Elevated Cytokine Levels in Plasma of Patients with SARS-CoV-2 Do Not Contribute to Pulmonary Microvascular Endothelial Permeability.

The vascular endothelial injury occurs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, but the mechanisms are poorly understood. We sought to determine the frequency and type of cytokine elevations and their relationship to endothelial injury induced by plasma from patients with SARS-CoV-2 versus controls. Plasma from eight consecutively enrolled patients hospitalized with acute SARS-CoV-2 infection was compared to controls. Endothelial cell (EC) barrier integrity was evaluated using ECIS (electric cell-substrate impedance sensing) on human lung microvascular EC. Plasma from all SARS-CoV-2 but none from controls decreased transendothelial resistance to a greater degree than that produced by tumor necrosis factor-alpha (TNF-α), the positive control for the assay. Thrombin, angiopoietin 2 (Ang2), and vascular endothelial growth factor (VEGF), complement factor C3a and C5a, and spike protein increased endothelial permeability, but to a lesser extent and a shorter duration when compared to SARS-CoV-2 plasma. Analysis of Ang2, VEGF, and 15 cytokines measured in plasma revealed striking patient-to-patient variability within the SARS-CoV-2 patients. Pretreatment with thrombin inhibitors, single, or combinations of neutralizing antibodies against cytokines, Ca3 and C5a receptor antagonists, or with ACE2 antibody failed to lessen the SARS-CoV-2 plasma-induced EC permeability. The EC barrier destructive effects of plasma from patients with SARS-CoV-2 were susceptible to heat inactivation. Plasma from patients hospitalized with acute SARS-CoV-2 infection uniformly disrupts lung microvascular integrity. No predicted single, or set of, cytokine(s) accounted for the enhanced vascular permeability, although the factor(s) were heat-labile. A still unidentified but potent circulating factor(s) appears to cause the EC disruption in SARS-CoV-2 infected patients. IMPORTANCE Lung vascular endothelial injury in SARS-CoV-2 patients is one of the most important causes of morbidity and mortality and has been linked to more severe complications including acute respiratory distress syndrome (ARDS) and subsequent death due to multiorgan failure. We have demonstrated that in eight consecutive patients with SARS-CoV-2, who were not selected for evidence of endothelial injury, the diluted plasma-induced intense lung microvascular damage, in vitro. Known endothelial barrier-disruptive agents and proposed mediators of increased endothelial permeability in SARS-CoV-2, induced changes in permeability that were smaller in magnitude and shorter in duration than plasma from patients with SARS-CoV-2. The effect on endothelial cell permeability of plasma from patients with SARS-CoV-2 was heat-labile. The main plasma factor that causes the increased endothelial permeability remains to be identified. Our study provides a possible approach for future studies to understand the underlying mechanisms leading to vascular injury in SARS-CoV-2 infections.

Influence of the Covid-19 pandemic on out-of-hospital cardiac arrest. A Spanish nationwide prospective cohort study.

AIMS: The influence of the COVID-19 pandemic on attendance to out-of-hospital cardiac arrest (OHCA) has only been described in city or regional settings. The impact of COVID-19 across an entire country with a high infection rate is yet to be explored. METHODS: The study uses data from 8629 cases recorded in two time-series (2017/2018 and 2020) of the Spanish national registry. Data from a non-COVID-19 period and the COVID-19 period (February 1st-April 30th 2020) were compared. During the COVID-19 period, data a further analysis comparing non-pandemic and pandemic weeks (defined according to the WHO declaration on March 11th, 2020) was conducted. The chi-squared analysis examined differences in OHCA attendance and other patient and resuscitation characteristics. Multivariate logistic regression examined survival likelihood to hospital admission and discharge. The multilevel analysis examined the differential effects of regional COVID-19 incidence on these same outcomes. RESULTS: During the COVID-19 period, the incidence of resuscitation attempts declined and survival to hospital admission (OR = 1.72; 95%CI = 1.46-2.04; p < 0.001) and discharge (OR = 1.38; 95%CI = 1.07-1.78; p = 0.013) fell compared to the non-COVID period. This pattern was also observed when comparing non-pandemic weeks and pandemic weeks. COVID-19 incidence impinged significantly upon outcomes regardless of regional variation, with low, medium, and high incidence regions equally affected. CONCLUSIONS: The pandemic, irrespective of its incidence, seems to have particularly impeded the pre-hospital phase of OHCA care. Present findings call for the need to adapt out-of-hospital care for periods of serious infection risk. STUDY REGISTRATION NUMBER: ISRCTN10437835.

Perioperative Considerations in Urgent Surgical Care of Suspected and Confirmed COVID-19 Orthopaedic Patients: Operating Room Protocols and Recommendations in the Current COVID-19 Pandemic.

By April 7, 2020, severe acute respiratory syndrome coronavirus 2 was responsible for 1,383,436 confirmed cases of Coronavirus disease 2019 (COVID-19), involving 209 countries around the world; 378,881 cases have been confirmed in the United States. During this pandemic, the urgent surgical requirements will not stop. As an example, the most recent Centers of Disease Control and Prevention reports estimate that there are 2.8 million trauma patients hospitalized in the United States. These data illustrate an increase in the likelihood of encountering urgent surgical patients with either clinically suspected or confirmed COVID-19 in the near future. Preparation for a pandemic involves considering the different levels in the hierarchy of controls and the different phases of the pandemic. Apart from the fact that this pandemic certainly involves many important health, economic, and community ramifications, it also requires several initiatives to mandate what measures are most appropriate to prepare for mitigating the occupational risks. This article provides evidence-based recommendations and measures for the appropriate personal protective equipment for different clinical and surgical activities in various settings. To reduce the occupational risk in treating suspected or confirmed COVID-19 urgent orthopaedic patients, recommended precautions and preventive actions (triage area, emergency department consultation room, induction room, operating room, and recovery room) are reviewed.

Identification of COVID-19 can be quicker through artificial intelligence framework using a mobile phone-based survey when cities and towns are under quarantine.

We propose the use of a machine learning algorithm to improve possible COVID-19 case identification more quickly using a mobile phone-based web survey. This method could reduce the spread of the virus in susceptible populations under quarantine.