONCLUSIONS: The P.A.R.M.A. protocol is the result of a periodic review literature update, which has allowed us to take charge of patients affected by COVID-19 according to the most up-to-date clinical evidences, guaranteeing a shared and uniform treatment within a local reality in an era of health emergency.

Investigation of the mechanisms underpinning IL-6 cytokine release in bystander responses: the roles of radiation dose, radiation quality and specific ROS/RNS scavengers.

PURPOSE: To investigate the mechanisms regulating the pathways of the bystander transmission in vitro, focusing on the radiation-perturbed signalling (via Interleukine 6, IL-6) of the irradiated cells after exposure to low doses of different radiation types. MATERIALS AND METHODS: An integrated 'systems radiation biology' approach was adopted. Experimentally the level of the secreted cytokine from human fibroblasts was detected with ELISA (Enzyme-Linked ImmunoSorbent Assay) method and subsequently the data were analyzed and coupled with a phenomenological model based on differential equations to evaluate the single-cell release mechanisms. RESULTS: The data confirmed the important effect of radiation on the IL-6 pathway, clearly showing a crucial role of the ROS (Reactive Oxygen Species) in transducing the effect of initial radiation exposure and the subsequent long-term release of IL-6. Furthermore, a systematic investigation of radiation dose/radiation quality dependence seems to indicate an increasing efficiency of high LET (Linear Energy Transfer) irradiation in the release of the cytokine. Basic hypotheses were tested, on the correlation between direct radiobiological damage and signal release and on the radiation target for this endpoint (secretion of IL-6). CONCLUSIONS: The results demonstrate the role of reactive oxygen and nitrogen species in the signaling pathways of IL-6. Furthermore the systems radiation biology approach here adopted, allowed us to test and verify hypotheses on the behavior of the single cell in the release of cytokine, after the exposure to different doses and different qualities of ionizing radiation.

Effects of ionizing radiation on cell-to-cell communication.

Cell-to-cell signaling has become a significant issue in radiation biology due to experimental evidence, accumulated primarily since the early 1990s, of radiation-induced bystander effects. Several candidate mediators involved in cell-to-cell communication have been investigated and proposed as being responsible for this phenomenon, but the current investigation techniques (both theoretical and experimental) of the mechanisms involved, due to the particular set-up of each experiment, result in experimental data that often are not directly comparable. In this study, a comprehensive approach was adopted to describe cell-to-cell communication (focusing on cytokine signaling) and its modulation by external agents such as ionizing radiation. The aim was also to provide integrated theoretical instruments and experimental data to help in understanding the peculiarities of in vitro experiments. Theoretical/modeling activities were integrated with experimental measurements by (1) redesigning a cybernetic model (proposed in its original form in the 1950s) to frame cell-to-cell communication processes, (2) implementing and developing a mathematical model, and (3) designing and carrying out experiments to quantify key parameters involved in intercellular signaling (focusing as a pilot study on the release and decay of IL-6 molecules and their modulation by radiation). This formalization provides an interpretative framework for understanding the intercellular signaling and in particular for focusing on the study of cell-to-cell communication in a "step-by-step" approach. Under this model, the complex phenomenon of signal transmission was reduced where possible into independent processes to investigate them separately, providing an evaluation of the role of cell communication to guarantee and maintain the robustness of the in vitro experimental systems against the effects of perturbations.

Experimental and theoretical analysis of cytokine release for the study of radiation-induced bystander effect.

PURPOSE: To clarify the experimental conditions that might influence the release of cytokines in the culture medium and give some basic input for building a model for cytokine (e.g., Interleukin-6, IL-6) regulation in the case of 'sham irradiation' and after ionising radiation exposure. MATERIALS AND METHODS: The influence of cell type, cell density, medium volume, medium storage temperature and other methodological aspects on IL-6 and Interleukin-8 (IL-8) release were investigated. In addition, the effects over the time of different doses of gamma irradiation on the clonogenic survival of bystander cells and on the secretion of these cytokines were studied. RESULTS: We observed significant decreases of clonogenic survival in AG01522 and T98G cells after the transfer of medium collected 5 and 20 h after low doses of gamma irradiation. Concerning the Interleukins' measurements, our experiments showed that the aggregate removal modalities tested, and up to 10 freeze-thaw cycles, do not have significant influence on the measurements of IL-6 concentration in the medium. We also observed that the IL-6 accumulated in the medium of human fibroblasts is not degraded when maintained at 37 degrees C. Sets of experiments demonstrated that cell density or medium volume do not influence the release of IL-6. On the contrary, our results showed that IL-8 released by glioblastoma cells strongly depends on the amount of medium. Finally, the exposure of fibroblasts to gamma irradiation has influence on the release kinetics of both IL-6 and IL-8 with peculiar features. CONCLUSIONS: This study solved some of the methodological doubts concerning the study of bystander effects by means of the medium transfer technique; moreover it also highlighted some experimental aspects that need to be considered when approaching this sort of experiments.