bluuebunny/crossref_metadata_2025_split huggingface dataset:
453. Distribution of cycle threshold values and the associated factors of SARS-CoV-2 omicron variant in a community setting in Japan
Authors: Mutoh Yoshikazu , Umemura Takumi , Ichihara Toshihiko 
Published: November 2023

Abstract

Background
Little is known regarding the viral dynamics of omicron variant, although the number of severe cases of COVID-19 has decreased due to the expansion of vaccines and emerging of omicron variant. Therefore, we investigated the distribution of cycle threshold (Ct) values and related characteristics in this study.
Distribution of cycle threshold values of SARS-Cov-2 PCR by symptoms

Methods
Patients who tested positive for SARS-CoV-2 using PCR test at Tosei General Hospital between April 2022 and March 2023 were retrospectively analyzed. SARS-CoV-2 was detected using nasopharyngeal swab or saliva via Xpress SARS-CoV-2 assay (Cepheid, Sunnyvale, USA) and Cobas 8800 system (Roche). Age, sex, days since onset, symptoms, comorbidities, prognosis, and vaccination status were collected for each patient. The date of onset was estimated from the contact history of asymptomatic patients.

Results
Of 605 patients, mean age was 51.0 (±26.0) years, 323 were men (53.4 %), 77 (12.7 %) were asymptomatic, and 360 (59.5 %) had more than three times of vaccination. The most frequent comorbidity was chronic pulmonary diseases in 83 (13.7%) patients, followed by diabetes in 61 (10.1%), chronic heart diseases in 61 (10.1%), and malignancy in 55 (9.1%). The distribution of Ct value was 27.8 (IQR: 21.5–34.8) for within 5 days of onset, 27.5 (IQR: 22.5–34.0) for 6–14 days of onset, 35.6 (IQR: 30.4-40.7) for 15 days or later of onset. More than 38.6% (68/176) of the cases diagnosed at symptom onset showed a Ct value of &gt;32.
Among 494 patients diagnosed within 5 days of onset, symptomatic patients showed significantly lower median Ct values than those of not (27.19 vs 32.54; P value &lt; 0.001). However, in multivariable analysis, age, disease severity, vaccination status, and comorbidities were not associated with Ct values.

Conclusion
Ct values of SARS-CoV-2 omicron variant might be able to estimate the onset of disease onset. Conversely, certain number of cases revealed high Ct values from the early phase of infection. Physicians should focus on the interpretation of Ct values for infection prevention and control.

Disclosures
All Authors: No reported disclosures
476. Increased Depression and Anxiety Associated with COVID-19 among Recipients of HIV Healthcare Services at Sexual Health Clinic in NYC
Authors: Huang Simian , Zucker Jason , Castor Delivette , Carnevale Caroline , LaSota Elijah , Klein Joshua , Kim Tae Yoon , Quigee Daniela , Theodore Deborah , Gordon Peter , Cohall Alwyn , Meyers Kathrine , Sobieszczyk Magdalena E 
Published: November 2023

Abstract

Background
The COVID-19 epidemic disrupted routine healthcare services and affected mental health. Within Stick2PrEP, a suite of studies aimed at increasing pre-exposure prophylaxis (PrEP) uptake and healthcare engagement among men who have sex with men (MSM) and trans women (TW) in New York City, participants enrolled from November 2018 to February 2020 (Stick2PrEP2) and, after pandemic onset, from May 2021 onward (Stick2PrEP3). To understand the impact of the pandemic on the mental health of MSM/TW, we compared Stick2PrEP2 and Stick2PrEP3 participants' self-reports of depression and anxiety.

Methods
All participants in the two studies completed a baseline enrollment questionnaire that surveyed demographics, sexual behaviors, depression, anxiety, and intimate partner violence. We compared baseline characteristics of Stick2PrEP3 vs Stick2PrEP3 among participants enrolled between November 2018 and April 2022 using relevant statistics (e.g., Pearson's Chi-squared test or Wilcoxon rank sum test).

Results
We analyzed 345 participants, 141 in Stick2PrEP2 and 204 in Stick2PrEP3. Participants were similar in age, self-identified gender, race/ethnicity, income, rates of adverse childhood events, HIV and sexually transmitted infection (STI) risk scores, and PrEP adherence norms. More participants were on Medicaid or uninsured in Stick2PrEP3 (p&lt; 0.001). Additionally, both PHQ9 (2 vs. 4, p&lt; 0.001) and GAD7 (2 vs. 4, p=0.002) scores were significantly higher in Stick2PrEP3. More participants reported experience of intimate partner violence (24% vs. 45%, p=0.002) in Stick2PrEP3, but had higher PrEP engagement (INDEX score &gt;45, 66% vs. 86%, p&lt; 0.001).
Demographic information of participants in Stick2PrEP2 and Stick2PrEP3.
Results of different measurements from the enrollment survey that each participant completed.

Conclusion
The baseline results suggest that depression and anxiety levels were lower before COVID-19 among MSM and TW. The experiences during the COVID-19 pandemic may have contributed to increased depression and anxiety levels which may be multifactorial and modified by disruption in PrEP services. Further investigation is crucial to uncover the link between COVID-19, mental health, and health services delivery for people at risk of HIV acquisition.

Disclosures
All Authors: No reported disclosures
482. Long-Term Outcomes of Coronavirus disease 2019 and Risk Factors for Prolonged SARS-CoV-2 Infection in Lymphoma Patients: Multicenter, Retrospective Cohort Study
Authors: Lee Jung Ah , Han Min , Ahn Sangmin , Lee Yongseop , Yeom Joon-sup , Choi Jun Yong , Ku Nam Su , Jeong Su Jin , Kim Jung Ho , Kim Jin Seok , Chung Haerim , Cho Hyunsoo , Kim Yu Ri , Ahn Jin Young 
Published: November 2023

Abstract

Background
In lymphoma patients, SARS-CoV-2 is often detected continuously even after a sufficient amount of time has passed since being confirmed with COVID-19. We aim to describe the long-term outcomes of COVID-19 and identify the risk factors for prolonged SARS-CoV-2 infection in lymphoma patients.

Methods
A multicenter retrospective cohort study was conducted on patients receiving treatment for lymphoma at three tertiary hospitals in South Korea who were quarantined after being diagnosed with COVID-19 by polymerase chain reaction (PCR) testing or antigen test from August 2021 to July 2022. Prolonged COVID-19 is defined as a case where PCR remains positive even after 30 days of COVID-19 confirmation or when COVID-19 pneumonia occurs or worsens after 30 days of COVID-19 confirmation.

Results
A total of 77 lymphoma patients with COVID-19 were studied. Among them, 24 (31%) patients were classified as prolonged COVID-19 and seven patients (9.1%) died within 90 days after the diagnosis of COVID-19. (Table 1) Prolonged COVID-19 was more frequently identified in follicular lymphoma patients with a history of bendamustine and rituximab (BR) treatment (22.6% vs. 50.0%, p=0.016), especially those who maintained rituximab maintenance treatment after BR treatment (11.3% vs. 37.5%, p=0.012). (Table 2) At the time of initial COVID-19 diagnosis, the 'prolonged COVID-19 group' did not show clinically significant differences compared to the non-prolonged COVID group. (Table 3) Multivariable analysis showed that BR treatment followed by rituximab maintenance is one of the risk factors for persistent PCR positivity (OR 3.375, 95% CI 1.104-10.317, p=0.033), delayed or persistent pneumonia (OR 8.833, 95% CI 2.527-30.879, p=0.001), and COVID-19 related admission after quarantine period (OR 11.1, 95% CI 2.758-44.678, p=0.001). Prolonged COVID-19 had an impact on the delay of cancer treatment but did not increase the risk of 90-day or 180-day mortality significantly. (Table 4)

Conclusion
In this study, patients with lymphoma who have received certain treatments may have a higher risk of developing COVID-19 pneumonia due to prolonged infection. Further study is needed to understand the immune responses in this patient group and find treatment methods.

Disclosures
All Authors: No reported disclosures
495. De novo emergence of resistance mutations during treatment of SARSCoV-2 infection in immunocompromised patients
Authors: Johnson Katherine , Soave Rosemary , Wang Wei , Albert Joshua , Kodiyanplakkal Rosy Priya , Salpietro Maria , Jing-Mei Hsu , Diel Diego G , Ghedin Elodie , Salvatore Mirella 
Published: November 2023

Abstract

Background
Vaccination and therapeutic strategies for COVID-19 are constantly hindered by the rapid emergence of new viral variants less sensitive to antibodies or antivirals. Emerging evidence points to prolonged replication in the immunocompromised host as a key factor contributing to emergence of viral genomic mutations. We analyzed viral evolution and emergence of intra-host variants in response to treatments including antivirals and monoclonal antibodies in immunocompromised subjects with hematological malignancies infected with SARS-CoV2.

Methods
From April 2020 to August 2022, we collected 245 nasopharyngeal samples from 92 patients including longitudinal samples of 31 subjects with persistent infection (detection of SARS-CoV-2 RNA ≥30 days regardless of symptomatology). The number of samples per subject ranged from 1-14. To identify SARS-CoV-2 mutations, we performed whole genome sequencing using an amplicon-based approach and the Illumina NextSeq platform. Only samples that had 75% genome covered at 5x read depth were included in the analysis.

Results
After quality control filtering, 21 subjects had at least 2 samples available for longitudinal analyses. Ten of them had no consensus changes during infection (compared to the first sample collected), and 11 had at least 1 change. The spike protein was the most likely location for a consensus change (9 patients), followed by consensus changes in nsp3, nsp12, nsp13, N, ORF8, and nsp4. Mutations tended to appear mostly following treatment, with an increased number of changes apparently associated with worse outcome. After treatment, 3 patients developed mutations in the RNA-dependent RNA polymerase (nsp12) that are known to be associated with remdesivir resistance. One Paxlovid treated patient developed a nsp5 protease mutation potentially associated with resistance. Another patient developed a spike mutation associated with resistance to sotrovimab.

Conclusion
Our results underscore the need for augmented efforts to study intra-host evolution in the immunocompromised host, identify and isolate viruses resistant to treatment(s) and identify host determinants associated with accelerated resistance. These results are important for implementing optimal treatment strategies and to inform infection control measures.

Disclosures
All Authors: No reported disclosures
499. Level of Cord Blood Anti-SARs-CoV-2 Antibodies in Infants Born During 2021-2023 to The Mothers Who Had Received COVID-19 Vaccination During Pregnancy
Authors: Sojisirikul Nophathai , Lapphra Keswadee , Chokephaibulkit Kulkanya 
Published: November 2023

Abstract

Background
Maternal antibodies against SARS-CoV-2 actively transfer across placenta providing passive immunity to neonates. However, levels of cord blood anti-SARS-CoV2 antibodies and protective effects are still unclear. The objectives of the study was to investigate level of cord blood SARs-CoV-2 antibody of infants born to the mothers who received at least 1 dose of COVID-19 vaccine during pregnancy or within 3 months before pregnancy, as well as having SARS-CoV-2 infection during pregnancy.

Methods
Prospective observational study was conducted in Bangkok between March 2022 to March 2023. Cord blood samples were tested for anti-receptor binding protein IgG (anti-RBD IgG). Medical records were review for history of SARS-CoV-2 infections in the mothers.

Results
A total of 154 neonates were enrolled. The highest cord blood geometric mean concentration (GMC) of anti-RBD IgG was observed in infants who was born from the mother who received COVID-19 vaccine and were diagnosed with COVID-19 during pregnancy (n= 28; anti-RBD IgG: 7684.8 [95% confidential interval (CI) 4215.9-14007.8] AU/ml), while the lowest GMC was found in the infants born from mothers who received COVID-19 vaccination before pregnancy and did not have COVID-19 during pregnancy (n=18, anti-RBD IgG 1453.5 [95% CI 648.1-3259.6 AU/ml]. Maternal SARs-CoV-2 infection during pregnancy had a significant association with anti-RBD IgG levels (P=0.03).
Figure of Anti-RBD IgG comparison at birth

Conclusion
Vaccinating and having SARs-CoV-2 infection during pregnancy induced several folds higher antibody level in cord blood that could effectively provide protection in infants.

Disclosures
All Authors: No reported disclosures
523. Efficacy and Safety of Nirmatrelvir/Ritonavir for COVID-19 in Adolescents
Authors: Lee Kiriam Escobar , Lee Philip J , Anosike Brenda I 
Published: November 2023

Abstract

Background
Nirmatrelvir/ritonavir (n/r) is a currently 1 of 2 oral medications FDA-approved for treatment of COVID-19 in patients ≥ 12 years of age AND ≥ 40 kg. To date, dosing recommendations for adolescents are extrapolated primarily from adult studies. We conducted a retrospective study at a large pediatric academic center to evaluate the efficacy and safety of n/r in adolescent patients.

Methods
Retrospective electronic chart review of adolescents ages 12-18 years diagnosed with COVID-19 between 1/1/2022 to 3/31/2022. We included those with laboratory confirmed COVID-19 by either PCR or rapid antigen, treated with n/r within 5 days of symptom onset. The primary endpoint was COVID-related hospital admissions, ER and/or outpatient visits within 30 days after completion of n/r. Our secondary endpoint was COVID-related adverse event(s) due to n/r.

Results
A total of 91 unique patients were prescribed n/r therapy; 1 was prescribed twice. All but 2 were ordered in the outpatient setting. 34.1% (29/85) had a BMI ≥ 30 kg/m2. Thirty-eight (41.8%) and 25 (27.5%) patients received 2 and 3 COVID-19 vaccines, respectively. Asthma (26/91, 28.6%) was the most common underlying condition; (16/91, 16.6%) were immunocompromised. Median time from initial COVID-19 positivity to n/r prescription was 0 days (range: 0-4). 2.2 % (2/90) of those who received outpatient prescriptions returned to the ER with COVID-19 like symptoms within 30 days. Another 2 different patients who were prescribed n/r inpatient expired at 28 and 48 days after completion of therapy. Only 2.2% (2) experienced an adverse event after completion of n/r. (Table 1)

Demographic and outcome information of adolescent patients treated with nirmatrelvir/ritonavir for COVID-19 infection at a large pediatric academic medical center.

Conclusion
Though limited, this single center study demonstrated low rates of COVID-related hospital admissions, ER and/or other outpatient visits as well as adverse events suggesting that n/r may be a safe and well tolerated by most adolescents diagnosed with COVID-19. Larger/prospective pediatric studies are still needed.

Disclosures
All Authors: No reported disclosures
526. Treatment Inconsistencies of Patients Hospitalized with COVID-19 during Four Waves in Almaty, Kazakhstan, 2020-2021
Authors: Gazezova Saya , Horth Roberta , Smagul Manar , Kasabekova Lena , Usmanov Shokhruh , ZIKRIYAROVA S A N A M , Nabirova Dilyara 
Published: November 2023

Abstract

Background
Clinical management guidelines were continually changing during the COVID-19 pandemic to reflect best available evidence for a novel virus. In Kazakhstan, the treatment guidelines have been modified 16 times since the pandemic began. We assessed compliance with guidelines during four waves of COVID-19 in Kazakhstan.

Methods
We conducted a cross-sectional study among people hospitalized with COVID-19 in an infectious disease hospital in Almaty during 4 waves: T1 (June 1-August 30, 2020); T2 (October 1-31 December 2020); T3 (April 1-May 31, 2021); and T4 (July 1-October 26, 2021). Changes in COVID-19 diagnostic and treatment guidelines published during these periods were studied. We abstracted data from patient electronic medical records.

Results
Seven of 16 COVID-19 diagnostic and treatment guidelines adopted in Kazakhstan were updated during this time. In T1, all people with COVID-19 including those with asymptomatic and mild disease. Antibiotics were recommended only for bacterial infections in T1-T4. Glucocorticosteroids were recommended only to patients with severe disease in T1-T4. Anticoagulants were recommended prophylactically in T1-T3 but only empirically in T4. Of 1,146 COVID-19 patients hospitalized, 14% were in T1, 14% in T2, 22% in T3, and 50% in T4. Mean age was 57 years (range 18-96 years) and 59% were female. In T1-T4 respectively: Antibiotics were given to 78%, 64%, 71%, and 67% of patients with no documentation of bacterial infections; glucocorticosteroids were given to 36%, 31%, 33%, and 28% of patients with non-severe disease; non-COVID-19-specific antivirals were given to 28%, 10%, 4%, and 8% of patients; and anticoagulants given to 18%, 24%, 6%, and 7% of patients with mild disease.
Treatment of hospitalized COVID-19 patients inconsistent with national treatment guidelines, Almaty, Kazakhstan, 2020-2021
T1: June 1-August 30, 2020; T2: October 1-31 December 2020; T3: April 1-May 31, 2021; T4: July 1-October 26, 2021

Conclusion
We identified inconsistencies with patient treatment and national guidelines. Inappropriate use of antibiotics and non-specific antivirals can result in adverse treatment outcomes and rise in resistance. Improved communication with additional training is needed when guidelines are updated.

Disclosures
All Authors: No reported disclosures
530. Population Pharmacokinetic Analysis of Ensitrelvir, an Inhibitor of 3C-like (3CL) Protease of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) for patients with SARS-Cov-2 Infection
Authors: Ishibashi Toru , Nomura Luna , Shimizu Ryosuke , Kubota Ryuji 
Published: November 2023

Abstract

Background
Ensitrelvir is a novel oral inhibitor of 3CL protease of SARS-CoV-2, which is essential for viral replication. Ensitrelvir which is administered at once daily for 5 days with 375 mg on Day 1 followed by 125 mg, was approved in Japan for the treatment SARS-CoV-2 infection under the Emergency Regulatory Approval System in November 2022. The aim of this study is to build a population pharmacokinetic (PK) model to assess covariates on ensitrelvir PK.

Methods
A population PK analysis was performed using a total of 8034 plasma ensitrelvir concentrations from 2060 healthy participants in Phase 1 studies and patients in Phase 2/3 study. A 2-compartment model with first order absorption was used as a structural PK model for a base model. The effects of covariates were evaluated including age, body weight (BWT), AST, ALT, albumin, total bilirubin, creatinine clearance, GFR, sex, race, health status, formulation, food conditions and so on. The exposures (individual post-hoc maximum concentration [Cmax], area under the time-concentration [AUC] and plasma concentration at 24 hours post-dose [C24]) in the patients were estimated with an empirical Bayesian approach based on the final model to assess the pharmacokinetic/pharmacodynamic (PK/PD) relationship between SARS-CoV-2 viral RNA load and exposures.

Results
The population PK model well described the plasma ensitrelvir concentration data. The effects of BWT on clearance and volume of distribution, food conditions and formulation on absorption rate constant were found to be significant covariates. The anti-viral effect did not change in the range of ensitrelvir exposure in Phase 2/3 study, while the efficacy of ensitrelvir was demonstrated by significant reduction of viral RNA compared with placebo.

Conclusion
The population PK model was developed based on the plasma ensitrelvir concentration data from participants including patients infected with SARS-CoV-2 and the BWT was the most important covariate on ensitrelvir PK. The expected exposures for anti-viral effect at the clinical dose were obtained regardless BWT. The population PK model would be useful for understanding PK characteristics of ensitrelvir and the PK/PD results supported that the clinical dose of 375/125 mg is appropriate for treatment of SARS-CoV-2 infection.

Disclosures
All Authors: No reported disclosures
536. Development of post acute sequelae of SARS-Cov-2 infection (long Covid) in outpatient receiving monoclonal antibodies
Authors: Neto Amelia , Kak Vivek 
Published: November 2023

Abstract

Background
The development of post-acute sequelae of SARS-Cov-2 infection (long COVID), is a complex condition defined as a persistence of symptoms at least 3 months after initial infection. Although the etiology of long COVID is poorly understood, studies suggest it is related to immune dysregulation following infection. The development of long COVID is unclear with studies suggesting it can occur in up to 15% of individuals, however most of this data focuses on hospitalized patients. We examined the occurrence of long COVID in patients who received the monoclonal antibody (mAb) treatment at an outpatient infusion center.

Methods
We performed a study of high-risk symptomatic COVID patients who received the mAb treatment at an OP center from April 2021-22. Patients who received the mAb treatment were characterized based on the following criteria: age &gt; 65, BMI &gt; 25, or comorbidity. A follow up closed-ended survey was used to determine if patients experienced any of the following long COVID symptoms: fatigue, exertion intolerance, persistent cough or chest pain, dyspnea, brain fog, headaches, issues sleeping, myalgia, or loss of smell/taste.

Results
We called 1100 patients, yielding 615 responses, of which 57.7% (n = 355) fully recovered, while 42.3% (n = 260) reported experiencing long COVID. From the subset of individuals who experienced long COVID, 4.6% (n = 12) were hospitalized. In addition, 50% (n = 129) of long COVID patients reported having 3 or more symptoms, with fatigue, brain fog, and loss of smell/taste being the most prevalent. The characteristics and outcomes of patients who received the mAb treatment are shown in Table 1.

Conclusion
Long COVID was documented in almost half of high-risk symptomatic patients suggesting a higher incidence compared to the literature, despite a low hospitalization rate. Female sex, unvaccinated patients and those who received the mAb later were more likely to develop long COVID. Patients given steroids on/before the date of their mAb also had more long COVID. Predictors of long COVID based on our data includes female sex, vaccination status, and the administration/timing of immune modulators. Modulation of the immune system is likely important in controlling the development of long COVID. These results need to be validated in larger cohorts.

Disclosures
All Authors: No reported disclosures