Coronavirus COVID-19
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The role of combination immunomodulatory therapy with systemic corticosteroids and tocilizumab (TCZ) for aged patients with COVID-19-associated cytokine release syndrome remains unclear. Methods: We conducted a retrospective single-center study including consecutive patients ≥65 years that developed severe COVID-19 between March 3 and May 1, 2020 and were treated with corticosteroids at various doses (methylprednisolone [0.5 mg/Kg/12 hours to 250 mg/24 hours]), either alone (“CS group”) or associated to intravenous tocilizumab (400-600 mg, one to three doses) (“CS-TCZ group”). Primary outcome was all-cause mortality by day +14, whereas secondary outcomes included mortality by day +28 and clinical improvement (discharge and/or a ≥2-point decrease on a six-point ordinal scale) by day +14. Propensity score (PS)-based adjustment and inverse probability of treatment weights (IPTW) were applied. Results: Overall, 181 and 80 patients were included in the CS and CS-TCZ groups. All-cause 14-day mortality was lower in the CS-TCZ group, both in the PS-adjusted (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.17 – 0.68; P-value = 0.002) and IPTW-weighted models (odds ratio [OR]: 0.38; 95% CI: 0.21 – 0.68; P-value = 0.001). This protective effect was also observed for 28-day mortality (PS-adjusted HR: 0.38; 95% CI: 0.21 – 0.72; P-value = 0.003). Clinical improvement by day +14 was higher in the CS-TCZ group in the IPTW analysis only (OR: 2.26; 95% CI: 1.49 – 3.41; P-value <0.001). The occurrence of secondary infection was similar between both groups. Conclusions: The combination of corticosteroids and TCZ was associated with better outcomes among patients ≥65 years with severe COVID-19.
The current work is of interest to introduce a detailed analysis of the novel fractional COVID-19 model. Non-local fractional operators are one of the most efficient tools in order to understand the dynamics of the disease spread. For this purpose, we intend as an attempt at investigating the fractional COVID-19 model through Caputo operator with order . Employing the fixed point theorem, it is shown that the solutions of the proposed fractional model are determined to satisfy the existence and uniqueness conditions under the Caputo derivative. On the other hand, its iterative solutions are indicated by making use of the Laplace transform of the Caputo fractional operator. Also, we establish the stability criteria for the fractional COVID-19 model via the fixed point theorem. The invariant region in which all solutions of the fractional model under investigation are positive is determined as the non-negative hyperoctant . Moreover, we perform the parameter estimation of the COVID-19 model by utilizing the non-linear least squares curve fitting method. The sensitivity analysis of the basic reproduction number is carried out to determine the effects of the proposed fractional model’s parameters on the spread of the disease. Numerical simulations show that all results are in good agreement with real data and all theoretical calculations about the disease.
This is a Brighton Collaboration Case Definition of the term “Multisystem Inflammatory Syndrome in Children and Adults (MIS-C/A)” to be utilized in the evaluation of adverse events following immunization. The case definition was developed by topic experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of vaccines for SARS-CoV-2. The format of the Brighton Collaboration was followed, including an exhaustive review of the literature, to develop a consensus definition and defined levels of certainty. The document underwent peer review by the Brighton Collaboration Network and by selected expert external reviewers prior to submission. The comments of the reviewers were taken into consideration and edits incorporated into this final manuscript.


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