bluuebunny/crossref_metadata_2025_split huggingface dataset:
384. Invasive aspergillosis in COVID-19 patients in an intensive care unit in Mexico City
Authors: Velez-Pintado Mariana , Aguilar-Soto Mercedes , Camiro Antonio , Cuenca-Abruch Dalia , Pérez-Doramae Renzo Alberto , Crabtree-Ramirez Brenda , Mercado-Atri Moises 
Published: January 2021

Abstract

Background
An elevated incidence of invasive pulmonary aspergillosis (IPA) in patients with COVID-19 without traditional risk factors for IPA has been recently reported around the world. This co-infection has been described in patients requiring treatment in an intensive care unit. The risk factors for its development are still unclear.

Methods
We conducted a nested case-control study using the COVID-19 registry of the ARMII study group, based in the Centro Médico ABC, a private hospital in Mexico City. We included all patients that required admission to the intensive care unit (ICU) from March 12 to June 15, 2020, and excluded patients without serum galactomannan measurements or bronchial secretion cultures. We used the modified definition of IPA proposed by Schauwvlieghe et al for IPA in influenza patients. The control group was formed by patients with ruled-out IPA (negative galactomannan and secretion cultures). We compared both groups to identify risk factors for IPA using the chi-squared test or the Mann-Whitney U test as applicable.

Results
Out of a total 239 patients, 54 met the inclusion criteria. We identified 13 patients with IPA (24.07%) that met the definition of IPA (2 with positive cultures and 11 with positive galactomannan) and 41 without IPA. Only three patients with IPA had important comorbidities (COPD, chronic kidney disease, and HIV). Patients with IPA tended to have a higher median age (64.6 vs 53.59, p=0.075) and a higher serum glucose at their arrival (145 vs 119, p=0.028). All patients with IPA presented to the hospital with ARDS (100% vs 72.5%, p=0.034), but ultimately did not have a higher requirement for mechanical ventilation (100% vs 82.93%, p=0.110). There were no statistical significant differences in use of Tocilizumab, use of glucocorticoids, mortality (23.07% vs 17.50%, p=0.563) or length of stay.

Conclusion
It has been previously described that patients with acute respiratory disease syndrome triggered by viral infection, like the influenza virus, are prone to invasive aspergillosis even in the absence of underlying immunodeficiency. The use of antifungals to prevent aspergillosis in COVID-19 patients should be assessed because of the gravity presented in the patients with this co-infection.

Disclosures
All Authors: No reported disclosures
388. Multidrug Resistant Gram Negative Organisms Prevalence in Hospitalized Patients in an Italian Tertiary Level Hospital During COVID-19 Pandemia: First Detection is More Frequent in Clinical Samples than in Surveillance Rectal Swabs with Respect to the Previous 14-Month Period
Authors: Basso Monica , Zago Daniela , De Canale Ettore , Biasolo Maria Angela , Franchin Elisa , Onelia Francesco , Scaggiante Renzo , Crisanti Andrea , Parisi Saverio Giuseppe 
Published: January 2021

Abstract

Background
In Italy the pandemic of COVID-19 infection has placed an enormous burden on health authorities: contact precautions are required to avoid viral transmission and people should be subjected to standard infection control procedures. This is crucial in a country experiencing a high number of confirmed cases of COVID-19 infection in Europe and where multidrug-resistant Gram-negative bacteria (MDR-GN) are endemic.The aim of this study was to compare the prevalence of MDR-GN in surveillance rectal swabs (SRS) and in clinical samples (CS) in the period March 1,2020-April, 24 2020 with respect to the previous 2-month period and to the previous year.

Methods
The first SRS and the first CS with a MDR-GN isolate detected from 01/01/2019 to 24/04/2020 were included. Analysis was made by comparing three different study periods in 2019 and 2020 (Jan-Dec 2019, Jan-Feb 2020, and Mar-Apr 2020), for medical department, surgical department and intensive care department.

Results
Overall, 612 MDR-GN organisms were identified (399 SRS and 213 CS): carbapenemase-producing Klebsiella pneumoniae and Acinetobacter baumanii (CPAB) were the most frequently detected (Figure 1). We observed an increased relative frequency of patients with MDR-GN detected in CS respect to those found in SRS (32.7% vs 44.5% vs 70.6%, p=0.0005): 5/12 CS detected in the last period were isolated from the respiratory tract (Figure 2). Nine patients with COVID-19 pneumonia had MDR-GN. All but two patients had a previous negative SRS performed 4 days before (median value) and the median interval between COVID-19 positivity and MDR-GN positivity was 7 days.The six patients with CPAB isolation were all hospitalized in the same ward, with partially overlapping hospital stays during the study period. In 5 of them, CPAB was detected in the respiratory tract (Figure 3).

Conclusion
The first detection of MDR-GN in CS and the nosocomial MDR-GN acquisition despite cohorting due to COVID-19 infection underline the need to reinforce infection control measures in a high prevalence country during COVID-19 pandemia. A correct antimicrobial policy urged because, according to published data, most patients with COVID-19 infection received antimicrobial therapy: furthermore MDR-GN infection could play a role in the negative outcome of these patients.

Disclosures
All Authors: No reported disclosures
395. Rapid, Non-invasive Detection of Infection Using Plasma-based Next-Generation Sequencing for Microbial Cell-free DNA in Individuals Testing Negative for SARS-CoV-2 in a Pandemic Setting
Authors: Via William V La , Dalai Sudeb , de Vries Christiaan R , Macintyre Ann , Ahmed Asim A 
Published: January 2021

Abstract

Background
The clinical presentation of patients with severe COVID-19 infection can be protracted and deteriorate to ARDS and multi-organ dysfunction with prolonged fever. As such, there is clinical overlap with many infectious diseases especially those that cause pneumonia. Due to of the prevalence of COVID-19 illness amidst the pandemic, concerns about testing sensitivity and the attendant risk to health care personnel (HCP) delivering care, patients are frequently tested multiple times to ascertain that they are SARS-CoV-2 free. Often, alternative diagnoses are not considered because some diagnostic modalities—such as bronchoalveolar lavage (BAL)—pose an unacceptable risk to the patient and/or HCP.

Methods
We interrogated plasma for microbial cell-free DNA from 58 patients who were known to be SARS-CoV-2 negative. Clinical information is taken from information submitted with the test requisition or obtained at the time of result reporting from clinical consultations with the ordering provider. In each case, a plasma sample was analyzed with the Karius Test (KT) which is a CLIA certified/CAP-accredited next-generation sequencing (NGS) plasma test designed to detect and quantify circulating microbial cell-free DNA (mcfDNA), which can assist with the diagnosis of deep-seated infections. After mcfDNA is extracted and NGS performed, human reads are removed and remaining sequences are aligned to a curated database of &gt;1400 organisms. Organisms present above a statistical threshold are reported. The time to result is on average 24 hours from sample receipt.

Results
In a subset of 20 samples, we found a broad range of pathogens. Pneumocystis jirovecii was the most common. These detections were unexpected in the majority of these patients. (see Table)
Broad range of Karius detected pathogens (including fastidious bacteria, mycobacteria, fungi and viruses)

Conclusion
Open-ended, plasma-based NGS for mcfDNA with the KT provides a rapid, non-invasive method to diagnose deep-seated infection like pneumonia. This broad-based test detected a wide range of pathogens – many unsuspected – in patients with severe pneumonia and other invasive infections during the COVID-19 pandemic. These detections highlight the utility of the tool; which allowed better management including de-escalation of SARS-CoV-2 testing and selection of appropriate antibiotic therapy for the unexpected diagnoses.

Disclosures
William V. La Via, MD, Karius (Employee) Sudeb Dalai, MD, Karius (Employee) Christiaan R. de Vries, MD, PhD, Karius (Consultant, Independent Contractor)Stanford University (Employee) Ann Macintyre, DO, Karius (Employee) Asim A. Ahmed, MD, Karius (Employee)
401. Short Term Outcomes in Multisystem Inflammatory Syndrome in Children (MIS-C) Related to COVID-19
Authors: Riollano Mariawy , Marshall Christina L , kowalsky shanna , Tosi Michael , Posada Roberto , Trachtman Rebecca , Paniz-Mondolfi Alberto , Sordillo Emilia 
Published: January 2021

Abstract

Background
MIS-C is a multi-system inflammatory syndrome which has been described in pediatric patients after COVID-19 since late April. Our objective is to describe the short-term outcomes of the first 15 cases with MIS-C, who presented for care to a tertiary pediatric referral center.

Methods
This is a retrospective chart review of patients who met MIS-C criteria based on the New York State Department of Health case definition and who were admitted to the Mount Sinai Hospital in New York City, between April 24 and May 14, 2020. We collected clinical and laboratory data during their hospital admission and subsequent outpatient follow up.

Results
The range of the length of hospital stay was 6–13 days (mean=7 days). One patient expired on day 9 of hospitalization. At the time of discharge, all patients had normalization of inflammatory markers. All patients were discharged on anticoagulation therapy for 14 days. One patient was readmitted with a subdural hematoma at day 13 post discharge and 3 patients had bruising at their follow up visit 7–12 days after hospital discharge. All patients had normalization of cardiac enzymes prior to hospital discharge. Abnormalities in coronary arteries and cardiac function which were observed during hospitalizations in 4 (27%) and 8 (53%) patients respectively, had resolved by day 6–35 post discharge (mean=20 days).

Conclusion
Although patients with MIS-C can present with severe multi-organ involvement and shock, the majority of the patients in our experience had resolution of symptoms and normalization of laboratory parameters within a few weeks of initial symptoms. Our findings underscore the need to carefully weigh the risk and benefits of anticoagulation therapy and to monitor this treatment closely. Further research is needed to determine long-term outcomes of these patients.

Disclosures
All Authors: No reported disclosures
403. Study of early and late readmissions with COVID-19: A retrospective analysis
Authors: Tariq Zain , Vahia Amit T , Grover Kunal , Ignacio Shalimar , Kaur Ikjot , Talari Goutham , Chaudhry Zohra Sarfraz , Bhargava Pallavi 
Published: January 2021

Abstract

Background
Michigan was one of the severely impacted regions during the initial COVID-19 surge. An institutional protocol with early methylprednisolone (MP) to treat COVID-19 patients requiring supplemental oxygen was implemented. We sought to study characteristics of these patients who were readmitted with infectious and non-infectious diagnoses.

Methods
A retrospective analysis of 21 COVID-19 readmitted patients initially admitted between 3/10/2020 and 4/20/2020 (early 0–7, late 8–30 days) was done. Total of 455 COVID-19 patients, confirmed by a positive nasopharyngeal RT-PCR were admitted during this time period. Demographic data, clinical characteristics, laboratory and radiographic results and treatments were compared among the early and late readmission groups. Univariate and logistic regression analysis were performed to study the risk factors associated with early readmission and worsening of COVID-19 pneumonia. Secondary analyses were performed comparing worsening COVID-19 pneumonia with other readmission diagnoses.

Results
4.6% (21/455) were readmitted, 14 early vs 7 late (median age 75 vs 65 yrs). Most early readmissions were COVID-19 related and 8 out of 14 had worsening COVID-19 pneumonia based on clinical picture, laboratory and imaging findings. Readmitted patients with worsening COVID-19 related pneumonia had significantly elevated CRP and lower ALC compared to last discharge value (Table 1). None of the late readmissions required MP. A total of 8 readmissions had bacterial coinfections (1/8 COVID-19 related) (Table 2). Bacterial infections unrelated to COVID-19 were aspiration pneumonia (2), urinary tract infection (2), enterococcal bacteremia from stercoral colitis (1), sacral osteomyelitis (1), and infected BKA stump (1). Each increasing day of MP duration during the first admission reduced the likelihood of early readmission by approximately 10% (OR 0.90, 95% CI 0.63–1.2, p=0.56) (Table 3). 1/14 and 0/7 patients died amongst early and late readmissions respectively.
Table 1: Characteristics of early and late readmissions in COVID-19 patients

Table 2: Readmission Diagnosis

Table 3: Univariate and Multivariate Analysis of Readmissions

Conclusion
Early MP in COVID-19 pneumonia was not associated with increased risk of early secondary bacterial infections in the readmitted patients. Optimal duration of MP in patients with COVID-19 pneumonia needs to be defined.

Disclosures
All Authors: No reported disclosures
404. The occurrence of stroke in COVID-19
Authors: Wanahita Anna , Musher Daniel M 
Published: January 2021

Abstract

Background
Patient with COVID-19 may exhibit a wide array of neurologic manifestations, including stroke; in some cases, stroke is the presenting or predominant manifestation. The frequency of stroke in COVID-19 has varied greatly in previous reports, probably reflecting the intensity with which neurologic abnormalities have been sought. The great majority of stroke have been thought to be ischemic.

Methods
Review of data, case reports, and case series

Results
See table 1 for a summary of reported data on neurologic manifestations of COVID-19. When MRI has been done, the great majority of strokes have been shown to be ischemic. COVID-19 causes a generalized hypercoagulable state, and arterial thromboses have been recognized in other organs, as well, involving pulmonary, mesenteric and coronary arteries. Coronavirus infection causes an intense release of cytokines with widespread activation of the coagulation cascade. In addition, SARS-CoV-2 attaches to ACE 2 receptors on endothelial surfaces via the S (spike) protein and invades causing a localized inflammatory response, with a resulting increase in local thrombotic activity. Antiphospholipid antibodies are sometimes present. New data suggest possible role of alpha-defensin level in creation and prevention of disintegration of blood clots. To date, reports of neurologic disease are based on case series, so there is no way, at present, to calculate the frequency of neurologic complications of COVID-19. A systematic, prospective study focusing on neurologic examination supplemented by MRI in hospitalized patients would answer the question of the incidence of this complication, but logistical problems including patients’ need for ICU care and concern for contagion resulting from sending patents out of the ICU for procedures mitigate against the likelihood of such a study being done.

Conclusion
We hypothesize that: (1) stroke occurs in COVID-19 more frequently than is recognized; (2) a hypercoagulable state with inflammation at the site of local invasion of vascular endothelial cells by SARS-CoV-2, perhaps with a role for antiphospolipid antibodies all contribute to the pathogenesis of stroke; and (3) more liberal use of anticoagulation in COVID-19 cases should be considered.

Disclosures
All Authors: No reported disclosures
409. Rapid Development of a Multiplexed PCR Prototype Method that Offers a Syndromic Diagnostic Option by Integrating Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Detection with Twenty-One Other Common Respiratory Pathogens
Authors: Spaulding Usha , Antosch Jeremiah , stone Jessica , Robinson Tanner , Halo Kerrin , Kavetska Iryna , Healy Tyler , Taylor Alex , Jones Matthew , Todorov Toma , Lu Zhenmei , Cloud Joann , Buccambuso Maggie , Graham Brad , Boone Jeremy , Wood Hillary , Rogatcheva Margarita 
Published: January 2021

Abstract

Background
The US Food and Drug Administration (FDA) has granted Emergency Use Authorization (EUA) for multiple PCR-based tests to aid in the diagnosis and containment of COVID-19. A vast majority of these tests detect only SARS-CoV-2 which causes symptoms similar to those caused by other respiratory pathogens. Hence, other etiologies or co-infections requiring a different therapy may be missed. The prototype BioFire® Respiratory Panel 2.1 (RP2.1) continues the syndromic approach of the FDA-cleared BioFire® Respiratory Panel 2 (RP2), to provide the ability to simultaneously detect 22 common respiratory pathogens, including SARS-CoV-2, from nasopharyngeal swab (NPS) specimens. The goal of this study was to rapidly develop a RP2.1 prototype that contains high-performing SARS-CoV-2 assays and maintains the performance of assays retained from RP2.

Methods
Twelve assays designed for four SARS-CoV-2 genes were tested for compatibility with the RP2 assays and conditions. All retained RP2 assays were evaluated to verify established RP2 performance. The sensitivity of novel SARS-CoV-2 assays was estimated with nucleic acids at BioFire and contrived live virus NPS samples at MRIGlobal. Primer homology of SARS-CoV-2 assays to &gt; 15,000 SARS-CoV-2 genomes from accessible databases was assessed for in silico inclusivity

Results
A prototype multiplexed PCR panel containing assays for 22 pathogens was developed in a 5-week period. Of the 12 SARS-CoV-2 assays, 7 were compatible with the RP2 conditions; 2 were selected for the prototype. No false positive results due to cross-reactivity with unintended analytes or non-specific amplification in negative samples were observed for any assays. All retained RP2 assays were detected at or near their established LoD. The SARS-CoV-2 LoD was estimated at 103 -102 genomes/mL with both nucleic acid and live virus spiked into NPS. Together, the assays are 100% inclusive for all 15,370 complete SARS-CoV-2 genomes assessed in silico for reactivity.

Conclusion
The results of this study indicate a strong potential for RP2.1 to serve as a sensitive comprehensive syndromic option to aid in the diagnosis of COVID-19 as well as respiratory syndromes caused by other pathogens, including co-infections.
This study was performed with a test not cleared for diagnostic use.

Disclosures
All Authors: No reported disclosures
413. Association of SARS-CoV-2 Genomic Load in Nasopharyngeal Samples with Adverse COVID-19 Patient Outcomes: A Retrospective Analysis from an Academic Hospital Center in New York City
Authors: Zacharioudakis Ioannis , Prasad Prithiv , Zervou Fainareti , Basu Atreyee , Inglima Kenneth , Weisenberg Scott , Aguero-Rosenfeld Maria E 
Published: January 2021

Abstract

Background
SARS-CoV-2, the cause of COVID-19 pneumonia, is associated with heterogenous presentations ranging from asymptomatic infection to severe respiratory failure. We explored the association of SARS-CoV-2 genomic load as a risk factor for adverse patient outcomes.

Methods
We included adult patients admitted to the hospital with clinical and radiographic findings of pneumonia and a confirmatory polymerase chain reaction (PCR) test of SARS-CoV-2 within 24 hours of admission. We segregated patients into 3 genomic load status groups: low (Cycle threshold (Ct) ≥35) intermediate (25&lt; Ct&lt; 35) and high (Ct ≤25) using real-time PCR. The primary outcome was a composite outcome of death, intubation and/or use of extracorporeal membrane oxygenation. Secondary outcomes included severity of pneumonia on admission, as measured by the Pneumonia Severity Index (PSI). Sensitivity analyses were performed to include Acute Respiratory Distress Syndrome (ARDS) in the composite outcome and varying Ct classification breakpoints.

Results
Of 457 patients positive for SARS-CoV-2 assay from March 31st to April 10th 2020, 316 met inclusion criteria and were included in the final analysis. Included patients were followed for a median of 25 days (IQR 21–28). High genomic load at presentation was associated with higher Charlson Comorbidity Index scores (p=0.005), transplant recipient status (p&lt; 0.001) and duration of illness less than 7 days (p=0.005). Importantly, patients with high genomic load were more likely to reach the primary endpoint (p=0.001), and had higher PSI scores on admission (p=0.03). In multivariate analysis, high genomic load remained an independent predictor of primary outcome. Results remained significant in sensitivity analyses.
Flow Chart

Prediction of Outcomes Based on Genomic Load

Prediction of Outcomes Based on Genomic Load and Pneumonia Severity Index

Conclusion
High genomic load of SARS-CoV-2 in nasopharyngeal samples at the time of admission is independently associated with mortality and intubation. This finding should prompt further research on the role of viral load as a clinical predictor and possible modifiable risk factor for adverse outcomes as treatment strategies evolve in this global pandemic.

Disclosures
All Authors: No reported disclosures
414. Association of SARS-CoV-2 Genomic Load Trends with Clinical Status in COVID-19:A Retrospective Analysis from an Academic Hospital Center in New York City
Authors: Zacharioudakis Ioannis , Zervou Fainareti , Prasad Prithiv , Shao Yongzhao , Basu Atreyee , Inglima Kenneth , Weisenberg Scott , Aguero-Rosenfeld Maria E 
Published: January 2021

Abstract

Background
The Infectious Diseases Society of America has identified the potential use of SARS-CoV-2 genomic load for prognostication purposes as a key research question.

Methods
We designed a retrospective cohort study that included adult patients with COVID-19 pneumonia who had at least 2 positive nasopharyngeal tests at least 24 hours apart to study the correlation between the change in the genomic load of SARS-CoV-2 in nasopharyngeal samples, as reflected by the Cycle threshold (Ct) value of the real-time Polymerase Chain Reaction (PCR) assay, with change in clinical status. The Sequential Organ Failure Assessment (SOFA) score was used as a surrogate for patients’ clinical status. A linear mixed-effects regression analysis was performed.

Results
Among 457 patients who presented to the emergency department between 3/31/2020- 4/10/2020, we identified 42 patients who met the inclusion criteria. The median initial SOFA score was 2 (IQR 2–3). 20 out of 42 patients had a lower SOFA score on their subsequent tests. We identified a statistically significant inverse correlation between the change in SOFA score and change in the Ct value with a decrease in SOFA score by 0.05 (SE 0.02; p &lt; 0.05) for an increase in Ct values by 1. This correlation was independent of the duration of symptoms.
Flow chart

A graph of the Cycle Threshold (Ct) values of the of Cepheid Xpert® Xpress SARS-CoV-2 assay measured on repeat screening of the 42 included patients.

Graph of the fitted SOFA scores based on the Cycle Threshold values per patient.

Conclusion
Our findings suggest that an increasing Ct value in sequential tests may be of prognostic value for patients diagnosed with COVID-19 pneumonia. Before repeat testing can be recommended routinely in clinical practice as a predictor of disease outcomes, prospective studies with a standardized interval between repeat tests should confirm our findings.

Disclosures
All Authors: No reported disclosures