bluuebunny/crossref_metadata_2025 huggingface dataset:
296. Description of Super-infections in Hospitalized Patients with COVID-19
Authors: Kludjian Geena , Spivack Stephanie , Gallucci Stefania , Kilpatrick Laurie , Mishkin Aaron D , Sajjan Umadevi , Tam Vincent , Gallagher Jason C , Gallagher Jason C
Published: December 2021

Background

The rate of bacterial and fungal super-infections (SI) in inpatients with COVID-19 is unknown. In this study, we aimed to identify and describe patients that developed secondary infections while hospitalized with COVID-19.

Methods

We performed a retrospective chart review on patients admitted to our health system between March and May 2020 with confirmed COVID-19 by nasopharyngeal PCR. We reviewed patients with positive cultures from urine, blood, sputum, and sterile sites. Patients with positive cultures had cases reviewed to determine if they represented a true infection, defined by CDC criteria. SIs were defined as infections that occurred at least 48 hours or longer after the initial positive SARS-CoV-2 test. Additional data was collected on patient demographics, COVID-related therapies, types of infections, and outcomes.

Results

902 patients were admitted with COVID-19 during our study period. Of these, 52 patients (5.8%) developed a total of 82 SIs. Tables 1 and 2 describe patient and infection characteristics. Patients identified as having a SI were admitted for a median of 30 days; 56% had mortality, and 39% of remaining patients were readmitted within 90 days.

Table 1. Patient Characteristics

Table 2. Super-infections

Conclusion

Overall, the rate of SIs in patients admitted with COVID-19 is low. These patients had a long length of stay, which may be either a cause of SI or an effect. Further analysis with matched COVID-positive control patients who do not develop SIs is needed to evaluate the risk of development of SIs in relation to presenting respiratory status, COVID-related therapies, and other patient-specific factors.

Disclosures

Jason C. Gallagher, PharmD, FIDP, FCCP, FIDSA, BCPS, Astellas (Consultant, Speaker’s Bureau)Merck (Consultant, Grant/Research Support, Speaker’s Bureau)Qpex (Consultant)scPharmaceuticals (Consultant)Shionogi (Consultant) Jason C. Gallagher, PharmD, FIDP, FCCP, FIDSA, BCPS, Astellas (Individual(s) Involved: Self): Speakers’ bureau; Merck (Individual(s) Involved: Self): Consultant, Grant/Research Support; Nabriva: Consultant; Qpex (Individual(s) Involved: Self): Consultant; Shionogi (Individual(s) Involved: Self): Consultant
315. A Multi-center Study to Describe Obese Pediatric Patients with COVID-19 Across the United States
Authors: Hammoud Roukaya Al , Murphy James , Del Bianco Gabriela P , Heresi Gloria , Chang Michael L
Published: December 2021

Background

Obesity is linked to increased risk of complications and is reported to be the most common underlying condition for severely ill SARS-CoV-2 infected individuals. Therefore, we aim further to explore the clinical outcomes of obese children with COVID-19.

Methods

Data were from the Pediatric COVID-19 Case Registry, which includes any patient < 21 years of age diagnosed with COVID-19 at 170 instructions across the United States. A total of 778 COVID-19 positive non-immunocompromised hospitalized patients aged 24 months or older were included. Patients were assigned as obese or non-obese based on BMI as reported from medical records referenced to CDC BMI by gender and age classification (https://www.cdc.gov/growthcharts/clinical_charts.htm).

Results

Patients meeting inclusion criteria included 56% not obese and 44% obese. Compared to matched US population, obese children and adolescents appeared in this database at a rate of 2.3 times their frequency in the population. Obese patients were more likely to be Hispanic and older, symptomatic, have abnormal radiological findings, and require oxygen and ICU admission. Mortality, in this analysis, was similar across the groups.

Demographic and clinical characteristics. NS: Not significant *within seven days of COVID diagnosis ***mild: no need for supplemental oxygen; moderate: need for supplemental oxygen and severe: need for mechanical ventilation.

Conclusion

The incidence of obesity in hospitalized COVID children is higher than that of the general population (34% vs. 19%), highlighting obesity as an important risk factor for hospitalization associated with SARS-CoV-2 infected. Therefore, obese children and adolescents with COVID should be prioritized for COVID immunization and managed aggressively, given their significant COVID morbidity.

Disclosures

All Authors: No reported disclosures
342. Secondary Infections following Tocilizumab for Treatment of COVID-19 Pneumonia
Authors: Warner Adam , Abbas Mujahed , Avner Benjamin S , Flynn Thomas E , Walroth Todd A , Jagger Brett W
Published: December 2021

Background

Guidelines recommend use of tocilizumab (TCZ), an inhibitor of pro-inflammatory IL-6 signaling, for hospitalized patients with progressive severe or critical Coronavirus disease 2019 (COVID-19). The incidence of infectious complications following the use of TCZ for COVID-19 has not been well-described.

Methods

We conducted a retrospective, observational matched cohort study of severely ill, hospitalized adult patients with confirmed COVID-19 who were treated with TCZ between 2/24/2021 and 6/1/2021. The intervention group, comprised of patients who received a single dose of TCZ, was matched based on c-reactive protein (CRP) and fraction of inspired oxygen (FiO2) with a control group who did not receive TCZ, and were hospitalized between 10/12/2020 and 3/6/2021. The primary outcome of the study was diagnosis of a bacterial or fungal infection after day 3 of the index hospitalization. Secondary outcomes included all-cause mortality during the study period and length of stay.

Results

75 patients who received TCZ were identified during the study period, and matched 1:1 with 75 control patients. Baseline CRP and FiO2 were similar between groups, while the median age in the TCZ group was younger (61 versus 71 years), reflecting the epidemiology of the outbreak during the TCZ and control study periods. 15 bacterial and fungal infections were identified in the TCZ group (20.0%) and 4 (5.3%) infections in the control group (p = 0.012). The majority of infections in both groups were bacterial, with a disproportionate number of bloodstream infections in the TCZ group [7 (9.3%) vs 2(2.6%); p = 0.166]. 28 patients (37.3%) died in the TCZ group compared to 39 (52.0%) in the matched control (p = 0.068). Median time to discharge was similar between TCZ and control patients (11 versus 12 days; 95% CI -2,2).

Conclusion

Secondary infections in adult patients with severe and critical COVID-19 were more common in patients who had received TCZ. Prospective studies are needed to confirm and further describe this association.

Disclosures

All Authors: No reported disclosures
353. New-Onset Diabetes as an Acute Complication of COVID-19: A National Population Cohort Analysis
Authors: Hong Kwan , Kim Jeehyun , Yum Sujin , Gómez Raquel Elizabeth Gómez , Chun Byung Chul
Published: December 2021

Background

Diabetes is emerging as one of the complications of coronavirus disease 2019 (COVID-19), but this is hard to be revealed with cross-sectional studies since it is also known as the major predisposing factor for high-risk COVID-19. Therefore, this study aimed to estimate the risk of new-onset diabetes after COVID-19 through a population follow-up study.

Methods

All COVID-19 confirmed cases in Korea from January 20 to June 4, 2020, were matched with national health insurance data and their health screening data, both provided by the National Health Insurance Service of Korea. Controls were selected as the people who received the PCR test for COVID-19 and showed negative results in the same period and followed up until July 19, 2020. We selected the outcome as the diagnosis of diabetes according to the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10, E10 – E14). People who were diagnosed with diabetes in the past five years were excluded from both groups. After performing a log-rank test between groups, adjusted incidence rate and hazard ratio were estimated using Cox proportional hazard modeling. Demographic characteristics (age, sex, region, family histories of hypertension/diabetes, and income) and underlying health conditions such as hypertension, dyslipidemia, heart disease, alcohol consumption, cigarette smoking, and BMI were adjusted. Proportional assumptions were tested by the zph test and the sensitivity analysis by excluding each factor in turn and comparing results.

Results

A total of 6,247 COVID-19 patients and 143,594 controls without diabetes in the past were included for the analysis. The number of new-onset diabetes were 759 (12.15%) in COVID-19 patients and 3,465 (2.41%) in controls (P < 0.01). The adjusted incidence of diabetes was 15.34 (95% confidence interval, CI: 14.10 – 16.66) and 11.18 (95% CI: 10.67 – 11.72) per 100 person-year, respectively, with the mean follow-up time as 46.31 (standard deviation: 16.37) days. The adjusted hazard ratio of diabetes in COVID-19 cases was 2.97 (95% CI: 2.44 – 3.63).

Conclusion

Since COVID-19 patients showed a higher incidence of new-onset diabetes in a short-time follow-up, we should consider diabetes as one of the possible complications of COVID-19.

Disclosures

All Authors: No reported disclosures
365. Assessing Provider Utilization of COVID-19 Inflammatory Marker Trends in Hospitalized Patients and Implications in Optimizing Value-Based Care During a Pandemic
Authors: Subramanian Praveen , Stun Lucy , Bahr Nathan , Satterwhite Lewis , Bhakta Maharshi , Atrouni Wissam El , Plapp Fred , Newman Jessica
Published: December 2021

Background

Numerous inflammatory markers may serve a role in prognostication of patients hospitalized with COVID-19. Early in the pandemic, our health system created an admission order set which included daily d-dimer, c-reactive protein (CRP), lactate dehydrogenase (LDH), and ferritin. Given more available outcomes data, limiting standing order of studies that do not affect daily management could result in significant cost savings to the health system without adverse patient outcomes. The purpose of this study was to determine ordering and utilization patterns of inflammatory markers by physicians caring for patients hospitalized with COVID-19 infections.

Methods

An anonymous 10-question survey was distributed to 125 physicians (Infectious Diseases, Hospitalist, Pulmonary and Critical Care faculty). Responses were tallied and values greater than 50% were identified as the majority of the surveyed group.

Results

Of the 125 physicians surveyed, 77 (62%) responded. A total of 57.1% (44/77) of physicians reported ordering daily inflammatory markers for 3-10 days from admission. Another 31.2% (24/77) ordered markers until clinical improvement or hospital discharge. D-dimer was used for care decisions by 83.1% (64/77) of respondents; 93.8% (60/64) of those reported utilizing it in determining anticoagulation dose. CRP was used by 61% (47/77) of physicians to help identify a secondary infection or determine steroid dose or duration. LDH and ferritin were not used for management decisions by the majority of physicians. Inflammatory markers were not used routinely after isolation precautions had been discontinued, even when ongoing care required mechanical ventilation.

Conclusion

Of the markers studied, both d-dimer and CRP were considered useful by most respondents. LDH and ferritin were used less frequently and were not considered as useful in guiding medical decision making. Discontinuation of standing daily LDH and ferritin orders is believed to have potential to result in cost savings to the health care system with no adverse patient outcomes.

Disclosures

All Authors: No reported disclosures
414. Observed Time Burden with Nursing Practices in an Emergency Room COVID-19 Isolation Zone at a University Affiliated Hospital in Korea
Authors: Choi Imyoung , Kang JaHyun
Published: December 2021

Background

The coronavirus disease 2019 (COVID-19) has caused great burdens on emergency room (ER) and front-line ER healthcare personnel faced with great challenges, including threats to their safety. This study aimed to provide a basis for additional workload of ER nurses who are charged with providing care for COVID-19 confirmed or suspicious cases.

Table 1. Summary of Frequency and Time Burden with Nursing Practices in an Emergency Room COVID-19 Isolation Zone. Note. IV, intravenous; IM, intramuscular; ID, intradermal; SC, subcutaneous; PPE, personal protective equipment; CPR, cardiopulmonary resuscitation

Methods

With institutional review board approval, we recruited ER nurses who were assigned to COVID-19 isolation zone with more than 6 months’ ER work experience. After their demographic information were collected through a questionnaire, their nursing practices and practice time during their 1 shift (day or evening) were recorded by one researcher using a stopwatch and an observation form. For each observation shift, unit-related information was collected, including the numbers of hospitalized patients, admission, discharge, and transfer of patients. For each nursing practice, frequency and total time spent were analyzed using descriptive statistics with SPSS 26.0 program.

Results

From January 4 to February 22, 2021, a total 18 nurses (27.4 years old on average with 25.2 months of ER experience) were observed from 20 different shifts. During the observation period, the average number of nurses’ working hours was 8.27 ± 0.39 hours. A total of 6,567 tasks were monitored with 337,703 seconds (93.81 hours) of the total time spent. Infection control practices were most frequent (33.88%) followed by nursing management (27.80%), assessment and observation (11.07%), medication (10.35%), pre and post examination care(4.86%), education (4.37%), communication (4.10%), safety care (1.10%), and others (0.03; Table 1). Nursing management (e.g., nursing recording) was most time-consuming (49.29%) followed by assessment and observation (15.03%), medication (12.94%), patient education (6.10%), infection control (5.30%), and safety care (1.64%).

Conclusion

This study showed that infection control practices were most frequent while time spent was relatively insignificant among ER nurses in charge of COVID-19 isolation zones. Further studies for more observations or with different study designs at other ER settings are necessary to understand nurse’s burdens with COVID-19 emergency care.

Disclosures

All Authors: No reported disclosures
415. A Whole Genome Sequencing Analysis of a Multi-unit Long-term Care Facility COVID-19 Outbreak
Authors: Kong Ling Yuan , Parkes Leighanne , Longtin Yves , Greenaway Christina , Zaharatos Jerry , Loo Vivian , Savard Noémie , Dion Réjean , Éric Fournier , Roger Michel , Moreira Sandrine
Published: December 2021

Background

The coronavirus disease (COVID-19) pandemic has affected residents in long-term care facilities (LTCF) significantly. Understanding transmission dynamics in this setting is crucial to control the spread of COVID-19 in this population. Using whole genome sequencing (WGS) of SARS-CoV-2, we aimed to delineate the points of introduction and transmission pathways in a large LTCF in Quebec, Canada.

Methods

Between 2020-10-28 and 2021-01-09, COVID-19 cases occurred in 102 residents and 111 HCW at a 387-bed LTCF; cases were distributed in 11 units on 6 floors. As part of outbreak analysis, SARS-CoV-2 isolates underwent WGS using the Oxford Nanopore Minion and the Artic V3 protocol. Lineage attribution and sequence types (ST, within 3 mutations) were assigned based on Pangolin classification and variant analysis. Epidemiologic data including date of positive PCR test, resident room number and HCW work location were collected. Self-reported high-risk exposures were collected by HCW questionnaire via phone interview after consent. Cases and their ST, geo-temporal relations and HCW-reported exposures were examined via network plots and geography-based epidemic curves to infer points of introduction and paths of transmission.

Results

Of 170 isolates available from 100/102 residents and 70/111 HCW, 130 (76.4%) were successfully sequenced. Phylogenetic analysis revealed 7 separate introductions to the LTCF. Grouping of ST by units was observed, with temporal appearance of ST supporting HCW introduction in 7/11 units. Proportion of phone interview completion was low at 35% (26/70). Few HCW recalled specific high-risk exposures. Recalled exposures supported by genetic linkage revealed potential between-unit introductions from HCW-to-HCW transmission at work and outside the workplace (e.g. carpooling). On one unit, a wandering resident was identified as a likely source of transmission to other residents (Figure 1).

Network plot of cases clustered by geographic unit, colour-coded by sequence type. Circles represent residents; addition signs represent healthcare workers. Blue lines represent identified high-risk exposures. Node labels represent floor and unit identifiers; 2 units per floor.

Conclusion

We demonstrate the complex genomic epidemiology of a multi-unit LTCF outbreak, putting into evidence the importance of a multi-faceted approach to limit transmission. This analysis highlights the utility of using WGS to uncover unsuspected transmission routes, such as HCW contact outside work, which can prompt new infection control measures.

Disclosures

All Authors: No reported disclosures
422. Sustainability of Improvements to Hand Hygiene Performance Throughout the COVID-19 Pandemic
Authors: Williams Victoria R , Muller Matthew , Powis Jeff , Ricciuto Daniel R , Mertz Dominik , Katz Kevin , Castellani Lucas , Hota Susy S , Hota Susy S , Payne Michael , Johnstone Jennie , Leis Jerome A
Published: December 2021

Background

Hand hygiene (HH) is a standard infection prevention and control precaution to be applied in healthcare settings to prevent transmission of COVID-19. Many healthcare institutions observed significant improvements in HH performance during wave one of the COVID-19 pandemic but the sustainability of this change is unknown. Our aim was to evaluate long-term HH performance throughout subsequent waves of the pandemic across acute care hospitals in Ontario, Canada.

Methods

HH adherence was measured using a previously validated group electronic monitoring system which was installed on all alcohol handrub and sink soap dispensers inside and outside each patient room across 56 inpatient units (35 wards and 21 critical care units) spanning 13 acute care hospitals (6 university and 7 community teaching hospitals) from 1 November 2019 to 31 May 2021. Daily HH adherence was compared with daily COVID-19 case count across Ontario. During this period, weekly performance continued to be reported to units but unit-based quality improvement discussions were inconsistent due to the COVID-19 response.

Results

Figure 1 depicts daily aggregate HH adherence plotted against the new daily COVID-19 case count across Ontario. An elevation in HH adherence was seen prior to the start of the first wave, rising almost to 80% and then remained above 70% for the peak of wave one. During waves two and three, peak COVID-19 case counts were associated with a maximum HH adherence of 51%, only marginally above the pre-pandemic baseline. After the end of wave one (from 1 July 2020 to 31 May 2021) the median HH performance was only 49% (interquartile range 47%-50%).

Figure 1. Hand hygiene adherence across 13 acute care hospitals in comparison to overall new daily COVID-19 cases in Ontario

Conclusion

Initial improvements in HH adherence preceding the start of the COVID-19 pandemic were not sustained, possibly due to increasing comfort and reduced anxiety associated with providing care to COVID-19 patients leading to a perception of reduced COVID-19 transmission risk. These findings highlight the need for HH monitoring to be tied to longitudinal unit-led quality improvement in order to achieve durable changes in practice.

Disclosures

Susy S. Hota, MSc MD FRCPC, Finch Therapeutics (Research Grant or Support) Susy S. Hota, MSc MD FRCPC, Finch Therapeutics (Individual(s) Involved: Self): Grant/Research Support
444. County-level COVID-19 Case Fatality Rate in Medicaid Expansion States Compared to Non-Expansion States
Authors: El-Nahal Walid , Berry Stephen , Psoter Kevin , Gebo Kelly
Published: December 2021

Background

Medicaid expansion has been adopted by 38 states and the District of Columbia,1,2 contributing to lower rates of uninsured individuals in the US.3 During the COVID-19 pandemic, Medicaid enrollment offset employer-based insurance losses precipitated by the recession.4 The aim of this study was to evaluate whether Medicaid expansion may have impacted COVID-19 mortality.

Methods

We conducted an ecologic study that included all US counties in the 50 states and District of Columbia. County-specific Medicaid expansion status was based on whether expansion was adopted within the state. COVID-19 cases and deaths for each county were obtained from the Centers of Disease Control (CDC). Unadjusted and multivariable negative binomial regression with robust standard errors to account for clustering of counties within each state were used to evaluate the association of COVID-19 case fatality rate and Medicaid expansion status. Adjusted models included the addition of four sets of county-level covariates thought to influence the association of Medicaid status and COVID-19 fatality rate: demographics, comorbidities, economic indicators, and physician density. These analyses were then performed in subgroups of counties defined by urbanicity (metro, suburban or rural) and quartiles of poverty rates. Incidence Rate Ratios (IRR) and 95% confidence intervals (CI) are reported.

Results

A total of 1,814 Medicaid expansion and 1,328 non-expansion counties were included in the analysis. Crude case fatality rates were 2.1% (non-expansion) and 1.8% (expansion). Medicaid expansion was not associated with a significantly lower COVID-19 case fatality rate in either the unadjusted (IRR: 0.86; 95% CI: 0.74, 1.01) or fully adjusted (IRR: 1.02; 95% CI: 0.90, 1.16) models. In adjusted models, Medicaid expansion status was also not associated with differences in COVID-19 case fatality rate when counties were stratified by either urbanicity or percent of individuals living below the poverty line.

Conclusion

In this county-level analysis, Medicaid expansion status was not associated with a significant difference in county-level COVID-19-related case fatality rates among people of all ages. Future individual-level studies are needed to better characterize the effect of Medicaid on COVID-19 mortality.

Disclosures

All Authors: No reported disclosures
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

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< 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< 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

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 < 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

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< 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< 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

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< 0.001) or nursing home/long term care facility (-0.36, 95% CI -0.51 to -0.21, p< 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< 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

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

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< 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

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

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 < 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

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 >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)