bluuebunny/crossref_metadata_2025_split huggingface dataset:
1045. Longitudinal Evaluation of the QuantiFERON-TB Gold Plus Assay in Hospitalized COVID-19 Patients with a First Indeterminate Result: Resolution of Inflammation and Restoration T-lymphocyte Counts and Interferon-gamma Production
Authors: Imeneo Alessandra , Alessio Grazia , Lorenzo Andrea Di , Campogiani Laura , Lodi Alessandra , Barreca Filippo , Crea Angela , Vitale Pietro , Spalliera Ilaria , Compagno Mirko , Coppola Luigi , Malagnino Vincenzo , Teti Elisabetta , Andreoni Massimo , Sarmati Loredana , Marco Iannetta 
Published: December 2022

Abstract

Background
Several studies reported an increased rate of indeterminate QuantiFERON-TB Gold Plus (QFT-P) assay results in patients with severe Coronavirus Disease (COVID)-19.

Methods
Aim of the study was to longitudinally evaluate QFT-P responses in patients who survived COVID-19, with a previous indeterminate result.

Results
We observed 223 patients with an indeterminate QFT-P assay among 949 patients hospitalized because of COVID-19 (23,5%) during 2020 and 2021. 36 patients among those with an indeterminate QFT-P assay were enrolled for reassessing the test. In 12 patients peripheral blood lymphocyte subsets were also reassessed. Considering disease severity, 30 were classified as severe and 6 as non-severe. Median age was 57,5 (interquartile range [IQR]: 49,5-63,8), with a prevalence of male sex (M/F: 24/12); median Charlson Comorbidity Index was 2 (IQR: 1-3). The second QFT-P assay was performed after at least 1 month from the first assay (median time 7 months, IQR: 5-12 months). All QFT-P assays gave a determined result: 2 positive (5.5%) and 34 negatives (94,4%). A statistically significant difference was observed after comparing the laboratory parameters at the time of the first and the second QFT-P assay: the absolute counts of total lymphocyte, total CD3+, CD4+ and CD8+ T-lymphocytes were significantly increased (p&lt; 0.001) while neutrophil absolute counts, neutrophil to lymphocyte (N/L) ratio, D-dimer, fibrinogen, ferritin, C-reactive protein (CRP) were significantly reduced (p&lt; 0.0001). Concerning the QFT-P assay, interferon gamma (INF-γ) production in the Mitogen-Nil, TB1-Nil and TB2-Nil conditions were significantly increased (p&lt; 0.0001; p=0.0019; p=0.0205, respectively) (Table 1 and Figure 1).

Conclusion
Once the acute phase of COVID-19 is resolved, inflammatory markers and peripheral blood leucocyte counts tend to normalize with an effective INF-γ production after specific and nonspecific stimulation. All the 36 QFT-P showed a determinate result. Moreover, we observed 2 positive QFT-P assay, supporting the importance of retesting patients with indeterminate result to identify latent tuberculosis infection and monitor patients for possible reactivation because of the immune-suppression associated with COVID-19.

Disclosures
All Authors: No reported disclosures.
1060. Duration of Seroprevalence among Individuals Previously Infected with SARS-CoV-2 and their Household Contacts
Authors: Altamirano Jonathan , Lopez Marcela , Lopez Marcela , Chun Leanne X , Tam Grace K , Robinson India , Shaikh Nuzhat , Leary Sean , Stainton Emma , Robinson Makeda L , Behl Rasika , Thiessen Rosita , Govindarajan Prasanthi , Blomkalns Andra L , Pinsky Benjamin A , Maldonado Yvonne A 
Published: December 2022

Abstract

Background
Serological tests directed against SARS-CoV-2 can provide information about the timing of infection and immunity against the virus. However, the kinetics of the host immune response to SARS-CoV-2 remain poorly understood. We established a household transmission study to analyze the serological responses within households, to determine longitudinal immune responses to infection.

Methods
From April 2020 to April 2022, we prospectively enrolled 76 households with at least one RT-PCR confirmed case of COVID-19. Participants were asked to provide blood samples at three time points: at baseline within 2 weeks of the index’s diagnosis of COVID-19, and at one- and three-months post-enrollment. Samples were tested for the presence of IgG antibodies against SARS-CoV-2 spike protein via an FDA EUA approved ELISA. Demographics, medical history, and symptomatology were also collected.

Results
To date, we have analyzed 238 serologic samples from 135 participants, including 82 baseline samples, 89 one-month samples, and 67 three-month samples. At baseline, 67.8% (n=40/59) of all confirmed cases tested positive for SARS-CoV-2 antibodies, which increased to 86.4% (n=57/66) at the one month, and 85.1% at three months (n=40/47). Of those confirmed infected participants that failed to seroconvert at baseline, almost all reported symptoms (n=14/19, 73.7%) and did not have chronic medical conditions (n=17/19, 89.5%). Of the 19, 3 failed to seroconvert by their third visit.
All individuals who were fully vaccinated at the time of each visit tested positive for antibodies at baseline (n=26), one-month (n=27), and three-months (n=20). Of those who were not fully vaccinated, 56 (41.1%) were positive for antibodies at baseline, 62 (59.7%) were positive at one -month, and 47 (63.8%) at three-months. Differences in seropositivity rates between pediatric and adult participants, as well as between index cases and household contacts, at each visit were also identified (Table 1).

Conclusion
Identifying differences in seroprevalence in various demographic groups can provide insight into longitudinal immune responses post-infection. Future analyses on seropositivity among previously infected individuals who received therapeutics may be of interest.

Disclosures
Andra L. Blomkalns, MD, MBA, Eli Lilly and Company: Grant/Research Support Yvonne A. Maldonado, MD, Pfizer: Grant/Research Support|Pfizer: Member, DSMB, Pfizer Meningococcal Vaccine clinical trial.
1062. Examining the impact of type 2 diabetes status and severity on in-hospital outcomes amongst patients hospitalized with COVID-19 in a southwest Virginia healthcare system
Authors: Bendetson Jesse , Baffoe-Bonnie Anthony 
Published: December 2022

Abstract

Background
Patients with type 2 diabetes mellitus (T2DM) who develop COVID-19 are at increased risk of hospitalization, longer hospital stays, ICU admission, and death. Additionally, measures of T2DM severity (e.g., hemoglobin A1c) have been found to be predictive of severe COVID-19. The present analysis was conducted to determine whether T2DM status and severity may be predictive of COVID-19 severity outcomes amongst patients hospitalized with COVID-19 in a southwest Virginia healthcare system.

Methods
All non-pregnant patients over the age of 18 who were hospitalized with COVID-19 on or before 6/11/2021 were included (n=2,099). T2DM status was treated as a binary variable; patients diagnosed with non-T2DM diabetes mellitus were excluded. Diabetes severity was quantified using the Diabetes Complications Severity Index (DCSI), a 13-point summary score covering 7 discrete categories of diabetes complications. We used two binary indicators of in-hospital COVID-19 severity: (1) progression to ICU admission, ventilatory assistance, and/or death; and (2) in-hospital mortality. Binary logistic regression with propensity score weighting was used to assess the relationship between diabetes status and COVID-19 severity. Multivariate logistic regression was used to assess the relationship between DCSI score and COVID-19 severity.

Results
Patients with T2DM had 1.51 times the odds of progressing to ICU admission, ventilatory assistance, and/or death (95% CI: 1.16, 1.96) and 1.39 times the odds of in-hospital mortality (95% CI: 1.02, 1.91) compared to non-diabetics. Amongst patients with T2DM (n=942), increasing DCSI score was associated with increased odds of in-hospital mortality; compared to patients with a DCSI score of 0, patients with a DCSI score of 1 had 3.23 times the odds (95% CI: 1.20, 8.70) and patients with a DCSI score of 5 or greater had 11.25 times the odds (95% CI: 4.46, 28.40) of dying in the hospital.

Conclusion
Our results indicate that diabetes status and DCSI score were both strongly predictive of in-hospital COVID-19 severity outcomes amongst this sample. Future work will focus on how changes in vaccine coverage and strain dominance over time may have affected these relationships.

Disclosures
All Authors: No reported disclosures.
1064. Intra-Host SARS-CoV-2 Evolution Dynamics
Authors: Haddad Kim El , Esper Frank , Mudiyanselage Thamali Madhushani Adhikari , Li Jing , Zheng Tu , Cheng Yu-Wei , Rhoads Daniel D , Farkas Daniel H , Ko Jennifer , Worley Sarah , Rubin Brian , Zhang Xiangyi , Leng Xiaoyi 
Published: December 2022

Abstract

Background
Our understanding of SARS-CoV-2 evolution is limited. Most estimates arise from analysis of global databases populated with unrelated sequences and is currently estimated at ∼27.7 substitutions/genome/year. SARS-CoV-2 polymerase contains a proofreading function encoded by NSP-14 limiting change. Additionally, virus evolution may be influenced by patient comorbidity. Intra-host mutational rate (MR) during infection remain poorly studied.

Methods
To minimize effect of vaccination and/or natural immunity on MR analysis, paired samples from adults originating from the initial pandemic wave (3/17/2020 through 5/27/2020) were retrieved and analyzed at Cleveland Clinic. Viral genome analysis was performed using next generation sequencing, and mutations between paired samples were quantified at allele frequencies (AF) ≥ 0.1, ≥ 0.5 and ≥ 0.75 and compared. MR was calculated employing F81 and JC69 evolution­­­­ models and compared between isolates with (Δ NSP-14) and without (wildtype, wt) non-synonymous mutations in NSP-14 and by comorbidity.

Results
A total of 40 patients (80 sample pairs) were identified. Median interval between paired tests was 15 days [range 5-32]. The estimated MR by F81 modeling was 317.2 (95%CI 312.0-322.3), 54.6 (95%CI 52.5-56.7) and 45.1 (95%CI 43.1-47.0) substitutions/genome/year at AF of ≥0.1, ≥0.5, ≥0.75 respectively. Rates in ΔNSP-14 (n=13) vs wt (n=27) groups were 557.7 (95%CI 537.0-578.2) vs 193.1 (95%CI 187.1-199.1) p-value 0.001, 50.8 (95%CI 44.3-57.3) vs 56.3 (95%CI 53.1-59.4) p-value 0.144, and 31.0 (95%CI 25.9-36.1) vs 51.3 (95%CI 48.3-54.3) p- value &lt; 0.001 at AF ≥0.1, ≥0.5, ≥0.75 respectively. Patients with immune comorbidities (n=6) had significantly higher MR of 137.6 (95%CI 114.6-160.5) vs 40.5 (95%CI 38.4-42.7) p-value &lt; 0.001, and 113.7 (95%CI 92.8-134.5) vs 33.4 (95%CI 31.5-35.4) p-value &lt; 0.001 at AF ≥0.5 and ≥0.75 respectively. Similar results were obtained when using the JC69 model.

Conclusion
Intra-host SARS-CoV-2 mutation rates are higher than those reported through population analysis. Virus strains with altered NSP-14 have accelerated MR at low AF. Immunosuppressed patients have elevated MR at higher AF. Understanding intra-host virus evolution will aid in current and future pandemic modeling.

Disclosures
Frank Esper, M.D, Johnson and Johnson: Advisor/Consultant Daniel D. Rhoads, M.D. PhD, Luminex: Advisor/Consultant|Talis Biomedical: Advisor/Consultant|Thermo Fisher: Advisor/Consultant.
1074. Surveillance of SARS-CoV-2 variants of concern (VOC) in hospital wastewater (WW) and its correlation with hospitalized cases of COVID-19 and the occurrence of outbreaks
Authors: Acosta Nicole , Chavarriaga Maria Bautista , Waddell Barbara Jean M , McCalder Janine , Du Kristine , Pradhan Puja , Sedaghat Navid , Papparis Chloe , Chen Jianwei , Doorn Jennifer Van , Xiang Kevin , Chan Leslie , Vivas Laura , Low Kashtin , Lu Xuewen , Chekouo Thierry , Dai Xiaotian , Cabaj Jason , Hrudey Steve , Bhatnagar Srijak , Ruecker Norma J , Achari Gopal , Cathryn Ryan M , Clark Rhonda , Pearce Craig , Harrison Joe , Meddings Jon , Leal Jenine , Missaghi Bayan , Kanji Jamil , Larios Oscar , May Elissa Rennert , Kim Joseph , Pang Xiao-Li , Lee Bonita , Frankowski Kevin , Conly John M , Hubert Casey R J , Parkins Michael 
Published: December 2022

Abstract

Background
WW surveillance enables real time monitoring of SARS-CoV-2 burden in defined sewer catchment areas. Here, we assessed the occurrence of total, Delta and Omicron SARS-CoV-2 RNA in sewage from three tertiary-care hospitals in Calgary, Canada.

Methods
Nucleic acid was extracted from hospital (H) WW using the 4S-silica column method. H-1 and H-2 were assessed via a single autosampler whereas H-3 required three separate monitoring devices (a-c). SARS-CoV-2 RNA was quantified using two RT-qPCR approaches targeting the nucleocapsid gene; N1 and N200 assays, and the R203K/G204R and R203M mutations. Assays were positive if Cq&lt; 40. Cross-correlation function analyses (CCF) was performed to determine the time-lagged relationships between WW signal and clinical cases. SARS-CoV-2 RNA abundance was compared to total hospitalized cases, nosocomial-acquired cases, and outbreaks. Statistical analyses were conducted using R.

Results
Ninety-six percent (188/196) of WW samples collected between Aug/21-Jan/22 were positive for SARS-CoV-2. Omicron rapidly supplanted Delta by mid-December and this correlated with lack of Delta-associated H-transmissions during a period of frequent outbreaks. The CCF analysis showed a positive autocorrelation between the RNA concentration and total cases, where the most dominant cross correlations occurred between -3 and 0 lags (weeks) (Cross-correlation values: 0.75, 0.579, 0.608, 0.528 and 0.746 for H-1, H-2, H-3a, H-3b and H-3c; respectively). VOC-specific assessments showed this positive association only to hold true for Omicron across all hospitals (cross-correlation occurred at lags -2 and 0, CFF value range between 0.648 -0.984). We observed a significant difference in median copies/ml SARS-CoV-2 N-1 between outbreak-free periods vs outbreaks for H-1 (46 [IQR: 11-150] vs 742 [IQR: 162-1176], P&lt; 0.0001), H-2 (24 [IQR: 6-167] vs 214 [IQR: 57-560], P=0.009) and H-3c (2.32 [IQR: 0-19] vs 129 [IQR: 14-274], P=0.001).

Conclusion
WW surveillance is a powerful tool for early detection and monitoring of circulating SARS-CoV-2 VOCs. Total SARS-CoV-2 and VOC-specific WW signal correlated with hospitalized prevalent cases of COVID-19 and outbreak occurrence.

Disclosures
All Authors: No reported disclosures.
1103. Virologic and Immunologic Outcomes in People Living with HIV in a Correctional Setting During the SARS-CoV-2 Pandemic
Authors: Patel Dimple , Michienzi Sarah M , Borgetti Scott , Patel Mahesh C , Zheng Anne , Zhu Michael , Badowski Melissa E 
Published: December 2022

Abstract

Background
It is known that the pandemic increased the risk of severe illness from SARS-CoV-2 infection in immunocompromised patients as compared to the general public. To combat this issue, telemedicine was utilized in various settings, but there is very little data on the adequate continuity of care (COC) and sustainability of telehealth throughout the pandemic. There is even less data on the effects of the pandemic in special populations, such as people living with human immunodeficiency virus (PLWH) and within the correctional setting. The purpose of this study was to investigate rates of HIV virologic suppression (VS) and the sustainability of telemedicine throughout the SARS-CoV-2 pandemic.

Methods
This was a retrospective, pre-post cohort study of PLWH who received antiretroviral therapy (ART) within Illinois Department of Corrections (IDOC) / University of Illinois Chicago telemedicine clinic between 3/2019 and 3/2021. Patients who were released from IDOC or reincarcerated during the study period were excluded. The primary endpoint compared the rate of HIV VS pre-, peri- and post-SARS-CoV-2 restrictions. Secondary endpoints included change in immunologic function pre-, peri- and post-SARS-CoV-2 restrictions, incidence of SARS-CoV-2 infection, number of hospitalizations, development of virologic failure, and change in ART post-pandemic. Other factors known to influence COC were also collected.

Results
Of 320 patients screened, 225 were included. The majority were Black males (73.7%) and 95.1% had a CD4 T-cell count &gt; 200 cells/mm3 at baseline. Approximately 88% of patients were on a single tablet regimen, with most receiving bictegravir/emtricitabine/tenofovir alafenamide. Rates of HIV VS are summarized in Figure 1 and secondary outcomes are summarized in table 1. Factors associated with disruption of COC included non-adherence to appointments (62.6%) and ART (4.4%). Figure 1Rates of HIV viral suppression (&lt;200 copies/mL), n(%)
Table 1 Secondary outcomes

Conclusion
Results demonstrated that PLWH within IDOC had sustained VS and COC throughout the SARS-CoV-2 pandemic with telemedicine. These results describe how the pandemic impacted PLWH in a correctional setting and future studies could contribute to creating national guidance for telemedicine models to streamline clinical practice.

Disclosures
All Authors: No reported disclosures.
1109. Rise and Fall of COVID-19 Therapies Throughout Different Waves of the Pandemic: Results of a Nationwide Survey
Authors: Mena Lora Alfredo J , Herald Fischer , Lindsey Brenna , Borgetti Scott , Chaisson Lelia H , Burgos Rodrigo M , Bleasdale Susan C 
Published: December 2022

Abstract

Background
The COVID-19 pandemic has caused a major public health crisis and is now a leading cause of death. At the start of the COVID-19 pandemic, treatment was limited to supportive care and off-label use of a variety of agents as we awaited the results of randomized controlled trials (RCTs). Our understanding of the disease has evolved and multiple evidence-based (EBM) treatment strategies supported by RCTs are now approved for use. Interpreting emerging data while responding to the pandemic can been challenging. We seek to understand the use of common medications during the COVID-19 pandemic.

Methods
A survey was developed and disseminated through Infectious Diseases Society of America (IDSA) IDea network, IDSA Antimicrobial Stewardship Centers for Excellence and the Society for Healthcare Epidemiology messaging boards. Data collected included city, therapeutic options including convalescent plasma (CP), hydroxychloroquine (HCQ), baricitinib and tocilizumab during each COVID-19 wave.

Results
A total of 78 responses were collected, representing wide geographic reach in the US (Figure 1). Use of HCQ declined by 96% and use of CP declined by 85% (Figure 2). The decline in CP was gradual each wave despite RCTs showing lack of benefit. Tocilizumab was used in 71% and 76% of hospitals during the first wave, prior to RCT data supporting its use. Baricitinib was used in 42% of hospitals prior to RCT data supporting its use. There was a 90% increase in baricitinib use after RCT data emerged. Figure 1Geographic distribution of hospitals represented in the survey
Figure 2 Use of Hydroxychloroquine, Convalescent Plasma, Tocilizumab and Baricitinib Throughout Different COVID-19 Waves

Conclusion
The use of therapies before proven benefit was common through the pandemic. Similarly, the use of therapies after benefit was in question continued. Hydroxychloroquine was widely used in the first wave and then halted by the majority of hospitals in subsequent COVID-19 surges. IL-6 and JAK-2 inhibitors were commonly used prior to evidence of benefit and were more widely adopted once evidence emerged. Convalescent plasma use was common despite lack of evidence and its use continued despite multiple negative RCTs. Overall, our survey shows a gap between evidence and practice. Communicating evidence-based treatment strategies is a vital priority for major professional societies. Translating evidence into practice remains challenging during public health emergencies like the COVID-19 pandemic.

Disclosures
All Authors: No reported disclosures.
1112. Evaluating the Effects of Casirivimab-Imdevimab in Mild-to-Moderate COVID-19 Disease: A Matched Cohort Study
Authors: Hage Cindy , Martinez Aileen , Dunham Alexis , Mohseni Nathan , Hernandez-Jimenez Jarelys , Cardona Lyssette L 
Published: December 2022

Abstract

Background
In November 2020, the FDA issued an Emergency Use Authorization (EUA) for casirivimab-imdevimab (CAS-IMD) for the treatment of mild to moderate coronavirus disease 2019 (COVID-19) in certain high-risk patients. CAS-IMD is a monoclonal antibody cocktail that binds to COVID-19 spike protein receptor. Delta was the predominant strain in the US at the time.
The purpose of this study is to evaluate if CAS-IMD administration to COVID-19 patients in the emergency department (ED) resulted in fewer hospitalizations and re-admissions.

Methods
A retrospective chart review was conducted at Cleveland Clinic Martin Health which is composed of 3 hospitals and 1 free-standing ED. Patients with COVID-19 who met criteria for CAS-IMD in the ED from June 2021 to December 2021 were randomized into those who received CAS-IMD and those who did not. Patients were excluded if they had COVID-19 symptoms for &gt;10 days or met EUA exclusion criteria for CAS-IMD. Cases and controls were matched by propensity score which was calculated by a logistic regression model including age, body mass index (BMI), sex, race and comorbidities. The primary outcome was the percentage of patients discharged from the ED who were hospitalized for COVID-19-related symptoms within 30 days. Secondary outcomes included number of CAS-IMD infusion-related reactions, ED return rate and subset analyses of severity of illness in the hospitalized. Statistical analyses were performed using two-sample t test or Wilcoxon rank sum test for continuous variables based on distribution, and Chi-square test or Fisher’s exact test for categorical variables. Conditional logistic regression was used to compare the odds of hospitalization between groups.

Results
Patients (N = 176) were matched 1:1 in each group. Eleven (12.5%) of the case group were hospitalized within 30 days of ED discharge vs. 36 (40.9%) in the control group. The odds of hospitalization in the CAS-IMD group were 81% lower than the control group (OR 0.19, 95% CI: 0.081-0.46, p&lt; 0.001). After adjustment of covariates, the adjusted odds ratio remained significant (OR 0.12, 95% CI: 0.025-0.57, p=0.008).

Conclusion
CAS-IMD use for mild-to-moderate COVID-19 infection in ED patients was associated with a lower incidence of hospitalization.

Disclosures
All Authors: No reported disclosures.