Virus Testing Research Articles

Cilgavimab and tixagevimab as pre-exposure prophylaxis in vaccine non-responder kidney transplant recipients during a period of prevalent SARS-CoV-2 BA.2 and BA.4/5 variants—a prospective cohort study (RESCUE-TX)

The response to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination is severely impaired in patients on maintenance immunosuppression after kidney transplantation. We conducted a prospective cohort study of 194 kidney transplant recipients (KTR) who exhibited no response to SARS-CoV-2 vaccinations (i.e., SARS-CoV-2 spike protein antibodies ≤264 U/mL) and had no prior documented infection. Patients received 300mg of cilgavimab/tixagevimab as SARS-CoV-2 pre-exposure prophylaxis (PrEP) between March 4, 2022, and May 3, 2022 and were contrasted to a matched cohort of 186 KTRs also without immunization again defined as SARS-CoV-2 spike protein antibodies ≤264 U/mL and no documented prior infection. The primary outcome was the serum kinetics of cilgavimab/tixagevimab, the secondary endpoints were time to SARS-CoV-2 breakthrough infection, severity of disease and variant specific live viral invitro neutralization tests of patient sera. Longitudinal serum level monitoring showed a half-life of 91 days for both antibodies (95% CI 86-95 days for cilgavimab and 85-96 days for tixagevimab) in KTRs. Invitro neutralization tests showed effectiveness against the BA.2 omicron subvariant but not BA.5. The cumulative incidence of SARS-CoV-2 infections until May 15, 2022, (BA.2 dominance) was 15/194 vs 36/186 in the PrEP and control group respectively (OR=0.35, 95% CI 0.18-0.66) but was not different thereafter (BA.4/5 dominance). The number of severe infections during the BA.2 period was lower in the prophylaxis than in the control group (OR=0.37, 95% CI 0.17-0.79). This study showed that SARS-CoV-2 PrEP with cilgavimab/tixagevimab demonstrated clinical effectiveness against variants that are neutralised (BA.2) but not against BA.4/5. This study was funded by the Medical University of Vienna and an unrestricted grant from AstraZeneca (ESR-21-21585).

Exposures and coexisting conditions in pediatric nodular tracheobronchitis.

The aim of our study was to investigate the prevalence of coexisting conditions and exposures in children with nodular tracheobronchitis diagnosed by flexible bronchoscopy. We conducted a single-center retrospective review of 100 children diagnosed with nodular tracheobronchitis by flexible bronchoscopy between 2012 and 2023. Common coexisting diagnoses included gastroesophageal reflux disease (GERD, 50%), dysphagia/aspiration (40%), asthma (30%), recurrent croup (30%), tracheostomy dependence (19%) and eosinophilic esophagitis (EOE) (12%). Bronchoalveolar lavage (BAL) demonstrated cellular inflammation with elevated proportions of neutrophils in 63%, and lymphocytes in 24%. Among 88 patients in whom bacterial cultures were performed, 52% were positive, with Moraxella, Haemophilus, Streptococcal and Pseudomonas species predominating. Among 30 patients who underwent viral testing, 57% were positive, with rhinovirus (82%) and adenovirus (29%) predominating. Patients with neutrophilic inflammation were more likely to have a positive respiratory bacterial culture and/or viral polymerase chain reaction (p = 0.003, 0.005). Evaluation of the gastrointestinal tract included 79 patients with a history of esophagogastroduodenoscopy, 45 patients with a videofluoroscopic swallow study (VFSS), and 45 patients with multi-channel intraluminal impedance and pH testing. The majority of VFSS were abnormal (60%) demonstrating either laryngeal penetration (33%) or intratracheal aspiration (27%). Median pH reflux and impedance proximal reflux indices were 3.8% and 0.5% respectively. Potential contributing factors in the pathophysiology of nodular tracheobronchitis include bacterial and viral infections, GERD, dysphagia/aspiration, and EOE. When nodular tracheobronchitis is observed during bronchoscopy, further evaluation to assess for these conditions should be considered.

High prevalence of cardiotropic viruses in endomyocardial biopsies from patients with inflammatory cardiomyopathy demonstrated by a novel targeted NGS approach

Abstract Background Viral infection of the heart muscle is a common cause of myocarditis and viral persistence can lead to chronic inflammatory cardiomyopathies (DCMi). A number of viruses including parvovirus B19 (B19V), adenovirus (AdV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes virus 6 (HHV-6) and enteroviruses (EV) are known to infect the myocardium, but their prevalence and role in persisting DCMi are not well understood. Virological etiologies can only be determined via endomyocardial biopsy (EMB), but the low tissue amount limits the number of conventional viral nucleic acid tests (virus-specific PCR) that can be performed in parallel. This study aimed to detect known and novel cardiotropic viruses in EMB of DCMi patients using a targeted next generation sequencing (NGS) approach. Methods A cohort of 33 patients with inflammatory cardiomyopathy (DCMi) (LVEF=29±12%) were retrospectively analyzed and compared to previous results of virus-specific PCR. DNA and RNA extracted from EMB were used for sequencing library preparation, and viral nucleic acids were enriched via a custom myBaits hybridization capture approach. Enriched libraries were sequenced on an Illumina MiSeq-platform in paired-end mode (500.000 reads/sample), and reads were taxonomically classified via Kraken2 and mapped against viral reference genomes using BWA-MEM2 or HiSat2, and subsequently deduplicated. Viral reads detected via both Kraken2 and mapping were classified as valid. Results Targeted NGS confirmed 19 out of 22 (86%) of the previous PCR-based viral detections. However, NGS was able to detect B19V DNA and RNA in an additional 11 and 15 patient samples respectively; CMV DNA/RNA in additional 5 and 4 samples respectively; EBV DNA/RNA in additional 5 and 1 samples respectively; and HHV-6 DNA/RNA in additional 3 and 1 samples respectively. Furthermore, viral reads of adenovirus type 2, adenovirus-associated virus type 2 (AAV-2), herpes viruses 7 and 8, and human parvovirus 4 were also found among the cohort. Thus, targeted NGS was able to identify 82 viral infections in a cohort of 33 DCMi patients, while only 22 were found using routine PCR tests. For routinely tested B19V, the use of the new NGS diagnostic approach improved sensitivity by 42% and specificity by 72%. Conclusions The presented NGS method represents a powerful new tool for the diagnosis of viral and inflammatory heart disease. The sensitivity is significantly higher than with conventional PCR approaches and the taxonomic classification is more specific. This enables the detection of previously false-negative routine viruses as well as potentially new cardiotropic pathogens from limited bioptic patient material – thus significantly increasing the diagnostic yield of EMB. In addition, our study demonstrates a high prevalence of non-enteroviral cardiotropic viruses in DCMi patients, shedding new light on the etiology of this heterogenous diseases and paving the way for more specific future treatments.

Characterizing CRP dynamics during acute infections.

C-reactive protein (CRP) is a common proxy of inflammation, but accurate characterizations of its dynamics during acute infections are scant. The goal of this study was to examine C-reactive protein (CRP) trajectories in hospitalized patients with viral infections, confirmed bacteremia (stratified by Gram-negative or Gram-positive bacteria), and non-bacteremic infections/inflammations, considering antibiotic treatment. Electronic medical records from Tel Aviv Sourasky Medical Center (July 2007-May 2023) were analyzed. Patients with blood cultures or positive viral tests were included. CRP levels were modeled using generalized additive mixed-effects models (GAMMs) and observed up to 150h after initial infection diagnosis. Patients with initial CRP levels > 31.9 were excluded, to remove individuals already in a highly active inflammatory process. The shapes of the CRP curves were characterized and peak CRP as well as area under the CRP curve were the primary variables of interest. Viral infections had the lowest and flattest CRP curves. Non-bacteremic infections showed intermediate levels, while bacteremia (especially Gram-negative under antibiotic treatment) had the highest CRP peaks. For instance, peak CRP ranged from 15.4mg/L in viral infections without antibiotics to 140.9mg/L in Gram-negative bacteremia with antibiotics. CRP trajectories significantly differ based on infection type and antibiotic treatment. Frequent CRP measurement could be a valuable diagnostic and risk stratification tool in hospitalized patients.

Hepatitis Delta Virus Testing and Prevalence Among Chronic Hepatitis B Patients Across Three U.S. Safety-Net Health Systems

Background & AimsDespite a high prevalence of risk factors associated with hepatitis delta virus (HDV) infection among safety-net populations, data evaluating HDV testing and prevalence are limited. We aim to evaluate HDV testing practices and HDV prevalence among an ethnically diverse, multi-center cohort of safety-net patients with chronic hepatitis B (CHB). MethodsWe retrospectively evaluated 13,218 patients with CHB (54.2% male, 57.9% non-white minorities, 12.5% HIV, 23.0% HCV) across three U.S. safety-net health systems from 2010-2022 to evaluate proportion tested for HDV and proportion positive among those tested. Adjusted multivariate logistic regression models evaluated for predictors of HDV testing and predictors of anti-HDV positive. ResultsAnti-HDV testing was performed in 6.1% overall and in 4.9% that met AASLD criteria for HDV testing. Greater odds of testing was observed in men vs. women (OR 1.49, 95%CI 1.27–1.75), Asian individuals vs. white individuals (OR 2.18, 95%CI 1.74-2.72), black/African American individuals vs. white individuals (OR 1.29, 95%CI 1.07-1.56), and patients with Medicare or Medicaid. Among CHB patients tested for HDV, 15.7% were positive (22.9% among those meeting AASLD HDV testing criteria). Only 2 (1.6%) patients had follow-up HDV RNA testing. Greater proportion of anti-HDV positive was observed in patients with baseline cirrhosis (47.4% vs. 13.3%, p<0.001), and patients with Medicare or Medicaid vs. those with commercial insurance. ConclusionsAmong an ethnically diverse, multi-center safety-net cohort of CHB patients, low rates of HDV testing were observed, even among those with high-risk HDV risk factors. Among those tested, 15.7% were positive, only 2 had follow up RNA testing. This highlights the need for greater awareness, education, and advocacy to improve HDV testing rates.

53 Clinical characteristics and outcomes of children hospitalized with RSV-associated acute respiratory infections

Abstract Background Respiratory syncytial virus (RSV) is one of the most common acute respiratory infections (ARI) in infants and young children. After the relaxation of COVID-19 pandemic restrictions, children’s hospitals worldwide experienced unprecedented volumes and severity in presentation of children admitted with ARIs, such as RSV. It is unknown whether the increase in volumes was also associated with changes in the typical demographic, severity and outcomes of patients with RSV infections. Objectives To describe sociodemographic characteristics, clinical presentation, management including diagnosis and disposition and clinical outcomes of children under the age of 18 years admitted to tertiary care paediatric hospital with RSV-associated ARI. Design/Methods Observational cohort of children and adolescents aged 0-18 years admitted to two large Canadian children’s hospitals between July 1, 2022 - December 31, 2022, who had microbiological evidence of RSV infection. Detailed clinical and demographic information were extracted, including admission and discharge diagnoses, diagnostic tests, viral and bacterial testing, interventions, and respiratory settings. Clinical outcomes and complications were collected, including length of hospital admission, paediatric intensive care unit (PICU) admission, need for invasive mechanical ventilation, disposition, and death. Results There were 455 patients admitted with an RSV infection, of which a third (35.0%, n=146) were transfers from other hospitals. Cases were 41.0% male and the median age was 1.22 years (interquartile range [IQR] 0.19-3.06). Nearly two-thirds of patients (62.0%, n=284) were younger than 2 years of age, 8.6% had a history of prematurity. One third (31.0%, n=142) of patients had at least one documented comorbid condition, the most common diagnosis was asthma (6.6%). In addition to RSV, 3.5% (n=16) of patients had a simultaneous bacterial pathogen identified. Most patients (73%, n=330) were only RSV positive, while 24% (n=109) had two pathogens identified. One quarter (25.9%) were admitted to the PICU. The median length of hospital stay was 3 days (IQR 2.00-5.00) and for those admitted to the PICU, nearly two thirds of patients (63.0%, n=75) were admitted for less than 4 days. 0 patients died. The most common discharge diagnosis in 61.0% of patients (n=279) was bronchiolitis. There were 56 patients (12.3%) who had an unscheduled return visit to the ED within 30 days of discharge with 23.0% (n=13) requiring readmission to the hospital. Conclusion There continues to be a substantial volume of hospitalizations secondary to RSV infection, predominantly in those &amp;lt;2 years of age, with a prominent diagnosis of bronchiolitis. A quarter of patients had notable severity requiring PICU admission.

Factors associated with positive human papillomavirus (HPV) test results in cervical precancer screening: a cross-sectional study at Souro Sanou National Teaching Hospital (SSNTH) in Bobo Dioulasso, Burkina Faso.

Human papilloma virus testing is a new method of screening for precancerous cervical lesions. Here we identified factors associated to the positive Human papilloma virus-testing in the context of cervical precancer screening at the Souro Sanou National Teaching Hospital in Burkina Faso. Conducted from June 2021-May 2022, this was a cross-sectional study, including patients aged between 25 and 55years-old and screened for precancerous lesions and received HPV-testing at the Department of Gynecology, Obstetrics and Reproductive Medicine (DGORM) of the SSNTH. The proportion of positive HPV-test was calculated, and we identified factors associated to positive HPV-test using logistic regression. Of the 759 patients came for precancerous lesions screening, 559 patients were included. Their mean-age was 38.8 ± 7.9years-old, 94.3% were from urban area and 50.3% identified as housewives. Regarding the past medical history, it noted: number of gestures (3.2 ± 2.0), parity (2.8 ± 1.9), number of living children (2.8 ± 1.9), having abortion experience (24.0%), age of first-sexual-intercourse(18.6 ± 2.3years), alcohol (9.1%) and tobacco (1.0%) consumption, sexually-transmitted-infection (27.0%), Human immunodeficiency virus (HIV)infection (5.0%); none had been vaccinated against HPV. Biologically, 16.6% [95% CI: 13.6-20] of the women had a positive HPV-test. The factors significantly associated with positive HPV-test were: occupation in the private sector [OR: 0.06(0.0-0.5); p < 0.001], having a sexually-transmitted-infection [OR: 3.9(2.0-7.7); p < 0.001], age of first-sexual-intercourse [OR: 0.7(0.6-0.9); p < 0.001], sexual-multiple-partnership [OR: 17.5(8.1-39.6); p < 0.001], and HIV status [OR: 13.2(4.4-40.5); p < 0.001]. These results call for health actions through the reinforcement for behavioral change mainly about sexually-transmitted-infections, and for the raising awareness of the population for the screening related to the precancerous lesions and HIV.

Respiratory syncytial virus (RSV) vaccine effectiveness against RSV-associated hospitalisations and emergency department encounters among adults aged 60 years and older in the USA, October, 2023, to March, 2024: a test-negative design analysis

Respiratory syncytial virus vaccines first recommended for use during 2023 were efficacious against lower respiratory tract disease in clinical trials. Limited real-world data regarding respiratory syncytial virus vaccine effectiveness are available. To inform vaccine policy and address gaps in evidence from the clinical trials, we aimed to assess the effectiveness against respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years. We conducted a test-negative design analysis in an electronic health records-based network in eight states in the USA, including hospitalisations and emergency department encounters with respiratory syncytial virus-like illness among adults aged at least 60 years who underwent respiratory syncytial virus testing from Oct 1, 2023, to March 31, 2024. Respiratory syncytial virus vaccination status at the time of the encounter was derived from electronic health record documentation, state and city immunisation registries, and, for some sites, medical claims. Vaccine effectiveness was estimated by immunocompromise status, comparing the odds of vaccination among respiratory syncytial virus-positive case patients and respiratory syncytial virus-negative control patients, and adjusting for age, race and ethnicity, sex, calendar day, social vulnerability index, number of underlying non-respiratory medical conditions, presence of respiratory underlying medical conditions, and geographical region. Among 28 271 hospitalisations for respiratory syncytial virus-like illness among adults aged at least 60 years without immunocompromising conditions, vaccine effectiveness was 80% (95% CI 71-85) against respiratory syncytial virus-associated hospitalisations, and vaccine effectiveness was 81% (52-92) against respiratory syncytial virus-associated critical illness (ICU admission or death, or both). Among 8435 hospitalisations for respiratory syncytial virus-like illness among adults with immunocompromising conditions, vaccine effectiveness was 73% (48-85) against associated hospitalisation. Among 36 521 emergency department encounters for respiratory syncytial virus-like illness among adults aged at least 60 years without an immunocompromising condition, vaccine effectiveness was 77% (70-83) against respiratory syncytial virus-associated emergency department encounters. Vaccine effectiveness estimates were similar by age group and product type. Respiratory syncytial virus vaccination was effective in preventing respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years in the USA during the 2023-24 respiratory syncytial virus season, which was the first season after respiratory syncytial virus vaccine was approved. The Centers for Disease Control and Prevention.

Integrating Universal Hepatitis C Screening into Adolescent Well Visits is a "Win-Win" Scenario: Rationale and Demonstration of Real-World Feasibility and Implementation.

Hepatitis C virus (HCV) testing is recommended for all adults 18 years and older to increase identification of those with infection and facilitate prompt referral for curative antiviral therapy. While critical to promote elimination, this strategy excludes a key demographic group who are clearly at risk of undetected HCV infection and who could benefit from early treatment: adolescents. In this paper, we review the available data on the burden of HCV and the close association with injection drug use, discuss the rationale of universal testing in adolescents and, finally, present data from a quality improvement project implementing HCV testing into routine adolescent health visits.

High-risk human papillomavirus diversity among indigenous women of western Botswana with normal cervical cytology and dysplasia

BackgroundCervical cancer remains a public health problem despite heavy global investment in health systems especially in low-and-middle-income countries (LMIC). Prophylactic vaccines against the most commonly detected human papillomavirus (HPV) types in cervical cancers are available and decisions on the selection of vaccine design depends on the prevalence of high-risk (hr) HPV genotypes for a particular region. In 2015, Botswana adopted the use of a quadrivalent HPV vaccine as a primary prevention strategy. Secondary prevention includes cervical smear screening whose uptake remains notably low among indigenous and marginalized communities despite efforts to improve access.AimTo determine the prevalence of hrHPV genotypes and cervical lesions’ burden in women from the indigenous and marginalized communities of Botswana.MethodsThis prospective survey enrolled 171 non-HPV vaccinated women aged 21 years and older. Face-to-face interviews, Pap smear screening, hr-HPV and Human Immuno-deficiency virus (HIV) testing were carried out. Conventional Papanicolau smears were analyzed and cervical brushes were preserved for hrHPV testing using the Ampfire Multiplex HR-HPV protocol which detects the following genotypes: HPV 16, 18, 31, 35, 39, 45, 51, 52, 53, 56, 58, 59 and 68.ResultsIn this study, 168/171 (98.6%) of the women consented to HIV testing; 53/171 (31%) were living with HIV and self-reported enrolment on antiretroviral therapy. Among the women examined, 23/171 (13.5%) had cervical dysplasia with most presenting with Atypical Squamous Cells of Undetermined Significance 8/23 (35%), Low-Grade Squamous Intraepithelial Lesions 8/23 (35%), Atypical Squamous Cells-High Grade 4/23 (17%), Atypical Endocervical Cells 2/23 (9%) and Atypical Endocervical Cell favoring neoplasia 1/23(4%). However, no High-Grade Squamous Intraepithelial Lesions (HSIL) or squamous cell carcinoma (SCC) were detected. Overall hrHPV prevalence in this study was at 56/171 (32.7%). The most commonly detected hrHPV genotypes in women with cervical dysplasia were HPV39 (6.25%), HPV51 (14.5%), HPV52 (12.5%) and HPV56 (4%). Notably, HPV 16 and 18 were not found in women with cervical dysplasia.ConclusionsOur study provides valuable insights into the prevalence and distribution of hrHPV genotypes in indigenous and marginalized communities in Botswana, and the need for further investigation of their potential role in cervical carcinogenesis in this population. These results may also serve as baseline data to facilitate future evaluation of the HPV vaccine needs.

Long-Term Trends in Antibiotic Use in a Low-Resource Medical Setting: Amman, Jordan (2010–2023)

Abstract Background Antimicrobial resistance (AMR) contributes to substantial morbidity and mortality. The misuse and overuse of antibiotics are major drivers of AMR. Lack of point-of-care testing to discern viral from bacterial infections complicates appropriate management in low-resource settings. This study examines antibiotic prescription practices in Amman, Jordan. Methods We conducted three prospective viral surveillance studies at the largest public hospital in Amman Jordan (2010–2013, 2020, and 2023). Our target population for this study was children &amp;lt;2 years old hospitalized with fever or respiratory symptoms. Through parental interviews and chart abstractions, we collected demographic and clinical data, including antibiotic use, as well as results of any blood, urine, and cerebrospinal fluid cultures performed at providers’ discretion. We classified antibiotics according to the 2023 World Health Organization AWaRe (Access, Watch, Reserve) antibiotic classification system, focusing on the utilization of Watch group antibiotics, which are recommended when first-line Access group antibiotics are ineffective or inappropriate. Research personnel also collected nasal or throat swabs from enrolled children, and these samples were tested in a research laboratory for common respiratory viruses using RT-PCR. Providers were unaware of viral testing results. We described categorical variables using absolute and relative frequencies and summarized continuous variables using the median and interquartile range (IQR). Results Of 4,950 children enrolled, we included 4,703. The median age was 3.5 months (IQR, 1.6–8.3), and 59.4% (n=2,793) were male. Most children were enrolled from the general ward (n=4,312 [91.9%]), with the remaining 380 (8.1%) being enrolled from the pediatric intensive care unit. Only 8 children (0.2%) among those eligible for seasonal influenza vaccination (n=1,624) had been vaccinated at presentation. The five most common admission diagnoses were bronchopneumonia (n=1,255 [26.7%]), rule-out sepsis (n=1,217 [25.9%]), bronchiolitis (n=866 [18.4%]), pneumonia (n=606 [12.9%]), and paroxysmal coughing or pertussis-like cough (n=273 [5.8%]). Blood, urine, or CSF samples were collected from 2,556 children (54.5%), 355 (13.9%) of whom tested positive for at least one bacterial species (Figure 1A). During hospitalization, 4,356 children (92.6%) received at least one antibiotic. Of those, 4,227 (97.0%) received at least one antibiotic from the Watch group (Figure 1B). The three most common Access group antibiotics prescribed were ampicillin (n=830 [17.7%]), gentamicin (n=96 [2.0%]), and amikacin (n=85 [1.8%]), whereas the three most common Watch group antibiotics prescribed were ceftriaxone (n=1,956 [41.7%]), cefuroxime (n=1,628 [34.7%]), and azithromycin (n=754 [16.1%]) Overall, 3,898 children (82.9%) were positive for at least one respiratory virus (Figure 1C). Providers ordered cultures most often for children 0–2 months old (n=1,575 [73.5%]) and those with an admission diagnosis of rule-out sepsis (n=1,161 [95.4%]). Despite seasonal variation, prescription and testing practices were consistent across study years. Conclusion Inappropriate antibiotic use remains a significant healthcare challenge in Jordan. Incorporating point-of-care viral testing for suspected respiratory infections and improving diagnostic testing for bacterial infections is crucial. Preventive strategies including influenza vaccination and the use of emerging therapies for RSV or other pathogens associated with high morbidity could indirectly limit inappropriate antibiotic use. Development of context-specific management guidelines and antimicrobial stewardship programs are urgently required to guide prescription practices.

Preparation of polyclonal antiserum to Tomato mosaic virus and its application as a viral diagnostic test

Preparation of polyclonal antiserum to Tomato mosaic virus and its application as a viral diagnostic test

Changes in use of multiplex respiratory panel testing during the COVID-19 pandemic.

COVID-19 changed the epidemiology of community-acquired respiratory viruses. We explored patterns of respiratory viral testing to understand which tests are most clinically useful in the postpandemic era. We conducted a retrospective observational study of discharge data from PINC-AI (formerly Premier), a large administrative database. Use of multiplex nucleic acid amplification respiratory panels in acute care, including small (2-5 targets), medium (6-11), and large panels (>11), were compared between the early pandemic (03/2020-10/2020), late pandemic (11/2020-4/2021), and prepandemic respiratory season (11/2019 - 02/2020) using ANOVA. A median of 160.5 facilities contributed testing data per quarter (IQR 155.5-169.5). Prepandemic, facilities averaged 103 respiratory panels monthly (sd 138), including 79 large (sd 126), 7 medium (sd 31), and 16 small panels (sd 73). Relative to prepandemic, utilization decreased during the early pandemic (62 panels monthly/facility; sd 112) but returned to the prepandemic baseline by the late pandemic (107 panels monthly/facility; sd 211). Relative to prepandemic, late pandemic testing involved more small panel use (58 monthly/facility, sd 156) and less large panel use (47 monthly/facility, sd 116). Comparisons among periods demonstrated significant differences in overall testing (P < 0.0001), large panel use (P < 0.0001), and small panel use (P < 0.0001). Postpandemic, clinical use of respiratory panel testing shifted from predominantly large panels to predominantly small panels. Factors driving this change may include resource availability, costs, and the clinical utility of targeting important pathogenic viruses instead of testing "for everything."

Risk and benefits of expanded donor screening: A viewpoint from Germany.

This review describes the risks and benefits of expanding screening for transmissible pathogens in deceased organ donors. The focus is on the experience and procedure in Germany to make a decision on how to proceed with a possible donor. Three issues are of interest in how screening policies impact the process with the aim of mitigating unexpected transmission risks: (1) Should we add universal or targeted nucleic acid testing to serological tests for common blood-borne viruses (BBVs; HIV, HBV, and HCV)? (2) Which tests should be added for screening in a geographically restricted region beyond testing for these BBVs? (3) Being faced with changes (e.g., climate and population) in the own geographically restricted region, what strategies are needed before implementing new tests, and which considerations apply for proper indication to do this? Testing may only be effective when during donor characterization the appropriate conclusions are drawn from the existing findings and screening tests are initiated. This statement overlaps the need to implement universal screening for a pathogen or targeted screening based on the risk that the donor has acquired the transmissible pathogen or is not as possible to identify by current methods of clinical judgment and/or specific tests.

7504 A Case of Methicillin Sensitive Staphylococcus Aureus Thyroiditis

Abstract Disclosure: K. Patel: None. P. Kachhadia: None. S. Khan: None. F. Akanbi: None. A. Abu Limon: None. S.A. Aldasouqi: None. Introduction: Acute suppurative thyroiditis refers to bacterial infection of the thyroid gland. It is rare as the thyroid gland is typically protected from infection due to isolation of the gland from neighboring structures as well as its rich blood supply and adequate lymphatic drainage. It shares characteristics with subacute and autoimmune thyroiditis which make for difficult diagnosis. Here we present a case of acute suppurative thyroiditis in the setting of methicillin sensitive staphylococcus aureus (MSSA) bacteremia. Case Presentation: We have a 45 year old gentleman with a history of polysubstance abuse who was admitted after a drug overdose. He was being treated for rhabdomyolysis and approximately ten days after admission he became febrile with Tmax 103.3 Farenheit with a sore throat and dysphagia. Workup showed leukocytosis, ESR 86 mm/h [0-15], CRP 45.5 mg/dL [0-1], blood cultures with MSSA, negative viral upper respiratory panel, throat culture, Syphilis and HIV testing. He had a positive Hepatitis C antibody without a detectable viral load. Echocardiogram ruled out vegetations. He was treated with cefazolin. CT neck was obtained and showed thyroid enlargement. Subsequent ultrasound showed heterogeneous echotexture and increased color flow and a left inferior pole nodule 2.3 x 2.1 x 2.0 cm. Thyroid labs showed TSH 0.16 [0.35 - 4.01 u[IU]/mL,] Free T4 3.91 ng/dL [0.61 - 1.37], TPO &amp;lt;0.3. The nodule was biopsied and endocrinology was consulted. On exam thyroid was nontender. He was started on beta blockers and thyroid labs were monitored. TSI and TRAB were negative. TSH, Free T4 and Free T3 improved to normal range. Nodule biopsy results showed benign follicular cells with abundant acute inflammation suggestive of an abscess. Metronidazole was added after biopsy results. Post antibiotic therapy, CRP improved to 1.7 mg/dL. Discussion/Conclusion: Incidence of acute suppurative thyroiditis has been published as occurring &amp;lt;1% of all thyroid diseases. One systematic review found 200 cases reported from January 2000 to January 2020. Prior case reports have described acute suppurative thyroiditis in adult patients with prior thyroid gland pathology or an immunocompromised state and some demonstrated a correlation with intravenous drug users. The most common culprits include Staphylococcus spp, Streptococcus spp, Salmonella spp, Escherichia spp. Management includes antimicrobial therapy and/or needle aspiration. Non-responders can undergo incision and drainage of abscess or thyroidectomy. Mortality was reported in about 8% of the reported 200 cases. In our patient, his history of drug use and Hepatitis C likely made him prone to infection. Although there was no description of pus during biopsy, pathology suggested acute inflammation. This along with elevated inflammatory markers led to the diagnosis. This case highlights an uncommon but potential cause of thyroiditis. Presentation: 6/3/2024

Utility of respiratory viral testing in the risk stratification of young febrile infants presenting to emergency care settings: a protocol for systematic review and meta-analysis

IntroductionFebrile infants under 3 months of age are at risk of invasive bacterial infection (IBI). It is currently unclear if testing for respiratory viruses may have a role in IBI...

Respiratory viral testing for young febrile infants presenting to emergency care: a planned secondary analysis of the Febrile Infants Diagnostic assessment and Outcome (FIDO) prospective observational cohort study

ObjectiveTo describe the association of respiratory viral test results and the risk of invasive bacterial infection (IBI) for febrile young infants presenting to emergency care.DesignA planned secondary analysis within the...

Diagnostic accuracy of point-of-care tests for acute respiratory infection: a systematic review of reviews.

Acute respiratory infections are a common reason for consultation with primary and emergency healthcare services. Identifying individuals with a bacterial infection is crucial to ensure appropriate treatment. However, it is also important to avoid overprescription of antibiotics, to prevent unnecessary side effects and antimicrobial resistance. We conducted a systematic review to summarise evidence on the diagnostic accuracy of symptoms, signs and point-of-care tests to diagnose bacterial respiratory tract infection in adults, and to diagnose two common respiratory viruses, influenza and respiratory syncytial virus. The primary approach was an overview of existing systematic reviews. We conducted literature searches (22 May 2023) to identify systematic reviews of the diagnostic accuracy of point-of-care tests. Where multiple reviews were identified, we selected the most recent and comprehensive review, with the greatest overlap in scope with our review question. Methodological quality was assessed using the Risk of Bias in Systematic Reviews tool. Summary estimates of diagnostic accuracy (sensitivity, specificity or area under the curve) were extracted. Where no systematic review was identified, we searched for primary studies. We extracted sufficient data to construct a 2 × 2 table of diagnostic accuracy, to calculate sensitivity and specificity. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies version 2 tool. Where possible, meta-analyses were conducted. We used GRADE to assess the certainty of the evidence from existing reviews and new analyses. We identified 23 reviews which addressed our review question; 6 were selected as the most comprehensive and similar in scope to our review protocol. These systematic reviews considered the following tests for bacterial respiratory infection: individual symptoms and signs; combinations of symptoms and signs (in clinical prediction models); clinical prediction models incorporating C-reactive protein; and biological markers related to infection (including C-reactive protein, procalcitonin and others). We also identified systematic reviews that reported the accuracy of specific tests for influenza and respiratory syncytial virus. No reviews were found that assessed the diagnostic accuracy of white cell count for bacterial respiratory infection, or multiplex tests for influenza and respiratory syncytial virus. We therefore conducted searches for primary studies, and carried out meta-analyses for these index tests. Overall, we found that symptoms and signs have poor diagnostic accuracy for bacterial respiratory infection (sensitivity ranging from 9.6% to 89.1%; specificity ranging from 13.4% to 95%). Accuracy of biomarkers was slightly better, particularly when combinations of biomarkers were used (sensitivity 80-90%, specificity 82-93%). The sensitivity and specificity for influenza or respiratory syncytial virus varied considerably across the different types of tests. Tests involving nucleic acid amplification techniques (either single pathogen or multiplex tests) had the highest diagnostic accuracy for influenza (sensitivity 91-99.8%, specificity 96.8-99.4%). Most of the evidence was considered low or very low certainty when assessed with GRADE, due to imprecision in effect estimates, the potential for bias and the inclusion of participants outside the scope of this review (children, or people in hospital). Currently evidence is insufficient to support routine use of point-of-care tests in primary and emergency care. Further work must establish whether the introduction of point-of-care tests adds value, or simply increases healthcare costs. This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR159948.

B-207 Clinical Evaluation of ExiStation™ FA 96 RV for the detection of human respiratory viruses in human nasopharyngeal swab specimen

Abstract Background There has been growing demand for fully automated multiplex testing of respiratory viruses in molecular diagnostics following the COVID-19 pandemic. ExiStation™ FA 96 RV developed by BIONEER is a multiplex real-time RT-PCR assay. It is designed for the simultaneous detection and differentiation of SARS-CoV-2, Influenza A, Influenza B, and RSV RNA in human nasopharyngeal swab specimens from individuals showing signs and symptoms of respiratory viral infection. ExiStation™ FA 96 automates the entire process from RNA extraction to real-time RT-PCR for up to 96 samples at once within 100 minutes. Moreover, the system is equipped to decap sample tubes, eliminating the need for handling sample transport media. In this study, the clinical performance of the ExiStation™ FA 96 RV assay was evaluated using nasopharyngeal swab samples. Methods Nasopharyngeal swab samples, totaling 859 samples, are collected according to the procedures by the clinical institution in France and preserved in Virus transport media. Once anonymized and randomly allocated, the swab transport media tube, without capping procedure, are directly placed onto the ExiStation™ FA 96. Subsequently, both extraction and real-time RT-PCR are automatically processed. Clinical sensitivity, specificity, and agreement are analyzed by comparing results with confirmatory reagents SARS-CoV-2 RT-qPCR Reagent Kit, PKAmp™ Respiratory SARS-CoV-2 RT-PCR Panel Kit, and Bosphore SARS-CoV-2/Flu/RSV Panel Kit, as well as comparator reagent Allplex™ Respiratory Panel 1 and Allplex™ SARS-CoV-2 Assay. Results The comparison between confirmatory reagents and the ExiStation™ FA 96 RV resulted in a clinical sensitivity of at least 96.4% (164/164 for SARS-CoV-2, 64/65 for Influenza A, 74/75 for Influenza B, and 53/55 for RSV) and a clinical specificity of 100% (500/500 for all targets). When compared with the comparator reagent, the overall agreement and Cohen's kappa value were both determined to be above 99.1% and 0.989, respectively (664/664 for SARS-CoV-2, 564/565 for Influenza A, 573/575 for Influenza B, and 550/555 for RSV). Additionally, any discrepant samples identified in comparison with the comparator reagent were verified through sequencing analysis. Upon sequencing analysis on a total of 8 samples and aligning the confirmed results with the analysis content, no alterations observed in the analysis of clinical sensitivity and specificity. Conclusions The evaluation of the ExiStation™ FA 96 RV assay showed outstanding clinical performance in detecting four respiratory viruses, SARS-CoV-2, Influenza A, Influenza B, and RSV, with high sensitivity and specificity. This study supports that the ExiStation™ FA 96 RV assay is a reliable tool for simultaneous molecular diagnostics of various respiratory infections in clinical laboratories.

A-268 Comparison of the Elecsys® HCV Duo Assay to Standard of Care Algorithmic Testing

Abstract Background Traditional hepatitis C virus (HCV) testing methods, though effective, may miss crucial diagnostic opportunities. The goal of this study was to assess the utility of Elecsys® HCV Duo antibody/antigen (Ab/Ag) assay as an alternative to traditional HCV algorithmic testing in the United States. Methods A prospective study was conducted at Barnes Jewish Hospital in St. Louis, Missouri. Patients with concurrent HCV Ab and molecular testing ordered within 48 h were enrolled. A total of 1,351 remnant serum and plasma-EDTA specimens were frozen following standard of care testing, which consisted of the Abbott Architect anti-HCV assay with reflex to cobas® HCV molecular assay. Patient demographics, risk factors, and results from both standard of care and HCV Duo testing were recorded. Results Among 1351 specimens, the HCV positivity rate as defined by algorithm was 19.9% (269/1351). Risk factors including homelessness and prior intravenous drug use were significantly associated with HCV diagnosis (P&amp;lt;0.0001). HCV Duo testing demonstrated a positivity rate of 19.6% (263/1345) based on Ab/Ag dual positivity. Comparing the HCV Duo Ab module to standard of care serology revealed a 95.1% PPA (95% CI, 93.1-96.5) and 98.8% NPA (95% CI, 97.7-99.4), while the HCV Duo Ag component exhibited a 72.3% PPA (95% CI, 66.7-77.3) and 99.6% NPA (95% CI, 99.1-99.9) when compared to molecular testing. In HCV-RNA+ patients, the Ag component was positively correlated to viral load with a Spearman r of 0.770 (95% CI, 0.715-0.815). The median viral load with for patients with Ag+ results was 6.27 log10 IU/mL (IQR, 5.90-6.69) and for patients with Ag- results was 5.08 log10 IU/mL (IQR, 4.47-5.61). Of HCV-RNA+ specimens , 266/271 (98.2%) were successfully detected on the Ab module. Among anti-HCV+/HCV-RNA+ cases, 99.2% (261/263) were detected as Ab+/Ag+ on the HCV Duo assay. These had a turnaround time (TAT) from serology to molecular results of 28.1 ± 23.5 h, which may have been significantly decreased if Ab/Ag dual positivity was solely used to establish a diagnosis (average TAT of 27 min). The remaining two discrepant specimens were from patients with a prior history of HCV infection, which may represent false negatives or seronegative chronic HCV infections. Notably, 5/8 (62.5%) anti-HCV-/HCV-RNA+ specimens were detected on the HCV Duo assay, which would have been missed by traditional algorithmic testing. These five patients had viral loads ranging from 323-41,400,000 IU/mL, compared to &amp;lt;15-5,400 IU/mL in the three undetected specimens. Of these five additional patient specimens captured on HCV Duo, two patients received an organ from an HCV+ donor, while the remaining three had no known history of HCV infection or transplant from an HCV+ donor. Conclusions The Elecsys® HCV Duo Ab/Ag assay, with its high sensitivity and specificity, drastically shortens the diagnostic window. Importantly, it successfully identified several anti-HCV-/HCV-RNA+ cases, a subgroup often undiagnosed by current algorithmic testing, demonstrating promise for improved diagnostic efficiency and accuracy in HCV detection. Further investigation is needed to determine whether improved diagnostic efficiency is due to enhanced antibody or antigen detection.