High-flow Ventilation Research Articles

Nasal high flow or noninvasive ventilation? navigating hypercapnic COPD exacerbation treatment: A randomized noninferiority clinical trial

BackgroundNoninvasive ventilation (NIV) has been the cornerstone for managing acute exacerbations of COPD (AECOPD) with hypercapnic respiratory failure. Nasal high flow (NHF) oxygen therapy has emerged as a potential alternative, offering a more tolerable modality with promising outcomes. The aim of the present study was to evaluate whether NHF respiratory support is noninferior to NIV with respect to treatment failure, in patients with mild-to-moderate hypercapnic AECOPD. MethodsIn this multi-center, randomized, noninferiority trial, 105 patients with AECOPD and respiratory failure type II were enrolled. Participants were randomly assigned to receive either NHF therapy or NIV. The primary endpoint was the frequency of treatment failure, defined as the need for intubation and invasive mechanical ventilation or a switch to the alternative treatment group. Secondary endpoints included changes in respiratory parameters, patient comfort indicators, and the occurrence of complications. ResultsThe findings revealed no significant difference in the primary outcome between the groups, with a treatment failure rate of 19.6 % (10 out of 51) in the NHF group and 14.8 % (8 out of 54) in the NIV group. Interestingly, NHF users reported significantly lower levels of dyspnea and discomfort at multiple follow-up points. Despite the differences in patient comfort, respiratory parameters such as respiratory rate, arterial blood gases, and use of accessory muscles of respiration showed no significant disparities between the groups throughout the study period. ConclusionsNHF therapy was similar to NIV in preventing treatment failure among patients with hypercapnic AECOPD, offering a viable alternative with enhanced comfort. Trial registrationThe study was prospectively registered in ClinicalTrials.gov (Identifier: NCT03466385) on March 15, 2018.

Assessing the predictors for paediatric intensive care unit for inter-hospital transfer patients on high-flow nasal cannula or continuous positive airway pressure ventilation at a tertiary Australian paediatric hospital.

The aim of the present study was to assess the predictors of need for paediatric intensive care unit (PICU) admission for inter-hospital transfer patients to a tertiary paediatric hospital ED on high flow (HF) or continuous positive airway pressure (CPAP) ventilation. Single-centre retrospective study of patients transferred to the state's tertiary paediatric hospital. Demographic information and disease management information was obtained. Between October 2021 and September 2022, 53 patients were transferred to the tertiary hospital on HF or CPAP. Of these, 23 required admission to PICU. Those admitted to PICU had a higher median fraction of inspired oxygen than those not admitted (0.4 vs 0.3, respectively, P = 0.013). Patients transported by road (vs flight) were more likely (20/23 patients, RR = 3.15, P = 0.016) to be admitted to PICU (56% vs 18%). Those who had received CPAP prior to or during transfer were more likely to require PICU admission (P = 0.012). We have demonstrated that children who require CPAP to manage their respiratory disease are more likely to require PICU care on transfer to the tertiary paediatric hospital. In addition, those patients being transferred from secondary metropolitan hospitals after a trial of HF are also likely to require PICU care. This suggests that these patients should be directly admitted to PICU, allowing for improved patient experience and flow as well as reducing unnecessary ED resource utilisation.

COVID-19 outbreak among employees of a German hospital: risk factor analysis based on a follow-up questionnaire and seroprevalence

BackgroundThe Co-FriSero study describes a COVID-19 outbreak at the Friedrichroda hospital in Thuringia, Germany, with 185 beds and 404 employees, at the onset of the pandemic between March 30th, 2020, and April 13th, 2020. This study aimed to analyze potential sources of SARS-CoV-2 transmission amongst hospital employees.MethodsAfter the outbreak, a comprehensive follow-up was conducted through a questionnaire and a seroprevalence study using two different immunoassays for IgG detection and a third for discordant results.ResultsPCR screenings confirmed SARS-CoV-2 infection in 25 of 229 employees, with an additional 7 detected through serology. Statistical analysis indicated that direct patient contact, exposure to high flow ventilation in non-isolated rooms, direct contact with colleagues, shared use of recreational rooms, and carpooling were associated with an increased infection risk. Conversely, contact with family and friends, public transportation, public events, and use of locker rooms were not associated with infection. Male gender showed a lower infection likelihood, independent of age and other risk factors.ConclusionThis study highlights the role of direct patient care and internal staff interactions in the spread of SARS-CoV-2 in the hospital setting. It suggests that non-traditional transmission routes like carpooling require consideration in pandemic preparedness.

Efficiency of continuous positive airway pressure and high-flow nasal oxygen therapy in critically ill patients with COVID-19.

Critically ill patients with COVID-19 develop acute respiratory distress syndrome characterized by relatively well-preserved pulmonary compliance but severe hypoxemia. The challenge in managing such patients lies in optimizing oxygenation, which can be achieved through either high oxygen flow or noninvasive mechanical ventilation. This study was performed to compare the efficiency of two methods of noninvasive oxygen therapy: continuous positive airway pressure (CPAP) and high-flow nasal oxygen therapy (HFNO). This retrospective cohort study involved 668 patients hospitalized in the intensive care unit (ICU) of the "Sf. Apostol Andrei" Emergency Clinical Hospital, Galati, Romania from 1 April 2020 to 31 March 2021 (CPAP, n = 108; HFNO, n = 108). Mortality was significantly lower in the CPAP and HFNO groups than in the group of patients who underwent intubation and mechanical ventilation after ICU admission. Mortality in the ICU was not significantly different between the CPAP and HFNO groups. HFNO and CPAP represent efficient alternative therapies for patients with severe COVID-19 whose respiratory treatment has failed. Studies involving larger groups of patients are necessary to establish a personalized, more complex management modality for critically ill patients with COVID-19.

Integrated adjustable acoustic metacage for multi-frequency noise reduction

Effectively controlling the multi-frequency noise of engines while keeping air flowing is of great significance for power machines. This article presents an adjustable acoustic metacage to attenuate multi-frequency noise from diesel engines while maintaining high-flow ventilation. The metacage consists of combined reflection and absorption units to achieve reverberation attenuation, with nested C-shaped unit cells forming the reflection units and microperforated panels with porous material infills forming the absorption units. The frequency of the reflection unit can be tuned by changing the relative angles of C-shaped rings. Firstly, we present a prototype of the acoustic metacage and explore the acoustic properties of the nested C-shaped unit cell. Secondly, we demonstrate the superiority of the proposed design in attenuating power machines' noise by comparing various schemes of the acoustic metacage and investigate the influence of the sound absorption coefficient of the absorption part. Finally, taking an 8 kW diesel generator as example, we optimize the metacage using the genetic algorithm and experimentally verify its performance, the insertion loss (IL) at two noise peaks reaches 13.2 dB and 18.4 dB, respectively, with an average IL of 8 dB in 100–500 Hz, while retaining a ventilated area of 25 %.

CFD Analysis of Indoor Ventilation for Airborne Virus Infection

CFD Analysis of Indoor Ventilation for Airborne Virus Infection Indoor airflow patterns and air residence times significantly influence the spread of airborne infectious viruses, such as COVID-19. These factors can be quantified using computational fluid dynamics (CFD). In this study, CFD was utilized to assess the indoor airflow patterns and calculate air residence times in a typical restroom with high personnel flow and low ventilation efficiency. The results identified regions with high air residence times, indicating potential risk areas for airborne virus retention. Furthermore, the effects of different ventilation strategies on these high-risk areas were analyzed. Despite meeting air change standards, certain regions were found to potentially pose a higher risk due to prolonged air residence times. Based on these findings, recommendations for improving ventilation systems to reduce the risk of airborne virus infection were proposed. This study highlights the necessity of a more nuanced approach to indoor air assessment than simply calculating air changes per hour. It was concluded that (1) different ventilation strategies can greatly affect the air residence time in the room and (2) the variance of air residence time in the air circulation area are large in some locations, even with simple ventilation adjustments.

Asymmetrical nasal high flow ventilation improves clearance of CO2 from the anatomical dead space and increases positive airway pressure.

Positive airway pressure that dynamically changes with breathing, and clearance of anatomical dead space are the key mechanisms of noninvasive respiratory support with nasal high flow (NHF). Pressure mainly depends on flow rate and nare occlusion. The hypothesis is that an increase in asymmetrical occlusion of the nares leads to an improvement in dead-space clearance resulting in a reduction in re-breathing. Clearance was investigated with volumetric capnography in an adult upper-airway model, which was ventilated by a lung simulator with entrained carbon dioxide (CO2) at respiratory rates (RR) of 15-45 min-1 and at 18 min-1 with chronic obstructive pulmonary disease (COPD) breathing patterns. Clearance was assessed at NHF of 20-60 L/min with a symmetrical interface (SI) and an asymmetrical interface (AI). CO2 kinetics visualized by infrared spectroscopy and mathematical modeling were used to study the mechanisms of clearance. At a higher RR (35 min-1) and NHF of 60 L/min, clearance in the upper airway was significantly higher with the AI when compared with the SI (29.64 ± 9.96%, P < 0.001), as opposed to at a lower RR (15 min-1) (1.40 ± 6.25%, P > 0.05), (means ± SD). With COPD breathing, clearance by NHF was reduced but significantly improved with the AI by 45.93% relative to the SI at NHF 20 L/min (P < 0.0001). The maximum pressure achieved with the AI was 6.6 cmH2O and NHF was 60 L/min at the end of expiration. Pressure differences between nasal cavities led to the reverse flow observed in the optical model. Asymmetrical NHF increases dead-space clearance by reverse flow through the choanae and accelerates purging of expired gas via the less occluded nare.NEW & NOTEWORTHY The asymmetrical interface generated reverse flow in the nasal cavities and across the choana, which led to unidirectional purging of expired gas from the upper airways. This accelerated the clearance of anatomical dead space and reduced re-breathing while increased resistance to flow resulted in higher positive end-expiratory pressure (PEEP). These findings are relevant to patients with elevated respiratory rates or with expiratory flow limitations where dead-space clearance by NHF can be substantially reduced.

1942. Effect of SARS-CoV-2 Vaccination in a Frailty COVID-19 Cohort: a Real Life Experience in a Northern Italy Hospital

Abstract Background Clinical trial demonstrated that SARS-CoV-2 vaccines have the ability of reduce mortality and morbidity due to COVID-19. The aim of this study is to describe the effect of vaccination in term of mortality, type of ventilation and ICU admission among patients hospitalized for COVID-19 from May to December 2021 in a Ligurian Hospital. Methods This is a retrospective, single-center study conducted in San Martino Hospital (Genoa, Italy), including patients ≥ 18 years hospitalized for COVID-19 in Infectious Disease and Emergency Units from 1st May to 31st December 2021. We collected demographical data, multimorbidity and disability score, vaccination time (“vaccinated” all patients hospitalized ≥ 14 days after first dose or ≥ 7 days after second/third dose), therapy for COVID-19, mortality at 7 and 30 days, ICU admission, ventilation type. Characteristics of vaccinated (group A) versus non vaccinated (group B) patients were compared using Chi-squared/Fisher's exact test for categorical variables and t-test /Kruskal-Wallis test for the continuous ones. Cox proportional hazards models for death at 30 days were performed as univariate analysis as well as adjusting for age, Cumulative Illness Rating Scale [CIRS], gender, Remdesivir, Monoclonal antibodies, Tocilizumab use. Results Overall, 405 patients SARS-CoV-2 infected were enrolled. Data about timing of vaccination were available for 360 patients (89%). We compared clinical characteristics and outcomes of group A (32%) versus group B (68%). In group A patients were older (p&amp;lt; 0.001) and frailer (higher CIRS score and lower Barthel index, p&amp;lt; 0.001) than in group B. Among patients requiring oxygen, 76 (31.5%) in group B vs 26 (22.41%) in group A needed high flow ventilation (p=0.036); 33 (13.52%) vs 3 (2.59%) respectively were admitted to ICU (Figure 1). Mortality at 30 days after hospitalization was higher in group A at univariate analysis [HR(95%CI) 1.44(0.82; 2.53), p=0.208], lower at multivariate analysis [0.57(0.31; 1.02), p=0.059]. Conclusion The results of this study confirm that SARS-CoV-2 vaccination reduces rate of admission to ICU and 30 days mortality among patients hospitalized for COVID-19. In our cohort mortality among vaccinated patients remains high and we hypothesized this is due to high frailty of evaluated population. Disclosures Chiara Dentone, CD, Angelini: Advisor/Consultant|Gilead: Advisor/Consultant|Menarini: Advisor/Consultant|Novartis: Advisor/Consultant Matteo Bassetti, PhD, Angelini: Advisor/Consultant|Astellas: Grant/Research Support|Bayer: Advisor/Consultant|Bayer: Honoraria|BioMe ́ rieux: Advisor/Consultant|BioMe ́ rieux: Honoraria|Cidara: Advisor/Consultant|Cidara: Honoraria|Cipla: Advisor/Consultant|Cipla: Honoraria|Gilead: Advisor/Consultant|Gilead: Honoraria|Menarini: Advisor/Consultant|Menarini: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Nabriva: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Board Member|Pfizer: Grant/Research Support|Pfizer: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria|Tetraphase: Advisor/Consultant.

КЛИНИЧЕСКИЙ СЛУЧАЙ ТЯЖЕЛОГО ТЕЧЕНИЯ ИНФЕКЦИИ COVID-19 У РОДИЛЬНИЦЫ В РАННЕМ ПОСЛЕРОДОВОМ ПЕРИОДЕ С ПРИМЕНЕНИЕМ ЭКСТРАКОРПОРАЛЬНОЙ МЕМБРАННОЙ ОКСИГЕНАЦИИ

A new coronavirus infection (COVID-19) raises reasonable concerns about the impact of the Sars-CoV-2 virus on pregnant women and women in the postpartum period, given the high risk of COVID-19-associated acute respiratory distress syndrome with refractory hypoxemia, even against the background of artificial lung ventilation. When this situation arises, the use of Extracorporeal membrane oxygenation (ECMO) is justified to improve respiratory function and support blood circulation. In the given clinical case, the experience of successful treatment of a patient with COVID-19 infection in the early postpartum period with ECMO for 22 days, who was hospitalized at the Grodno Regional Clinical Cardiology Center, is presented. In the current clinical situation, all methods of respiratory support have been consistently used: from oxygen therapy through high-flow ventilation and non-invasive mechanical ventilation, to invasive mechanical ventilation. During her stay on ECMO, the patient experienced two hemorrhagic events that required surgical interventions. During therapy, it was possible to avoid thrombosis of the circuit and prevent the development of rebleeding against the background of anticoagulant therapy by carefully monitoring the hemostasis system using clotting hemostasiological tests and ROTEM indicators and correcting their violations.

COVID-19 in Immunocompromised Children and Adolescents.

COVID-19 in Immunocompromised Children and Adolescents.

Microlaryngeal Laser Surgery Using High-flow Nasal Ventilation at Two Oxygen Concentration Deliveries.

Ventilation using 100% oxygenation creates a risk of fire during laser microlaryngeal surgery (MLS). The purpose of this study is to describe the technique of transnasal high-flow ventilation using laser safe (30%) oxygen conditions, measure the intraoperative real-time laryngeal oxygen concentration, and examine patient saturation status using this technique. Prospective IRB approved study of patients undergoing tubeless laser MLS using high-flow nasal oxygenation. Delivered oxygen concentration was reduced from 100% to 30% before lasering using an oxygen-air blender then increased to 100% post-laser procedure. Outcome measures included time for laryngeal oxygen concentration to equalize to laser safe levels; time to, methods of and duration of rescue ventilation; and desaturation rates and apnoeic times at both 100% and 30% oxygen deliveries. Fifty patients were recruited (mean age=47.4 years). Mean laryngeal oxygen concentration (%) at 100% and 30% deliveries was 98.46 and 31.45, respectively. Mean (SD) of laryngeal oxygen concentration equalization time to 30% (seconds) was 9.4 (3.69). At 30% oxygen delivery desaturation rate was faster and apneic time shorter compared with 100%. Eighteen patients required rescue (jet) ventilation and they had a faster apneic desaturation rate (%/minute) than patients not requiring rescue. Mean (SD) apneic time (minutes) at 30% delivery was 4.56 (2.25) and 4.41 (2.18) in rescue versus non-rescue groups respectively. BMI was the only significant predictor of desaturation rate at 30% oxygen delivery. It is possible to achieve a safe time window for use of laser during MLS using transnasal humidified high-flow ventilation by delivering 30% oxygen concentration. 4 Laryngoscope, 133:634-639, 2023.

Predictors of Noninvasive Respiratory Support Failure in COVID-19 Patients: A Prospective Observational Study.

Background and Objective: Respiratory assistance tactic that is best for COVID-19-associated acute hypoxemic respiratory failure (AHRF) individuals has yet to be determined. Patients with AHRF may benefit from the use of a high-flow nasal cannula (HFNC) and non-invasive ventilation (NIV). The goals of this prospective observational research were to estimate predictive factors for HFNC and NIV failure in COVID-19-related AHRF subjects. Materials and Methods: The research enlisted the participation of 124 patients. A stepwise treatment approach was used. HFNC and NIV were used on 124 (100%) and 64 (51.6%) patients, respectively. Thirty (24.2%) of 124 patients were intubated and received invasive mechanical ventilation. Results: 85 (68.5%) patients were managed successfully. Patients who required NIV exhibited a higher prevalence of treatment failure (70.3% vs. 51.6%, p = 0.019) and had higher mortality (59.4% vs. 31.5%, p = 0.001) than patients who received HFNC. Using logistic regression, the respiratory rate oxygenation (ROX) index at 24 h (odds ratio (OR) = 0.74, p = 0.018) and the Charlson Comorbidity Index (CCI) (OR = 1.60, p = 0.003) were found to be predictors of HFNC efficacy. It was the ROX index at 24 h and the CCI optimum cut-off values for HFNC outcome that were 6.1 (area under the curve (AUC) = 0.73) and 2.5 (AUC = 0.68), respectively. Serum ferritin level (OR = 0.23, p = 0.041) and lymphocyte count (OR = 1.03, p = 0.01) were confirmed as predictors of NIV failure. Serum ferritin level at a cut-off value of 456.2 ng/mL (AUC = 0.67) and lymphocyte count lower than 0.70 per mm3, (AUC = 0.70) were associated with NIV failure with 70.5% sensitivity, 68.7% specificity and sensitivity of 84.1%, specificity of 56.2%, respectively. Conclusion: The ROX index at 24 h, CCI, as well as serum ferritin level, and lymphocyte count can be used as markers for HFNC and NIV failure, respectively, in SARS-CoV-2-induced AHRF patients.

Tracheomegaly as a Potential Predictor of Severe Tracheal Damage in COVID-19 Patients on Long-Term Mechanical Ventilation

Tracheomegaly (TM) is a rare appearance that is radiologically defined as an excessive enlargement of the tracheal diameter. We present a comprehensive analysis of tracheal diameter measurements and TM incidence in patients admitted and treated due to COVID-19 pneumonitis and its association with possible respiratory complications. In this retrospective study, we included 1015 patients divided into three groups: 383 patients treated using mechanical ventilation (MV), 132 patients treated using high-flow ventilation (HFV), and 500 randomly selected patients using nasal catheter (NC) oxygenation. The tracheal lumen diameter was measured continuously using a chest X-ray, and the cuff/trachea (C/T) diameter ratio was calculated. We detected TM in 71 patients (18.54%). Regression analysis showed statistical significance in MV patients for the trachea diameter at the level of the cuff, maximal trachea diameter and C/T diameter ratio, and days on MV. Respiratory complications showed a significant association with the C/T diameter ratio. The C/T diameter ratio was shown to be a reliable potential predictor of the occurrence of respiratory complications. The results of the study highlight the importance of the early detection and prevention of TM in COVID-19 patients on MV using a chest X-ray and measurement of the C/T diameter ratio.

Neonatal resuscitation practices in Italy: a survey of the Italian Society of Neonatology (SIN) and the Union of European Neonatal and Perinatal Societies (UENPS)

BackgroundProviding appropriate care at birth remains a crucial strategy for reducing neonatal mortality and morbidity. We aimed to evaluate the consistency of practice and the adherence to the international guidelines on neonatal resuscitation in level-I and level-II Italian birth hospitals.MethodsThis was a cross-sectional electronic survey. A 91-item questionnaire focusing on current delivery room practices in neonatal resuscitation was sent to the directors of 418 Italian neonatal facilities.ResultsThe response rate was 61.7% (258/418), comprising 95.6% (110/115) from level-II and 49.0% (148/303) from level-I centres. In 2018, approximately 300,000 births occurred at the participating hospitals, with a median of 1664 births/centre in level-II and 737 births/centre in level-I hospitals. Participating level-II hospitals provided nasal-CPAP and/or high-flow nasal cannulae (100%), mechanical ventilation (99.1%), HFOV (71.0%), inhaled nitric oxide (80.0%), therapeutic hypothermia (76.4%), and extracorporeal membrane oxygenation ECMO (8.2%). Nasal-CPAP and/or high-flow nasal cannulae and mechanical ventilation were available in 77.7 and 21.6% of the level-I centres, respectively. Multidisciplinary antenatal counselling was routinely offered to parents at 90.0% (90) of level-II hospitals, and 57.4% (85) of level-I hospitals (p < 0.001). Laryngeal masks were available in more than 90% of participating hospitals while an end-tidal CO2 detector was available in only 20%. Significant differences between level-II and level-I centres were found in the composition of resuscitation teams for high-risk deliveries, team briefings before resuscitation, providers qualified with full resuscitation skills, self-confidence, and use of sodium bicarbonate.ConclusionsThis survey provides insight into neonatal resuscitation practices in a large sample of Italian hospitals. Overall, adherence to international guidelines on neonatal resuscitation was high, but differences in practice between the participating centres and the guidelines exist. Clinicians and stakeholders should consider this information when allocating resources and planning perinatal programs in Italy.

Outcomes of SARS-CoV-2 Infection in Lung Transplant Recipients: A Single Center Experience

PurposeOutcomes of Covid-19 in lung transplant recipients (LTr) were reported in the beginning of the pandemic. Only few centers reported on their experience since December 2020 when vaccines received emergency use authorization. We aim to investigate the outcome of SARS-CoV-2 infection in a cohort of LTr at our center in Detroit, Michigan.MethodsRetrospective chart review study of adult LTr with confirmed SARS-CoV-2 infection from March 2020 to August 2021.ResultsThirty LTr were diagnosed with SARS-CoV-2 infection confirmed by RT PCR of nasopharynx. Median age at diagnosis was 63; 53% were males; 57% Caucasians and 40% of African descendance. Most patients underwent bilateral LT for interstitial lung disease (46%) and for pulmonary sarcoidosis (23%). The median time post LT was 3.1 years. Most patients needed hospitalization for respiratory failure secondary to Covid-19 (73%). Eleven patients were initially managed as outpatient. Five patients received outpatient combination of monoclonal antibodies with three of them later requiring hospitalization for development of hypoxia. None of the patients with initial out of the hospital management died. Amongst 21 hospitalized LTr, six patients were diagnosed with severe pneumonia and ARDS requiring heated high flow and invasive mechanical ventilation (IMV) in 4 patients. 28-day mortality was 10% and ICU mortality was 25% (50% mortality in those on IMV). Twelve hospitalized patients (57%) were treated with remdesivir. Augmented systemic corticosteroids was used in 85% of cases. Cycle cell inhibitor was held in 71% of the cases. Bilateral ground glass opacities of the allografts were common. None of the patients that received at least one dose of mRNA vaccine died.ConclusionOutcomes in LTr infected with SARS-CoV-2 varies. Early reports showed high mortality rate in severe and critical Covid-19 in LTr. Although hospitalization rate in this cohort was high, only four patients in our cohort required IMV during acute Covid-19. Two of them died; both were unvaccinated. Another unvaccinated patient died due to allograft rejection two months after testing positive to SARS-CoV-2. Most cases were mild to moderate despite frequent radiographic findings of pneumonia. Underreporting and exclusion of mild cases as well as likely protective effect of vaccination and use of monoclonal antibodies may explain our different outcomes.

The role of Janus kinases in the pathogenesis and treatment of covid-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is severe pneumonia caused by an enveloped, single-stranded RNA beta coronavirus, belonging to the coronaviridae family. SARSCoV- 2 is due to severe hyperinflammation in response to the coronavirus 2 infection. This results in overproduction of cytokines, chemokines, and growth factors by macrophages, such as interleukin- 1β (IL-1β), IL-2, IL-6, IL-8, IL-10, and tumour necrosis factor-α, which cause lung and multi-organ damage. Covid-19 pneumonia is characterized by diffuse alveolar damage due to direct infection of alveolar type II pneumocytes, pulmonary enema, interstitial infiltrates, microthrombi, and ventilation/perfusion mismatch. Covid-19 is a progressive disease which ultimately results in acute respiratory distress syndrome, respiratory failure, multi-organ failure, and death. The standard of care of Covid-19, includes high-flow nasal oxygen (HFNO), dexamethasone, remdesivir, and mechanical ventilation or extracorporeal membrane oxygenation in severe disease. However, the mortality is exceptionally high even with these therapies. IL-6 plays a key role in orchestrating the hyperinflammation and the cytokine storm, which lead to respiratory failure, and multi-organ failure. Interleukin-6 signalling is via the transmembrane IL-6 receptor-α (mIL-6Rα), and the soluble IL- 6Rα. Tocilizumab, and sarilumab are IL-6Rα antagonists, and have been issued an emergency use authorization (EUA) by the FDA. Both biologics are safe, and effective in the treatment of severe Covid-19, particularly in patients requiring HFNO, and mechanical ventilation. Another therapeutic approach to treat Covid-19 is to target the downstream JAK/STAT pathway which plays a critical role in promoting IL-6, and other cytokines in orchestrating acute respiratory distress syndrome. Baricite and tofacitinib have been granted EUA by the FDA. Both Janus kinase inhibitors have been shown to significantly decrease odds of mortality, and ICU admission. Additionally, JAK inhibitors significantly increase odds for patients’ discharge within 2 weeks. Tofacitinib has been reported to lead to a lower risk of respiratory failure or death through day 28 than placebo in hospitalized patients with Covid-19. Baricitinib in addition to standard of care, including dexamethasone was associated with reduced mortality in hospitalized adults with Covid-19. Baricitinib is effective in reducing mortality in patients with Covid-19, even in progressive disease stages on mechanical ventilation. Selective JAK inhibitors in addition to usual care are effective in the treatment of hospitalized patients with Covid-19, and in reducing mortality. Keywords: Covid-19; Cytokine storm; Interleukin-6; Janus kinase; JAKinibs; Baricitinib

Management and implications of severe COVID-19 in pregnancy in the UK: data from the UK Obstetric Surveillance System national cohort.

IntroductionThere is a lack of population level data on risk factors and impact of severe COVID‐19 in pregnancy. The aims of this study were to determine the characteristics, and maternal and perinatal outcomes associated with severe COVID‐19 in pregnancy compared with those with mild and moderate COVID‐19 and to explore the impact of timing of birth.Material and methodsThis was a secondary analysis of a national, prospective cohort study. All pregnant women admitted to hospital in the UK with symptomatic SARS‐CoV‐2 from March 1, 2020 to October 31, 2021 were included. The severity of maternal infection (need for high flow or invasive ventilation, intensive care admission or died), pregnancy and perinatal outcomes, and the impact of timing of birth were analyzed using multivariable logistic regression.ResultsOf 4436 pregnant women, 13.9% (n = 616) had severe infection. Women with severe infection were more likely to be aged ≥30 years (adjusted odds ratio [aOR] aged 30–39 1.48, 95% confidence interval [CI] 1.20–1.83), be overweight or obese (aOR 1.73, 95% CI 1.34–2.25 and aOR 2.52 95% CI 1.97–3.23, respectively), be of mixed ethnicity (aOR 1.93, 95% CI 1.17–3.21) or have gestational diabetes (aOR 1.43, 95% CI 1.09–1.87) compared with those with mild or moderate infection. Women with severe infection were more likely to have a pre‐labor cesarean birth (aOR 8.84, 95% CI 6.61–11.83), a very or extreme preterm birth (28–31+ weeks’ gestation, aOR 18.97, 95% CI 7.78–14.85; <28 weeks’ gestation, aOR 12.35, 95% CI 6.34–24.05) and their babies were more likely to be stillborn (aOR 2.51, 95% CI 1.35–4.66) or admitted to a neonatal unit (aOR 11.61, 95% CI 9.28–14.52). Of 112 women with severe infection who were discharged and gave birth at a later admission, the majority gave birth ≥36 weeks (85.7%), noting that three women in this group (2.7%) had a stillbirth.ConclusionsSevere COVID‐19 in pregnancy increases the risk of adverse outcomes. Information to promote uptake of vaccination should specifically target those at greatest risk of severe outcomes. Decisions about timing of birth should be informed by multidisciplinary team discussion; however, our data suggest that women with severe infection who do not require early delivery have mostly good outcomes but that those with severe infection at term may warrant rapid delivery.

Use of Systemic Anticoagulation in COVID-19: Delving Beyond Theoretical Hypothesis.

BackgroundStudies suggest that COVID-19 infection may induce increased hypercoagulability, leading to thrombotic complications. The high rates of thrombotic complications among patients receiving standard-dose deep venous thrombosis (DVT) prophylaxis have prompted some clinicians to support the empiric increase of anticoagulation (AC) doses used for prophylaxis in patients with COVID-19. At present, the optimal anticoagulant agents, dosages, and duration have not been designated. We conducted a retrospective study to assess for outcomes in patients who received treatment for COVID-19 based on various dosings of AC.MethodsThis was a single-institution, retrospective cross-sectional study including patients with a positive COVID-19 test who were admitted within the St. Joseph’s Health Network from September to November of 2020. The inclusion criteria were men and women aged 18 years or older who had confirmed COVID-19 by polymerase chain reaction (PCR). Medical charts of patients who met the inclusion criteria were audited to obtain information. The patients were separated into three cohorts: those who received DVT prophylactic dose of AC, those who received an intermediate dose of AC, and those who received therapeutic AC.ResultsA total of 440 patients were included in the study, of whom 236 were Hispanic (50.3%), 131 were Caucasian (27.1%), 47 were African American (10.7%), and 26 were Asian (5.9%). The most common comorbidities were hypertension (273/440 [62.2%]), diabetes 189/440 [43.1%]), and coronary artery disease (60/440 [13.7%]). In the DVT prophylactic dose of AC cohort, there were 215 patients, and the average length of stay was 10.3 days. Eleven patients experienced bleeding events, five patients experienced thrombotic events, 16 patients required mechanical ventilation, and 20 patients died. In the intermediate dose of AC cohort, there were 63 patients, and the average length of stay was 10.3 days. Three patients experienced bleeding events, two patients experienced thrombotic events, seven patients required mechanical invasive ventilation, and 11 patients died. In the therapeutic dose of AC cohort, there were 162 patients, and the average length of stay was 14 days. In this cohort, 19 patients experienced bleeding events, 12 patients experienced thrombotic events, 26 patients required invasive mechanical ventilation, and 29 patients died. Patients who received intermediate dosing of AC also had the lowest risk of thrombotic events (0.05). Patients who received intermediate dosing of AC had the lowest rates of requiring both high-flow nasal cannula (p = 0.0001) and invasive mechanical ventilation (p = 0.031). Patients who received intermediate dosing of AC had a lower rate of bleeding compared to those who received the DVT prophylaxis dose and systemic AC dose (p = 0.037). The DVT prophylactic and intermediate dosing of AC groups had a shorter length of stay in comparison to the systemic AC group (p = 0.0002).ConclusionIn comparison to the venous thromboembolism prophylaxis dose and systemic AC dose groups, intermediate dosing of AC had the lowest rates of hemorrhage, mortality, length of stay, and requirement of high-flow nasal cannula or mechanical invasive ventilation. In the systemic dose AC group, there were worse clinical outcomes in terms of length of stay, incidence of bleeding events, requirement of mechanical ventilator use, and rate of mortality.

541. Comparing Patients with Severe COVID-19 Who Improve to the Point of Discharge Following an Abbreviated Course (&amp;lt; 5 Days) of Remdesivir (RDV) Versus a Standard Course (≥5 Days)

BackgroundThe COVID-19 pandemic has negatively affected our healthcare system. Our hospitals have reached maximum capacity on several occasions. Because of the need to make beds available to new patients, some patients with severe COVID-19 who were on low flow O2 supplementation have been discharged home prior to completion of the standard (≥ 5-day) RDV course. To date, data are limited regarding clinical outcomes on these patients. Because of this, we conducted a retrospective study to assess the clinical outcomes of patients who received an abbreviated treatment course of RDV.MethodsRetrospective (chart review) studySubject populationAll nonpregnant adult patients who were hospitalized at Kaiser Permanente Riverside Medical Center and Kaiser Permanente Moreno Valley Medical Center in 2020 with severe COVID-19 who required low flow O2 supplement during hospitalization who received RDV and discharged from hospital alive. Severe COVID-19 = positive SARS-CoV-2 PCR + evidence of lung involvement on lung imaging (X-ray or CT) + O2 saturation ≤ 94% on room air or requirement of O2 supplement.Inclusion criteriaAge ≥ 18 years; Hospitalized with severe COVID-19; Given RDVExclusion criteriaPregnancy; O2 requirement > 6 L including high flow and mechanical ventilation (noninvasive or invasive); discontinuation of RDV due to adverse effectsFigure 1. Patient Section. ResultsMortality rate: no difference (2.1% vs 1.8%, p=0.84). 30 day post-discharge ED visit: twice more likely in the abbreviated RDV group as compared to the group receiving the standard duration (16.1% vs 8.5%, p=0.03). 30 day readmission: almost 10 times more likely in the abbreviated RDV group as compared to the group receiving the standard duration (11.9% vs 1.2%, p=< 0.001).Table 1. Patient's Characteristics Table 2. Clinical Outcomes. *8 Patients Who Died Within 30-Day from Discharge Were Excluded ConclusionThough there is no difference in 30 day mortality rate, the patients who received the abbreviated RDV course are twice more likely to have ER visit and 10 times more likely to have readmission within 30 day post discharge despite more patients in the abbreviated course receiving steroids. The findings suggest that completing an at least 5-day course of RDV may be beneficial even in patients who demonstrate a clinical response earlier in course.Disclosures All Authors: No reported disclosures

S2911 A Case of Hepatitis B Reactivation Associated Hepatitis After Tocilizumab Therapy in a Patient With SARS-CoV-2 Infection

Introduction: Tocilizumab (TCZ) is an interleukin 6 (IL-6) receptor inhibitor well known as an immunomodulatory agent used in rheumatic disease that has currently gained greater relevance as an investigational agent in SARS-COV-2 patients. TCZ results in a profound immunosuppressive state, impairing the IL-6 physiologic effects in protective processes such as the HBV infection clearance, HBV replication suppression, and prevention of the accumulation of HBV covalently. We present a case of TCZ-associated HBV reactivation with acute hepatitis in a patient with SARS-COV-2 disease. Case Description/Methods: A 55-year-old Vietnamese man with a history of inactive chronic hepatitis B since childbirth presented in view of progressive shortness of breath. He was diagnosed with SARS-COV-2, placed on supplemental oxygen with no favorable clinical response. The patient was subsequently admitted to the intensive care unit and started in high-flow ventilation, dexamethasone, and apixaban in view of acute respiratory disease syndrome. He received convalescent plasma with no improvement. Therefore, a trial of TCZ was given. The patient gradually showed signs of respiratory and functional status improvement. Supplemental oxygen was de-escalated to a nasal cannula and the patient was discharged to acute rehabilitation. Laboratory workup after discharge revealed elevated liver tests with normal bilirubin and INR. HBV panel showed a rise in the DNA levels to 10 million IU/ml (table 1). Serologies for viral hepatitis were negative (Table 1). Imaging ruled out hepatocellular carcinoma but showed cirrhosis. The patient was started on Tenofovir with gradual improvement in liver enzymes and reduction in HBV viral load >1 log (figure 1). Discussion: TCZ interferes with IL-6 which plays a protective role in the HBV infection with inversely proportional disease severity correlation in HBV infection. Guidelines regarding HBV reactivation reports that TCZ has a moderate risk of reactivation in patients with HBsAg positive. Guidelines regarding therapeutic approaches of Hepatitis B virus recommend preventive therapy for those patients considered at high risk of re-activation such as undergoing immunosuppressive therapy, regardless of the duration, or previous HBV status. Hepatitis B reactivation is often seen within 2 weeks and up to 1 year after the onset of immunosuppressive therapy. No previous cases exist to our knowledge looking at short and long-term effects of TCZ in SARS-COV-2 patients with HBV infection.Figure 1.: Liver enzymes trend pre and post-Tocilizumab and Tenofovir therapies.Table 1.: Hepatitis viral serologies pre and post-Tocilizumab and Tenofovir therapies.