CHOLINERGIC AGONISTS AGAINST COVID-19 IN HUMANS. RESULTS FROM A RANDOMIZED OPEN LABEL PILOT TRIAL

Background: Since the SARS-CoV-2 pandemic emerged in December 2019, it has triggered 4.4 million deaths and strained health systems across the world. Yet more than a year and a half since the pandemic emerged, therapeutic drugs to treat COVID-19 disease are limited. Objective To investigate the therapeutic potential of a nicotinic Cholinergic Agonists Mixture (CAM), delivered daily as oral drops and as nasal spray, in alleviating ten common COVID-19 related symptoms in 80 symptomatic human adults with confirmed SARS-CoV-2. Methods This randomized open-label pilot trial recruited 80 symptomatic adults with confirmed SARS-CoV-2 infection after RT-PCR test less than five days. Participants were recruited from databases of several Colombian hospitals and were randomly assigned to the control group, which received the Standard of Care (SOC) treatment (outpatient treatment), or the intervention group, which received SOC combined with the Cholinergic Agent Mixture (CAM SOC). Both groups received their treatment for a total of 14 days. The duration of symptoms was compared across the 14-day period. Results: This study found statistically significant reductions in symptom duration for 5 out of 10 symptoms, including dyspnea (reduction of 4.43 days [95% CI: 2.70 ;6.15], p <0.0001), cough (reduction of 3.18 days [95% CI: 1.29 ;5.06], p=0.0089), cephalea (reduction of 3.13 days [95% CI: 1.53 ;4.72], p= 0.0019), muscle fatigue (reduction of 4.18 days [95% CI: 2.03 ;6.32], p=0.0019) and general malaise (reduction of 5.98 days [95% CI: 4.20 ;7.76], p <0.0001).The study found no significant reductions in the duration of the following symptoms: fever, ageusia, anosmia, chest tightness, and nasal congestion. Conclusion: In comparison to the control group, the intervention group witnessed statistically significant and clinically relevant reductions in the duration of 5 out of 10 common COVID-19 disease symptoms within two weeks. This includes a reduction of approximately 4.4 days in the duration of dyspnea, a symptom that appears to be strongly correlated to severe COVID-19 disease and admission to Intensive Care Units. Further studies are needed to confirm these preliminary findings and to evaluate whether this specific nicotinic cholinergic agonists mixture could have implications for public health.

EFFECTIVENESS IN HUMANS OF AN ANTIVIRAL DRUG BASED ON CHOLINERGIC AGONISTS WITH SPECIFIC DESIGN AND ROUTE OF ADMINISTRATION AGAINST COVID-19 SYMPTOMS IN A GROUP OF INFECTED PATIENTS VS. CONTROL GROUP

Objective: To establish the therapeutic action of a nicotinic cholinergic agonist agent composition in synergy with other non-cholinergic molecules (CA) in the COVID-19 symptoms in a group of human patients infected with SARS-CoV-2 vs. control group. Methods Randomized open-label trial pilot study where 80 patients were randomly assigned to receive standard of care (SOC) treatment as outpatient treatment after PCR test;SOC plus CA was administered in the intervention group (40 patients). SOC was administered in the control group (40 patients). Basic Odds Ratio study (95% confidence interval) in 40 patients for intervention group and 40 patients for the control group. The evaluation in the groups was carried out during 15 days assessing the improvement or worsening of each symptom daily. Results: Fever (OR=0.897), Cough (OR = 0.571), Dyspnea (OR = 0.460), Muscle fatigue (OR = 0.250), Cephalea (OR = 0,570), Ageusia (OR = 0.150), Anosmia (OR = 0.650), General malaise (OR = 0.316), Nasal congestion (OR= 0.890), are less than 1 converting the use of the cholinergic agent in a protective and therapeutic factor showing therefore improvement of these symptoms, after its use, compared to the control group. Conclusions: The positive results obtained on the symptoms caused by COVID-19 by delivering mixture of cholinergic agonists molecules and other non-cholinergic supportive molecules (CA) with special oral and nasal route of administration and specific pharmacological design against COVID-19 in humans infected by SARS-CoV-2 versus the control group is a (novel) promising therapeutic approach to fight SARS-COV-2. Larger multicentrical trials in humans are encouraged.

Extended reality as a training method for medical first responders in mass casualty incidents: A protocol for a systematic review.

INTRODUCTION/BACKGROUND: Mass-casualty incidents (MCIs) and disasters require an organised and effective response from medical first responders (MFRs). As such, novel training methods have emerged to prepare and adequately train MFRs for these challenging situations. Particular focus should be placed on extended reality (XR), which encompasses virtual, augmented and mixed reality (VR, AR, and MR, respectively), and allows participants to develop high-quality skills in realistic and immersive environments. Given the rapid evolution of high-fidelity simulation technology and its advantages, XR simulation has become a promising tool for emergency medicine. Accordingly, this systematic review aims to: 1) evaluate the effectiveness of XR training methods and 2) explore the experience of MFRs undergoing such training. METHODS: A comprehensive search strategy will encompass four distinct themes: MFRs, disasters/MCIs, education and simulation, and XR. Four databases (MEDLINE, EMBASE, CINAHL and LILACs) will be searched along with an in-depth examination of the grey literature and reference lists of relevant articles. MetaQAT will be used as a study quality assessment tool and integrated into Covidence as part of the data extraction form. Given the predicted high heterogeneity between studies, it may not be possible to standardise data for quantitative comparison and meta-analysis. Thus, data will be synthesised in a narrative, semi-quantitative manner. DISCUSSION: This review will examine the existing literature on the effectiveness of XR simulation as a tool to train MFRs for MCIs, which could ultimately improve preparedness and response to disasters. TRIAL REGISTRATION: Protocol registration: PROSPERO CRD42021275692.

Hospital bed occupancy rate is an independent risk factor for COVID-19 inpatient mortality: a pandemic epicentre cohort study.

INTRODUCTION: COVID-19 first struck New York City in the spring of 2020, resulting in an unprecedented strain on our healthcare system and triggering multiple changes in public health policy governing hospital operations as well as therapeutic approaches to COVID-19. We examined inpatient mortality at our centre throughout the course of the pandemic. METHODS: This is a retrospective chart review of clinical characteristics, treatments and outcome data of all patients admitted with COVID-19 from 1 March 2020 to 28 February 2021. Patients were grouped into 3-month quartiles. Hospital strain was assessed as per cent of occupied beds based on a normal bed capacity of 1491. RESULTS: Inpatient mortality decreased from 25.0% in spring to 10.8% over the course of the year. During this time, use of remdesivir, steroids and anticoagulants increased; use of hydroxychloroquine and other antibiotics decreased. Daily bed occupancy ranged from 62% to 118%. In a multivariate model with all year's data controlling for demographics, comorbidities and acuity of illness, percentage of bed occupancy was associated with increased 30-day in-hospital mortality of patients with COVID-19 (0.7% mortality increase for each 1% increase in bed occupancy; HR 1.007, CI 1.001 to 1.013, p=0.004) CONCLUSION: Inpatient mortality from COVID-19 was associated with bed occupancy. Early reduction in epicentre hospital bed occupancy to accommodate acutely ill and resource-intensive patients should be a critical component in the strategic planning for future pandemics.

Incidence of new-onset atrial fibrillation in COVID-19 is associated with increased epicardial adipose tissue.

PURPOSE: Coronary artery calcium (CAC) and epicardial adipose tissue (EAT) can predict AF in the general population. We aimed to determine if CAC and EAT measured by computed tomographic (CT) scanning can predict new-onset AF in patients admitted with COVID-19 disease. METHODS: We performed a retrospective, post hoc analysis of all patients admitted to Montefiore Medical Center with a confirmed COVID-19 diagnosis from March 1st to June 23rd, 2020, who had a non-contrast CT of the chest within 5 years prior to admission. We determined ordinal CAC scores and quantified the EAT volume and examined their relationship with inpatient mortality. RESULTS: A total of 379 patients were analyzed. There were 16 events of new-onset AF (4.22%). Patients who developed AF during the index admission were more likely to be male (75 vs 47%, p < 0.001) and had higher EAT (129.5 [76.3-197.3] vs 91.0 [60.0-129.0] ml, p = 0.049). There were no differences on age (68 [56-71] vs 68 [58-76] years; p = 0.712), BMI (28.5 [25.3-30.8] vs 26.9 [23.1-31.8] kg/m2; p = 0.283), ordinal CAC score (3 [1-6] vs 2 [0-4]; p = 0.482), or prevalence of diabetes (56.3 vs 60.1%; p = 0.761), hypertension (75.0 vs 87.3%, p = 0.153), or coronary artery disease (50.0 vs 39.4%, p = 0.396). Patients with new-onset AF had worse clinical outcomes (death/intubation/vasopressors) (87.5 vs 44.1%; p = 0.001). CONCLUSION: Increased EAT measured by non-contrast chest CT identifies patients hospitalized with COVID-19 at higher risk of developing new-onset AF. Patients with new-onset AF have worse clinical outcomes.

Coronary artery calcification and epicardial adipose tissue as independent predictors of mortality in COVID-19.

Recent epidemiological studies have demonstrated that common cardiovascular risk factors are strongly associated with adverse outcomes in COVID-19. Coronary artery calcium (CAC) and epicardial fat (EAT) have shown to outperform traditional risk factors in predicting cardiovascular events in the general population. We aim to determine if CAC and EAT determined by Computed Tomographic (CT) scanning can predict all-cause mortality in patients admitted with COVID-19 disease. We performed a retrospective, post-hoc analysis of all patients admitted to Montefiore Medical Center with a confirmed COVID-19 diagnosis from March 1st, 2020 to May 2nd, 2020 who had a non-contrast CT of the chest within 5 years prior to admission. We determined ordinal CAC scores and quantified the epicardial (EAT) and thoracic (TAT) fat volume and examined their relationship with inpatient mortality. A total of 493 patients were analyzed. There were 197 deaths (39.95%). Patients who died during the index admission had higher age (72, [64-80] vs 68, [57-76]; p < 0.001), CAC score (3, [0-6] vs 1, [0-4]; p < 0.001) and EAT (107, [70-152] vs 94, [64-129]; p = 0.023). On a competing risk analysis regression model, CAC ≥ 4 and EAT ≥ median (98 ml) were independent predictors of mortality with increased mortality of 63% (p = 0.003) and 43% (p = 0.032), respectively. As a composite, the group with a combination of CAC ≥ 4 and EAT ≥ 98 ml had the highest mortality. CAC and EAT measured from chest CT are strong independent predictors of inpatient mortality from COVID-19 in this high-risk cohort.

Surge-in-Place: Conversion of a Cardiac Catheterization Laboratory Into a COVID-19 Intensive Care Unit and Back Again.

In Spring 2020, the United States epicenter of COVID-19 was New York City, in which the borough of the Bronx was particularly affected. This Fall, there has been a resurgence of COVID-19 in Europe and the Midwestern United States. We describe our experience transforming our cardiac catheterization laboratories to accommodate an influx of COVID-19 patients so as to provide other hospitals with a potential blueprint. We transformed our pre/postprocedural patient care areas into COVID-19 intensive care and step-down units and maintained emergent invasive care for ST-segment elevation myocardial infarction using existing space and personnel.

Statin Use and In-Hospital Mortality in Patients With Diabetes Mellitus and COVID-19.

Background Severe coronavirus disease 2019 (COVID-19) is characterized by a proinflammatory state with high mortality. Statins have anti-inflammatory effects and may attenuate the severity of COVID-19. Methods and Results An observational study of all consecutive adult patients with COVID-19 admitted to a single center located in Bronx, New York, was conducted from March 1, 2020, to May 2, 2020. Patients were grouped as those who did and those who did not receive a statin, and in-hospital mortality was compared by competing events regression. In addition, propensity score matching and inverse probability treatment weighting were used in survival models to examine the association between statin use and death during hospitalization. A total of 4252 patients were admitted with COVID-19. Diabetes mellitus modified the association between statin use and in-hospital mortality. Patients with diabetes mellitus on a statin (n=983) were older (69±11 versus 67±14 years; P<0.01), had lower inflammatory markers (C-reactive protein, 10.2; interquartile range, 4.5-18.4 versus 12.9; interquartile range, 5.9-21.4 mg/dL; P<0.01) and reduced cumulative in-hospital mortality (24% versus 39%; P<0.01) than those not on a statin (n=1283). No difference in hospital mortality was noted in patients without diabetes mellitus on or off statin (20% versus 21%; P=0.82). Propensity score matching (hazard ratio, 0.88; 95% CI, 0.83-0.94; P<0.01) and inverse probability treatment weighting (HR, 0.88; 95% CI, 0.84-0.92; P<0.01) showed a 12% lower risk of death during hospitalization for statin users than for nonusers. Conclusions Statin use was associated with reduced in-hospital mortality from COVID-19 in patients with diabetes mellitus. These findings, if validated, may further reemphasize administration of statins to patients with diabetes mellitus during the COVID-19 era.

T-wave inversion as a manifestation of COVID-19 infection: a case series.

PURPOSE: Cardiac involvement with COVID-19 infection has become evident by elevated troponin, cardiac arrhythmias, ST segment elevation, myocarditis, fulminant heart failure, and sudden cardiac death. We aimed to describe the association of COVID-19 and T-wave inversion (TWI) in a large case series. METHODS: We conducted an observational, retrospective study of confirmed COVID-19 cases with at least one electrocardiogram (ECG) in a large hospital in New York City (March 23, 2020-April 23, 2020). Patients with new TWI or pseudonormalization were further analyzed. Mortality and the need for invasive mechanical ventilation were the main outcomes. RESULTS: A total of 3225 patients were screened; 195 (6%) were selected for further analysis: 181 with TWI and 14 with T-wave pseudonormalization. Mean age was 66 ± 7 years; 51% were male. TWI were more commonly noted in the lateral (71%), followed by anterior (64%), inferior (57%), and septal (26%) leads. A total of 44 patients (23%) had elevated troponin. A total of 50 patients died (26%). Mortality rates of 35%, and 52% were observed in patients with diffuse TWI, and elevated troponin, respectively. Mortality rate of 80% was observed in patients with both elevated troponin and diffuse TWI. Additionally, 30% of the entire cohort and 58% of patients with elevated troponin required invasive mechanical ventilation. CONCLUSION: Our study demonstrates that new TWI is a relatively common finding in COVID-19 patients. Importantly, our findings suggest that new TWI or T-wave pseudonormalization, particularly with elevated troponin, was associated with higher rates of mechanical ventilation and in-hospital mortality.