bluuebunny/crossref_metadata_2025 huggingface dataset:
398. Multicenter Evaluation of Outcomes of SARS-CoV-2 Positive Patients Treated at Rural vs Urban Hospitals in the United States
Authors: Bauer Karri A , Yu Kalvin , Gupta Vikas , Puzniak Laura A
Published: December 2021

Background

The SARS-CoV-2 pandemic has revealed socioeconomic and healthcare inequities in the US. With approximately 20% of the population living in rural areas, there are limitations to healthcare access due to economic constraints, geographical distances, and provider shortages. There is limited data evaluating outcomes associated with SARS-CoV-2 positive patients treated at rural vs. urban hospitals. The aim of the study was to evaluate characteristics and outcomes of SARS-CoV-2 positive patients treated at rural vs. urban hospitals in the US.

Methods

This was a multicenter, retrospective cohort analysis of adult (≥ 18 years) hospitalized patients from 241 US acute care facilities with >1 day inpatient admission with a discharge or death between 3/6/20-5/15/21 (BD Insights Research Database [Becton, Dickinson & Company, Franklin Lakes, NJ]), which includes both small and large hospitals in rural and urban areas. SARS-CoV-2 infection was identified by a positive PCR or antigen during or < 7 days prior to hospital admission. Descriptive statistics were completed. P value of ≤0.05 was considered statistically significant.

Results

Overall, 42 (17.4%) and 199 (82.6%) of hospitals were classified as rural and urban, respectively. A total of 304,073 patients were admitted to a rural hospital with 12,644 (4.2%) SARS-CoV-2 positive. In comparison, a total of 2,844,100 patients were treated at an urban hospital with 132,678 (4.7%) SARS-CoV-2 positive. Patients admitted to rural hospitals were older compared to those treated at an urban hospital (65.2 ± 17.3 vs. 61.5 ± 18.7, P=0.001) (Table 1). Patients treated at an urban facility had significantly higher rates of ICU admission, severe sepsis, and mechanical ventilation. ICU length of stay was significantly longer for patients admitted to an urban hospital compared to a rural hospital (8.1 ± 9.9 vs. 6.1 ±7.2 days, P=0.001) (Table 2). No difference in mortality was observed.

Table 1. Characteristics of SARS-CoV-2 positive patients treated at rural vs. urban hospitals.

Table 2. Outcomes of SARS-CoV-2 patients treated at rural vs. urban hospitals. *Patients with available data.

Conclusion

In this large multicenter evaluation of hospitalized patients positive for SARS-CoV-2, there were significant differences in patient characteristics. There was no observed difference in mortality. These findings are important in evaluating the pandemic’s impact on patients in rural and urban healthcare settings.

Disclosures

Karri A. Bauer, PharmD, Merck & Co., Inc. (Employee, Shareholder) Kalvin Yu, MD, BD (Employee) Vikas Gupta, PharmD, BCPS, Becton, Dickinson and Company (Employee, Shareholder) Laura A. Puzniak, PhD, Merck & Co., Inc. (Employee)
406. Incidence of Community and Hospital Acquired Infections in Critically Ill COVID-19 Patients in the Dominican Republic
Authors: Rojas-Fermin Rita Alexandra , Guzman Anel E , Sanchez Ann , Germosen Edwin , Matos Cesar , Mena Lora Alfredo J
Published: December 2021

Background

The disease caused by SARS-CoV-2, COVID-19, has caused a global public health crisis. COVID-19 causes lower respiratory tract infection (LRTI) and hypoxia. There is a paucity of data on bacterial and fungal coinfection rates in patients with COVID-19 at low and middle income countries (LMICs). Our objective is to describe the clinical characteristics of critically ill patients with COVID-19 in the Dominican Republic (DR)

Methods

We performed a retrospective review of patients admitted to the ICU with COVID-19 from March 14th to December 31st 2020, at a 296-bed tertiary care level and teaching Hospital in the Dominican Republic. Demographic and clinical information was collected and tabulated. Laboratory confirmed bacterial and fungal infections were defined as community acquired infections (CAI) if diagnosed within 48 hours of admission and hospital acquired infections (HAI) when beyond 48 hours. Microbiologic data was tabulated by source and attribution.

Results

Our cohort had 382 COVID-19 patients. Median age was 64 and most were male (64.3%) and 119 (31.1%) were mechanically ventilated and 200 (52%) had central venous catheters. A total of 28 (7%) laboratory confirmed community acquired infections and 55 (14%) HAIs occurred. Community acquired infections included 13 (46%) bloodstream infections (BSIs), 11 (39%) urinary tract infections (UTI) and 6 (21%) LRTIs. HAIs included 39 (70%) BSIs, 11 (20%) UTIs and 6 (11%) ventilator associated pneumonias (VAP). Causal organisms of community and hospital acquired BSI and UTI are in Figure 1 and Figure 2 respecively. All-cause mortality was 35.3% (135/382) in our cohort, and 100% mortality (76) in those with coinfections.

Figure 1. Community acquired and hospital acquired bloodstream infections in COVID-19 patients admitted to the ICU

Figure 2. Community acquired and hospital acquired urinary tract infections in COVID-19 patients admitted to the ICU

Conclusion

Community and hospital acquired infections were common and in the ICU and likely contributed to patient outcomes. More than two thirds of HAIs in the ICU were BSIs. Central venous catheter device utlization and maintenance may play a role in BSIs, along with immunosuppression from COVID-19 therapeutics and translocation from mucosal barrier injury. Mortality in patients with coinfections was higher than those without. Infection prevention strategies to reduce device utilization during COIVD-19 in LMICs may have an impact on HAIs.

Disclosures

All Authors: No reported disclosures
408. Impact of the COVID-19 Pandemic on Antimicrobial Use and Resistance in the United States and the Dominican Republic
Authors: Lora Alfredo J Mena , Rojas-Fermin Rita Alexandra , Echeverria Stephanie L , Castro Katia , Guzman Anel E , Borgetti Scott , Bleasdale Susan C
Published: December 2021

Background

The disease caused by SARS-CoV-2, COVID-19, has caused a global public health crisis. Lower respiratory tract infections (LRTIs) caused by COVID-19 has led to an increase in hospitalizations. Disease severity and concerns for bacterial co-infections can increase antimicrobial pressure. Our aim is to define and compare the impact of COVID-19 on antimicrobial use (AU) and antimicrobial resistance (AMR) in the Dominican Republic (DR) and the United States (US).

Methods

We performed a retrospective review of AU and antimicrobial susceptibility patterns from 2019-20 at a hospital in the US (H-US) and the DR (H-DR). Our sites are community teaching hospitals with 151 beds in H-US and 295 beds in H-DR. After AU was tabulated, percent changes between 2019-20 were calculated. Resistance patterns for extended-spectrum beta-lactamase producing (ESBL) E coli, ESBL Klebsiella pneumoniae (ESBL-Kp), carbapenem resistant Pseudomonas aeruginosa (CR-PSAR) and Klebsiella pneumoniae (CR-Kp) were tabulated and percent changes between 2019-20 were calculated.

Results

AU increased by 10% in H-US and 25% in H-DR, with carbapenem use increasing by 268% and 144% respectively. Ceftriaxone use increased by 30% in H-US and 33% in H-DR. Azithromycin increased 54% in H-US and 338% in the H-DR. Resistance increased from 10% to 28% for ESBL-Kp and from 10% to 12% for ESBL E coli at H-US. CR-PSAR decreased from 20% to 12%, while cefepime and piperacillin resistance increased from 5% to 20% and 3% to 16% respectively (Figure 1). At H-DR, ESBL-Kp resistance decreased from 68% to 64% and increased from 58% to 59% for ESBL E coli. CR-PSAR and cefepime resistance increased from 5% to 19% and from 9% to 29% respectively (Figure 2).

Figure 1. Antimicrobial resistance (%) for select organisms at H-US in 2019 and 2020

Figure 2. Antimicrobial resistance (%) for select organisms at H-DR in 2019 and 2020

Conclusion

COVID-19 had a major impact on antimicrobial consumption and resistance in the US and DR. A greater impact was seen on ESBL rates in the US whilst a greater impact on carbapenem resistance was seen in the DR. The rise in carbapenem use in H-US reflected a rise in ESBL rates. In the DR, ESBL producing organisms were common prior to COVID-19 and carbapenem use was more widespread. The impact of the COVID-19 pandemic on AU may accelerate AMR worldwide. The scale up of antimicrobial stewardship across the globe is urgently needed to curb AMR.

Disclosures

All Authors: No reported disclosures
421. Effect of SARs-Cov-2 mRNA Vaccination in Healthcare Workers with Household COVID Exposure
Authors: Selby Laura , Starlin Richard
Published: December 2021

Background

Healthcare workers have experienced a significant burden of COVID-19 disease. COVID mRNA vaccines have shown great efficacy in prevention of severe disease and hospitalization due to COVID infection, but limited data is available about acquisition of infection and asymptomatic viral shedding.

Methods

Fully vaccinated healthcare workers at a tertiary-care academic medical center in Omaha Nebraska who reported a household exposure to COVID-19 infection are eligible for a screening program in which they are serially screened with PCR but allowed to work if negative on initial test and asymptomatic. Serial screening by NP swab was completed every 5-7 days, and workers became excluded from work if testing was positive or became symptomatic.

Results

Of the 94 employees who were fully vaccinated at the time of the household exposure to COVID-19 infection, 78 completed serial testing and were negative. Sixteen were positive on initial or subsequent screening. Vaccine failure rate of 17.0% (16/94).

Healthcare workers exposed to household COVID positive contact

Conclusion

High risk household exposures to COVID-19 infection remains a significant potential source of infections in healthcare workers even after workers are fully vaccinated with COVID mRNA vaccines especially those with contact to positive domestic partners.

Disclosures

All Authors: No reported disclosures
423. Implementation of a Hierarchy of Controls in a Mobile Health Unit to Safely Care for Inpatients with COVID-19 during Healthcare System Surge
Authors: Reason Paige , Leis Jerome A , Cocco Claudia , Stroud Lynfa , Hladunewich Michelle , Carew Debra , Burgess Robert , Chan Christina , Williams Victoria R , Tomiczek Nicholas , Salt Natasha , Chan Adrienne
Published: December 2021

Background

In April 2021, Sunnybrook Health Sciences Centre opened a Mobile Health Unit (MHU, i.e. medical tents) under the direction of the Ontario Ministry of Health and Long Term Care in response to a surge in hospitalized patients with COVID-19 during wave three of the pandemic. Providing care to patients in non-conventional spaces is not new, however, experience in safely caring for COVID-19 patients in these settings is lacking. Our aim is to describe the implementation of our MHU and associated outcomes of these COVID-19 patients.

Methods

A multidisciplinary clinical and operations team was created to plan, execute and operate a safe environment for COVID-19 patients and healthcare workers within the MHU. Patient selection was restricted to patients with COVID-19 who were clinically recovering from severe COVID-19 pneumonia. Ventilation was optimized with air flow directed away from patient areas, velocity reduced to below 0.25 meters per second, and air exchanges of 24-28 per hour. All healthcare workers working in the MHU were offered COVID-19 vaccine and required to complete mandatory education if they declined (vaccination rate of 87% was achieved among dedicated staff). Universal masking and eye protection was used throughout the MHU with designated areas for donning and doffing personal protective equipment.

Results

In total, 32 patients with COVID-19 were managed in the MHU between 26 April and 21 May, 2021. Table 1 provides the summary of patient characteristics. All patients had a median of one-day of transmission-based precautions remaining in their course and were infected with Alpha variant with exception of one patient with the Gamma variant. Among those patients with genotyping available, all were infected with SARS-CoV-2 carrying the N501Y mutation. Four of the 32 patients required transfer to the main hospital for medical indication while the others were discharged home or to rehabilitation. None of the healthcare workers who worked within the MHU developed COVID-19 infection.

Conclusion

We safely cared for patients recovering from COVID-19 infection in an MHU to support system healthcare capacity. Our experience, including the specific hierarchy of controls implemented, may be helpful for future pandemic planning.

Disclosures

All Authors: No reported disclosures
449. Performance of the Brighton Case Definition for Multisystem Inflammatory Syndrome in Children (MIS-C) Among a Large Single Center Cohort
Authors: Nguyen Jessica , Osuna Isabella , Muscal Eyal , Sexson Kristen , DeGuzman Marietta , Munoz Flor M , Vogel Tiphanie
Published: December 2021

Background

Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare, life-threatening, hyperinflammatory condition presumed to follow SARS-CoV-2 infection. Whether MIS-C can also follow SARS-CoV-2 vaccination is not clear, making MIS-C an adverse event of special interest following immunization. Monitoring for post-vaccine MIS-C is complicated by the clinical overlap of MIS-C with numerous other inflammatory conditions including Kawasaki Disease, toxic shock syndrome, and viral myocarditis. A case definition for MIS-C was recently created with the Brighton Collaboration (BC). We aimed to determine the performance of the BC MIS-C case definition among a large, single-center MIS-C cohort.

Methods

Retrospective review was performed for the first 100 MIS-C cases at our institution (May 2020-February 2021). All cases met the Centers for Disease Control and Prevention (CDC) case definition. Data on age, presentation, laboratory results and cardiac studies were collected and used to determine cases that fulfilled the BC case definition for MIS-C (see figure).

Case Definition: Definite Case

Results

Of 100 children (age < 21 years) diagnosed with MIS-C using the CDC case definition, 93 patients also fulfilled the BC definition. All 100 patients had elevated laboratory markers of inflammation and positive SARS-CoV-2 antibodies. However, 1 patient was excluded for significant respiratory symptoms (pulmonary hemorrhage), 5 were excluded due to only 1 clinical feature, and an additional patient was excluded for having none of the measures of disease activity. Among the 93 patients fulfilling the revised case definition, 88 (95%) met criteria for a definite case. Five of the 93 patients (5%) were considered probable cases, 1 reported only 1 day of fever and 4 had only 1 measure of disease activity.

Conclusion

The original case definitions for MIS-C were created rapidly following the first emerging reports of this hyperinflammatory state. Knowledge of the varied clinical presentations of this disorder has grown substantially. Modification of the case definition to include features truly representative of MIS-C will allow for more precise diagnosis in the face of conditions which mimic MIS-C, and for accurate and reliable monitoring for adverse events following immunization.

Disclosures

Flor M. Munoz, MD, Biocryst (Scientific Research Study Investigator)Gilead (Scientific Research Study Investigator)Meissa (Other Financial or Material Support, DSMB)Moderna (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Pfizer (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Virometix (Other Financial or Material Support, DSMB)
467. COVID-19 Infection in Persons Living with HIV in a Network of Community Health Centers in New York
Authors: Khan Aisha S , Kerr Christine A , Doyle Jenny , Punj Sonia , Coleman Julie , Arzu Iris , Mehta Rani , Reid Logan , Nagaraja Aarathi
Published: December 2021

Background

COVID-19 infection amongst persons living with HIV (PLWH) at Federally Qualified Healthcare Centers (FQHC) is not yet well understood. FQHC patients are frequently impoverished and marginalized due to socioeconomic instability and structural inequities. The virus has a wide-ranging clinical presentation, and little is known about how it affects specific populations such as PLWH and whether specific patterns of immunocompromise confer increased risk. Patients in community health centers and those living with HIV are often underrepresented from clinical trials. Patients seen at FQHC’s are more likely to be uninsured or living in poverty, or of Black or Latinx racial and ethnic backgrounds. Sun River Health is a not-for-profit, New York State licensed Article 28 Diagnostic & Treatment Center and FQHC. Sun River Health provides HIV primary care and supportive services caring for more than 2,500 PLWH primarily concentrated in 16 sites throughout the region. This study is a retrospective analysis of a vulnerable community at the heart of this pandemic.

Methods

We gathered COVID-19 diagnosis related data from the clinic’s electronic medical record and the New York State Health Information Exchange (HIE). We did chart reviews on 122 PLWH who had positive COVID PCR or antibody test between March 10 2020 and June 10 2020. Data collected included presence of symptoms, presence of comorbidities, CD4 counts, Hospitalization rate, ICU admission, and number of deaths.

Results

71.3% of cases occurred between the ages of 40-69 years. There were 85 cases (69.7%) in men and 37 cases (30.3%) in women. 54 cases (44.3%) occurred in African Americans, and 46 cases (37.7%) in Caucasians. 48 cases (39.3%) occurred in Latinx individuals, and 68 cases (55.7%) in Non-Hispanics. 91 cases (74.6%) were symptomatic and had either a positive COVID-19 PCR or antibody test. Symptomatic COVID-19 was present at higher rates in those with multiple predisposing comorbidities. 101 cases (82.8%) were virally suppressed. 89 cases (72.9%) were not hospitalized while 27 cases (22.1%) were hospitalized.

Conclusion

Most PLWH with COVID-19 were managed on an outpatient basis. PLWH with COVID-19 are not at a greater risk of severe disease or death as compared to HIV negative patients.

Disclosures

Christine A. Kerr, MD, Galileo Health (Employee, Shareholder)
471. Descriptive Analysis of Multiinflammatory Syndrome in Children (MIS-C) Secondary to COVID 19 Infection in a Predominantly Latino Population in Western Massachusetts
Authors: Rodriguez Julieta , Karr Nicholas , Danielczok Grzegorz , Fisher Donna J , Camelo Ingrid Y
Published: December 2021

Background

COVID-19 infection is usually mild in children. Progression to severe disease with multiple organ systems compromise described as Multi Inflammatory Syndrome in Children (MIS-C) is a rare occurrence believed to be immunologically mediated. Previous reports describe a possible link between children of Latino origin and high incidence of MIS-C in the US. 40% of the total population in Western Massachusetts is of Latino origin.

Methods

Retrospective chart review of 30 children admitted to Baystate Medical Center in Springfield, Massachusetts from April 2020-June 2021 meeting Centers for Disease Control and Prevention (CDC) criteria for MIS-C. Demographics, laboratory data, and clinical outcomes including progression to Macrophage Activation Syndrome (MAS) were analyzed.

Results

60% of children were Hispanic. Mean age (9.1 yrs). Range (3m-20 yrs). COVID PCR positive (78%) and COVID Antibody positive (68%). The most common symptom was fever (96.8%) followed by gastrointestinal symptoms (84%). Respiratory symptoms (29%), dermatological manifestations (39%). Most common comorbidity, asthma (19%) followed by obesity (17%). Leukocytosis (47%), lymphopenia (45%), Anemia (55%), thrombocytopenia (20%), high CRP (90%), ferritinemia (57%), acute kidney injury (20%), elevated liver enzymes (53%), 52% children had electrocardiogram (EKG) abnormalities, 34% had abnormal echocardiograms, none displayed coronary artery dilation. Progression to MAS (20%). All patients were treated with intravenous immunoglobulin G, steroids, aspirin, and anakinra (IL1 receptor antagonist) if progression to MAS. All patients survived.

Conclusion

In our population, gastrointestinal symptoms were predominant despite a high prevalence of asthma and obesity, previous reports of children with MIS-C describe predominance of respiratory manifestations. We did not encounter any coronary aneurysms during admission. Most children had positive PCR or Antibodies for COVID 19 and showed important abnormalities in multiple cell lines and inflammatory markers. More research is needed to fully understand ethnical risk factors associated with disease severity especially the risk of progression to MAS from MIS-C in children of Latino origin diagnosed with COVID 19 infection.

Disclosures

All Authors: No reported disclosures
477. Increased Referrals for New PFAPA (Aphthous Stomatitis, Pharyngitis, Adenitis) Diagnosis During the COVID-19 Pandemic
Authors: Geevarghese Bessey , Sun Shan , Jhaveri Ravi
Published: December 2021

Background

COVID-19 pandemic caused by SARS-CoV-2 resulted in a global health crisis in 2020. Quarantining, wearing masks and physical distancing- key infection prevention strategies implemented to stop the spread of COVID-19, also led to dramatic decreases in rates of common respiratory viral infection seen in young children. Due to lack of school and daycare exposure, we evaluated a larger than usual number of patients with periodic fevers without any known infectious contacts. Based on this observation, we conducted an analysis of all suspected cases of periodic fevers seen at our institution during the COVID-19 lockdown compared to prior seasons.

Methods

The clinical charts were queried for all patients presenting to any Lurie Children’s Hospital outpatient specialty clinic or laboratory with ICD diagnosis code of MO4.1 and MO4.8 (all recurrent and periodic fever syndromes) from June 1, 2020 through September 30, 2020, and compared to similar months the previous 2 years (2018 and 2019). Each patient chart was reviewed by the lead investigator to verify all new diagnoses of PFAPA. The number of new patients with PFAPA diagnosis were tallied and analyzed. Statistical comparisons were made using Kruskal-Wallis tests for monthly distributions in different years.

Results

We noted a significant increase in patients with new PFAPA diagnosis between June through August 2020 compared to similar months in 2018 and 2019 (Figure1). Experienced pediatric infectious disease physicians and rheumatologists diagnosed majority of the cases. During these months, a monthly median (IQR) of 13 (11.5, 14.5) patients were diagnosed among different Lurie specialty clinics, which is more than 2.5 folds increase in new PFAPA patients from the previous two years which were about 5 (3.5, 6) (Figure 2).

Number of Patients with New PFAPA Diagnosis

There was a significant increase in number of new patients diagnosed with PFAPA between June through August 2020 compared to similar months in 2018 and 2019.

Monthly Distribution Summary for New PFAPA Diagnosis

Statistical comparisons were made using Kruskal- Wallis tests for monthly distributions in different years

Conclusion

We observed a significant increase in PFAPA patients referred to our institution soon after introduction of public health measures to slow spread of COVID-19. Given that most children were not in daycare, schools, or camps, we suspect that parents and pediatricians were able to recognize patterns of periodic fevers in children much quicker than preceding years, when fevers would typically be attributed to an infectious process.

Disclosures

Ravi Jhaveri, MD, AstraZeneca (Consultant)Dynavax (Consultant)Elsevier (Other Financial or Material Support, Editorial Stipend as Co-editor in Chief, Clinical Therapeutics)Seqirus (Consultant)
480. Alternate Diagnoses in Children Evaluated for Multisystem Inflammatory Syndrome in Children (MIS-C)
Authors: Kaneta Kelli , Mohandas Sindhu , Szmuszkovicz Jackie , White Sarah , Wu Susan
Published: December 2021

Background

SARS-CoV-2 infection is typically a mild illness in children. Multisystem inflammatory syndrome in children (MIS-C) is a rare, post-infectious, hyperinflammatory condition associated with SARS-CoV-2 infection. The presentation of MIS-C is nonspecific and diagnostic criteria is broad. The Centers for Disease Control (CDC) defines MIS-C as a hospitalized patient < 21 years presenting with fever, laboratory evidence of inflammation, no alternative plausible diagnosis, and with positive exposure history or testing for current or recent SARS-CoV-2 infection. Since there is no single diagnostic test for MIS-C, there are other disease processes that can mimic its presentation and delay prompt diagnosis and management.

Methods

Between March 2020 and February 2021, we reviewed 282 charts of patients admitted for evaluation of MIS-C at our institution.

Results

101 were found to have MIS-C, 45 found to have Kawasaki Disease (KD), and 129 were ruled out. Of the ruled-out group, the most common final diagnoses were viral infection, urinary tract infection, and acute SARS-CoV-2 infection. Other diagnoses included rickettsial infections, pneumonia, rheumatologic conditions, and bloodstream infection. Rhinovirus/enterovirus, adenovirus, Epstein-Barr virus (EBV), and Herpes Simplex Virus (HSV) were the most common viruses other than SARS-CoV-2 identified.

Conclusion

These findings highlight the importance of maintaining a broad differential when evaluating a patient for MIS-C, especially as community seroprevalence rises, making antibody presence less predictive of MIS-C.

Disclosures

Susan Wu, MD, Eli Lilly (Shareholder)
496. Comparison of Severe COVID 19 and Influenza Infections in Pediatric Patients Requiring PICU in Bogota, Colombia
Authors: Gutiérrez Tobar Ivan Felipe , Patiño Tatiana , Rico Paola , Figueroa Nicolas , Londono-Ruiz Juan Pablo , Avila Diana N , Sanabria Mayra A , Vergara Angie , Gonzalez Paula , Rodriguez Carolina , Beltran Sandra
Published: December 2021

Background

COVID 19 infection represents a global threat and now a frequent cause of hospitalization in pediatrics. COVID 19, as well as Influenza virus could have a severe course. There are few studies, and no local or regional information comparing severe disease between COVID 19 and Influenza virus in children.

Methods

Confirmed COVID 19 between March 2020 to October 2021 and influenza infections from Jan-2017 to dec-2019 were included. Asymptomatic or ambulatory COVID 19 infections were excluded. The main objective was to compare clinical, laboratory and outcome characteristic of PICU admitted patients.

Results

71 patients were included, 32(45,1%) with COVID 19 and 39 (54,9%) influenza virus. COVID 19 patients were older than influenza patients: 67 (20,5-143) vs. 10 (2- 46) p=0.0002. The majority of influenza patients were younger than two years, with different distributions in COVID 19 patients. Figure 1. Respiratory distress was more frequent in influenza (92,3% vs. 62,5%) p=0.002, but exanthema (28,1% vs 2,6%), shock (68,7% vs. 7,7%) and central nervous system manifestations (40,6% vs. 7,7%) were significantly more common in COVID19 than in Influenza respectively. COVID 19 had lower platelets and lymphocyte counts than inlfuenza. There were no differences in treatment, nor deceased either, but Influenza patients had slightly longer hospital stays 12 (7 – 23) vs. 9.5 (6–15.5) p=0.1592 than COVID 19 (Table 1).

Table 1. Comparison of demographic and clinical characteristics of COVID 19 vs. Influenza patients.

Conclusion

COVID 19 and influenza severe infections can have some differences including age of presentation. Inlfuenza main manifestation requiring UCIP is respiratory distress, while COVID19 can have other presentations including shock and central nervous manifestation. Lower lymphocyte counts as well as lower platelets were significantly more common in COVID 19 patients. Although there are no unique characteristics of each infection, some particularities could guide clinician to the etiology of the infection.

Disclosures

Ivan Felipe Gutiérrez Tobar, n/a, Pfizer and MSD (Advisor or Review Panel member, Research Grant or Support, Speaker’s Bureau, Has received support from Pfizer and MSD for participation in congresses and has received conference payments from Pfizer)Pfizer and MSD (Speaker’s Bureau, Other Financial or Material Support, Has received support from Pfizer for participation in congresses) Sandra Beltran, n/a, Pfizer (Other Financial or Material Support, Has received support from Pfizer for participation in congresses)
516. Evaluation of COVID-19 Monoclonal Antibody Therapies for the Treatment of Non-hospitalized Patients with COVID-19
Authors: Morado Faiza , Nanda Neha
Published: December 2021

Background

In an effort to reduce strain on healthcare systems with patient hospitalizations and deaths due to COVID-19, the US Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for 2 monoclonal antibodies for the treatment of COVID-19 in November 2020: bamlanivimab (BAM) and casirivmab-imdevimab (CAS-IMD). While clinical trial data demonstrated reductions in hospitalization rate, real-world data at the time of approval was vastly limited.

Methods

A retrospective chart review of non-hospitalized patients who received either BAM or CAS-IMD from November 27th, 2020 to February 16th, 2021. Variables included timing of monoclonal antibody infusion, adverse events, and 30-day hospitalization rate. Descriptive statistics were calculated for all data.

Results

101 patients received either BAM (75.2%) or CAS-IMD (24.8%) at a median of 6 days (IQR 4-7) from reported symptom onset. The most commonly reported symptoms of COVID-19 at time of referral were cough (57.4%), fever (29.7%), and myalgia (27.7%). All patients (100%) had at least 1 documented EUA defined risk factor for severe COVID-19 (Table 1). Following transfusion, 7/101 (6.9%) and 3/101 (3.0%) experienced mild to moderate and severe adverse events, respectively (Table 2). At day 30, 5 patients (5.0%) were hospitalized with COVID-19 at a median of 7 days (IQR 3-8) post monoclonal antibody infusion.

Conclusion

We observed a higher frequency of hospitalization compared to 1.6% for BAM in BLAZE-1 and 3% for CAS-IMD in REGN-COV-2. This observation may reflect our higher risk population as all patients presented with at least 1 risk factor for severe disease compared to 69.6% and 65.0% in BAM and CAS-IMD clinical trials, respectively. Additionally, patients presented with longer durations of symptoms prior to infusion in our study population compared to 3 days reported in BAM and 4 days reported in CAS-IMD trials. Since the conclusion of this study, the FDA revoked the EUA for BAM administered alone based on increased observations of resistant variants to BAM monotherapy. However, our observations highlight the need for further exploration in the prevention of hospitalization in high risk populations as well as the optimal timing of monoclonal antibody therapy.

Disclosures

All Authors: No reported disclosures
520. Pharmacokinetic and Safety Phase 1 Study and Microneutralization Assay Results with BRII-196/BRII-198, a Novel Antibody Cocktail Active Against a Wide Range of SARS-CoV-2 Variants
Authors: Margolis David A , Zhang Fujie , Hao Xiaohua , Li Yanyan , Wang Mingming , Li Chunming , Zhang Yao , Ma Ji , Ji Yun , Zhu Qing
Published: December 2021

Background

BRII-196 and BRII-198 are human monoclonal antibodies (mAb) with an extended half-life targeting distinct epitopes of the spike protein on SARS-CoV-2. Mutations in these epitope regions are continuously emerging, potentially conferring resistance to COVID-19 therapeutics in development. Individual phase I studies showed that BRII-196 or BRII-198 alone were safe and well tolerated in healthy subjects. The BRII-196 and BRII-198 cocktail is currently under evaluation in Phase 2/3 studies for the treatment of COVID-19.

Methods

Preclinical study: BRII-196 and BRII-198 were evaluated in the microneutralization assay using pseudo-viruses encoding mutations identified in the spike protein of a panel of SARS-CoV-2 variants of concerns, including strains originating in UK, SA, BR, CA, and India. The fold-change in neutralization IC50 titers relative to wild-type virus was calculated. Phase 1 study: healthy adults received sequential IV BRII-196 and BRII-198 (n=9) or placebo (n=3); and were followed for 180 days. Two dose levels (750mg/750mg and 1500mg/1500mg) were evaluated for safety, pharmacokinetics and immunogenicity. Interim analysis results are presented.

Results

Preclinical: BRII-196 and BRII-198 exhibited neutralizing activity against pseudo-virus variants that contained spike mutations of a panel of variants including B.1.1.7 (UK), B.1.351(SA), P.1(BR), B.1.427/429 (CA), B.1.526 (NY), and B.1.617 (IN), comparable to that against wild-type virus. Phase I study: BRII-196 plus BRII-198 was well tolerated with no dose-limiting adverse events (AEs), deaths, serious adverse events, or infusion reactions. The majority of AEs were isolated asymptomatic grade 1-2 laboratory abnormalities. (Table 1). Each mAb displayed pharmacokinetic characteristics expected of extended half-life YTE-antibodies.

Conclusion

The BRII-196 and BRII-198 cocktail was well-tolerated, and maintains neutralization against currently reported circulating variants of concern. These preclinical and clinical results support further development of BRII-196 and BRII-198 as a therapeutic or prophylactic option for SARS-CoV-2.

Disclosures

David A. Margolis, MD MPH, Brii Biosciences (Employee) Yao Zhang, MD, Brii Biosciences (Employee) Yun Ji, PhD, Brii Biosciences (Employee, Shareholder)
521. Predictors of Hospitalization Due to Coronavirus Disease 2019 (COVID-19) at a Veterans Affairs Medical Center
Authors: Ho Macy , Le Sarah , Sevak Rajkumar J , Chapman-Bueno Jamie G , Berman Stephen M , Chun Patricia , Moon Yong S
Published: December 2021

Background

During the COVID-19 pandemic, the Veterans Affairs Long Beach Healthcare System (VALB HCS) saw a surge of patients with a positive SARS-CoV-2 test. There is a lack of guidance on triaging patients with COVID-19 in the clinical literature. To address this need, our study evaluated factors that predicted hospitalization of patients due to COVID-19.

Methods

This was a retrospective cohort study of patients with a positive SARS-CoV-2 test and medical evaluation at the VALB HCS between August 1 and December 31, 2020. SARS-CoV-2 positive patients admitted to the hospital for a non-COVID-19 related diagnosis were excluded. At the time of initial evaluation, demographic, clinical, and laboratory data, and PCR cycle threshold were collected and compared between patients admitted to the hospital and those managed in the community. A multiple logistic regression analysis was conducted to evaluate predictors for hospitalization due to COVID-19.

Results

Of 748 patients, 94 were admitted to the hospital and 654 were community-managed. The outcomes from the logistic regression analysis indicated that the model explained 58.8% of variance and was a significant predictor of hospitalization (X2 [8, 737] = 277.5, p< 0.0001). Patients with self-reported shortness of breath (OR=12.14, 95% CI=6.43-22.92) or diarrhea (OR=2.78, 95% CI=1.33-5.84) were more likely to be hospitalized, whereas patients with sore throat (OR=0.095, 95% CI=0.017-0.53) or body ache (OR=0.42, 95% CI=0.20-0.89) were less likely to be hospitalized than patients not having such symptoms. Every unit increase in patients’ age and temperature increased the likelihood of hospitalization by 7.6% and 62.7%, respectively. Every unit increase in patients’ diastolic pressure and SpO2% decreased the likelihood of hospitalization by 6.1% and 3.6%, respectively.

Conclusion

Our findings indicate that patients with shortness of breath, diarrhea, temperature, and old age were more likely to be hospitalized due to COVID-19. The results may help providers in clinical decision making regarding whether to admit the patient or not. These findings may be especially helpful when hospital bed availability is limited.

Disclosures

All Authors: No reported disclosures
522. Evaluation of Three COVID-19 Monoclonal Antibody Regimens in the Context of Rising B.1.526 Prevalence in New York City
Authors: Bao Hongkai , Guo Yi , Cowman Kelsie , Chen Victor , Nori Priya , Nori Priya
Published: December 2021

Background

Monoclonal antibodies were given emergency use authorization (EUA) by the Food and Drug Administration for the treatment of high-risk, outpatient COVID-19 infection. In New York City (NYC), the emergence and rapid growth of the B.1.526 variant of concern (VOC) possessing the E484K mutation was first noted in February 2021. In-vitro studies subsequently confirmed attenuated monoclonal antibody neutralization against VOCs. At our institution, bamlanivimab (BAM) alone or with etesevimab (B/E) and casirivimab/imdevimab (C/I) were utilized at different phases of the pandemic. The objective of this study was to assess their comparative efficacies in a highly variant prevalent setting.

Methods

This retrospective analysis was conducted at an urban hospital in the Bronx, NY and evaluated adult monoclonal antibody recipients from any of our infusion sites. Patients initially received BAM but given the high prevalence of variants, treatment was transitioned to first B/E and then C/I exclusively. We compared BAM versus combination therapy as well as B/E versus C/I individually. The primary outcome was all-cause hospital admission within 30 days post infusion.

Results

From February 1 to March 7, 2021, 358 patients received BAM and from March 17 to May 9, 2021, 86 and 179 patients received B/E and C/I, respectively. Compared to any combination infusion, patients who received BAM were significantly older, more likely to possess ≥ 2 qualifying EUA criteria, and less likely to be vaccinated for COVID-19 prior to infusion (Table 1). Following B/E and C/I, 4.5% of patients were admitted versus 10.1% for BAM, p=0.011. There were no significant differences in admission between B/E and C/I recipients, p=0.485. After excluding fully vaccinated patients (n=14) and adjusting for age and ≥ 2 EUA criteria, combination therapy remained associated with decreased odds of hospitalization compared to BAM (odds ratio, 0.48; 95% confidence interval, 0.24-0.94).

Conclusion

Combination therapy may be associated with fewer hospital admissions following infusion, although there were no statistically significant differences between the individual combination infusions. We suggest similar studies be conducted by other sites to understand the clinical impact of local SARS-CoV-2 variants on antibody efficacy.

Disclosures

Yi Guo, PharmD, BCIDP, Merck (Research Grant or Support) Kelsie Cowman, MPH, Merck (Research Grant or Support) Priya Nori, MD, Merck (Grant/Research Support) Priya Nori, MD, Nothing to disclose
525. Atovaquone for Treatment of COVID-19 (Ataq COVID-19) Trial
Authors: Jain Mamta K , Jain Mamta K , Sadek Hesham , de Lemos James , mcGuire Darren , Ayers Colby , Eiston Jennifer L , Lucas Claudia , Kamel Dena , Li Xilong , Agbor Barbine Agbor , Williams Noelle , Schoggins John
Published: December 2021

Background

Our group performed an in-silico screen to identify FDA approved drugs that inhibit SARS-C0V-2 main protease (Mpro), followed by in vitro viral replication assays, and in vivo pharmacokinetic studies in mice. These studies identified atovaquone as a promising candidate for inhibiting viral replication.

Methods

Enrolled patients were randomized in a 2:1 fashion to atovaquone 1500 mg twice daily versus matched placebo. Patients received standard of care treatment including remdesivir, dexamethasone, or convalescent plasma as deemed necessary by the treating team. Patients agreed to allow collection of saliva at baseline and twice a day while hospitalized or up to 10 days. Saliva was collected and RNA extracted for viral load (VL) measurement by Real-time PCR. Our primary outcome was to examine the between group differences in log transformed VL(copies/mL) using generalized linear mixed-effect models of repeated measures from all samples. Additional analysis of Atovquone plasma concentrations were examined and correlated with viral load and body mass index (BMI).

Results

Of the 61 patients enrolled; 41 were received atovaquone and 19 placebo. Overall the population was predominately male Hispanic with a mean age of 51 years. The two groups were balanced (Table 1) with regard to age, gender, race, co-morbidities, days from onset of symptoms, baseline oxygen requirements, and receipt of COVID-19 specific standard of care treatment. A higher proportion with diabetes was noted in the Atovaquone arm. The log10 VL was 5.25 copies/mL vs. 4.79 copies/mL at baseline in the atovaquone vs. placebo group. Although there was a decrease in VL over time, there was no differences between the atovaquone plus standard of care arm versus the standard of care arm (Figure 1). Additional analysis of atovaquone plasma concentration demonstrated a wide variation in atovaquone levels, inverse association between atovaquone levels and BMI (rho -0.44, p=0.03), and Day 5 concentrations and VL (rho -0.54, p=0.005).

Figure 1. Mean viral load of COVID-19 over time of atovaquone (blue) vs. placebo (red).

Table 1. Baseline characteristics

Conclusion

Although atovaquone showed promising in vitro antiviral properties for COVID-19, in this pilot study we did not detect a change in VL in patients who received atovaquone compared to placebo, possibly due to failure of patients achieve adequate drug levels.

Disclosures

Mamta K. Jain, MD, MPH, Gilead Sciences Inc. (Individual(s) Involved: Self): Research Grant or Support, Scientific Research Study Investigator; GlaxoSmithKline (Individual(s) Involved: Self): Scientific Research Study Investigator; Merck (Individual(s) Involved: Self): Scientific Research Study Investigator; Vasgene (Individual(s) Involved: Self): Scientific Research Study Investigator
556. Ruxolitinib for the Management of Severe Pneumonia Caused by SARS-CoV-2. Exploring the Combination with dexamethasone
Authors: Molina Aaron , Olmedo-Reneaum Alejandro , Reyes-Paniagua Maria Del Rocio , Molina Mariana
Published: December 2021

Background

Mexico is one of the top five countries with a higher mortality rate of hospitalized patients of 30.1%. Since COVID-19 has been associated with immune dysregulation and hyper inflammation, JAK-12 inhibitors have been tested to reduce IL6 production. Studies have shown improvements when using ruxolitinib (rxb) in severely hospitalized patients with COVID-19. These have included patients in combination with corticosteroids such as dexamethasone (dxm). This work aims to test the response of hospitalized patients with severe or critical COVID-19 treated with rxb with or without dxm.

Methods

An experimental, open, prospective study in a single third-level hospital in Mexico was performed. The primary outcome was favorable clinical response defined as withdrawal or decline of supplementary oxygen. Secondary outcomes such as mean hospital stay, improvement in systemic inflammatory response parameters, and mortality were also evaluated. Statistical differences for baseline and final measure and the use and not use of dxm were estimated. The study included adults with SARS-CoV-2 infection confirmed with polymerase chain reaction, radiological pneumonia, and oxygen saturation less than 90%. Rxb was administered 5mg/12hrs/15days, IV dxm 6mg/day/10days.

Results

The final sample was 108 adults with complete information and informed consent. Sixty-two patients (57%) received only rxb. There were no differences between groups for any parameter at the beginning of treatment, and all patients were receiving supplemental oxygen. After 28-day follow-up, 70% reduce supplemental oxygen requirement (74% rxb and 71% rxb+dxm; p=0.628), 18% remained, and 2% increases support (1% with rxb, and 5% rxb+dxm; p< 0.001); 87% of patients were discharged (89% rxb and 85% rxb+dxm; p=0.603). In both groups, there was a significant reduction of CRP, LDH, and Ferritin on day 15. The mortality rate was 9% (no difference in groups; p=0.453), and a higher proportion died for Pseudomonas aeruginosa superinfection in the rxb+dxm group (p< 0.001).

Differences for support oxygen at baseline and discharge

Final health outcomes of patients with severe or critical COVID-19 in a third-level hospital in Mexico

Conclusion

The use of rxb could be considered as a treatment helping clinical improvement in hospitalized patients with severe COVID-19. Combination with dxm apparently did not add clinical benefits. It should be further evaluated.

Disclosures

All Authors: No reported disclosures
557. Trends in Remdesivir Treatment Over the Course of the COVID-19 Pandemic
Authors: Xin Liao J , Lopes Vrishali , Caffrey Aisling
Published: December 2021

Background

Remdesivir is approved for use in the United States for treatment of COVID-19 requiring hospitalization. Real-world data on trends in remdesivir use may elucidate its benefits and place in therapy.

Methods

Hospitalized Veterans with a positive SARS-CoV-2 polymerase chain reaction (PCR) test that were treated with remdesivir at a Veterans Affairs Medical Center from May 2020 to April 2021 were included. Monthly trends in remdesivir treatment, as well as patient characteristics and clinical outcomes among patients treated with remdesivir, were assessed with joinpoint regression to calculate average monthly percent change and corresponding 95% confidence intervals (CI).

Results

A total of 30,333 Veterans were hospitalized with a positive PCR test over the study period, and 13,639 were treated with remdesivir (45%). Throughout the study period, the proportion of Veterans treated with remdesivir increased significantly (4.5% per month, 95% CI 0.5%-8.6%) and median time to remdesivir initiation decreased significantly (12% per month, 95% CI -15.8% to -8.0%). Though demographic characteristics of Veterans treated with remdesivir remained stable, including age, race, and obesity, improvement in clinical outcomes were observed, including median length of hospital stay which decreased by 6.5% per month (95% CI -9.1% to -3.8%), intensive care admissions which decreased by 4.6% per month (95% CI -6.3% to -2.8%) and inpatient mortality which decreased by 6.3% per month (95% CI -9.4% to -3.1%). By April 2021, most patients initiated remdesivir on the day of admission, and the inpatient mortality rate decreased to 7.9% from 19.2% in May 2020.

Conclusion

Over the course of the COVID-19 pandemic, utilization of remdesivir increased while initiation of remdesivir occurred earlier in the hospital admission, with concurrent reductions in length of hospital stay, intensive care admissions, and inpatient mortality.

Disclosures

Aisling Caffrey, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Shionogi, Inc (Research Grant or Support)