Noninvasive Mechanical Ventilation and Conventional Oxygen Therapy

COVID-19 pneumonia often presents with severely impaired oxygenation. In patients presenting with hypoxemic acute respiratory failure (ARF), one of the most important goals is to avoid invasive mechanical ventilation. Therefore, in this chapter, we will review the current evidence and rationale for using noninvasive oxygenation and ventilation strategies in patients presenting with COVID-19 and hypoxemic ARF. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Corrigendum: Comfort during non-invasive ventilation.

[This corrects the article DOI: 10.3389/fmed.2022.874250.].

Comfort During Non-invasive Ventilation.

Non-invasive ventilation (NIV) has been shown to be effective in avoiding intubation and improving survival in patients with acute hypoxemic respiratory failure (ARF) when compared to conventional oxygen therapy. However, NIV is associated with high failure rates due, in most cases, to patient discomfort. Therefore, increasing attention has been paid to all those interventions aimed at enhancing patient's tolerance to NIV. Several practical aspects have been considered to improve patient adaptation. In particular, the choice of the interface and the ventilatory setting adopted for NIV play a key role in the success of respiratory assistance. Among the different NIV interfaces, tolerance is poorest for the nasal and oronasal masks, while helmet appears to be better tolerated, resulting in longer use and lower NIV failure rates. The choice of fixing system also significantly affects patient comfort due to pain and possible pressure ulcers related to the device. The ventilatory setting adopted for NIV is associated with varying degrees of patient comfort: patients are more comfortable with pressure-support ventilation (PSV) than controlled ventilation. Furthermore, the use of electrical activity of the diaphragm (EADi)-driven ventilation has been demonstrated to improve patient comfort when compared to PSV, while reducing neural drive and effort. If non-pharmacological remedies fail, sedation can be employed to improve patient's tolerance to NIV. Sedation facilitates ventilation, reduces anxiety, promotes sleep, and modulates physiological responses to stress. Judicious use of sedation may be an option to increase the chances of success in some patients at risk for intubation because of NIV intolerance consequent to pain, discomfort, claustrophobia, or agitation. During the Coronavirus Disease-19 (COVID-19) pandemic, NIV has been extensively employed to face off the massive request for ventilatory assistance. Prone positioning in non-intubated awake COVID-19 patients may improve oxygenation, reduce work of breathing, and, possibly, prevent intubation. Despite these advantages, maintaining prone position can be particularly challenging because poor comfort has been described as the main cause of prone position discontinuation. In conclusion, comfort is one of the major determinants of NIV success. All the strategies aimed to increase comfort during NIV should be pursued.

The role of non-invasive ventilation

Patients with severe COVID-19 usually develop acute respiratory distress syndrome (ARDS) characterised by acute hypoxemic respiratory failure (HRF) and bilateral pulmonary infiltrates [1, 2]. The common reason for HRF occurring in the course of ARDS is the ventilation-perfusion mismatch or the intrapulmonary shunt [3]. Generally, HRF is defined as an acute condition where the arterial oxygen tension is below 60 mmHg on room air or oxygen is required to maintain measurements of pulse oximetry above 90% with low or normal partial carbon dioxide pressure [4]. Therapeutic options are limited to target the ongoing pathological processes of ARDS, and hence mechanical ventilation continues to be the mainstay for patient management [5]. Non-invasive ventilation (NIV) and high flow nasal cannula oxygen therapy (HFNC) can play a role in providing respiratory support to COVID-19 patients before developing severe HRF or in circumstances where there is limited access to more invasive techniques [1]. © Springer Nature Switzerland AG 2020.

Molecular Analysis of SARS-CoV-2 Spike Protein-Induced Endothelial Cell Permeability and vWF Secretion.

Coronavirus disease COVID-19, which is caused by severe acute respiratory syndrome coronavirus SARS-CoV-2, has become a worldwide pandemic in recent years. In addition to being a respiratory disease, COVID-19 is a 'vascular disease' since it causes a leaky vascular barrier and increases blood clotting by elevating von Willebrand factor (vWF) levels in the blood. In this study, we analyzed in vitro how the SARS-CoV-2 spike protein S1 induces endothelial cell (EC) permeability and its vWF secretion, and the underlying molecular mechanism for it. We showed that the SARS-CoV-2 spike protein S1 receptor-binding domain (RBD) is sufficient to induce endothelial permeability and vWF-secretion through the angiotensin-converting enzyme (ACE)2 in an ADP-ribosylation factor (ARF)6 activation-dependent manner. However, the mutants, including those in South African and South Californian variants of SARS-CoV-2, in the spike protein did not affect its induced EC permeability and vWF secretion. In addition, we have identified a signaling cascade downstream of ACE2 for the SARS-CoV-2 spike protein-induced EC permeability and its vWF secretion by using pharmacological inhibitors. The knowledge gained from this study could be useful in developing novel drugs or repurposing existing drugs for treating infections of SARS-CoV-2, particularly those strains that respond poorly to the existing vaccines.

Incidence, etiology, sociodemographic and clinical characterization of acute respiratory failure in pediatric patients at a high-altitude city: A multicenter cohort study.

Background: Acute respiratory failure is a life-threatening medical condition, associated with a variety of conditions and risk factors, including acute respiratory diseases which are a frequent cause of pediatric morbidity and mortality worldwide. In Colombia, the literature related to ARF is scarce. Objective: To determine the incidence, causes, and sociodemographic and clinical characteristics of ARF in three hospitals in Bogota, a high-altitude city located in Colombia, during the COVID-19 pandemic. Methods: A multicenter prospective cohort study called the FARA cohort was developed between April 2020 - December 2021. Patients older than one month and younger than 18 years with respiratory distress who developed ARF were included. Results: 685 patients with respiratory distress were recruited in 21 months. The incidence density of ARF was found to be 41.7 cases per 100 person-year CI 95%, (37.3-47.7). The median age was 4.5 years.. Most of the patients consulted during the first 72 h after the onset of symptoms. Upon admission, 67.2% were potentially unstable. The most frequent pathologies were asthma, bronchiolitis, pneumonia, and sepsis. At admission, 75.6% of the patients required different oxygen delivery systems, 29,5% a low-flow oxygen system, 36,8% a high-flow oxygen system, and 9,28% invasive mechanical ventilation. SARS-COV-2, respiratory syncytial virus, rhinovirus/enterovirus, and adenovirus were the most frequently isolated viral agents. The coinfection cases were scarce. Conclusions: This multicenter study, the FARA cohort, developed at 2,600 meters above sea level, shows the first data on incidence, etiology, sociodemographic and clinical characterization in a pediatric population with ARF that also concurs with the COVID-19 pandemic. These results, not only have implications for public health but also contribute to the scientific and epidemiological literature on a disease developed at a high altitude.

Secondary prevention of rheumatic heart disease in Ethiopia: a multicenter study.

BACKGROUND: Ethiopia has a high acute rheumatic fever (ARF) and rheumatic heart disease (RHD) prevalence, and to our knowledge, there are no data on the status of secondary prevention in children with RHD. This study describes the status of secondary RHD prevention. METHODS: A multicenter, prospective study was performed on children aged 5-17 years with RHD in Ethiopia. Good adherence was defined as at least 80% completion of benzathine penicillin (BPG) or oral Amoxicillin within the previous year. The primary outcome measure was adherence to prophylaxis, expressed as a proportion. Socio-demographics, severity of RHD, and ARF recurrence were evaluated. RESULTS: A total of 337 children with a mean age of 12.9 ± 2.6 years were included. The majority (73%) had severe aortic/mitral disease. Participants were on BPG (80%) or Amoxicillin (20%) prophylaxis. Female sex (P = 0.04) use of BPG (0.03) and shorter mean duration of prophylaxis in months (48.5 ± 31.5 vs. 60.7 ± 33, respectively, P < 0.008) predicted good adherence. Running out of medications (35%), interrupted follow-up (27%), and the COVID-19 pandemic (26%) were the most common reasons for missing prophylaxis. Recurrence of ARF was higher in participants on Amoxicillin compared with BPG (40% vs. 16%, P < 0.001) and in those with poor adherence compared with good adherence (36.8% vs. 17.9%, respectively, P = 0.005). Type and duration of prophylaxis (OR 0.5, CI = 0.24, 0.9, P = 0.02; OR = 1.1, CI = 1.1, 1.2, P = 0.04, respectively), and sex (OR = 1.9, CI = 1.1, 3.4, P = 0.03) were independent predictors of poor adherence. CONCLUSION: Poor adherence is prevalent in Ethiopian children living with RHD. Amoxicillin is a suboptimal option for prophylaxis as its use is associated with lower adherence and a higher rate of ARF recurrence.

Postacute Sequelae of SARS-CoV-2 Infection-Lessons Learned From a Coordinated Health System Response.

Objective: To outline a consensus-designed process for triaging and managing patients with post-coronavirus disease (COVID-19) syndrome at Mayo Clinic. Patients and Methods: We convened a central multidisciplinary team including members from the departments of general internal medicine, occupational medicine, physical medicine and rehabilitation, psychology, allergy and immunology, infectious disease, pulmonology, neurology, cardiology, and pediatrics and otorhinolaryngology with membership from all Mayo Clinic sites in Arizona, Florida, Iowa, Minnesota, and Wisconsin. Results: Consensus recommendations were made for the best practice guidelines on triaging and managing patients. Several innovations were agreed upon, including a postacute sequelae of COVID-19-specific appointment request form for data collection, a bioregistry, a biorepository, and a postacute sequelae of COVID-19-specific treatment program. Conclusion: Given that each clinical site had individual clinical practices, these recommendations were implemented using different models, which may provide broad applicability to other clinical settings.

SARS-CoV-2 pseudovirus enters the host cells through spike protein-CD147 in an Arf6-dependent manner.

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants is threatening public health around the world. Endocytosis functions as an important way for viral infection, and SARS-CoV-2 bears no exception. However, the specific endocytic mechanism of SARS-CoV-2 remains unknown. In this study, we used endocytic inhibitors to evaluate the role of different endocytic routes in SARS-CoV-2 pseudovirus infection and found that the viral infection was associated with caveolar/lipid raft- and cytoskeleton-mediated endocytosis, but independent of the clathrin-mediated endocytosis and macropinocytosis. Meanwhile, the knockdown of CD147 and Rab5a in Vero E6 and Huh-7 cells inhibited SARS-CoV-2 pseudovirus infection, and the co-localization of spike protein, CD147, and Rab5a was observed in pseudovirus-infected Vero E6 cells, which was weakened by CD147 silencing, illustrating that SARS-CoV-2 pseudovirus entered the host cells via CD147-mediated endocytosis. Additionally, Arf6 silencing markedly inhibited pseudovirus infection in Vero E6 and Huh-7 cells, while little change was observed in CD147 knockout-Vero E6 cells. This finding indicated Arf6-mediated CD147 trafficking plays a vital role in SARS-CoV-2 entry. Taken together, our findings provide new insights into the CD147-Arf6 axis in mediating SARS-CoV-2 pseudovirus entry into the host cells, and further suggest that blockade of this pathway seems to be a feasible approach to prevent the SARS-CoV-2 infection clinically.

Awake pronation with helmet continuous positive airway pressure for COVID-19 acute respiratory distress syndrome patients outside the ICU: A case series.

OBJECTIVE: Continuous positive airway pressure (CPAP) is an important therapeutic tool in COVID-19 acute respiratory distress syndrome (ARDS) since it improves oxygenation, reduces respiratory rate and can prevent intubation and intensive care unit (ICU) admission. CPAP during pronation has seldom been described and never during sedation. DESIGN: Case series. SETTING: High dependency unit of San Carlo University Hospital (Potenza, Italy). PATIENTS: Eleven consecutive patients with COVID-19 ARDS. INTERVENTION: Helmet CPAP in prone position after failing a CPAP trial in the supine position. MAIN VARIABLE OF INTEREST: Data collection at baseline and then after 24, 48 and 72h of pronation. We measured PaO2/FIO2, pH, lactate, PaCO2, SpO2, respiratory rate and the status of the patients at 28-day follow up. RESULTS: Patients were treated with helmet CPAP for a mean±SD of 7±2.7 days. Prone positioning was feasible in all patients, but in 7 of them dexmedetomidine improved comfort. PaO2/FIO2 improved from 107.5±20.8 before starting pronation to 244.4±106.2 after 72h (p<.001). We also observed a significantly increase in Sp02 from 90.6±2.3 to 96±3.1 (p<.001) and a decrease in respiratory rate from 27.6±4.3 to 20.1±4.7 (p=.004). No difference was observed in PaCO2 or pH. At 28 days two patients died after ICU admission, one was discharged in the main ward after ICU admission and eight were discharged home after being successfully managed outside the ICU. CONCLUSIONS: Helmet CPAP during pronation was feasible and safe in COVID-19 ARDS managed outside the ICU and sedation with dexmedetomidine safely improved comfort. We recorded an increase in PaO2/FIO2, SpO2 and a reduction in respiratory rate.

Noninvasive ventilation in patients with COVID-19 from the perspective of the risk of contamination: a narrative review.

INTRODUCTION: noninvasive ventilation (NIV) can be a useful resource to treat acute respiratory failure (ARF), which occurs in patients with COVID-19. However, it is important to consider that there are still no clinical studies that have verified the safety of its use in increase of contamination. AREAS COVERED: Given the potential benefits and simultaneous concerns over the use of NIV in patients with COVID-19, further inquiry is necessary to reach a clinical consensus and provide recommendations for safe use, avoiding contamination. In this context, this narrative review, which included articles published in the Embase, SciELO, PEDro, PubMed and Cochrane up to August 2021, is focused to evaluate available studies related to interfaces, types of circuits, recommended filters, cares for the environment and protective factors for NIV use in patients with COVID-19. EXPERT OPINION: The studies analyzed recommend that the use of NIV can be safe: 1) with equipment that allows the use of the helmet as a safer interface; 2) with double circuit and antimicrobial filter in the expiratory branch; 3) in an environment that allows negative pressure, reducing the dispersion of aerosol particles in the environment; 4) the health team must use the recommended PPE to avoid contamination.

Outcomes Among Patients Hospitalized With COVID-19 and Acute Kidney Injury.

RATIONALE & OBJECTIVE: Outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19) and acute kidney injury (AKI) are not well understood. The goal of this study was to investigate the survival and kidney outcomes of these patients. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Patients (aged≥18 years) hospitalized with COVID-19 at 13 hospitals in metropolitan New York between March 1, 2020, and April 27, 2020, followed up until hospital discharge. EXPOSURE: AKI. OUTCOMES: Primary outcome: in-hospital death. SECONDARY OUTCOMES: requiring dialysis at discharge, recovery of kidney function. ANALYTICAL APPROACH: Univariable and multivariable time-to-event analysis and logistic regression. RESULTS: Among 9,657 patients admitted with COVID-19, the AKI incidence rate was 38.4/1,000 patient-days. Incidence rates of in-hospital death among patients without AKI, with AKI not requiring dialysis (AKI stages 1-3), and with AKI receiving dialysis (AKI 3D) were 10.8, 31.1, and 37.5/1,000 patient-days, respectively. Taking those without AKI as the reference group, we observed greater risks for in-hospital death for patients with AKI 1-3 and AKI 3D (HRs of 5.6 [95% CI, 5.0-6.3] and 11.3 [95% CI, 9.6-13.1], respectively). After adjusting for demographics, comorbid conditions, and illness severity, the risk for death remained higher among those with AKI 1-3 (adjusted HR, 3.4 [95% CI, 3.0-3.9]) and AKI 3D (adjusted HR, 6.4 [95% CI, 5.5-7.6]) compared with those without AKI. Among patients with AKI 1-3 who survived, 74.1% achieved kidney recovery by the time of discharge. Among those with AKI 3D who survived, 30.6% remained on dialysis at discharge, and prehospitalization chronic kidney disease was the only independent risk factor associated with needing dialysis at discharge (adjusted OR, 9.3 [95% CI, 2.3-37.8]). LIMITATIONS: Observational retrospective study, limited to the NY metropolitan area during the peak of the COVID-19 pandemic. CONCLUSIONS: AKI in hospitalized patients with COVID-19 was associated with significant risk for death.

Estimating Shortages in Capacity to Deliver Continuous Kidney Replacement Therapy During the COVID-19 Pandemic in the United States.

RATIONALE & OBJECTIVE: During the coronavirus disease 2019 (COVID-19) pandemic, New York encountered shortages in continuous kidney replacement therapy (CKRT) capacity for critically ill patients with acute kidney injury stage 3 requiring dialysis. To inform planning for current and future crises, we estimated CKRT demand and capacity during the initial wave of the US COVID-19 pandemic. STUDY DESIGN: We developed mathematical models to project nationwide and statewide CKRT demand and capacity. Data sources included the Institute for Health Metrics and Evaluation model, the Harvard Global Health Institute model, and published literature. SETTING & POPULATION: US patients hospitalized during the initial wave of the COVID-19 pandemic (February 6, 2020, to August 4, 2020). INTERVENTION: CKRT. OUTCOMES: CKRT demand and capacity at peak resource use; number of states projected to encounter CKRT shortages. MODEL, PERSPECTIVE, & TIMEFRAME: Health sector perspective with a 6-month time horizon. RESULTS: Under base-case model assumptions, there was a nationwide CKRT capacity of 7,032 machines, an estimated shortage of 1,088 (95% uncertainty interval, 910-1,568) machines, and shortages in 6 states at peak resource use. In sensitivity analyses, varying assumptions around: (1) the number of pre-COVID-19 surplus CKRT machines available and (2) the incidence of acute kidney injury stage 3 requiring dialysis requiring CKRT among hospitalized patients with COVID-19 resulted in projected shortages in 3 to 8 states (933-1,282 machines) and 4 to 8 states (945-1,723 machines), respectively. In the best- and worst-case scenarios, there were shortages in 3 and 26 states (614 and 4,540 machines). LIMITATIONS: Parameter estimates are influenced by assumptions made in the absence of published data for CKRT capacity and by the Institute for Health Metrics and Evaluation model's limitations. CONCLUSIONS: Several US states are projected to encounter CKRT shortages during the COVID-19 pandemic. These findings, although based on limited data for CKRT demand and capacity, suggest there being value during health care crises such as the COVID-19 pandemic in establishing an inpatient kidney replacement therapy national registry and maintaining a national stockpile of CKRT equipment.

Lung microbiome and coronavirus disease 2019 (COVID-19): Possible link and implications.

Coronavirus disease 2019 (COVID-19) is a rapidly emerging disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease begins as an infection of lungs, which is self-limiting in the majority of infections; however, some develop severe respiratory distress and organ failures. Lung microbiome, though neglected previously have received interest recently because of its association with several respiratory diseases and immunity. Lung microbiome can modify the risk and consequences of COVID-19 disease by activating an innate and adaptive immune response. In this review, we examine the current evidence on COVID-19 disease and lung microbiome, and how lung microbiome can affect SARS-CoV-2 infection and the outcomes of this disease. To date there is no direct evidence from human or animal studies on the role of lung microbiome in modifying COVID-19 disease; however, related studies support that microbiome can play an essential role in developing immunity against viral infections. Future studies need to be undertaken to find the relationship between lung microbiome and COVID-19 disease.

Urgent Peritoneal Dialysis in Patients With COVID-19 and Acute Kidney Injury: A Single-Center Experience in a Time of Crisis in the United States.

At Montefiore Medical Center in The Bronx, NY, the first case of coronavirus disease 2019 (COVID-19) was admitted on March 11, 2020. At the height of the pandemic, there were 855 patients with COVID-19 admitted on April 13, 2020. Due to high demand for dialysis and shortages of staff and supplies, we started an urgent peritoneal dialysis (PD) program. From April 1 to April 22, a total of 30 patients were started on PD. Of those 30 patients, 14 died during their hospitalization, 8 were discharged, and 8 were still hospitalized as of May 14, 2020. Although the PD program was successful in its ability to provide much-needed kidney replacement therapy when hemodialysis was not available, challenges to delivering adequate PD dosage included difficulties providing nurse training and availability of supplies. Providing adequate clearance and ultrafiltration for patients in intensive care units was especially difficult due to the high prevalence of a hypercatabolic state, volume overload, and prone positioning. PD was more easily performed in non-critically ill patients outside the intensive care unit. Despite these challenges, we demonstrate that urgent PD is a feasible alternative to hemodialysis in situations with critical resource shortages.