bluuebunny/crossref_metadata_2025_split huggingface dataset:
447. An Ordinal Scale Assessing SARS-CoV-2 Infected Patient Outcomes Using Electronic Health Records
Authors: Khodaverdi Maryam , Price Bradley S , Santangelo Susan L , Anzalone Alfred (Jerrod) , Kimble Wesley , Porterfield J Zachary , Vest Michael T , Hodder Sally L , Hendricks Brian , Rosen Clifford james , Bunnell H TImothy , Moradi Hamidreza 
Published: December 2021

Abstract

Background
A major challenge to identifying effective treatments for COVID-19 has been the conflicting results offered by small, often underpowered clinical trials. The World Health Organization (WHO) Ordinal Scale (OS) has been used to measure clinical improvement among clinical trial participants and has the benefit of measuring effect across the spectrum of clinical illness. We modified the WHO OS to enable assessment of COVID-19 patient outcomes using electronic health record (EHR) data.

Methods
Employing the National COVID Cohort Collaborative (N3C) database of EHR data from 50 sites in the United States, we assessed patient outcomes, April 1,2020 to March 31, 2021, among those with a SARS-CoV-2 diagnosis, using the following modification of the WHO OS: 1=Outpatient, 3=Hospitalized, 5=Required Oxygen (any), 7=Mechanical Ventilation, 9=Organ Support (pressors; ECMO), 11=Death. OS is defined over 4 weeks beginning at first diagnosis and recalculated each week using the patient’s maximum OS value in the corresponding 7-day period. Modified OS distributions were compared across time using a Pearson Chi-Squared test.

Results
The study sample included 1,446,831 patients, 54.7% women, 14.7% Black, 14.6% Hispanic/Latinx. Pearson Chi-Sq P&lt; 0.0001 was obtained comparing the distribution of 2nd Quarter 2020 OS with the distribution of later time points for Week 4.
Table 1. OS at week 1 and 4 by quarter

The study sample included 1,446,831 patients, 54.7% women, 14.7% Black, 14.6% Hispanic/Latinx. Pearson Chi-Sq P&lt; 0.0001 was obtained comparing the distribution of 2nd Quarter 2020 OS with the distribution of later time points for Week 4.

Conclusion
All Week 4 OS distributions significantly improved from the initial period (April-June 2020) compared with subsequent months, suggesting improved management. Further work is needed to determine which elements of care are driving the improved outcomes. Time series analyses must be included when assessing impact of therapeutic modalities across the COVID pandemic time frame.

Disclosures
Sally L. Hodder, M.D., Gilead (Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Viiv Healthcare (Grant/Research Support, Advisor or Review Panel member)
450. Type I Interferon Autoantibodies Are Detected in Those with Critical COVID-19, Including a Young Female Patient
Authors: Yee Debra , Tso Marana , Shaw Elana , Rosen Lindsey B , Samuels Emily , Bastard Paul , Casanova Jean-Laurent , Holland Steven M , Su Helen C , Richard Stephanie A , Mende Katrin , Lalani Tahaniyat , Lindholm David A , Lindholm David A , Simons Mark P , Tribble David , Malloy Allison , Laing Eric , Agan Brian , Pollett Simon , Burgess Timothy , Snow Andrew L 
Published: December 2021

Abstract

Background
Approximately 10-20% of patients with critical COVID-19 harbor neutralizing autoantibodies (auto-Abs) that target type I interferons (IFN), a family of cytokines that induce critical innate immune defense mechanisms upon viral infection. Studies to date indicate that these auto-Abs are mostly detected in men over age 65.

Methods
We screened for type I IFN serum auto-Abs in sera collected &lt; 21 days post-symptom onset in a subset of 103 COVID-19 inpatients and 24 outpatients drawn from a large prospective cohort study of SARS-CoV-2 infected patients enrolled across U.S. Military Treatment Facilities. The mean age of this n = 127 subset of study participants was 55.2 years (SD = 15.2 years, range 7.7 – 86.2 years), and 86/127 (67.7%) were male.

Results
Among those hospitalized 49/103 (47.6%) had severe COVID-19 (required at least high flow oxygen), and nine subjects died. We detected neutralizing auto-Abs against IFN-α, IFN-ω, or both, in four inpatients (3.9%, 8.2% of severe cases), with no auto-Abs detected in outpatients. Three of these patients were white males over the age of 62, all with multiple comorbidities; two of whom died and the third requiring high flow oxygen therapy. The fourth patient was a 36-year-old Hispanic female with a history of obesity who required mechanical ventilation during her admission for COVID-19.

Conclusion
These findings support the association between type I IFN auto-antibody production and life-threatening COVID-19. With further validation, reliable high-throughput screening for type I IFN auto-Abs may inform diagnosis, pathogenesis and treatment strategies for COVID-19, particularly in older males. Our finding of type I IFN auto-Ab production in a younger female prompts further study of this autoimmune phenotype in a broader population.

Disclosures
David A. Lindholm, MD, American Board of Internal Medicine (Individual(s) Involved: Self): Member of Auxiliary R&D Infectious Disease Item-Writer Task Force. No financial support received. No exam questions will be disclosed ., Other Financial or Material Support David Tribble, M.D., DrPH, Astra Zeneca (Other Financial or Material Support, HJF, in support of USU IDCRP, funded under a CRADA to augment the conduct of an unrelated Phase III COVID-19 vaccine trial sponsored by AstraZeneca as part of USG response (unrelated work)) Simon Pollett, MBBS, Astra Zeneca (Other Financial or Material Support, HJF, in support of USU IDCRP, funded under a CRADA to augment the conduct of an unrelated Phase III COVID-19 vaccine trial sponsored by AstraZeneca as part of USG response (unrelated work))
457. High Levels of Serum Troponin I Indicate Higher Mortality Risk in Patients with COVID-19
Authors: Ramirez Paula , Parra-Tanoux Daniela , Bustos-Moya Ingrid G , Fuentes Yuli , Ibañez-Prada Elsa Daniela , Narváez - Ramírez Oriana , Morales-Cely Lina , Bravo-Castelo Laura A , Gomez-Duque Salome , Gamboa-Silva Enrique , Caceres Edar , Reyes Luis F 
Published: December 2021

Abstract

Background
Up until this day, over 3.5 million fatalities related to coronavirus disease 2019 (COVID-19) have been registered worldwide by the World Health Organization. Healthcare professionals require prognostic tools for COVID-19 patients in order to guide treatment strategies. Elevated troponin levels, a biomarker of cardiac injury, have been detected among patients with COVID-19, hence associating it with cardiac injury. Although several studies have mentioned it, the role of troponin as a prognosis biomarker is unclear. Elevation in troponin levels has been observed in patients with community-acquired pneumonia (CAP). However, its association with mortality is scarcely mentioned in literature. Thus, we sought to determine the utility of serum troponin I levels as a mortality predictor for patients with COVID-19 and CAP.

Methods
A prospective observational study was carried out at Clinica Universidad de La Sabana, Colombia, with patients hospitalized due to CAP and COVID-19. Troponin biomarker was quantified in serum samples using the PATHFAST system within the first 24 hours of hospital admission. Serum concentrations of troponin were compared among study groups. To assess the biomarker′s capacity to predict mortality, ROC curves were used, quantifying their differences through the DeLong′s test.

Results
A total of 88 patients with CAP and 152 with COVID-19 were included in the study. In all cohort the median [IQR] serum concentration of troponin (ng/ml) was higher in those who died (34.2, [9.74-384] vs 5.89, [2.44-27.9] p&lt; 0.001). Furthermore, troponin was higher in deceased patients with COVID-19 vs those who survived (77.35 [11.9-346.5] vs. 4.88 [2.10-13.02], p&lt; 0.001). However, there was no significant difference between CAP deceased and not deceased patients (18.1 [8.52-398] vs 15.7 [3.75-62.8], p=0.16). Although sample size might be a limitation when analyzing these results, the AUC ROC of troponin I to predict mortality was 0.799 for COVID-19 and 0.615 for CAP, the DeLongs test for compared ROC curves was a p= 0.0351.

A. Serum troponin I and mortality due to lower respiratory tract infections B. Serum troponin I to predict mortality in patients with lower tract infections C. ROC curve for serum troponin I to predict risk of mortality

Conclusion
Overall, troponin levels were higher among deceased patients. Our findings suggest that high troponin levels are a mortality predictor for patients with COVID-19.

Disclosures
All Authors: No reported disclosures
463. Factors of Social Determinants of Health Associated with Length of Stay in COVID-19 Patients with Multimorbidity in Southwest Georgia, United States
Authors: Golpayegany Sahand , Osae Sharmon P , Thomas Geren , Young Henry N , Martínez Andrés F Henao , Franco-Paredes Carlos , Chastain Daniel B 
Published: December 2021

Abstract

Background
Previous studies have observed that multimorbidity, defined as two or more comorbidities, is associated with longer lengths of stay (LOS) and higher mortality in patients with COVID-19. In addition, inequality in social determinants of health (SDOH), dictated by economic stability, education access and quality, healthcare access and quality, neighborhoods and built environment, and social and community context have only added to disparities in morbidity and mortality associated with COVID-19. However, the relationship between SDOH and LOS in COVID-19 patients with multimorbidity is poorly characterized. Analyzing the effect SDOH have on LOS can help identify patients at high risk for prolonged hospitalization and allow prioritization of treatment and supportive measures to promote safe and expeditious discharge.

Methods
This study was a multicenter, retrospective analysis of adult patients with multimorbidity who were hospitalized with COVID-19. The primary outcome was to determine the LOS in these patients. The secondary outcome was to evaluate the role that SDOH play in LOS. Poisson regression analyses were performed to examine associations between individual SDOH and LOS.

Results
A total of 370 patients were included with a median age of 65 years (IQR 55-74), of which 57% were female and 77% were African American. Median Charlson Comorbidity Index was 4 (IQR 2-6) with hypertension (77%) and diabetes (51%) being the most common, while in-hospital mortality was 23%. Overall, median length of stay was 7 days (IQR 4-13). White race (-0.16, 95% CI -0.27 to -0.05, p=0.003) and residence in a single-family home (-0.28, 95% CI -0.38 to -0.17, p&lt; 0.001) or nursing home/long term care facility (-0.36, 95% CI -0.51 to -0.21, p&lt; 0.001) were associated with decreased LOS, while Medicare (0.24, 95% CI 0.10 to 0.38, p=0.001) and part-time (0.35, 95% CI 0.13 to 0.57, p=0.002) or full-time (0.25, 95% CI 0.12 to 0.38, p&lt; 0.001) employment were associated with increased LOS.

Conclusion
Based on our results, differences in SDOH, including economic stability, neighborhood and built environment, social and community context, as well as healthcare access and quality, have observable effects on COVID-19 patient LOS in the hospital.

Disclosures
All Authors: No reported disclosures
470. Relapsing COVID-19 Pneumonia in Patients Receiving Rituximab Therapy
Authors: Gallagher Jolie , Hall Kevin H , Albrecht Benjamin 
Published: December 2021

Abstract

Background
Rituximab is a monoclonal antibody against the CD20 antigen on B-lymphocytes leading to B-cell death and depletion. Patients who receive rituximab and are infected with the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) causing coronavirus disease (COVID-19) may have increased difficultly clearing the virus and be at risk for persistent disease. While the limited literature available is mixed regarding the severity of COVID-19 in patients receiving rituximab, there is minimal literature regarding persistent and relapsing COVID-19 in this patient population. This is a case series of patients with persistent COVID-19 who previously received rituximab.

Methods
This is a retrospective review of 5 patients admitted between 1/1/2021 and 5/1/2021 to our institution with confirmed COVID-19 and receipt of rituximab for any indication within the previous 12 months. Information regarding hospital readmissions, time course of positive infection, medical management, disease severity, and discharge disposition were collected.

Results
Five patients, median age of 46, currently or recently on rituximab therapy were admitted a median of 2 times due to persistent, severe COVID-19 (Table 1). Patients received their initial COVID-19 diagnosis a median of 34 days (8-102 days) since their last rituximab administration and had documented SARS-CoV-2 infection a median of 66 days (19-195 days; Figure 1). All 5 patients received remdesivir and corticosteroids over the course of their COVID-19 disease and 2 patients received convalescent plasma therapy 1 and 5 days prior to a positive SARS-CoV-2 antibody IgG.
Figure 1. Patient SARS-CoV-2 Infection Course

Table 1. Patient Clinical and Therapeutic Data

Conclusion
Rituximab therapy may be associated with persistent or relapsing COVID-19 disease. Controlled investigations are necessary to evaluate the exact impact anti-CD20 agents have on the course of COVID-19 and whether convalescent plasma or other therapies can prevent relapsing disease.

Disclosures
All Authors: No reported disclosures
474. Unique Treatment Challenges with Multisystem Inflammatory Syndrome in Children (MIS-C) compared to Kawasaki Disease Shock Syndrome
Authors: Quick Rachel Downey , Hasbani Keren , Murphey Donald , Fernandez Mariosl , Shaffer Kenneth , Quirt Rachel A , Hauger Sarmistha Bhaduri 
Published: December 2021

Abstract

Background
Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) associated with Coronavirus Disease 2019 present similarly with mucocutaneous symptoms and fever. Both syndromes can progress to shock. Successful treatments for MIS-C are largely based on proven KD management. As more patients with MIS-C are treated, protocols are adjusted. Infectious Diseases (ID) specialists are often early consultants in these cases. Understanding differences in how body systems are affected in MIS-C versus KD is essential for management.
Figure 1. Cardiac changes among patients with Kawasaki Disease shock syndrome (KDSS) and Muti-system Inflammatory Syndrome (MIS-C)

Methods
This is a single hospital comparison of 25 cases of MIS-C with mucocutaneous presentation and symptoms of shock and 25 consecutive cases of KD Shock Syndrome (KDSS). Cases were compared for demographics, symptoms, cardiac abnormalities, medical treatments, and cardiac recovery.

Results
Patients with MIS-C develop symptoms of shock including sustained hypotension and tachycardia at 3 times the rate of patients with KD (45% vs 13%; p&lt; 0.001). On echocardiogram, left ventricular myocardial dysfunction, assessed by ejection fraction, is more commonly noted in cases of MIS-C than KDSS (fig 1). About half of patients with MIS-C show left ventricular myocardial dysfunction initially with normalization by 6 months post-presentation in the majority (96%).

Conclusion
Cardiac changes and shock events related to KD and MIS-C are thought to be caused by differing inflammatory mediators. By comparing these two syndromes, we can determine ways to manage each optimally. MIS-C often results in left ventricular myocardial dysfunction, which is rarer in KD cases. Fluid resuscitation with multiple fluid boluses followed by inotropes to treat hypotension in cases of in MIS-C puts increased strain on the already weakened myocardium. Early intravenous immunoglobulin (IVIG) administration, even in the presence of mild hypotension, can simultaneously provide the patient with additional fluid and decrease the underlying inflammatory process. This prompt treatment might reduce the need for pressor support while protecting the myocardium from further damage. As early consultants in MIS-C, ID providers should be educated regarding the unique cardiac challenges of MIS-C and avoid delay in IVIG treatment and cardiologist and intensivist consultation.

Disclosures
All Authors: No reported disclosures
493. Incidence and Characterization of Chronic Active COVID Among Patients Infected with the Novel Coronavirus (COVID-19) Receiving B-cell Depleting Therapies (BCDTs)
Authors: Kartes Jacob , Spivak Emily S , Imlay Hannah 
Published: December 2021

Abstract

Background
There have been reports of COVID-19 infection characterized by prolonged viral replication [chronic active COVID-19 (CAC)] among immunocompromised patients, including those receiving B-cell depleting therapies (BCDTs). We aimed to characterize the severity and incidence of CAC among patients on BCDTs with COVID-19, and to identify associated risk factors.

Methods
We retrospectively reviewed all patients who received an anti-CD20 BCDT within 1 year of a positive COVID test at University of Utah Health. Demographics, comorbidities, indications, and timing of BCDT were documented. Chart review was performed to characterize the clinical course, including need for hospitalization, COVID-specific therapies, need for ICU and ventilatory support, and mortality. We defined CAC as: (1) despite initial clinical improvement, progression of illness extending beyond 14 days, characterized by ongoing fevers or progressive respiratory failure; or (2) ongoing symptoms with demonstration of absent seroconversion ≥ 14 days into illness. In some patients the diagnosis of CAC was supported by low viral PCR crossing thresholds that occurred ≥ 14 days into illness. Logistic models were used to identify risk factors for CAC among the cohort of patients who survived through the initial period of infection.

Results
We identified 66 individuals who received a BCDT within 1 year of a positive COVID test; 29 (44%) were hospitalized, 4 (6%) required ventilation, and 7 (11%) died within 60 days. Among 63 patients who survived their initial COVID course, 16 (25%) had courses compatible with CAC. Nine (56%) who received a BCDT within 1 month before or 2 weeks after their COVID diagnosis developed CAC; OR 7.4 (95% CI 1.7, 31.6, p=0.002).

Conclusion
We clinically observed COVID-19 infection lasting longer than the typical course and propose a definition for CAC. Incidence of CAC was highest among patients who received BCDT within 30 days before or 2 weeks after COVID-19 diagnosis. High suspicion for CAC is warranted among patients receiving these therapies. Additional study is needed to better define risk for CAC among varying immunosuppressed populations and determine whether COVID-specific treatments early in disease may benefit these patients.

Disclosures
Hannah Imlay, MD, MS, Gilead Sciences, Inc. (Scientific Research Study Investigator)
508. Title Favipiravir for the Treatment of Coronavirus Disease 2019; A Propensity Score Matched Cohort Study
Authors: Alattar Rand A , Ahmed Shiema A , Abdallah Tasneem , Kazman Rashid , Qadmour Aseelah N , Ibrahim Tawheeda , Alhariri Bassem , Shaar Shahd H , Bajwa Abeer , Alimam Abeir , Qazi Rabia , Abid Fatma Ben , Daghfal Joanne , Eldeeb Ali M , Shukri Kinda , Elsayed Ahmed , Rustom Fatima , AlSamawi Musaed S , Abdelmajid Alaaeldin A , Basulto Miguel , Cobian Armando , Khattab Mohammed Abu , Almaslamani Muna , Khal Abdullatif Al , Omrani Ali S 
Published: December 2021

Abstract

Background
We investigated clinical outcomes of favipiravir in patients with COVID-19 pneumonia.

Methods
Patients who between 23 May 2020 and 18 July 2020 received ≥24 hours of favipiravir were assigned to the favipiravir group, while those who did not formed the non-favipiravir group. The primary outcome was 28-day clinical improvement, defined as two-category improvement from baseline on an 8-point ordinal scale. Propensity scores (PS) for favipiravir therapy were used for 1:1 matching. Cox regression was used to examine associations with the primary endpoint.

Results
The unmatched cohort included 1,493 patients, of which 51.7% were in the favipiravir group, and 48.3% were not receiving supplemental oxygen at baseline (table 1). Favipiravir was started within a median of 5 days from symptoms onset. Significant baseline differences between the two unmatched groups existed, but not between the PSmatched groups (N = 774) (table 1). After PS-matching, there were no significant differences between the two groups in the proportion with 28-day clinical improvement (93.3% versus 92.8%, P 0.780), or 28-day all-cause mortality (2.1% versus 3.1%, P 0.360) (Table 2). Favipiravir was associated with more viral clearance by day 28 (79.8% versus 64.1%, P &lt; 0.001) (table 2). In the adjusted Cox proportional hazards model, favipiravir therapy was not associated 28-day clinical improvement (adjusted hazard ratio 0.978, 95% confidence interval 0.862 –1.109, P 0.726) (Table 3).

Conclusion
Favipiravir therapy for COVID-19 pneumonia is well tolerated but is not associated with an increased likelihood of clinical improvement or reduced all-cause mortality by 28 days.

Disclosures
All Authors: No reported disclosures
511. Treatment with Molnupiravir in the MOVe-In and MOVe-Out Clinical Trials Results in an Increase in Transition Mutations Across the SARS-CoV-2 Genome
Authors: Strizki Julie , Grobler Jay , Zhang Ying , Du Jiejun , Zhao Shunbing , Levitan Diane , Therien Alex , Butterton Joan R , Murgolo Nicholas 
Published: December 2021

Abstract

Background
Molnupiravir (MOV), (MK-4482, EIDD-2801) is being clinically developed for the treatment of COVID-19 disease caused by SARS-CoV-2. MOV is the orally administered 5′-isobutyrate prodrug of the active, antiviral ribonucleoside analogue, N-hydroxycytidine (NHC, EIDD-1931) which inhibits viral replication by induction of mutations in the viral genome, leading to viral error catastrophe. In 2 clinical studies, hospitalized (MOVe-In) and non-hospitalized (MOVe-Out) participants were treated for 5 days with MOV and followed up to Day 29. Viral RNA isolated from nasal swab samples were sequenced to determine the rate, distribution and type of viral mutations observed after MOV treatment.

Methods
RNA isolated from nasopharangeal swab samples collected during study conduct was quantified by RT-PCR. Samples containing &gt;22,000 copies/mL of RNA underwent complete genome NGS using the Ion AmpliSeq SARS-CoV-2 research panel and Ion Torrent sequencing. Mutation rates were calculated by determining the number of nucleotide changes observed across the entire genome at Day 3 and/or Day 5 compared to baseline.

Results
Combined data from both studies showed an increase of ~2-4 fold in the viral mutation rate post-baseline in MOV treated compared with placebo. Mutations were distributed across the entire genome with only a minority being observed in more than one sample. The most frequent mutations were transitions of C to U observed in the highest MOV dose group (800 mg/BID).

Conclusion
Consistent with the proposed mechanism of action of MOV, an increase in the rate of transition mutations in the virus was observed in post-baseline nasal swab samples from participants treated with MOV compared with placebo.

Disclosures
Julie Strizki, PhD, Merck & Co., Inc. (Employee, Shareholder) Jay Grobler, PhD, Merck & Co., Inc. (Employee, Shareholder) Ying Zhang, PhD, Merck & Co., Inc. (Employee, Shareholder) Jiejun Du, PhD, Merck & Co., Inc. (Employee, Shareholder) Shunbing Zhao, PhD, Merck & Co., Inc. (Employee, Shareholder) Diane Levitan, PhD, Merck & Co., Inc. (Employee, Shareholder) Alex Therien, PhD, Merck & Co., Inc. (Employee, Shareholder) Joan R. Butterton, MD, Merck Sharp & Dohme Corp. (Employee, Shareholder) Nicholas Murgolo, PhD, Merck & Co., Inc. (Employee, Shareholder)