Verification of the Performance of the Panbio COVID-19 Ag Rapid Test Device for Implementation in the Clinical Laboratory

Objectives: The Panbio COVID-19 Ag Rapid Test Device (Panbio COVID-19 Ag, Abbott Rapid Diagnostics) is a lateral flow immunochromatographic assay targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein in nasopharyngeal specimens for the diagnosis of coronavirus disease 2019 (COVID-19). This study aimed to verify the performance of the Panbio COVID-19 Ag for implementation in clinical laboratories. Method(s): Sixty nasopharyngeal swab specimens (30 positive and 30 negative) dipped in transport medium, and COVID-19 was confirmed using real-time RT-PCR using Allplex SARS-CoV-2 assay (Seegene), were tested using the Panbio COVID-19 Ag. Reproducibility was evaluated using positive and negative control materials. Sensitivity and specificity were calculated based on the results of realtime RT-PCR as the standard test method. Result(s): Reproducibility was confirmed by the consistent results of repeated tests of the quality control materials. The overall sensitivity and specificity of Panbio COVID-19 Ag were 50.0% and 100.0%, respectively. Panbio COVID-19 Ag demonstrated high sensitivity (88.2%) in analyzing the detection limit cycle threshold (Ct) value of 26.67 provided by the manufacturer as a positive criterion, and the sensitivity was 100.0% for the positive criterion of Ct values <25, although it was less sensitive for Ct > 25. Conclusion(s): Considering the high sensitivity for positive samples with Ct values <25 and the rapid turnaround of results, Panbio COVID-19 Ag can be used in clinical laboratories to diagnose COVID-19 in limited settings. Copyright © 2023 Ewha Womans University College of Medicine and Ewha Medical Research Institute.

Investigating the efficacy of baricitinib in new onset type 1 diabetes mellitus (BANDIT)-study protocol for a phase 2, randomized, placebo controlled trial.

BACKGROUND: Type 1 diabetes (T1D) places an extraordinary burden on individuals and their families, as well as on the healthcare system. Despite recent advances in glucose sensors and insulin pump technology, only a minority of patients meet their glucose targets and face the risk of both acute and long-term complications, some of which are life-threatening. The JAK-STAT pathway is critical for the immune-mediated pancreatic beta cell destruction in T1D. Our pre-clinical data show that inhibitors of JAK1/JAK2 prevent diabetes and reverse newly diagnosed diabetes in the T1D non-obese diabetic mouse model. The goal of this study is to determine if the JAK1/JAK2 inhibitor baricitinib impairs type 1 diabetes autoimmunity and preserves beta cell function. METHODS: This will be as a multicentre, two-arm, double-blind, placebo-controlled randomized trial in individuals aged 10-30 years with recent-onset T1D. Eighty-three participants will be randomized in a 2:1 ratio within 100 days of diagnosis to receive either baricitinib 4mg/day or placebo for 48 weeks and then monitored for a further 48 weeks after stopping study drug. The primary outcome is the plasma C-peptide 2h area under the curve following ingestion of a mixed meal. Secondary outcomes include HbA1c, insulin dose, continuous glucose profile and adverse events. Mechanistic assessments will characterize general and diabetes-specific immune responses. DISCUSSION: This study will determine if baricitinib slows the progressive, immune-mediated loss of beta cell function that occurs after clinical presentation of T1D. Preservation of beta cell function would be expected to improve glucose control and prevent diabetes complications, and justify additional trials of baricitinib combined with other therapies and of its use in at-risk populations to prevent T1D. TRIAL REGISTRATION: ANZCTR ACTRN12620000239965 . Registered on 26 February 2020. CLINICALTRIALS: gov NCT04774224. Registered on 01 March 2021.

ONE-YEAR FOLLOW-UP CT FINDINGS IN PATIENTS WITH COVID-19: A SYSTEMATIC REVIEW AND META-ANALYSIS

SESSION TITLE: What Lessons Will We Take From the Pandemic? SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Coronavirus disease 2019 (COVID-19) often causes radiological and functional pulmonary sequelae. However, evidence on 1-year follow-up of pulmonary sequelae is limited. This study aimed to elucidate (1) the proportion of residual computed tomography (CT) abnormalities 1 year after COVID-19 recovery;(2) characteristics of the remaining CT findings at 1-year follow-up;and (3) the relationship between the disease severity and time course of radiological sequelae. METHODS: We searched PubMed and EMBASE databases on February 25, 2022, and included studies with CT findings at the 1-year follow-up. We collected CT and pulmonary function tests (PFT) data at 1-year follow-up. The residual findings at mid-term (4-7 months) follow-up were also collected when available. The extracted data on CT and PFT findings were analyzed using a one-group meta-analysis. We further analyzed the data in relation to the COVID-19 severity, improvement rate, and lung function. RESULTS: Fifteen eligible studies (N = 3,134) were included. One year after COVID-19, 1,495 patients underwent CT, and 46.0% (95% confidence interval [CI] 32.7-59.4, I2 = 96.9%) presented with residual CT abnormalities. Ground-glass opacity (GGO) and fibrotic-like changes were frequently observed in 27.3% (95% CI 20.1-34.4, I2 =86.7%) and 26.1% (95% CI 14.2-38.0, I2 =94.6%) of the patients, respectively. While the proportion of GGO decreased from the mid-term to long-term follow-up (34.0% [23.4-44.5] to 27.3% [20.1-34.4]), fibrotic-like changes (14.9% [5.1-24.8] to 26.1% [14.2-38.0]), bronchiectasis (12.5% [4.1-20.9] to 13.3% [7.7-18.9]), and interlobular septal thickening (13.2% [2.9-23.5] to 12.8% [7.1-18.5]) did not improve. Furthermore, the frequency of CT abnormalities at 1-year follow-up was higher in the severe/critical cases than in the mild/moderate cases (54.8% [40.6-69.0] vs. 32.2% [1.6-62.7]). In particular, fibrotic-like changes were frequently observed among severe/critical patients 1 year after COVID-19 (30.4% [11.3-49.5]). Regarding pulmonary function tests, 29.9% (22.5-37.3) and 8.0% (5.4-10.6) of the patients presented reduced (< 80% of predicted value) diffusing capacity of the lung for carbon monoxide (DLCO) and total lung capacity (TLC) at 1-year follow-up. These residual PFT abnormalities were more prevalent in severe/critical cases (DLCO: 30.1% [21.1-39.0], TLC: 10.5% [5.0-16.0]) than mild/moderate cases (DLCO: 21.5% [9.6-33.3], TLC: 5.6% [2.6-8.6]). CONCLUSIONS: Our meta-analysis indicated that residual CT abnormalities were common in COVID-19 patients 1 year after recovery, especially fibrotic changes in severe/critical cases. CLINICAL IMPLICATIONS: Physicians should be aware of the high frequency of lung sequelae even 1 year after COVID-19. As these sequelae may last for a long time, vigilant observations and more extended follow-up periods are warranted. DISCLOSURES: no disclosure on file for Koichi Fukunaga;No relevant relationships by Masao Iwagami No relevant relationships by Hiroki Kabata No relevant relationships by Toshiki Kuno No relevant relationships by Matsuo So No relevant relationships by Hisato Takagi No relevant relationships by Atsuyuki Watanabe

Clinical Features and Mortality of COVID-19-Associated Mucormycosis: A Systematic Review and Meta-Analysis

Rationale. Invasive fungal infection secondary to the coronavirus disease 2019 (COVID-19) has been increasing. Whereas COVID-19-associated pulmonary aspergillosis has been shown to be associated with high mortality, less is known about COVID- 19-associated mucormycosis (CAM). The overall mortality of non-COVID-19 mucormycosis ranges from 20% to 100%, depending on the infection site. Delayed diagnosis, neurological symptoms, and pre-existing malignancies are associated with worse outcomes. Herein, our study aimed to elucidate the characteristics, risk factors, and outcomes of CAM. Methods. We searched all observational studies reporting CAM through PubMed and EMBASE on September 13th, 2021. Case reports, case series, and observational studies without clearly documented diagnostic criteria for COVID-19 or mucormycosis were excluded. We collected data on the comorbidities, initial symptoms, site of infection, treatment for COVID-19, frequency of orbital exenteration, and mortality. One-group meta-analyses were performed for the potential risk factors, orbital exenteration, and mortality. Results. Our systematic review identified 32 eligible observational studies. The largest number of studies were conducted in India, followed by Egypt, Iran, and Turkey. A total of 4,463 patients were included in the analysis. The most common initial presentation was ocular symptoms: 78%, followed by facial: 48%, nasal: 21%, constitutional: 12%, oral: 4.4%, neurological: 1.1%, and others: 0.4%. Diabetes mellitus (DM) and glucocorticoid therapy were present in 81% (95% CI, 76-86;I2=96%) and 79% (95% CI, 75-84;I2=91%), respectively. Among those with DM, the percentage of newly-diagnosed DM was 30% (216/711). Diabetic ketoacidosis, malignancy, and immunosuppression were found in 4.9% (165/3353), 0.7% (25/3471), and 0.6% (18/2921), respectively. Regarding the outcomes, orbital exenteration was performed in 17% (95% CI, 13-21;I2=83%) of the patients. Pooled estimate of mortality of CAM was 29% (95% CI, 22-36;I2=94%). Conclusion. The most prevalent type of CAM was rhino-orbital-cerebral mucormycosis. In addition to DM, severe hyperglycemia and immune dysregulation provoked by excessive corticosteroid therapy may have played a critical role in the recent rise of mucormycosis cases among COVID-19 patients. This systematic review and meta-analysis revealed a high frequency of orbital exenteration and mortality. The development of CAM can be associated with poorer prognoses in COVID-19 patients. Keeping the possible risk factors in mind and paying attention to the usual clinical presentation will be crucial to suspect CAM as early as possible.

Prophylactic versus therapeutic anticoagulation for survival of patients with covid-19 on steroid and remdesivir

Introduction: Previous observational and randomized studies suggested potential benefit of therapeutic anticoagulation during hospitalization, but this treatment remains controversial Objective: We aimed to investigate the association of prophylactic and therapeutic anticoagulation with mortality for patients with COVID-19 who were treated with steroids and Remdesivir, which is the current standard treatments. Methods: This retrospective study was conducted by review of the electronic medical records for 9,565 patients with laboratory confirmed COVID-19 hospitalized in the Mount Sinai Health system between March 1 2020 and March 30 2021. The primary outcome of interest was the in-hospital mortality. Acute kidney injury was defined as any increase of creatinine by more than 0.3mg/dL or to more than 1.5 times baseline. A propensity score analysis (matching and weighting by inverse probability treatment weights) and multiple imputation was performed. Results: Of the 1,443 patients, 420 (29.1%) had therapeutic anticoagulation therapy. The 1,023 (70.9%) patients with prophylactic anticoagulation were older and had more comorbidities. After matching by propensity score (N=334 in each group), in-hospital mortality was not significantly different between patients with therapeutic anticoagulation and those with prophylactic anticoagulation (26.9% vs. 22.8%, P=0.24). Furthermore, IPTW and multiple imputation for missing data did not change the result (therapeutic versus prophylactic;odds ratio [95% confidential interval]: 1.14 [0.83-1.59], P=0.40];1.20 [0.84-1.73], P=0.31, respectively). Interestingly, patients with therapeutic anticoagulation had higher rate of acute kidney injury as compared to patients with prophylactic anticoagulation (26.6% vs. 16.8%, P=0.003). Conclusions: In conclusion, prophylactic versus therapeutic anticoagulation showed similar inhospital mortality of COVID-19 patients treated with steroids and remdesivir, but therapeutic anticoagulation increased the risk of acute kidney injury compared to prophylactic anticoagulation.

The association of statins use with survival of covid-19 patients

Introduction: Statins are frequently prescribed for patients with hypertension, dyslipidemia and diabetes mellitus. These comorbidities are highly prevalent in COVID-19 patients. Statin's beneficial effect on mortalities in COVID-19 infection has been reported in several studies, but still inconclusive. Hypothesis: The inconclusive study results in association of satin use and COVID-19 can be resulted from variable timing of statins used among the studies. Our aim was to investigate whether consistent use of statins before and during hospitalization was effective to decrease the mortality due to COVID-19. Methods: We conducted a retrospective study among 6,095 patients with COVID-19 hospitalized in New York City between March 1st 2020 and May 7th 2021. Patients were stratified into two groups: statins use prior or during hospitalization (N=2,423) versus no statins (N=3,672). We evaluated inhospital mortality as a primary outcome using propensity score matching and inverse probability treatment weighted (IPTW) analysis. In addition, we compared continuous use of statins (N=1,108) versus no statins. Results: Statins use prior or during hospitalization group were older (70.8±12.7 versus 59.2±18.2, P<0.001) and had more comorbidities compared to no statins group. After matching by propensity score (1,790 pairs), there were no significant differences in in-hospital mortality between patients with statins versus those without (28.9% versus 31.0%, P=0.19, odds ratio (OR) [95% confidence interval (CI)]: 0.91 [0.79-1.05]). This result was confirmed using IPTW analysis (OR [95% CI]: 0.96 [0.81-1.12], P=0.53). As the additional analysis comparing continuous use of statins versus no statins group, in-hospital mortality was significantly lower in continuous use of statins compared to no statins group (26.3% versus 34.5%, P<0.001, OR [95% CI]: 0.68 [0.55-0.82]) after matching by propensity score (944 pairs). IPTW analysis showed the similar result (OR [95% CI]: 0.77 [0.64-0.94], P=0.009). Conclusions: Use of statins prior or during hospitalization was not associated with a decreased risk of in-hospital mortality, however, continuous use of statins might have potential benefit of a decreased risk of in-hospital mortality due to COVID-19.

The association of obesity level and inhospital survival of patients with covid-19 who received corticosteroids

Introduction: Obesity is one of the most frequent comorbidities among COVID-19 patients. Although previous studies have shown higher body mass index (BMI) is associated with higher mortality, steroids as the current standard treatment for moderate to severe COVID-19 infection were not applied in most patients in these studies. Hypothesis: We hypothesized that patients with higher BMI still have higher mortality even on steroids. Methods: We conducted a retrospective study of 4,587 hospitalized patients with COVID-19 who received corticosteroids between March 1 , 2020, and March 30 , 2021. We divided patients into 6 groups by BMI[MOU1] (less 18.5, 18.5-25, 25-30, 30-35, 35-40, 40 or greater, kg/m2 ) and investigated in-hospital mortality as the primary outcome, in-hospital mortality among severe COVID-19 patients which was defined as requiring intensive care unit or endotracheal intubation as a subgroup analysis, and acute kidney injury (AKI) incidence rate as the secondary outcome. Results: Patients with higher BMI were younger and more likely to have a history of asthma, obstructive sleep apnea, diabetes, and less likely to have malignancies. The smooth spline curve showed J curve association of BMI with risk adjusted in-hospital mortality with flexion point at BMI between 25 and 30 kg/m2 (Figure 1). Compared to overweight (25≤BMI<30 kg/m2 ) patients, class III obesity (BMI>40 kg/m2 ) was associated with higher risk adjusted in-hospital mortality overall (Table 1) as well as among patients with severe COVID-19 (OR [95% CI]: 3.21 [1.86-5.66], P<0.001). Class III obesity was also associated with a higher risk adjusted incidence of AKI (OR [95% CI]: 1.52 [1.06-2.18], P=0.024) compared to overweight patients. Conclusions: Class III obesity was associated with higher in-hospital mortality and AKI incidence rate in COVID-19 patients with steroids treatment.

The characteristics and outcomes of critically ill patients with COVID-19 who received systemic thrombolysis forpresumed pulmonary embolism: An observational study

Background : Coronavirus disease 2019 (COVID-19) is associated with abnormal hemostasis, autopsy evidence of systemic microthrombosis, and a high prevalence of venous thromboembolic disease (VTE). Tissue plasminogen activator (tPA) has been used in COVID-19 patients with severe hypoxia with high clinical suspicion of pulmonary embolism (PE). Aims : We aimed to describe the clinical outcomes of critically ill COVID-19 patients who received tPA. Methods : A retrospective cohort study was conducted on 6,095 hospitalized COVID-19 patients in the Mount Sinai Health System at 5 hospitals in New York. 57 patients with COVID-19, who were admitted from 3/10 to 4/27, 2020 and received tPA for presumed PE were included in the analysis. Baseline demographic and clinical characteristics, indication for tPA, and overall mortality were reported. Results : Among the 57 patients who received tPA, the mean age was 60.8 ± 10.8 years, and 71.9% (41/57) were male. PE was suspected among 75.4% (43/57) of patients with supporting findings who had rapidly worsening hypoxia or hypotension. Right ventricular (RV) strain was present in 15.8% (9/57), deep venous thrombosis (DVT) in 7.0% (4/57), increased dead space ventilation (V d ) in 31.6% (18/57) of patients. RV strain and RV thrombus were present in 3.5% (2/57), RV strain and DVT in 5.3% (3/57), RV strain and increased V d in 8.8% (5/57), and DVT and increased V d in 3.5% (2/57) of patients. No chest CT angiography was performed for any patients due to clinical instability from critical illness. Following tPA infusion, 49.1% (28/57) of patients demonstrated improvement in either of PaO 2 /FiO 2 ratio, blood pressure or partial arterial carbon dioxide. Bleeding complication was seen in 1 patient. Six patients (10.5%) survived to hospital discharge. Overall mortality was 89.5% (51/57). Conclusions : The overall mortality of critically ill COVID-19 patients who received tPA for presumed PE was 89.5 %. The utility of tPA for this indicaition warrants further studies.

THE ASSOCIATION OF INHALED CORTICOSTEROID BEFORE ADMISSION AND SURVIVAL OF PATIENTS WITH COVID-19

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: Inhaled corticosteroids (ICS) are widely used in patients with asthma and chronic obstructive pulmonary disease (COPD). The pooled epidemiological studies have shown that patients with asthma or COPD are at lower hospitalization risk, which could be related to the protective effect of ICS. However, some studies showed no protective effects of ICS on the prognosis of COVID-19. The very recent study suggested that the use of ICS, within 2 weeks of admission, improved survival only for patients aged 50 years and older with asthma, but not for those with chronic pulmonary disease. Herein, we are highly concerned about whether the use of ICS affects the prognosis of COVID-19. METHODS: We retrospectively analyzed over 6,095 hospitalized patients with laboratory confirmed COVID-19 at the Mount Sinai Health System in New York between March 1stand May 2nd, 2020. Patients were stratified into those with or without ICS before admission and were assessed for in-hospital mortality as a primary outcome. Patients were matched by propensity score using 1:1 matching scheme without replacement. We performed this analysis with and without multiple imputation for missing data and then performed an inverse probability weighted analysis. All statistical calculations and analyses were performed in R, with p-values <0.05 considered statistically significant. RESULTS: Of the 6,095 patients admitted due to COVID-19 infection, 333 patients (5.5%) used ICS before admission. The patients with ICS were older and had more comorbidities compared to the patients without ICS. However, in-hospital mortality, intensive care unit admission, and endotracheal intubation rate were not significantly different, although the d-dimer levels were significantly lower in patients with ICS compared to those without (1.48 [0.88, 2.76] versus 1.66 [0.88, 3.51] mg/mL, P=0.043). After matching by propensity score (N=204 in each group), in-hospital mortality and intensive care unit admission rate were not different, while endotracheal intubation rate was significantly decreased in the patients with ICS. Multiple imputation for missing data and inverse probability weighted analysis revealed no significant difference in in-hospital mortality between the groups (odds ratio [95% confidential interval]: 0.90 [0.61-1.34], P=0.63;odds ratio [95% confidential interval]: 0.83 [0.54-1.29], P=0.42). To identify the population ICS improves the prognosis of COVID-19, we performed a subgroup analysis among patients with asthma and COPD (N=378). There was no significant difference in in-hospital mortality between patients with ICS and those without even after propensity score matched analysis or inverse probability weighted analysis (odds ratio [95% confidential interval]: 0.86 [0.47-1.60], P=0.64) (Table 1). CONCLUSIONS: In our study, antecedent ICS use showed numerically better outcomes in the propensity score matching analysis and the subgroup analysis of patients with asthma and COPD even though the patients with antecedent ICS use had more comorbidities. Particularly, our propensity score matching analysis revealed that patients with antecedent ICS use showed decreased endotracheal intubation rate. CLINICAL IMPLICATIONS: The potential benefit of antecedent ICS use on COVID-19 patients needs to be examined with larger sample size. DISCLOSURES: No relevant relationships by Natalia Egorova, source=Web Response No relevant relationships by Hiroki Kabata, source=Web Response no disclosure on file for Toshiki Kuno;No relevant relationships by Matsuo So, source=Web Response No relevant relationships by Mai Takahashi, source=Web Response

Radiological and Functional Lung Sequelae of COVID-19: Systematic Review and Meta-Analysis

Rationale: The coronavirus diseas e 2019 (COVID-19) causes a wide spectrum of lung manifestations ranging from mild asymptomatic disease to severe respiratory failure. Recently, it has been suggested that respiratory damage remains for a long time after recovery from COVID-19. We aimed to clarify the characteristics of radiological and functional lung sequelae of COVID-19 patients described in follow-up period. Method: sPubMed and EMBASE were searched on October 20th, 2020 to investigate characteristics of lung sequelae in COVID-19 patients through retrospective studies according to PRISMA guidelines. Radiological and pulmonary function test (PFT) data were collected and analyzed using one-group meta-analysis in a random-effects model. Results: Our search identified 9 eligible retrospective studies with follow-up period up to 3 months. A total of 581 discharged patients were evaluated by chest CT scans or PFT. The frequency of residual CT abnormalities after hospital discharge was 61.5% ([95% confidential interval (CI)]: [41.3-81.7], I2=96.0%, 243/421 patients). Pulmonary fibrosis and ground glass opacity was found in 42.7% ([95% CI]: [10.4-74.9], I2=96.31%, 56/166 patients) and 42.4% ([95% CI]: [33.3-51.5], I2=43.0%, 107/250) of patients, respectively. The frequency of abnormal pulmonary function test was 39.2% ([95% CI]: [19.8-58.6], I2=79.4%, 48/123 patients) and impaired diffusion capacity was most frequently observed in 32.8% ([95% CI]: [18.2-47.4], I2=86.2%, 93/272 patients) of patients. Restrictive pattern and obstructive pattern were observed in 10.5% ([95% CI]: [6.9-14.0], I2=0%, 31/290 patients) and 4.8% ([95% CI]: [0.9-8.6], I2=45.8%, 14/240 patients), respectively. Conclusion: This systematic review analyzed the frequency of chest CT and PFT abnormalities after hospital discharge. 61.5% and 39.2% of patients had abnormal chest CT and PFT results within a period of 3 months after hospital discharge. The most frequent PFT abnormality was impaired diffusion capacity which is potentially suggestive of residual impact of microthromboembolism in lung vasculature due to hypercoagulability. Further studies with longer follow-up term are warranted to elucidate long term consequences of COVID-19 disease.

Impacts of the COVID-19 pandemic on financial market connectedness

In this paper, we study the impacts of the COVID-19 pandemic on the connectedness of the Hong Kong financial market. We construct dynamic financial networks based on correlations and partial correlations of stock returns to assess the impacts of COVID-19 and to compare the impacts in the previous financial crises in the past 15 years. Compared to other crises where the network density and clustering can be explained by co-movement with market indices as in normal periods, both network density and clustering are higher in the partial correlation networks during the COVID-19 outbreak. © 2020 Elsevier Inc.