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Immunization is heralded as a key tool to combat the COVID-19 pandemic. One key technology, messenger RNA (mRNA) vaccines have demonstrated an efficacy greater than 94%1,2. While mRNA vaccines create strong protection in the majority of patients, the antibody response in solid organ recipients has been reported to be less reliable3. Herein, we report the incidence and mortality of COVID-19 in lung transplant recipients after receiving a messenger RNA vaccine (BNT162b2 [Pfizer-BioNTech] or mRNA1273 [Moderna]). From February 1, 2021 to September 1, 2021, SARS-CoV-2 positivity, admissions to the hospital, and mortality among lung transplant recipients was recorded at our institution. This timeframe was selected as the mRNA vaccine became available to recipients of lung transplantation in February of 2021. To obtain the immunization status of lung transplant recipients eligible for vaccination with one of the two mRNA vaccines, a query of the electronic medical record was performed during the previously mentioned dates. Among 317 patients, 276 had received at least two doses of mRNA vaccine (87%). Twenty-six tested positive (8.2%). Of the 26 individuals who developed COVID-19, 20 (76.9%) required admission to the hospital with eight deaths (30.8%). Four deaths occurred among the 13 individuals who contracted SARS-CoV-2 despite having received a minimum of two doses of mRNA vaccine representing a 30.7% mortality. The average duration between immunization and a positive PCR result was 86 days (SD 56 days) for individuals who had received at least two doses of a vaccine. Recent studies have shown that a third dose of the mRNA vaccine BNT162b2 (Pfizer-BioNTech) can augment the antibody response in solid organ transplantation recipients4. The immunogenicity of the mRNA vaccine in this population still remains less vigorous compared to the immunocompetent. The reduced efficacy of mRNA vaccines combined with the elevated rate of admission and mortality described above, demonstrate that vaccination alone cannot annul the impact of COVID-19 in these patients. When mask wearing, social distancing, and hand-washing fail, therapies such as casirivimab and imdevimab (REGN-COV2), neutralizing monoclonal antibodies against SARS-CoV-2 could be considered in early disease to suppress viral load5 and protect this vulnerable population despite immunization status. [ FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)
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Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF), a myeloid cell growth factor and pro-inflammatory cytokine, may drive the overactive host immune response in COVID-19. We conducted a clinical trial assessing the anti-GM-CSF monoclonal antibody gimsilumab for hyperinflammatory COVID-19 pneumonia (BREATHE). Here, we report a pre-specified subgroup analysis demonstrating a signal of benefit in patients invasively ventilated at baseline. Methods: BREATHE (NCT04351243) was a double-blind, randomized, placebo-controlled trial at 21 US locations. Patients were randomized 1:1 to receive two doses of IV gimsilumab or placebo one week apart. The study included hospitalized COVID-19 patients with hyperinflammation (CRP ≥50 mg/L or ferritin ≥1,000 ng/mL) and pre-ARDS lung injury or ARDS. The primary endpoint was all cause mortality at day 43, and key secondary outcomes assessed ventilator use and hospitalization length. Results: 225 patients were randomized and dosed. 41 patients were invasively ventilated at baseline. Steroid use and baseline characteristics were generally balanced across study arms in this subgroup. Ventilated patients treated with gimsilumab demonstrated improvements over placebo on the primary and key secondary endpoints (Table 1). Contrasting the placebo group, gimsilumabtreated patients did not experience a sharp rise in NT-proBNP, a marker of heart failure, through day 43 (Figure 1). Conclusions: GM-CSF inhibition may be therapeutic in ventilated COVID-19 patients through a neurohormonal mechanism. More studies are needed to assess the role of GM-CSF in COVID-19-associated cardiomyopathy, volume status, and ARDS.
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RATIONALE: The alveolar epithelium is the barrier between inhaled air and the underlying tissue. Alveolar type II (ATII) cells produce and secrete pulmonary surfactant and restore the injured epithelium. It has been reported that SARS-CoV-2 infection causes diffused alveolar damage in the lung. However, host factors facilitating virus infection and COVID-19 pathogenesis are not well known. METHODS: We isolated ATII cells from young and elderly non-smoker, smoker, and ex-smoker organ donors. Also, cells were obtained from lung transplants of emphysema patients. Gene and protein expression related to SARS-CoV-2 infection were analyzed using RT-PCR and Western blotting, respectively. RESULTS: ACE2 was identified as a receptor mediating infection. We found that its levels were significantly increased in ATII cells isolated from elderly smokers compared to non-smokers as detected by Western blotting. ACE2 expression was also higher in ATII cells obtained from emphysema patients compared to non-smokers. ACE2 mRNA levels were increased in elderly non-smokers and smokers compared to young organ donors regardless of smoking status. The viral entry depends on TMPRSS2 protease activity. We detected its increased levels in elderly smokers than young non-smokers by Western blotting. Both ACE2 and TMPRSS2 mRNA levels were higher in emphysema in comparison with non-smokers. Moreover, we found increased CD209L gene and protein levels in young smokers and emphysema patients compared to non-smokers. Furthermore, GRP78, an endoplasmic reticulum chaperone, is an important host factor for viral infection. We detected its increased expression in ATII cells isolated from young and elderly smokers compared to non-smokers by Western blotting. Also, its higher levels were observed in emphysema patients than in non-smokers. CONCLUSION: Our results suggest dysregulation of SARS-CoV-2 infection-related genes and proteins especially in elderly smokers and emphysema patients, which may provide insight into the pathogenesis of COVID-19.
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Background: Comorbid disease was identified early during the COVID-19 pandemic as a risk factor for severe infection, however, initial rates of chronic obstructive pulmonary disease (COPD) in case series were low and severity of COVID-19 in COPD patients was variable. Methods: We performed a retrospective study of patients admitted with COVID-19 and evaluated outcomes in those with and without COPD and/or emphysema. Patients were identified as having COPD if they had a diagnosis in the medical record and a history of airflow-obstruction on spirometry, or a history of tobacco use and prescribed long-acting bronchodilator(s). Computed tomography scans were evaluated by radiologists. Propensity matching was performed for age, body-mass index (BMI), and serologic data correlated with severity of COVID-19 disease (D-dimer, C-reactive protein, ferritin, fibrinogen, absolute lymphocyte count, lymphocyte percentage, and lactate dehydrogenase).Results: Of 577 patients admitted with COVID-19, 103 had a diagnosis of COPD and/or emphysema. The COPD and/or emphysema cohort was older (67 years vs 58 years, p<0.0001) than the other cohort and had a lower BMI (28.3 kg/m2 vs 31.1 kg/m2, p<0.01). Among unmatched cohorts those with COPD and/or emphysema had higher rates of intensive care unit (ICU) admission (35% vs 24.9%, p=0.036) and maximal respiratory support requirements (p=0.007), with more frequent invasive mechanical ventilation (21.4% vs 11.8%), and a trend towards higher mortality (12.6% vs 8.2%) that was not statistically significant (p=0.158). After propensity-matching there was no difference in rates of ICU admission, maximal respiratory support requirements, or mortality. The propensity-matched group with COPD and/or emphysema had higher median pack-years of tobacco use (35.0 vs 17.5, p=0.046) and rates of active smoking (28.2% vs 9.7%, p<0.01). Propensity matching was not performed for rates of comorbid disease such as coronary artery disease but the propensity-matched groups had no significant differences in cardiac comorbidities.DiscussionOur propensity-matched retrospective cohort study suggests that patients hospitalized with COVID-19 that have COPD and/or emphysema may not have worse outcomes than those without these comorbid conditions.
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Introduction: Currently the main diagnostic modality for COVID-19 (Coronavirus disease-2019) is reverse transcriptase polymerase chain reaction (RT-PCR) via nasopharyngeal swab which has high false negative rates (diagnostic yield∼70%). We evaluated the performance of high-resolution computed tomography (HRCT) imaging in the diagnosis of suspected COVID-19 infection compared to RT-PCR nasopharyngeal swab alone in patients hospitalized for suspected COVID-19 infection. Methods: This was a retrospective analysis of 324 consecutive patients admitted to Temple University Hospital. All hospitalized patients who had RT-PCR testing and HRCT were included in the study. HRCTs were classified as Category 1, 2 or 3. Category 1 scans were high probability scans (i.e: ground glass opacities (GGOs), crazy-paving, reverse halo/peri lobular pattern irrespective of location and laterality). Category 3 were low probability scans consistent with an alternate diagnosis. Category 2 scans were indeterminate. Patients were then divided into four groups based on HRCT category and RT-PCR swab results for analysis (Group 1: COVID (+) PCR and Category 1 CT scan, Group 2: COVID (+) PCR and Category 2 and 3 CT scan, Group 3: COVID (-) PCR and Category 1 CT scan, Group 4: COVID (-) PCR and Category 2 and 3 CT scan). Inflammatory markers and treatments were compared across these groups. Results: The average age of patients was 59.4(+15.2) years and 123(38.9%) were female. Predominant ethnicity was African American 148 (46.11%). 161 patients tested positive by RT-PCR, while 41 tested positives by HRCT. 167 (52.02%) had category 1 scan, 63 (19.63%) had category 2 scan and 91 (28.35%) had category 3 HRCT scans. There was substantial agreement between our radiologists for HRCT classification (κ = 0.64). Sensitivity and specificity of HRCT classification system was 77.6 and 73.7 respectively. 38.9 % (n=125) patients were classified as Group 1);11.2% (n=36) as Group 2, 12.8% (n=41) as Group 3 and 34.8 % (n=115) as Group 4. In group 3, 38 (92.7 %) patients received respiratory viral panels (RVP) which were all negative;21(51.2%) had sputum cultures, only 1 was positive for staph aureus. When comparing Group 1 to Group 3, there were no statistically significant differences in inflammatory markers. There were no statistically significant differences amongst Groups 1 and 3 with respect to treatments Conclusion: Due to its high infectivity and asymptomatic transmission, until a highly sensitive and specific COVID-19 test is developed, HRCT is a valuable assessment tool for patients who are hospitalized with suspected COVID-19.
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Background: Coronavirus disease 2019 (COVID-19) is the cause of a global pandemic which has strained the resources of health systems around the world. Health systems, patients, and healthcare providers may benefit from knowledge regarding which factors predict length of stay (LOS), and therefore healthcare resource allocation, in patients presenting with COVID-19. Methods: 559 patients were retrospectively identified who were admitted to Temple University Hospital in Philadelphia, PA between February and May of 2020. All patients tested positive for COVID-19 by nasopharyngeal swab and received computed tomography screening for viral pneumonia. We collected data present at time of hospital admission and performed a retrospective analysis to determine factors associated with hospital LOS. Results: Mean hospital LOS for our cohort was 9.0 days. In this cohort, most patients received antibiotics. 100% of patients received glucocorticoids and 8.1% received remdesivir. 31.2% participated in clinical trials of monoclonal antibodies. 26.8% of patients required intensive care during their hospitalization, 17.4% required invasive or noninvasive mechanical ventilation, and 11.1% died. On multivariable linear regression analysis, increasing leukocyte count and a diagnosis of diabetes mellitus predicted decreased LOS. Increased respiratory support within the first 24 hours, patient age, creatinine, and total bilirubin were associated with increased LOS. Conclusion: Patient past medical history, admission laboratory values, and severity of hypoxemia at hospital admission may predict LOS in patients hospitalized for COVID-19. (Table Presented).
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Rationale: Coronavirus disease 2019 (COVID-19) has provoked an unprecedented global pandemic. Invasive mechanical ventilation (IMV) rates in COVID-19 have been reported to be from 2.3% to 33%. The wide range in reported intubation rates is attributed in part to diverging institutional practices for the care of patients presenting with hypoxemic respiratory failure. The role of high flow nasal therapy (HFNT) in the treatment of COVID-19 has been controversial and underreported. Objectives: To report a retrospective analysis comparing the outcomes of patients treated with HFNT and IMV for hypoxemic respiratory failure secondary to COVID-19. Methods: This was an analysis of consecutive patients admitted to Temple University Hospital between March 10, 2020, and May 17, 2020, for moderate to severe hypoxemic respiratory failure from COVID-19 pneumonia. Patients were divided into three groups: IMV group-not placed on HFNT prior to intubation. HFNT group-received only HFNT. HFNT to intubation group-received HFNT prior to intubation. Comparisons were made between demographics, baseline laboratory values, and outcomes. Results: 1396 patients admitted to Temple University Hospital between March 10, 2020, and May 17, 2020 with suspected COVID-19 infection were retrospectively screened for this study. 837 patients tested positive for COVID-19 by nasopharyngeal RT-PCR or deemed positive based on clinical features. There were no statistically significant differences in terms of demographics between all three groups. However, the intubation and HFNT to intubation groups had a higher incidence of malignancy compared to the HFNT only group. There was a higher incidence of smoking in the intubation group (59.2%) and HFNT to intubation group (53.7%) compared to HFNT only group (29.2%). Laboratory data were similar between all three groups besides admission BUN/creatinine. In terms of therapies, high-dose steroids were administered more frequently to patients in the HFNT (84.3%) and HFNT to intubation (90.2%) groups compared to the intubated group (56.5%). Overall, 49 (28.1%) were intubated, 84 (48.2%) were treated with HFNT only, and 41 (23.5%) progressed from HFNT to intubation. The mortality was 36.7% in the intubation group, 6% in the HFNT only group, and 43.9% in the HFNT to intubation group. Overall mortality was 25.7%. Conclusion: Our institutional decision to utilize HFNT as the primary treatment for moderate to severe hypoxemic respiratory failure led to a low intubation rate thus reducing overall morbidity and mortality. In the appropriate clinical context HFNT should be the considered the oxygen modality of choice in moderate to severe hypoxemic respiratory failure secondary to COVID-19 pneumonia.
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Introduction Use of high flow nasal therapy (HFNT) to treat COVID-19 pneumonia has been greatly debated around the world due to concern for increased healthcare worker transmission and delays in invasive mechanical Ventilation (IMV). Herein we analyze the utility of the ROX index to predict the need and timing for IMV in a retrospective analysis of patients with COVID-19 with moderate to severe hypoxemic respiratory failure treated with HFNT. Methods This was a retrospective analysis of 129 consecutive patients with COVID-19 admitted to Temple University Hospital in Philadelphia, Pennsylvania, from March 10, 2020, to May 17, 2020 with moderate to severe hypoxemic respiratory failure treated with High Flow nasal therapy (HFNT). HFNT patients were divided into two groups: HFNT only and HFNT progressed to IMV. The primary outcome was the ability of the ROX index to predict the need of IMV. Secondary outcomes were mortality, rates of intubation, length of stay (LOS) and rates of nosocomial infections in our cohort treated with HFNT were also reported. Results 837 patients with COVID-19 were screened, 129 met inclusion criteria. The mean age was 60.8(+13.6) years, BMI 32.6(+8), 58(45 %) were female, 72(55.8%) were African American, 40 (31%) Hispanic. 48 (37.2%) were smokers. Of the 129, 89 were HFNT only group whereas 40 in the HFNT progressed to IMV group. Mean time to intubation was 2.5 days(+ 3.3). The 89 HFNT only patients had a significant improvement in ROX from initiation of HFNT at all recorded time points. In contrast, the ROX in HFNT progressed to IMV patients remained unchanged or decreased over time. ROX index of less than 5 at HFNT initiation was predictive of progression to IMV (OR = 2.137, p = 0,052). Any decrease in ROX index after HFNT initiation was predictive of intubation (OR= 14.67, p <0.0001). In multivariate analysis, ΔROX (<=0 versus >0), peak D-dimer >4000 and admission GFR < 60 ml/min were very strongly predictive of need for IMV (ROC = 0.86, p=0.001). Mortality was 11.2% in HFNT only group versus 47.5% in the HFNT progressed to IMV group (p = 0.0001). Mortality and need for pulmonary vasodilators were higher in the HNFT progressed to IMV group. Conclusion ROX index is a valuable, noninvasive tool to evaluate patients with moderate to severe hypoxemic respiratory failure in COVID-19 treated with HFNT. ROX helps predicts need for IMV and thus limiting morbidity and mortality associated with IMV.
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Introduction COVID-19 can lead to a severe inflammatory response and cytokine storm, which is associated with activation of blood coagulation, platelets, and endothelium leading to a severe prothrombotic state. Recent studies have interpreted TEG parameters of increased maximum amplitude (MA) and alpha angle (AA) as indicating a hypercoagulable pattern in patients with COVID-19. The definition of hypercoagulability in literature has been variable while some have used increased MA, others used increased coagulation index (CI) as a surrogate for a hypercoagulable state. Here we report our center experience using TEG to evaluate coagulation in COVID-19 patients. Methods Retrospective analysis of 37 critically ill patients that were evaluated using TEG on a single occasion along with standard coagulation tests. We defined hypercoagulable pattern as CI > 3;hypocoagulable pattern was defined as CI <-3;and normal pattern if CI was between-3-3. Results TEG patterns were interpreted as hypercoagulable in 5 (13.5%), normal in 22 (59.5%) and hypocoagulable in 10 (27%) patients using the TEG coagulation index (CI). MA and AA were elevated in 13 (35.1%) and 10 (27%) patients, respectively, and both were elevated in 8 (21.6%). Discussion Our results show a normal TEG pattern in most of our critically ill COVID-19 patients based on CI (Figure 1);only 5 (13.5%) showed a hypercoagulable pattern. These findings differ from previous reports of TEG in COVID-19 patients, where a hypercoagulable TEG pattern was shown in 83-90% of patients, in these reports interpretation of hypercoagulability was based on AA or MA. We used the CI to define a hypercoagulable state, which has been used to define hypercoagulability in orthopedic surgery and during pregnancy. An elevated MA or AA was seen in only 15 (40%) of our patients. Plasma fibrinogen, an acute-phase reactant, is also elevated in COVID-19 patients. The mean fibrinogen level in our patients was 364 mg/dl, which is lower than those reported by Panigada and Mortus, where mean fibrinogen levels were 680 and 740 mg/dl, respectively. The high MA may reflect the high fibrinogen observed in COVID-19 patients and this may explain the differences in the number of patients considered as “hypercoagulable” in our cohort compared to others. Conclusion;Our study in COVID-19 patients advances a caution in the interpretation of TEG parameters and its use as an indicator of a hypercoagulable state in COVID-19 patients.
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Rationale: The novel coronavirus disease-19 (COVID-19) has presented major challenges for global health systems. Given limited availability of diagnostic testing and delays in test results during the first wave of the pandemic, our hospital used computed tomography (CT) to risk stratify patients with suspected COVID-19. The aim of this study was to describe the various patterns of disease on chest CT and relate them to chest x-ray (CXR) findings. Methods: This is a retrospective review of 559 symptomatic patients infected with COVID-19 (diagnosed by real-time reverse transcription polymerase chain reaction) admitted from March 2020 to May 2020 at Temple University Hospital (Philadelphia, PA) who received admission CXR and chest CT scans that were performed within 24 hours of admission. Scans were independently reviewed by a group of radiologists. CXRs was interpreted as “consistent with COVID-19” if there were lower lobe peripheral opacities. Chest CTs were evaluated for the presence of ground glass opacities, consolidations, interlobular septal thickening, centrilobular nodules, and crazy paving pattern. Chest CT was also assessed for background lung disease (emphysema, interstitial lung disease). Results: Of the 559 patients, median age was 58 years old, 55.5% were female, and 56.7% were African American. Median BMI was 31.61. Median duration of symptoms at time of chest imaging was 5 days. 153 (27.4%) of patient's admission CXR was not consistent with COVID-19. Of those, 124 (81%) had abnormalities on chest CT. Median number of lobes involved with disease on CT was 3.8 and 317 patients (56.7%) had all 5 lobes with disease. The most common abnormalities found were ground glass opacities (n=507, 90.7%), consolidations (n=224, 40%) and centrilobular nodules (n=127, 22.7%). Less common findings included pleural effusion (n=62, 11.8%), lymphadenopathy (n=55, 9.8%), pericardial effusion (n=24, 4.2%), and pneumothorax (n=3, 0.53%). Of note, 82 (14.7%) patients were found to have emphysema, and 2 (0.35%) were found to have interstitial lung disease. Conclusion: We present one of the largest reviews of CT scans in patients admitted for COVID-19. The majority of our population had significant burden of disease on CT at time of presentation. Ground glass opacities and consolidations were the predominant findings. Most patients did not have background emphysema or interstitial lung disease. The fact that many patients with normal CXR had abnormalities on chest CT highlights the utility of chest CT in evaluating patients with COVID-19.
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Introduction: The “obesity paradox” has been reported in critically ill patients with acute respiratory distress syndrome (ARDS). Obese patients with ARDS were shown to have more ventilator free days and lower mortality compared to non-obese patients. One proposed explanation was increased levels of pro-inflammatory cytokines creating a protective environment from acute inflammation. In COVID-19, BMI ≥ 30 increases risk of illness severity, need for critical care, respiratory failure requiring use of invasive mechanical ventilation (IMV), and mortality. It is unknown if the “obesity paradox” applies to patients with SARS-CoV2 who require IMV. We examined a cohort of patients with respiratory failure due to COVID-19 who required IMV and compared outcomes between obese and non-obese patients. Methods: Data was collected from patients treated in the COVID Intensive Care Unit (ICU) from March to June 2020. A total of 85 patients were identified. All patients were COVID nasopharyngeal swab positive. Results: There were 38 (44.7%) patients with BMI < 30, and 47 (55.3%) with BMI ≥ 30. The median BMI was 25.5 in the BMI < 30 group, and 37.5 in the BMI ≥ 30 group. In the BMI < 30 group, median age was 67 years, majority male (65.8%) and African American (50%). The BMI ≥ 30 group had a median age of 63.5, majority male (53.2%) and African American (63.8%). Median Sequential Organ Failure Assessment score on admission was higher in the BMI ≥ 30 group at 3 (1.5-4.5) vs. 2 (1.0-4.0). There was elevated creatinine on admission with higher percentage of diabetes, heart failure, and renal disease in the BMI ≥ 30 group. Inflammatory markers, such as CRP and IL-6 were lower in the higher BMI group at presentation. There was higher in-hospital mortality in the BMI ≥ 30 group at 57.5%, with longer ICU length of stay (12.35 vs. 7.6 days), longer days on ventilator (10.2 vs. 4 days), and lower PaO2/FiO2 ratio after intubation (146 vs 348). The higher BMI group had higher rates of prone ventilation, paralytic use, and extracorporeal membrane oxygenation support. Discussion: From our data, obesity did not appear to have better outcomes in ARDS due to COVID-19 infection. Higher BMI was associated with higher disease severity, severe respiratory failure, longer ventilator days, longer ICU length of stay, and higher mortality. Interestingly, inflammatory markers were initially lower in obese patients, suggesting a possible adaptive physiologic response to inflammation, but without effect on overall outcomes.
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Rationale: The novel coronavirus disease-19 (COVID-19) has overwhelmed global healthcare systems. It would be beneficial to identify clinical signs that predict adverse outcomes to anticipate clinical deterioration and optimize management. COVID-19 has presented with a variety of patterns on computed tomography (CT) and these findings may assist in disease stratification. This study aims to identify potential CT characteristics that may portend adverse outcomes. Methods: This is a retrospective review of 559 symptomatic patients infected with COVID-19 admitted from March 2020 to May 2020 at Temple University Hospital (Philadelphia, PA) who received thorax CT scans on admission. These scans were independently reviewed by a chest radiologist and evaluated for the presence of ground glass opacities, consolidations, interlobular septal thickening, enlarged pulmonary artery (PA) diameter, centrilobular nodules, and crazy paving pattern. Common CT findings were then associated with a combined adverse inpatient outcome (requiring high-flow oxygen, mechanical ventilation, and/or death) through univariate and multivariate logistic regression. Results: Of the 559 patients, 182 (32.6%) required high-flow oxygen, mechanical ventilation, and/or died. The cohort with adverse outcomes were older (mean age 65.0 years vs 56.7 years, p<0.0001), but had statistically similar gender, BMI and duration of symptoms compared to the cohort without adverse outcomes. The adverse outcome cohort had more COPD (18.7% vs 8.2%) but had statistically similar proportions of hypertension, diabetes, asthma, coronary artery disease, and congestive heart failure. On multivariate logistic regression, a PA diameter greater than 30mm (OR 1.056 [95% CI 1.015-1.097], p=0.0064), segmental consolidations (OR 2.359 [95% CI 1.446-3.848], p=0.0009), and non-segmental consolidations (OR 2.441, [95% CI 1.440-4.140], p=0.0009) were found to be significant predictors of adverse inpatient outcomes of either requiring high-flow nasal cannula, mechanical ventilation, or death. Conclusion: In symptomatic COVID-19 patients, enlarged PA diameter and consolidations on chest CT were associated with worse outcomes. These findings are likely representative of advanced pulmonary involvement and may be predictors of patients who require more aggressive upfront therapy. Multicenter analysis would be beneficial to confirm these findings.
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Introduction: COVID19 pandemic has led to a significant increase in telemedicine utilization due to risk of healthcare acquired infection. Lung transplant recipients are high risk for infection and have extraordinary health care needs. The HGE remote symptom monitoring has been shown to be beneficial in COPD patients to decrease exacerbations and time to treatment1-8. During peak pandemic restrictions we transitioned to a telemedicine only system and patients were encouraged to enroll in the “HGE COVIDCare” for reporting daily symptoms suspicious for COVID19. With a combination of remote symptom monitoring and telemedicine, we aimed to provide early intervention and necessary care, while decreasing the risk of infection. This study assesses the feasibility and short-term outcomes of using this combination in lung transplant recipients. Methods: Single center, retrospective study of lung transplant recipients of who were enrolled in the HGE COVIDCare symptoms tracker program in March 2020. Pre-pandemic data was collected prior to March 15 and post pandemic restriction data was collected after July 15th, 2020. Patients were asked to report daily symptoms via HGE-COVID website, which was triaged by transplant nurses. We recorded self-reported symptoms from the symptom tracker, details of tele medicine visits and hospitalizations, and changes in pulmonary function tests. Results: The first 50 lung transplant recipients enrolled were included in this short-term analysis with most patients within one-year post transplant (66%). During the four-month pandemic restriction, 6 patients (12%) had “symptom events” reported via the tracker. None of the symptoms were due to COVID19. Etiologies included pneumonia, bronchial stenosis, diarrhea due to C diff and medication or symptoms self-resolving prior to team outreach. 8 patients (16%) were admitted to the hospital for non COVID indications and 2 patients died during this period due to sepsis. Post pandemic limitation PFTs were available for 35 (70%) patients. None of the patients had a decline in PFTs, compared to the “pre pandemic” values. The incidence of hospitalization or acute rejection was similar in the months preceding the pandemic compared to the 4-month pandemic restriction period. Conclusions: In lung transplant recipients, a combination of telemedicine and remote symptom monitoring is feasible and safe. It did not lead to increased rate of hospitalization, acute rejection or worsening lung function in this short term follow up. This model could be potentially followed to help decrease risk of healthcare acquired infections, patient visits and health care costs without impacting outcomes. .
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Background: Remdesivir (RDV) has been shown to shorten recovery time and was well tolerated in patients with severe COVID-19. Here we report safety of RDV in patients with moderate COVID-19. Methods: We conducted an open-label, phase 3 trial (NCT04252664) in hospitalized patients with confirmed SARS-CoV-2 infection, evidence of pulmonary infiltrates, and oxygen saturation >94% on room air. Patients were randomly assigned to receive RDV (5 or 10 days) or standard of care (SOC). RDV was dosed intravenously at 200 mg on day 1, 100 mg daily thereafter. Adverse events (AEs) and laboratory abnormalities were evaluated through the day 11 data cut;safety data through day 28 will be presented at the meeting. Results: 584 patients were randomized and treated (5d RDV: n=191;10d RDV, n=193;SOC: n=200). Baseline characteristics were balanced among groups;median (range) age was 57y (12-95y), 39% were female and 19% Black, 39% had arterial hypertension, 15% hyperlipidemia, 11% asthma. Briefly, across both the 5d and 10d arms, RDV was well tolerated with a similar rate of Grade 3 or 4 AEs and fewer SAEs compared to SOC (Table). AEs more common with RDV vs SOC included nausea, headache, and hypokalemia. Overall, across the 3 arms, incidence of AEs leading to discontinuation and death were low and no clinically relevant changes in laboratory parameters were observed. In addition, median changes in renal and liver function tests from baseline were not statistically significant between the RDV 5d and RDV 10d groups compared to the SOC only group at d14 (Table 1). Conclusion: RDV given for 5d or 10d was well tolerated in patients with moderate COVID-19. No clinically significant safety signals were observed with RDV vs SOC. (Figure Presented).
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Background: Remdesivir (RDV), a RNA polymerase inhibitor with potent in vitro activity against SARS-CoV-2, is the only treatment with demonstrated efficacy in shortening the duration of COVID-19. Here we report regional differences in clinical outcomes of severe COVID-19 patients treated with RDV, as part of an open-label, randomized phase-3 trial establishing RDV treatment duration. Methods: Hospitalized patients with oxygen saturation ≤94%, a positive SARS-CoV-2 PCR in the past 4 days and radiographic evidence of pneumonia were randomized 1:1 to receive 5d or 10d of intravenous RDV. We compared d14 clinical outcomes of patients from different geographical areas, as measured by mortality rates, change in clinical status from baseline (BL) on a 7-point ordinal scale and change in O2 requirements from BL. Based on previous analyses in compassionate use data showing region as an important predictor of outcome, Italy was examined separately from other regions. Results: 397 patients were treated with RDV, of which 229 (58%) were in the US, 77 (19%) Italy, 61 (15% in Spain), 12 (3%) Republic of Korea, 9 (2%) Singapore, 4 (1%) Germany, 4 (1%) Hong Kong and 1 (< 1%) Taiwan. BL clinical status was worse in Italy compared to other regions (72% vs 17% requiring high-flow oxygen delivery or higher), and Italian patients were more likely to be male than patients from other regions (69% vs 63%). Overall results showed 5d RDV was as effective as 10d. Mortality at d14 was higher in Italy (18%) compared to all other countries except Italy (7%). Similarly, clinical improvement at d14, measured as ≥2-point increase in the ordinal scale, was lower in Italian patients (39%) compared to all other countries combined (64%). (Fig.1). Conclusion: Overall, our results demonstrate significant geographical differences in the clinical course of severe COVID-19 patients treated with RDV. We observed worse outcomes, such as increased mortality and lower rate of clinical improvement, in patients from Italy compared to other regions. (Table Presented).