Mild COVID-19 outpatients managed by General Practitioners in Northern Italy (Lombardy)

Mild, moderate and severe inpatients managed in different Italian Hospitals, mostly in Northern Italy (Lombardy)

COVID-19

Cardiovascular Risk Factor

Istituto Auxologico Italiano

Predictors of Cardiovascular Risk in Covid-19 Patients During Acute Disease and at Short Term Follow-up

Cardiovascular Risk in COVID-19 Patients: Metabolic, Prothrombotic and Proinflammatory Mechaninsms Associated With Outcome and With Cardiorespiratory Features During the Acute Viral Disease and at Short Term Follow-up

To obtain a multivariable model based on anthropometric, clinical and therapeutic variables that will allow to predict the development of severe COVID-19 and its complications

To Identify the role of selected clinical, pathophysiological and molecular mechanisms in the development of COVID-19 disease and its clinical manifestations of different severity

To Identify the clinical, immunological, inflammatory, viral, cardiorespiratory consequences of COVD-19 that may persist a few months after discharge and may affect mid- and long-term prognosis

Sharing individual participants data that underlie the results included in published articles, after deidentification

Patient with hypermetabolic response of skeletal musculature by causes related with Malignant Hyperthermia in the literature.

50 variants have been described that can be considered "diagnostic mutations" of RYR1 and CACNA1S, and other under study.

Hyperthermia, Malignant

In vitro study of muscle contraction after exposure to different substances (caffeine and halothane).

In vitro contracture test (IVCT)

In vitro study of the activation of lymphocytes B after being incubated with a cocktail of primary antibodies and measuring the acidification in response to the RyR1, 4-CmC agonist, using ryanodine as a positive control.

In vitro test of hypermetabolism in B lymphocytes

Analysis of genes related to MH (CACNA1S and RYR1).

Genetic test

Hospital Universitario La Paz

Population at Risk of Malignant Hyperthermia: Ambispective Cohort.

Measured by the tension induced by the muscular contraction in response to the presence of caffeine and halothane.

Identifying determined genes related with Malignant Hyperthermia risk.

Extracellular acidification curve in B lymphocytes in response to the agonist RyR1 and 4-CmC.

Instituto de Investigación Hospital Universitario La Paz

Universidad Autonoma de Madrid

A one hour infusion of a single 8mg/kg dose (max. 800mg) of tocilizumab to attenuate systemic inflammation after out-of-hospital cardiac arrest, given as early as possible after hospital admission.

Heart Arrest

Out-Of-Hospital Cardiac Arrest

Systemic Inflammatory Response Syndrome

Tocilizumab is suspended in isotonic saline to a total volume of 100mL prior to infusion

Tocilizumab 20 Mg/mL Intravenous Solution

A one hour infusion of 100mL isotonic saline

isotonic saline

Rigshospitalet

IL-6 Inhibition for Modulating Inflammation After Cardiac Arrest

Interleukin-6 Receptor Antibodies for Modulating the Systemic Inflammatory Response After Out-of-Hospital Cardiac Arrest - a Randomized Clinical Trial

Markers of cerebral injury: Neuron-specific enolase (NSE) levels (routine biochemistry), and other markers of cerebral injury (analysis of samples in biobank).
Markers of cardiac injury: Troponin T (TnT) and CKMB levels. Markers of kidney injury: Creatinine levels. Markers of hepatic injury: ALAT, ASAT, bilirubin, INR. Markers of endothelial injury: soluble thrombomodulin levels.

Interleukin levels: INF-g, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8 IL-10, IL-12, IL-13, IL-17A, G-CSF, GM-CSF, MCP-1 og MIP-1beta and TNF-α (analysis of samples in biobank).

Daily Sequential Organ Failure Assessment (SOFA) scores.

The possible downstream effect of dampened inflammation on the coagulation system is evaluated by the concentration of plasma-fibrinogen.

The possible downstream effect of dampened inflammation on the coagulation system is evaluated by whole blood thrombelastography.

Swan-Ganz based measurements of cardiac output, central venous pressure, pulmonary capillary wedge pressure, and systemic vascular resistance.

Arterial blood gasses including lactate and base excess at frequent intervals.

Transthoracic echocardiography including assesment of left ventricular ejection fraction (LVEF) and tricuspid annular plane systolic excursion (TAPSE).

Montreal Cognitive Assessment (MOCA) score at 90 days.

Cerebral Performance Category (CPC) at 30 days, 90 days and 180 days, assessed by telephone interview and/or review of medical file after completion of the 180 days.

Cumulated incidence of adverse events the first 7 days.

A subset of the trial participants will be enrolled in a sub-study focusing on cardio protection and neuroprotection as a pilot investigation. This sub-study will include an echocardiography, a cerebral MR scan and a cardiac MR scan; all three modalities being performed the day following admission.

Christian Hassager

Professor, MD, DMSc, FESC

Subjects will be randomized in a 1:1 fashion to receive IL-6RA or placebo. Patients being allocated to IL-6RA will receive a one-hour infusion of 8 mg tocilizumab per kg body weight (maximum dose 800 mg, 40 mL), equivalent to 0.4 mL per kg bodyweight (study drug concentration 20 mg/mL). Patients being allocated to placebo will receive a one-hour infusion of 0.4 mL /kg body weight of normal saline (maximum dose 40 mL)

disseminated intravascular coagulation/hypoxie

Predictors of Cardiovascular Risk in Covid-19 Patients During Acute Disease and at Short Term Follow-up

Population at Risk of Malignant Hyperthermia: Ambispective Cohort.

IL-6 Inhibition for Modulating Inflammation After Cardiac Arrest

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