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COVID-19 disease has been a challenge for health systems worldwide due to its high transmissibility, morbidity, and mortality. Severe COVID-19 is associated with an imbalance in the immune response, resulting in a cytokine storm and a hyperinflammation state. While hematological parameters correlate with prognosis in COVID patients, their predictive value has not been evaluated specifically among those severely ill. Therefore, we aim to evaluate the role of hematological and immune response biomarkers as a prognostic factor in critically ill patients with COVID-19 admitted to the intensive care unit. From May 2020 to July 2021, a retrospective cohort study was conducted in a reference hospital in Manaus, which belongs to the Brazilian public health system. This study was carried out as single-center research. Clinical and laboratory parameters were analyzed to evaluate the association with mortality. We also evaluated the role of neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein-to-lymphocyte ratio (CLR). We gathered information from medical records, as well as from prescriptions and forms authorizing the use of antimicrobial medications. During the study period, 177 patients were included, with a mean age of 62.58 ± 14.39 years. The overall mortality rate was 61.6%. Age, mechanical ventilation (MV) requirement, leukocytosis, neutrophilia, high c-reactive protein level, NLR, and CLR showed a statistically significant association with mortality in the univariate analysis. In the multivariate logistic regression analysis, only MV (OR 35.687, 95% CI: 11.084-114.898, p< 0.001) and NLR (OR 1.026, 95% CI: 1.003-1.050, p = 0.028) remained statistically associated with the outcome of death (AUC = 0.8096). While the need for mechanical ventilation is a parameter observed throughout the hospital stay, the initial NLR can be a primary risk stratification tool to establish priorities and timely clinical intervention in patients with severe COVID-19 admitted to the ICU.

COVID-19 is a contagious infection caused by the SARS-CoV-2 virus, responsible for more than 5 million deaths worldwide, and has been a significant challenge for healthcare systems worldwide. Characterized by multiple manifestations, the most common symptoms are fever, cough, anosmia, ageusia, and myalgia. However, several organs can be affected in more severe cases, causing encephalitis, myocarditis, respiratory distress, hypercoagulable state, pulmonary embolism, and stroke. Despite efforts to identify appropriate clinical protocols for its management, there are still no fully effective therapies to prevent patient death. The objective of this study was to describe the demographic, clinical, and pharmacotherapeutic management characteristics employed in patients hospitalized for diagnosis of COVID-19, in addition to identifying predictive factors for mortality. This is a single-center, retrospective cohort study carried out in a reference hospital belonging to the Brazilian public health system, in Manaus, from March 2020 to July 2021. Data were obtained from analyzing medical records, physical and electronic forms, medical prescriptions, and antimicrobial use authorization forms. During the study period, 530 patients were included, 51.70% male, with a mean age of 58.74 ± 15.91 years. The overall mortality rate was 23.58%. The variables age, number of comorbidities, admission to the ICU, length of stay, oxygen saturation, serum aspartate transaminase, and use of mechanical ventilation showed a positive correlation with the mortality rate. Regarding pharmacological management, 88.49% of patients used corticosteroids, 86.79% used antimicrobials, 94.15% used anticoagulant therapy, and 3.77% used immunotherapy. Interestingly, two specific classes of antibiotics showed a positive correlation with the mortality rate: penicillins and glycopeptides. After multivariate logistic regression analysis, age, number of comorbidities, need for mechanical ventilation, length of hospital stay, and penicillin or glycopeptide antibiotics use were associated with mortality (AUC = 0.958).

Tomato brown rugose fruit virus (ToBRFV) is a member of Tobamovirus infecting tomato and pepper. Within North America, both the United States and Mexico consider ToBRFV to be a regulated pest. In Canada, the presence of ToBRFV has been reported, but an efficient diagnostic system has not yet been established. Here, we describe the development and assessment of a loop-mediated isothermal amplification (LAMP)-based assay to detect ToBRFV. The LAMP test was efficient and robust, and results could be obtained within 35 min with an available RNA sample. Amplification was possible when either water bath or oven were used to maintain the temperature at isothermal conditions (65°C), and results could be read by visual observation of colour change. Detection limit of the LAMP was eight target RNA molecules. Under the experimental conditions tested, LAMP was as sensitive as qPCR and 100 times more sensitive than the currently used RT-PCR. We recommend this sensitive, efficient LAMP protocol to be used for routine lab testing of ToBRFV.

Hydrogen sulfide, as a novel gaseous mediator, has been suggested to play a key role in atherogenesis. However, the precise mechanisms by which H(2)S affects atherosclerosis remain unclear. Therefore, the present study aimed to investigate the potential role of H(2)S in atherosclerosis and the underlying mechanism with respect to chemokines (CCL2, CCL5 and CX3CL1) and chemokine receptors (CCR2, CCR5, and CX3CR1) in macrophages. Mouse macrophage cell line RAW 264.7 or mouse peritoneal macrophages were pre-incubated with saline or NaHS (50 µM, 100 µM, 200 µM), an H(2)S donor, and then stimulated with interferon-γ (IFN-γ) or lipopolysaccharide (LPS). It was found that NaHS dose-dependently inhibited IFN-γ or LPS-induced CX3CR1 and CX3CL1 expression, as well as CX3CR1-mediated chemotaxis in macrophages. Overexpression of cystathionine γ-lyase (CSE), an enzyme that catalyzes H(2)S biosynthesis resulted in a significant reduction in CX3CR1 and CX3CL1 expression as well as CX3CR1-mediated chemotaxis in stimulated macrophages. The inhibitory effect of H(2)S on CX3CR1 and CX3CL1 expression was mediated by modulation of proliferators-activated receptor-γ (PPAR-γ) and NF-κB pathway. Furthermore, male apoE(-/-) mice were fed a high-fat diet and then randomly given NaHS (1 mg/kg, i.p., daily) or DL-propargylglycine (PAG, 10 mg/kg, i.p., daily). NaHS significantly inhibited aortic CX3CR1 and CX3CL1 expression and impeded aortic plaque development. NaHS had a better anti-atherogenic benefit when it was applied at the early stage of atherosclerosis. However, inhibition of H(2)S formation by PAG increased aortic CX3CR1 and CX3CL1 expression and exacerbated the extent of atherosclerosis. In addition, H(2)S had minimal effect on the expression of CCL2, CCL5, CCR2 and CCR5 in vitro and in vivo. In conclusion, these data indicate that H(2)S hampers the progression of atherosclerosis in fat-fed apoE(-/-) mice and downregulates CX3CR1 and CX3CL1 expression on macrophages and in lesion plaques.

Hydrogen sulfide (H(2)S), as a novel gaseous mediator, plays important roles in mammalian cardiovascular tissues. In the present study, we investigated the cardioprotective effect of S-diclofenac (2-[(2,6-dichlorophenyl)amino] benzeneacetic acid 4-(3H-1,2,dithiol-3-thione-5-yl)phenyl ester), a novel H(2)S-releasing derivative of diclofenac, in a murine model of doxorubicin-induced cardiomyopathy. After a single dose injection of doxorubicin (15 mg/kg, i.p.), male C57BL/6J mice were given daily treatment of S-diclofenac (25 and 50 µmol/kg, i.p.), diclofenac (25 and 50 µmol/kg, i.p.), NaHS (50 µmol/kg, i.p.), or same volume of vehicle. The cardioprotective effect of S-diclofenac was observed after 14 days. It showed that S-diclofenac, but not diclofenac, dose-dependently inhibited the doxorubicin-induced downregulation of cardiac gap junction proteins (connexin 43 and connexin 45) and thus reversed the remodeling of gap junctions in hearts. It also dose-dependently suppressed doxorubicin-induced activation of JNK in hearts. Furthermore, S-diclofenac produced a dose-dependent anti-inflammatory and anti-oxidative effect in this model. As a result, S-diclofenac significantly attenuated doxorubicin-related cardiac injury and cardiac dysfunction, and improved the survival rate of mice with doxorubicin-induced cardiomyopathy. These effects of S-diclofenac were mimicked in large part by NaHS. Therefore, we propose that H(2)S released from S-diclofenac in vivo contributes to the protective effect in doxorubicin-induced cardiomyopathy. These data also provide evidence for a critical role of H(2)S in the pathogenesis of doxorubicin-induced cardiomyopathy.