bluuebunny/crossref_metadata_2025_split huggingface dataset:
1114. Comparative analysis between Polymerized Type I Collagen and Baricitinib as potential treatment for COVID-19
Authors: Carpio-Orantes Luis Del , García-Mendez Sergio , Sánchez-Díaz Jesús Salvador , Aguilar-Silva Andrés , García-Hernández Omar , Salazar-Lizárraga Raúl Enrique , González-Arce América Alejandrina , Martínez-Rojas Manuel , Jiménez-Flores Oscar Rodrigo , Villalobos-López Luis Roberto , Hernández-Gómez Héctor Nahín , Domínguez-Cámara Rubén 
Published: December 2022

Abstract

Background
Baricitinib is a treatment authorized by the FDA for the treatment of moderate to severe COVID-19, despite this there are few approved drugs; polymerized type I collagen (PTIC) is a drug that has been used in Mexico with great potential for treating moderate to severe cases of COVID-19.

Methods
Comparative, descriptive and retrospective analysis of two populations of adult patients affected by COVID-19 confirmed by antigen test or RT-PCR as well as CO-RADS 6 CT, who consented to be treated between 2020 and 2021, a population using oral baricitinib at a dose of 4mg/day/14 days and another using polymerized type I collagen intramuscularly at a dose of 1.5ml every 12 hours for 3 days, followed by 1.5ml every 24 hours for 4 days; The most affected age and gender, comorbidities and laboratory abnormalities are analyzed, as well as improvement in inflammatory and oxygenation indices measured by pulse oximetry and SAFI (SpO2/FiO2), finally the outcome of the patients and the presence of adverse events.

Results
80 patients for each group, the most affected gender was male; the average age in the PTIC group was 51 years and in the baricitinib group it was 56 years; the main comorbidities were obesity, diabetes and hypertension in both groups; the decrease in acute phase reactants such as CRP, D-dimer and ferritin was greater in the PTIC group compared to the baricitinib group, the latter drug requiring a regimen of more days to achieve the objectives of the first drug (PTIC 7 days and baricitinib 14 days); Similarly, in oxygenation measured, the PTIC group reached goals in less time compared to the baricitinib group, which required twice as many days of treatment to achieve adequate oxygenation; Regarding the outcomes, there was a higher mortality in the baricitinib group compared to the PTIC group (6.25% vs 3.75%). Regarding adverse events reported for the PTIC group, they were minor and related to the intramuscular administration of the drug in 7 patients, while in the baricitinib group, 5 patients were reported with added bacterial pneumonia.

Conclusion
Polymerized type I collagen has anti-inflammatory and immunomodulatory potential similar to baricitinib in cases of moderate to severe COVID-19, even reaching treatment goals in less time both in inflammatory indices and in oxygenation indices.

Disclosures
All Authors: No reported disclosures.
1116. Comparative Efficacy of Tocilizumab and Baricitinib in Treatment of Severe COVID-19 Infections
Authors: Pellot Phylicia , Vyas Nikunj M , Hou Cindy , Rosati Michael 
Published: December 2022

Abstract

Background
Tocilizumab (TOCI) and baricitinib (BARI) have been shown to improve mortality in patients with severe COVID-19. However, there is limited comparative data between the two agents head to head. The purpose of this study was to evaluate patient characteristics and efficacy of BARI versus TOCI for the treatment of severe COVID-19.

Methods
A retrospective, observational chart review was conducted during September 2020 to November 2021 in a three hospital health system in New Jersey. Hospitalized patients were included if they were ≥ 18 years old, requiring supplemental oxygenation and being treated for severe COVID-19 with TOCI. These patients were then matched based on BMI, age, and severity of hypoxemia with patients who received BARI. Patients were excluded if they required invasive mechanical ventilation (IMV) at the start of therapy. The primary outcome of the study was to assess incidence of all cause inpatient mortality (ACIM) in patients receiving TOCI or BARI. A subgroup analysis was performed that assessed clinical improvement and progression to IMV between both treatment groups. Secondary endpoints included analysis of independent variables associated with ACIM.

Results
Total of 194 patients were screened for eligibility and of these 87 patients in the TOCI group were matched with 87 patients in the BARI group. Overall, there was no difference seen in ACIM between TOCI compared to BARI (22% vs 33% OR 1.11 (0.49-2.71, P=0.18). For subgroup analysis, more patients in TOCI group experienced clinical improvement compared to BARI group (44% vs 22%, P=0.004). Additionally, patients in TOCI group were less likely to progress to require IMV (10% vs 26%, P=0.02). When logistic regression model was used to assess mortality predicting factors, patients receiving BARI who required ICU level of care (OR 2.10, CI 0.91-0.08, p=0.00055) and IMV (OR 2.40, CI 1.16-3.64, p=0.00015) had higher odds of ACIM compared to TOCI.
Mortality predicting factors among patients receiving tocilizumab or baricitinib

Conclusion
There was no difference seen in ACIM between TOCI and BARI. At the end of hospitalization patients receiving TOCI were more likely to experience clinical improvement compared to BARI. TOCI should be preferred in patients requiring ICU level of care and IMV.

Disclosures
All Authors: No reported disclosures.
1117. COVID-19 Monoclonal Antibodies: A Single Center Real World Experience
Authors: Brenner Sara , Knee Alexander , Salvador Douglas , Housman Erica , Fernandez Gladys , Paez Armando 
Published: December 2022

Abstract

Background
COVID-19 monoclonal antibodies (mAb) have been shown to reduce risk of ED visit and hospitalization when administered early in disease course. However, there has been little data evaluating the challenges and barriers to delivering an outpatient mAb infusion.

Methods
This was a retrospective cohort review of patients referred 12/7/20-5/20/21 to evaluate factors associated with selection and treatment with mAb. Inclusion criteria included symptom onset within 10 days of referral, high-risk for severe disease, not hospitalized or meeting hospitalization criteria, and followed by in-network primary care provider. We collected data on demographics, high risk comorbidities, illness course, infusion selection, and adverse events. Using unadjusted regression models, we estimated effect sizes (mean difference or percentage point difference) and 95% confidence intervals to estimate baseline factors associated with infusion.

Results
Of the 230 eligible subjects, 179 (78%) were selected for mAb treatment and 119 (66%) were infused. Those with a Social Vulnerability Index &gt; 0.5 were more likely to be selected (86% vs 71%) but among those selected were less likely to be infused (59% vs 74%). Other predictors for selection (Fig 1) included Spanish language preference, 3+ symptoms at the time of referral, shortness of breath, headache, immunosuppressive medications, and chronic respiratory disease. Predictors of mAb infusion (Fig 2) included 3+ symptoms at time of referral, diarrhea, myalgias, male gender, being employed, and history of chronic kidney or respiratory disease. Time of onset of symptoms-to-referral was &lt; 5 days and test-to-referral was 2-3 days (Fig 3). 60 subjects were selected but not infused. 19 (32%) were not infused due to becoming ineligible after referral. Reasons for ineligibility included clinical decompensation or passing eligibility window. 39 (65%) were not infused due to refusal after selection. Most common reasons for refusal included feeling better (12, 20%), concerns about mAb (6, 10%), and lack of caregiver for a family member (4, 7%). Figure 1.Predictors of Selection for mAb InfusionFigure 2.Predictors of mAb Infusion After SelectionFigure 3.Days of Symptoms to Testing and Referral

Conclusion
Our study identified factors that impact selection and infusion of mAb in a real-world setting. This can help address potential barriers in operationalizing the administration of COVID-19 mAb in the future.

Disclosures
All Authors: No reported disclosures.
1127. Effectiveness of Remdesivir as Treatment for COVID-19 Positive US Veterans
Authors: Jeyapalina Sujee , Lundquist Margaret , Wei Guo , Stoddard Gregory , Agarwal Jay 
Published: December 2022

Abstract

Background
The COVID 19 disease has claimed over 6.3 million lives, globally. Despite such high casualties, the treatment options are limited. Although the FDA issued emergency use authorizations for oral antivirals to treat mild-to-moderate COVID 19 disease, intravenous Remdesivir treatment remains the only fully FDA-approved antiviral. However, many early studies questioned its efficacy. Accordingly, the WHO initially recommended against its use in COVID 19 positive patients. Based on the newly emerging data, as of 22 April 2022, WHO suggests that Remdesivir can be effectively used in mild or moderate COVID 19 cases. This retrospective cohort data analysis was undertaken to evaluate and clarify the effectiveness of Remdesivir use in older US veterans.

Methods
The deidentified veterans' data were accessed from the VA COVID 19 Shared Data Resources with local ethical approvals. Propensity matched cohorts with and without Remdesivir treatment were analyzed using Cox regression models, constructed in a way to avoid immortal time and calendar time biases. Limited to hospitalized veterans, patients were followed for 60 days to the outcomes of mechanical ventilation (MV) and death in separate models. The cohort was also limited to those who received low flow without high flow oxygen and a combination of low and high flow oxygen in another set of models.

Results
A total of 3,372 veterans were included in this study who were hospitalized between 01 January to 31 December 2021 for COVID 19 disease. Of those, 1,686 received Remdesivir treatment, while their matches never received it. After propensity score matching that included demography, vaccination status, comorbidities, medication use, lab tests, Remdesivir recipients and controls were similar in age (66.8±14.1 vs. 67.0±13.8 years). Relative risk reductions (1-HR), 53% for MV, and 42% for death (Fig. 1) were observed with low flow oxygen and Remdesivir therapy. In veterans who received high and low flow oxygen, although there was a significant 18% reduction in risk for death, progression to MV was not significant (P=0.22). Figure 1A forest plot showing the hazard ratios (HRs) for death and mechanical ventilator use in hospitalized US veterans with COVID-19 positivity between 01st of January to 31st of December 2021.

Conclusion
The data showed significant risk reductions of disease progression to MV/death when Remdesivir was used in COVID 19 positive patients with low supplementary oxygen flow, supporting the current NIH recommendation.

Disclosures
Sujee Jeyapalina, PhD, Dr. Jeyapalina received funding from Gilead Sciences, Inc. for COVID-19 data research: Grant/Research Support Gregory Stoddard, Mstat, Greg Stoddard received funding from Gilead Sciences, Inc. for COVID-19 data research: Grant/Research Support Jay Agarwal, MD, Dr. Agarwal received funding from Gilead Sciences, Inc. for COVID-19 data research: Grant/Research Support.
1128. Efficacy and Safety of Nelfinavir in Asymptomatic and Mild COVID-19 Patients: A Multicenter, Randomized Controlled Trial
Authors: Kohno Shigeru , Miyazaki Taiga , Hosogaya Naoki , Morimoto Shinpei , Yamamoto Hiroshi , Iwami Shingo , Miyazaki Yoshitsugu , Hanaoka Hideki 
Published: December 2022

Abstract

Background
Nelfinavir, an orally administered inhibitor of human immunodeficiency virus protease, inhibited the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro. To evaluate the efficacy and safety of nelfinavir, we conducted a randomized controlled trial.

Methods
Adult patients testing positive for SARS-CoV-2 infection within 3 days were eligible for the study if they had no or mild symptoms of coronavirus disease 2019. Exclusion criteria included the followings: onset of symptoms ≥ 8 days before enrollment; oxygen saturation of 95% or less on room air; and vaccinated patients. Patients were randomly assigned (1:1) to receive oral nelfinavir 750 mg (×3 times daily) combined with standard-of-care or standard-of-care alone. The primary endpoint was the time to clearance of SARS-CoV-2. Saliva was collected every day and viral load was measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Nelfinavir was administered for 14 days. However, the treatment could be discontinued by the decision of investigator, if patients had 2 consecutive negative test results by qRT-PCR. Clinical course and safety information were collected through day 28. The study is registered with the Japan Registry of Clinical Trials (number, jRCT2071200023).

Results
Between July 2020 and October 2021, 123 patients (63 in the nelfinavir group and 60 in the control group) were enrolled into the study and included in the analysis. The median time to viral clearance was 8.0 (95% confidence interval [CI] 7.0 to 12.0) days in the nelfinavir group and 8.0 (95% CI 7.0 to 10.0) days in the control group without statistically significant difference between the treatment group (hazard ratio 0.815, 95% CI 0.563 to 1.182; P = 0.1870).
Adverse events were reported in 47 (74.6%) patients in the nelfinavir group and 20 (33.3%) in the control group. The most common adverse events in the nelfinavir group were diarrhea (49.2%) and nausea (6.3%).

Conclusion
Nelfinavir did not reduce the time to viral clearance in this setting.

Disclosures
Shigeru Kohno, n/a, Pfizer: Grant/Research Support|Pfizer: Honoraria Taiga Miyazaki, n/a, Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria.
1133. Investigation of Treatment-Emergent Amino Acid Substitutions in Nonstructural Protein 5 from Ph2a Study of Ensitrelvir, a Novel Oral SARS-CoV-2 3C-Like Protease Inhibitor
Authors: Sanaki Takao , Baba Keiko , Yamamoto Atsuko , Nobori Haruaki , Uehara Shota , Kajiwara Yoko , Yoshida Ryu , Sakaguchi Hiroki , Hasegawa Takahiro , Hatanaka Akifumi , Ichihashi Genki , Takeda Yosuke , Shishido Takao , Uehara Takeki 
Published: December 2022

Abstract

Background
Ensitrelvir is a novel oral SARS-CoV-2 3C-like protease inhibitor, and under late clinical development stage for COVID-19 disease. In Ph2a and Ph2b studies, ensitrelvir demonstrated rapid decline of viral titer and viral RNA compared with placebo, and tolerability. To investigate treatment-emergent amino acid substitutions (TEAASs), we analyzed viral RNA sequences of nonstructural protein 5 (NSP5), target of ensitrelvir from Ph2a study in Japan.

Methods
In Ph2a study, 69 patients with confirmed SARS-CoV-2 infection were randomized 1:1:1 to ensitrelvir with the loading dose on Day 1/maintenance dose on Day 2-5 (375/125 mg or 750/250 mg), or placebo. Intent-to-treat (ITT) population was defined as participants confirmed with positivity by qualitative RT-PCR at baseline. TEAASs were defined as novel amino acid substitutions identified after treatment with ensitrelvir. NSP5 sequence analysis was performed with sanger sequencing using nasopharyngeal swab samples at Day 1, 6, 9, 14, and 21 with allowances from ITT population with ensitrelvir. Infectious viral titer was measured by virus-induced cytopathic effects in VeroE6/TMPRSS2 cells. Viral RNA was quantified by RT-PCR.

Results
By NSP5 sequence analysis, TEAASs were observed in 1 patient from 375/125 mg group and 2 patients from 750/250 mg group. H246Y in 375/125 mg was detected from specimen on Day 8, and A234S and T198I in 750/250 mg were detected from specimens on Day 8 and Day 14, respectively. Structural analysis revealed that these mutations are located outside of the active center of 3C-like protease which is the binding site of ensitrelvir. Viral titer and viral RNA in each specimen, in which TEAASs were observed, were below lower limit of detection and lower limit of quantification, respectively. Furthermore, H246Y, A234S and T198I are rare substitution (&lt; 0.05%) among SARS-CoV-2 variants according to Global Initiative on Sharing Avian Influenza Data.

Conclusion
In Ph2a study, H246Y, A234S, and T198I in NSP5 were detected as TEAASs. However, results of viral titer and viral RNA, and structural information suggest that these mutations do not have the impact on antiviral efficacy of ensitrelvir.

Disclosures
All Authors: No reported disclosures.
1135. Monoclonal Antibody Therapeutics in US Veterans against Delta and Omicron SARS-CoV-2 Variants
Authors: Mann Inderjit , Froehlich Morgan , Lier Audun J , Psevdos George 
Published: December 2022

Abstract

Background
Anti-SARS-CoV-2 monoclonal antibodies (mABs) target the viral spike protein and have been shown to have clinical benefit in treating COVID-19. The FDA had given emergency use authorization to mAB products: bamlanivimab+etesevinab (BAM), casirivimab+imdevimab (CAS), sotrovimab (SOT). However, due to reduced activity against the omicron variant the FDA recommended against use of BAM and CAS. SOT has retained efficacy against omicron. We reviewed the utilization of mABS in our institution during the pandemic as delta variant was replaced by omicron.

Methods
Retrospective chart review of US Veterans (USV) with confirmed SARS-CoV-2 infection who received mABs from 9/1/2021 to 2/28/22 at Northport Veterans Affairs Medical Center. Demographic data, comorbidities, choice of mAB, history of COVID-19 vaccination, SARS-CoV-2 sequencing, and IgG levels to the receptor-biding domain (RBD) of the spike protein in vaccinated USV were reviewed.

Results
66 USV received mAB therapy, tolerated well. 30 got CAS, 29 BAM, 7 SOT. 52 doses were given from Dec 2021 to Jan 2022, none were given in Feb. The median age of the cohort was 72.5 (range 32 to 97 years). 97% were men. 85% White, 12% Black, 3% Hispanic. 22 USV were not vaccinated. The vaccine recipients were: 3 Janssen, Moderna-2 shots (MOD-2): 6; MOD-3: 3; Pfizer 2 (PFZ-2) shots: 22; PFZ-3:10 The median days of COVID diagnosis from last dose of vaccine: Janssen 211 days (104 to 257); MOD-2 291 (205-322); MOD-3 56 (16-61), PFZ-2 222 (96-302) PFZ-3 78 (8-112). 62% had cough, dyspnea 24%, malaise 50%, diarrhea 11%, anosmia 11%, sore throat 17%, nasal congestion 41%, fever 32% Median BMI 30.8 (16.6 - 47.3). 36% had Diabetes, HTN 67%. COPD 23%, Asthma 11%, CAD 32%, HLD 67%; one woman was 28 weeks pregnant. Two coinfections with rhinovirus, 1 with RSV. 20 vaccine recipients had anti-SARS-CoV-2 RBD titers at presentation, median 2.60 (0.06-48.08). 11 USV were hospitalized but only 4 got steroids/remdesivir. 3 USV died but not directly due to COVID. 15 USV with omicron who received CAS (8) and BAM (7) survived. See tables for further data.
Demographic Data of US Veterans after receiving monoclonal antibody therapy
Data on hospitalized US Veterans after receiving monoclonal antibody therapy

Conclusion
As the pandemic transitioned from Delta to Omicron variants, mAB treatments in USV remained successful even in those USV who received therapies not active for omicron. Delta and omicron infections were seen in vaccinated and boosted USV.

Disclosures
All Authors: No reported disclosures.
1139. Oral Antivirals Against SARS-CoV-2: a New Valid Strategy Against COVID-19
Authors: Braccialarghe Neva , Cavasio Rosario Alessandro , Zaçe Drieda , Spalliera Ilaria , Coppola Luigi , Marco Iannetta , Sarmati Loredana , Andreoni Massimo 
Published: December 2022

Abstract

Background
Since the outbreak of COVID-19 pandemic the scientific community efforts have been focused on finding a vaccine and a treatment for infected people. Several antivirals with activity against SARS-CoV-2 were investigated and since the end of 2021 orally administered antivirals have been used in positive patients.

Methods
We conducted a retrospective, single-center study including data from 135 outpatients who resulted positive for SARS-CoV-2 and were selected according to AIFA criteria to receive Molnupiravir (M) or Nirmatrelvir/Ritonavir (N/R) in the Infectious Disease Clinic of the Tor Vergata Hospital from January 2022 to February 2022.

Results
Our cohort included 135 patients with a median age of 71 years (IQR 56,5 – 80,5), 51% were male, 91% received M and 9% received N/R. The median time of antiviral administration from symptoms onset was of 3,4 days. 75% of patients were vaccinated with booster dose, 19% were vaccinated with two doses and 7% were unvaccinated. The most frequent criteria of eligibility are summarized in Figure 1. Only 2 patients were hospitalized receiving oxygen support, 1 patient died, 84% of patients did not need hospitalization and 14% of the enrolled subjects were lost at follow up. Time of negativization at the nasopharyngeal swab (NPS) had a negative correlation to the value of anti-Spike (r=-0.29; p=0.01).
The difference between cycle threshold (Ct) value of NPS at T7 and Ct value at the first positive NPS (T0) was higher among not hospitalized (NH) vs hospitalized (H) patients, for Gene E [12.1 (SD 5.8) vs -1.7 (SD 10.8); p=0.02], Gene N [12.3 (SD 10.8) vs -0.9 (SD 11.6); p=0.01] and Gene RdRp [11.8 (SD 5.3) vs -1.5 (SD 11.1); p=0.01]. Anti-Spike were higher among NH vs H patients [1714 (SD 1044.7) vs [43 (SD 60.3); p=0.028].
Delta Ct E, delta Ct N and delta Ct RdRp were significantly higher in patients without neoplastic disease (p=0.04, p=0.02, p=0.01, respectively) and had a negative correlation with creatinine levels (r=-0.36, p&lt; 0.001; r=-0.3, p=0.03; r=-0.32, p=0.02).
Percentage of eligibility criteria of our patients
The majority of patients had more than one criterion

Conclusion
Oral antivirals represent a new effective treatment against COVID-19 in selected patients, reducing the time of negativization and the risk of hospitalization and death. Solid tumor or oncohematologic diseases are associated to a slower negativization of NPS.

Disclosures
All Authors: No reported disclosures.