bluuebunny/crossref_metadata_2025_split huggingface dataset:
1880. Detection of Infectious SARS-CoV-2 in Specimens with High CT Values Is More Common for Omicron than for Delta Variants
Authors: Tassetto Michel , Garcia-Knight Miguel , Anglin Khamal , Kelly Dan , Lu Scott , Pineda-Ramirez Jesus , Saydah Sharon , Briggs-Hagen Melissa , Zhang Amethyst , Sanchez Ruth Diaz , Donohue Kevin , Romero Mariela , Peluso Michael J , Martin Jeffrey , Andino Raul , Midgley Claire 
Published: December 2022

Abstract

Background
Although not validated, cycle threshold (Ct) values from real-time (r)RT-PCR are sometimes used as a proxy for infectiousness to inform public health decision-making. A better understanding of variant-specific viral dynamics, including RNA and infectious virus relationships, is needed to clarify implications for diagnostics and transmission.

Methods
Non-hospitalized SARS-CoV-2-infected individuals were recruited ≤ 5 days post-onset and self-collected nasal swabs daily for two weeks. Sequencing was used to determine variant, an in-house quantitative rRT-PCR targeting N gene was used to produce Ct values and determine RNA load, and cytopathic effect was used to assess the presence or absence of infectious virus (binary outcome). We used a Ct threshold of 30 to define high-Ct (Ct &gt; 30) or low-Ct (Ct ≤ 30) specimens and assessed the percentage of RNA-positive specimens that had infectious virus; variant-specific percentages were compared by Χ2 test.

Results
We included 113 and 200 RNA-positive specimens from 18 and 28 Omicron- and Delta-infected participants, respectively; timing of RNA-positive specimen collection was similar in both groups (median = 8d post-onset). Maximum observed RNA levels occurred at median of 5 days post-onset for both variants but were lower for participants with Omicron vs Delta [mean RNA copies/mL = 105.2 vs 107.9]. Despite lower RNA levels, infectious virus was frequently detected for both variants [Omicron: median duration = 4.5d; Delta: median = 6d; p = 0.13]. Omicron specimens with infectious virus had higher Cts vs Delta specimens [mean Ct = 29.9 vs 23.2, p &lt; 0.001]. In high-Ct specimens (Ct &gt; 30; Table), the percentage of specimens with infectious virus was typically higher for Omicron vs Delta, and was significantly higher in adults [27.3% vs 9.5%]. In low-Ct specimens (Ct ≤ 30), the percentage with infectious virus was similar or higher for Omicron vs Delta, and was significantly higher in children [87.5% vs 53.8%] and in those unvaccinated [94.1% vs 47.4%].

Conclusion
CDC does not recommend the use of Ct values as a proxy for infectiousness. These data further highlight that Ct values may not provide a reliable or consistent proxy for infectiousness across variants.

Disclosures
All Authors: No reported disclosures.
1890. Molecular Biology of SARS-CoV-2 and its Evolution within the Princeton University Campus Community
Authors: Brewer Jesse T , Yang Qiqi , Aranovich Irina , Wang Wei , Notterman Daniel , Daskalaki Irini 
Published: December 2022

Abstract

Background
SARS-CoV-2, a novel and highly pathogenic coronavirus, has caused unprecedented global disruption following its introduction into the human population. Beginning in January 2021, a NJ university invited all students to campus and initiated an asymptomatic testing protocol using weekly to twice-weekly PCR-based detection of human saliva samples. RNA extracted from PCR-positive human saliva samples was sequenced for surveillance purposes.

Methods
Positive samples were submitted for RNA-Seq analysis (ARTIC amplicon sequencing protocol, Illumina MiSeq) and analyzed using Nextclade and USHER (comparison data from GISAID). Using sequencing data, the evolution, transmission, and emergence of SARS-CoV-2 variants were monitored over time in the campus community. Using sequencing data from NY, PA, and NJ in combination with University data, we performed an IQ-TREE based phylogenetic analysis.

Results
Analyzing sequencing data of 1,011 University positive samples we demonstrate that SARS-CoV-2 variants Delta (B.1.617.2) and Omicron (BA.1 and BA.2) were first to emerge following widespread vaccination and, quickly, became predominant. These trends witnessed on campus preceded those same variants emerging in New Jersey, providing evidence of local campus spread distinct from the state-wide pandemic. The analysis of 2,359 total sequences from NY, PA, and NJ in combination with University data, provided evidence of the SARS-CoV-2 transmission chain on campus evolving from out-of-state (January 2021) to local (January 2022) spread over one year of the virus circulating within the community at large. Upon performing a Ct value analysis of 2,822 Princeton University sequences, no significant differences were discovered between N gene Ct values when grouped by age or vaccination status. However, there were significant differences in Ct values between strains.
The Emergence of SARS-CoV-2 Variants at Princeton University
This plot represents the emergence of SARS-CoV-2 clades at Princeton University, organized by Nextstrain clade and displayed as a proportion out of one. Dates of sample collection range from January 25, 2021, to March 1, 2022. X-axis represents SARS-CoV-2 sample test date (grouped by month); Y-axis represents the count per day organized by Nextstrain clade.

Conclusion
Sequencing of positive SARS-CoV-2 samples from population screening of a highly vaccinated University campus community allowed the detection of emergence of new variants that became predominant on campus irrespective of the circulation of variants in the surrounding area.

Disclosures
All Authors: No reported disclosures.
1892. Rise of COVID-19 Re-infections as Omicron Variant Prevailed: Implications on Monitoring the Course of the Pandemic
Authors: Mellou Kassiani , Gkolfinopoulou Kassiani , Tryfinopoulou Kyriaki , Panagoulias Ioannis , Psallida Panagiota , Gerolymatos Gerasimos , Tsiodras Sotirios , Panagiotakopoulos Georgios , Paraskevis Dimitrios , Zaoutis Theoklis 
Published: December 2022

Abstract

Background
The emergence of the highly infectious Omicron variant at the end of 2021 changed the pandemic dynamics, also causing an increase in COVID-19 re-infections. Our aim was to investigate suspected re-infections and the characteristics of individuals with multiple infections since the beginning of the pandemic until early April 2022.

Methods
Since the beginning of the pandemic, all COVID-19 positive tests (Rapid Antigen Tests - RAT and PCR) have been recorded in the COVID-19 National Electronic Registry. Cases were extracted and reported daily based on the first positive test for each individual (first episodes). Establishment of the Omicron variant, associated with a re-infection surge, triggered the decision for modifying case definition and applying a different methodology to include suspected re-infections in the number of daily reported cases after 3rd of April. Suspected re-infections were defined as “positive PCR or RAT sample ≥90 days following a previous positive PCR or RAT”. The number of re-infections were estimated retrospectively on the Registry’s data.

Results
Overall, 6,348 suspected re-infections were recorded up to 15/12/2021 (0.6% of the laboratory confirmed tests), whereas until 3/4/22 the number was increased at 115.201, raising the percentage to 4%. Distribution of the number of reinfections per ISO week is depicted in Figure 1, along with the number of first episodes. Suspected re-infections stand for 3.7% of the total number of first episodes recorded up to 3/4/22 (3,077,711), with their integration having a noticeable effect on case counting. Among them, 99.3% represent a second episode of infection and 0.7% multiple re-infections. Median age of suspected re-infections was 29 years (IQR: 19-44) (Figure 2). The median length of the time interval between two subsequent infections was 8 months (IQR: 5-12) (Figure 3).

Conclusion
Up until mid-December 2021, COVID-19 re-infection was uncommon, changing to higher rates after the emergence of Omicron variant, thus documenting the immune escape capacity of this variant. Besides the improvement in surveillance, knowledge about the re-infections and their characteristics provides a proxy of the immune protection from previous exposure to COVID-19, against circulating variants over time.

Disclosures
All Authors: No reported disclosures.
1893. Risk Categorization and Outcomes among Healthcare Workers Exposed to COVID-19: A Cohort Study from A Thai Tertiary-care Center
Authors: Khawcharoenporn Thana , Chancharoenrat Watcharee , Sajak Sirinporn , Phetsaen Suphannee , Hanchai Padcharadda , Thongphubeth Kanokporn , Pienthong Thanus 
Published: December 2022

Abstract

Background
A risk categorization tool for healthcare workers (HCWs) exposed to severe acute respiratory syndrome coronavirus-2 is crucial for preventing coronavirus disease 2019 (COVID-19) transmission and requires validation and modification according to local context. We conducted this study to evaluate the performance of the study risk categorization tool and COVID-19-related outcomes among HCWs.

Methods
From 1 January to 31 December 2021, a prospective cohort study was conducted among COVID-19 exposing HCWs at a Thai tertiary-care center. The study risk categorization tool was specifically created in this study and modified from the United States Centers for Disease Control and Prevention recommendations, which classified HCWs into low-risk (LR), intermediate-risk (IR), and high-risk (HR) groups based on types of activities, duration of exposure, and protective methods used during exposure. Subsequent measures were determined for the HCWs based on the risk categories. The primary outcome was the difference in rates of COVID-19 in the LR, IR and HR HCWs.

Results
There were 1,892 HCWs included; 52%, 25% and 23% were LR, IR, and HR, respectively. The median age was 30 years (IQR, 26-36 years). The majority was female (79%) and nurses (33%). The most common risk activities were being in the same room with closed space without wearing a mask with COVID-19 cases (75%). COVID-19 was diagnosed in 157 HCWs and 27%, 5% and 1% of HR, IR and LR HCWs, respectively (P&lt; 0.001). By multivariable analysis, factors associated with COVID-19 included household or community exposure [adjusted odds ratio (aOR), 1588.68; P&lt; 0.001], being HR group (aOR, 11.94; P&lt; 0.001), working at outpatient departments (aOR, 2.54; P&lt; 0.001), and no history of COVID-19 vaccination (aOR, 2.05; P=0.01). The monthly rates of COVID-19 among LR, IR, and HR HCWs significantly decreased after the incremental rate of full vaccination. In-hospital transmission between HCWs occurred in 8% and was mainly due to eating at the same table (58%).

Conclusion
The study risk categorization tool can differentiate risks of COVID-19 among the HCWs. Prevention of COVID-19 should be focused on HCWs with the identified risk factors and behaviors associated with COVID-19 development and encouraging receipt of full vaccination.

Disclosures
All Authors: No reported disclosures.
1909. Steak with a Side of Omicron? Efficacy of Coordinated Outbreak Response during an early COVID-19 Omicron Outbreak amongst Restaurant Workers in Riverside County, CA
Authors: Tsang Shunling , Hetherington Wendy , Hetherington Wendy , Landeros-Tavera Juan , Chevinsky Jennifer , Penny Marshare 
Published: December 2022

Abstract

Background
On Dec 9, 2021, Riverside University Health System-Public Health (RUHSPH) identified a large outbreak of COVID-19 with staff at an upscale restaurant. Omicron was emerging as a Variant of Concern (VOC) and not well understood within the county. This study offers safe reopening strategies during a VOC outbreak.

Methods
RUHSPH worked with county supervisors, counsel, environmental health, and California Department of Public Health outbreak consultation team. Collaboration with corporate restaurant leaders resulted in voluntary closure of operations on Dec 21, 2021. RUHSPH teams were deployed to test and interview 33 staff over 2 days. Specimens were sent to RUHSPH lab for rapid processing. Positive samples were sent to California Viral and Rickettsial Disease Laboratory for whole genomic sequencing (WGS). Outbreak mitigation measures were agreed upon with restaurant leaders. Demographics of cases were summarized using descriptive statistics. Differences by vaccination status and Omicron VOC confirmation were tested with Pearson's Chi-Square.

Results
Between Nov 18-Dec 28, 2021, 31 cases were identified with a mean age of 34.9 years, including 4 positives during the 2-day outbreak investigation. (Table 1) Staff were demographically diverse with no significant differences among those who completed their primary vaccine series. 7 Omicron BA.1 cases were detected amongst staff who completed their primary vaccine series. (Figure 1) Significantly more Omicron cases were observed among females (p&lt; 0.05). Phylogenetic analysis of the Omicron specimens showed three distinct introductions with one clear cluster of 4 cases.
A framework of staff clearance was detailed with restaurant leaders. Clearance criteria allowed for reopening the next day. Contact tracing occurred for 79 total staff. No additional cases were identified amongst restaurant staff and the outbreak was closed on Jan 2, 2022. Table 1.Characteristics of the 31 employees that tested positive, including those tested during the 2-day investigation.Figure 1.Employees Infected with COVID-19 by Date of Symptom Onset or Specimen Collection

Conclusion
This response highlights the importance of collaboration between state, local, and workplaces to develop a concise approach in an emerging VOC outbreak. WGS provided evidence of distinct introductions and workplace transmission amongst restaurant staff. This approach will be imperative to evaluate and contain future VOC outbreaks.

Disclosures
All Authors: No reported disclosures.
1922. Outbreak and Management of COVID-19 and Infection Prevention Control Practices at a Community Living Center in Veterans Administration Hospital, North Texas
Authors: Hanna John J , Silva-Rodriguez Denisse , Christie-Smith Angela , Psenicka Andrew O , Reid Sherry R , Oboho Ikwo K 
Published: December 2022

Abstract

Background
The increase in SARS-CoV-2 cases due to the omicron wave led to significant utilization of healthcare resources and reduced acute care hospital beds at the Veterans Administration Hospital, North Texas Health Care System (VANTHCS). As a result, veterans with non-severe disease were managed at a VANTHCS community living center (CLC) during a COVID-19 outbreak.

Methods
Veterans residing at the CLC with laboratory-confirmed cases of SARS-CoV-2 (the virus that causes COVID-19) by polymerase chain reaction diagnosed from January 1 to February 15, 2022, were included in the descriptive analysis. We described resident characteristics and outcomes and infection control practices (IPC) implemented to control the outbreak. Resident data was ascertained from the COVID-19 facility dashboard and medical record system.

Results
From January 1–February 15, 2022, 33 adults residing at the CLC were diagnosed COVID-19. Most infections (93.9%) occurred between January 12–24 (figure 1). The median age was 76 years [interquartile range, 71–80 years] and 30 (90.9%) were men and 25 (75.8%) were white and 5 (15.2%) African American (table 1). Among the total cases, 9 (27.3%) resided in the dementia unit. Nineteen of 33 (57.6%) were asymptomatic. Overall, 28 (84.8%) were documented to be fully vaccinated against SARS-CoV-2 and 24 (72.7%) were boosted. Obesity, ischemic heart disease, chronic obstructive pulmonary disease, and stroke were the most common comorbidities. Residents were cohorted based on COVID-19 results. A multidisciplinary team was convened, and staff were fit tested for appropriate personal protective equipment (PPE) and received refresher training on hand hygiene, donning and doffing of PPE. Most residents were determined to have mild or moderate COVID-19 and managed at the CLC while 7 (21.2%) were hospitalized in the acute care hospital. For management of COVID-19, 11 (33.3%) received dexamethasone and 25 (75.8%) received remdesivir. Overall, 32 (97%) residents survived while one hospice resident was transferred to acute care and died; only 1 resident required ICU admission.
Epidemic curve of laboratory-confirmed coronavirus disease 2019 (COVID-19) disease at a Community Living Center, Veterans Administration Hospital, North Texas Health Care System, January–February 2022. Table 1Epidemiological Characteristics, and Outcomes of Laboratory-confirmed COVID-19 cases (N=33)Abbreviation: BMI, body mass index; COPD, Chronic Obstructive Pulmonary Disease; ESRD, end stage renal disease1Other comorbidity (asthma n=1 and chronic liver disease n=2)

Conclusion
It is feasible to administer COVID-19 therapies to high-risk residents with mild-moderate disease in a CLC with a multidisciplinary team and IPC strategies.

Disclosures
All Authors: No reported disclosures.
1932. Antibody Response to SARS-CoV-2 Vaccination in US Veterans Living with HIV
Authors: Njoroge Alexander , Ford Florence M , Psevdos George 
Published: December 2022

Abstract

Background
COVID-19 (C-19) vaccines have demonstrated effectiveness in reducing SARS-CoV-2 related morbidity/mortality. The duration of protection in the general population is showing a waning immunity over time. Variable antibody responses to C-19 vaccines have been shown in persons living with HIV. We followed the anti-SARS-CoV-2 receptor biding domain (RBD) antibody titers, after 2 and 3 (booster) C-19 vaccinations, in US Veterans living with HIV (USVLH).

Methods
Retrospective chart review of USVLH who had received C-19 vaccinations at Northport VAMC. Testing was done with the © Beckman Coulter enzyme immunoassay measuring total IgG antibody to the RBD, a critical target of neutralizing antibodies within the spike protein encoded in the mRNA vaccines. Titers were drawn after the 2nd and 3rd doses C-19 vaccines in variable timing. Demographic data, CD4+ T cell counts nadir and current, HIV viral load, comorbid conditions were reviewed.

Results
We analyzed the SARS CoV-2 RBD IgG titers in 50 vaccinated USVLH. The median age is 65 years (range 36-75). 50% were Black, Caucasian 40%, Hispanic 10%. Risk factor for HIV infection, Heterosexual 52%, IVDU 18%, MSM 26%, needle stick 2%, blood transfusion 2%. The median CD4 nadir was 200/µL (5- 600), median current CD4 656 (174-1529). All USVLH were on HAART, 92% on INSTI-based therapy. 45 had undetectable HIV viral load (&lt; 20), 5 had viremia from 22 to 563 copies. Medical conditions: diabetes 30%, CAD 18%, HTN 60%, COPD 8%, HLD 66%, smokers 18%. Six USV had C-19 prior to vaccination, and six had C-19 after vaccination with median 102 days (90-148) from last vaccine dose. Vaccines given: Janssen in 3 USVLH: Moderna (MOD)- 2 doses: 4; MOD-3 doses:5; Pfizer (PFZ)-2: 6; PFZ-3: 32. IgG titers decrease with time after 2nd vaccine dose and increase after booster dose. IgG titers checked after 2nd dose median days 120 (11-392) {titers: median 4.63 S/CO [0.17 – 53.66]}, 91 days (5-181) after 3rd dose {titers: median 16.22 [1.15-73.92]}. Titers were higher in MOD-2 vs. PFZ-2, median 25.7 vs. 4.63, P: 0.039, MOD-3 vs. PFZ-3 33.89 vs. 15.5, P: 0.117. No death due to C-19 was seen.
SARS-CoV-2 RBD IgG titers in US Veterans living with HIV after 2nd dose of COVID vaccine.
COVID-19 VACCINATED IN US VETERANS LIVING WITH HIV N=50

Conclusion
In a cohort of USVLH, well controlled on HAART, C-19 vaccinations produced a serologic response that decayed over time and increased after booster dose. MOD vaccine may have achieved higher titers than PFZ.

Disclosures
All Authors: No reported disclosures.
2349. Elucidating the Pathogenesis of Staphylococcus aureus During Hyperglycemic Osteomyelitis
Authors: Butrico Casey E , Eichelberger Kara R , Good Christopher J , Neumann Elizabeth K , Spraggins Jeffrey M , Cassat James E 
Published: December 2022

Abstract

Background
Staphylococcus aureus is a leading cause of antibiotic-resistant bacterial infections and can infect nearly every organ of the human body. One common manifestation of S. aureus disease is invasive bone infection, or osteomyelitis. Osteomyelitis is one of the most difficult to treat infections, often necessitating prolonged antibiotic treatment and surgical interventions. Hyperglycemia, or elevated blood glucose concentration, increases the risk for developing osteomyelitis. We hypothesized that S. aureus adapts specifically to the altered host environment during hyperglycemic osteomyelitis, thereby contributing to the increased infection severity.

Methods
To model hyperglycemic osteomyelitis, we treated mice with streptozotocin prior to infection with S. aureus in a post-traumatic osteomyelitis model. We analyzed bacterial burdens in homogenized tissues and bone parameters with microcomputed tomography. To identify changes in the spatial molecular architecture of infected, hyperglycemic femurs, we utilized imaging mass spectrometry. Finally, to obtain a comprehensive understanding of S. aureus metabolic and virulence changes and identify genes essential for staphylococcal growth in vivo in hyperglycemic mice, we performed a transposon sequencing experiment.

Results
We discovered that hyperglycemic mice sustained increased bacterial burdens within infected femurs and greater dissemination to other organs. We also found that hyperglycemic infected mice experienced increased rates of bone destruction and loss of trabecular bone volume, suggesting that hyperglycemia exacerbates infection-associated bone loss. Finally, we identified 71 genes as uniquely essential for S. aureus growth during hyperglycemic infection compared to euglycemic infection.

Conclusion
Hyperglycemia results in increased osteomyelitis infection severity. Multiple S. aureus genes involved in metabolism with roles in bacterial fitness in acidic environments were uniquely essential for bacterial fitness during comorbid infection. By identifying genes contributing to S. aureus survival during hyperglycemic osteomyelitis, we have the potential to inform targeted therapeutic development for treatment of exacerbated infections in patients with comorbid hyperglycemia.

Disclosures
All Authors: No reported disclosures.