Use of glucocorticoids and azithromycin in the therapy of COVID-19.

In December 2019, a new variant coronavirus, SARS-CoV-2, emerged in China, which was initially described as a pneumonia of an unknown agent. The new coronavirus spreads mainly by person-to-person transmission through close contact. The pathophysiology of COVID-19 is related to a complex immune system response that varies between people and, in severe cases of the disease, is characterized by excessive responses called "cytokine storms," which are associated with complications that can lead to a state of hypercoagulation and death. Glucocorticoids and azithromycin are drugs that may be effective in the treatment. This review aims to highlight the clinical findings that demonstrate the effectiveness of glucocorticoid and azithromycin therapy in the treatment of COVID-19. To date, many drugs have been studied for use in combination therapy, and the rapid expansion of knowledge about the virology of SARS-CoV-2 generates a more accurate direction in therapy.

Perspectives on glucocorticoid treatment for COVID-19: a systematic review.

Coronavirus disease 2019 (COVID-19) is a viral pneumonia that can lead to acute respiratory distress syndrome (ARDS). Until the commercialization of a vaccine, pharmacological treatment still represents an important strategy to fight against the ongoing pandemic. Glucocorticoids (GC) were widely used in the past coronavirus pandemics and have been used against the coronavirus 2 severe acute respiratory syndrome (SARS-CoV-2). This article aimed to review the studies that described the treatment with GC in COVID-19 patients. Randomized or nonrandomized clinical trials and retrospective or prospective-controlled longitudinal studies were screened for this systematic review. Studies in English, Portuguese, and Spanish published since 2019, with participants of any clinical status, geographic location, age, and sex were included. The most significant interest was related to the length of stay, radiological profile changes, viremia, and mortality. The research was done electronically on the Pubmed database using the following terms: "corticosteroids", "glucocorticoids", "dexamethasone", "methylprednisolone", "COVID-19", "SARS- CoV-2", "ADRS". We identified 6332 publications, and at the end, 14 retrospective observational studies that met all the inclusion criteria were selected. These studies included only patients infected with SARS-CoV-2 confirmed by RT-PCR, involving 2,713 participants. The results showed great heterogeneity in their designs and results, which precludes a reliable conclusion on the use of GCs in the treatment of COVID-19.

Time course of cardiomyopathy induced by doxorubicin in rats.

BACKGROUND: Doxorubicin (DOX)-related cardiotoxicity may expose cancer survivors to increased risk of cardiovascular morbidity and mortality. Here, we characterized the time course of DOX-induced cardiomyopathy in rats. METHODS: Sprague-Dawley male rats (12 wk old) received doxorubicin hydrochloride (1 mg/kg/d, ip) during 10 consecutive days and they were euthanized one (DOX1), two (DOX2) or four (DOX4) weeks after the last drug injection. Control group received NaCl 0.9% (ip). Hearts were mounted on a Langendorff perfusion system, left ventricle fragments were processed for microscopy and oxidative stress-related assays, and blood was collected for cardiac troponin I assay. RESULTS: All DOX-treated groups showed swollen and vacuolated cardiomyocytes with myofilaments disarray and mitochondrial damage. These changes were already evident after one week and became more pronounced after four weeks. Cardiac troponin I plasma levels were significantly increased in DOX1 and further increased in DOX4 compared to control group. Increased oxidative damage to lipids was observed in DOX1, and to proteins in DOX4. Glutathione peroxidase activity increased in DOX4. The morphological changes resulted in cardiac remodeling, including interstitial fibrosis, apoptosis and significant impairment of both contractile and relaxation function in DOX 4 compared to control group. Hearts from all animals displayed an early reduction in the responsiveness to norepinephrine. CONCLUSIONS: These findings support the view that DOX cardiotoxicity occurs in a "continuum", and as the hypothesis of an irreversible cardiac injury is being challenged, understanding the progression of morphological and functional changes caused by DOX may allow proper timing of initiation of prophylactic treatment.

Increased vascular function and superoxide dismutase activity in physically active vs inactive adults living with HIV.

This study compared macro- and microvascular endothelial function and redox status in active vs inactive HIV-infected patients (HIVP) under antiretroviral therapy. Using a cross-sectional design, macro- and microvascular reactivity, systemic microvascular density, and oxidative stress were compared between 19 HIVP (53.1 ± 6.1 year) enrolled in a multimodal training program (aerobic, strength and flexibility exercises) for at least 12 months (60-minutes sessions performed 3 times/wk with moderate intensity) vs 25 sedentary HIVP (51.2 ± 6.3 year). Forearm blood flow during reactive hyperemia (521.7 ± 241.9 vs 361.4% ± 125.0%; P = 0.04) and systemic microvascular density (120.8 ± 21.1 vs 105.6 ± 25.0 capillaries/mm2 ; P = 0.03) was greater in active than inactive patients. No significant difference between groups was detected for endothelium-dependent and independent skin microvascular vasodilation (P > 0.05). As for redox status, carbonyl groups (P = 0.22), lipid peroxidation (P = 0.86), catalase activity (P = 0.99), and nitric oxide levels (P = 0.72) were similar across groups. However, superoxide dismutase activity was greater in active vs inactive HIVP (0.118 ± 0.013 vs 0.111 ± 0.007 U/mL; P = 0.05). Immune function reflected by total T CD4 and T CD8 counts (cell/mm3 ) did not differ between active and inactive groups (P > 0.82). In conclusion, physically active HIVP exhibited similar immune function, but greater macrovascular reactivity, systemic microvascular density, and superoxide dismutase activity than inactive patients of similar age.

The impact of exercise frequency upon microvascular endothelium function and oxidative stress among patients with coronary artery disease.

PURPOSE: This study compared the effects of low and high weekly exercise frequencies on microvascular endothelium function and oxidative stress among patients with coronary artery disease. METHODS: Thirty-four male patients completed a 6-month cardiac rehabilitation programme, from which 23 performed exercise with a high frequency (HF) and 11 with a low frequency (LF). Systemic microvascular blood flow, maximal aerobic capacity, blood lipids, oxidative stress and anthropometric data were assessed prior to and after the cardiac rehabilitation programme. Microvascular blood flow was assessed in the skin of the forearm using laser speckle contrast imaging coupled with iontophoresis of acetylcholine. RESULTS: Maximal aerobic capacity, biochemical analysis and anthropometric data were similar between groups prior to and after the cardiac rehabilitation programme (P>0·05). However, after 6 months of cardiac rehabilitation performed with HF, there was an increase in the peak response to acetylcholine compared with LF (83·5 ± 58·5 versus 21·8 ± 22·4%; P<0·05). Changes in lipid peroxidation (HF: -5·5 ± 9·4 versus LF: 2·2 ± 12·0 pmol MDA mg-1 ; P = 0·19), catalase activity (HF: 0·07 ± 0·17 versus LF: 0·04 ± 0·08 U mg-1 ; P = 0·74) and nitric oxide levels (HF: 1·8 ± 15·3 versus LF: -3·2 ± 12·3 µM; P = 0·36) were similar between groups after cardiac rehabilitation. CONCLUSION: Six months of aerobic exercise training performed with high frequency is preferable to low frequency aiming endothelium microvascular function increases in patients with coronary artery disease. The mechanisms involved in this response are unclear and warrant additional research.