Supplemental Oxygen Requirement Research Articles

Smartphone-Guided Self-prone Positioning vs Usual Care in Nonintubated Hospital Ward Patients With COVID-19: A Pragmatic Randomized Clinical Trial

BackgroundSafe, effective, and easily implementable treatments that reduce the progression of respiratory failure in COVID-19 are urgently needed. Despite the increased adoption of prone positioning during the pandemic, the effectiveness of this technique on progression of respiratory failure among nonintubated patients is unclear.Research QuestionWhat is the effectiveness of smartphone-guided self-prone positioning recommendations and instructions compared with usual care in reducing progression of respiratory failure among nonintubated patients with COVID-19?Study Design and MethodsAwake Prone Position for Early Hypoxemia in COVID-19 (APPEX-19) is a multicenter randomized clinical trial that randomized nonintubated adults with COVID-19 on < 6 L/min of supplemental oxygen to receive a smartphone-guided self-prone positioning intervention or usual care. The primary outcome was the composite of respiratory deterioration (an increase in supplemental oxygen requirement) or ICU transfer. Using a Bayesian statistical approach, the posterior probability of superiority within each treatment arm (superiority threshold 95%) was calculated.ResultsThe trial was stopped early for slow enrollment. A total of 293 participants were included in the modified intention-to-treat analysis (159 self-prone positioning intervention and 134 usual care). Among participants who self-reported body positioning (n = 139 [70 intervention, 69 usual care]), 71.4% in the intervention arm and 59.4% in the usual care arm attempted prone positioning. Thirty-one participants (posterior mean, 24.7%; 95% credible interval, 18.6-31.4) receiving usual care and 32 participants (posterior mean, 22.1%; 95% credible interval, 16.6-28.1) receiving the self-prone positioning intervention experienced the primary outcome; the posterior probability of superiority for the self-prone positioning intervention was 72.1%, less than the 95% threshold for superiority. Adverse events occurred in 26.9% of participants in the usual care arm and in 11.9% of participants in the intervention arm.InterpretationAmong nonintubated patients with COVID-19, smartphone-guided self-prone positioning recommendations and instructions did not promote strong adherence to prone positioning.Clinical Trial RegistrationClinicalTrials.gov; No.: NCT04344587; URL: www.clinicaltrials.gov.

A SARS-CoV-2 outbreak due to vaccine breakthrough in an acute-care hospital

Background: The δ (delta) variant has spread rapidly worldwide and has become the predominant strain of SARS-CoV-2. We analyzed an outbreak caused by a vaccine breakthrough infection in a hospital with an active infection control program where 91.9% of healthcare workers were vaccinated. Methods: We investigated a SARS-CoV-2 outbreak between September 9 and October 2, 2021, in a referral teaching hospital in Korea. We retrospectively collected data on demographics, vaccination history, transmission, and clinical features of confirmed COVID-19 in patients, healthcare workers, and caregivers. Results: During the outbreak, 94 individuals tested positive for SARS-CoV-2 using reverse transcription-polymerase chain reaction (rtPCR) testing. Testing identified infections in 61 health care workers, 18 patients, and 15 caregivers, and 70 (74.5%) of 94 cases were vaccine breakthrough infections. We detected 3 superspreading events: in the hospital staff cafeteria and offices (n = 47 cases, 50%), the 8th floor of the main building (n = 22 cases, 23.4%), and the 7th floor in the maternal and child healthcare center (n = 12 cases, 12.8%). These superspreading events accounted for 81 (86.2%) of 94 transmissions (Fig. 1, 2). The median interval between completion of vaccination and COVID-19 infection was 117 days (range, 18–187). There was no significant difference in the mean Ct value of the RdRp/ORF1ab gene between fully vaccinated individuals (mean 20.87, SD±6.28) and unvaccinated individuals (mean 19.94, SD±5.37, P = .52) at the time of diagnosis. Among healthcare workers and caregivers, only 1 required oxygen supplementation. In contrast, among 18 patients, there were 4 fatal cases (22.2%), 3 of whom were unvaccinated (Table 1). Conclusions: Superspreading infection among fully vaccinated individuals occurred in an acute-care hospital while the δ (delta) variant was dominant. Given the potential for severe complications, as this outbreak demonstrated, preventive measures including adequate ventilation should be emphasized to minimize transmission in hospitals.Funding: NoneDisclosures: None

A phase 2 randomized, double-blinded, placebo-controlled, multicenter trial evaluating the efficacy and safety of raloxifene for patients with mild to moderate COVID-19

SummaryBackgroundCurrent available therapeutic options for Coronavirus Disease-2019 (COVID-19) are primarily focused on treating hospitalized patients, and there is a lack of oral therapeutic options to treat mild to moderate outpatient COVID-19 and prevent clinical progression. Raloxifene was found as a promising molecule to treat COVID-19 due to its activity to modulate the replication of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and act as an immunomodulator to decrease proinflammatory cytokines.MethodsThis was a phase 2 multicenter, randomized, placebo-controlled trial to evaluate the efficacy and safety of raloxifene in adult patients with mild to moderate COVID-19 between October 2020 to June 2021 in five centers located in Italy. This was a planned 2/3 adaptive study, but due to operational difficulties, the study was discontinued during the phase 2 study segment. Participants were randomized 1:1:1 to receive oral placebo, raloxifene 60 mg, or raloxifene 120 mg by self-administration for a maximum of two weeks. The primary outcomes were the proportion of patients with undetectable SARS-CoV-2 via nasopharyngeal swabs at day 7 and the proportion of patients who did not require supplemental oxygen therapy or mechanical ventilation on day 14. Safety was assessed. The trial is registered (EudraCT 2021–002,476–39, and ClinicalTrials.gov: NCT05172050).FindingsA total of 68 participants were enrolled and randomized to placebo (n = 21), raloxifene 60 mg (n = 24), and raloxifene 120 mg (n = 23). The proportion of participants with undetectable SARS-CoV-2 after seven days of treatment with raloxifene 60 mg [36.8%, 7/19 vs. 0.0%, 0/14] and 120 mg [22.2%, 4/18 vs. 0.0%, 0/14] was better compared to placebo, [risk difference (RD) = 0·37 (95% C.I.:0·09–0·59)] and [RD = 0·22 (95% C.I.: -0·03–0·45)], respectively. There was no evidence of effect for requirement of supplemental oxygen and/or mechanical ventilation with effects for raloxifene 60 mg and raloxifene 120 mg over placebo, [RD = 0·09 (95% C.I.: -0·22–0·37)], and [RD = 0·03 (95% C.I.: -0·28–0·33)], respectively. Raloxifene was well tolerated at both doses, and there was no evidence of any difference in the occurrence of serious adverse events.InterpretationRaloxifene showed evidence of effect in the primary virologic endpoint in the treatment of early mild to moderate COVID-19 patients shortening the time of viral shedding. The safety profile was consistent with that reported for other indications. Raloxifene may represent a promising pharmacological option to prevent or mitigate COVID-19 disease progression.FundingThe study was funded by Dompé Farmaceutici SpA and supported by the funds from the European Commission – Health and Consumers Directorate General, for the Action under the Emergency Support Instrument- Grant to support clinical testing of repurposed medicines to treat SARS-COV-2 patients (PPPA-ESI-CTRM-2020-SI2.837140), and by the COVID-2020–12,371,675 Ricerca finalizzata and line 1 Ricerca Corrente COVID both funded by Italian Ministry of Health.

Opaganib in Coronavirus Disease 2019 Pneumonia: Results of a Randomized, Placebo-Controlled Phase 2a Trial.

BackgroundOpaganib, an oral sphingosine kinase-2 inhibitor with antiviral and anti-inflammatory properties, was shown to inhibit severe acute respiratory syndrome coronavirus 2 replication in vitro. We thus considered that opaganib could be beneficial for moderate to severe coronavirus disease 2019 (COVID-19) pneumonia. The objective of the study was to evaluate the safety of opaganib and its effect on supplemental oxygen requirements and time to hospital discharge in COVID-19 pneumonia hospitalized patients requiring supplemental oxygen.MethodsThis Phase 2a, randomized, double-blind, placebo-controlled study was conducted between July and December 2020 in 8 sites in the United States. Forty-two enrolled patients received opaganib (n = 23) or placebo (n = 19) added to standard of care for up to 14 days and were followed up for 28 days after their last dose of opaganib/placebo.ResultsThere were no safety concerns arising in this study. The incidence of ≥Grade 3 treatment-emergent adverse events was 17.4% and 33.3% in the opaganib and placebo groups, respectively. Three deaths occurred in each group. A numerical advantage for opaganib over placebo was observed in in this nonpowered study reflected by total supplemental oxygen requirement from baseline to Day 14, the requirement for supplemental oxygen for at least 24 hours by Day 14, and hospital discharge.ConclusionsIn this proof-of-concept study, hypoxic, hospitalized patients receiving oral opaganib had a similar safety profile to placebo-treated patients, with preliminary evidence of benefit for opaganib as measured by supplementary oxygen requirement and earlier hospital discharge. These findings support further evaluation of opaganib in this population.

Mortality Risk Stratification Using Cluster Analysis in Patients With Myositis-Associated Interstitial Lung Disease Receiving Initial Triple-Combination Therapy.

ObjectiveTo stratify patients with polymyositis/dermatomyositis-associated interstitial lung disease (ILD) who were initially treated with an intensive regimen consisting of high-dose corticosteroids, a calcineurin inhibitor, and intravenous cyclophosphamide (triple-combo therapy) into subgroups based on mortality outcomes by a cluster analysis using a large-scale multicenter retrospective cohort of Japanese patients with myositis-associated ILD (JAMI).MethodsTwo-step cluster analysis of preclustering and subsequent hierarchical clustering was conducted in 185 patients who received triple-combo therapy in an unbiased manner. Initial predictors for mortality previously reported in patients with myositis-associated ILD were used as variables and included age, sex, disease duration, classification of myositis, requirement of supplemental oxygen, anti-aminoacyl tRNA synthetase (ARS) antibody, anti-melanoma differentiation-associated gene 5 (MDA5) antibody, and serum levels of C-reactive protein (CRP) and Krebs von den Lungen-6 (KL-6). The cluster model was further applied to 283 patients who received conventional regimens consisting of corticosteroids with or without a single immunosuppressive agent (dual-combo therapy or monotherapy). Cumulative survival rates were compared using Kaplan-Meier analysis, and the log-rank test was used to test for significant differences between two groups.ResultsWe developed a cluster model consisting of 6 clusters, which were categorized by age at onset, clinically amyopathic dermatomyositis, CRP, KL-6, requirement of supplemental oxygen, anti-ARS antibody, and anti-MDA5 antibody. This model was judged to be of good quality based on the silhouette measure of cohesion and separation of 0.6. These clusters were regrouped into three subsets based on low (<10%), moderate (10-50%), and high (>50%) mortality rates. The performance of the clustering was generally replicated in patients who received initial dual-combo therapy or monotherapy. Survival benefits of triple-combo therapy over dual-combo therapy or monotherapy were not observed in any of the clusters.ConclusionWe successfully developed a cluster model that stratified patients with myositis-associated ILD who were treated with initial triple-combo therapy into subgroups with different prognoses, although this model failed to identify a patient subgroup that showed survival benefits from triple-combo therapy over dual-combo therapy or monotherapy.

Hyperbaric oxygen for COVID-19 patients with severe hypoxia prior to vaccine availability

Introduction: Few treatments have demonstrated mortality benefits among hospitalized hypoxic COVID-19 patients. We evaluated the use of hyperbaric oxygen (HBO2) therapy as a therapeutic intervention among hospitalized patients with a high oxygen requirement prior to vaccine approval. Methods: We extracted data on patients with COVID-19 hypoxia who required oxygen supplementation ranging from a 6L nasal cannula up to a high-flow nasal cannula at 100% FiO2 at 60L/minute with a 100% non-rebreather mask at 15 L/minute and were eligible for off-label HBO2 therapy from October 2020 to February 2021. We followed the Monitored Emergency use of Unregistered and Investigational Interventions or (MEURI) in conjunction with the consistent re-evaluation of the protocol using the Plan-Do-Study-Act (PDSA) tool [1]. We compared patient characteristics and used Fisher’s exact test and a survival analysis to assess the primary endpoint of inpatient death. Results: HBO2 therapy was offered to 36 patients, of which 24 received treatment and 12 did not receive treatment. Patients who did not receive treatment were significantly older (p &lt; 0.01) and had worse baseline hypoxia (p = 0.06). Three of the 24 (13%) patients who received treatment died compared to six of 12 (50%) patients who did not receive treatment (RR ratio: 0.25, p = 0.04, 95% CI: 0.08 to 0.83). In the survival analysis, there was a statistically significant reduction in inpatient mortality in the treatment group (HR: 0.19, p = 0.02, 95% CI: 0.05-0.74). However, after adjusting for age and baseline hypoxia, there was no difference in inpatient mortality (hazard ratio: 0.48, p = 0.42, 95% CI: 0.08-2.86). Conclusions: The survival benefit of HBO2 therapy observed in our unadjusted analysis suggests that there may be therapeutic benefits of HBO2 in treating COVID-19 hypoxia as an adjunct to standard care.

MO878: Does Haemodiafiltration Versus Haemodialysis Have Clinical Benefits for Covid-19 Severity and Mortality in Maintenance Haemodialysis Patients?

BACKGROUND AND AIMSIt has been demonstrated that online haemodiafiltration (HDF) provides higher clearance of middle molecular solutes compared with high-flux haemodialysis (HD) due to its convective component and may improve clinical outcomes in maintenance haemodialysis patients. However, the clinical superiority of HDF compared with standard HD is still controversial. Moreover, there is a general lack of these data on the current topic in patients infected with COVID-19. The present study aimed to prospectively analyze whether HDF has benefits for COVID-19 severity and mortality in maintenance haemodialysis patients.METHODA total of 340 maintenance haemodialysis patients aged 53.5 ± 12.9 years and a median dialysis vintage of 40 (24–74) months were included in this prospective multicentre cohort study conducted across 5 dialysis centers. All patients were not infected with COVD-19 at the time of the enrollment and subsequently followed up from March 2020 to September 2021 (the mean duration was 7 (4.2–15.4) months). The study outcomes were COVID-19-associated hospitalization needs due to supplemental oxygen requirements and COVID-19-associated mortality.The data were presented as the mean and the standard deviation (M ± SD) or the median and the interquartile ranges [Me (Q25–Q75)] and compared using the Student's t-test or the Mann–Whitney U-test as appropriate. The Chi-squared test was used to determine the differences between categorical variables. The univariate logistic regression analyses were performed to evaluate the predictive factors for COVID-19-associated severity and mortality. Then, the Cox proportional-hazards regression model was carried out using the factors found to be significant by the univariate analysis.RESULTSAmong the enrolled patients, there were 312 (91.7%) patients on HDF and 28 (8.3%) patients treated with HD. Sex (χ2 = 1.12 P = 0.29), age (55.3 ± 12.9 versus 59.6 ± 12.5 years; P = 0.07) and dialysis vintage [40 (23–72) versus 45 (29–84) months; P = 0.39] did not differ between the HDF and the HD groups at the study entry. During the follow-up period, 98 out of 312 (31.4%) of the HDF patients and 16 out of 28 (57.1%) of the HD patients were infected with COVID-19 (χ2 = 9.6; P = 0.001). Among them, there were 54 out of 98 (55.1%) of the HDF patients and 12 out of 16 (75%) of the HD patients who required hospitalization with oxygen supplementation (χ2 = 12.6; P = 0.0004). Out of 98, 4 (4.1%) of the HDF patients and 5 out of 16 (31.2%) of the HD patients died (χ2 = 31.3, P < 0.0001) during the follow-up period. In the univariate logistic regression analysis, older patient age {OR: 1.03, [95% confidence interval (95% CI) 1.01–1.05]}, diabetic status (OR: 2.8, 95% CI 1.4–5.5), long dialysis vintage (OR: 1.07, 95% CI 1.03–1.1), low blood flow (OR: 1.04, 95% CI 1.02–1.08) and HD treatment (OR: 4.1, 95% CI 1.5–11.2) were significantly associated with the requirement of oxygen supplementation. In the Cox regression model adjusted for all mentioned factors, HD treatment was significantly associated with COVID-19 severity and oxygen requirement (Figure 1). However, when we performed the same model to predict COVID-associated mortality, HD treatment lost its significance, and only patient age (P = 0.02) and dialysis vintage (P = 0.004) were significantly associated with reduced survival.FIGURE 1:Probability curves of COVID-19-associated hospitalization with oxygen supplementation (adjusted for age, diabetic status, dialysis vintage and blood flow) in the HDF patients compared with the HD patients.CONCLUSIONThe HDF patients required fewer hospitalizations and oxygen support and had a lower mortality rate compared with the HD patients. Although HDF treatment versus HD treatment was significantly associated with better COVID-19 outcomes in our cohort, a predictive conclusion of the study was limited by the small sample size of the HD group and a relatively short follow-up period. Further large-scale studies are needed to determine the role of HDF versus HD in COVID-19-associated severity and mortality in maintenance haemodialysis patients.

Risk factors and medical resource utilization in US adults hospitalized with influenza or respiratory syncytial virus in the Hospitalized Acute Respiratory Tract Infection study.

BackgroundInfluenza and respiratory syncytial virus (RSV) are associated with substantial morbidity and mortality in the United States. We assessed risk factors for severe disease and medical resource utilization (MRU) among US adults hospitalized with influenza or RSV in the Hospitalized Acute Respiratory Tract Infection (HARTI) study.MethodsHARTI was a prospective global (40 centers, 12 countries) epidemiological study of adults hospitalized with acute respiratory tract infections conducted across the 2017–2019 epidemic seasons. Patients with confirmed influenza or RSV were followed up to 3 months post‐discharge. Baseline characteristics, prevalence of core risk factors (CRFs) for severe disease (age ≥65 years, chronic heart or renal disease, chronic obstructive pulmonary disease, or asthma), and MRU were summarized descriptively.ResultsThe US cohort included 280 influenza‐positive and 120 RSV‐positive patients. RSV patients were older (mean: 63.1 vs. 59.7 years) and a higher proportion had CRFs (87.5% vs. 81.4%). Among those with CRFs (influenza, n = 153; RSV, n = 99), RSV patients required longer hospitalizations (median length of stay: 4.5 days) and a greater proportion (79.8%) required oxygen supplementation during hospitalization compared with influenza patients (4.0 days and 59.5%, respectively). At 3 months post‐discharge, a greater proportion of RSV patients with CRFs reported use of antibiotics, antitussives, bronchodilators, and inhaled and systemic steroids versus those with influenza and CRFs. Many patients with CRFs reported hospital readmission at 3 months post‐discharge (RSV: 13.4%; influenza: 11.9%).ConclusionsMRU during and post‐hospitalization due to RSV in adults is similar to or greater than that of influenza. Enhanced RSV surveillance and preventive and therapeutic interventions are needed.

Machine Learning Prediction for Supplemental Oxygen Requirement in Patients with COVID-19

The coronavirus disease (COVID-19) poses an urgent threat to global public health and is characterized by rapid disease progression even in mild cases. In this study, we investigated whether machine learning can be used to predict which patients will have a deteriorated condition and require oxygenation in asymptomatic or mild cases of COVID-19.This single-center, retrospective, observational study included COVID-19 patients admitted to the hospital from February 1, 2020, to May 31, 2020, and who were either asymptomatic or presented with mild symptoms and did not require oxygen support on admission. Data on patient characteristics and vital signs were collected upon admission. We used seven machine learning algorithms, assessed their capability to predict exacerbation, and analyzed important influencing features using the best algorithm.In total, 210 patients were included in the study. Among them, 43 (19%) required oxygen therapy. Of all the models, the logistic regression model had the highest accuracy and precision. Logistic regression analysis showed that the model had an accuracy of 0.900, precision of 0.893, and recall of 0.605. The most important parameter for predictive capability was SpO2, followed by age, respiratory rate, and systolic blood pressure.In this study, we developed a machine learning model that can be used as a triage tool by clinicians to detect high-risk patients and disease progression earlier. Prospective validation studies are needed to verify the application of the tool in clinical practice.

Impact of Vaccination and Early Monoclonal Antibody Therapy on Coronavirus Disease 2019 Outcomes in Organ Transplant Recipients During the Omicron Wave.

BackgroundSolid organ transplant (SOT) recipients are at high risk for complications from coronavirus disease 2019 (COVID-19) and vaccine breakthrough infections are common. We determined the effectiveness of ≥3 doses of mRNA vaccine and early monoclonal antibody therapy in reducing disease severity against the Omicron (B.1.1.529) variant.MethodsProspective cohort study of consecutive SOT recipients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection referred to our transplant center who were followed for at least 30 days. The primary outcome was supplemental oxygen requirement. Effectiveness of sotrovimab and ≥3 vaccine doses was estimated using adjusted risk ratios (RR).ResultsThree hundred adult organ transplant recipients were included. Seventy-one patients (24.1%) were hospitalized, 44 (14.9%) required supplemental oxygen, 19 (6.5%) were admitted to the intensive care unit (ICU), 15 (5.1%) required mechanical ventilation (MV), and 13 (4.4%) died. On multivariate analysis, age and multiple comorbidities were risk factors for oxygen requirement. Both receipt of ≥3 vaccine doses prior to SARS-CoV-2 infection and receipt of sotrovimab in the first 7 days of symptom onset was associated with a reduction in the need for supplemental oxygen (RR 0.30 [95% confidence interval {CI}: .17 to .54] and RR 0.24 (95% CI: .1 to .59), respectively]. For sotrovimab, the number needed to treat (NNT) to prevent one patient requiring oxygen was 6.64 (95% CI: 4.56–13.66). Both sotrovimab use and having received ≥3 vaccine doses were also associated with a shorter hospitalization length of stay.ConclusionsIn a cohort of SOT recipients with Omicron variant COVID-19 infection, prior receipt of ≥3 mRNA vaccine doses and early monoclonal antibody therapy were independently associated with significantly reduced disease severity.

Being small for gestational age is not an independent risk factor for mortality in neonates with congenital diaphragmatic hernia: a multicenter study.

Congenital diaphragmatic hernia (CDH) accounts for 8% of all major congenital anomalies. Neonates who are small for gestational age (SGA) generally have a poorer prognosis. We sought to identify risk factors and variables associated with outcomes in neonates with CDH who are SGA in comparison to neonates who are appropriate for gestational age (AGA). We used the multicenter Diaphragmatic Hernia Research & Exploration Advancing Molecular Science (DHREAMS) study to include neonates enrolled from 2005 to 2019. Chi-squared or Fisher's exact tests were used to compare categorical variables and t tests or Wilcoxon rank sum for continuous variables. Cox model analyzed time to event outcomes and logistic regression analyzed binary outcomes. 589 neonates were examined. Ninety were SGA (15.3%). SGA patients were more likely to be female (p = 0.003), have a left sided CDH (p = 0.05), have additional congenital anomalies and be diagnosed with a genetic syndrome (p < 0.001). On initial single-variable analysis, SGA correlated with higher frequency of death prior to discharge (p < 0.001) and supplemental oxygen requirement at 28 days (p = 0.005). Twice as many SGA patients died before repair (12.2% vs 6.4%, p = 0.04). Using unadjusted Cox model, the risk of death prior to discharge among SGA patients was 1.57 times the risk for AGA patients (p = 0.029). There was no correlation between SGA and need for ECMO, pulmonary hypertensive medication at discharge or oxygen at discharge. After adjusting for confounding variables, SGA no longer correlated with mortality prior to discharge or incidence of unrepaired defects but remained significant for oxygen requirement at 28 days (p = 0.03). Infants with CDH who are SGA have worse survival and poorer lung function than AGA infants. However, the outcome of SGA neonates is impacted by other factors including gestational age, genetic syndromes, and particularly congenital anomalies that contribute heavily to their poorer prognosis.

Glycated Albumin and Glycated Albumin/HbA1c Predict the Progression of Coronavirus Disease 2019 from Mild to Severe Disease in Korean Patients with Type 2 Diabetes.

Hyperglycemia is among the main risk factors for severe COVID-19. We evaluated the association of glycated albumin (GA) and GA/HbA1c ratio with progression of COVID-19 from mild to severe disease in patients with type 2 diabetes mellitus (T2DM). Our retrospective study included 129 patients aged over 18 years with COVID-19 and T2DM who did not have any need of oxygen supplement. Of these, 59 patients whose COVID-19 was aggravated and required oxygen supplementation eventually were classified as having severe disease. Clinical and laboratory data were compared between mild and severe cases. The median of GA (18.4% vs. 20.95%, p = 0.0013) and GA/HbA1c (2.55 vs. 2.68, p = 0.0145) were higher in severe disease than in mild disease and positively correlated with C-reactive protein (Kendal Tau coefficient 0.200 and 0.126, respectively; all p < 0.05). Multiple logistic regression analysis showed that GA (odds ratio (OR), 1.151; 95% confidence interval (CI), 1.024–1.294) and GA/HbA1c (OR, 8.330; 95% CI, 1.786–38.842) increased the risk of severe disease. Patients with GA 20% or higher were 4.03 times more likely to progress from mild to severe disease. GA and GA/HbA1c ratio predicted progression of COVID-19 from mild to severe disease in patients with T2DM.

Efficacy and feasibility of awake proning in patients with COVID-19-related acute hypoxemic respiratory failure: an observational, prospective study.

IntroductionMost of COVID-19 patients present with hypoxemic respiratory failure. Proning is one of the management options proven to improve oxygenation and reduce mortality in non-COVID-19-related acute respiratory distress syndrome. As a response to COVID-19 pandemic surge, a dedicated COVID-19 respiratory ward for the management of mild to moderate ARDS patients who require oxygen therapy, non-invasive ventilation (NIV), or high-flow nasal cannula (HFNC) was established. We adopted a policy of early awake proning in such patients.AimsTo determine the physiological changes, improvement in oxygenation, the need for intubation, alongside with the duration, tolerance, and adverse effects of awake proning. Study design and methodsSingle-center, prospective observational cohort study. All awake, non-intubated, spontaneously breathing patients with COVID-19, and hypoxemic acute respiratory failure requiring oxygen supplementation, NIV, or HFResultsFifty patients were enrolled. There was a significant improvement in oxygenation when turning the patients from supine to prone position with mean PFR was 85 (SD 13.76) in supine position which increased to 124 (SD 34.08) in prone position with substantial increase in mean PFR 1-h post proning to 138 (SD 28.01) and P-value 0.0001. Prone positioning was feasible in 41 (82%) patients (mean duration 8.5 (SD 3.13) h), and 38 (76%) patients reported that it was well tolerated.ConclusionAwake proning was feasible, tolerable, and effective in improving oxygenation in patients with COVID-19-related pneumonia and acute hypoxemic respiratory failure in this prospective study.

Impact of COVID19 Infection Among Heart Transplanted Recipients: The Experience of a Latin American Center

PurposeHeart transplanted recipients are at a high risk for COVID19 infection. Clinical presentation, complications, and related outcomes have been described worldwide. However, there is a paucity of data in Latin America.MethodsRetrospective cohort of heart transplanted recipients followed at a center in Rio Grande do Sul, Brazil, between March 1st 2020 to October 1st 2021. Data are presented as absolute numbers (percentage) or median (interquartile).ResultsAmong 62 recipients in follow-up, 21 (34%) were infected by COVID19. 58 (36-63) years, 67% male, body mass index of 26 kg/m², 48% with hypertension, 43% with chronic kidney disease, 5% diabetes, 3.1 (1.0-4.2) years post-transplant. Most common symptoms at presentation were fever (62%), myalgia (33%), cough (33%), and headache (33%). Dyspnea occurred in only 19% patients. Hospitalization was required for 13 (62%) with a time from symptoms onset to admission of 5 (1-12) days. In 38%, supplementary oxygen was needed, 19% required intensive care, and 10% mechanical ventilation. Main complications were bacterial pneumonia (38%), renal replacement therapy (19%), sepsis (10%), venous thromboembolism (10%), and pancreatitis (5%). Immunosuppression therapy was modified in 48% (in majority 89%, reduced). Median hospitalization time was 17 (8-28) days. Two (10%) patients died in hospital due to refractory hypoxemia and multiorgan dysfunction. The prevalence of COVID19 among heart transplanted patients was comparable to the general population in the state of Rio Grande do Sul (Figure 1) with a peak in December 2020.ConclusionCOVID19 infection prevalence among heart transplanted recipients was elevated, presenting mostly with typical symptoms, and frequent hospitalizations, supplementary oxygen requirement, and complications. Although the COVID19 prevalence in Latin America was amongst the highest reported, in-hospital mortality among infected heart transplanted recipients was similar to previously published data worldwide.

The Use of Intermittent Non-Invasive Ventilation as an Alveolar Recruitment Method for Patient with Severe COVID-19 Pneumonia

Background: The use of non-invasive ventilation (NIV) as a therapy for acute respiratory distress syndrome (ARDS) secondary to COVID 19 pneumonia has been controversial. NIV is an aerosol generating procedure which may increase the risk of viral transmission amongst patients and staff. Because of fear of aerosolizing the virus and transmitting the disease, initial expert recommendation was to avoid NIV and proceed with early intubation. With further experience of the virus, this recommendation has been challenged and NIV has been used widely with some retrospective studies quoting between 11 to 56 percent of COVID 19 related respiratory failures being treated with NIV. Objective: The objective of this study is to assess the efficacy and safety of using non-invasive mechanical ventilation as an alveolar recruitment method for patients with severe COVID 19 pneumonia. This method was used by our respiratory team on selected patients during the early phase of the COVID 19 pandemic. Methods: We reviewed the charts of patients that were admitted to the American Hospital Dubai intensive care unit, or our medical step-down unit who had diffuse bilateral infiltrates requiring oxygen supplementation between March and October 2020. We identified patients who were on intermittent BiPAP in addition to standard care. We also monitored the rate of infection among staff taking care of these patients. Results: Average length of stay after starting BIPAP therapy was 6.8 days, while the average total length of stay was 13.6 days. Only one patient was transferred to the ICU after being on the BIPAP protocol and did not need intubation. All patients were discharged home either without oxygen or with their chronic baseline home oxygen requirement. Radiological improvement in aeration was seen in 100% of patients at follow-up x-ray post-intervention. There were no reported pulmonary complications from barotrauma, such as pneumothorax or pneumomediastinum. There were no reported cases of staff infection to the health care workers that were taking care of these patients Conclusion: Our first of its kind observational study showed clearly that using BIPAP therapy for one hour three times daily during nebulization therapy in addition to standard care resulted in a significant reduction in hospital length of stay and hastened the clinical and radiological improvement of patients with severe COVID 19 pneumonia.

The Diagnostic Dilemma of a Nodule Appearing as a Mass

<h3>Introduction</h3> Posttransplant lymphoproliferative disorder (PTLD) after lung transplantation (LT) occurs due to immunosuppressant therapy that limits antiviral host immunity and permits Epstein-Barr viral (EBV) replication and transformation of B cells. <h3>Case Report</h3> We present the case of a 61-year-old man with history of bone marrow transplant (08/2009) for non-Hodgkin's lymphoma and bilateral LT (04/2021) for idiopathic pulmonary fibrosis - EBV status: D+/R+. The transplant was complicated by prolonged duration of ECMO and a lengthy post-LT hospital stay for renal failure, significant deconditioning, and acute on chronic respiratory failure requiring tracheostomy and fiberoptic bronchoscopic airway stent placement to limit atelectasis. He also required a muscle flap for right bronchial anastomotic dehiscence in this time course. After 4 months, he was finally discharged to home with tracheostomy in place, requiring oxygen supplementation based only on physical demands. On his return to clinic, an inspection bronchoscopy was performed to assess the airway stent, which was found to have purulent secretions concerning for infection. Bronchoalveolar lavage was positive for pan-sensitive <i>Pseudomonas</i> requiring intravenous antibiotic therapy. At the same time, a chest CT revealed multiple pulmonary nodules in the right lung base, the largest measuring 2.8 cm in diameter. A CT-guided biopsy confirmed EBV-positive polymorphic PTLD. Immunostaining yielded positive results for CD20, CD138, CD79a, MUM1, and EBV-encoded RNAs (EBER) (<b>Figure 1</b>). Notably, this patient never had a positive EBV-viral load. Given his undetectable EBV levels, a decision was made to reduce immunosuppression and follow imaging and blood counts as appropriate. <h3>Summary</h3> EBV-positive PTLD with negative EBV viremia is an unusual combination in an EBV-seropositive recipient with donor non-mismatch. The patient's tenuous respiratory status requiring intensive corticotherapy likely contributed significant risk for PTLD in this case.

Impact of COVID-19 Vaccination After Orthotopic Heart Transplantation

PurposeThe effect of COVID-19 vaccination in orthotopic heart transplant (OHT) patients is unknown. After OHT, patients are increased risk of COVID infection and hospitalization.MethodsWe retrospectively analyzed 119 patients who underwent OHT between 2017 and 2021. Eleven patients were excluded who died prior to the COVID outbreak in the United States.ResultsThe mean age was 51 years (IQR 26). The known vaccination rate (partial or complete) was 83%. The overall infection rate was 14% (17 COVID cases were identified.) Five patients were infected prior to the availability of the COVID vaccine. Of the remaining 2 (16%) and 5 (42%) were in vaccinated and unvaccinated patients respectively. The hospitalization rate due to COVID infection or COVID-related complications such as supplemental oxygen use was 29%. All hospitalized subjects underwent changes in their antirejection therapies, and half required oxygen supplementation therapy at discharge. No COVID-related deaths were identified. There were 2 partially/fully vaccinated patients at the time of COVID infection. One patient had mild symptoms and did not require hospitalization while the other patient was asymptomatic.ConclusionHospitalization rates were markedly higher in the OHT cohort compared to Kentucky state data (29% vs 4%.) Multiple factors contribute to this finding. Patients with OHT have more co-morbidities and after OHT and immunosuppressant therapy blunts host response to infection placing these patients at higher risk of complications. There was a higher vaccination rate in our OHT cohort compared to Kentucky state data (83% vs 61%). Breakthrough COVID infection was found in only 4% of OHT patients strongly supporting the efficacy of the vaccination in this immunosuppressant subgroup. While there were no COVID related deaths in our cohort, downstream complications related to immunosuppression changes and organ rejection detection require long term follow up. The vaccine has proved highly efficacious in this group and should be implemented up front, prior to transplantation. We suggest pre-transplant COVID-19 vaccination should become mandatory in patients being evaluated for OHT.

An Analytical Study of the Early COVID-19 Cases in Jordan

Background: The daily cases and fatalities in the COVID-19 pandemic are still on the rise. This study aimed to examine the epidemiological trends of the COVID-19 patients at an early stage in the pandemic. Methods: This study included all COVID-19 positive patients who were admitted to the Prince Hamza Hospital between the 2nd and 31st of March 2020. The demographic, clinical, and laboratory data of the COVID-19 positive patients were reviewed and analysed.Results: Of the 132 patients admitted during the period of study, 81 were males, with a mean age of 38.9 years (SD ± 19 yrs). Of those, 55 (41.7%) had comorbidities, 9% required oxygen supplementation, and 3 (2.2%) died. The most common clinical manifestations on admission were fever (36.4%), dry cough (17.4%), shortness of breath (12.9%), and anosmia (10.6%). CRP was elevated in 45.4%, and ESR was also high in 22.7% of patients with CRP elevation and was statistically significant in symptomatic patients (p = 0.004). Likewise, D-dimer was markedly elevated in 42.1% of the symptomatic patients (p = 0.025). Chest CT scans in symptomatic patients showed statistically significant bilateral lung infection (17.2%) as compared to non-symptomatic patients (p = 0.049). Conclusion: The COVID-19 outbreak in Jordan at the beginning of the pandemic had presented clinically significant symptoms associated with higher values of CRP and CT chest findings.

Clinical presentation and outcomes of chronic dialysis patients with COVID-19: A single center experience from Greece

BACKGROUNDCoronavirus disease 2019 (COVID-19) is still a menacing pandemic, especially in vulnerable patients. Morbidity and mortality from COVID-19 in maintenance hemodialysis (MHD) patients are considered worse than those in the general population, but vary across continents and countries in Europe. AIMTo describe the clinical course and outcomes of hospitalized MHD patients with COVID-19 in a retrospective observational single center study in Greece. METHODSWe correlated clinical, laboratory, and radiological data with the clinical outcomes of MHD patients hospitalized with COVID-19 during the pandemic. The diagnosis was confirmed by real-time polymerase chain reaction. Outcome was determined as survivors vs non-survivors and “progressors” (those requiring oxygen supplementation because of COVID-19 pneumonia worsening) vs “non-progressors”.RESULTSWe studied 32 patients (17 males), with a median age of 75.5 (IQR: 58.5-82) years old. Of those, 12 were diagnosed upon screening and 20 with related symptoms. According to the World Health Organization (WHO) score, the severity on admission was mild disease in 16, moderate in 13, and severe in 3 cases. Chest computed tomography (CT) showed 1-10% infiltrates in 24 patients. Thirteen “progressors” were recorded among included patients. The case fatality rate was 5/32 (15.6%). Three deaths occurred among “progressors” and two in “non-progressors”, irrespective of co-morbidities and gender. Predictors of mortality on admission included frailty index, chest CT findings, WHO severity score, and thereafter the increasing values of serum LDH and D-dimers and decreasing serum albumin. Predictors of becoming a “progressor” included increasing number of neutrophils and neutrophils/lymphocytes ratio.CONCLUSIONPatients on MHD seem to be at higher risk of COVID-19 mortality, distinct from the general population. Certain laboratory parameters on admission and during follow-up may be helpful in risk stratification and management of patients.

Effectiveness of Favipiravir on Nonsevere, Early-Stage COVID-19 in Japan: A Large Observational Study Using the COVID-19 Registry Japan.

IntroductionSeveral randomized controlled trials have compared the effectiveness of favipiravir with that of placebo. However, evidence regarding its effect on nonsevere, early-stage coronavirus disease 2019 (COVID-19) remains insufficient.MethodsWe used the COVID-19 Registry Japan, a nationwide registry of inpatients with COVID-19, for evaluating the effectiveness of favipiravir on patients with nonsevere, early-stage COVID-19. Eligible patients, who did not need supplementary oxygen therapy at admission, were classified according to two regimens (starting favipiravir therapy within 4 days from admission vs. no favipiravir during hospitalization) and were then compared using a three-step method (cloning, censoring, and weighting). The primary outcome was supplementary oxygen requirement during hospitalization, and the secondary outcomes were the need for invasive mechanical ventilation or extracorporeal membrane oxygenation (IMV/ECMO) and overall mortality at 30 days.ResultsA total of 7654 cases were analyzed. The “start favipiravir” regimen did not show substantial differences in the primary outcome [hazard ratio 0.825, 95% confidence interval (CI) 0.657–1.04, p = 0.098] and both of the secondary outcomes [need for IMV/ECMO and overall 30-day mortality, hazard ratio 1.02 (95% CI 0.649–1.60) and 0.869 (95% CI 0.519–1.46), p = 0.929 and 0.594, respectively].ConclusionsIn this large cohort from a COVID-19 registry, favipiravir was not associated with a positive effect on the clinical outcome on patients with nonsevere, early-stage COVID-19, suggesting that it is not an essential drug for COVID-19 treatment.