ABSTRACT Background: Cases of coronavirus disease 2019 (COVID-19) requiring hospitalization continue to appear in vulnerable populations, highlighting the importance of novel treatments. The hyperinflammatory response underlies the severity of the disease, and targeting this pathway may be useful. Herein, we tested whether immunomodulation focusing on interleukin (IL)-6, IL-17, and IL-2, could improve the clinical outcomes of patients admitted with COVID-19. Methods: This multicenter, open-label, prospective, randomized controlled trial was conducted in Brazil. Sixty hospitalized patients with moderate-to-critical COVID-19 received in addition to standard of care (SOC): IL-17 inhibitor (ixekizumab 80 mg SC/week) 1 dose every 4 weeks; low-dose IL-2 (1.5 million IU per day) for 7 days or until discharge; or indirect IL-6 inhibitor (colchicine) orally (0.5 mg) every 8 hours for 3 days, followed by 4 weeks at 0.5 mg 2x/day; or SOC alone. The primary outcome was accessed in the “per protocol” population as the proportion of patients with clinical improvement, defined as a decrease greater or equal to two points on the World Health Organization’s (WHO) seven-category ordinal scale by day 28. Results: All treatments were safe, and the efficacy outcomes did not differ significantly from those of SOC. Interestingly, in the colchicine group, all participants had an improvement of greater or equal to two points on the WHO seven-category ordinal scale and no deaths or patient deterioration were observed. Conclusions: Ixekizumab, colchicine, and IL-2 were demonstrated to be safe but ineffective for COVID-19 treatment. These results must be interpreted cautiously because of the limited sample size. Background 201 COVID19 COVID 19 (COVID-19 populations useful Herein IL6, IL6 IL 6, 6 (IL)-6 IL17, IL17 17, 17 IL2, IL2 2, 2 COVID19. 19. Methods multicenter openlabel, openlabel open label, label open-label prospective Brazil moderatetocritical moderate critical COVID-1 (SOC) IL-1 ixekizumab SC/week SCweek SC week lowdose low IL- 1.5 15 5 (1. discharge (colchicine 05 0 (0. 0. 2x/day 2xday xday 2x x alone protocol Organizations Organization s (WHO sevencategory seven category 28 Results Interestingly group observed Conclusions Ixekizumab treatment size 20 COVID1 (COVID-1 (IL)- IL1 COVID- (SOC 1. (1 (0 (COVID- (IL) ( (COVID (IL

OBJETIVO: Analisar o comportamento mecânico do terço proximal do fêmur de ratos submetidos ao treinamento aeróbio e resistido crônicos. MÉTODOS: Ratos Wistar machos (80 dias, 300 a 350 g) foram divididos em 3 grupos (n=8 por grupo): Treinamento aeróbio/8 semanas (TA), Treinamento resistido/8 semanas (TR) e controle/8 semanas (CO). Ao término do período de treinamento os animais foram sacrificados e o fêmur direito coletado. Para análise do comportamento mecânico do fêmur foram realizados ensaios de flexo-compressão. RESULTADOS: O treinamento resistido ocasionou redução significante da força máxima (Fmáx) do fêmur. Por outro lado, promoveu um aumento (23,7%) relevante, porém não significante, da deformação da força máxima (DFmáx). O treinamento aeróbio não afetou a Fmáx, porém promoveu uma redução (26,6%) considerável, também não significante, da DFmáx. CONCLUSÕES: Os resultados demonstram que o treinamento resistido e aeróbio, promoveram redução da Fmáx e da DFmáx óssea, respectivamente. Os dados evidenciam uma ação diferencial de ambos os modelos de treinamento físico sobre as propriedades mecânicas do fêmur de ratos.

OBJECTIVE: To analyze the mechanical behavior of rat femur proximal thirds submitted to chronic aerobic and resistance training. METHODS: Male Wistar rats (80 days of age, weighing 300 to 350 g) were divided into 3 groups (n=8 per group): control (CO), aerobic training (TA) and resistance training (TR). At the end of the training, the animals were euthanized and the right femur was collected. Flexion-compression tests were carried out to analyze the mechanical behavior of the femurs. RESULTS: The resistance training promoted a significant reduction in maximum force (Fmáx) of the femur. However, it also promoted a relevant increase (23.7%), though without statistical significance, in maximum force deformation (DFmáx). The aerobic training did not affect maximum force, however, it caused a considerable reduction in DFmáx (26.6%), though this was also not statistically significant. CONCLUSIONS: The results show that resistance and aerobic training promoted a reduction in the Fmáx and DFmáx, respectively. The data showed a different response of both physical training models on the mechanical properties of the rat femurs.