bluuebunny/crossref_metadata_2025 huggingface dataset:
1094. Multisystem Inflammatory Syndrome in Children (MIS-C) in Persons Fully Vaccinated with Two Doses of mRNA COVID-19 Vaccine Compared with Persons with Partial or No Vaccination Reported, U.S. National MIS-C Surveillance
Authors: Yousaf Anna R , Miller Allison D , Lindsey Katherine , Wu Michael J , Melgar Michael , Zambrano Laura D , Campbell Angela P
Published: December 2022

Background

CDC began collecting COVID-19 vaccination status of persons with MIS-C as part of national surveillance in May, 2021. We describe and compare MIS-C in fully vaccinated persons with MIS-C in persons with partial or no vaccination reported.

Methods

We identified COVID-19 vaccine age-eligible persons meeting the CDC MIS-C case definition reported by health departments as of March 28, 2022 and divided them into 3 groups for this analysis: 1) fully vaccinated (receipt of a 2-dose mRNA primary vaccine series with MIS-C onset ≥28 days after vaccine dose 2 to account for the delay between infection and MIS-C), 2) partially vaccinated (MIS-C onset after dose 1 or < 28 days from dose 2 or receipt of Janssen [Johnson & Johnson] vaccine and 3) no vaccination reported. We compared characteristics between the groups.

Results

Of 7,880 MIS-C cases reported, 1,085 were vaccine eligible: 45 were fully vaccinated, 64 partially vaccinated, and 976 had no vaccine reported. Demographic characteristics were similar, although the Northeast had the lowest percentage of persons with vaccination not reported (Table). Though not statistically significant, fully vaccinated persons less frequently had severe cardiac involvement (67% vs 74%), shock (33% vs 44%), severe hematologic involvement (47% vs 54%), and mucocutaneous involvement (53% vs 63%) compared with those with no vaccine reported (Table). Forty-four percent of those fully vaccinated required ICU-level care vs 59% with no vaccine reported (p=0.053). Nineteen (2%) of those without vaccine reported died; no fully or partially vaccinated persons died. Table.Demographic and clinical characteristics of individuals with MIS-C with COVID-19 vaccine not reported compared to partially and fully vaccinated individuals

Conclusion

Persons who acquire SARS-CoV-2 infection after being fully vaccinated can develop MIS-C, with similar clinical characteristics to those with no vaccination reported. A lower but not statistically significant percentage of fully vaccinated persons required ICU-level care compared with those without vaccination, and there were no deaths in the fully vaccinated group. These data do not account for trends in MIS-C over time, including the influence of circulating SARS-CoV-2 variants on MIS-C clinical manifestations. We will continue to evaluate these comparisons as the sample size of reported MIS-C cases increases.

Disclosures

All Authors: No reported disclosures.
1100. SARS-CoV-2 Seroprevalence in Kenyan Youth living with HIV
Authors: Boyle Mary , Nyandiko Winstone , DeLong Allison , Chory Ashley , Aluoch Josephine , Ashimosi Celestine , Munyoro Dennis , Biegon Whitney , Gillette Emma , Lidweye Janet , Nyagaya Jack , Sang Edwin , Singh Manjot , Jepkemboi Eslyne , Orido Millicent , Novitsky Vladimir , Hogan Joseph , Vreeman Rachel , Kantor Rami
Published: December 2022

Background

SARS-CoV-2 seroprevalence studies can inform pandemic spread. By February 2021, estimates demonstrated 11%-62% seroprevalence in diverse Kenyan populations, with geographic variability and temporal increase, and well in excess of 0.2% laboratory-confirmed cases. The impact of HIV on seropositivity, particularly in youth living with HIV (YLWH) is unclear.

Methods

During February to September 2021, before SARS-CoV-2 vaccination, we cross-sectionally enrolled perinatally-infected YLWH in western Kenya in four sites (Eldoret, tertiary referral center; urban Kitale, peri-urban Turbo, rural Webuye), and determined seropositivity using the Bio-Rad Platelia assay. Additional evaluations included HIV viral load (VL), CD4 and a COVID-19-focused survey. Multiple logistic regression was used to measure associations of seropositivity with age, gender, enrollment month, site, HIV treatment failure (VL > 1,000 copies/ml), and CD4 (≥ 500 vs < 500 cells/μL).

Results

Of 241 YLWH, 29% were seropositive, 68% seronegative and 4% equivocal. Temporal trends (linear relationship per subsequent enrollment month; Odds Ratio (OR) 1.29 [95% Confidence Interval (CI), 1.06-1.58], p=0.013) and geographic variability (Eldoret-25%, Kitale-20%, Turbo-25%, Webuye-56%; p=0.027) were observed. Presumptive or laboratory-confirmed COVID-19 diagnosis, hospitalization, or death were absent. Self-reported illness was similar among seropositives and seronegatives, and highest in Webuye. Seropositivity was significantly associated with being male (OR, 1.06 [95% CI, 0.57-1.98], p=0.848), and age 15-17 years vs < 15 (OR, 2.57 [95% CI, 1.16-5.93], p=0.023), not with VL or CD4. Among seropositives, above-range titers were seen in 57%.

Conclusion

Of 241 Kenyan YLWH, 29% were SARS-CoV-2 seropositive by August 2021, with geographical, temporal, and age differences, and most seropositives mounting a robust response. Increased prevalence in rural Webuye may reflect less widespread mask-wearing, or its location on a busy transit route. Speculations on why seropositivity is low compared to earlier estimations, like HIV status, failed seroconversion, waning immunity, perception of risk promoting adherence to mitigations, or exposure to research-related guidance, should be investigated.

Disclosures

Rami Kantor, MD, Gilead Sciences: Grant/Research Support.
1101. Spectrum of Disease in Children Infected with SARS-CoV-2
Authors: Gillen Sarah , Wells Taylor , Sharon Bazak
Published: December 2022

Background

The COVID-19 pandemic is affecting children worldwide. Although pediatric infections are usually mild, children are at risk for complicated disease. It is imperative that we collect key data of children with COVID-19 to expand understanding of the epidemiology and pathophysiology of this disease. The objective of this research was to describe the demographic and range of pathology in children infected with SARS-CoV-2.

Methods

Pediatric COVID care at the University of Minnesota is coordinated through a multidisciplinary team that also contributes to a national registry for children infected with SARS-CoV-2. Utilizing these mechanisms, we identified children infected with SARS-CoV-2 including those presenting to our health system to create a COVID-19 cohort. Inclusion criterion was confirmed SARS-CoV-2 infection, and exclusion criterion was opt-out of research on general consent form. Following IRB approved protocol, we collected demographic data and clinical information on those with symptomatic disease following SARS-CoV-2 infection.

Results

As of February 2022, we reported 7440 children with SARS-CoV-2 to the national registry. We identified a cohort of 163 children with new onset disease or exacerbation of existing illnesses in association with COVID-19. The majority (110) experienced mild-to- moderate acute COVID-19, while 10 had severe COVID-19 pneumonia. Multisystem Inflammatory Syndrome in Children (MIS-C) was diagnosed and successfully treated in 34 children. Inflammatory diseases and invasive infections developed in 40 children. Long COVID was diagnosed in 42 children with lingering symptoms affecting daily function at least 3 months following infection.

Conclusion

This cohort includes children across clinical settings and can be regarded as a representation of COVID-related illness. Of those with symptomatic illness, acute illness is most common, usually mild-to-moderate with 6% developing severe pneumonia. Long COVID syndrome is also commonly seen in children. 24% of children infected with the virus present with inflammatory and immune-mediated illnesses suggesting the role of SARS-CoV-2 in triggering immune dysregulation pathologies. The overall spectrum of pediatric COVID-19 infection suggests a multiphase, immune-mediated contagion.

Disclosures

All Authors: No reported disclosures.
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

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

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

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 > 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 < 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

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

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

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 (< 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

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

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< 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.
1159. Treatment experience of regdanvimab for mild to moderate COVID-19 hospitalized patients in the Delta variant-predominant period in Korea
Authors: Kwak Yee Gyung , Song Je Eun , Lee Myung Jin , Kim Baek-Nam
Published: December 2022

Background

Regdanvimab is the only monoclonal antibody available in Korea that targets the receptor-binding domain of SARS-CoV-2. Although the efficacy of regdanvimab against the original and beta variant viruses was demonstrated, it remains uncertain whether it has therapeutic effect on delta variant in the real world.

Methods

We retrospectively evaluated the characteristics and clinical outcome of patients hospitalized for COVID-19 and treated with regdanvimab in two university-affiliated hospitals between September and December 2021, during the delta variant-predominant period in Korea.

Results

A total of 374 mild to moderate COVID-19 patients treated with regdanvimab were included in this study. The median age was 65 (interquartile range, IQR 17-92) and 178 (47.6%) patients were male. A total of 322 (86.1%) patients had median 2 (IQR 1-3) risk factors for disease progression. The most common underlying disease was cardiovascular disease (198, 52.9%), followed by diabetes mellitus (95, 25.4%), cancer (40, 10.7%), chronic lung disease (34, 9.1%), immunosuppression (1 7, 4.5%), and chronic kidney disease (12, 3.2%). There were 43 (11.5%) patients with a body mass index ≥ 30. The median time to regdanvimab treatment from symptom onset was 4 (IQR 2-6) days. 226 (60.4%) patients were fully vaccinated, and 109 (29.1%) were not vaccinated at all. 185 (49.5%) patients had pneumonia. Most (342/374, 91.4%) patients improved without any other treatment for COVID-19 and were discharged. Only 32 (8.6%) patients required other therapeutic agents such as remdesivir, corticosteroids or oxygen therapy after regdanvimab administration. The time from regdanvimab infusion to addition of other therapeutic agents was median 5 days (IQR 3-6.5). When comparing the characteristics of 32 patients who needed other treatment with those who improved only with regdanvimab treatment, there was a significant difference in the presence of pneumonia (27/32, 84.4% vs. 158/342, 46.2%, P< 0.001) and there was no significant difference in vaccination status (15/32, 46.9% vs. 211/342 61.7% P=0.101).

Conclusion

This study shows the potential clinical benefits of regdanvimab in mild to moderate COVID-19 patients in the real world during the delta variant predominant period in Korea.

Disclosures

All Authors: No reported disclosures.
1161. Vaccination During Acute COVID-19 Infection Protects Against 30 Day Adverse Outcomes
Authors: Casazza Julia A , Turer Robert W , Saleh Sameh N , Pickering Madison , Diaz Marlon , Ho Milan , Shah Pankil , Shah Dimpy , Lehmann Christoph U , Thakur Bhaskar , Medford Richard J
Published: December 2022

Background

Therapeutic vaccination following SARS-CoV-2 infection might stimulate anti-viral immunity and improve patient outcomes. We investigated, amongst previously unvaccinated patients, whether vaccination with the Pfizer, Moderna, or Johnson & Johnson vaccines within 14 days of a positive SARS-CoV-2 test affected 30-day patient outcomes.

Methods

Using a deidentified national electronic health record dataset (Optum, Inc.), we identified previously unvaccinated patients who tested positive for COVID-19 between 12/11/2020 and 12/19/2021. Among this cohort, 1,909 patients received a first vaccine dose within 14 days (vaccinated) while 446,309 did not receive a first dose of vaccine within 30 days of their first positive test (unvaccinated). We performed 1:1 propensity score matching based on age, gender, race, ethnicity, region, BMI, insurance, and comorbidities from the Charlson Comorbidity Index. Next, we compared odds of severe outcomes within 30 days between vaccinated and unvaccinated groups using a partial proportional odds model with the following ordinal severity outcome: no hospitalization, hospitalization, ICU stay, or death (Stata version 17.0, α = 0.05).

Results

1,909 vaccinated patients were propensity score-matched to 1,909 unvaccinated patients. The final matched cohort was statistically indistinguishable (p > 0.05) for all metrics used in propensity score calculation. This matched cohort (n = 3,818) was 58.6% female, 67.7% white, 12.6% Hispanic, and 56.4% commercially insured, with a mean age of 50.6 years and a similar comorbidity profile. A partial proportional odds model showed that unvaccinated patients were at increased risk for hospitalization and higher ordered outcomes (OR = 1.19, 95% CI: 1.02-1.39), ICU stay and higher ordered outcomes (OR 1.63, 95% CI: 1.21-2.20), and death (OR 4.57, 95% CI: 2.50-8.37).

Conclusion

Among previously unvaccinated patients, those who received a first dose vaccine within 14 days of a positive COVID-19 test were less likely to experience hospitalization, ICU stay, or death compared to matched peers who did not receive a first dose in the acute phase of infection. The sample size of patients vaccinated during the acute phase is limited, so further studies are indicated to evaluate the safety and efficacy of this practice.

Disclosures

Christoph U. Lehmann, MD, FAAP, FACMI, FIAHSI, Celanese: Stocks/Bonds|Markel: Stocks/Bonds|Springer: Honoraria.
Work and Time
Authors: Adams Zoe
Published: December 2022

Chapters 4, 5, and 6 all explore the implications of the way in which the boundaries of the labour commodity are constructed in law, focusing on the boundaries it constructs between work and non-work on one hand, and work and worker on the other. This chapter traces these boundaries through their articulation in the context of the evolution of working time regulation, paying close attention to the implications of a juridical conception of work that conceptualizes the latter through the lens of contractually mediated control over time. The chapter provides a detailed analysis of working time in the context of factory legislation, tracing its evolution to the present day in the context of the Working Time Regulations 1998, as influenced by EU law. The chapter uses this analysis to shed light on recent trends in the organization of work, including trends towards casualization, fragmentation, and overwork, and how this tends to ‘invisibilize’ certain forms of, or periods of, work, with not insignificant distributive implications.
Odonata as indicators of pollution, habitat quality, and landscape disturbance
Authors: Šigutová Hana , Dolný Aleš , Samways Michael J. , Sönke Hardersen , José Max Oliveira- Junior , Juen Leandro , Dinh Khuong Van , Bried Jason T.
Published: December 2022

The Odonata have well resolved taxonomy, conspicuous diurnal adults, contact with aquatic and terrestrial environments, and a broad range of environmental sensitivity across species, making them a valuable group for environmental appraisals. Odonate nymphs are commonly tested in aquatic ecotoxicological and bioaccumulation studies and often applied with other aquatic macroinvertebrate taxa in pollution-based biotic indices. Some of the more recent work aims to explain the evolutionary context of contamination risk and to increase mechanistic understanding of contaminant effects. Adults or exuviae are typically featured in habitat quality assessments with tools such as the Dragonfly Biotic Index, regional lotic quality indices, and coarse taxonomic metrics that will be especially useful in regions lacking descriptions and keys. Adults are further being used in landscape disturbance assessments where removal of non-breeding occurrences can reduce noise and strengthen signal. The future may move toward macro-ecological health assessments enabled by extensive citizen science and vulnerability trait data.
Theocratic Secularism
Authors: Ghobadzadeh Naser
Published: December 2022

This book articulates a religious rationale for political secularism in the Iranian/Shīʿī context. The genealogy of Twelver Shīʿī political theology shows that the bitter experience and lack of success of the Shīʿa in governance during the early centuries of Islamic history led them to link the realization of their ideal political system to transcendental factors. Belief in theocracy has been the basis of Shīʿī political theology, but with the messianic conception of the twelfth Imām in the fourth/tenth century, its realization came to depend on divine will and intervention. As a result, Shīʿī leaders, while awaiting the return of the twelfth Imām, not only do not have the authority or responsibility to take over government but have been forbidden to do so. For more than thirteen hundred years, the political thought and action of Shīʿī religious leaders were shaped by the political theology formulated in this book as theocratic secularism. In opposition to orthodox Shīʿī theology, a new politico-religious discourse emerged at the initiative of Ayatollah Khomeini toward the end of the twentieth century, referred to in this book as governmental Shīʿism. Governmental Shīʿism considers the occupation of the government apparatus as the duty of Shīʿī religious leaders. This book argues that governmental Shīʿism was neither the product of a theological transformation of Shīʿī orthodoxy nor used as a blueprint to establish the Islamic Republic. Rather, the formation of the Islamic Republic and the clergy’s rise to power led to the birth of governmental Shīʿism and bestowed importance on Khomeini’s wilāyat-i faqīh doctrine.
The Age of Perplexity
Authors: Ghobadzadeh Naser
Published: December 2022

This chapter shows that Shīʿism experienced an epistemic transformation in the first century of the Major Occultation. The compilation of ḥadīth collections played a role in shaping this epistemic transformation, as it was through these collections that Shīʿī thinkers began to engage in discourse production. It will be argued that a considerable proportion of the fundamental elements of Shīʿī political theology were formed at this time. Among these elements were the transfer of the religious and political authority of the Imāms to the ʿulamāʾ, the fixing of the number of Imāms at twelve, and the messianic conceptualization of the twelfth Imām. In fact, it was with the messianic conceptualization of the twelfth Imām that theocratic secularism was embedded in Shīʿī theology in the form that has persisted until the present day. This conceptualization transformed the nature of the Shīʿa’s hope and expectation about the formation of the ideal Shīʿī government from a concrete hope for the here and now to a distant anticipation of an unknown future time dependent on transcendental factors.
Conceptualizing the International Policing Agenda
Authors: Sinclair Georgina
Published: December 2022

This chapter sets out the historical framework outlining the what and the types of activities of international policing, its investigation within the Western literature, the terminology and concepts encapsulated (including transnational policing, global policing, democratic police reform, capacity building), and their interpretation by theorists (academics) and practitioners. The chapter introduces the nature of international policing as part of wider processes of policing assistance within peace operations, police assistance to other countries under the umbrella international development, and broader security sector reform (including police reform). It provides an overview of key overlapping trends including pre-1989 UK police history, international aid and development, and the commercialization of policing.
The UK Policing Brand in Historical Context
Authors: Sinclair Georgina
Published: December 2022

This chapter considers UK policing history through the development of two policing models—English/civil and Irish/colonial—from the nineteenth century to the present day, and outlines key reforms and historical contexts that have contributed to a multifaceted UK policing brand. It explores the myths and realities of UK policing through Whig and revisionist histories, from the emergence of the ‘New Police’ in London and the Irish Constabulary in Ireland; the model for the British colonial policing. This chapter considers the cross-fertilization of both policing models through the case study of the Ceylon Police in the nineteenth century and, post-Second World War international policing advisors and UK support to missions including Germany, Italy, Greece, Columbia, and Vietnam, and looks at how the export of UK policing resulted in a ‘pick-and-mix’ approach for either English or Irish policing styles. While an English notion of policing with historical links to its pseudo-Peelian origins theoretically prevailed, the importance of an Irish tradition of policing grew and circulated across the British Isles, empire, and commonwealth and was reinforced by the history of policing in Northern Ireland. It further explores the cross-fertilization of both policing models that have become part of the UK policing offer internationally post 1989: England and Wales, Scotland, and Northern Ireland.
UK Policing in Afghanistan, Iraq, and Libya
Authors: Sinclair Georgina
Published: December 2022

9/11 and the global war on terror cemented security sector reform within foreign and security policies. This chapter looks at the continuing UK support for hostile environment and post-conflict policing through the case studies of Iraq, Afghanistan, and Libya. It considers how international policing involved the whole spectrum of UK policing including MDP who supported the military and services police under Operation Herrick. The case studies consider the extent to which the UK was able to meet ‘demand’ with the growth in international missions at the planning and operational stages. This focused particularly on senior-ranking officers to fill posts that held strategic priority for the UK (Iraq and Afghanistan) in contrast to United Nations missions that were rankless. The limited uniformed presence in planning and delivery for the post-intervention phase underlined a critical gap in the UK government’s approach to security sector reform as highlighted in the Iraq Inquiry. The numbers of officers volunteering for overseas missions declined due to the lack of benefits to their official career pathway and promotion prospects and opportunities for police contracting rose exponentially at this time.
Athenian Ostracism and its Original Purpose
Authors: Węcowski Marek
Published: December 2022

Athenian Ostracism and its Original Purpose. A Prisoner’s Dilemma is the first book in English about Athenian ostracism, by far the most emblematic institution of Athenian democracy, in many decades. It offers a reassessment of ostraka (or potsherds, on which the names of the ‘candidates’ for exile were inscribed by citizens) from several Greek cities outside Athens, a reconstruction of the history and of the procedure of ostracism in Athens, and a comprehensive account of the political circumstances of the introduction of the law about ostracism by Cleisthenes in 508/507 bc. The novelty of the book is its focus on the entire operation procedure of this institution, whereas earlier scholarship concentrated mainly on its last step, i.e., on the day of the vote of ostraka. Following the logic of the political play in Athens between the first and the last stage of ostracism, it is argued that Athenian ostracism was a mechanism devised to impose compromise on the main political players of the Athenian political life. Otherwise, the entire political elite of Athens would be randomly punished by the Athenian people, by exiling one of the leading politicians in an unpredictable vote by huge masses of citizenry. To support this hypothesis, the author turns to the theory of the ‘evolution of cooperation’ as formulated by the American mathematician and political scientist Robert Axelrod based on the ‘iteratated prisoner’s dilemma’ in game theory—as a probabilistic analogy to the dynamics of Athenian political life under democracy.
Remarkably high rate of meiotic recombination in the fission yeastSchizosaccharomyces pombe
Authors: Lian Qichao , Maestroni Laetitia , Gaudin Maxime , Llorente Bertrand , Mercier Raphael
Published: December 2022

In most eukaryotes, the number of meiotic crossovers (COs) is limited to 1–3 per chromosome, which are prevented from occurring close to one another by CO interference. The fission yeastSchizosaccharomyces pombe, an exception to this general rule, lacks CO interference and seems to have the highest CO number per chromosome. However, global CO frequency was indirectly estimated in this species, raising doubts about this exceptional recombination level. Here, we used an innovative strategy to directly determine COs genome-wide inS. pombe. We confirm the absence of crossover interference and reveal the presence of co-variation in CO number across chromosomes within tetrads, suggesting that a limiting pro-CO factor varies stochastically between meiocytes. CO number per chromosome varies linearly with chromosome size, with the three chromosomes having, on average, 15.9, 12.5, and 7.0 COs, respectively. This is significantly lower than previous estimates but reinforcesS. pombe’sexceptional status as the eukaryote with the highest CO number per chromosome described to date and among the species with the highest rate of COs per unit of DNA.