Clinical characteristics and risk factors of patients with COVID-19 developing barotrauma

Background: At our hospital, people with COVID-19 (coronavirus disease 2019) had a high rate of pulmonary barotrauma. Therefore, the current study looked at barotrauma in COVID-19 patients getting invasive and non-invasive positive pressure ventilation to assess its prevalence, clinical results, and features. Methodology: Our retrospective cohort study comprised of adult COVID-19 pneumonia patients who visited our tertiary care hospital between April 2020 and September 2021 and developed barotrauma. Result(s): Sixty-eight patients were included in this study. Subcutaneous emphysema was the most frequent type of barotrauma, reported at 67.6%;pneumomediastinum, reported at 61.8%;pneumothorax, reported at 47.1%. The most frequent device associated with barotrauma was CPAP (51.5%). Among the 68 patients, 27.9% were discharged without supplemental oxygen, while 4.4% were discharged on oxygen. 76.5% of the patients expired because of COVID pneumonia and its complications. In addition, 38.2% of the patients required invasive mechanical breathing, and 77.9% of the patients were admitted to the ICU. Conclusion(s): Barotrauma in COVID-19 can pose a serious risk factor leading to mortality. Also, using CPAP was linked to a higher risk of barotrauma.Copyright © 2021 Muslim OT et al.

Corrigendum: Helmet ventilation for pediatric patients during the COVID-19 pandemic: A narrative review.

[This corrects the article DOI: 10.3389/fped.2022.839476.].

Respiratory support for adult patients with COVID-19

The COVID-19 pandemic is creating unique strains on the healthcare system. While only a small percentage of patients require mechanical ventilation and ICU care, the enormous size of the populations affected means that these critical resources may become limited. A number of non-invasive options exist to avert mechanical ventilation and ICU admission. This is a clinical review of these options and their applicability in adult COVID-19 patients. Summary recommendations include: (1) Avoid nebulized therapies. Consider metered dose inhaler alternatives. (2) Provide supplemental oxygen following usual treatment principles for hypoxic respiratory failure. Maintain awareness of the aerosol-generating potential of all devices, including nasal cannulas, simple face masks, and venturi masks. Use non-rebreather masks when possible. Be attentive to aerosol generation and the use of personal protective equipment. (3) High flow nasal oxygen is preferred for patients with higher oxygen support requirements. Non-invasive positive pressure ventilation may be associated with higher risk of nosocomial transmission. If used, measures special precautions should be used reduce aerosol formation. (4) Early intubation/mechanical ventilation may be prudent for patients deemed likely to progress to critical illness, multi-organ failure, or acute respiratory distress syndrome (ARDS).Copyright © 2020 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of the American College of Emergency Physicians.

Placental Thrombosis Resulting in Hypoxic Ischemic Encephalopathy in an Infant of a Mother with Covid-19

Case Report: Since the beginning of the Coronavirus Disease 2019 (COVID-19) pandemic, there has been much work to understand the negative effects of SARS-CoV-2 on tissues expressing the Angiotensin Converting Enzyme-2 (ACE2) receptor, including the placenta. However, there is limited information regarding placental pathology findings in mothers with COVID-19 and the effects of SARS-CoV-2 on the placenta. The available research reports effects on the fetus ranging from minimal to intrauterine fetal demise. Case Description: A 4680g baby boy was born at 38+1 weeks of gestation to 36y old G4P1021 female via repeat cesarian section. The pregnancy was complicated by advanced maternal age, chronic hypertension with superimposed pre-eclampsia with severe features, BMI of 80, and SARS-CoV-2 infection. The mother had mild COVID-19 symptoms and did not require hospitalization or oxygen support. Prenatal ultrasounds were limited due to body habitus. At the time of delivery, there was clear amniotic fluid. Upon delivery the infant was cyanotic and limp and was brought to the warmer immediately. Non-invasive positive pressure ventilation was initiated at 5 minutes of life with improvement in infant color and oxygen saturation. He was then admitted to the Neonatal Intensive Care Unit (NICU). APGARs were 2, 3, 5, and 7 at 1, 5, 10, and 15 minutes respectively. Cord gases showed severe metabolic acidosis. The patient was diagnosed with hypoxic-ischemic encephalopathy (HIE) and therapeutic hypothermia was initiated. Both the NICU and obstetric teams were unable to identify a clear perinatal cause of HIE in this patient. Later, the placenta pathology report revealed a large placenta for estimated gestational age corresponding to the 75th percentile, villous parenchyma with focal chorangiosis and thrombi, with unremarkable fetal membrane and three vessel umbilical cord. The cause of HIE was then thought to be due to the placental thrombi likely caused by SARS-CoV-2 infection. Discussion(s): Fetal vascular malperfusion and fetal vascular thrombus have been noted as a common finding in the placentas of pregnant women who test positive for SARS-CoV-2. There are various causes of HIE, from maternal, placental and fetal factors. This patient had no clinically evident hypoxic event, but information was limited due to the lack of monitoring of the fetus in utero. Given the mother's SARS-CoV-2 infection and the placental pathology findings, it is likely that the cause of this patient's HIE was related to the effects on the placenta from SARS-CoV-2. Conclusion(s): As more information comes to light about the effects of SARS-CoV-2 on the placenta, it is important to consider a maternal SARS-CoV-2 infection during pregnancy as a cause of HIE in a newborn.

Ventilator avoidance among critically ill COVID-19 patients with acute respiratory distress syndrome

Introduction: Misinformation citing mechanical ventilation, not the virus, as causing death in COVID-19 patients with respiratory failure has led to ventilator avoidance (initial refusal of intubation) during the pandemic. Method(s): Prospective observational cohort study (March 2020- June 2021) evaluating the incidence and significance of initial refusal of intubation in patients with critical COVID-19 defined as ARDS requiring > 55% sustained FiO2 on high flow nasal canula (HFNC), non-invasive positive-pressure ventilation (NIPPV) or requiring intubation. Outcomes included in-hospital mortality and 1-year modified Rankin Scale (mRS) score. Logistic regression was used to estimate the age and Charlson Comorbidity Index adjusted odds ratio (OR) of in-hospital death. The Wilcoxon rank-sum test was used to evaluate differences in the mRs. Result(s): The cohort was predominantly non-Latino white (76%), male (65%), unvaccinated (99.4%), mean age of 66, and good pre- COVID-19 functional status (median mRs score of 0). Overall, 315 patients were critically ill due to COVID-19 with an in-hospital mortality of 41.9% (132/315;95% CI 36-47%). In patients in whom intubation was recommended 39% initially refused (40/102;95% CI 30-49%). Utilization of HFNC (90%) and NIPPV (72%) were similar between groups, however actual use of mechanical ventilation differed (98.4% in those that did not initially refuse compared to 20% in those that initially refused (p = 0.001)). In-hospital mortality was 79.3% (49/62) in those who initially did not refuse intubation compared to 77.5% (31/40) in those who refused (adjusted OR 1.3;95% CI 0.5-.5). The distribution of 1-year mRS was not significantly different between groups (p = 1.0) (Fig. 1). Conclusion(s): Among critically ill patients with COVID-19 associated ARDS, ventilator avoidance was common however, it was not associated with increased in-hospital mortality or a difference in 1-year functional outcome.

Lung ultrasound scoring system vs ROX index as a predictor for progression to the invasive mechanical ventilation in COVID-19 patients

Background: During the outbreak of the highly contagious Coronavirus disease 19 (COVID19), rapid and simple prognostic tools were needed to support clinical decisions and predict the need of invasive mechanical ventilation. the ROX index, and the lung ultrasound score (LUSS) were proposed to objectively predict patient prognosis in addition to the subjective clinical assessment Aim: This study aimed to compare lung ultrasound score with ROX index in predicting the need of invasive ventilation in COVID-19 patients requiring advanced oxygen therapy. Patients and Methods: We studied 50 patients with severe COVID-19 pneumonia in the intensive care unit in the isolated area at Kasr Al-Ainy hospital. Complete Medical history, physical examination and laboratory investigations were obtained on admission. All patients underwent bedside lung ultrasonography scan and LUSS was calculated at the 2nd and the 12th hours, also ROX index was calculated at the 2nd, 6th and 12th hours from initiating the advanced oxygen therapy. Result(s): From a total of fifty patients with COVID-19, 56.0% were males, with mean age of 65.98 + 11.68 years, and mortality rate was 68%. The optimal cut off value of the ROX index at (2, 6, 12 hour) is (2.495, 2.675, 3.06) respectively, (p <0.001) with sensitivity 90.9% and specificity 76.5% at the 12 hour. Also the optimal cut off point of LUSS is 25.50 (p <0.001) with sensitivity 93.9% and specificity 88.2% for prediction of the invasive mechanical ventilation. Conclusion and recommendations: The study concluded that LUSS is more sensitive in predicting the need of invasive mechanical ventilation than ROX index.Copyright © 2023, Codon Publications. All rights reserved.

Pneumomediastinum (PM) as a complication of COVID-19 disease

Case report Introduction: PM is a rare, but potentially life-threatening complication during COVID 19 pandemic, being reported in patients affected by COVID-19 pneumonia, even in the absence of mechanical ventilation-related barotrauma. Case details: We reported the clinical data of 4 cases affected by COVID-19 pneumonia complicated with PM. Chest CT scan showed multiple confluent areas of ground-glass opacities, crazy paving pattern, PM, cervical subcutaneous emphysema, and pneumothorax in one case. Management included pharmacological treatment, oxygen supplementation and no acute intervention recommended by cardiothoracic surgery. Case 1: 50-year- old male without past medical history, non-smoker, hypoxic on the day of admission. During the hospital stay, he continued to require increasing levels of oxygen and was subsequently flown to a tertiary care center for higher level of care. Case 2: 38-year- old male admitted with a 7-day history of fever, dyspnea and cought. He continues to be symptomatic with neurological manifestations (COVID19 Encephalopathy). Finally whose dyspnea regressed during hospitalization, he was discharged at his own request to come for control. Case 3: 73-year- old male with a history of hypertension, non-smoker, presented with complaints of shortness of breath for 1 week. He did not receive non invasive positive pressure ventilation. The pneumothorax and PM were managed conservatively. Case 4: 53-year- old lady with no significant past medical history, presented with fever and cough for 10 days and worsening shortness of breath for two days. Progressive deterioration of respiratory function transferred her to the intensive care unit. In view of worsening hypoxia and increased work of breathing, she was intubated on the same day and was started on volume control ventilator support. Despite the support measures she developed multiple organ failure and passed 35 days after the symptoms initiated. Conclusion(s): PM is usually self-limiting and is managed conservatively. Treatment of the underlying causes and least damaging ventilator settings possible to achieve adequate oxygenation are the mainstays in managing PM. COVID-19 patients with PM seem to have a more complicated clinical course and poor outcome.

Factors associated with non-invasive positive pressure ventilation failure in a COVID-19 Intermediate Care Unit

Aim: To evaluate the efficacy of NIPPV (CPAP, HELMET-CPAP or NIV) in COVID-19 patients treated in the dedicated COVID-19 Intermediate Care unit of Coimbra Hospital and University Centre (CHUC), Portugal, and to assess factors associated with NIPPV failure. Method(s): Patients admitted to the Intermediate Care Unit of CHUC, from December 1st 2020 to February 28th 2021, treated with NIPPV due to confirmed COVID-19 were included. The primary outcome was NIPPV failure (orotracheal intubation (OTI) or death during hospital stay). Factors associated with NIPPV failure were included in an univariate binary logistic regression analysis and those with a significance level of p<0.001 were selected to enter a multivariate regression model. Result(s): 163 patients were included, 64.4% were males (n=105) and the median age was 66 years (IQR 56-75). Overall, 97 patients (59.5%) were successfully treated with NIPPV, while failure was observed in 66 (40.5%), of which 26 (39.4%) were intubated and 40 (60.6%) died during hospital stay. Highest CRP during hospital stay (OR 1.164;95%CI 1.036-1.308) and morphine use (OR 24.771;95%CI 1.809-339.241) were identified as independent predictors in the multivariate logistic model. Adherence to prone positioning (OR 0.109;95%CI 0.017-0.700) and a higher value of the lowest platelet count during hospital stay (OR 0.977;95%CI 0.960-0.994) were associated with a favourable outcome. Conclusion(s): Highest CRP and morphine use were independent predictors of OTI or death. Adherence to prone positioning and a higher value of the lowest platelet count during hospital stay were associated with a favourable outcome.

Guideline-based management of acute respiratory failure and acute respiratory distress syndrome.

Acute respiratory failure (ARF) is defined by acute and progressive hypoxemia caused by various cardiorespiratory or systemic diseases in previously healthy patients. Among ARF, acute respiratory distress syndrome (ARDS) is a serious condition with bilateral lung infiltration, which develops secondary to a variety of underlying conditions, diseases, or injuries. This review summarizes the current standard of care for ARF and ARDS based on current major guidelines in this field. When administering fluid in patients with ARF, particularly ARDS, restrictive strategies need to be considered in patients without shock or multiple organ dysfunction. Regarding oxygenation targets, avoiding excessive hyperoxemia and hypoxemia is probably a reasonable choice. As a result of the rapid spread and accumulation of evidence for high-flow nasal cannula oxygenation, it is now weakly recommended for the respiratory management of ARF in general and even for initial management of ARDS. Noninvasive positive pressure ventilation is also weakly recommended for the management of certain ARF conditions and as initial management of ARDS. Low tidal volume ventilation is now weakly recommended for all patients with ARF and strongly recommended for patients with ARDS. Limiting plateau pressure and high-level PEEP are weakly recommended for moderate-to-severe ARDS. Prone position ventilation with prolonged hours is weakly to strongly recommended for moderate-to-severe ARDS. In patients with COVID-19, ventilatory management is essentially the same as for ARF and ARDS, but awake prone positioning may be considered. In addition to standard care, treatment optimization and individualization, as well as the introduction of exploratory treatment, should be considered as appropriate. As a single pathogen, such as SARS-CoV-2, exhibits a wide variety of pathologies and lung dysfunction, ventilatory management for ARF and ARDS may be better tailored according to the respiratory physiologic status of individual patients rather than the causal or underlying diseases and conditions.

Supportive Care in Patients with Critical Coronavirus Disease 2019.

Specific therapies for the treatment of coronavirus disease 2019 (COVID-19) have limited efficacy in the event a patient worsens clinically and requires admission to the intensive care unit (ICU). Thus, providing quality supportive care is essential to the overall management of patients with critical COVID-19. Patients with respiratory failure not requiring intubation should be supported with noninvasive positive pressure ventilation, continuous positive airway pressure, or high flow oxygenation. Use of these respiratory modalities may prevent patients from subsequently requiring intubation. Basic components of supportive care for the critically ill should be applied equally to patients with COVID-19 in the ICU.

A CASE SERIES OF RAPID PROGRESSIVE FIBROTIC LUNG DISEASE AS A SEQUELA OF COVID-19 PNEUMONIA

SESSION TITLE: Pulmonary Issues in Transplantation Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Fibrotic interstitial lung disease (fILD) can be idiopathic or associated with several underlying conditions and in response to various types of injury. Post COVID-19 fILD is an increasingly recognized clinical entity with the potential for a large burden of morbidity and mortality.[1] We present a series of 6 patients with progressive pulmonary fibrosis as sequela of COVID-19 requiring lung transplantation. CASE PRESENTATION: Four of the 6 patients had known underlying chronic ILD prior to COVID-19 infection (2 with idiopathic pulmonary fibrosis [IPF] and 1 each with scleroderma and rheumatoid arthritis associated ILD). The other 2 patients had no prior history of lung disease and asymptomatic before infection. One of these had a strong family history of IPF. The presentations involved signs of progressive respiratory failure after the initial lung injury from COVID-19. 4 patients were hospitalized during their acute COVID-19 illness and had varying treatments including steroids, antibiotics, anti-virals, convalescent plasma, Tocilizumab, and non-invasive positive pressure ventilation. At the time of transplant evaluation, CT imaging showed prominent interstitial thickening, honeycombing consistent with fibrotic processes for all our patients;PFT revealed severe restrictive ventilatory defect with reduced diffusion capacity ranging 24%-53%;3 patients required venous-venous extracorporeal membrane oxygenation (ECMO) as a bridge to transplantation for 14 and 93 days. The remainder required 6-10 L of supplemental oxygenation at rest. Two patients underwent initial transplant evaluation while in respiratory failure.5 patients received bilateral lung transplantation and one single left lung transplantation.Duration of time between initial COVID-19 induced lung injury and transplantation ranged from 3-13 months, with a median 6-7 months.Lung explant pathology showed advanced usual interstitial pneumonia in all. Superimposed diffuse alveolar damage was noted in 3 cases. Post-transplant to discharge ranged 10-31 days and at 2 months follow-up, all patients were liberated of oxygen needs. All subjects remain alive at a median 11-12 months, with no evidence of allograft dysfunction. DISCUSSION: Since the emergence of SARS-COV2 in 2019, histopathological fibrotic anomalies have been found to be present in up to one-third of those who recover from ARDS due to COVID-19 [2] and their incidence increases as duration of ARDS increases [3]. Further work is required to understand the pathogenesis of the fibrotic process following acute COVID-19. CONCLUSIONS: We highlight this syndrome with our case series of 6 patients who showed progressive fibrotic disease after COVID-19. Patients with pre-exiting ILD appear to be particularly at risk but this entity may occur in those without pre-existing ILD. Lung transplantation offers a viable treatment option for selected patients with an otherwise poor prognosis. Reference #1: 1.Bharat, A., Querrey, M., Markov, N. S., Kim, S., Kurihara, C., Garza-Castillon, R., Manerikar, A., Shilatifard, A., Tomic, R., Politanska, Y., Abdala-Valencia, H., Yeldandi, A. V., Lomasney, J. W., Misharin, A. V., & Budinger, G. (2020). Lung transplantation for pulmonary fibrosis secondary to severe COVID-19. medRxiv : the preprint server for health sciences, 2020.10.26.20218636. https://doi.org/10.1101/2020.10.26.20218636 Reference #2: 2. Rai DK, Sharma P, Kumar R. Post covid 19 pulmonary fibrosis. Is it real threat?. Indian J Tuberc. 2021;68(3):330-333. doi:10.1016/j.ijtb.2020.11.003 Reference #3: 3. Williamson EJ, Walker AJ, Bhaskaran K, Bacon S, Bates C, Morton CE, Curtis HJ, Mehrkar A, Evans D, Inglesby P, Cockburn J, McDonald HI, MacKenna B, Tomlinson L, Douglas IJ, Rentsch CT, Mathur R, Wong AYS, Grieve R, Harrison D, Forbes H, Schultze A, Croker R, Parry J, Hester F, Harper S, Perera R, Evans SJW, Smeeth L, Goldacre B. Factors associated with C VID-19-related death using OpenSAFELY. Nature. 2020 Aug;584(7821):430-436. doi: 10.1038/s41586-020-2521-4. Epub 2020 Jul 8. PMID: 32640463;PMCID: PMC7611074. DISCLOSURES: no disclosure on file for Philip Camp;research relationship with United Therapeutics Please note: 2016- ongoing by Reda Girgis, value=Grant/Research research relationship with Pfizer Please note: 2014-2020 by Reda Girgis, value=Grant/Research Speaker/Speaker's Bureau relationship with Boehringher Ingelheim Please note: 2016-ongoing by Reda Girgis, value=Honoraria Speaker/Speaker's Bureau relationship with Genentech Please note: 2016-ongoing by Reda Girgis, value=Honoraria No relevant relationships by Ryan Hadley No relevant relationships by Sheila Krishnan No relevant relationships by Sheetal Maragiri No relevant relationships by Edward Murphy No relevant relationships by Jay Patel No relevant relationships by Keval Ray No relevant relationships by Gayathri Sathiyamoorthy No relevant relationships by Neel Shah No relevant relationships by Subhan Toor

OUT OF THIN AIR: A CASE OF SEVERE SUBCUTANEOUS EMPHYSEMA, PNEUMOMEDIASTINUM, AND PNEUMOTHORAX ASSOCIATED WITH COVID-19

SESSION TITLE: COVID-19 Case Report Posters 3 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: One of the greatest challenges of the coronavirus (COVID-19) pandemic has been deciphering its unique properties, such as the propensity to infect and damage lung epithelium, thereby increasing susceptibility to pulmonary complications.(1, 2) A 2020 cohort study comparing patients with acute respiratory distress syndrome (ARDS) from COVID-19 and ARDS from other causes showed a significantly higher rate of subcutaneous emphysema and pneumomediastinum in the COVID-19 group, suggesting these diagnoses may be due to direct viral damage rather than exposure to positive pressure alone.(3) Presented here is a patient with no underlying lung pathology who was diagnosed with COVID-19 and developed severe subcutaneous emphysema, pneumomediastinum, and pneumothorax. CASE PRESENTATION: A 74 year old male with a history of hypertension presented to the emergency room with a 5-day history of difficulty breathing, cough, fever, chills, and weakness. He tested positive for COVID-19, required non-invasive positive pressure ventilation (NIPPV), and was started on ceftriaxone, doxycycline, and daily dexamethasone. He received a five-day course of remdesivir and one dose of convalescent plasma. By day 9, a chest x-ray revealed a left apical pneumothorax, bilateral subcutaneous emphysema, and pneumomediastinum. On day 12, his respiratory status deteriorated, necessitating invasive mechanical ventilation. A chest CT showed extensive subcutaneous emphysema involving the chest, supraclavicular and axillary regions, and abdominal wall, as well as extensive pneumomediastinum and a moderate left pneumothorax. A left-sided thoracostomy tube was placed and he was proned per ICU protocol. He required placement of a second left-sided chest tube due to persistent worsening pneumothorax. On day 28, despite all aggressive measures, he expired from acute hypoxemia. DISCUSSION: Although this patient was exposed to NIPPV, the severe degree of lung pathology was inconsistent with the amount of positive pressure administered. Furthermore, he lacked underlying pulmonary disease that would compromise his lung compliance to this magnitude. Combining evidence that COVID-19 can cause epithelial lung damage, the patient's absence of pulmonary risk factors, and his severe degree of lung damage incongruent with his exposure to positive pressure, is reasonable to extrapolate that a significant portion of his lung pathology was a result of direct damage from COVID-19. CONCLUSIONS: Patients with COVID-19 may be at higher risk for the development of subcutaneous emphysema, pneumomediastinum, and pneumothorax, likely due to direct viral effect. Lung damage seen may be disproportionate to exposure of positive pressure and may also be seen in the absence of any underlying pulmonary comorbidities. Awareness of this observed pathophysiology may help guide clinicians to optimize ventilator management as well as anticipate potential complications. Reference #1: Hu B, Guo H, Zhou P, Shi ZL. Characteristics of SARS-CoV-2 and COVID-19 [published correction appears in Nat Rev Microbiol. 2022 Feb 23;:]. Nat Rev Microbiol. 2021;19(3):141-154. doi:10.1038/s41579-020-00459-7 Reference #2: Miró Ò, Llorens P, Jiménez S, et al. Frequency, Risk Factors, Clinical Characteristics, and Outcomes of Spontaneous Pneumothorax in Patients With Coronavirus Disease 2019: A Case-Control, Emergency Medicine-Based Multicenter Study. Chest. 2021;159(3):1241-1255. doi:10.1016/j.chest.2020.11.013 Reference #3: Lemmers DHL, Abu Hilal M, Bnà C, et al. Pneumomediastinum and subcutaneous emphysema in COVID-19: barotrauma or lung frailty?. ERJ Open Res. 2020;6(4):00385-2020. Published 2020 Nov 16. doi:10.1183/23120541.00385-2020 DISCLOSURES: No relevant relationships by Shanaz Azad No relevant relationships by Sarah Monaghan No relevant relationships by Brandon Nance No relevant relationships by Samantha Peterson

High-flow nasal cannulae for respiratory support in adult intensive care patient

Background High-flow nasal cannulae (HFNC) deliver high flows of blended humidified air and oxygen via wide-bore nasal cannulae and may be useful in providing respiratory support for adults experiencing acute respiratory failure, or at risk of acute respiratory failure, in the intensive care unit (ICU). This is an update of an earlier version of the review. Objectives To assess the effectiveness of HFNC compared to standard oxygen therapy, or non-invasive ventilation (NIV) or non-invasive positive pressure ventilation (NIPPV), for respiratory support in adults in the ICU. Search methods We searched CENTRAL, MEDLINE, Embase, CINAHL, Web of Science, and the Cochrane COVID-19 Register (17 April 2020), clinical trial registers (6 April 2020) and conducted forward and backward citation searches. Selection criteria We included randomized controlled studies (RCTs) with a parallel-group or cross-over design comparing HFNC use versus other types of non-invasive respiratory support (standard oxygen therapy via nasal cannulae or mask;or NIV or NIPPV which included continuous positive airway pressure and bilevel positive airway pressure) in adults admitted to the ICU. Data collection and analysis We used standard methodological procedures as expected by Cochrane.

IDF21-0311 Pre-Admission, Diabetic Glycemic Control on 60-Day Mortality and Major Adverse Cardiovascular Events from COVID-19

Background: Patients with diabetes mellitus (DM) are at increased risk for intubation, death, and other complications from COVID-19. However, the importance of a patient’s glycemic control preceding the COVID-19 infection is less well understood. Method: From March to November 2020, data from adult patients with confirmed COVID-19 admitted to Rush University System for Health (RUSH) was studied. Patients with both a pre-existing history of diabetes mellitus (DM) and a hemoglobin A1c (HbA1c) measurement during their hospitalization were included. Based on their HbA1c, patients were then divided into 4 groups: adequate glycemic control (≤ 6.5), mild elevation (6.5 – 7.4), intermediate elevation (7.5 – 8.4), and severe elevation (≥ 8.5). Multivariable logistic regression, adjusted for age, body mass index, and pre-existing history of atrial fibrillation, coronary artery disease, hypertension, and chronic obstructive pulmonary disorder, was performed with glycemic control group as a predictor for 60-day mortality and severe COVID-19, which was a composite of 60-day mortality or requiring the intensive care unit, non-invasive positive pressure ventilation, or mechanical ventilation. Major adverse cardiac events (MACE) were defined as nonfatal myocardial injury, nonfatal stroke, or cardiovascular death. Results: Of the 1682 patients admitted, 774 had pre-existing DM, and 534 had HbA1c measurement during their hospitalization. The median HbA1c value was 8.0% (interquartile range 6.6% – 9.9%). In our entire cohort, 75 (14.0%) and 280 (52.4%) patients suffered 60-day mortality and severe COVID-19 infection, respectively. When adjusting for baseline characteristics and comorbidities, patients with mild (adjusted odds ratio [aOR] 2.39 [CI 1.04 – 5.83];p < 0.05) and intermediate (aOR 3.59 [CI 1.49 – 9.12];p < 0.01) HbA1c elevation were at increased risk of 60-day mortality compared to those with adequate glycemic control;no statistically significant difference was present in those with severe elevation (aOR 2.19 [CI 0.95 – 5.44];p = 0.08). Furthermore, only the mild HbA1c elevation group was at increased risk for severe COVID-19 infection (aOR 1.88 [CI 1.06 – 3.38];p < 0.05). Those with intermediate (aOR 1.77 [CI 0.94 – 3.33];p = 0.08) or severe (aOR 1.57 [CI 0.92 – 2.70];p = 0.10) HbA1c elevation were not at higher risk for severe COVID-19 infection. When comparing other 60-day outcomes, there was no difference between the glycemic groups in MACE, life-threatening arrhythmia, deep venous thrombosis, acute renal failure requiring renal replacement therapy, and pulmonary embolism (Table 1). Discussion: In our cohort, patients with DM with an HbA1c of 6.5 – 8.4 were at increased risk of 60-day mortality, while those with an HbA1c of 6.5 – 7.4 were at an increased risk of severe COVID-19 infection.

Suspected Neonatal COVID-19 Infection in an Extremely Premature Infant

Introduction: The COVID-19 pandemic has been widely described, however, there is limited data regarding neonatal infection. We present an extremely premature neonate with suspected COVID-19 pneumonia treated with Remdesivir. Case Description: Our patient is an infant born via emergency cesarean section for chorioamnionitis at 24 weeks gestational age with extremely low birth weight (ELBW). Mother is a 23-yearold primigravid female whose pregnancy was complicated by asymptomatic COVID-19 infection diagnosed by nasopharyngeal PCR ten days prior to delivery. Antenatal steroids were given for imminent premature delivery. Infant was intubated during initial resuscitation then extubated to non-invasive positive pressure ventilation (NIPPV) on day three of life. On day seven of life, she developed increasing apneic spells and feeding intolerance. Empiric antibiotics were initiated while awaiting blood and cerebrospinal fluid cultures. Blood culture grew Serratia marcescens and antibiotic coverage was tailored to cefepime monotherapy. Our patient remained stable on non-invasive respiratory support seven days into her sepsis event. Around this time, histopathological analysis of the placenta revealed acute villitis and intervillositis highly suggestive of COVID-19 placentitis. A positive nasopharyngeal COVID-19 PCR was noted on day ten of life. Our patient remained stable on non-invasive respiratory support until day fourteen of life, when she suddenly developed refractory hypoxemia requiring intubation. This coincided with acute changes in her chest x-ray (Fig 1). The negative bacterial respiratory culture, timing of clinical deterioration, and placental findings increased our suspicion for symptomatic co-infection with COVID-19. Patient continued to have refractory hypoxia and poor ventilation despite maximum settings and inhaled nitric oxide. After an extensive multidisciplinary discussion, patient received Remdesivir as a compassionate measure. Neonatal dosage was well tolerated with no adverse effects at 5 mg/kg loading dose followed by four days of maintenance dosing at 2.5 mg/kg. Significant clinical improvement was noted after the second day by decreasing FiO2 requirements. COVID-19 PCR remained positive ten days after Remdesivir treatment was completed. Patient was extubated to NIPPV on day thirty-six of life and is currently requiring no respiratory support at 37 weeks corrected age. Discussion: We present an ELBW neonate with placental findings typical of COVID-19 infection and refractory hypoxemia likely due to COVID-19 pneumonia. To date, the mechanism for this infant's infection is unclear. Based on the Acharya et al. Classification for Maternal-Fetal-Neonatal SARS-CoV-2 infection, our patient fits into probable neonatal infection acquired post-partum category. We have strong evidence of infection but lack of absolute proof to confirm congenital disease as no testing was done at birth. We acknowledge that part of the clinical course was complicated by sepsis, however, the peak of illness correlates with the typical clinical course for COVID-19 infection. Conclusion: To our knowledge, this may be the youngest patient documented to have COVID-19 pneumonia and received Remdesivir treatment.

A Case of Rapidly Progressive Interstitial Lung Disease Due to Antisynthetase Syndrome

Introduction: Antisynthetase syndrome is a rare autoimmune disease. Clinical characteristics include interstitial lung disease (ILD), myositis, Raynaud's phenomenon, mechanic's hands, and arthritis. The condition is characterized by antibodies targeting an aminoacyl transfer RNA synthetase. Compared to other inflammatory myopathies, there is a higher prevalence and increased severity of ILD. Case Report: A 34-year-old female with a history of polycystic ovarian syndrome presented with progressive dyspnea during her third trimester of pregnancy. Initial computed tomography angiography (CTA) chest showed widespread multifocal and multilobar ground-glass opacities and nodular areas of consolidation. COVID-19 testing was negative. She went into preterm labor and delivered her baby at 30 weeks. About 10 days after delivery, her respiratory symptoms worsened. Transbronchoscopic lung biopsy was nondiagnostic. She subsequently underwent surgical lung biopsy which revealed organizing pneumonia and interstitial fibrosis. Laboratory studies revealed a high Jo-1 antibody of 1033U (normal less than 20U), positive ANA, creatine kinase 186 U/L, as well as aldolase 22.3 U/L leading to a diagnosis of antisynthetase syndrome. The patient continued to be dyspneic and developed increased oxygen requirements. Treatment was initiated with 1 dose of 125 mg of methylprednisolone followed by 1 g of methylprednisolone for 3 days, after which she was continued on oral prednisone. She was additionally started on 250 mg of mycophenolate mofetil. Despite these therapies she continued to have increased oxygen requirements, eventually requiring noninvasive positive pressure ventilation and ultimately intubation with mechanical ventilation. Chest x-ray demonstrated worsening bilateral patchy infiltrates. Given her clinical deterioration, she underwent 5 treatments of plasma exchange after which she received 1000 mg of rituximab. The patient improved on this therapy and was able to be extubated after 3 days. Her oxygen requirements subsequently decreased and she was discharged on a prednisone taper;mycophenolate with a goal dose of 1000 mg twice daily;and plan for continued rituximab infusions. At 2 months follow-up, the patient was doing well without the need for supplemental oxygen. Discussion: This case demonstrates a rare disease in a peripartum patient. A high suspicion for antisynthetase syndrome is required to initiate autoimmune testing, particularly since there can be ILD predominant phenotypes without significant evidence of a myositis. Treatment is not standardized but typically consists of corticosteroids and other immunosuppressive agents. In severe cases of antisynthetase syndrome that are refractory to initial corticosteroid therapy, therapeutic plasma exchange can be performed.

A Single Center Experience with Early Initiation of ECMO Prior to Mechanical Ventilation in COVID-19 Patients with Severe ARDS

Background: Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic that results in a viral pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Prognosis is poor among those that develop acute respiratory distress syndrome and progress to mechanical ventilation. Due to the high mortality associated with mechanical ventilation and the unique physiology associated with COVID-19, we compared outcomes in COVID-19 patients placed on ECMO prior to initiation of mechanical ventilation (early group) to patients treated with ECMO after mechanical ventilation (conventional group). Methods: This is a single center retrospective analysis of COVID-19 patients placed on veno-venous (VV) ECMO between 04/06/2020 and 01/15/2021 in a tertiary high-volume ECMO center. Patients between 18 - 70 years of age with a diagnosis of SARS-CoV-2 and diagnosed with ARDS. Patients were considered for ECMO if they had a P/F ratio of less than 50 mmHg for at least three hours, a P/F ratio of less than 80 mmHg for at least 6 hours or an arterial blood pH of less than 7.25 with a pCO2 greater than or equal to 60 mmHg for at least six hours despite optimized ventilator settings (RR> 35 breaths/minute, plateau pressure ≤ 32, tidal volume of 6ml/kg of predicted body weight, FiO2 ≥ 80% and PEEP ≥ 10 cm water). A subset of patients with a rapid deterioration (rapid escalation of O2 requirements, tachypnea RR > 30, tachycardia HR >100) or with clinical signs consistent with poor tolerance to positive pressure ventilation such as a pneumothorax or pneumomediastinum were considered for ECMO prior to mechanical ventilation if they had a P/F <80 despite selfproning with either HFNC 40L/100% in addition to a nonrebreather mask with 15L/100% or non-invasive positive pressure ventilation (NIPPV) with an FiO2 100%. The primary outcome was survival to discharge assessed as a binary outcome of survived or non-survived. Secondary outcomes evaluated included discharge location, length of stay, and incidence of adverse events such as bleeding events, infection, CVA, and pneumothorax requiring chest tube placement. Results: A total of 100 patients were reviewed, including 24 early ECMO patients and 76 conventional ECMO patients. The mean age of the cohort was 48.9 + 11.5 years, 28% were female, and 74% were Hispanic. At baseline, the mean BMI was 31.6 + 5.8, 55% had a history of hypertension, 36% were diabetic and 9% had a history of asthma. Overall, 57% of patients survived to discharge with a median of 23.3 (7.8-40.6) days on ECMO. There were no significant differences in age, gender, BMI, comorbidities, or APACHE scores between the two groups. Prior to ECMO, the early group had lower P/F ratios (52.7 + 11.5 vs. 71.1 + 20.7, p <0.0001), higher pH (7.4 + 0.0 vs. 7.3 + 0.1, p <0.0001), and lower CO2 (36.1 + 6.8 vs 50.9 + 19.1, p <0.0001) than the conventional cohort. Though not significant, there was a trend towards survival in the early ECMO group compared to the conventional group (71% survival vs. 53%, p= .12). Of the early cohort, 15 patients required intubation at some point after cannulation for a median time of 2.5 days (0- 27.0 days). Of the nine patients never intubated, two patients expired, two received a lung transplant, three were discharged home, one discharged to rehab and one to an LTAC facility. There was no difference in adverse events between the two groups. Conclusions: Certain patients with severe ARDS due to COVID-19 may benefit from VV-ECMO cannulation prior to mechanical ventilation with similar outcomes and a trend towards improved mortality.

Respiratory outcomes after twelve weeks in patients recovered from COVID-19 managed with non-invasive positive pressure ventilation

Aim: To assess the respiratory outcomes twelve weeks after the management with non-invasive positive pressure ventilation (NIPPV) in patients recovered from severe corona virus disease 2019 (COVID-19). Methodology: The cross-sectional analytical study was conducted in the Department of Pulmonology, Sir Ganga Ram Hospital Lahore between October 2020 and March 2021. Total 124 patients visiting the hospital twelve weeks after recovery from COVID-19 were enrolled using convenience sampling. After excluding patients with a history of previous respiratory symptoms before the development of COVID-19, data from 87 patients who required oxygen >15 L/minute and NIPPV support were subjected to final analysis. Results: The proportion of middle-aged adults was 52.9%, males 64.4% and smokers 49.4%. Twelve weeks after treatment with NIPPV, O2 saturation <97.0% at rest was found in 97.7% patients, PR >100 at rest in 16.1% patients, severe dyspnea in 65.5% patients, O2 dependency >5 L/min in 2.3% patients, severe CXR abnormalities in 20.7% patients and lung fibrosis in 27.6% patients. The distribution of SpO2, PR, and dyspnea status twelve weeks after recovery from severe COVID-19 were not significantly different between NIPPV duration groups (p-value >0.05). However, the number of patients with O2 dependency, severe CXR abnormality, and lung fibrosis were significantly different between NIPPV duration groups (all p-values <0.05). Conclusion: Oxygen desaturation, severe dyspnea and severe CXR abnormalities twelve weeks after the treatment with NIPPV were common among patients recovered from COVID-19. Severe CXR abnormality, lung fibrosis, and O2 dependency were significantly associated with prolonged duration of NIPPV.

Role of helmet ventilation during the 2019 coronavirus disease pandemic.

Coronavirus disease 2019 (COVID-19) has been declared a pandemic by the World Health Organization; it has affected millions of people and caused hundreds of thousands of deaths. Patients with COVID-19 pneumonia may develop acute hypoxia respiratory failure and require noninvasive respiratory support or invasive respiratory management. Healthcare workers have a high risk of contracting COVID-19 while fitting respiratory devices. Recently, European experts have suggested that the use of helmet continuous positive airway pressure should be the first choice for acute hypoxia respiratory failure caused by COVID-19 because it reduces the spread of the virus in the ambient air. By contrast, in the United States, helmets were restricted for respiratory care before the COVID-19 pandemic until the Food and Drug Administration provided the 'Umbrella Emergency Use Authorization for Ventilators and Ventilator Accessories'. This narrative review provides an evidence-based overview of the use of helmet ventilation for patients with respiratory failure.

Remdesivir and Tocilizumab for the Treatment of Severe COVID-19 in a Community Hospital: A Retrospective Cohort Study

Background. Growing evidence supports the use of remdesivir and tocilizumab for the treatment of hospitalized patients with severe COVID-19. The purpose of this study was to evaluate the use of remdesivir and tocilizumab for the treatment of severe COVID-19 in a community hospital setting. Methods. We used a de-identified dataset of hospitalized adults with severe COVID-19 according to the National Institutes of Health definition (SpO2 < 94% on room air, a PaO2/FiO2 < 300 mm Hg, respiratory frequency > 30/min, or lung infiltrates > 50%) admitted to our community hospital located in Evanston Illinois, between March 1, 2020, and March 1, 2021. We performed a Cox proportional hazards regression model to examine the relationship between the use of remdesivir and tocilizumab and inpatient mortality. To minimize confounders, we adjusted for age, qSOFA score, noninvasive positive-pressure ventilation, invasive mechanical ventilation, and steroids, forcing these variables into the model. We implemented a sensitivity analysis calculating the E-value (with the lower confidence limit) for the obtained point estimates to assess the potential effect of unmeasured confounding. Figure 1. Kaplan-Meier survival curves for in-hospital death among patients treated with and without steroids The hazard ratio was derived from a bivariable Cox regression model. The survival curves were compared with a log-rank test, where a two-sided P value of less than 0.05 was considered statistically significant. Figure 2. Kaplan-Meier survival curves for in-hospital death among patients treated with and without remdesivir The hazard ratio was derived from a bivariable Cox regression model. The survival curves were compared with a log-rank test, where a two-sided P value of less than 0.05 was considered statistically significant. Results. A total of 549 patients were included. The median age was 69 years (interquartile range, 59 - 80 years), 333 (59.6%) were male, 231 were White (41.3%), and 235 (42%) were admitted from long-term care facilities. 394 (70.5%) received steroids, 192 (34.3%) received remdesivir, and 49 (8.8%) received tocilizumab. By the cutoff date for data analysis, 389 (69.6%) patients survived, and 170 (30.4%) had died. The bivariable Cox regression models showed decreased hazard of in-hospital death associated with the administration of steroids (Figure 1), remdesivir (Figure 2), and tocilizumab (Figure 3). This association persisted in the multivariable Cox regression controlling for other predictors (Figure 4). The E value for the multivariable Cox regression point estimates and the lower confidence intervals are shown in Table 1. The hazard ratio was derived from a bivariable Cox regression model. The survival curves were compared with a log-rank test, where a two-sided P value of less than 0.05 was considered statistically significant. The hazard ratios were derived from a multivariable Cox regression model adjusting for age as a continuous variable, qSOFA score, noninvasive positive-pressure ventilation, and invasive mechanical ventilation. Table 1. Sensitivity analysis of unmeasured confounding using E-values CI, confidence interval. Point estimate from multivariable Cox regression model. The E value is defined as the minimum strength of association on the risk ratio scale that an unmeasured confounder would need to have with both the exposure and the outcome, conditional on the measured covariates, to explain away a specific exposure-outcome association fully: i.e., a confounder not included in the multivariable Cox regression model associated with remdesivir or tocilizumab use and in-hospital death in patients with severe COVID-19 by a hazard ratio of 1.64-fold or 1.54-fold each, respectively, could explain away the lower confidence limit, but weaker confounding could not. Conclusion. For patients with severe COVID-19 admitted to our community hospital, the use of steroids, remdesivir, and tocilizumab were significantly associated with a slower progression to in-hospital death while controlling for other predictors included in the models.