In Vitro Antiviral Activity of Nordihydroguaiaretic Acid against SARS-CoV-2.

The coronavirus infectious disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has been spreading rapidly worldwide, creating a pandemic. This article describes the evaluation of the antiviral activity of nordihydroguaiaretic acid (NDGA), a molecule found in Creosote bush (Larrea tridentata) leaves, against SARS-CoV-2 in vitro. A 35 µM concentration of NDGA was not toxic to Vero cells and exhibited a remarkable inhibitory effect on the SARS-CoV-2 cytopathic effect, viral plaque formation, RNA replication, and expression of the SARS-CoV-2 spike glycoprotein. The 50% effective concentration for NDGA was as low as 16.97 µM. Our results show that NDGA could be a promising therapeutic candidate against SARS-CoV-2.

Primary and Community Care Transformation in Post-COVID Era: Nationwide General Practitioner Survey.

Introduction: The health emergency caused by COVID-19 has led to substantial changes in the usual working system of primary healthcare centers and in relations with users. The Catalan Society of Family and Community Medicine designed a survey that aimed to collect the opinions and facilitate the participation of its partners on what the future work model of general practitioners (GPs) should look like post-COVID-19. Methodology: Online survey of Family and Community Medicine members consisting of filiation data, 22 Likert-type multiple-choice questions grouped in five thematic axes, and a free text question. Results: The number of respondents to the questionnaire was 1051 (22.6% of all members): 83.2% said they spent excessive time on bureaucratic tasks; 91.8% were against call center systems; 66% believed that home care is the responsibility of every family doctor; 77.5% supported continuity of care as a fundamental value of patient-centered care; and >90% defended the contracting of complementary tests and first hospital visits from primary healthcare (PHC). Conclusions: The survey responses describe a strong consensus on the identity and competencies of the GP and on the needs of and the threats to the PHC system. The demand for an increase in health resources, greater professional leadership, elimination of bureaucracy, an increase in the number of health professionals, and greater management autonomy, are the axes towards which a new era in PHC should be directed.

In vitro inhibition of SARS-CoV-2 Infection by dry algae powders.

Chlorella spp., Spirulina spp., and fucoidan dry powders, are commercialized as food supplements and are considered safe for human consumption. Their broad-spectrum antiviral properties have been studied, however, their effect against SARS-CoV-2 remains unknown. We investigated the potential antiviral activity of three algae powders: Chlorella vulgaris, Arthrospira maxima (Spirulina) and fucoidan purified from marine brown algae Sargassum spp. against SARS-CoV-2 infection in vitro. Vero cells were incubated with 70 µg/ml of each algae powder and either 50 or 100 TCID50/ml of SARS-CoV-2, in two types of experiments (pretreatment and simultaneous) and comparing two kinds of solvents (DMEM and DMSO). Chlorella vulgaris powder, inhibited SARS-CoV-2 infection in all assays; viral RNA was significantly reduced in supernatants at 24, 48, 72, and 96 h post-infection, the highest difference in viral load (8000-fold) was observed after 96 h. Arthrospira maxima powder inhibited SARS-CoV-2 infection using 50 TCID50/ml for both experimental schemes, but protection percent was lower when viral inoculum was increase to 100 TCID50/ml; viral RNA decreased 48 h after infection, reaching a 250-fold difference at 72 h. Fucoidan powder partially inhibited SARS-CoV-2 infection since no CPE was observed in 62.5% of trated cultures in DMEM, but the antiviral activity was increased to 100% of protection when DMSO was used as solvent. All the algae samples showed high antiviral activity against SARS-CoV-2 with a SI above of 18. These results suggest that all three algae samples are potential therapeutic candidates for the treatment of COVID-19.

Flipped Inflammatory Time and the Role of Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2: Optimizing Tocilizumab Against Coronavirus Disease 2019.

Use of interleukin (IL-6) inhibitors has become one of the most complicated clinical issues in treating coronavirus disease 2019 (COVID-19). Recently, randomized open-label platform trials have found that IL-6 inhibitors have a beneficial effect on mortality in severe COVID-19. However, several questions arise around their mechanism of action in this disease, as well as how, when, and at which dose they should be used. IL-6 has both proinflammatory and anti-inflammatory effects, which may modulate the course of COVID-19, whose immunopathogenesis is driven by the innate immune system, autoantibodies, and interferon. Given that patients with delayed seroconversion against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein would be at the highest risk of complications beyond the second week of disease, we propose that considering patient serostatus at admission could optimize the use of IL-6 inhibitors in COVID-19. We predict that the net treatment benefits could be higher in the subgroup of patients with delayed seroconversion as compared to those who seroconvert more rapidly after SARS-CoV-2 infection.

The Impact of Grounding in Running Shoes on Indices of Performance in Elite Competitive Athletes.

The introduction of carbon fiber plate shoes has triggered a plethora of world records in running, which has encouraged shoe industries to produce novel shoe designs to enhance running performance, including shoes containing conductor elements or "grounding shoes" (GS), which could potentially reduce the energy cost of running. The aim of this study was to examine the physiological and perceptual responses of athletes subjected to grounding shoes during running. Ten elite runners were recruited. Firstly, the athletes performed an incremental running test for VO2max and anaerobic threshold (AT) determination, and were familiarized with the two shoe conditions (traditional training shoe (TTS) and GS, the latter containing a conductor element under the insole). One week apart, athletes performed running economy tests (20 min run at 80% of the AT) on a 400 m dirt track, with shoe conditions randomized. VO2, heart rate, lactate, and perceived fatigue were registered throughout the experiment. No differences in any of the physiological or perceptual variables were identified between shoe conditions, with an equal running economy in both TTS and GS (51.1 ± 4.2 vs. 50.9 ± 5.1 mL kg-1 min-1, respectively). Our results suggest that a grounding stimulus does not improve the energy cost of running, or the physiological/perceptual responses of elite athletes.

Cardiac magnetic resonance in recovering COVID-19 patients. Feature tracking and mapping analysis to detect persistent myocardial involvement.

BACKGROUND: Post-COVID-19 patients may incur myocardial involvement secondary to systemic inflammation. Our aim was to detect possible oedema/diffuse fibrosis using cardiac magnetic resonance imaging (CMR) mapping and to study myocardial deformation of the left ventricle (LV) using feature tracking (FT). METHODS: Prospective analysis of consecutively recruited post-COVID-19 patients undergoing CMR. T1 and T2 mapping sequences were acquired and FT analysis was performed using 2D steady-state free precession cine sequences. Statistical significance was set to p < 0.05. RESULTS: Included were 57 post-COVID-19 patients and 20 healthy controls, mean age 59 ± 15 years, men 80.7%. The most frequent risk factors were hypertension (33.3%) and dyslipidaemia (36.8%). The contact-to-CMR interval was 81 ± 27 days. LV ejection fraction (LVEF) was 61 ± 10%. Late gadolinium enhancement (LGE) was evident in 26.3% of patients (19.3%, non-ischaemic). T2 mapping values (suggestive of oedema) were higher in the study patients than in the controls (50.9 ± 4.3 ms vs 48 ± 1.9 ms, p < 0.01). No between-group differences were observed for native T1 nor for circumferential strain (CS) or radial strain (RS) values (18.6 ± 3.3% vs 19.2 ± 2.1% (p = 0.52) and 32.3 ± 8.1% vs 33.6 ± 7.1% (p = 0.9), respectively). A sub-group analysis for the contact-to-CMR interval (<8 weeks vs ≥ 8 weeks) showed that FT-CS (15.6 ± 2.2% vs 18.9 ± 2.6%, p < 0.01) and FT-RS (24.9 ± 5.8 vs 33.5 ± 7.2%, p < 0.01) values were lower for the shorter interval. CONCLUSIONS: Post-COVID-19 patients compared to heathy controls had raised T2 values (related to oedema), but similar native T1, FT-CS and FT-RS values. FT-CS and FT-RS values were lower in post-COVID-19 patients undergoing CMR after < 8 weeks compared to ≥ 8 weeks.

Acute coronary thrombosis as a complication of COVID-19.

COVID-19 has varied cardiovascular manifestations including microvascular and macrovascular thrombi leading to multiorgan system injury and failure. This case describes a patient presenting with acute hypoxaemic respiratory failure from COVID-19 who abruptly developed a large thrombus in the right coronary artery leading to myocardial infarction. This case report reviews the ECG, heart catheterisation images prepercutaneous and postpercutaneous coronary intervention, critical care management and outcome in the context of the height of the COVID-19 pandemic in the Virginia area. A brief review of relevant literature regarding cardiovascular complications of COVID-19 is also provided. Unfortunately, the patient ultimately passed after 2 weeks of inability to wean off the ventilator.

Kaggle Competitions in the Classroom: Retrospectives and Recommendations

Ruiz et al discuss the use of Kaggle in classrooms. Kaggle is an online data science platform best known for its public machine learning competitions. Since its inception in 2008, Kaggle has hosted thousands of competitions to advance research on a myriad of topics ranging from satellite imagery feature detection to COVID-19 research analysis. Besides hosting these global competitions, Kaggle has grown into an expansive data science educational platform that offers full courses, an open-source dataset repository, and a feature known as Kaggle InClass competitions (KICs). These KICs are contests specifically tailored for use in an academic setting that are completely customizable by the hosting professor or teaching assistant. In turn, the Kaggle platform provides a leaderboard, centralized location to access the competition data, and support for various popular code libraries.

Healthcare Worker With Large Vessel Acute Ischemic Stroke Likely Related to Mild SARS-CoV-2 Infection.

We report the case of a healthcare worker who presented with a large vessel acute ischemic stroke in setting of a mild SARS-CoV-2 infection and provide a review of the emerging literature on COVID-related stroke. A 43-year-old female presented with right-sided hemiparesis, aphasia and dysarthria. She had a nonproductive of cough for 1 week without fever, fatigue or dyspnea. A CT Head, CT angiography and CT perfusion imaging revealed a M1 segment occlusion of the left middle cerebral artery requiring transfer from a primary to a comprehensive stroke center. A nasopharyngeal swab confirmed SARS-CoV-2 infection prior to arrival at the accepting center. During the thrombectomy a 3 cm thrombus was removed. Thrombus was also evident in the 8 French short sheath during closure device placement so a hypercoagulable state was suspected. Stroke work-up revealed a glycosylated hemoglobin of 8.7%, elevation of inflammatory markers and an indeterminate level of lupus anticoagulant IgM. On discharge home, she had near complete neurological recovery. This case highlights suspected mechanisms of hypercoagulability in SARS-CoV-2 infection and the importance of optimizing stroke care systems during the COVID-19 pandemic.

Clinical characteristics and outcomes among hospitalized adults with severe COVID-19 admitted to a tertiary medical center and receiving antiviral, antimalarials, glucocorticoids, or immunomodulation with tocilizumab or cyclosporine: A retrospective observational study (COQUIMA cohort).

BACKGROUND: The COVID-19 outbreak challenges the Spanish health system since March 2020. Some available therapies (antimalarials, antivirals, biological agents) were grounded on clinical case observations or basic science data. The aim of this study is to describe the characteristics and impact of different therapies on clinical outcomes in a cohort of severe COVID-19 patients. METHODS: In this retrospective, single-center, observational study, we collected sequential data on adult patients admitted to Hospital Universitario Quironsalud Madrid. Eligible patients should have a microbiological (positive test on RT-PCR assay from a nasal swab) or an epidemiological diagnosis of severe COVID-19. Demographic, baseline comorbidities, laboratory data, clinical outcomes, and treatments were compared between survivors and non-survivors. We carried out univariate and multivariate logistic regression models to assess potential risk factors for in-hospital mortality. FINDINGS: From March 10th to April 15th, 2020, 607 patients were included. Median age was 69 years [interquartile range, {IQR} 22; 65% male). The most common comorbidities were hypertension (276 [46·94%]), diabetes (95 [16·16%]), chronic cardiac (133 [22·62%]) and respiratory (114 [19·39%]) diseases. 141 patients (23·2%) died. In the multivariate model the risk of death increased with older age (odds ratio, for every year of age, 1·15, [95% CI 1·11 - 1·2]), tocilizumab therapy (2·4, [1·13 - 5·11]), C-reactive protein at admission (1·07, per 10 mg/L, [1·04 - 1·10]), d-dimer > 2·5 µg/mL (1·99, [1·03 - 3·86]), diabetes mellitus (2·61, [1·19 - 5·73]), and the PaO2/FiO2 at admission (0·99, per every 1 mmHg, [0·98 - 0·99]). Among the prescribed therapies (tocilizumab, glucocorticoids, lopinavir/ritonavir, hydroxychloroquine, cyclosporine), only cyclosporine was associated with a significant decrease in mortality (0·24, [0·12 - 0·46]; p<0·001). INTERPRETATION: In a real-clinical setting, inhibition of the calcineurin inflammatory pathway, NF-κΒ, could reduce the hyperinflammatory phase in COVID-19. Our findings might entail relevant implications for the therapy of this disease and could boost the design of new clinical trials among subjects affected by severe COVID-19. FUNDING: Hospital Universitario Quironsalud Madrid. Own fundings for COVID-19 research.