bluuebunny/crossref_metadata_2025 huggingface dataset:
318. Beta-lactam Therapeutic Drug Monitoring Improves Attainment of Target Drug Levels in Critically Ill Patients
Authors: Ausman Sara , Braga Shienna , Hagy Natalie T , Rivera (O'Connor) Christina G , Moreland-Head Lindsay , Rebecca Wessel , Abu Saleh Omar M , Rule Andrew D , Gajic ognjen , Barreto Erin F
Published: November 2023

Background

Critically ill patients, particularly those treated with extracorporeal devices or at extremes of weight, experience pharmacokinetic variability which can compromise beta-lactam (BL) antibiotic target attainment and treatment response. Therapeutic drug monitoring (TDM) for BL antibiotics can improve precision pharmacotherapy but has had limited implementation. The objective of this study was to evaluate the frequency of BL target attainment among adult intensive care unit (ICU) patients who underwent TDM.

Methods

This observational study evaluated adults treated with cefepime, piperacillin/tazobactam or meropenem in ICUs at the Mayo Clinic in Rochester, Minnesota who underwent TDM from June-September 2022. During the study timeframe, multidisciplinary teams were encouraged to perform BL TDM on patients requiring extracorporeal membrane oxygenation, continuous kidney replacement therapy, or at an extreme of body weight (weight < 40 kg or >120 kg or BMI < 18 kg/m2 or > 40 kg/m2). Percentage of patients with initial serum trough concentrations within the therapeutic range was calculated (Table 1).

Results

During the study timeframe, 59 trough concentrations were performed on critically ill patients, of which 5 were excluded due to uninterpretable results. Of the remaining 54 BL trough concentrations analyzed, 49 (91%) were initial troughs during the antibiotic course, and 5 (9%) were repeat troughs. Thirty-six (73%) of the initial trough concentrations were within the therapeutic range. Among the trough concentrations outside the therapeutic range, 10 (77%) were too high, and 3 (23%) were too low (Table 2). Dose adjustment occurred in 19 (39%) of initial trough evaluations, including 6 which were adjusted despite a level within the therapeutic range. All of the repeat trough concentrations drawn during the same antibiotic course were within the therapeutic range (n = 5/5; 100%).

Conclusion

One-fourth of initial BL trough concentrations were outside of the therapeutic range. BL levels outside the therapeutic range prompted dose adjustment to improve the potential for effectiveness or limit the potential for toxicity. BL TDM appears to be a promising strategy to enhance precision pharmacotherapy in the critically ill.

Disclosures

Sara Ausman, PharmD, Gilead: Honoraria Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria
330. Outpatient Parenteral Antimicrobial Therapy in People who Inject Drugs
Authors: Hawes Armani , Yanek Lisa , Buresh Megan E , Bodnar Alia , Keller Sara C
Published: November 2023

Background

People with opioid use disorder (OUD) make up a significant and increasing proportion patients requiring outpatient parenteral antimicrobial therapy (OPAT). Many of these patients do not receive OUD treatment during their index hospitalization, leading to missed opportunities for treatment, recurrent hospitalizations, worse outcomes, and increased costs. We describe predictors of addiction medicine consultation among people with OUD requiring OPAT, and the impact of addiction medicine consultation on receipt of medications for opioid use disorder (MOUD) after discharge.

Methods

We reviewed records from 172 patients with OUD who were discharged on OPAT from Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center 4/2020-9/2022. We described differences between those who received and did not receive inpatient addiction medicine consults by demographics, service (medicine vs surgical), type of insurance, type of infection, disposition, and addiction treatment.

Results

The addiction medicine team was consulted for 120 patients and was not consulted for 46 patients. Addiction medicine was more likely to be consulted on younger patients (43.3 years vs 48.3 years, p=0.01), for patients with endovascular infections (23.3% vs 2.3%, p< 0.01) or bloodstream infections (31.9% vs 13.6%, p=0.02), and when the infectious organism was methicillin-resistant Staphylococcus aureus (40.7% vs 20.9%, p=0.02). When the addiction medicine team was consulted, patients were more likely to be discharged on MOUD, specifically buprenorphine (32.5% vs 17.4%, p< 0.01) or methadone (57.5% vs 39.1%, p< 0.01). Overall, most patients were discharged to a skilled nursing facility (SNF), but patients who received addiction medicine team consult were more likely to be discharged to SNF than home (92.9% vs 7.0%, p< 0.01). Patients discharged to SNF were less likely to have a 30 day readmission compared to patients discharged home (14.4% vs 32.0%, p=0.03).

Conclusion

Addiction medicine consultations were associated with an increased likelihood of evidence-based MOUD among patients with OUD requiring OPAT. By maximizing the resources of the addiction medicine team, we hope to improve outcomes for patients with opioid use disorder who require OPAT.

Disclosures

Sara C. Keller, MD, MPH, MSPH, Pfizer: Advisor/Consultant
345. Unaccounted Costs Associated with Different Outpatient Parenteral Antimicrobial Therapy (OPAT) Models of Care
Authors: Player Jacob , Bouzigard Rory , Arnold Mark , Mang Norman S , Hall Brenton , Lane Michael , Perl Trish M , Castellino Laila M
Published: November 2023

Background

OPAT decreases length of stay/inpatient costs while benefiting patients. However, OPAT costs incurred in the ambulatory setting are poorly quantified. We evaluated unaccounted costs and potential savings from OPAT delivered via patient self-administration (S-OPAT), home care agencies/hemodialysis centers (HH-OPAT), and skilled nursing facilities (SNF-OPAT).

Methods

The electronic health record (EHR) for all adult patients discharged on OPAT from Parkland Hospital (PH), a 900-bed safety-net hospital, during April - June 2021 and January - March 2022 was reviewed for the number and duration of antibiotics administered and post-discharge non-billable encounters (defined as an encounter on any day without a corresponding billable visit). Encounters on the day of a billable visit were excluded. Inpatient days avoided were defined as days post-discharge on which the patient received OPAT. An average daily hospital adjusted expense per inpatient day of $3,764 for Texas state hospitals and wholesale acquisition cost data from the Texas Department of State Health Services were used to estimate cost savings from OPAT. 340B pricing was used to calculate the cost of drugs provided to S-OPAT patients by PH. Antibiotics with different formulations were converted to equivalent daily doses and costs were averaged to estimate a daily antibiotic cost. The institutional IRB approved this study.

Results

Of 340 patients, 84 (25%) received SNF-OPAT, 115 (34%) HH-OPAT, and 141 (41%) S-OPAT. There were 255 non-billable encounters in the S-OPAT group, 242 in the HH-OPAT, and 220 in the SNF-OPAT group, with the highest rate per 100 person-days in SNF-OPAT recipients (Table 1), nearly twice that of S-OPAT. Antibiotic costs avoided by discharging patients on OPAT were $383,240 for HH-OPAT patients and $505,588 for SNF-OPAT patients (Table 2). For S-OPAT patients, costs incurred by PH based on 340B pricing were $33,785.

Conclusion

All OPAT care models saved costs compared to hospitalization. Our study likely underestimates the unaccounted costs associated with OPAT; however, costs incurred may be significant and differ between care models. Personnel time and non-billable work should additionally be considered in determining true OPAT cost.

Disclosures

All Authors: No reported disclosures
360. A First-in-Human Study to Assess the Safety, Tolerability, Pharmacokinetics, and Neutralization Profile of Two Long-Acting Anti-SARS-CoV-2 Monoclonal Antibodies
Authors: Asiago Josephat , Albizem Moetaz , Tieu Holly L , Stecco Kathryn , Moullan Norman , Fenwick Craig , Lin Kai , Poffenbarger Lauren , Lengsfeld Thomas , Liu David W , Hock Björn M , Venkayya Rajeev , Bhuyan Prakash
Published: November 2023

Background

COVID-19 remains a significant risk to the immunodeficient population, which is more vulnerable to severe consequences and less likely to mount a protective immune response following vaccination. Monoclonal antibodies (mAbs) have been effective and safe, but the emergence of omicron and its subvariants has created an unmet need for new broadly protective and long-acting agents.

AER001 and AER002 are human immunoglobulin-G1 under development for pre-exposure prophylaxis and treatment of COVID-19. These mAbs were isolated from persons previously infected and/or vaccinated against SARS-CoV-2. AER001 and AER002 bind to the receptor binding domain of the spike protein on non-overlapping epitopes and compete with angiotensin converting enzyme-2 (ACE-2) to block viral attachment. AER002 showed strong in vitro neutralization activity against omicron strains including BA.2.12.1, BA.4 and BA.5.

Methods

The study is a phase I, randomized, double-blind, placebo-controlled, dose escalation study in healthy adults (n=80) with a primary objective to evaluate the safety and tolerability of the combination of AER001 and AER002 or AER002 alone vs placebo, administered intravenous with dose ranging (100 mg to 1200 mg). The secondary objectives are to assess pharmacokinetics (PK)s, anti-drug antibodies (ADA)s, and neutralization activity levels and safety evaluation through 6-months of follow-up.

Results

As of 21 March 2023, enrolment was completed. A total of 154 adverse events (AE)s were reported in 62 subjects. Most frequent AEs were infusion-related site reactions (IRSRs) 20.13% (31/154), headache 16.23% (25/154) and common cold 10.39% (16/154). Most (98.7%) of the reported AEs were grade 1 (mild) severity. There were no serious adverse events (SAE)s or ADAs and 2 non-AE-associated discontinuations. Only 1.3% (2/154) AEs (IRSRs, erythema and tenderness) were rated as possibly related to the investigational products by the principal investigator.

Conclusion

Based upon preliminary data, AER001 and AER002 show adequate safety with no SAEs or ADAs. Complete safety and PK data through 6 months will be presented at the meeting.

Disclosures

Moetaz Albizem, MD, Regeneron: Stocks/Bonds Norman Moullan, PhD, Aerium Therapeutics: Stocks/Bonds Kai Lin, PhD, Aerium Therapeutics: Employee
391. Patients Hospitalized for Acute Coronary Syndrome with Concomitant COVID-19 have Worse Clinical Outcomes
Authors: Sharath Deepali Boothankad , Khokhlov Leonid , Thapa Usha , Aboelnasr Amr , Pereira Leanne , Improvola Jose , Patel Anar
Published: November 2023

Background

Since the onset of the global pandemic caused by COVID-19, there has been a multitude of studies that demonstrate the association between COVID-19 infection and adverse clinical outcomes. To date, there is a paucity of evidence showing how COVID-19 affects morbidity and mortality among patients admitted with cardiac events in large heterogeneous populations. We aimed to investigate the clinical outcomes in patients hospitalized with acute coronary syndrome (ACS) with co-existing COVID-19 infection using the National Inpatient Sample.

Methods

We queried the Nationwide Inpatient Sample (NIS) database for the year 2020 for adult patients who were hospitalized with ACS with a concomitant diagnosis of COVID-19. The primary outcome was inpatient mortality. The secondary outcomes measured were cardiogenic shock, cardiac arrest, severe sepsis, invasive mechanical ventilation, length of stay (LOS), and total hospital cost. Multivariable logistic and Poisson regression analyses were used to estimate clinical outcomes. The p-value < 0.05 was significant.

Results

There were 582,424 hospitalizations with ACS, of which 6,074 (1.1%) had COVID-19 infection. Patient characteristics are shown in Table 1. Patients with comorbid COVID-19 infection had significantly higher mortality and worse clinical outcomes (Table 2 and Figure 1).

Conclusion

Patients hospitalized with ACS and concomitant COVID-19 infection had a significantly increased risk for adverse clinical outcomes and higher resource utilization. They were younger, female, with more prevalent STEMI, acute myocarditis, PE, DM, AKI, and stroke. COVID-19 infection in the setting of ACS was associated with higher mortality and poor outcomes including cardiogenic shock and cardiac arrest as well as respiratory failure requiring mechanical ventilation. Further research to elucidate the correlation between COVID-19 infection and cardiac events is needed.

Disclosures

All Authors: No reported disclosures
393. Comparison of COVID-19 Associated Complications in Children during the First and Second Omicron Waves in Taiwan
Authors: Chen Jiun-An , Lai Huan-Cheng , Hsu Yu-Lung , Lin Hsiao-Chuan , Lin Chien-Heng , Wei Hsiu-Mei , Low Yan-Yi , Chiu Yu-Ting , Hwang Kao-Pin
Published: November 2023

Background

In early 2022, the Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Taiwan and caused two waves of COVID-19 outbreaks throughout the year. The emergence of the Omicron variant in Taiwan has led to an increased incidence of COVID-19 associated complications in children. This study aims to compare COVID-19 associated complications in children admitted during the peak of the first wave (late May, 2022, BA.2 predominance) and the second wave (early October, 2022, BA.5 predominance) of the Omicron-driven outbreaks in Taiwan.

Methods

This retrospective, single-center, observational study was conducted at China Medical University Children's Hospital (CMUCH), a tertiary hospital in central Taiwan. The study population included children under 18 years of age who were admitted with a confirmed SARS-CoV-2 infection between May 1 and October 31, 2022. Medical records of these children were collected. The study period was divided into two periods based on the peak of the outbreak: May 1 to June 30, 2022 and September 1 to October 31, 2022. During these periods, the COVID-19 associated complications of hospitalized children were compared.

Results

A total of 228 pediatric patients with SARS-CoV-2 infection were included, with 145 (63.6%) from the first wave and 83 (36.4%) from the second wave. The median age (IQR) was similar between the two waves [18 (6-43) months vs. 16 (5-62) months, p = 0.796]. The proportion of patients with underlying comorbidities was similar between the two waves (7.6% vs. 12.1%, p = 0.262). Patients in the second wave had a lower ICU admission rate (16.6% vs. 9.6%, p = 0.148). The proportion of patients with bacterial coinfection was higher in the second wave (15.9% vs. 24.1%, p = 0.126). The proportion of patients with febrile convulsion (13.8% vs. 16.9%, p = 0.531), myositis (5.5% vs. 2.4%, p = 0.334), and croup (11.0% vs. 16.9%, p = 0.148) were similar between the two waves.

Conclusion

There was no significant difference in the frequency of admission for COVID-19 associated complications between the BA.2 and BA.5 predominance periods. However, it was observed that children admitted during the second wave had a lower rate of ICU admission and a higher rate of bacterial coinfection.

Disclosures

All Authors: No reported disclosures
404. Impact of cross-coronavirus humoral immunity in post-acute sequelae of COVID-19 in systemic autoimmune rheumatic diseases patients
Authors: Herman Jonathan , Atyeo Caroline , Zur Yonatan , Cook Claire , Patel Naomi , Vanni Kathleen , Kowalski Emily , Qian Grace , Srivatsan Shruthi , Shadick Nancy , Rao Deepak , Kellman Benjamin , Mann Colin , Lauffenburger Douglas A , Wallace Zachary , Sparks Jeffrey , Alter Galit
Published: November 2023

Background

Beyond the acute illness caused by SARS-CoV-2, about one-fifth of infections unpredictably result in long-term persistence of symptoms despite the apparent clearance of infection. Insights into the mechanisms that underlie post-acute sequelae of COVID-19 (PASC) will be critical for the prevention and clinical management of long-term complications of COVID-19. Several hypotheses have been proposed that may account for the development of PASC, including persistence of virus or the dysregulation of immunity. Among the immunological changes noted in PASC, alterations in humoral immunity have been observed in some patient subsets.

Methods

To begin to determine whether SARS-CoV-2 or other pathogen specific humoral immune responses evolve uniquely in PASC, we performed comprehensive antibody profiling against SARS-CoV-2, a panel of endemic pathogens, and a panel of routine vaccine antigens using Systems Serology in two independent cohorts of patients with pre-existing systemic autoimmune rheumatic disease (SARD) who either developed or did not develop PASC.

Results

A distinct qualitative shift observed in Fcγ receptor binding was observed in individuals with PASC. Specifically, individuals with PASC harbored weaker Fcγ receptor binding anti-SARS-CoV-2 antibodies and a significantly stronger Fcγ receptor binding antibody response against endemic Coronavirus OC43. Individuals with PASC, further, generated more avid IgM responses and developed an OC43 S2-specific antibody response with stronger Fcγ-receptor binding, linked to cross reactivity across SARS-CoV-2 and common coronaviruses.

Conclusion

These findings from two independent cohorts implicate previous common Coronavirus imprinting as a marker for the development of PASC in individuals with SARDs.

Disclosures

Douglas A. Lauffenburger, PhD, Sanofi: Board Member|Sanofi: Honoraria|Sanofi: Honoraria Zachary Wallace, MD, MSc, Bristol-Myers Squibb: Grant/Research Support|Horizon: Advisor/Consultant|MedPace: Advisor/Consultant|Principia/Sanofi: Grant/Research Support|Sanofi: Advisor/Consultant|Shionogi: Advisor/Consultant|Viela Bio: Advisor/Consultant|Zenas BioPharma: Advisor/Consultant Jeffrey Sparks, MD, AbbVie: Advisor/Consultant|Amgen: Advisor/Consultant|Boehringer Ingelheim: Advisor/Consultant|Bristol Myers Squibb: Advisor/Consultant|Bristol Myers Squibb: Grant/Research Support|Gilead: Advisor/Consultant|Inova Diagnostics: Advisor/Consultant|Janssen: Advisor/Consultant|Optum: Advisor/Consultant|Pfizer: Advisor/Consultant Galit Alter, PhD, Leyden Labs: Ownership Interest|Moderna Therapeutics: Employee|Seromyx Systems: Ownership Interest
422. Impact of Respiratory Virus Co-Infection in Pediatric COVID-19
Authors: Mareboina Manvita , Bakhl Katrina , Fisher James , Jassal Simrat , Ericson Jessica E , Gavigan Patrick
Published: November 2023

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a viral infection that emerged in December 2019, leading to the COVID-19 pandemic. Despite significant research, there are still significant knowledge gaps, particularly with regards to COVID-19 in children and the impact of respiratory virus co-infection.

Methods

A retrospective chart review was conducted at Penn State Children’s Hospital including children who tested positive for SARS-CoV-2 by multiplex polymerase chain reaction from nasopharyngeal swabs between March 2020 and June 2022. Demographics, symptoms, clinical features, and treatments of patients who tested positive for SARS-CoV-2 alone were compared to those who had co-detection of another respiratory virus.

Results

A total of 464 episodes of SARS-CoV-2 detection were included, with 123 (26.5%) involving of co-detection of another respiratory virus. Patients with viral co-detection more commonly presented with upper respiratory tract infection (URI) symptoms and, cough, and were more likely to require any supplemental oxygen therapy. However, there were no differences in rates of mechanical ventilation, intensive care unit admission, mortality, or receipt of SARS-CoV-2 specific antivirals [Table 1]. Co-detections occurred throughout the study period [Figure 1]. Of the 123 episodes of viral co-detection, 99 (80.5%) had one other virus detected. The most commonly co-detected virus was rhino/enterovirus, which was found in 100 (81.3%) of the co-detection episodes.

Outcomes of SARS-CoV-2 and Viral Co-Detection

Numbers of SARS-CoV-2 and Viral Co-Detections

Conclusion

This study provides insight into the impact of respiratory virus co-infections in pediatric COVID-19. Co-infection was more often associated with URI symptoms, but otherwise appeared clinically similar to SARS-CoV-2 mono-detection. Additionally, while children with co-infection more often needed any supplemental oxygen, there were no differences with regard to other markers of clinical severity. As SARS-CoV-2 continues to circulate with other respiratory viruses, ongoing studies will be needed to determine if alternative treatment strategies are needed.

Disclosures

Jessica E. Ericson, MD, MPH, Abbvie: Advisor/Consultant
442. Unveiling Factors Associated with Mortality in Mucormycosis Patients: Insights from Second and Third Waves of COVID-19 Pandemic in India
Authors: Sharma Vagisha , Kriplani Kushal , Tuli Isha Preet
Published: November 2023

Background

Mucormycosis is one of the most aggressive opportunistic fungal infections. Though conventionally limited to the demographics of immunocompromised and those on the diabetes spectrum. It has recently propelled to the frontline in investigations of COVID-19 complications. For patients present in varied stages and severity of Mucormycosis, it's crucial to discuss the presenting factors that impact mortality in order to provide more intensive care and treatment from the beginning to those more at risk of death.

Methods

All patients presenting to a tertiary care hospital in New Delhi, India with clinicopathological confirmed Mucormycosis were enrolled in the study. Detailed history and physical examination were performed, and a questionnaire of patient demographic details and comorbidities was filled out.

Results

There were 75 patients who met the inclusion criteria and were assessed after obtaining informed consent. Of these 75, 64 patients survived. The most common comorbidity in the study population was Diabetes spectrum(89.33%), followed by antecedent COVID-19 infection(64%) and hypertension(12%). Despite a high prevalence, none of these was significantly associated with mortality. The only comorbidity associated with mortality was Coronary Artery Disease(p-value< 0.05). The symptomatology at presentation was also assessed. Most commonly reported symptoms at presentation were Orbital/facial edema(45.33%), nasal discharge(29.33%), nasal block(29.33%) and diminution of vision(26.66%). The presence of proptosis at presentation in the patient was found to be significantly associated with a mortality outcome(p-value< .0.05). The glycemic control at presentation was also measured and compared between the survivors and non-survivors, however, no significant association was found.

Mucormycosis patient with Proptosis

Conclusion

Mucormycosis patients with presenting symptoms of proptosis should be prognosticated early and managed in the intensive care unit from the beginning due to the increased risk of mortality. Also, patients with coronary artery disease should be similarly given special attention and care due to the association with mortality. Other factors like antecedent COVID-19, diabetes, hypertension, tobacco and alcohol use and the extent of hyperglycemia do not impact patient outcome

Disclosures

All Authors: No reported disclosures
445. An Ongoing Battle from a Forgotten War: Long COVID in Mississippi, October 2021 - September 2022
Authors: Staneva Manuela , Dobbs Thomas
Published: November 2023

Background

Due to the lack of a well-established definition, long COVID—unlike its acute counterpart—has been evading statewide surveillance systems. In October 2021, however, the adoption of an ICD-10-CM code for long COVID, created the prerequisite needed for such retrospective state-level surveillance of long COVID. To seize this opportunity and establish baseline information, we used Mississippi’s hospital discharge data to examine hospitalizations associated with long COVID.

Methods

Hospital discharge data are a population-level data source that captures data from all non-federal hospitals in the state and contains information on diagnoses, procedures, and resource utilization. In this cross-sectional study, we utilized the latest available data that incorporates long COVID diagnoses (10/01/2021-09/30/2022). The study included only adult Mississippi residents (≥ 18 years) and the unit of analysis was individual patients. We performed descriptive and inferential (chi-squared tests) statistical analyses.

Results

Among the 1,213 patients hospitalized with post-COVID-19 complications, the majority were white (69.7%), elderly (average age = 66), rural residents (60.3%), and females (53.8%). The most common comorbidities were hypertension (73.6%), diabetes (39.4%), chronic pulmonary disease (28.4%), and congestive heart failure (28.4%). Among long haulers, 22.1% were admitted to ICU, 13.6% needed respiratory support, and 8.5% died in the hospital. The in-hospital mortality proportion among long haulers did not differ by race, residence, or insurance status. In-hospital deaths were more likely to occur, however, among patients ≥ 65 years (68.7% vs. 56.3%, p < .01). Compared to survivors, deceased patients with long COVID had a slightly higher average number of comorbid conditions (2.8 vs. 2.2). For patients with long COVID, the mean length of stay was 11 days and the mean hospital charges were $109,739.

Conclusion

In our study, we identified that hypertension was highly prevalent among long haulers. The severity of illness as measured by ICU care, in-hospital mortality, length of stay, and hospital charges was also high among patients with long COVID. These findings underscore the importance of long-term surveillance of COVID-19 complications.

Disclosures

All Authors: No reported disclosures
454. How Useful is SARS-CoV-2 Antigen Detection in Individuals Admitted to the Hospital With no Respiratory Symptoms?
Authors: Prince Monique A , Aiman Wajeeha , Owolabi Modupeoluwa , Muhanna Alaa , Martin Evans , Hessell Joe , Slim Jihad
Published: November 2023

Background

Clinical findings and laboratory data have been crucial for timely diagnosis and transmission reduction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes Coronavirus disease (COVID-19). We have observed an increase in incongruent same day antigen and reverse transcription polymerase chain reaction (RT-PCR) results in all patients presenting to the hospital. This study aims to correlate SARS-CoV-2 test results with the presence of respiratory symptoms and to find the significance of performing the antigen screening test.

Methods

We conducted a single-center retrospective study, using electronic medical records of adults over 18 years of age who were tested routinely for COVID-19 with the Lyra SARS-CoV-2 RT-PCR Assay and the QuickVue SARS Antigen Test on presentation for any complaint from February 2022 to January 2023. We included all the patients who had a positive rapid antigen or RT-PCR test for COVID-19 admitted to the medical, or psychiatry unit. Patients admitted to the intensive care unit (ICU) or cardiac care unit (CCU) or those who returned a negative antigen and RT-PCR test were excluded from our study. We used the R software program to find the relative risk of pneumonia in these patients and performed pooled analysis with the random effects model.

Results

Overall, 178 adults were identified with at least one test positive and were divided into three groups. In patients with positive antigen and negative RT-PCR test 20.8% had respiratory symptoms while 79.1% did not. In patients with negative antigen and positive RT-PCR, 32% had respiratory symptoms and 68% did not. In the group that returned positive for both antigen and RT-PCR tests, only 40% had respiratory symptoms and 60 % did not. Fig. 1 demonstrates the relative risk (RR) of pneumonia (PNA) in all three groups which is less than 1.Figure 1Demonstrates the relative risk of pneumonia in patients who returned a positive COVID-19 testAg-Antigen PCR- Polymerase Chain Reaction Sx-Presence of Respiratory Symptoms Asx- Abscence of Respiratory Symptoms

Conclusion

The relative risk of COVID-19 pneumonia is low in all three groups including those with a positive RT-PCR test, therefore COVID-19 antigen tests are not necessary until patients have severe respiratory symptoms or confirmed exposure. There is an ongoing need for clear guidelines for reliable detection of infection in hospitalized patients.

Disclosures

Jihad Slim, MD, FACP, ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support
461. COVID-19 Hospitalizations among Vaccinated and Unvaccinated Immunocompromised Children, 23 States, December 2022 – April 2023
Authors: Campbell Angela P , Zambrano Laura D , Newhams Margaret M , Wu Michael J , Simeone Regina , Orzel Amber , Halasa Natasha B , Fleming-Dutra Katherine E , Randolph Adrienne G
Published: November 2023

Background

Immunocompromised (IC) persons are at increased risk of severe COVID-19 and can have a suboptimal immune response to a primary 2-dose COVID-19 vaccine series; thus, vaccination recommendations for IC persons include additional COVID-19 vaccine doses. We describe outcomes and vaccination status among US IC children hospitalized with laboratory-confirmed COVID-19 during a period of SARS-CoV-2 Omicron circulation.

Methods

Children with and without an IC condition hospitalized for COVID-19 were enrolled as case-patients into a vaccine effectiveness investigation as part of the Overcoming COVID-19 network of 31 hospitals across 23 states. Data on IC conditions abstracted from the medical record included the presence of an “active or prior oncologic disorder” or a “non-oncologic immunosuppressive disorder.” Results for IC case-patients with COVID-19 enrolled from 12/18/2022–4/3/2023 (Omicron period) were analyzed by age group and vaccination status.

Results

Of 239 IC case-patients, 127 (53%) had an oncologic disorder and 112 (47%) non-oncologic; 120 (50%) had > 1 additional underlying medical condition (Table 1). Thirty (13%) IC case-patients were aged 8 months–4 years, 115 (48%) 5–11 years, and 94 (39%) 12–18 years. Life-threatening illness or death occurred in 1 (3%) IC case-patient aged 8 months–4 years, 8 (7%) aged 5–11 years , and 13 (14%) aged 12-18 years (including 2 deaths). Among 209 IC case-patients aged 5–18 years, 26 (23%) of those with oncologic and 27 (28%) with non-oncologic disorders had received 2 doses of a monovalent primary COVID-19 vaccine series; 6 (5%) and 14 (14%) had received > 3 doses, respectively (p=.03; Table 2). A significantly higher proportion of IC case-patients (n=73/209; 35%) had received at least 2 COVID-19 vaccine doses compared with non-IC patients (n=284/1021; 28%; p=0.04; Table 2).

Conclusion

During Omicron, immunocompromised children hospitalized for COVID-19 were more frequently aged > 5 years and > 99% survived. Vaccination coverage was low among all case-patients. A higher proportion of IC children who received >2 vaccine doses were among those case-patients hospitalized for COVID-19 compared with non-IC children. Additional doses to improve protection in IC children are recommended.

Disclosures

Regina Simeone, PhD, Pfizer: Stocks/Bonds Natasha B. Halasa, MD, MPH, Merck: Grant/Research Support|Quidell: Grant/Research Support|Quidell: donation of kits|Sanofi: Grant/Research Support|Sanofi: vaccine support
472. The impact of sarcopenia on unfavorable outcomes in lung transplant patients with COVID-19
Authors: Han Min , Lee Jung Ah , Jeong Su Jin , Kim Jung Ho , Ahn Jin Young , Choi Jun Yong , Ku Nam Su , Yeom Joon-sup
Published: November 2023

Background

Coronavirus disease 2019 (COVID-19) in immunocompromised patients has become an important issue owing to the high transmissibility of the Omicron variant of severe acute respiratory syndrome coronavirus 2. Sarcopenia in lung transplant patients is associated with a poor prognosis, and lung transplant patients are more vulnerable to COVID-19. However, the effect of sarcopenia on lung transplant patients with COVID-19 remains unclear. This study aimed to investigate the effect of sarcopenia on lung transplant patients with COVID-19 and the risk factors for sarcopenia following COVID-19 in lung transplant patients.

Methods

We performed a retrospective cohort study of lung transplant patients with COVID-19. Sarcopenia was defined as being within the lower 25% of the thoracic muscle index based on cross-sectional area measurements of the pectoralis, paraspinal, serratus, and latissimus muscles at the fourth vertebral using computed tomography (CT). Multivariable logistic analysis was conducted to identify the factors associated with sarcopenia in lung transplant patients following COVID-19.

Results

Of the 445 patients receiving follow-up care after lung transplantation, 81 were diagnosed with COVID-19. The median age was 59.0 (interquartile range 48.0–64.0) years, and 55 (67.9%) patients were male. Among patients within three years of lung transplantation, the sarcopenic group had a significantly higher rate of hospitalization (100.0% and 46.9%, P = 0.006) and oxygen demand (63.6% and 18.8%, P = 0.016) than the non-sarcopenic group. Multivariable analysis showed that body mass index before COVID-19 [odds ratio (OR), 0.77; confidence interval (CI), 0.58–0.96; P = 0.040] and serum albumin (OR, 0.12; CI, 0.01–0.79; P = 0.047) were associated with sarcopenia after COVID-19.Table 1.Comparing characteristics of lung transplant patients according to pre-COVID-19 sarcopenia statusTable 2.Comparing muscle index and outcome of COVID-19 in lung transplant patients according to pre-COVID-19 sarcopenia status

Conclusion

Sarcopenia was associated with poor outcomes of COVID-19 in patients within three years of lung transplantation. Low albumin levels and body mass index were identified as risk factors for post-COVID-19 sarcopenia. Assessments and interventions for sarcopenia are needed to improve the prognosis of lung transplant patients with COVID-19.

Disclosures

All Authors: No reported disclosures
481. Trends in SARS-CoV-2-related Pediatric Hospitalizations in the Canadian Nosocomial Infection Surveillance Program, March 2020 to December 2022
Authors: Lee Diane , Mitchell Robyn , Pelude Linda , Frenette Charles , Lee Bonita , Lefebvre Marie-Astrid , Comeau Jeannette L , Srigley Jocelyn , Thampi Nisha
Published: November 2023

Background

National surveillance can provide insights into trends in pediatric SARS-CoV-2-related hospitalizations during the pandemic and healthcare-associated infections.Figure:Proportion of all pediatric hospitalizations by age group and wave

Methods

From March 1, 2020, to December 31, 2022, the Canadian Nosocomial Infection Surveillance Program collected patient-level data on pediatric patients (under age 18 years) hospitalized with laboratory-confirmed SARS-CoV-2 from 9 pediatric and 25 mixed adult-pediatric hospitals. Pediatric COVID-19 vaccines became available for 12-17 years in May 2021 and for 5-11 years in November 2021.

Results

Of 4,878 pediatric patients, most (80.3%) were hospitalized with SARS-CoV-2 infection during the Omicron-dominant period (since Jan 2022); a higher proportion involved patients under five years of age (58.5% vs 46.9%, p < 0.001). Most hospitalizations pre-Omicron involved children not vaccinated against COVID-19 (92%) versus 70% during Omicron (p < 0.001). However, a lower proportion required intensive care during Omicron (15% vs 20%, p < 0.001). There was no difference in pre-existing comorbidities or mortality between periods.

Overall, there were 257 healthcare-associated COVID-19 infections (HA-COVID) reported (5.4%); 89% occurred during Omicron. While there was no difference in median ages of patients with HA-COVID and community-associated COVID-19 infections (CA-COVID), 62% of patients with HA-COVID had a pre-existing comorbidity compared to 44% with CA-COVID (p < 0.001), and 24% remained in hospital at 30 days after HA-COVID, compared to 2.2% with CA-COVID (p < 0.001). Nearly 50% of patients with HA-COVID had received at least one vaccine dose, compared to 25% with CA-COVID.

Conclusion

During the Omicron-dominant period, a higher proportion of admitted patients with SARS-CoV-2 infection were under five years, but a lower proportion were unvaccinated and a lower proportion required intensive care and mortality was comparable between both periods. Only 5.4% of pediatric COVID-related hospitalizations were HAI, with most during Omicron. Patients with HAI were more likely to have a pre-existing comorbidity and increased hospital stay, potentially related to their underlying conditions.

Disclosures

All Authors: No reported disclosures
486. Phenotypic Clusters of Clinical Presentation and Severity Among Children with Multisystem Inflammatory Syndrome — United States, February 2020–October 2022
Authors: Ma Kevin , Yousaf Anna R , Lindsey Katherine N , Melgar Michael , Miller Allison D , Shah Ami B , Wu Michael J , Campbell Angela P , Zambrano Laura D
Published: November 2023

Background

Multisystem inflammatory syndrome in children (MIS-C) is an uncommon but severe hyperinflammatory syndrome occurring weeks after SARS-CoV-2 infection. Presentation can vary and overlap with other conditions, including acute COVID-19 and Kawasaki disease. Identifying clusters of MIS-C phenotypes informs efforts to reduce misclassification, characterize pathogenesis, and tailor treatments. Here we describe clusters of presentation using the largest collection of U.S. MIS-C cases to date.

Methods

We analyzed 9131 MIS-C cases reported to CDC from 55 U.S. health departments; onset dates ranged from February 2020–October 2022. Thirty-one dichotomous clinical variables were selected for clustering after excluding ones with high (≥ 15%) missingness or rare (≤ 10%) or high (≥ 90%) prevalence. We excluded 595 cases with ≥ 5 missing variables and conducted multiple imputation on the remaining 8536 cases. Latent class analysis (LCA) was run using the poLCA R package; the number of clusters was selected based on decreasing information criteria and automated variable selection.

Results

LCA identified five clusters, two of which were characterized by distinct organ system involvement: a respiratory symptom-driven cluster primarily affecting older children (N = 483 [5.7% of cases]; median age 14.4 years), and a mucocutaneous symptom-driven cluster primarily affecting young children (N = 1956 [22.9%]; median age 5.8 years) (Fig. 1). The remaining three clusters delineated a spectrum of clinical severity, with clinically mild and moderate clusters with infrequent shock (N = 2566 [30.0%] and N = 1650 [19.3%], respectively), and a severe cluster (N = 1881 [22.0%]) with shock and ICU admission for nearly all cases (Fig. 2). The proportion of cases belonging to this clinically severe cluster decreased over time as proportions of the mild/moderate clusters increased (Fig. 3). The case fatality ratio was highest in the respiratory (5.0%) and clinically severe clusters (1.6%) compared with other MIS-C cases (0.2%; P < 0.001).Figure 1.Prevalence of respiratory and mucocutaneous/dermatologic symptoms for the respiratory and mucocutaneous clusters compared to all other MIS-C cases.Figure 2.Prevalence of organ system involvement, shock, and ICU admission for the three severity-defined clusters.Figure 3.Proportions of MIS-C cases by LCA-inferred cluster and month (primary y-axis); number of monthly MIS-C cases (secondary y-axis).

Conclusion

MIS-C cases reported to CDC national surveillance clustered into five groups with distinct symptoms and severity. Use of MIS-C phenotypic clusters in future studies may inform treatment decisions and assist with prognosis.

Disclosures

All Authors: No reported disclosures
492. Risk Factors for COVID-19 Mortality in ≥90 year old Inpatients: Retrospective Case Series
Authors: Pineda Raphaela Martina C , Castro Monica , Boy Gerald Kristoffer E , Pant Sushil
Published: November 2023

Background

Despite what we know about COVID-19, current literature is still lacking on some aspects of the disease. This is probably because the disease continues to evolve and there is still much to discover. COVID-19 outcomes in the elderly is one aspect that has not been fully explored.

This study investigated short-term outcomes of COVID-19 Infection on ≥90 year old patients in the context of COVID vaccination availability. We sought to identify risk factors for in-patient all-cause mortality during the peak of daily COVID-19 infections in this population.

Methods

52 admitted patients aged ≥90 years old with SARS-CoV-2 RT-PCR positive observed from Nov 2021 to Mar 2022 at New Rochelle Hospital in NY, USA.

We conducted a retrospective case study of ≥ 90 years old patients admitted at New Rochelle Hospital in NY, USA from Nov 2021 to Mar 2022. Electronic health records were reviewed.

Logistic regression was used to determine odds ratio for risk factors that contribute to COVID-19 mortality. Univariate analysis was used to analyze patients’ comorbidities, symptoms, lab abnormalities, and imaging with mortality as the independent variable.

Results

The most frequent risk conditions for COVID-19 mortality are congestive heart failure (p< 0.048) and atrial fibrillation (p< 0.009). The odds of dying from COVID19 is 5 times greater for nursing home residents than those patients residing at home or already admitted in the hospital. Shortness of breath and fever were found to be statistically significant with COVID 19 mortality. Patients who had x-ray results typical for COVID (p< 0.004), leukocytosis (p< 0.039), acute kidney injury (p< 0.003), and elevated transaminases (p< 0.001) are more at risk for dying from COVID.

Conclusion

Managing elderly individuals with COVID-19 can be challenging due to increased risk of severe illness and complications associated with age. We found that certain risk factors such as co-morbidities, previous residence, presenting symptoms and laboratories are associated with increased mortality in patients ≥ 90 years old. Currently, limited guidelines and studies are available for the geriatric population. Further research can be done by stratifying severity of comorbidities, determining vaccination status, and increasing sample size.

Disclosures

All Authors: No reported disclosures
494. Real-world effectiveness of tixagevimab/cilgavimab for COVID-19 pre-exposure prophylaxis in solid organ transplant recipients during the Omicron variant period
Authors: Rojanakit Gun , Kiertiburanakul Sasisopin , Boongird Sarinya , Sutharattanapong Napan , Yingchoncharoen Teerapat , Sobhonslidsuk Abhasnee , Bruminhent Jackrapong
Published: November 2023

Background

Pre-exposure prophylaxis (PrEP) with a combination of long-acting monoclonal antibodies with tixagevimab/cilgavimab (T/C) have provided viral neutralizing activity against SARS-CoV-2 and protected solid organ transplant recipients (SOTRs) that produced poor immunogenicity after COVID-19 immunization. However, real-world data on the effectiveness and safety of T/C in SOTRs during the Omicron wave is limited.

Methods

A prospective study at a single transplant center was conducted to evaluate the effectiveness and adverse events (AE) of T/C among SOTRs during the BA.2.75 Omicron lineages period (August 2022 to February 2023). T/C of 150/150 and 300/300 mg doses were provided from August 2022 to December 2022 and after, respectively.

Results

A total of 39 SOTRs comprising kidney (n= 29), liver (n=2), and heart (n=8) transplant recipients were included in the study. Thirty-three (85%) and 6 (15%) SOTRs received 150/150 and 300/300 mg of T/C, respectively. The median (IQR) age was 52 (35-62) years. Twenty-two (56%) had a prior history of COVID-19. The median (IQR) number of COVID-19 vaccine was 4 (3-4) doses. During the median follow-up of 6.35 (5-8.33) months, COVID-19 developed in 5 (12.8%) out of 39 SOTRs with a median (IQR) time of 73 (36-115) days from receiving T/C. None of those who received a 300/300 mg dose developed COVID-19. There was no severe COVID-19 or death observed. Five (12.8%) SOTRs reported mild and reversible AEs with pain at injection (n=2), fever (n=3), and muscle aches (n=1). There was no allograft rejection reported.

Conclusion

Breakthrough SARS-CoV-2 infection remains among fully vaccinated SOTRs receiving T/C as PrEP and subjects to concurrent circulating strain in the community. However, the disease severity appears mild, and the short-term safety profile seems tolerable.

Disclosures

All Authors: No reported disclosures
500. Durability of antibody response after booster vaccination against SARS-CoV-2 in kidney transplant recipients with or without prior infection
Authors: Ueaphongsukkit Thornthun , Banjongjit Athiphat , Avihingsanon Yingyos , Udomkarnjananun Suwasin , Townamchai Natavudh , Jutivorakool Kamonwan , Vanichanan Jakapat
Published: November 2023

Background

Kidney transplant recipients (KTR) are at increased risk of severe COVID-19 infection due to their immunosuppressive drugs. COVID-19 vaccination is recommended to prevent infection and severe illness. However, the knowledge on the durability of vaccine response and appropriate timing of booster vaccination is not well established. This study aimed to evaluate the anti-SARS-CoV-2 S antibody response > 12 weeks after the fourth vaccination and to identify factors associated with a good antibody response in KTR.

Methods

This single-center cross-sectional study was conducted at King Chulalongkorn Memorial hospital in Bangkok, Thailand between January and April 2023. It enrolled adult KTR who had been transplanted for more than 6 months and had received the fourth COVID-19 vaccine dose for more than 12 weeks. KTR with prior long acting antibody (LAAB) were excluded. Baseline characteristics, laboratory data, COVID-19 vaccine certificates, and history of prior infection were collected. Blood samples were taken at enrollment for anti-SARS-CoV-2 S antibody testing (Elecsys®, Cobas e 411 analyzer; Roche Diagnostics, Basel, Switzerland). An antibody level ≥ 1,000 BAU/mL was considered a high sustained response. All statistical analyses were performed using Stata 15.1 (Stata Corp., College Station, TX, USA).

Results

A total of 132 KTR were enrolled. The median age was 52 years, and 60% were male. Most KTR received two doses of viral vector vaccine as their first two primary shots with two doses of mRNA vaccine as the additional primary and booster shots. The overall anti-SARS-CoV-2 S antibody level was 4,917 (IQR 884.4 – 16,888.5) BAU/mL at the median of 261.5 (IQR 202 – 297.5) days since last vaccination. There were 96 (73%) of KTR with antibody level ≥ 1,000 BAU/mL. Baseline characteristics were shown in Table 1. History of COVID-19 infection was significantly associated with a good antibody response after multivariate logistic regression analysis with adjusted OR of 3.87 (95% CI 1.64 – 9.08) (Figure 1).

Conclusion

This study showed a high anti-SARS-CoV-2 S antibody response in KTR after the 4th vaccine dose, with 73% achieving a good response at > 6 months. Prior COVID-19 infection was associated with a good antibody response, indicating role of hybrid immunity among this patient population.

Disclosures

All Authors: No reported disclosures