COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options.

The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.

Initial assessment and management of respiratory infections in persons with spinal cord injuries and disorders in the COVID-19 era.

As the COVID-19 pandemic unfolds, emergency department (ED) personnel will face a higher caseload, including those with special medical needs such as persons living with spinal cord injuries and disorders (SCI/D). Individuals with SCI/D who develop COVID-19 are at higher risk for rapid decompensation and development of acute respiratory failure during respiratory infections due to the combination of chronic respiratory muscle paralysis and autonomic dysregulation causing neurogenic restrictive/obstructive lung disease and chronic immune dysfunction. Often, acute respiratory infections will lead to significant mucus production in individuals with SCI/D, and aggressive secretion management is an important component of successful medical treatment. Secretion management techniques include nebulized bronchodilators, chest percussion/drainage techniques, manually assisted coughing techniques, nasotracheal suctioning, and mechanical insufflation-exsufflation. ED professionals, including respiratory therapists, should be familiar with the significant comorbidities associated with SCI/D and the customized secretion management procedures and techniques required for optimal medical management and prevention of respiratory failure. Importantly, protocols should also be implemented to minimize potential COVID-19 spread during aerosol-generating procedures.

Economic Consequences of an Implanted Neuroprosthesis in Subjects with Spinal Cord Injury for Restoration of an Effective Cough.

Objective: To determine if an implanted neuroprosthesis for restoration of an effective cough is less costly than conventional methods of respiratory management. Methods: Nonrandomized clinical trial of participants (N = 14) with spinal cord injury (SCI) using the Cough Stimulator device in the inpatient hospital setting for Cough Stimulator implantation and outpatient hospital or residence for follow-up. A neuroprosthesis was implanted for restoration of an effective cough. The annual costs associated with respiratory management, without (pre implantation) and with (post implantation) the neuroprosthesis, were examined over a 4-year period. Results: The total cost related to implantation of the Cough Stimulator was $59,891, with no maintenance costs over subsequent years. The incidence of respiratory tract infections and the need for caregiver support fell significantly following implantation. The costs associated with respiratory tract infections fell significantly from a mean of $36,406 ± 11,855/year to $13,284 ± 7,035/year (p < .05) pre and post implantation, respectively. Costs fell further to $8,817 ± 5,990 and $4,467 ± 4,404 following the 2nd and 3rd years post implantation (p < .05), respectively. The costs associated with caregiver support fell significantly from $25,312 ± 8,019/year to $2,630 ± 2,233/year (p < .05) pre and post implantation, respectively, and remained low in subsequent years (p < .05). Other costs related to secretion management fell significantly and remained low in subsequent years (p < .05). Break-even analysis demonstrated that this point was reached in the first year. Conclusion: The results of this investigation demonstrate that implantation and use of the Cough Stimulator resulted in significant reductions in the overall costs of respiratory management in this patient population.

Safety assessment of epidural wire electrodes for cough production in a chronic pig model of spinal cord injury.

BACKGROUND: It is our hypothesis that high intensity spinal cord stimulation (SCS) to restore an effective cough mechanism using wire leads, will result in significant activation of target neurons without tissue injury or electrode corrosion. METHODS: Adult mini-pigs underwent chronic spinal cord compression, followed by implantation of parallel wire leads on the dorsal epidural surface of the spinal cord, with stimulation contacts at the T9 and T12, and control electrode contacts at the T2 and T5 levels. After 3 months of daily SCS, airway pressure generation (P), tissue in the area of the stimulating and control electrodes and electrode leads were examined. P was also assessed in acute animals, which served as controls. RESULTS: Mean P at FRC was 54±5cmH2O and 109±11cmH2O in the control and chronically stimulated animals, respectively (p<0.05). There was minimal tissue reaction in the area of the stimulating and control electrodes. All sets of leads revealed no evidence of electrode corrosion. COMPARISON WITH EXISTING METHODS: Previous porcine models of chronic spinal cord injury (SCI) were developed to study neurological and regenerative outcomes. Our method of chronic SCI porcine model was developed to evaluate the safety of electrical SCS to restore expiratory muscle function. CONCLUSION: Chronic SCS with wire lead electrodes results in significant increases in P without evidence of significant adverse tissue reaction, nor evidence of electrode corrosion. This method may be a safe and useful technique to restore a functional cough in spinal cord injured subjects.