bluuebunny/crossref_metadata_2025 huggingface dataset:
537. Outpatient Parenteral Antimicrobial Therapy Readmissions from Post-Acute Care Facilities due to Coronavirus Disease 2019
Authors: Burnett Yvonne , Hamad Yasir
Published: January 2021

Background

Risk factors for morbidity and mortality in coronavirus disease 2019 (COVID-19) include older age, and cardiac and pulmonary comorbidities. In addition, nursing home residents have been one of the most heavily affected populations during this pandemic. Due to insurance reasons, patients requiring outpatient parenteral antimicrobial therapy (OPAT) may be discharged to a post-acute care facility (PACF) for the sole purpose of receiving intravenous antibiotics, placing these patients at higher risk of COVID-19 infection. This study evaluated hospital readmissions due to COVID-19 in OPAT patients.

Methods

Adult patients who received OPAT between March 16 and May 31, 2020 were included. Patients were identified via an OPAT database and reason for readmission was reviewed via the electronic medical record. Patients with ongoing courses of OPAT as of May 31, 2020 were excluded. The primary outcome was readmission due to COVID while receiving OPAT. Results were analyzed using descriptive statistics.

Results

During the study period, 266 OPAT patients were identified, with 88 (31%) patients discharged to PACFs. There were 49 (18%) total readmissions, with 3 (6%) readmitted due to COVID-19. All 3 patients were readmitted from unique PACFs. This resulted in 3/16 (19%) readmissions due to COVID-19 in patients discharged to PACFs as compared to none for OPAT patients discharged to home.

Conclusion

Patients discharged to PACFs are at increased risk of COVID-19 infection. Efforts should be made to increase availability of home OPAT services for patients who have no need for skilled care other than intravenous antimicrobials.

Disclosures

All Authors: No reported disclosures
541. Rapid Migration to Telemedicine in a Boston Community Health Center is Associated with Maintenance of Effective Engagement in HIV Care
Authors: Mayer Kenneth H , Levine Kenneth , Grasso Chris , Multani Ami , Gonzalez Alex , Biello Katie
Published: January 2021

Background

The COVID-19 pandemic has disrupted many health care activities. The impact of the pandemic on HIV primary care in a Boston community health center (CHC) that has specialized HIV, sexual and gender minority care is analyzed here.

Methods

The CHC has used the Centricity Practice SolutionTM electronic medical record (EMR) system since 1997. The current analyses used data abstracted from the EMR, testing for significant differences in HIV care utilization using the Student t-test for means and chi-square tests for proportions.

Results

There were 2,016 HIV+ patients among 25,606 patients (7.9%) engaged in primary care in 2019. In 2019, HIV+ patients had between 563 and 689 in-person visits per month. On average, monthly visits for HIV care increased (p< 0.0001) in the first two months of 2020 (mean=626, sd=60.1) compared to 2019 (mean=617, sd=40.6), but dropped to 370 and 36 in person visits by HIV+ patients in March and April 2020 respectively

(mean=203, sd=236.2; p< 0.0001), when statewide stay-at-home policies were recommended. There were 263 telemedicine visits by HIV+ patients in March and 751 in April, 2020. When telemedicine and in-person visits were combined, mean number of visits per month by HIV+ patients were higher compared to the same two-month period in 2019 (p< .0001). The mean number of plasma HIV RNA viral load (VL) tests performed each month was 279 in 2019 (range 257–312, sd=18.3), versus 219 in March and 274 in April 2020 (mean=246.5, sd=38.9; p< 0.0001). Among those tested, monthly rates of virological suppression ranged from 71–81% in 2019, with 11–20% having VL < 100 copies/ml. Eighty percent had an undetectable VL as their last measurement in 2019; an additional 14% had last VL detectable but < 100 copies/ml. In March and April, 2020, the rates of VL suppression were 77% and 74% and 14% and 18% had VL detectable but < 100 copies/ml, respectively (p=0.209).

Conclusion

The COVID-19 pandemic has led to a significant decrease in in-person visits by HIV+ and other patients at a Boston CHC, but with a rapid migration to the use of telemedicine, patient engagement, as expressed by visits and VL suppression does not appear to be adversely affected

Disclosures

All Authors: No reported disclosures
544. Severe COVID-19 in Children and Young Adults in the Washington DC Metropolitan Region
Authors: DeBiasi Roberta L , Song Xiaoyan , Ansusinha Emily , Smith Karen L , Bell Michael , Pershad Jay , Hahn Andrea , Hamdy Rana , Hanisch Benjamin , Harik Nada , Jantausch Barbara A , Koay Adeline , Campos Joseph M , Delaney Meghan , Simpson Joelle , Cora-Bramble Denice , Wessel David
Published: January 2021

Background

Children and young adults were initially reported as largely spared from severe complications of SARS-CoV-2 infection, but the impact to this population has been significant.

Methods

This observational retrospective cohort study includes 420 symptomatic children and young adults with lab confirmed SARS-CoV-2 infection treated between March 15 and June 16, 2020 at Children’s National Hospital in Washington DC. We identified and compared cohorts of non-hospitalized (N=324) and hospitalized (N=96) patients, including non-critically ill (N=64) and critically ill hospitalized (N=32) patients. Clinical and demographic data were extracted from medical records

Results

Of 420 SARS-CoV-2-infected symptomatic patients, 23% required hospitalization, of which 67% were non-critically ill and 33% were critically ill. All age groups were represented in the symptomatic cohort, with a median age of 8.6 years. Patients > 15 years of age represented 44% of critical care admissions. Males and females were equally represented in all cohorts. Underlying medical conditions were present in 36%, but more common in hospitalized (59 %) and critically ill (66 %) patients. The most frequent underlying diagnosis overall was asthma (16 %), but also included neurologic (6 %), diabetes (3 %), obesity (3 %), cardiac (3 %), hematologic (3 %) and oncologic (1 %) conditions. The majority (66 %) of SARS-CoV-2 infected patients presented with respiratory symptoms with or without fever. Other symptoms were also present, including diarrhea/vomiting (21 %), myalgia (11 %), chest pain (8 %) and loss of sense of smell or taste (7%). Hospitalized patients required varying levels of respiratory support, including mechanical ventilation, BiPAP, RAM cannula and HFNC. Additional presentations included diabetic hyperglycemia, sickle cell vaso-occlusive crisis, vascular complications, and multisystem inflammation. Treatment included remdesivir, convalescent plasma, tocilizumab and other therapies.

Conclusion

Although children/young adults have been less affected than elderly adults, the impact of SARS-CoV2 on this population has been significant in Washington DC and informs other regions anticipating their surge.

Disclosures

Andrea Hahn, MD, MS, Johnson and Johnson (Consultant)
545. The Impact of COVID-19 on African Americans’ Health Attitudes and Information Seeking Behavior
Authors: Kricorian Katherine , Equils Ozlem , Kricorian Karin , Rochebrun Brianna
Published: January 2021

Background

African-Americans suffer a disproportionate impact from COVID-19, comprising about 24% of deaths while representing 13% of the US population. We conducted a study to understand COVID-19’s impact on African-Americans’ health attitudes.

Methods

In April 2020, we surveyed online a national sample of US adults on their health attitudes and behaviors before and after the COVID-19 outbreak. Comparisons were analyzed using chi-squared tests.

Results

A total of 2,544 individuals completed the survey: 473 African-Americans, 282 Hispanics and 1,799 Caucasians responded. The mean ages of each group were 41.4 ± 11 years, 38.0 ± 11 years and 45.7 ± 13 years, respectively. Before COVID-19, African-Americans were least likely to report they had trust in science (53% vs. 68% for Hispanics and 77% for Caucasians; p< .01) and government (16% vs. 27% and 28%; p< .01). After COVID-19, the percentage of African-Americans who had trust in science and government fell further to 44% (p< .01) and 9% (p< .01), respectively, and remained significantly lower than the other two groups. Twice as many African-Americans vs. Caucasians stopped following science and health news after COVID-19 (9% vs. 4%, p< .01). The percentage of African-Americans who reported anxiety about their health rose from 30% pre-COVID to 53% after the outbreak (p< .01), and the percentage who reported anxiety about their family members’ health rose from 35% to 61% (p< .01). Only 25% of African-Americans surveyed agreed that if they contracted COVID-19, they were confident they would get the healthcare needed.

Conclusion

After COVID-19, African-Americans’ trust in science and government fell and a meaningful percentage stopped following science and health news, possibly reducing access to important health information. The percentage of African-Americans reporting anxiety about the future, about their health and about their family members’ health all increased significantly after COVID-19. Only a minority of African-Americans agreed they would get the needed healthcare if they contracted COVID-19. These findings have implications for the mental health and behavioral impacts of COVID-19 on African-Americans and for the development of health communications to high-disease-incidence populations.

Disclosures

All Authors: No reported disclosures
550. Clinical impact of Tocilizumab therapy in SARS-CoV-2 respiratory infections in ICU and non-ICU patients
Authors: Vyas Nikunj M , Hou Cindy , Levin Todd P , Fussa Mark , DeRose Joseph , Condoluci Mark , Williams James , Ghayad Zeina , Barnish Michael , Ali Shereef N , Kerr Kathryn H , Scheiblein Scott W , Fryckberg Anthony J , Chauhan Gauri
Published: January 2021

Background

Tocilizumab (TCZ) is a monoclonal antibody against the interleuikin-6 receptor which is potentially beneficial in COVID-19 induced cytokine release syndrome (CRS). However, there are limited studies showing anti-inflammatory effect and clinical benefit of TCZ in COVID-19 patients. This retrospective study examines treatment responses of criteria based TCZ therapy for SARS-CoV-2 respiratory infection for ICU vs. non-ICU patients.

Methods

We established institutional criteria to identify patients at risk of CRS from COVID-19. Patients were included if they received at least 1 dose of TCZ and were admitted for at least 72 hours. Primary endpoint was to assess clinical improvement (CI) at the end of admission. CI was defined by extubation, downgrade from ICU, discharged or improvement in Clinical Ordinal Scale by 2. Secondary endpoint of the study was to assess inpatient mortality (IM) and risk factors associated with IM. Subgroup analysis included impact of early (< 96 hours) vs late (≥ 96 hours) TCZ therapy on IM.

Results

Between March 25 to May 6, 2020, 170 patients met criteria and received TCZ. There were 83 non-ICU patients and 87 in the ICU. Forty five patients needed invasive mechanical ventilation (IMV). ICU patients tended to be obese, receive 2 doses of TCZ and have longer length of stay. Overall CI was seen in 71% of patients. CI was higher in non-ICU vs ICU patients (85.5% vs 57.5%, P=0.002). Overall IM was 18.8%; however, IM was lower in non-ICU vs ICU patients (8.4% vs 28.7%, P=0.0014). IM was higher in patients on IMV vs. non-IMV (30% vs 15.4%, P=0.03). Risk factors of ICU admission, BMI ≥ 30 kg/m2 and AKI were associated with higher risk of IM. Many IM patients were made comfort care. No differences were observed in early vs late TCZ therapy on inpatient mortality, but there was a trend toward lower mortality with early TCZ.

COS Review of Tocilizumab Patients

Conclusion

TCZ is an effective treatment option in patients with SARS-CoV-2 patients at risk of CRS. Patients receiving TCZ in non-ICU setting had a better response to treatment compared to ICU patients. Obesity and AKI were associated with higher risk of mortality, but there was no statistical difference in early vs late therapy. Further studies with control group and larger sample size are warranted.

Disclosures

All Authors: No reported disclosures
554. Early Clinical Outcomes with Tocilizumab for Covid-19: A Two-Center Retrospective Study
Authors: Smoke Steven , Raja Karan , Hilden Patrick , Daniel Nicole
Published: January 2021

Background

Severe Covid-19 is associated with elevated inflammatory markers, consistent with cytokine release syndrome (CRS). Tocilizumab is an IL-6 inhibitor, effective in treating CRS secondary to CAR-T cell therapy. The efficacy of tocilizumab in treating Covid-19 is unknown.

Methods

This was a retrospective cohort study conducted at two hospitals in northern New Jersey. All patients treated with tocilizumab for confirmed or suspected Covid-19 between the dates of 3/10/20 and 4/9/20 at the study sites were included. The primary endpoint was clinical improvement on day 7 after treatment as assessed by respiratory status. Univariate analysis compared data between those who improved and those who did not.

Results

Forty five severe and critically ill patients treated with tocilizumab for Covid-19 were evaluated. Eleven (24%), 22 (49%) and 12 (27%) patients improved, had no change and worsened by day 7 after treatment, respectively. Lower WBC and LDH at the time of drug administration as well as shorter time from supplemental oxygen initiation to dose were significantly associated with clinical improvement in the univariate analysis.

Conclusion

Tocilizumab administration was associated with a low rate of clinical improvement within 7 days in this cohort of severe and critically ill patients with Covid-19.

Disclosures

All Authors: No reported disclosures
556. Evaluation of Hydroxychloroquine-based Combination Therapies for the Treatment of COVID-19
Authors: Berti Andrew David , Kale-Pradhan Pramodini , Giuliano Christopher , Aprilliano Bianca , Miller Christopher R , Alyashae Basma , Bhargava Ashish , Johnson Leonard B
Published: January 2021

Background

During the early COVID-19 pandemic a large number of investigational agents were utilized due to lack of therapeutic options. We evaluate the utility of commonly-used investigational agents combined with hydroxychloroquine (HCQ).

Methods

This multicenter observational cohort study included patients admitted with COVID-19 between March - May 2020 in Detroit, Michigan who received at least 2 doses of HCQ. Our primary outcome was the change in Sequential Organ Failure Assessment (SOFA) score from presentation to day 5 of HCQ therapy with a secondary outcome of in-hospital mortality. Data collected included demographics, Charlson Comorbidity index (CCI), daily SOFA score, laboratory data and COVID-directed therapies. Multiple linear regressions were performed to control for potential confounders between different therapies and change in SOFA score.

Results

Three hundred thirty-five patients receiving HCQ were included. Patients were 62 ± 14.8 years of age, male (54%) and African-American (82%) with a mean CCI of 1.7 ± 1.9. In our cohort, 32% were admitted to the intensive care unit and 35% expired. Therapies received by more than 20% of patients in addition to HCQ included azithromycin (80%), zinc (76%) and vitamin D (29%). In our unadjusted analysis, a significant improvement in SOFA score was observed with zinc (0.76) while no significant change was observed with azithromycin (-0.46) or vitamin D (0.05). However, there was no significant change in SOFA score after adjusting for confounders for azithromycin, zinc and vitamin D. No difference in mortality was observed between the groups.

Conclusion

Overall, no benefit in end-organ damage or mortality was observed with the addition of azithromycin, zinc or vitamin D to HCQ. Further studies are needed to confirm this observation.

Disclosures

All Authors: No reported disclosures
560. Repurposing Eravacycline for the Treatment of SARS-CoV-2 Infections
Authors: Reig Núria , Shin Dong-Hae
Published: January 2021

Background

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is seriously impacting health and economies all over the world. With more than 8 million diagnosed cases and close to 450.000 deaths worldwide by mid-June 2020, the need of safe and effective treatments is extremely urgent. Drug repurposing is a suitable approach to bring new treatments to the clinics in a very fast and cost-effective way.

Methods

We have applied an artificial intelligence screening technology based on molecular fields to find drugs that could inhibit the SARS-CoV-2 3-chymotrypsin-like cysteine protease (3CLpro) among a library of compounds with clinical experience, approved drugs and drugs in clinical development. The results were refined by covalent docking at the catalytic domain of the protein and thirty compounds were chosen for experimental validation on a protease assay with recombinant SARS-CoV-2 3CLpro. The compounds were also tested for their inhibition of SARS-CoV and MERS-CoV 3CLpro. Positive hits were further tested in a VeroE6 cell infection assay with pathogenic SARS-CoV-2 using nucleocapsid protein staining at 24h post infection as a readout.

Results

Eravacycline was identified at the top positions of the screening and its potent inhibitory activity was demonstrated in vitro against recombinant SARS-CoV-2, SARS-CoV and MERS-CoV 3CL proteases, with IC50 of 1.65, 10.04 and 16.36 µM respectively. In addition, eravacycline inhibited infection of VeroE6 cells by pathogenic strains of SARS-CoV-2, with an IC50 of 30.61 µM in the absence of drug induced cell toxicity.

Conclusion

Eravacycline is an FDA and EMA-approved antibiotic that was launched in the US in 2018. It is a safe drug that is known to accumulate in the lungs at concentrations that are compatible with its in vitro activity against SARS-CoV-2. This, together with its known antibacterial activity that could help prevent secondary infections in hospitalized COVID-19 patients, and the known anti-inflammatory actions of tetracyclines, warrant further research on the potential role of eravacycline for the treatment of patients with COVID-19 or infected with SARS-CoV-2 but with milder symptoms.

Disclosures

Núria Reig, PhD, SOM Biotech (Employee) Dong-Hae Shin, PhD full professor, SOM Biotech (Scientific Research Study Investigator)
563. Tocilizumab in the Treatment of Critical COVID-19 Pneumonia
Authors: Fisher Matthew , Marcos Luis , Monteforte Melinda , Taub Erin , Go Roderick
Published: January 2021

Background

The anti-interleukin-6 receptor monoclonal antibody tocilizumab has been proposed as a treatment for COVID-19 pneumonia although the efficacy remains unknown.

Methods

Patients with COVID-19 confirmed by nasal swab PCR for SARS-CoV-2 who were admitted to Stony Brook University Hospital in Suffolk County, New York between March 10th and April 2nd and received tocilizumab while undergoing mechanical ventilation in any intensive care unit were retrospectively analyzed from data available in the electronic medical record. Baseline characteristics and clinical outcomes were compared to mechanically ventilated patients admitted during the same time period who received standard hospital protocol.

Results

Forty-five patients received tocilizumab compared to seventy controls. Mean dose of tocilizumab given was 4.8mg/kg and mean time to receipt from initial intubation was 2.5 days. Baseline demographic characteristics, inflammatory markers, treatment with corticosteroids, and SOFA scores were similar between the two cohorts (Table 1). Patients who received tocilizumab had significantly lower Charlson co-morbidity index (2.0 versus 3.0, p = 0.01) and higher temperature (38.7 C versus 38.2 C, p = 0.004) than controls. There was no significant association between receipt of tocilizumab and the rate of extubation within fourteen days (44.4 percent versus 34.2 percent; OR = 1.53, 95% C.I. 0.71 – 3.30), discharge from hospital (51.1 percent versus 40.0 percent; OR = 1.568, 95% C.I. 0.737 – 3.337), or mortality (31.1 percent versus 41.4 percent; OR = 0.639, 95% C.I. 0.290 – 1.4407) (Table 2). Patients who were administered tocilizumab within two days of intubation had increased likelihood of extubation within fourteen days compared to those who were treated later (OR = 3.50, 95% C.I. 1.01 – 12.18). There was no observed increased risk of secondary infection in patients given tocilizumab (28.9 versus 25.7, OR = 1.1736, 95% C.I. = 0.507 – 2.714).

Table 1: Patient Demographics and Baseline Characteristics

Table 2: Primary Outcomes

Conclusion

Tocilizumab was not associated with a significant improvement in rate of extubation, hospital discharge, or reduction in mortality in this retrospective cohort study of mechanically ventilated patients with COVID-19 pneumonia. Further studies are needed to determine whether earlier treatment may result in improved outcomes.

Disclosures

All Authors: No reported disclosures
564. Tocilizumab Induces Rapid, Sustained Improvement of Inflammatory Markers in COVID-19
Authors: Colgrove Robert , Morin Scott , Jani Chinmay , Rupal Arashdeep , Bourque Daniel L
Published: January 2021

Background

Frequent observation of increasing fever and rising inflammatory markers late after onset of COVID-19 suggests Cytokine Release Syndrome (CRS, “Cytokine Storm”) may contribute to pathophysiology. Tocilizumab (TCZ), a monoclonal antibody targeting the receptor for the pro-inflammatory cytokine, IL-6, is effective in suppressing pathological inflammation in several rheumatological diseases. After administering TCZ to COVID-19 patients with suspected CRS, we observed a sharp fall in inflammatory indices. We analyzed this effect using results from the first 19 COVID-19 patients receiving TCZ at our hospital.

Methods

Data for all patients with confirmed COVID-19 who received TCZ at our center, a 200 bed community hospital in New England, were extracted from the Electronic Medical Record, including demographics, body temperature, C-Reactive Protein (CRP), IL-6 levels, clinical severity on the Ordinal Scale for Clinical Improvement (OSCI), and clinical outcome (recovery/discharge home, partial recovery/discharge rehab, death). Results were tabulated and statistical significance of changes in indices pre- and post- TCZ assessed by Wilcoxon Signed-Rank Test.

Results

19 patients received TCZ: 16 got 400mg x1, 2 got 400 mg x2, 1 got 660 mg x1. Median age was 64 years (range: 44–94), 68% male. Mean interval from symptom onset to receiving TCZ was 11.5 days. Mean IL-6 was 145 pg/mL. Demographics, OSCI scores, and discharge status are shown in Table 1. Average daily peak temperatures (Tmax) pre- and post- TCZ were 100.7 and 98.9°F, p< 0.001. Mean CRP pre- and post- were 234 and 84.6 mg/L, p=0.001 (Fig.1). Decrease in Tmax and CRP was rapid and sustained (Fig. 2, 1st 8 patients shown for clarity.). 58% had improved clinical improvement by OSCI by day 7, 68% by day 14. 7 of 19 of patients were discharged home, 6 to rehab or acute care facility, and 6 died.

Table 1: Patient Demographics, Clinical Severity Score, and Discharge Status

Conclusion

In this cohort of patients with moderate-to-severe COVID-19 and evidence of Cytokine Release Syndrome, tocilizumab was associated with rapid resolution of fever and marked decline in CRP. Most patients showed improvement in clinical severity scores and no adverse reactions were noted. Tocilizumab may be useful in control of pathological inflammation in COVID-19. Controlled trials will be needed to assess overall clinical benefit.

Disclosures

All Authors: No reported disclosures
565. Tocilizumab Use in COVID-19: Act(emra) to Inhibit Intubation and Decompensation
Authors: Willner Debra M , Bengualid Victoria , Zada Ilanit , Berger Judith , Patel Nigam
Published: January 2021

Background

Tocilizumab is an IL-6 receptor inhibitor that has been utilized for the prevention and treatment of the cytokine storm inflammatory reaction in COVID-19. The objectives of this analysis were to evaluate clinical outcomes of tocilizumab treatment in relation to respiratory status improvements and to analyze the association between initial inflammatory markers and treatment outcomes.

Methods

IRB approved retrospective chart review of adult patients with confirmed COVID-19 treated with tocilizumab from March- May 2020. Data collection focused on relevant past medical history, hematologic and inflammatory markers before and after tocilizumab administration, concomitant COVID-19 treatments, and disease outcomes such as mortality and discharge. Assessed baseline characteristics and treatment outcomes in patients who received tocilizumab prior to intubation versus after intubation, and evaluated for any significant markers of treatment success and failure.

Results

84 patients were evaluated. Baseline characteristics did not vary between intubated and not intubated patients (Figure 1). Overall mortality in patients who received an IL-6 inhibitor was 43%. Mortality in patients who received IL-6 inhibitor when intubated (63%) compared to patients who were not intubated (26%) was significantly higher (p = 0.005). Patients with BMI’s of 30 or above and patients with diabetes had a higher rate of treatment failure (p < 0.05) (Figure 2). Patients with IL-6 levels of 1000 or above had higher rates of treatment failure (p = 0.0001); however, given the small sample size larger studies are required for further analysis (Figure 3).

Baseline Characteristics by Respiratory Status Pre-Tocilizumab Administration

Subgroup Analysis

Outcome by Baseline IL-6 Levels

Conclusion

Overall mortality in our patients was 43%; however, our sample size was small and the study did not have a control group to fully assess treatment success or failure. Comorbidities such as diabetes and obesity, and elevated IL-6 levels were associated with significantly higher rates of treatment failure. Randomized control trials are needed to determine the true benefit of tocilizumab in COVID-19.

Disclosures

All Authors: No reported disclosures
567. Use of corticosteroids and COVID-19 mortality in patients with pneumonia in a tertiary care center in México City
Authors: Cabrera-Ruiz Maria L , Castillo-Álvarez José Luis , Barragán-Reyes Armando , Bay-Sansores Daniela , Pulido-Enríquez Jessica Isabel , Castañeda-Mendez Paulo F , Soto-Ramírez Luis Enrique
Published: January 2021

Background

The use of corticosteroids, specifically dexamethasone has been associated to low mortality in COVID-19 patients. We present here the mortality related to the use of corticosteroids in the first two months of the SARS-CoV-2 outbreak in México City.

Methods

We conducted a case series of patients with the diagnosis of pneumonia due to SARS-CoV-2 virus admitted to a tertiary care center in Mexico City, between March 14th and May 14th, 2020. Data collected included demographic information, comorbidities, treatment and outcomes including mortality.

Results

We included 109 patients with diagnosis of COVID-19 associated pneumonia with computed tomography; 76(69.7%) were male and 33(30.3%) female with a median age of 52 yo (24–85) and 51 yo (25–81), respectively. Most common comorbidities were overweight (48.6%), obesity (35.8%), hypertension (23.8%), and diabetes (18.3%). Thirty-eight patients received corticosteroids (Methylprednisolone 30, Hydrocortisone 6 and dexamethasone and prednisone in on case). Mortality in those that used corticosteroids was 21% (8/38) and 5.6% for those that did not received (4/71), p=0.014.

Forty cases needed mechanical ventilation from the beginning, and 24 of those received corticosteroids with a mortality of 29% (7/24), while the mortality was 18.7% (3/16) in those with no steroid use, p=0.45.

Conclusion

Mortality in our small cohort with predominantly use of methylprednisolone is not lower in those using steroids. In fact, mortality was significantly higher in those that received corticosteroids, while this significance was not maintained in those that needed immediate mechanical ventilation. Use of corticosteroids for COVID-19 patients with pneumonia, should be further investigated.

Disclosures

All Authors: No reported disclosures
574. De-escalation of Broad Spectrum Antibiotics during Cytokine Release Syndrome with Haploidentical Hematopoietic Stem Cell Transplantation
Authors: Schiffer Molly , Perreault Sarah , McManus Dayna , Foss Francine , Gowda Lohith , Isufi Iris , Seropian Stuart , Topal Jeffrey E
Published: January 2021

Background

Fever is a common component of cytokine release syndrome (CRS) occurring in 90% of patients undergoing haploidentical hematopoietic stem cell transplantation (Haplo-HSCT). Fevers typically occur between the stem cell infusion (Day 0) and initiation of post-transplant cyclophosphamide and are often confused with febrile neutropenia (FN). Due to longer time to engraftment in Haplo-HSCT, CRS/FN exposes patients to prolonged courses of empiric broad spectrum antibiotic (BSA) therapy increasing the risk for multi-drug resistant organisms. Recently, at Yale New Haven Health, our practice has changed to now recommend antibiotic de-escalation to prophylaxis after 7 days of BSA if no infection is identified. The objective of this study was to assess the incidence of breakthrough infections with the de-escalation of BSA in CRS/FN. Secondary endpoints include rate of FN, rate of de-escalation, rate of recurrent fevers, duration of BSA, and positive blood culture data.

Methods

The patient population included those undergoing Haplo-HSCT between July 2016 and February 2020 and who developed CRS/FN between Day 0 and Day +5. Patients were excluded if they had prolonged hospitalization due to non-infectious complications or engraftment failure. Bacteremia was defined using NHSN definitions.

Results

Of the 53 Haplo-HSCTs assessed, 43 experienced CRS/FN. Thirty-five Haplo-HSCT (81%) with CRS/FN had negative cultures and 23 (66%) of these were de-escalated back to antibacterial prophylaxis. The median duration of BSA in the de-escalated group was 7 days (range 5–13) compared to 16.5 days range (13–21) in the non-de-escalated group (p< 0.001). Among those de-escalated, 7 (30%) had recurrent fever occurring at a median of 4 days (range 2–14) and were placed back on BSA. Two Haplo-HSCT (9%) that had fever after de-escalation developed a breakthrough bacteremia. No Haplo-HSCT after de-escalation had fever or re-admission for bacteremia 30 days after engraftment. Four Haplo-HSCT (9%) with CRS/FN had positive blood cultures; however, three (7%) were still able to be de-escalated from BSA to narrower agents based on susceptibilities.

Conclusion

De-escalation of BSA in FN/CRS in Haplo-HSCT patients reduced unnecessary, prolonged antibiotic exposure with a low incidence of breakthrough infections.

Disclosures

All Authors: No reported disclosures
576. Half-dose Valganciclovir Prophylaxis is Safe and Cost-effective in CMV Seropositive Renal Transplant Recipients
Authors: shi yiyun , Rogers Ralph , Vieira Kendra , Merhi Basma , Osband Adena , Bayliss George , Gohh Reginald , Morrissey Paul , Farmakiotis Dimitrios
Published: January 2021

Background

Observational studies suggest that half-dose valganciclovir (VGV) prophylaxis (450 mg daily for normal renal function) is as effective as full-dose (900 mg daily) in preventing CMV infection among kidney transplant recipients (KTR). However, this practice is not supported by current guidelines, for fear of selecting resistance, mainly in high-risk, i.e. donor CMV seropositive/recipient negative (D+/R-) KTR. Full-dose VGV is costly, and possibly associated with higher incidence of neutropenia and BK viremia. Our institution adopted half-dose VGV prophylaxis for R+ KTR in January 2018.

Methods

We included R+ KTR transplanted between 1/1/2014 and 12/31/2018 at our center. Data were censored at 1-year post-transplant, graft loss or death. Primary outcomes were early (< 6 months from transplant) and any CMV viremia. Secondary outcomes were neutropenia, BK viremia, graft loss and death. Categorical variables were compared with χ 2 or Fisher’s exact tests, continuous variables with the Mann-Whitney test. We used log-rank and Gray’s tests to compare cumulative incidence of outcomes, after adjustment by propensity score for differences in baseline characteristics.

Results

106 R+ KTR received full-dose and 35 half-dose VGV. Antithymocyte globulin (ATG) induction was associated with significantly higher cumulative incidence of both early (P=0.017) and any (P=0.02) CMV viremia, compared to basiliximab induction (Fig. 1). After adjusting for gender and induction regimen, we noted a signal for higher cumulative incidence of any (P=0.044), but not early (P=0.598) CMV viremia in the full-dose VGV group (Fig. 2). There were no significant differences (P >0.1) in incidence of neutropenia, BK viremia, graft loss or death between the two groups. Cost savings were estimated at $2630 per CMV R+ KTR (Table 1).

Table 1. Comparison of outcomes and cost between the two anti-CMV prophylaxis groups. Data are presented as n (%), unless otherwise indicated.

Fig 1. Probability of CMV viremia in KTR who received ATG vs. basiliximab induction.

Fig 2. Probability of CMV viremia in KTR who received full-dose vs. half-dose VGV prophylaxis.

Conclusion

In our pilot series, half-dose VGV was at least as effective as full-dose VGV in preventing CMV viremia in R+ RTR, and less costly. If larger scale studies verify generalizability of these results, half-dose VGV may be considered as standard of care for R+ KTR. In KTR, the antimetabolite probably contributes to neutropenia more than VGV prophylaxis.

Disclosures

All Authors: No reported disclosures
578. Infections in Patients Treated with Chimeric Antigen Receptor T-cells (CAR-T) therapy
Authors: Tran Nikki , Eschenauer Gregory , Scappaticci Gianni , Frame David , Miceli Marisa H , Patel Twisha S
Published: January 2021

Background

Although chimeric antigen receptor T cells (CAR-T) is a promising novel therapy for the treatment of relapsed or refractory (R/R) B-cell malignancies, data on infectious complications associated with this therapy are limited. Therefore, further assessment of infections after CAR-T therapy is warranted.

Methods

We retrospectively reviewed and analyzed infectious complications for 6 months following CAR-T therapy infusion (CTI) in 39 adult and pediatric patients with R/R acute lymphoblastic leukemia (ALL) and Non-Hodgkin Lymphoma (NHL) at Michigan Medicine.

Results

Overall, 20 infections were identified in 16 of 39 patients (41%) following CTI [detailed in Table 1]; 8 (40%) infections occurred in the early period (Day 0–30) and 12 (60%) infections occurred during late period (Day 31–180). The most common infections were viral (n=10, 50%; 80% of viral infections were respiratory viruses), followed by 8 bacterial infections (40%), and 2 fungal infections (10%). More bacterial infections were seen in the early period post-CTI (30% vs. 10%, p = 0.019), whereas viral infections were more common during the late period (40% vs. 10%, p = 0.68). Antimicrobial prophylaxis prior to CTI and following CTI were similar (Table 2). The majority of patients included in the study had NHL (n=32, 82%). Mean age of the cohort was 52 ± 22 years, and 64% were male. 85% of the population developed cytokine release syndrome (CRS) with 67% grade 1–2 and 18% grade 3–5. As shown in Table 2, most baseline characteristics were similar between patients with and without infections post CTI except infected patients were older (63.3 ± 11.3 vs. 44.8 ± 24.2, p = 0.01) and more received steroids for CRS (56% vs 17%, p = 0.02). All-cause mortality within 6 months following CTI was similar in infected and uninfected groups (38% vs 26%, p= 0.50).

Table 1

Table 2

Conclusion

Infectious complications are common following CAR-T therapy. We found the majority of infections to be caused by various bacteria or respiratory viruses in a cohort of patients with lymphoma as the most common underlying malignancy.

Disclosures

Marisa H. Miceli, MD, FIDSA, SCYNEXIS, Inc. (Advisor or Review Panel member)
579. Prophylactic Antibiotics Did Not Decrease Recurrent Cholangitis in Patients with Biliary Atresia After Kasai Portoenterostomy
Authors: Tarro Thomas M , Song Laurie , Carter Beth A , Yeh Meiyu , Pannaraj Pia S , Mohandas Sindhu
Published: January 2021

Background

Biliary atresia (BA) is a rare, progressive, idiopathic, fibro-obliterative disease of the extrahepatic biliary tree seen in children. The current standard treatment is surgical management with Kasai portoenterostomy (KP). Bacterial cholangitis is a frequent complication following KP and an important determinant of long-term prognosis. Use of prophylactic antibiotics is common but not universal and efficacy is controversial.

Methods

A retrospective study was performed that included all patients with BA who underwent KP from November 2002 to July 2019. Chart review was conducted to collect demographic information and evaluate the use of antibiotic prophylaxis, number of cholangitis episodes, time to liver transplantation (LVT), and survival.

Results

Ninety-one patients with BA underwent KP during the study period. Seventy-two (79%) received prophylactic antibiotics, and 19 (21%) did not. The median duration of prophylactic antibiotics was 7 months (interquartile range [IQR] 8.5). Patients in the no-prophylaxis group had significantly fewer cholangitis episodes (median 0, IQR 1) than in the antibiotic prophylaxis group (median 1, IQR 2), p= 0.0201. The median time to LVT was 8 months (IQR 8.5) in the antibiotic prophylaxis group, compared to 7 months (IQR 6) in the no-prophylaxis group, p=0.8827. Of the patients who were on antibiotic prophylaxis, 57 (79.2%) received trimethoprim-sulfamethoxazole (TMP-SMX) alone and 15 (20.8%) received multiple/other antibiotics. Seven patients (7.7%) had culture-positive cholangitis. Six of 7 received prophylaxis with TMP-SMX and 5 of 7 grew bacteria that were resistant to TMP-SMX. No deaths occurred between the postoperative KP period to the time of LVT in both groups.

Table 1. Characteristics of Patients in the Prophylaxis and No-prophylaxis Groups.

Table 2. Impact of Prophylactic Antibiotics in the Period Between Kasai Portoenterostomy and Liver Transplantation.

Table 3. Patients with Culture-positive Cholangitis after Kasai Portoenterostomy (n=7).

Conclusion

Antibiotic prophylaxis was frequently used after KP with TMP-SMX being the most common antibiotic used. Patients in the no-prophylaxis group had significantly fewer cholangitis episodes compared to those receiving antibiotic prophylaxis. Prophylactic antibiotics did not have an impact on time to LVT. Our findings suggest that antibiotic prophylaxis is not helpful in decreasing the frequency of cholangitis episodes after KP and may increase the risk for infections with resistant bacteria. Larger prospective randomized control studies are recommended.

Disclosures

Pia S. Pannaraj, MD, MPH, AstraZeneca (Grant/Research Support)Pfizer (Grant/Research Support)Sanofi Pasteur (Advisor or Review Panel member)
580. Refractory and Resistant CMV Infections in Hematopoietic Cell Transplant Recipients in the Letermovir Primary Prophylaxis Era
Authors: Sassine Joseph , Khawaja Fareed , Handy Victoria , Shigle Terri Lynn , Foolad Farnaz , Aitken Samuel L , Aitken Samuel L , Heredia Ella Ariza , Chemaly Roy F
Published: January 2021

Background

CMV reactivation is one of the most common infections after allogeneic hematopoietic cell transplantation (allo-HCT) and carries considerable morbidity and mortality. Primary prophylaxis with letermovir demonstrated in clinical trials reduction of the incidence of clinically significant CMV infection (CS-CMVi). This study aims at exploring the effect of letermovir primary prophylaxis on the occurrence of refractory or resistant CMV infections.

Methods

This is a single-center, retrospective cohort study of 537 consecutive allo-HCT CMV-seropositive recipients cared for between March 2016 and December 2018. Baseline demographics, transplant characteristics, CMV infections, treatment and mortality data were collected from the electronic medical record (Table 1). CMV outcomes were defined according to the standardized definitions for clinical trials. Data was analyzed on IBM® SPSS version 24 using a logistic regression model for multivariate analysis.

Results

Out of 537 patients identified, 123 received letermovir for primary prophylaxis during the first 100 days post-HCT and 414 did not. In a multivariate analysis, primary prophylaxis with letermovir was associated with a reduction in CS-CMVi (OR 0.11, 95% CI 0.06–0.20), CMV disease (OR 0.20, 95% CI 0.08–0.46) and refractory or resistant CMV infection (OR 0.11, 95% CI 0.02–0.49) (Table 2). Notably, there was no resistant CMV and no CMV-related mortality in the letermovir group. There was a trend towards lower all-cause mortality at day 100 in the letermovir group (OR 0.48, 95% CI 0.18–1.2).

Table 1 - Baseline Characteristics.

Table 2 - Multivariate Analysis of Clinical Outcomes.

Conclusion

Our study showed a strong association between primary prophylaxis with letermovir and reduction in refractory or resistant CMV infections and CMV disease in allo-HCT recipients.

Disclosures

Ella Ariza Heredia, MD, Merck Sharp & Dohme (Grant/Research Support)Oxford Immunotec (Grant/Research Support) Roy F. Chemaly, MD, MPH, FACP, FIDSA, Chimerix (Consultant, Research Grant or Support)Clinigen (Consultant)Merck (Consultant, Research Grant or Support)Novartis (Research Grant or Support)Oxford Immunotec (Consultant, Research Grant or Support)Shire/Takeda (Research Grant or Support)Viracor (Research Grant or Support)
582. Safety and Efficacy of High-Dose Ganciclovir versus Standard Dosing for Cytomegalovirus Viremia in Solid Organ Transplant (SOT) Recipients
Authors: Fitzmaurice Mary Grace , Srinivas Pavithra , Eckardt Jamie , Koval Christine , Koval Christine , Lum Jessica
Published: January 2021

Background

Standard dose ganciclovir (SD-GCV) for treatment of CMV infection/disease is 5 mg/kg every 12 hours, although higher doses (7.5–10 mg/kg every 12 hours) may be considered for resistant CMV. Literature on safety/efficacy of high dose GCV (HD-GCV) is limited. We sought to evaluate safety and clinical outcomes of SD-GCV vs HD-GCV strategies.

Methods

Retrospective single center study of adult SOT recipients with CMV viremia from 1/1/2017-1/31/2019 who received IV GCV therapy. Primary objective was to compare incidence of cytopenias between SD-GCV and HD-GCV. Secondary outcomes compared CMV viremia clearance, incidence of CMV disease and recurrent viremia within 30 days, granulocyte colony stimulating factor (G-CSF) use, and antiviral resistance testing rates.

Results

We evaluated 121 patients: 74 received SD-GCV, 47 received HD-GCV. Baseline characteristics were similar between groups. Most patients received a liver transplant (46% SD vs 36% HD) and had D+/R- CMV serostatus (55.4% SD vs 68% HD). Induction immunosuppression occurred in 75%, mostly with anti-thymocyte globulin. Median baseline CMV viral loads were similar (4620 IU/mL SD vs 7770 IU/mL HD, p=0.25).

Incidence of cytopenias was similar between groups: leukopenia (43% SD vs 43% HD, p=0.96), neutropenia (15% SD vs 13% HD, p= 0.75), thrombocytopenia (24% SD vs 31% HD, p=0.62). HD-GCV did not significantly impact CMV clearance (HR: 0.79 [95% CI 0.52–1.21], p=0.27). There was no difference in incidence of CMV disease (35% SD vs 38% HD, p=0.72) or incidence of recurrent CMV viremia (15% SD vs 28% HD, p=0.098).

G-CSF requirement was not different (23.7% SD vs 14.3% HD, p=0.295), however, patients on HD-GCV received more doses of G-CSF (median 2 SD vs 5 HD, p=0.001). More patients in HD-GCV group were tested for antiviral resistance: 15 (21%) SD vs 20 (43%) HD, p=0.01. Of these, there was no difference in rate of resistance detection (7/15 (47%) SD vs 11/20 (55%) HD, p=0.95).

Conclusion

Therapy with HD-GCV did not demonstrate increased incidence of cytopenias compared to SD-GCV, nor did we observe improved time to CMV clearance or incidence of CMV disease between groups. Opportunities exist for improving stewardship of antiviral resistance testing and use of G-CSF when considering HD-GCV therapy.

Disclosures

All Authors: No reported disclosures
583. Successful prevention of Strongyloides reactivation in liver transplant recipients with individualized screening and treatment: 10 year experience at a large transplant center in New York City
Authors: Rahman Farah , Taimur Sarah , Gitman Melissa R , Dunn Dallas , Baneman Emily , Fuller Risa , Jacobs Samantha E , Rana Meenakshi , Sullivan Timonthy
Published: January 2021

Background

Strongyloides stercoralis is an intestinal nematode that can establish chronic, asymptomatic infection in human hosts. Following solid organ transplantation, subclinical infection may progress to hyperinfection syndrome, which is associated with high morbidity and mortality. However, the optimal approach for screening and treatment of strongyloidiasis in liver transplant candidates in non-endemic areas is unknown.

Methods

We performed a retrospective chart review of all liver transplant (LT) recipients from 2010–2019. All patients were evaluated by an infectious diseases physician prior to transplant, and screening for Strongyloides exposure (with Strongyloides IgG antibody) was typically limited to those with risk factors for strongyloidiasis. Only patients with positive serologic testing or other evidence of strongyloidiasis were treated with ivermectin.

Results

One thousand and seventy-two LT cases (including 15 retransplants) were reviewed. Serologic testing was perfomed in 664 cases, of which 36 (5.4% of those tested, 3.4% of total) were positive. Of the 36 cases with positive serologic testing, 31 had identifiable risk factors including birth place, travel or eosinophilia. Eosinophilia (defined as peripheral eosinophila greater than 5%) was noted in 3 of the 36 recipients who had positive serology.

Of the total 36 cases with positive serology, 18 were treated both pre- and post-transplant, 7 were treated only pre-transplant and 9 were treated only post-transplant. One patient died prior to initiating treatment, and one did not have documented treatment. One patient with negative serologic testing was empirically treated due to persistent eosinophilia. There was one case of Strongyloides hyperinfection due to likely donor-derived infection. There were no cases of Strongyloides reactivation in the study cohort.

Conclusion

This study demonstrates that an individualized screening and treatment protocol can effectively prevent Strongyloides reactivation in LT recipients. Given the high mortality rate of Strongyloides hyperinfection, especially in solid organ transplant recipients, a methodical assessment of epidemiologic risk is essential for appropriate risk stratification and management of Strongyloides in LT candidates.

Disclosures

All Authors: No reported disclosures