Mapping disparities in viral infection rates using highly multiplexed serology.

Despite advancements in medical interventions, the disease burden caused by viral pathogens remains large and highly diverse. This burden includes the wide range of signs and symptoms associated with active viral replication as well as a variety of clinical sequelae of infection. Moreover, there is growing evidence supporting the existence of sex- and ethnicity-based health disparities linked to viral infections and their associated diseases. Despite several well-documented disparities in viral infection rates, our current understanding of virus-associated health disparities remains incomplete. This knowledge gap can be attributed, in part, to limitations of the most commonly used viral detection methodologies, which lack the breadth needed to characterize exposures across the entire virome. Additionally, virus-related health disparities are dynamic and often differ considerably through space and time. In this study, we utilize PepSeq, an approach for highly multiplexed serology, to broadly assess an individual's history of viral exposures, and we demonstrate the effectiveness of this approach for detecting infection disparities through a pilot study of 400 adults aged 30-60 in Phoenix, AZ. Using a human virome PepSeq library, we observed expected seroprevalence rates for several common viruses and detected both expected and previously undocumented differences in inferred rates of infection between our male/female and Hispanic/non-Hispanic White individuals. IMPORTANCE: Our understanding of population-level virus infection rates and associated health disparities is incomplete. In part, this is because of the high diversity of human-infecting viruses and the limited breadth and sensitivity of traditional approaches for detecting infection events. Here, we demonstrate the potential for modern, highly multiplexed antibody detection methods to greatly increase our understanding of disparities in rates of infection across subpopulations (e.g., different sexes or ethnic groups). The use of antibodies as biomarkers allows us to detect evidence of past infections over an extended period, and our approach for highly multiplexed serology (PepSeq) allows us to measure antibody responses against hundreds of viruses in an efficient and cost-effective manner.

Influenza Virus Genomic Surveillance, Arizona, USA, 2023-2024.

Influenza viruses are constantly evolving and are therefore monitored worldwide in the hope to reduce the burden of disease by annual updates to vaccine recommendations. We conducted genomic sequencing of 110 influenza A and 30 influenza B viruses from specimens collected between October 2023 and February 2024 in Arizona, USA. We identified mutations in the hemagglutinin (HA) antigenic sites as well as the neuraminidase (NA) gene in our samples. We also found no unique HA and NA mutations in vaccinated yet influenza-infected individuals. Real-time genomic sequencing surveillance is important to ensure influenza vaccine effectiveness.

Genomic Sequencing Surveillance to Identify Respiratory Syncytial Virus Mutations, Arizona, USA.

We conducted surveillance of respiratory syncytial virus (RSV) genomic sequences for 100 RSV-A and 27 RSV-B specimens collected during November 2022-April 2023 in Arizona, USA. We identified mutations within prefusion F-protein antigenic sites in both subtypes. Continued genomic surveillance will be critical to ensure RSV vaccine effectiveness.

Baseline Sequencing Surveillance of Public Clinical Testing, Hospitals, and Community Wastewater Reveals Rapid Emergence of SARS-CoV-2 Omicron Variant of Concern in Arizona, USA.

The adaptive evolution of SARS-CoV-2 variants is driven by selection for increased viral fitness in transmissibility and immune evasion. Understanding the dynamics of how an emergent variant sweeps across populations can better inform public health response preparedness for future variants. Here, we investigated the state-level genomic epidemiology of SARS-CoV-2 through baseline genomic sequencing surveillance of 27,071 public testing specimens and 1,125 hospital inpatient specimens diagnosed between November 1, 2021, and January 31, 2022, in Arizona. We found that the Omicron variant rapidly displaced Delta variant in December 2021, leading to an "Omicron surge" of COVID-19 cases in early 2022. Wastewater sequencing surveillance of 370 samples supported the synchronous sweep of Omicron in the community. Hospital inpatient COVID-19 cases of Omicron variant presented to three major hospitals 10.51 days after its detection from public clinical testing. Nonsynonymous mutations in nsp3, nsp12, and nsp13 genes were significantly associated with Omicron hospital cases compared to community cases. To model SARS-CoV-2 transmissions across the state population, we developed a scalable sequence network methodology and showed that the Omicron variant spread through intracounty and intercounty transmissions. Finally, we demonstrated that the temporal emergence of Omicron BA.1 to become the dominant variant (17.02 days) was 2.3 times faster than the prior Delta variant (40.70 days) or subsequent Omicron sublineages BA.2 (39.65 days) and BA.5 (35.38 days). Our results demonstrate the uniquely rapid sweep of Omicron BA.1. These findings highlight how integrated public health surveillance can be used to enhance preparedness and response to future variants. IMPORTANCE SARS-CoV-2 continues to evolve new variants throughout the pandemic. However, the temporal dynamics of how SARS-CoV-2 variants emerge to become the dominant circulating variant is not precisely known. Genomic sequencing surveillance offers unique insights into how SARS-CoV-2 spreads in communities and the lead-up to hospital cases during a surge. Specifically, baseline sequencing surveillance through random selection of positive diagnostic specimens provides a representative outlook of the virus lineages circulating in a geographic region. Here, we investigated the emergence of the Omicron variant of concern in Arizona by leveraging baseline genomic sequence surveillance of public clinical testing, hospitals, and community wastewater. We tracked the spread and evolution of the Omicron variant as it first emerged in the general public, and its rapid shift in hospital admissions in the state health system. This study demonstrates the timescale of public health preparedness needed to respond to an antigenic shift in SARS-CoV-2.

International, multicenter evaluation of a new D-dimer assay for the exclusion of venous thromboembolism using standard and age-adjusted cut-offs.

INTRODUCTION: We sought to determine the test characteristics of an automated INNOVANCE D-dimer assay for the exclusion of pulmonary embolism (PE) and deep venous thrombosis (DVT) in emergency department (ED) patients using standard and age-adjusted cut-offs. METHODS: Cross-sectional, international, multicenter study of consecutive patients with suspected DVT or PE in 24 centers (18 USA, 6 Europe). Evaluated patients had low or intermediate Wells PE or DVT scores. For the standard cut-off, a D-dimer result <500 ng/ml was negative. For the age adjusted cut-off, we used the formula: Age (years) ∗ 10. The diagnostic standard was imaging demonstrating PE or DVT within 3 months. We calculated test characteristics using standard methods. We also explored modifications of the age adjustment multiplier. RESULTS: We included 3837 patients and excluded 251. The mean age of patients evaluated for PE (n = 1834) was 48 ±â€¯16 years, with 676 (37%) male, and 1081 (59%) white. The mean age of evaluated for DVT (n = 1752) was 53 ±â€¯16 years, with 710 (41%) male, and 1172 (67%) white. D-dimer test characteristics for PE were: sensitivity 98.0%, specificity 55.4%, negative predictive value (NPV) 99.8%, positive predictive value (PPV) 11.4%, and for DVT were: sensitivity 92.0%, specificity 44.8%, NPV 98.8%, PPV 10.3%. Age adjustment increased specificity (59.6% [PE], 51.1% [DVT]), but increasing the age-adjustment multiplier decreased sensitivity without increasing specificity. CONCLUSIONS: INNOVANCE D-dimer is highly sensitive and can exclude PE and DVT in ED patients with low- and intermediate- pre-test probability. Age-adjustment increases specificity, without increasing false negatives.

Inpatient utilization of blood cultures drawn in an urban ED.

Bloodstream infections are now ranked as the 10th leading cause of death in the United States. Given the severity of bacteremia, physicians routinely order multiple sets of blood cultures in the emergency department. This is a retrospective chart review on 1124 patients admitted to the hospital for suspected bacteremia during calendar year 2004. The aims of the present investigation were to investigate the overall utility of blood cultures by the admitting services and to identify patient factors that might influence culture yield. Data were collected regarding patient demographics, comorbidities, vital signs, laboratory results, antibiotic use, blood culture results, and notation of blood culture results by admitting physicians. Increased age, elevated heart rate, use of chemotherapy, decreased sodium, and increased blood urea nitrogen significantly increased the likelihood of yielding a positive blood culture in our patient population. Culture results were noted in 517 patient charts by the primary medical team (46.0%) and were adjusted in 223 patients (43.3%). Of 1124 cultures, 10.3% were positive in at least 1 bottle for a pathogenic organism (true positive), and 6.3% were contaminants (false positive). In conclusion, cultures must be followed closely by the admitting physician after being obtained. Our data emphasize that blood cultures are currently not well used by the admitting physicians and that measures need to be taken to improve the overall utility of blood culture data by the admitting physician.

Ultrasound guidance for central venous catheter placement: results from the Central Line Emergency Access Registry Database.

BACKGROUND: Ultrasound guidance of central venous catheter (CVC) insertion improves success rates and reduces complications and is recommended by several professional and regulatory organizations. METHODS: This is a prospective observational study using data extracted from the Central Line Emergency Access Registry database, a multicenter online registry of CVC insertions from medical centers throughout the United States. We compared success rates with ultrasound and with the anatomic-landmark technique. RESULTS: A total of 1250 CVC placement attempts by emergency medicine residents during the study period were selected from the Central Line Emergency Access Registry database. Because a few attempts (n = 28) were made to place lines in either the left or right supraclavicular locations, data on these attempts were eliminated from the analysis. A total of 1222 CVC attempts from 5 institutions were analyzed. Successful placement on the first attempt occurred in 1161 (86%) cases and varied according to anatomic location. Ultrasound guidance was used in 478 (41%) of the initial attempts. The remainder of placements were presumably placed using the anatomic-landmark technique based on visible surface and palpatory subcutaneous structures. Overall successful placement rate did not vary according to the use of ultrasound guidance, nor did it vary at different anatomic sites. However, ultrasound was found to be significant for reducing the total number of punctures per attempt (P < .02, t = 2.30). CONCLUSIONS: Our study did not observe improved success with the use of ultrasound for CVC cannulation on the first attempt, but we did observe a reduced number of total punctures per attempt.

Board-certified emergency physicians' treatment of skin and soft tissue infections in the community-acquired methicillin-resistant Staphylococcus aureus era.

BACKGROUND: Emergency physicians commonly treat skin and soft tissue infections. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has become the prominent etiologic agent in these infections. The CA-MRSA is resistant to many antibiotics traditionally used to treat skin and soft tissue infections. STUDY OBJECTIVES: We aim to identify how the increased prevalence of CA-MRSA has changed emergency medicine physician (EMP) prescribing and treatment practices for community-acquired skin and soft tissue infections. METHODS: The EMPs in the United States were surveyed between June and December of 2006. Two cases of skin and soft tissue infection were presented, and questions were asked about management. RESULTS: Two hundred seventy-five surveys were returned. The EMPs used a variety of approaches in the antibiotic treatment of skin and soft tissue infections. Two hundred seven (75.3%) of 275 were board-certified EMPs and were included in the analysis. Commonly used agents for outpatient treatment include trimethoprim/sulfamethoxazole, clindamycin, cephalexin, rifampin, and tetracyclines. For patients requiring admission, 60% of providers would include vancomycin in their treatment regimen. CONCLUSION: Many clinicians have changed their practice patterns to include antibiotics that usually display activity against CA-MRSA. However, cephalexin remains a popular agent used for these infections.