Supplemental Oxygen Requirement Research Articles

Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19.

LettersFebruary 2023Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19FREEEleftherios Mylonakis, MD, PhD, Christina Barkauskas, MD, Garyfallia Poulakou, MD, PhD, Barnaby E. Young, MD, PhD, on behalf of the ACTIV-3/TICO Study Group*Eleftherios Mylonakis, MD, PhDWarren Alpert Medical School of Brown University, Providence, Rhode IslandSearch for more papers by this author, Christina Barkauskas, MDDuke University Medical Center, Durham, North CarolinaSearch for more papers by this author, Garyfallia Poulakou, MD, PhDNational and Kapodistrian University of Athens, Athens, GreeceSearch for more papers by this author, Barnaby E. Young, MD, PhDNational Centre for Infectious Diseases, SingaporeSearch for more papers by this author, on behalf of the ACTIV-3/TICO Study Group*Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L22-0456 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE: We share Dr. Narasaraju and colleagues' belief about the need to improve the care of patients hospitalized with COVID-19. Their concerns about the design of the ACTIV-3/TICO trial of ensovibep can be summarized as follows: it failed to establish the efficacy of ensovibep, used 7-category ordinal outcomes as a primary outcome rather than a surrogate marker, and had limitations imposed by combining remdesivir with ensovibep.Concerning the first 2 points, as discussed in our article, the antiviral management of patients hospitalized with COVID-19 remains a major challenge after several large clinical trials. ACTIV-3/TICO is a multigroup, multistage platform master protocol that aims to rapidly evaluate the safety and efficacy of novel antiviral therapeutic candidates for adults hospitalized with COVID-19. Given these aims, the primary outcome for agents tested in this platform was chosen for its immediate clinical relevance: time to sustained recovery over 90 days of follow-up. In order to efficiently evaluate multiple investigational agents, futility was assessed after approximately 300 patients had completed the day 5 assessment visit. This assessment was based on supplemental oxygen requirements and organ dysfunction on day 5. These intermediate clinical outcomes were used to determine clinical progression and improvement and strongly correlate with sustained recovery through 90 days (1).When selected judiciously, surrogate laboratory markers could be useful indicators of clinical response; in addition, there are established criteria for surrogacy (2). To our knowledge, no work has established a surrogate for the clinical outcomes that are most meaningful for the target population (that is, patients hospitalized with COVID-19). Neither serum viral load nor the proposed markers studied in animals are sufficiently robust. For example, concerning serum viral load, in Jacobs and associates' study (3) viremia was detected in only 52.6% of patients not in the intensive care unit. Such serum and sputum markers of lung alveolar epithelial cell injury as podoplanin or circulating epithelial cell markers similarly are not clinically tested markers of antiviral efficacy. Along with other markers—such as serum nucleocapsid antigen, which was included in our study—these are important areas for further research (4).Regarding the last point, the goal is to improve standard of care in adults hospitalized with COVID-19. According to established treatment guidelines (5), standard of care among such patients could include remdesivir. Withholding the standard of care treatment would challenge equipoise and would not advance the research question addressed in the trial: whether ensovibep improves relevant clinical outcomes when added to standard of care treatment.

Glucocorticoid Therapy in COVID-19-Induced Organizing Pneumonia: A Rare Occurrence.

Background Although the incidence of post-COVID-19 organizing pneumonia (OP) is low, the mortality and morbidity in select patients appear to be high. Anticipating specific populations who may be at higher risk and initiating treatment earlier could reduce mortality. Research question Does treatment with high dose, standard dose, or no glucocorticoids for COVID-19 infection impact the incidence and clinical outcome in COVID-19-induced OP? Study design and methods This was a single-center, retrospective, observational cohort study conducted from 03/01/2020 to 06/30/2021 in hospitalized patients over the age of 18 with confirmed COVID-19 infection and computed tomography (CT) scan evidence of OP. Institutional review board (IRB) approval was obtained from the institution (STUDY00002241). Patients'demographics and oxygen requirements at the time of diagnosis, at the time of discharge, and at one, three, six, 10, and 12 months post-discharge were obtained. The dose, duration, and choice of glucocorticoid therapy were recorded for each subject, as well as oxygen requirements during hospitalization. Despite radiological evidence of OP, patients on minimal supplemental oxygen requirements did not receive high-dose or long-duration glucocorticoidtherapy. Results A total of 881 patients were admitted with COVID-19, of which 42 met the study criteria. Three patients underwent a lung biopsy to confirm the diagnosis of organizing pneumonia. All other patients were diagnosed based on CT imaging and clinical presentation. Of the patients, 17% did not receive any steroid treatment, while 36% received dexamethasone and 43% received prednisone. The most common oxygen requirement at the time of discharge for steroid-treated patients was nasal cannula (55%) and room air (29%). The incidence of OP in this patient population was 0.05 with a mortalityrate of 14%. Interpretation and relevance The incidence of post-COVID-19 OP appears to be lower than anticipated. Steroids for patients on lower supplemental oxygen requirements were discontinued although they had radiological evidence of OP. Patients who were on higher supplemental oxygen requirements at 10 days were continued on steroids regardless of imaging. The decision to continue steroids should be based on individual patient characteristics such as oxygen requirements. In the future, larger multicenter cohort studies would help understand further treatment of post-COVID-19-associated OP. Anticipating specific populations who may be at higher risk and starting treatment earlier could help reduce mortality.

Cortical Grey matter volume depletion links to neurological sequelae in post COVID-19 “long haulers”

ObjectiveCOVID-19 (SARS-CoV-2) has been associated with neurological sequelae even in those patients with mild respiratory symptoms. Patients experiencing cognitive symptoms such as “brain fog” and other neurologic sequelae for 8 or more weeks define “long haulers”. There is limited information regarding damage to grey matter (GM) structures occurring in COVID-19 “long haulers”. Advanced imaging techniques can quantify brain volume depletions related to COVID-19 infection which is important as conventional Brain MRI often fails to identify disease correlates. 3-dimensional voxel-based morphometry (3D VBM) analyzes, segments and quantifies key brain volumes allowing comparisons between COVID-19 “long haulers” and normative data drawn from healthy controls, with values based on percentages of intracranial volume.MethodsThis is a retrospective single center study which analyzed 24 consecutive COVID-19 infected patients with long term neurologic symptoms. Each patient underwent Brain MRI with 3D VBM at median time of 85 days following laboratory confirmation. All patients had relatively mild respiratory symptoms not requiring oxygen supplementation, hospitalization, or assisted ventilation. 3D VBM was obtained for whole brain and forebrain parenchyma, cortical grey matter (CGM), hippocampus, and thalamus.ResultsThe results demonstrate a statistically significant depletion of CGM volume in 24 COVID-19 infected patients. Reduced CGM volume likely influences their long term neurological sequelae and may impair post COVID-19 patient’s quality of life and productivity.ConclusionThis study contributes to understanding effects of COVID-19 infection on patient’s neurocognitive and neurological function, with potential for producing serious long term personal and economic consequences, and ongoing challenges to public health systems.

Outcomes of Filipinos with inflammatory rheumatic diseases developing COVID-19 prior to vaccinations and new variants: a historical perspective.

We described the profile and outcome of Filipino patients with inflammatory rheumatic diseases (IRDs) who developed COVID-19 (IRD-C19) during the onset of the pandemic, prior to vaccinations and variants. We obtained de-identified data of Filipino patients with IRD-C19 from the Global Rheumatology Alliance registry from March 2020 to August 2021. Descriptive statistics and multivariate analyses were applied. Registered were 164 patients (mean age 44years; 70% female). The most common IRDs were systemic lupus erythematosus (SLE, 41.4%), rheumatoid arthritis (RA, 15.2%), and gout (14.6%). Majority were receiving conventional DMARDs (59.1%) and/or glucocorticoid therapy (GC, 51.2%). Half (58.5%) were hospitalized, with risk higher in active IRD (OR 3.7), heart disease(8.52), and hypertension(8.73); and lower in SLE patients (0.15). Among hospitalized patients, 76% needed supplemental oxygen. Heart disease (6.28), hypertension (7.6), and moderate-to-high IRD activity (3.37) were associated with higher odds of requiring oxygen supplementation. Hypertension was associated with mechanical ventilation (8.23).Twenty-four (15%) patients died, with odds lower if on prednisone ≥ 10mg/day (0.17) and with other autoimmune IRDs aside from SLE and RA (0.05). Among patients with IRD-C19 prior to vaccinations and variants, higher disease activity, hypertension, and heart disease were associated with poorer outcomes. Prednisone ≥ 10mg/day was associated with lower odds of death. This study provides valuable historical information, emphasizing the need for continued data collection to clarify COVID-19's impact.

The prevalence and prognostic effect of hyponatremia in children with COVID-19 pneumonia: a retrospective study.

The aim of the study was to examine the effect of hyponatremia at admission as a negative prognostic factor in children hospitalized with COVID-19 pneumonia. The data of patients aged 1 month-18 years, who were followed with the diagnosis of pneumonia at Çanakkale Onsekiz Mart University Hospital, Department of Pediatrics, between January 2018 and May 2021 were examined, retrospectively. Patients (n=661) were divided into two main groups; COVID-19 pneumonia (n=158) and the other pneumonias [other viral pneumonia (n=161) and pneumonia of unknown etiology (n=342)]. Six hundred and twenty-three patients with a median (Q1-Q3) age of 4 (1.5-8) years, 59.4% of whom were male were included in the study. The overall prevalence of hyponatremia at admission was 11.2% and was lower in those with COVID-19 pneumonia than in those with other viral pneumonia (6.4% vs. 15.2%, p=0.013). When evaluated irrespective of their COVID-19 status, hyponatremic patients had a higher supplemental oxygen requirement (OR 2.5 [1.4-4.3], p < 0.001), higher need for intensive care unit (ICU) admission (OR 3.7 [1.3-10.2], p=0.009) and longer duration of hospitalization (p=0.016) than the normonatremic patients. In patients with COVID-19 pneumonia, being hyponatremic had no effect on supplemental oxygen requirements or the duration of hospitalization. When hyponatremic patients were evaluated, the supplemental oxygen requirements and duration of hospitalization of those with COVID-19 pneumonia were similar to the other pneumonias (p > 0.05 for all comparisons). However, normonatremic COVID-19 pneumonias had higher supplemental oxygen requirements than other viral pneumonias and pneumonia of unknown etiology (OR 4.7 [2.2-10.3], p < 0.001; OR 1.6 [1 -2.7], p=0.043, respectively). This study found that hyponatremia at admission is rarer in children with COVID-19 pneumonia than other viral pneumonias and has no effect on supplemental oxygen requirements or the duration of hospitalization.

Retrospective evaluation and comparison of oxygen supply management with piped supply with cylinder manifold in first wave of COVID-19 against piped supply with liquid medical oxygen system in second wave of COVID-19

Background: COVID-19 infection is a major health pandemic all over world started in 2019. Due to respiratory tract involvement, major number of patients required oxygen supplementation. Dedicated COVID hospitals and others required high burden of oxygen all over world. During first wave, oxygen supply management to main hospital building of our institute was by the central piped supply with cylinder manifold whereas during second wave, it was piped supply with 20 KL liquid medical oxygen (LMO) SYSTEM. Aims and Objectives: With this background, we decided to compare these both systems by questionnaire-based interview of healthcare worker and data evaluation. We planned to conduct this study with aim to compare effectiveness and ease of oxygen supply management with both these oxygen supply systems. Materials and Methods: We took questionnaire-based interviews of oxygen store people, intensive care unit, and ward in charge sisters and doctors and manpower working at oxygen supply systems. Results: Both systems of oxygen supply provided uninterrupted supply of oxygen during COVID outbreak with statistically significant less stress level of healthcare workers, good pressure constancy, less cost, and more ease of operability of LMO system. Conclusion: During daily high demand of oxygen, LMO system is superior than piped supply with cylinder manifold system.

A Descriptive Study on the Clinical Profile and Outcomes of Patients with COVID-19 and Tuberculosis Co-infection.

Tuberculosis (TB) control has been a challenge in the country and its overall health impact remains significant. COVID-19 has caused significant morbidity and mortality especially among hospitalized patients. TB and COVID-19 co-infection (COVID-TB) may cause more catastrophic consequences and outcomes among afflicted individuals and management may be daunting. There is limited local data on COVID-TB. The clinical profile of COVID-TB patients who were admitted were described. Comparison of the clinical outcomes was also done versus the general admitted COVID-19 patients without concomitant TB in the same institution. Relevant patient outcomes were reported which included admission to an intensive care unit (ICU), length of hospital stay, and mortality rate. This is a descriptive study on the demographics and clinical outcomes of patients admitted in the Philippine General Hospital (PGH) for COVID-19 with TB co-infection from March 2020 to September 2020. We aimed to characterize patients with COVID-TB and analyzed their outcomes. There was a total of 79 patients who were admitted for COVID-19 (confirmed with RT-PCR) with TB co-infection during the study period. Majority of them were males (70.9%) with a median age of 54 (IQR 42 to 64) years. In terms of TB affliction, 75 (94.9%) patients were identified to have pulmonary tuberculosis. Majority of patients had at least one co-morbid illness with hypertension (16.5%), diabetes mellitus (13.9%), and heart failure (11.4%) as the most common. Respiratory symptoms (dyspnea and cough) were the predominant presenting complaint during hospital admission. Majority of the patients were classified as severe (8 or 10.1%) and critical (36 or 45.57%) COVID-19 disease. Fifty-six (70.9%) were bacteriologically confirmed tuberculosis. Radiologic imaging studies revealed findings consistent with pulmonary tuberculosis in 70 (88.61%) through plain radiograph. Forty-seven underwent HRCT and 46 of these (97.8%) had findings suggestive of PTB. Overall, 61 patients (77%) subsequently required oxygen supplementation. The in-hospital mortality within the study population was 36.7% (29/79) in contrast to the general COVID patients admitted in the same period which revealed significantly less fatality at 17.5% (35/200). The length of hospital stay was found to be 21.1 days ± 14.75 days across all study patients, and with median of 20 days for surviving patients. TB treatment outcomes were tracked in the 50 surviving COVID-19 patients where cure was declared in 8/50 (16%) while 22/50 (44%) successfully completed their six-month treatment regimen. This study of COVID-TB provides an initial evaluation of the potential association between active TB infection and COVID-19 severity and mortality. The data generated from this study may be a starting point to assess the interaction of these two diseases. Furthermore, bidirectional screening may be recommended even at hospitals' triage areas since both diseases may have similar presentations.

The optimal time for endotracheal intubation in subjects with coronavirus disease 2019 pneumonia: A retrospective observational study.

The optimal timing of intubation has been debated among healthcare professionals, current studies do not show any differences between early and late intubation. most studies failed to show any significant difference in clinical outcomes between early or late intubation. The study was conducted as a retrospective review of subjects with confirmed coronavirus disease 2019 admitted to the Dubai Hospital intensive care unit (ICU). Study variables included time to intubation, duration of supplemental oxygen requirement >15 L/min, and cumulative duration of tachypnea and tachycardia while on the aforementioned oxygen requirement on this oxygen usage level. Each time duration was assessed for correlation with clinical variables including mortality and length of stay in ICU and hospital. Subjects who require endotracheal intubation within 4 h after the start of oxygen >15 L/min have lower survival (P = 0.03). Subjects who have tachypnea on the aforementioned oxygen requirement for 6-19.5 h (P = 0.01) before they require intubation have better survival. No duration of tachycardia has any significant effect on survival. Only the duration of invasive mechanical ventilation (MV) correlated with the hospital length of stay. Subjects who require endotracheal intubation within 4 h after the start of oxygen >15 L/min have lower survival. The optimal time for intubation is after tachypnea of 6 h but before 19.5 h. No duration of tachycardia has any significant effect on survival. Only the duration of invasive MV correlated with the hospital length of stay.

Impact of concomitant gastroesophageal reflux disease symptomology on prognosis and pulmonary function of chronic hypersensitivity pneumonitis.

Comorbid risk factors in chronic hypersensitivity pneumonitis (CHP) are poorly characterised. Gastroesophageal reflux disease (GERD) is linked to interstitial lung diseases like idiopathic pulmonary fibrosis (IPF), but its association and treatment in CHP is less understood. This study aims to understand the role and prevalence of GERD in CHP, plus the effect of GERD treatment on lung function and mortality. A tertiary referral centre panel was retrospectively reviewed for 214 patients diagnosed with CHP based on clinical history, bronchoalveolar lavage fluid analysis, imaging and histopathology. GERD diagnostic criteria included symptomology, acid suppressive therapy use and diagnostic testing. CHP patients with GERD (n = 89) and without GERD (n = 125) were compared via descriptive statistical analysis. Pulmonary function, GERD diagnosis plus treatment and other comorbidities were evaluated against CHP outcomes. Respective differences between diagnosis and study termination dates in the GERD population versus without GERD for functional vital capacity (FVC) were - 1 L vs - 2.5 L, diffusing capacity of the lungs for carbon monoxide (DLCO) were - 2 mL/min/mmHg versus - 1 mL/min/mmHg, per cent alive at the time of study 88% versus 81%, median date of survival 574.5 versus 850 and supplemental oxygen requirement 41% versus 37%. GERD prevalence was higher in CHP patients relative to the general population. No statistical significance was found between survival curves, oxygen requirement, smoking history, FVC, or DLCO. GERD could be a harmful comorbidity in CHP though may not necessarily affect survival or functional outcomes. This aligns with previous IPF studies, though remains controversial. Further research is needed regarding this association and treatment benefit.

The Value of Integrated Pulmonary Index Monitoring After Electroconvulsive Therapy

Abstract&#x0D; Aim: The Integrated Pulmonary Index (IPI) is an algorithm integrated 4 major parameters end-tidal carbon dioxide (EtCO2), respiratory rate (RR), oxygen saturation (SpO2), and pulse rate (PR) measured by commercially available monitors in order to provide a simple indication of the patient’s overall ventilatory status. IPI provides to determine the need for additional clinical assessment or intervention by evaluating respiratory status of patient. The aim of the study was to study the value of IPI monitoring for assessment of respiratory status and recovery from anesthesia after electroconvulsive therapy (ECT).&#x0D; Methods: Total 64 patients, ranging in age from 18 to 65 years and undergoing ECT for various psychiatric disorders, were enrolled in this prospective observational study. All patients were anesthetized with a standardized technique. After the return of spontaneous breathing, in addition to the standard monitoring, all patients were monitored with microstream EtCO2, is a portable bedside monitor that continuously monitors a patient’s EtCO2, RR, SpO2, PR and IPI. All those parameters and also Modified Aldrete Score (MAS) were recorded during the first 5 minutes immediately after neuromuscular blockage recovery and the first 10 minutes in the post anesthesia care unit (PACU) stay, at 1-min intervals. Supplemental oxygen requirement, any interventions improving the patency of airway and any complications such as apnea, bradypnoea, tachypnoea etc. were also recorded.&#x0D; Results: There were 1088 IPI readings ranging from 1 to 10. IPI values during 5 minutes of recovery period were significantly lower in the respiratory intervention group, and also significantly low in patients who needed supplement oxygen in the PACU. Additionally, significant correlations were found between IPI and MAS or SpO2 during follow-up in PACU.&#x0D; Conclusions: The IPI monitorization can be useful over the standard monitorization in terms of better evaluation of respiratory status, and also provide to make decision about PACU recovery, after ECT.

Interventions and outcomes of COVID-19 patients in a community hospital-A single center study comparing the first and second waves.

We have had 3 coronavirus-related pandemics in the last two decades. Each has brought significant toll and with each case there was no cure. Even as vaccines have been developed for the current strain of the virus thereby increasing the prospects of bringing transmissions in communities to a minimum, lessons from this pandemic should be explored in preparation for future pandemics. Other studies have looked at differences in characteristics of patients and mortality rates between the first two waves. In our study we not only identify the differences in outcomes but also explore differences in hospital specific interventions that were implemented at Jersey City Medical Center, NJ, a community-based hospital. The aim of this study is to assess the differences between the first two waves of the COVID -19 pandemic in terms of management and outcomes to help identify any key lessons in the handling of future pandemics. We compared the population demographics, interventions and outcomes used during the first two waves of COVID-19 in a community-based hospital. This is a retrospective single-center cross-sectional study including Laboratory confirmed COVID-19 patients requiring oxygen supplementation admitted at Jersey City Medical Center during the first wave (April 1 to June 30, 2020) and the second wave between (October 1, 2020, and January 1, 2021). The Chi-squared test was used to assess the relationship between categorical variables and the T- test for continuous variables. A Logistic regression model was built comparing the second to the first wave while accounting for important covariates. There was a combined total of 473 patients from both waves. Patients in the first wave were older (66.17 years vs 60.38 years, p <0.01), had more comorbidities (2.75 vs 2.29, p 0.003), had more severe disease (50% vs 38.78% p of 0.002), had a longer length of stay (14.18 days vs 8.77 days, p <0.001) and were more likely to be intubated (32.49% vs 21.9 4%, p 0.01). In the univariate model, the odds of mortality in the second wave compared to the first wave was 0.63 (CI, 0.41-0.96) and 1.73 (CI, 0.65-4.66) in the fully adjusted model. Overall, there was no statistically significant difference in mortality between the two waves. Interventions that were noted to be significantly different between the two waves were, increased likelihood of mechanical intubation in the first wave and increased use of steroids in the second wave compared to the first.

2119. Predictive Value of the Immunodeficiency Scoring Index for COVID-19 Related Outcomes in Hematopoietic Transplant Recipients

Abstract Background The Coronavirus Disease 2019 (COVID-19) has significantly impacted cancer patients with some reported mortality as high as 25%. The Immunodeficiency Scoring Index (ISI) was developed as a prognostic tool in allogeneic hematopoietic cell transplant (allo-HCT) recipients with respiratory syncytial virus but also for other respiratory viruses to predict severe infections and mortality. The purpose of our study was to correlate the ISI in HCT recipients with COVID-19 and associated complications such as hospitalization, supplemental oxygen use, and mortality. Methods We performed a cohort study of HCT recipients of all ages with COVID-19 between March 2020 and October 2021. We included only patients who were diagnosed by a PCR-based assay. We excluded patients for whom an ISI score, as previously described, could not be calculated. Outcomes of interest included 60-day mortality, hospital and ICU admission due to COVID-19, and supplemental oxygen requirements. A univariate analysis using Fischer exact testing for nominal variables was performed. Results Out of the 219 HCT with COVID-19, 101 were excluded due to alternative methods of diagnosis (13), lack of laboratory values needed to calculate an ISI at time of COVID-19 diagnosis (79), or COVID-19 diagnosed prior to transplant (9). Out of the remaining 118 patients, the median age was 60 years (range 6-85), most were male (56%), Caucasian (57%), and had no smoking history (64%). Most patients had an alloHCT (66%) with matched related donor [MRD] (25%), or matched unrelated donor [MUD] (21%) (Table 1). Median time from transplant to COVID-19 was 615 days (range 2-5692), median ISI was 3 (range 0-11), and 92% of patients were unvaccinated prior to COVID-19 (Table 1). On univariate analysis, an ISI of moderate to high (score ≥3) was associated with COVID-19 related hospitalization [p=0.0147] and an ISI ≥ 4 was associated with 60-day all-cause (p=0.045) and COVID-19-related (p-0.019) mortality (Table 2). Table 1: Patient Characteristics Abbreviations: Hematopoietic Cell Transplant (HCT); Chronic Obstructive Pulmonary Disease (COPD); Chronic Kidney Disease (CKD); End-Stage Renal Disease (ESRD); Acute Lymphocytic Leukemia (ALL); Acute Myeloid Leukemia (AML); Myelodysplastic Syndrome (MDS); Chronic Lymphocytic Leukemia (CLL); Chronic Myelogenous Leukemia (CML) Myeloproliferative Disorder (MDS); Matched Related Donor (MRD); Matched Unrelated Donor (MUD); Mismatched Unrelated Donor (MMUD); Graft versus Host Disease (GvHD); Lower Respiratory Tract Infection (LRI); White Blood Cell (WBC); Absolute Neutrophil Count (ANC); Absolute Lymphocyte Count (ALC). Table 2: Univariate Analysis of Outcomes due to COVID-19 in HCT Recipients Abbreviations: Immunodeficiency Scoring Index (ISI); Hematopoietic Cell Transplant (HCT); Allogenic (Allo); Autologous (Auto); Lower Respiratory Infection (LRI); High-Flow Nasal Cannula (HFNC) Figure 1: Survival Curve (Kaplan-Meier Curve) Comparing Time to Death in Patients with an ISI Score of 4 or Greater. (Log-rank 0.0295) Conclusion An ISI of 4 or greater was a prognostic marker for worse outcomes such as COVID-related and all-cause mortality in HCT recipients. Whether an aggressive and prompt management of high-risk patients with COVID-19 may impact these outcomes needs to be determined in future studies. Disclosures Gabriella Rondon, MD, Omeros: Advisor/Consultant Ella Ariza-Heredia, MD, MERCK: Grant/Research Support Elizabeth Shpall, MD, Adaptimmune: Advisor/Consultant|Affimed: License agreement|Axio: Advisor/Consultant|Bayer Helathcare Pharmaceuticals: Honoraria|Fibroblasts and FibrioBiologics: Advisor/Consultant|Navan: Advisor/Consultant|NY Blood Center: Advisor/Consultant|Takeda: License agreement Roy F. Chemaly, MD/MPH, Karius: Advisor/Consultant|Karius: Grant/Research Support.

Different treatment response to systemic corticosteroids according to white blood cell counts in severe COVID-19 patients

Background Limited data are available in COVID-19 patients on the prediction of treatment response to systemic corticosteroid therapy based on systemic inflammatory markers. There is a concern whether the response to systemic corticosteroid is different according to white blood cell (WBC) counts in COVID-19 patients. We aimed to assess whether WBC count is related with the clinical outcomes after treatment with systemic corticosteroids in severe COVID-19. Methods We conducted a retrospective cohort study and analysed the patients hospitalised for severe COVID-19 and received systemic corticosteroids between July 2020 and June 2021. The primary endpoint was to compare the composite poor outcome of mechanical ventilation, extracorporeal membrane oxygenation, and mortality among the patients with different WBC counts. Results Of the 585 COVID-19 patients who required oxygen supplementation and systemic corticosteroids, 145 (24.8%) belonged to the leukopoenia group, 375 (64.1%) belonged to the normal WBC group, and 65 (11.1%) belonged to the leukocytosis group. In Kaplan-Meier curve, the composite poor outcome was significantly reduced in leukopoenia group compared to leukocytosis group (log-rank p-value < 0.001). In the multivariable Cox regression analysis, leukopoenia group was significantly associated with a lower risk of the composite poor outcome compared to normal WBC group (adjusted hazard ratio [aHR] = 0.32, 95% CI 0.14–0.76, p-value = 0.009) and leukocytosis group (aHR = 0.30, 95% CI = 0.12–0.78, p-value = 0.013). There was no significant difference in aHR for composite poor outcome between leukocytosis and normal WBC group. Conclusion Leukopoenia may be related with a better response to systemic corticosteroid therapy in COVID-19 patients requiring oxygen supplementation. KEY MESSAGES In severe COVID-19 treated with systemic corticosteroids, patients with leukopoenia showed a lower hazard for composite poor outcome compared to patients with normal white blood cell counts or leukocytosis. Leukopoenia may be a potential biomarker for better response to systemic corticosteroid therapy in COVID-19 pneumonia.

Corticosteroids use for COVID-19: an overview of systematic reviews.

A reappraisal of the validity of the conclusions of systematic reviews (SRs) and meta-analyses related to corticosteroids use for the treatment of COVID-19. An overview of SRs (umbrella review). The methodological quality of the SRs was assessed using tha AMSTAR-2 checklist; quality of the evidence was appraised following the GRADE approach. 35 SRs were included in this overview. Data were from 307 overlapping reports, based on 121 individual primary studies (25 randomized clinical trials (RCTs), 96 non-RCTs. In critically ill patients the use of steroids significantly reduced mortality compared to standard of care in 80% of the SRs, more often with moderate/high level of certainty; however, in patients not requiring oxygen supplementation the use of steroids increased the overall mortality in 2/3 of the comparisons. Clinical progression of diseases (need for mechanical ventilation, or for intensive care admission) was more commonly observed among controls compared to steroids recipients (in 9 out of 14 comparisons; certainty of evidence from very-low to moderate). The occurrence of adverse events was similar among steroids recipients and controls. Other outcomes (i.e., viral clearance, length of hospital stay) or issue related to optimal dose and type of steroids were addressed in a minority of SRs, with a high level of uncertainty, so that no definitive conclusions can be drawn. There is moderate certainty of evidence that corticosteroids reduce mortality and progression of disease in critically ill COVID-19 patients compared to standard of care, without increasing the occurrence of adverse events.

Bilateral Lung Transplantation With Donor Positive for COVID-19 Infection on Bronchoalveolar Lavage: A Case Report

Initial experience with lung transplant of COVID-19-positive donors was marked by disappointing results, including a reported case of mortality through donor to recipient transmission of infection. However, since that time a number of improvements in preventative and therapeutic measures against COVID-19 have been developed. We present the case of a 51-year-old woman with scleroderma-associated interstitial lung disease who was awaiting lung transplant. A potential donor with excellent lung physiology was located; however, initial testing on bronchoalveolar lavage (BAL) was positive for COVID-19. The donor had tested positive 2 weeks prior and had symptomatically recovered. Our patient had been fully vaccinated but not seroconverted. Given the history of a donor with recovering COVID infection and a fully immunized recipient, our multidisciplinary team elected to proceed with the transplant. The patient successfully underwent bilateral lung transplant with standard induction immunosuppression. Bebtelovimab was given post-transplant day 1 because the recipient remained seronegative to COVID-19. Serial bronchoalveolar lavages post transplant have been negative for COVID-19. The patient has done well after transplant. She was seen in the clinic 2 months post transplant and is ambulatory without supplemental oxygen requirements. To our knowledge, this represents the first reported successful case of lung transplant with a donor positive for COVID-19 on lower respiratory tract sampling.

PNEUMOCYSTIS JIROVECII AND CRYPTOCOCCUS NEOFORMANS COINFECTION IN AN HIV INFECTED PATIENT : A CASE REPORT

Opportunistic fungal infections have a high morality rate, occurring most often in immunocompromised subjects. We report the case of a 19-year-old girl who presented with progressively worsening dyspnea, hypoxemia requiring oxygen supplementation with bilateral pulmonary cystic lesions, treated with antibiotics for a presumptive diagnosis of pneumonia. The patient did not improve clinically. A diagnostic bronchoscopy was performed, which revealed ndings consistent with pulmonary pneumocystis. The patient tested positive for HIV, and had a positive cryptococcal antigenemia. She was put on treatment adapted to each fungal infection with a favorable evolution.

Abstract 11547: Red Blood Cell Distribution Width as a Predictive Indicator for Readmissions in Patients With Pulmonary Hypertension

Introduction: Elevated red cell distribution width (RDW) has been established as a predictive biomarker in patients with pulmonary hypertension (PH). Its value in predicting readmission rates in PH is not fully understood. Methods: PH patients were retrospectively identified between 1/1/2016 and 12/31/2017 and divided into normal (11.5-14.5%) and elevated (&gt;14.5%) RDW. The primary outcome was 90-day readmission related to heart failure (HF) exacerbation, increased supplemental oxygen (O2) requirements, and systemic inflammatory response syndrome (SIRS). Kaplan Meier survival curves were developed for the probability of primary outcomes-related readmissions. Results: Index admissions (n=74) had 78.38% elevated RDW (n=58) and 21.62% normal RDW (n=16). Age, sex, race and comorbidities were matched between the 2 cohorts (Figure 1). Of these, 70.3% (n=52) had readmissions in 90-days; 67.2% (n=39) with elevated RDW and 81.2% (n=13) with normal RDW. Log-rank p for 90-day readmission probability for HF exacerbation, increased O2 requirement and SIRS were statistically non-significant 0.945, 0.0931, and 0.351 respectively (Figure 2). Conclusions: Our findings do not support RDW alone as a predictive biomarker for readmission in patients with PH, albeit in a small sample size. This study could be viewed as a hypothesis-generating research to spawn further larger studies.

Characteristics and Outcomes of 360 Consecutive COVID-19 Patients Discharged From the Emergency Department With Supplemental Oxygen

To describe characteristics and outcomes of coronavirus disease (COVID-19) patients with new supplemental oxygen requirements discharged from a large public urban emergency department (ED) with supplemental oxygen. This observational case series describes the characteristics and outcomes of 360 consecutive COVID-19 patients with new supplemental oxygen requirements discharged from a large urban public ED between April 2020 and March 2021 with supplemental oxygen. Primary outcomes included 30-day survival and 30-day survival without unscheduled inpatient admission. Demographic and clinical data were collected through a structured chart review. Among 360 patients with COVID-19 discharged from the ED with supplemental oxygen, 30-day survival was 97.5% (95% confidence interval (CI) 95.3 to 98.9%; n=351), and 30-day survival without unscheduled admission was 81.1% (95% CI 76.7 to 85.0%; n=292). A sensitivity analysis incorporating worst-case-scenario for 12 patients without complete follow-up 30 days after index visit yields 30-day survival of 95.5% (95% CI 92.5 to 97.2%; n=343), and 30-day survival without unscheduled admission of 78.9% (95% CI 74.3 to 83.0%; n=284). Among study patients, 32.2% (n=116) had a nadir ED oxygen saturation of <90%, among these 30-day survival was 97.4% (95% CI 92.6 to 99.4%; n=113), and 30-day survival without unscheduled admission was 76.7% (95% CI 68.8 to 84.1%; n=89). COVID-19 patients with new supplemental oxygen requirements discharged from the ED had survival comparable to COVID-19 ED patients with mild exertional hypoxia treated with supplemental oxygen in other settings, and this held true when the analysis was restricted to patients with nadir ED index visit oxygen saturations <90%. Discharge of select COVID-19 patients with supplemental oxygen from the ED may provide a viable alternative to hospitalization, particularly when inpatient capacity is limited.

Benefit of epidural analgesia for postoperative pain control after a Kasai Portoenterostomy: A ten-year retrospective cohort study.

Biliary atresia is a rare obstructive cholangiopathy that presents in infants. The Kasai portoenterostomy procedure, which reestablishes biliary drainage into the intestine, is a surgical procedure that has been found to improve survival with the native liver. The options for postoperative analgesia include systemic opioids and epidural analgesia. The primary objective of this study was to compare the postoperative systemic opioids used in morphine equivalents (mg/kg) on postoperative days 0 through 3 between patients who underwent a Kasai portoenterostomy and received a thoracic epidural infusion to those without thoracic epidural analgesia. We conducted a retrospective cohort study of 91 infants with biliary atresia undergoing a Kasai portoenterostomy between January 1, 2009, and September 1, 2019, at the Children's Hospital of Philadelphia. Sixty-three of the 91 patients (69%) had a continuous epidural catheter placed intraoperatively for postoperative analgesia. The total opioid requirement (morphine equivalents) for the first 72 h in the epidural group of (Mean (95% confidence interval): 0.52 mg/kg (0.38, 0.67 mg/kg) was lower than the non-epidural group (Mean (95% confidence interval): 1.15 mg/kg (0.8, 1.48 mg//kg) for a difference in mean opioid requirement (95% confidence interval) of 0.63 mg/kg (0.32, 0.94 mg/kg). Patients in the non-epidural group had higher rates of unplanned ICU admissions (36% non-epidural group vs. 3.3% epidural group, difference in proportion (95% confidence interval) 32.7% (13, 52%), p < .01). A higher percentage of patients in the non-epidural group had a postoperative oxygen requirement (32.1% vs. 11.3%, difference in proportion (95% confidence interval) 21% (2, 40%), p=.02). In our cohort study, continuous thoracic epidural analgesia in patients undergoing a Kasai portoenterostomy was associated with lower postoperative opioid use. We also observed that the epidural group had a lower ICU admission rate and a lower rate of postoperative supplemental oxygen requirement over the first three postoperative days.

High-dose corticosteroids in patients hospitalized for COVID-19 pneumonia: an observational study of comparative effectiveness

ObjectivesTo assess whether high- compared with low-dose corticosteroids started upon hospitalization reduce mortality in patients with severe COVID-19 pneumonia or in subgroups stratified by severity of respiratory impairment on admission. MethodsWe conducted a retrospective cohort study of patients with confirmed SARS-CoV-2 infection who required oxygen supplementation upon hospitalization between March 1 and December 31, 2020. In-hospital death was analyzed using logistic regression with inverse probability of treatment weighting of receiving low- or high-dose corticosteroid (dexamethasone 6-10 mg daily or >10-20 mg daily or other corticosteroid equivalents). ResultsWe analyzed 13,366 patients who received low-dose and 948 who received high-dose corticosteroids, of whom 31.3% and 40.4% had severe respiratory impairment (>15 l/min of oxygen or mechanical ventilation) upon admission, respectively. There were no differences in the propensity score-adjusted odds of death (odds ratio 1.17, 95% CI 0.72-1.90) or infections (odds ratio 0.70, 95% CI 0.44-1.11) for patients who received high-dose compared with low-dose corticosteroids, beginning on the day of admission. No significant differences in subgroups stratified by severity of respiratory impairment were found. ConclusionInitiating high-dose compared with low-dose corticosteroids among newly hospitalized patients with COVID-19 pneumonia did not improve survival. However, benefit of high-dose corticosteroids in specific subgroups cannot be excluded.