bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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 >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

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

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

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

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 > 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

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< Ct< 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< 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

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 < 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
419. Diagnostic Utility of a Ferritin to Procalcitonin Ratio to Differentiate Patients with COVID-19 from Those with Bacterial Pneumonia
Authors: Jankousky Katherine C , Hyson Peter , Huang Jin , Chastain Daniel B , Franco-Paredes Carlos , Erlandson Kristine M , Henao-Martinez Andres , Shapiro Leland
Published: January 2021

Background

Accurate, rapid, inexpensive biomarkers are needed to differentiate COVID-19 from bacterial pneumonia, allowing effective treatment and antibiotic stewardship. We hypothesized that the ratio of ferritin to procalcitonin (F/P) reflects greater viral activity and host response with COVID-19 pneumonia, while bacterial pneumonia would be associated with less cytolysis (lower ferritin) and more inflammation (higher procalcitonin), thus a lower F/P ratio.

Methods

We conducted a retrospective study of adult patients admitted to a single University hospital in the US through May 2020, during the COVID-19 pandemic. We compared F/P ratio of patients diagnosed with COVID-19 or bacterial pneumonia, excluding patients with COVID-19 and bacterial co-infections. In a logistic regression, we controlled for age, sex, body mass index (BMI), diabetes (DM), and hypertension (HTN). We used a receiver operating characteristic analysis to calculate the sensitivity and specificity of F/P values for the diagnosis of COVID-19 versus bacterial pneumonia.

Results

Of 218 patients with COVID-19 and 17 with bacterial pneumonia, COVID-19 patients were younger (56 vs 66 years, p=0.04), male (66% vs 24%, p=0.009), had higher BMI (31 vs 27 kg/m2, p=0.03), and similar rates of HTN (59% vs 45%, p=0.3) and DM (32% vs 18%, p=0.2). The median F/P ratio was significantly higher in patients with COVID-19 (3195 vs 860, p=0.0003, Figure 1). An F/P ratio cut-off of ≥ 1250 generated a sensitivity of 78% and a specificity of 59% to correctly classify a COVID-19 case (Figure 2). When adjusted for age, gender, BMI, DM, and HTN, a ratio ≥ of 1250 was associated with significantly greater odds of COVID-19 versus bacterial pneumonia (OR: 4.9, CI: 1.5, 16.1, p=0.009).

Figure 1. Ferritin to Procalcitonin Ratios of patients with COVID-19 and patients with Bacterial Pneumonia (controls).

Figure 2. Receiver Operating Characteristic Analysis of Ferritin to Procalcitonin Ratio Cut-off Values Predicting COVID-19 Diagnosis.

Conclusion

We observed an elevated F/P ratio in patients with COVID-19 compared to those with bacterial pneumonia. A F/P ratio ≥ 1250 provides a clinically relevant increase in pre-test probability of COVID-19. Prospective studies evaluating the discriminatory characteristics of F/P ratio in larger cohorts is warranted.

Disclosures

All Authors: No reported disclosures
420. Diagnostic Utility of Chest CT scan for COVID-19, in the Early Stage of the Pandemic in Brooklyn, New York
Authors: Gibbs Rachel , Fu Lung H , Silver Michael , Lockerman Zachary S , Ghitan Monica , Chapnick Edward , Lin Yu Shia
Published: January 2021

Background

Diagnosis of coronavirus disease 2019 (COVID-19) in the early weeks of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in New York City posed unique challenges. Due to inadequate testing availability and long turnaround times, decisions on which patients to isolate were problematic. With sensitivity comparable to reverse transcription polymerase chain reaction (RT-PCR), the absence of ground glass opacities (GGOs) on chest CT scan was useful to rule out COVID-19. We evaluated the specificity of chest CT scan findings for COVID-19 along with other clinical and laboratory findings.

Methods

A retrospective chart review was done of 182 adult patients who were tested for SARS-CoV-2 by RT-PCR and underwent a chest CT scan while admitted to Maimonides Medical Center between March 1 to 23, 2020. Cases were defined as those with a positive RT-PCR result or who were treated for COVID-19. Negative cases were defined as those with negative RT-PCR and an alternative diagnosis confirmed by an ID physician. Beyond March 23, almost all newly admitted patients were isolated.

Results

There were 111 COVID-19 positive and 71 COVID-19 negative patients. Of the COVID-19 patients, 61% were male and 39% female, 56% white, 20% Hispanic, 14% black, 9% Asian, 36% Jewish, 35% had diabetes mellitus (DM), 50% had hypertension and 42% had cardiovascular disease. Clinical symptoms, signs, and laboratory values for COVID-19 positive and negative groups were not significantly different. COVID-19 patients had significantly higher BMI (p = 0.001). On chest CT scan, bilateral or unilateral, peripheral distribution and lower lobar GGOs were over 80% specific for COVID-19. The frequency of GGOs was significantly higher when chest CT scans were done during the second week of illness compared to the first week (p = 0.0195). Jewish patients were associated with higher rates of death (p = 0.0475) and underlying DM was associated with higher rates of ARDS, AKI, intubation, ICU admission and death (p < 0.05) compared to other demographic and comorbid groups.

Conclusion

Chest CT scan is an important component in the diagnostic process for patients with suspected COVID-19 infection, especially during the second week of symptoms. The findings may aid clinical decisions in the setting of a second surge of SARS-CoV-2.

Disclosures

All Authors: No reported disclosures
425. The Utility of Paired Upper and Lower COVID-19 Sampling in Patients with Artificial Airways
Authors: Kitt Eimear , Sammons Julia S , Chiotos Kathleen , Coffin Susan E , Coffin Susan E , Ballantine Allison , Gallagher Elizabeth , Mojica Coralee DelValle , O’Callaghan Kevin P , Kerman Caryn , Harris Rebecca , Bell Louis , Davis Daniela , Nord Ellen
Published: January 2021

Background

The Centers for Disease Control and Prevention (CDC) recommends upper respiratory tract (URT) polymerase chain reaction (PCR) testing as the initial diagnostic test for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Lower respiratory tract (LRT) testing for patients requiring mechanical ventilation is also recommended. The goal of this study was to evaluate concordance between paired URT and LRT specimens in children undergoing pre-admission/procedure screening or diagnostic testing. We hypothesized that < 10% of paired tests would have discordant results.

Methods

Single center cross-sectional study including children with artificial airways who had paired URT and LRT SARS-CoV-2 PCR testing between 4/1/2020 and 6/8/2020. URT specimens included nasopharyngeal (NP) swabs and aspirates. LRT specimens included tracheal aspirates and bronchoalveolar lavages. URT and LRT specimens were classified as paired if the two specimens were collected within 24 hours. Artificial airways included tracheostomies and endotracheal tubes. Tests were classified as diagnostic versus screening based on the indication selected in the order.

Results

102 paired specimens were obtained during the study period. Fifty-nine were performed for screening and 43 were performed for diagnosis of suspected SARS-CoV-2. Overall, 94 specimens (92%) were concordant, including 89 negative from both sources and 5 positive from both sources. Eight specimens (8%) were discordant, all of which were positive from the URT and negative from the LRT (Figure 1). Among patients undergoing screening, 3 of 4 positive tests were discordant and among symptomatic patients, 5 of 9 positive tests were discordant. There were no instances of a positive LRT specimen with a negative URT specimen.

Figure 1. Performance of upper and lower respiratory tract SARS-CoV-2 PCR testing in children with artificial airways

Conclusion

Overall, most paired samples from the URT and LRT yielded concordant results with no pairs positive from the LRT and negative from the URT. These data support the CDC recommendation that URT specimens are the preferred initial SARS-CoV-2 test, while LRT specimens should be collected only from mechanically ventilated with suspected SARS-CoV-2.

Disclosures

All Authors: No reported disclosures
426. Use of Real Time IP-10 Measurements to Identify and Monitor the Dysregulated Immune Response in COVID-19 Patients
Authors: Lev Shaul , Gottesman Tamar , Levin Gal Shachaf , Ber Tahel Ilan , Angel Alon , Kellerman Lior , Barash Eran , Navon Roy , Simon Einav , Avni Noa , Hainrichson Mary , Gottlieb Tanya , Oved Kfir , Eden Eran , Tadmor Boaz
Published: January 2021

Background

It is estimated that up to 10% of SARS-CoV-2 patients progress from early and pulmonary stages to the most severe stage of illness, which manifests as an extra-pulmonary systemic hyperinflammatory syndrome. Interferon gamma-induced protein 10 (IP-10) is an inflammatory marker that plays a role in the dysregulated host response of COVID-19 infected patients. Clinical monitoring of IP-10 has been restricted in the absence of a rapid diagnostic test. MeMed KeyTM is a novel platform recently cleared to provide IP-10 measurements in 15 minutes. We hypothesized that providing physicians with real time IP-10 measurements would support detection and continuous monitoring of patients with a dysregulated immune response and potentially allow personalized immunomodulation to improve patient outcome.

IP-10 levels reflect corticosteroid treatment

Methods

From 7th April 2020 to 10th May 2020 blood was routinely collected serially from 52 SARS-CoV-2 positive patients hospitalized at a COVID-19 dedicated medical center. A clinical decision support protocol was in place focused on managing viral response, oxygenation and inflammatory state (NCT04389645).

Results

The median age of the 52 patients was 69, 69% were male, 21% were ventilated, 4 died, 2 due to non-COVID-19 related complications. The most common comorbidities were Diabetes 40% and Hypertension 46%. IP-10 >1000 pg/ml correlated with ICU admission (p< 0.05) and increased COVID-19 severity score (p< 0.01). 19 of the 52 patients had IP-10 >1000 pg/ml, of these 12 were treated with corticosteroids. Monitoring IP-10 within the clinical decision support protocol assisted with personalized corticosteroid regimens with the aim of reducing IP-10 < 1000 pg/ml. The 10 patients that survived exhibited IP-10 levels >1000 pg/ml for 2.6 days on average. In contrast, the 2 patients that died of COVID-19 related complications displayed an average of 7.5 days with IP-10 >1000 pg/ml (p< 0.05).

Conclusion

Providing physicians with real time measurements of IP-10 in COVID-19 patients proved a useful tool as part of the clinical decision support protocol. Timely identification, monitoring and personalized treatment of COVID-19 patients exhibiting a dysregulated immune response may aid in improving patient outcome. Further studies are warranted.

Disclosures

Tahel Ilan Ber, MD, MeMed (Employee) Alon Angel, n/a, MeMed (Employee) Lior Kellerman, M.D, MeMed (Employee) Eran Barash, MA, MeMed (Employee) Roy Navon, MSc, MeMed (Employee) Einav Simon, PhD, MeMed (Employee) Noa Avni, PhD, MeMed (Employee) Mary Hainrichson, PhD, MeMed (Employee) Tanya Gottlieb, PhD, MeMed (Employee) Kfir Oved, MD, PhD, MeMed (Employee) Eran Eden, PhD, MeMed (Employee)
427. Variation in SARS-CoV-2 molecular diagnostic test performance in symptomatic versus asymptomatic populations
Authors: Kanjilal Sanjat , Baker Meghan , Woolley Ann E , Rhee Chanu , Petrides Athena K , Kim Junghyun , Patel Rajesh , Zaffini Rebecca , Klompas Michael , Brigl Manfred
Published: January 2021

Background

Growing recognition of the importance of asymptomatic and pre-symptomatic transmission for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to a substantial expansion of testing from symptomatic to asymptomatic patients, and particularly those with risk factors for infection. Viral burden in asymptomatic individuals can differ from symptomatic patients, which can impact test performance. We therefore evaluated the impact of expanded testing indications upon the sensitivity and specificity of molecular diagnostic assays for SARS-CoV-2.

Methods

We performed a retrospective review of laboratory results from 5,122 emergency room patients and inpatients tested for SARS-CoV-2 between 05/03/2020 and 06/13/2020 using the Hologic Panther Fusion and the Cepheid Xpert assays at the Brigham & Women’s Hospital in Boston, MA. Descriptive analyses were performed for trends in testing volume, rates of positivity and cycle thresholds (Cts) over time based on symptom status. We calculated the proportion of new diagnoses made on a patient’s first test as an indirect measure of sensitivity. We calculated the proportion of first tests that are positive with a Ct value < 35 as an indirect measure of specificity.

Results

The overall rate of positivity over the study period was 8.7% (599/7,510 tests; 440/4,795 people) and declined by 1.8% (95% CI -2.2% - -1.4%, P< 0.0001) each week. Relative to tests in symptomatic people, the asymptomatic population had a higher mean Ct value (35.1 vs 32.3; P < 0.0001). Ct values increased by 0.7 (95% CI -0.1 - +1.4, P=0.07) and 0.8 (95% CI +0.3 - +1.4; p=0.01), sensitivity declined by 4% (95% CI -9% - +1%, P=0.08) and 12% (95% CI -20% - -5%, P-0.01) and specificity declined by 8% (95% CI -3% to 20%; P=0.13) and 9% (95% CI 7% - 11%; P=0.0002), over the time period of the study for asymptomatic and symptomatic patients, respectively.

Figure 1: Trends in Ct values by symptoms

Figure 2: Trends in diagnosis by first versus second test by symptoms

Figure 3: Trends in proportion of people with their first test having Ct < 35 by symptoms

Conclusion

We show that the proportion of patients with low SARS-CoV-2 viral loads has increased as testing has expanded to the asymptomatic population and as transmission wanes in the community. This negatively impacts the performance of molecular assays by increasing the risk of false negatives and the detection of non-viable virus. Decision algorithms based on molecular assay results may need re-evaluation in light of these dynamics.

Disclosures

All Authors: No reported disclosures
430. Frontline doctors infected with Covid-19 during a hospital outbreak in Veracruz, Mexico
Authors: Del Carpio-Orantes Luis , Munguia-Sereno Alvaro Efren , Guerrero-Mancinas Zeltzin Olivia , Aparicio-Sánchez Elisa Estefanía , Segura-Rodríguez Orlando Israel , García-Hernández Omar , Escobar-Huerta Alejandro , Dorantes-Nava Claudia Leticia , Garcés-García Eustaquio , Ortiz-Espinoza Cirilo , Torres-Sánchez José Luis , López-Varela Luis Daniel , Pascual-Epigmenio Samuel , Márquez-Rodríguez Luis Alberto
Published: January 2021

Background

The current Covid-19 pandemic has affected health workers, some estimates mention more than 90,000 affected, even with deaths throughout the world.

Population characteristics

General symptoms

Methods

Descriptive, analytical and cross-sectional study. The cases of front-line doctors infected with Covid-19 during a hospitalary outbreak, in the General Hospital 71 “Lic. Benito Coquet Lagunes” of Veracruz, dependent on the Mexican Institute of Social Security, from April 1 to May 31, 2020.

Treatments

Results

Seven doctors were entered into the study, with an average age of 42.4 years, all of them male. The affectation by service was: Internal medicine 5 of 17 doctors (29.4%), Emergencies 1 of 15 doctors (6.6%) and Intensive care 1 of 6 doctors (16.6%) infected by Covid-19. Laboratory studies were only performed in 5 cases, the presence of leukopenia in 1 case (20%), leukocytosis in 2 cases (40%), lymphopenia in 4 cases (80%) stand out. Impaired fasting glucose was reported in all cases. There was no alteration in kidney function; in liver function, transaminemia was reported in 80%. Regarding the acute phase reactants, the intake of these was very inconsistent since it was not uniform in all cases, but the most representative was elevated ESR in 4 of 4 cases (100%), positive PCR in 3 of 4 cases (75%), procalcitonin negative in 3 of 3 cases (100%), elevated DHL in 2 of 5 cases (40%), elevated D-dimer in 1 of 3 cases (33.3%), elevated ferritinemia in 1 of 2 cases (50 %). The rest of the characteristics in the table and graphs.

Conclusion

The present cohort of doctors affected by Covid during a hospital outbreak shows that there are several factors to take into account, on the one hand, factors specific to the population (obesity, diabetes, hypertension), as well as the institutions that are in charge of medical personnel. they must identify the risk factors mentioned, influence them and protect said population that is vulnerable per se to a pandemic; Another constantly identified factor is occupational exposure to the pathogen without sufficient and adequate personal protective equipment.

Disclosures

All Authors: No reported disclosures
433. Mathematical Modeling of COVID-19 Transmission by a k Phases SEIR Model
Authors: Couto Braulio Roberto Gonçalves Marinho , Starling Carlos Ernesto Ferreira
Published: January 2021

Background

Mathematical models can provide insights on the spread of infectious diseases, such as the novel SARS-CoV-2 (COVID-19). This work applied a SEIR epidemiological compartmental model (susceptible-exposed-infected-recovered) with k phases to predict the actual spread of the COVID-19 virus.

Fig. 1 – SEIR model for COVID-19.

Methods

Four parameters of the SEIR model were obtained by international experiences: the incubation period = 3.7 in days, the proportion of critical cases = 0.05, the overall case-fatality rate = 0.023, and the asymptomatic proportion of COVID-19 = 0.18. The critical step in the prediction of COVID-19 by the model is the value of R0 (the basic reproduction number) and T_infectious (the infectious period, in days). R0 and T_infectious for each phase of the curve are calculated by mathematical constrained optimization, a numerical method. Differently from a statistical modelling, a numerical method is a type of mathematical modelling that is not dependent on a probability distribution. The objective function that measures the model error is minimized with respect to R0 and T_infectious in the presence of constraints on those variables. For R0, constraints are valid range of values (0.5 ≤ R0 ≤ 20). For T_infectious, constraints also are related to its range of values (2 ≤ T_infectious ≤ 14). A Solver from Excel or NEOS Server, for example, can be used for finding numerically minimum of a function Z, that represents the sum of absolute value of errors between COVID-19 new cases observed in one day, and COVID-19 cases predicted by the SEIR model (Fig. 2 and 3).

Fig. 2 - Mathematical Modeling of COVID-19 transmission by a SEIR model wiht three phases.

Fig.3 - Algorithm for the SEIR model applied to COVID-19 (calculation of new COVID-19 cases day-by-day).

Results

The ECDC has registered 8,142,129 COVID-19 in the world on Jun/17/2020. R0 and T_infectious calculated for a three phases curve in USA, with a stabilized scenario (Fig. 4: R0_1=1.0; T_infectious_1=2; R0_2=17.4; T_infectious_2=2; R0_3=1.0; T_infectious_3=14), a two phases curve in Brazil (Fig. 5: R0_1=8.0; T_infectious_1=9; R0_2=1.3; T_infectious_2=6), and a three phases model for France (Fig. 6: R0_1=4.3; T_infectious_1=11; R0_2=9.3; T_infectious_2=11; R0_3=0.5; T_infectious_3=12).

Fig. 4 - Three phases SEIR models for R0 and T_infectious that minimize the model error in predicting new COVID-19 cases day-by-day in USA.

Fig. 5 - Two phases SEIR models for R0 and T_infectious that minimize the model error in predicting new COVID-19 cases day-by-day in USA.

Fig. 6 - Two phases SEIR models for R0 and T_infectious that minimize the model error in predicting new COVID-19 cases day-by-day in USA.

Conclusion

The k phases SEIR model proved to be a useful to measure the COVID-19 transmission in a City, State or Country. More phases can be applied to fit a scenario with a new second COVID wave.

Disclosures

All Authors: No reported disclosures
434. Tracking COVID-19 in Real Time: Leveraging Public Data Sources to Inform Infection Prevention Practices
Authors: O’Callaghan Kevin P , Winser Kyle , Mehta Vaidehi , Kitt Eimear , Mojica Coralee DelValle , Kerman Caryn , Coffin Susan E , Coffin Susan E , Sammons Julia S
Published: January 2021

Background

Global spread of SARS-CoV-2 led to an urgent need for data on national and regional prevalence to inform public health policy. Healthcare systems were also in need of data to develop best practices around defining patient risk. We describe a data analytics tool developed at our institution which uses public data sources to track county-level prevalence of COVID-19 so as to delineate risk for individual patients.

Methods

We investigated a number of data sources tracking COVID-19 case counts, assessing for (1) frequency of updates, (2) granularity of geographic detail (optimally to zip-code or county) and (3) completeness of the data. We chose the Johns Hopkins University CSSE COVID-19 data set. This contains counts of new diagnoses per day by county using Federal Information Processing System (FIPS) codes. The dataset is updated daily with adjustments made for backdated corrections.

We developed a data analytics tool which allowed for direct comparison of county period prevalence. We developed a metric of 10-day rolling period prevalence calculated as a total case count from the preceding 10 days, divided by county population from 2018 American Community Survey (ACS) estimates.

Results

Benchmarking against local (peak of 3.12 cases per 1,000 persons) and regional prevalence, we set 6 cases/1,000 persons as the threshold for a Geographic Region with Widespread Community Transmission (GReWCoT). Counties have to reach this threshold for at least 4 out of 7 days within the period 3 to 10 days prior to the evaluation, to adjust for bulking of test results and delayed reporting.

We used the analytics tool to support a semimonthly review of geographic regions, and made specific recommendations for patients from qualifying regions including use of modified enhanced precautions (including surgical mask and eye protection), as well as restricted visitation of caregivers.

Figure 1. Epidemic curves for 10-day rolling period prevalence of COVID-19 in the Mid-Atlantic Region: Philadelphia County, PA

Figure 2. Epidemic curves for 10-day rolling period prevalence of COVID-19 in the Mid-Atlantic Region: Westchester County, NY

Figure 3. Epidemic curves for 10-day rolling period prevalence of COVID-19 in the Mid-Atlantic Region: Bergen County, NJ

Conclusion

This approach allowed for a nuanced investigation of COVID-19 prevalence in real-time, and provided support for risk stratification of patients throughout our large catchment area. The dashboard was shared on an inward-facing site to support staff messaging about regions of increased risk. Next steps include leveraging international data to inform a similar approach to international travel for our patients and staff.

Disclosures

All Authors: No reported disclosures
438. Characteristics and Epidemiology of a Native American Community with a High Prevalence of COVID-19
Authors: Bratsch Nicole A , Campbell Natalie , McAuley James , Close Ryan M
Published: January 2021

Background

COVID research and reporting has focused on large urban populations. However, limited data suggests that rural Native American (NA) populations are disparately impacted. We serve a well-defined NA population of ≈18,000 that is relatively geographically isolated in the White Mountains of eastern Arizona. Our first case SARS-CoV-2 was confirmed April 1st. We have since confirmed an attack rate significantly higher than most of the United States. We provide testing and case trends in addition to characteristics of the first 800 cases.

Methods

We sequentially reviewed the charts of all laboratory-confirmed COVID-19 patients from April 1 to June 3, 2020. In addition to calculating prevalence and rates, we provided summary statistics that were used to describe testing breakdown, demographics, symptoms, and co-morbidities.

Results

From April 1 to June 3, we tested 2,662 persons, of which 884 (33.2%) were positive. The estimated prevalence of the time of writing is 4.9% and the rate of 4,911 per 100,000 persons. Data compiled from the first 800 laboratory-confirmed patients is summarized in table 1. Median age for confirmed cases was 40.6 (IQR 28–54). 555 cases (72.1%) were symptomatic. The most common symptoms were cough (67.7%), subjective fever (39.5%), and muscle aches (36.8%). 30.6% of confirmed cases were asymptomatic at the time of testing. The majority of cases were among persons aged 30–39 years (22.9%). Some of the most common comorbidities in confirmed cases included cardiovascular disease (30.4%), substance abuse (30.1%), and diabetes (25.0%). There were 18 (2.04%) deaths.

Clinical findings among symptomatic patients

Conclusion

We observed a significantly higher prevalence (10-times) and attack rate of (17-times) COVID-19 in a well-defined NA population, when compared to the general Arizona population. We provide characteristics of these cases and report that nearly a third were asymptomatic at the time of testing. More research is needed to understand the rapid spread of COVID-19 in vulnerable rural communities.

Disclosures

All Authors: No reported disclosures