bluuebunny/crossref_metadata_2025_split huggingface dataset:
1960. Mucosal rAd5 Immunization against SARS-CoV-2 Spike Elicits Cross-Reactive Nasal and Serum Neutralizing Antibodies and Protects Against Beta Variant Challenge in African Green Monkeys
Authors: Flitter Becca A , Tedjakusuma Sarah N , Lester Colin A , Neuhaus Elena D , Johnson Susan , Dora Emery G , Peinovich Nadine , Jegede Clara B , Tucker Sean N 
Published: December 2022

Abstract

Background
Mucosal vaccination may offer increased protection against SARS-CoV-2 compared to parental immunization. Here, we describe immunogenicity and efficacy following viral challenge in non-human primates after intranasal delivery of three unique non-replicating adenoviral vector vaccine (rAd5) candidates.

Methods
African green monkeys (AMG) were prime boost immunized 29 days apart with vaccine candidates either expressing the parental spike protein alone (Wuhan-S), spike plus nucleocapsid (Wuhan-S-N), or the spike protein from the beta variant (beta-S). Serum and nasal swabs were collected every 14 days and humoral responses to full length spike (S) and receptor binding domain (RBD) were assessed. All AMGs were challenged with SARS-CoV-2 B.1.351 (beta variant) on day 56. Viral loads measured every two days by TCID50 in nasal washes and bronchial lavage fluid post challenge.

Results
Mucosal immunization with Wuhan-S induced significant increases in serum IgG and IgA responses against the homologous parental lineage, as well as beta, delta, and omicron variants. In nasal samples, Wuhan-S immunization elicited over 500-fold increases in in cross-reactive IgA against multiple variants of concern including delta and omicron. While the beta-S rAd5 vaccine candidate induced enhanced serum IgG responses to homologous S and RBD proteins, this approach resulted in less cross-reactive antibodies to other variants compared to Wuhan-S rAd5 vaccine. Despite the differences in the ability to elicit cross-reactive antibody responses, all vaccinated AMGs challenged with SARS-CoV-2 B.1.351 (beta variant), had a significant reduction in viral titers by TCID50 in the nasal passages and reduced viral load in bronchial lavage fluid compared to unvaccinated controls.

Conclusion
These results demonstrate mucosal administration of rAd5 clinical candidate vaccine, Wuhan-S, is immunogenic and offers cross-protective humoral responses in both serum and nasal compartments against a mismatched SARS-CoV-2 challenge virus.

Disclosures
Becca A. Flitter, PhD, MPH, Vaxart Inc: Stocks/Bonds Sarah N. Tedjakusuma, n/a, Vaxart Inc: Stocks/Bonds Colin A. Lester, n/a, Vaxart Inc: Stocks/Bonds Elena D. Neuhaus, n/a, Vaxart Inc: Stocks/Bonds Susan Johnson, PhD, Vaxart Inc: Stocks/Bonds Emery G. Dora, n/a, Vaxart Inc: Stocks/Bonds Nadine Peinovich, MPH, Vaxart Inc: Stocks/Bonds Clara B. Jegede, n/a, Vaxart Inc: Stocks/Bonds Sean N. Tucker, PhD, Vaxart Inc: Stocks/Bonds.
1966. Protection afforded by prior infection, vaccination, and hybrid immunity against symptomatic BA.1 and BA.2 Omicron infections.
Authors: Altarawneh Heba N , Chemaitelly Hiam , Ayoub Houssein H , Tang Patrick , Hasan Mohammad R , Yassine Hadi M , Al-Khatib Hebah A , Smatti Maria K , Coyle Peter , Al-Kanaani Zaina , Al-Kuwari Einas , Jeremijenko Andrew , Kaleeckal Anvar Hassan , Latif Ali Nizar , Shaik Riyazuddin Mohammad , Abdul-Rahim Hanan F , Nasrallah Gheyath K , Al-Kuwari Mohamed Ghaith , Butt Adeel A , Al-Romaihi Hamad Eid , Al-Thani Mohamed H , Al Khal Abdul Latif , Bertollini Roberto , Abu-Raddad Laith J 
Published: December 2022

Abstract

Background
Protection offered by five different forms of immunity, combining natural and vaccine immunity, was investigated against symptomatic SARS-CoV-2 infection from Omicron BA.1 or BA.2, and severe, critical, or fatal COVID-19 from BA.1 or BA.2, in Qatar, between December 23, 2021 and February 21, 2022.

Methods
Six national, matched, test-negative case-control studies were conducted on a sample of 272,861 PCR-positive tests and 669,628 PCR-negative tests to estimate effectiveness of BNT162b2 (Pfizer-BioNTech) vaccine, mRNA-1273 (Moderna) vaccine, natural immunity due to prior infection with pre-Omicron variants, and hybrid immunity from prior infection and vaccination.

Results
Effectiveness of prior infection alone against symptomatic BA.2 infection was 46.1% (95% CI: 39.5-51.9%). Effectiveness of two-dose BNT162b2 vaccination alone was negligible at -1.1% (95% CI: -7.1-4.6), but nearly all individuals received their second dose &gt;6 months earlier. Effectiveness of three-dose BNT162b2 vaccination alone was 52.2% (95% CI: 48.1-55.9%). Effectiveness of hybrid immunity of prior infection and two-dose BNT162b2 vaccination was 55.1% (95% CI: 50.9-58.9%). Effectiveness of hybrid immunity of prior infection and three-dose BNT162b2 vaccination was 77.3% (95% CI: 72.4-81.4%). Meanwhile, prior infection, BNT162b2 vaccination, and hybrid immunity all showed strong effectiveness ( &gt;70%) against severe, critical, or fatal COVID-19 due to BA.2. Similar patterns of effectiveness were observed for BA.1 and for the mRNA-1273 vaccine. Figure 1.Effectiveness of prior infection, vaccination, and hybrid immunity against symptomatic Omicron infection and against severe, critical, or fatal COVID-19 for the BA.1 (panels A and B, respectively) and BA.2 (panels C and D, respectively) subvariants in the BNT162b2-vaccine study.Figure 2.Effectiveness of prior infection, vaccination, and hybrid immunity against symptomatic Omicron infection and against severe, critical, or fatal COVID-19 for the BA.1 (panels A and B, respectively) and BA.2 (panels C and D, respectively) subvariants in the mRNA-1273-vaccine study.

Conclusion
There are no discernable differences between BA.1 and BA.2 in the effects of prior infection, vaccination, and hybrid immunity. Vaccination enhances the protection of those with a prior infection. Hybrid immunity resulting from prior infection and recent booster vaccination conferred the strongest protection.

Disclosures
Adeel A. Butt, MBBS, Gilead Sciences: Grant/Research Support.
1973. The Antibody Neutralization Level after a BNT162b2 Vaccine Booster in Korean Healthcare Workers
Authors: Choo Eun Ju , Park Sunghee 
Published: December 2022

Abstract

Background
We compared neutralizing antibodies in healthy healthcare workers against two different coronavirus 2019 disease (Covid-19) vaccines, a messenger RNA (mRNA)-based vaccine (BNT162b2) and a genetically modified organism (virus vector) vaccine (ChAdOx1), to obtain immunity. In our cohort, we tried to compare the level of neutralizing antibody production after a BNT162b2 vaccine booster and to analyze the level of neutralizing antibody titers for delta and omicron variant.

Methods
On November 23 to 25, 2021 and December 23 to 24, 2021, a total of 2,133 HCWs at Soonchunhyang University Bucheon Hospital had been vaccinated with BNT162b2 (Pfizer-BioNTech). Among the 115 HCWs who participated in the preceding study, all participants had no history of Covid-19 infection or suspected symptoms at the time of registration. We collected blood samples from participants four weeks after a third dose. All blood samples were analyzed using the commercial virus neutralization test kit (Genscript Biotech Corporation, Piscataway, NJ, USA).

Results
Titers were measured 2 months after the initial vaccination and before the booster of the BNT162b2 vaccine (i.e. 6 months after the initial vaccination), and 4 weeks after the booster. Neutralizing antibody level measured by percentage inhibition of surrogate virus neutralization test (sVNT) readings at negative control (unvaccinated) and 4 weeks after booster vaccination. BNT/BNT/BNT group was defined as a booster dose with BNT162b2 (Pfizer) after two doses of BNT162b2 vaccine (Pfizer) 3 weeks apart. ChA/ChA/BNT group was defined as a booster dose with BNT162b2 (Pfizer) after two doses of ChAdOx1 vaccine (AstraZeneca/Oxford) 12 weeks apart.

Conclusion
We found that the neutralizing antibody levels against omicron variant were higher among those who received a booster dose of the BNT162b2 vaccine.

Disclosures
All Authors: No reported disclosures.
1980. A Case Series of Serratia Marcescens Endocarditis in Persons Who Inject Drugs
Authors: Cook Julia Christine , Anderson Matthew B , Barnes Erin W 
Published: December 2022

Abstract

Background
Serratia marcescens is a gram-negative bacillus that is widespread in the environment and has been recognized as a rare cause of infective endocarditis (IE), particularly in persons who inject drugs (PWID). The literature consists of a 19 person case series in the 1970s followed by just a handful of case reports and small case series. At AHWFB (Atrium Health Wake Forest Baptist), we have noticed an increasing number of severe infections, including IE, with Serratia marcescens in PWID.

Methods
We conducted a retrospective chart review of all cases of Serratia grown from sterile culture sites in the AHWFB system between 8/1/2016 -10/31/2021. Charts were reviewed to confirm status of injection drug use in the 3 months prior to admission, ≥18 years old, and possible or definite IE by Modified Duke’s criteria.

Results
Twenty two participants were included in the study. The median age was 29.5 years. Eighteen (90%) were white and 16 (73%) were female. Sixteen (73%) had injection of opioids and 3 (14%) had injection of stimulants clearly indicated. Ten (45.5%) had stimulant use documented but the route was not clear. Nineteen (95%) had evidence of active or resolved HCV infection. The median duration of bacteremia was 2 days. Two cases of IE involved the aortic valve, 8 mitral, 3 pulmonic, and 10 tricuspid. Four (18%) of the participants had prosthetic valve IE. Nine (41%) of the participants had a history of previous IE episode. Eighteen participants had evidence of septic emboli: 10 pulmonary, 7 cerebral, and 5 major arterial. In terms of disposition, 4 (18%) patients died, 4 left against medical advice, 12 (54%) remained at a facility for the duration of their antibiotics. One patient was transferred to another facility and one was discharged to complete antibiotic therapy via peripheral IVs in an infusion center. Two patients expired before a final antibiotic regimen could be determined. Ten participants were treated with beta lactam monotherapy, 1 with fluoroquinolone monotherapy, and 9 with dual therapy with a beta lactam and fluoroquinolone.

Conclusion
Serratia marcescens, a rare cause of IE, has been found in a population of PWID in a North Carolina hospital system. More research is necessary to understand why this unusual infection is clustering in this population and the optimal treatment regimen.

Disclosures
All Authors: No reported disclosures.
1987. One-Year Mortality and Reoperation Among Patients with Infective Endocarditis After Transcatheter or Surgical Aortic Valve Replacement
Authors: Papamanoli Aikaterini , Abboud Alan , Muncan Brandon , Parikh Puja B , Skopicki Hal A A , Kalogeropoulos Andreas P 
Published: December 2022

Abstract

Background
Treatment of severe aortic valve stenosis with transcatheter aortic valve implantation (TAVI) was initially developed for older patients at high surgical risk. However, with improving technology and experience, indications for TAVI have expanded to include younger patients and those at moderate surgical risk, leading to increasing use of TAVI as an alternative to surgical aortic valve replacement (SAVR). As a result, post-TAVI infective endocarditis (IE) is increasingly common. Data on post-TAVI IE in comparison to post-SAVR IE outcomes are limited.

Methods
Using data from the TriNetX Research Network, we identified (1) a cohort of patients who underwent TAVI between 1/1/2016 and 12/31/2020 (CPT procedure code 1021150) and developed IE (captured with ICD-10 codes I33, I38, or I39) after the procedure; and (2) a propensity score-matched cohort of patients who underwent SAVR (CPT procedure codes 1006141, excluding any associated transcatheter procedures) and developed IE. Both cohorts were required to have at least 1 week follow-up, i.e., deaths within 7 days of IE were excluded. We matched the cohorts for demographics and clinically relevant background characteristics. We used Kaplan-Meier estimates for 1-year mortality and aortic valve reoperation and Cox proportional hazards models to compare event rates.

Results
We identified 616 patients with post-TAVI IE and 616 matched patients with post-SAVR IE. The baseline characteristics of the cohorts were well balanced, as indicated by standardized mean differences &lt; 0.1, Table 1. The Kaplan-Meier 1-year mortality between 7 days and 1 year (as deaths before 7 days were excluded) was 20.9% in the TAVI cohort (117 events) vs. 13.0% in the SAVR cohort (72 events), HR 1.66 (95%CI 1.24-2.22; P=0.001), Figure 1. Reoperation for the aortic valve by 1 year was uncommon in both groups, with 12 and 10 events in the TAVI and SAVR groups, respectively (2.0% vs. 1.4%; HR 1.49, 95%CI 0.61-3.65; P=0.56).
Baseline Patient Characteristics After Matching
Figure 1
One-year survival post infective endocarditis after transcatheter aortic valve implantation (TAVI IE) or surgical aortic valve replacement (SAVR IE). Deaths within 7 days of infective endocarditis diagnosis were excluded.

Conclusion
In this comparative, propensity-matched cohort study, 1-year mortality after an episode of IE was significantly higher among TAVI recipients vs their SAVR counterparts. Repeat aortic valve procedures were uncommon in both groups. Prospective studies are needed to elucidate the causes of excess mortality among TAVI recipients.

Disclosures
All Authors: No reported disclosures.
2355. Prison as a Driver of Recent Transmissions of Multidrug-Resistant Tuberculosis in Callao, Peru
Authors: Utpatel Christian , Zavaleta Milagros , Rojas-Bolivar Daniel E , Mulhbach Andreas , Picoy Janet , Portugal Walter Jose J , Esteve-Sole Ana , Alsina Laia , Miotto Paolo , Bartholomeu Daniella , Sanchez Jorge , Alarcon Jorge O , Niemann Stefan , Huaman Moises A 
Published: December 2022

Abstract

Background
Peru has one of the highest rates of multidrug-resistant tuberculosis (MDR-TB) in the Latin America region, with Callao being one of the hot spots. We sought to identify resistance patterns and key drivers of recent MDR-TB transmission in Callao, Peru.

Methods
Cross-sectional study including clinical specimens identified as MDR-TB strains in Callao, Peru between April 2017 and December 2019. DNA was extracted for whole genome sequencing and data used for phylogenetic classification, clustering, and resistance causing mutation analyses. Recent transmission was defined based on an isolate-to-isolate distance of ≤5 (D5) single nucleotide polymorphisms (SNPs). We used logistic regression models to analyze the relationship between MDR-TB clustering and epidemiologic factors including age, sex, history of diabetes mellitus, HIV infection, illicit drug use, known TB contact, prior TB disease, and imprisonment.

Results
171 unique MDR-TB strains were included; 93% were assigned to lineage 4 and 7% to lineage 2. The most prevalent sublineage was 4.3.3 LAM (57%), followed by 4.3.4.2 LAM (10%) and 4.1.2.1 Haarlem (9%). In the dominant 4.3.3 LAM sublineage, concomitant resistance was common, including resistance mutations to pyrazinamide (92%), ethambutol (22%), ethionamide (23%), and quinolones (10%); 4 isolates harbored bedaquiline resistance mutations. Seventy-four percent of 4.3.3 LAM isolates were D5-clustered, with 53 (30%) isolates within a single dominant cluster. Male sex (odds ratio [OR], 3.6; 95% confidence interval [CI], 1.5 – 8.9), drug use (OR, 4.9; 95% CI, 1.9 – 12.7), and current or prior history of imprisonment (OR, 12; 95% CI, 3.3 – 43.5) were associated with the dominant D5 cluster in unadjusted analyses. History of imprisonment remained independently associated with the dominant D5 cluster in multivariate analyses (adjusted OR, 8.9; 95% CI, 1.6 – 50.6). History of imprisonment was also independently associated with being part of any D5 clusters in multivariate analyses (adjusted OR, 4.8; 95% CI, 1.2 – 20.3).

Conclusion
History of imprisonment was linked to current MDR-TB transmissions, indicating an important role of prisons in driving the MDR-TB epidemic.

Disclosures
Moises A. Huaman, MD, MSc, Gilead: Grant/Research Support|Insmed: Grant/Research Support.
2008. Real-World Experience of Administration of Bezlotoxumab in an Outpatient Infusion Center Upon Discharge in Recurrent Clostridioides difficile patients
Authors: Bradley Logan , Bland Christopher M , Jones Bruce M 
Published: December 2022

Abstract

Background
Bezlotoxumab is a humanized monoclonal antibody administered as single IV infusion that binds to Clostridioides difficile toxin B. It is currently recommended as a co-intervention in the updated 2021 IDSA guidelines for patients with recurrent C. difficile infection (CDI) in the last 6 months in addition to standard of care (SOC) antibiotics (vancomycin or fidaxomicin) to decrease CDI recurrence. Due to logistical issues and cost restrictions, administration is difficult as part of the inpatient stay. This case series evaluated a novel practice of discharging patients to receive bezlotoxumab immediately upon discharge from our not-for-profit community health system.

Methods
This was a retrospective chart review of all adult patients who received an outpatient infusion of bezlotoxumab after discharge between June 2019 and January 2022 for recurrent CDI. CDI was defined as ≥ 3 loose stools within 24 hours and a positive stool test for toxigenic C. difficile. The primary objectives were to evaluate the safety of bezlotoxumab in the outpatient setting and the rate of recurrent CDI at 12 weeks and 1 year. Recurrent CDI was defined using the same parameters as initial infection.

Results
Ten patients received bezlotoxumab in the outpatient setting after discharge and were included. Of the 10 patients, 2 were immunocompromised, 6 had at least stage 2 chronic kidney disease, and 4 required dialysis. All patients had &gt; 1 previous CDI in the past 6 months, ranging between 1-6 with the average being 2.4. The average time to infusion was 9.8 days after starting SOC antibiotics and 80% of patients received treatment within 24 hours of discharge. No patients reported adverse reactions during treatment. One patient with a previous diagnosis of heart failure was readmitted for a heart failure exacerbation 69 days after receiving bezlotoxumab. Two patients and 4 patients experienced CDI recurrence within 12 weeks and 1 year of infusion, respectively.

Conclusion
Discharging patients to receive bezlotoxumab as an outpatient infusion is a safe and effective way to treat recurrent CDI logistically and may offer a financial advantage to institutions to shift costs to an outpatient payment model. Recurrence rates compared to phase III trials of bezlotoxumab were similar at 12 weeks (20% vs. 16%).

Disclosures
Christopher M. Bland, PharmD, FCCP, FIDSA, BCPS, biomerieux, Inc.: Honoraria|Merck Pharmaceuticals: Advisor/Consultant|Merck Pharmaceuticals: Honoraria Bruce M. Jones, Pharm.D., FIDSA, BCPS, AbbVie: Advisor/Consultant|AbbVie: Honoraria|La Jolla: Honoraria|Melinta: Advisor/Consultant|Paratek: Honoraria|Regeneron: Honoraria.
2014. Central Line - Associated Bloodstream Infections and Their Increase With the COVID-19 Pandemic at Veterans Affairs in San Antonio, Texas
Authors: Chandramohan Divya , Ford Delvina , Beck Erica , Garza Lauren N , Reveles Kelly R , Cadena Jose 
Published: December 2022

Abstract

Background
Coronavirus disease-19 (COVID-19) has been associated with an increase in healthcare-associated infections (HAI). This increase is likely multifactorial (i.e. higher hospitalization rates, COVID-19 and post-COVID-19 complications, lower staffing, delayed care among others). The objective of this study was to determine the association between COVID-19 hospitalization rates and central line- associated blood stream infections (CLABSI).

Methods
We conducted a retrospective study in acute care unit hospitalizations in a Veterans Affairs (VA) hospital in San Antonio, Texas from October 2017 to December 2021. Individuals over 18 years of age admitted with a new diagnosis of COVID-19, determined by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) polymerase chain reaction (PCR) were included in the study. CLABSIs were defined by the National Healthcare Safety Network (NHSN) criteria for laboratory confirmed bloodstream infections. Pearson correlation was used to determine correlation of CLABSI and COVID-19 disease hospitalization rates. CLABSI rates were also compared pre-COVID-19 (Oct 2017-Feb 2020) to COVID-19 (Mar 2020-Dec 2021) periods using the chi-square test.

Results
During the study period, a total of 0.69 CLABSIs per 1,000 central line days occurred in the pre-COVID-19 period compared to 1.98 per 1,000 in the COVID-19 period (p=0.004). There was a significant correlation between CLABSI and ICU COVID-19 hospitalization rates (R=0.459; p=0.001) as well as CLABSI and acute care COVID-19 hospitalization rates (R=0.341; p=0.014). During the COVID-19 period only, there continued to be a significant correlation between CLABSI and COVID-19 ICU hospitalization rates (R=0.426; p=0.048).

Conclusion
CLABSI rates significantly increased during the COVID-19 period compared to the pre-COVID-19 period and CLABSI rates were significantly correlated with COVID-19 ICU and acute care hospitalizations. Accounting for this variable allows us to factor in impact of post-COVID-19 related complications and association with CLABSI rate. We urge for careful implementation of HAI prevention strategies during the pandemic. Awareness of anticipated increase is important in allocating resources essential for prevention of HAIs.

Disclosures
All Authors: No reported disclosures.