Retrospective validation of a rapid Lyme fluorescent immunoassay in differentiating Lyme arthritis from other musculoskeletal presentations in children in a Lyme-endemic region.

Lyme arthritis can present similarly to other causes of joint pain and swelling including septic arthritis and other acute and chronic arthropathies of childhood. Septic arthritis, although rare, constitutes an orthopedic emergency and requires early surgical intervention to reduce the risk of permanent joint damage. Currently, results of standard serologic tests to diagnose Lyme disease take days to weeks, which is unhelpful in acute clinical decision-making. Thus, some children with Lyme arthritis are treated empirically for septic arthritis undergoing unnecessary invasive procedures and hospital admission while on inappropriate antibiotic therapy. We retrospectively validated the Quidel Sofia Lyme Fluorescent Immunoassay, a rapid serologic assay that can detect IgG and/or IgM antibodies to Borrelia burgdorferi in 10 minutes, in residual serum samples collected from 51 children who had Lyme arthritis and 55 children with musculoskeletal presentations who were Lyme negative. The sensitivity and specificity of the Sofia IgG to identify cases of Lyme arthritis in children were 100% (95% confidence interval [CI] of 93.0%-100%) and 96.4% (95% CI: 87.5%-99.6%), respectively. The positive likelihood ratio (LR) was 27.5 (95% CI 7-107), and the negative LR was 0.00 (95% LR 0.00-0.15). We propose that the Sofia IgG, a rapid method for identifying Lyme arthritis, may be useful in differentiating Lyme arthritis from other forms of arthritis. Used in conjunction with readily available clinical and laboratory variables, it could help to rapidly identify children who are at low risk of septic arthritis in Lyme-endemic regions. IMPORTANCE: Lyme arthritis is a common manifestation of Lyme disease in children, with clinical features overlapping with other causes of acute and chronic joint pain/swelling in children. We have demonstrated that the Sofia IgG is a reliable test to rule in and rule out the diagnosis of Lyme arthritis in children with musculoskeletal presentations in a Lyme-endemic region. When used in conjunction with clinical and laboratory variables routinely considered when differentiating Lyme arthritis from other diagnoses, the Sofia IgG has the potential to fill an important gap in care, especially when acute decision-making is necessary. The Sofia IgG should be included in prospective research studies examining clinical prediction tools to identify children at low risk of septic arthritis.

Taqman PACMAN: a simple molecular approach for positive rapid antigen test confirmation during periods of low prevalence.

Antigen-based rapid diagnostic tests (Ag-RDTs) were widely deployed to enhance SARS-CoV-2 testing capacity during the COVID-19 pandemic. Consistent with national guidance for low prevalence settings, positive Ag-RDTs were confirmed using nucleic acid amplification tests (NAATs) to avoid false positive results. However, increasing demands for positive Ag-RDT confirmation competed with other testing priorities in clinical laboratories. This work hypothesized that real-time RT-PCR without nucleic acid extraction (NAE) would be sufficiently sensitive to support positive Ag-RDT confirmation. Ag-RDT and NAAT results from community-based asymptomatic testing sites prior to the omicron variant wave were compared to calculate the weekly false positive rate (FPR) and false detection rate (FDR). Real-time RT-PCR was compared with and without NAE using 752 specimens previously tested positive for SARS-CoV-2 using commercial NAATs and 344 specimens from Ag-RDT-positive individuals. The impact of SARS-CoV-2 prevalence on laboratory resources required to sustain Ag-RDT confirmation was modeled for the RT-PCR with and without NAE. Overall, FPR was low [0.07% (222/330,763)] in asymptomatic testing sites, but FDR was high [30.7% (222/724)]. When RT-PCR was compared with and without NAE, 100% concordance was obtained with NAAT-positive specimens, including those from Ag-RDT-positive individuals. NAE-free RT-PCR significantly reduced time to results, human resources, and overall costs. A 30.7% FDR reaffirms the need for NAAT-based confirmation of positive Ag-RDT results during low SARS-CoV-2 prevalence. NAE-free RT-PCR was shown to be a simple and cost-sparing NAAT-based solution for positive Ag-RDT confirmation, and its implementation supported data-driven broader Ag-RDT deployment into communities, workplaces, and households. IMPORTANCE: Rapid antigen testing for SARS-CoV-2 was widely deployed during the COVID-19 pandemic. In settings of low prevalence, national guidance recommends that positive antigen test results be confirmed with molecular testing. Given the high testing burden on clinical laboratories during the COVID-19 pandemic, the high volume of positive antigen tests submitted for confirmatory testing posed challenges for laboratory workflow. This study demonstrated that a simple PCR method without prior nucleic acid purification is an accurate and cost-effective solution for positive rapid antigen test confirmation. Implementing this method allowed molecular confirmatory testing for positive antigen tests to be sustained as antigen testing was expanded into large populations such as workplaces, schools, and households.

Impact and cost-effectiveness analyses of vaccination for prevention of respiratory syncytial virus disease among older adults in Ontario: A Canadian Immunization Research Network (CIRN) study.

BACKGROUND: Two prefusion F protein-based vaccines, Arexvy and Abrysvo, have been approved by Health Canada for protecting older adults against respiratory syncytial virus (RSV)-associated lower respiratory tract disease. We estimated the health benefits and cost-effectiveness of these vaccines under a publicly funded single-dose vaccination program in Ontario that targets residents of long-term care homes (LTCHs). Additionally, we evaluated an extended program that broadens vaccination to include community-dwelling older adults. METHODS: A discrete-event simulation model was parameterised with the burden of RSV disease including outpatient care, hospitalisation, and death among adults aged 60 years or older in Ontario, Canada. Accounting for direct and indirect costs (in 2023 Canadian dollars) associated with RSV-related outcomes, we calculated the net monetary benefit using quality-adjusted life-year (QALY) gained, and determined the range of price-per-dose (PPD) for vaccination programs to be cost-effective from both healthcare and societal perspectives over two RSV seasons. The incremental cost-effectiveness ratio (ICER) was calculated to estimate the additional costs required to gain one QALY. RESULTS: Using a willingness-to-pay of $50,000 per QALY gained, we found that vaccinating 90% of residents in LTCHs with Arexvy would be cost-effective from a societal perspective for a PPD up to $163, producing a mean ICER value of $49,984 (95% CI: $47,539 to $52,704) per QALY gained with a two-year budget impact of $463,468 per 100,000 older adults. The reduction of hospitalizations was estimated at 7.0% compared to the no-vaccination scenario. Extending the program to include community-dwelling older adults with a 74% coverage akin to influenza vaccination, Arexvy remains cost-effective for a PPD up to $139, with a mean ICER value of $49,698 (95% CI: 48,022 to 51,388) per QALY gained and a two-year budget impact of $8.63 million. Compared to the no-vaccination scenario, the extended program resulted in a 57.3% reduction in RSV-related hospitalisations. CONCLUSIONS: Vaccinating residents of LTCHs against RSV disease would be cost-effective depending on PPD; extending the program to community-dwelling older adults would provide substantial health benefits, averting significant direct healthcare costs and productivity losses.

Clinical features and outcomes of influenza and RSV coinfections: a report from Canadian immunization research network serious outcomes surveillance network.

BACKGROUND: Influenza and RSV coinfections are not commonly seen but are concerning as they can lead to serious illness and adverse clinical outcomes among vulnerable populations. Here we describe the clinical features and outcomes of influenza and RSV coinfections in hospitalized adults. METHODS: A cohort study was performed with pooled active surveillance in hospitalized adults ≥ 50 years from the Serious Outcomes Surveillance Network of the Canadian Immunization Research Network (CIRN SOS) during the 2012/13, 2013/14, and 2014/15 influenza seasons. Descriptive statistics summarized the characteristics of influenza/RSV coinfections. Kaplan-Meier estimated the probability of survival over the first 30 days of hospitalization. RESULTS: Over three influenza seasons, we identified 33 cases of RSV and influenza coinfection, accounting for 2.39 cases per 1,000 hospitalizations of patients with acute respiratory illnesses. Adults aged 50 + years commonly reported cough (81.8%), shortness of breath (66.7%), sputum production (45.5%), weakness (33.3%), fever (27.3%), and nasal congestion (24.2%) as constitutional and lower respiratory tract infection symptoms. The mortality rate was substantial (12.1%), and age, comorbidity burden, and frailty were associated with a higher risk for adverse clinical outcomes. CONCLUSIONS: Older adults are at higher risk for complications from influenza and RSV coinfections, especially those over 65 with a high comorbidity burden and frailty.

Real-world evaluation of the Lucira Check-It COVID-19 loop-mediated amplification (LAMP) test.

IMPORTANCE: In hospitals during the COVID-19 pandemic, laboratory testing was important to reduce SARS-CoV-2 transmissions, while facilitating patient flow in the emergency department and pre-operative settings, and allowing for the safe return to work of exposed healthcare workers. Delayed test results from laboratory nucleic acid amplification tests (NAATs) posed a barrier to maximizing efficient patient flow and minimizing staffing shortages. This quality improvement project sought to evaluate the analytical and clinical performance of the Lucira Check-It COVID-19 Test, a point-of-care test that used NAAT technology, in the perioperative setting, emergency department, and community testing sites. We found the Lucira Check-It to have comparable performance to laboratory NAATs. It can be employed with little training for specimen collection, processing, and interpretation, and at a cost justifiable from the resources saved from avoiding sample transport and laboratory testing.

Neglected SARS-CoV-2 variants and potential concerns for molecular diagnostics: a framework for nucleic acid amplification test target site quality assurance.

IMPORTANCE: Molecular tests like polymerase chain reaction were widely used during the COVID-19 pandemic but as the pandemic evolved, so did SARS-CoV-2. This virus acquired mutations, prompting concerns that mutations could compromise molecular test results and be falsely negative. While some manufacturers may have in-house programs for monitoring mutations that could impact their assay performance, it is important to promptly report mutations in circulating viral strains that could adversely impact a diagnostic test result. However, commercial test target sites are proprietary, making independent monitoring difficult. In this study, SARS-CoV-2 test target sites were sequenced to monitor and assess mutations impact, and 29 novel mutations impacting SARS-CoV-2 detection were identified. This framework for molecular test target site quality assurance could be adapted to any molecular test, ensuring accurate diagnostic test results and disease diagnoses.

Vaccine Effectiveness of non-adjuvanted and adjuvanted trivalent inactivated influenza vaccines in the prevention of influenza-related hospitalization in older adults: A pooled analysis from the Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN).

BACKGROUND: Influenza vaccines prevent influenza-related morbidity and mortality; however, suboptimal vaccine effectiveness (VE) of non-adjuvanted trivalent inactivated influenza vaccine (naTIV) or quadrivalent formulations in older adults prompted the use of enhanced products such as adjuvanted TIV (aTIV). Here, the VE of aTIV is compared to naTIV for preventing influenza-associated hospitalization among older adults. METHODS: A test-negative design study was used with pooled data from the 2012 to 2015 influenza seasons. An inverse probability of treatment (IPT)-weighted logistic regression estimated the Odds Ratio (OR) for laboratory-confirmed influenza-associated hospitalization. VE was calculated as (1-OR)*100% with accompanying 95% confidence intervals (CI). RESULTS: Of 7,101 adults aged ≥ 65, 3,364 received naTIV and 526 received aTIV. The overall VE against influenza hospitalization was 45.9% (95% CI: 40.2%-51.1%) for naTIV and 53.5% (42.8%-62.3%) for aTIV. No statistically significant differences in VE were found between aTIV and naTIV by age group or influenza season, though a trend favoring aTIV over naTIV was noted. Frailty may have impacted VE in aTIV recipients compared to those receiving naTIV, according to an exploratory analysis; VE adjusted by frailty was 59.1% (49.6%-66.8%) for aTIV and 44.8% (39.1%-50.0%) for naTIV. The overall relative VE of aTIV to naTIV against laboratory-confirmed influenza hospital admission was 25% (OR 0.75; 0.61-0.92), demonstrating statistically significant benefit favoring aTIV. CONCLUSIONS: Adjusting for frailty, aTIV showed statistically significantly better protection than naTIV against influenza-associated hospitalizations in older adults. In future studies, it is important to consider frailty as a significant confounder of VE.

Leveraging Influenza Virus Surveillance From 2012 to 2015 to Characterize the Burden of Respiratory Syncytial Virus Disease in Canadian Adults ≥50 Years of Age Hospitalized With Acute Respiratory Illness.

Background: Respiratory syncytial virus (RSV) disease in older adults is undercharacterized. To help inform future immunization policies, this study aimed to describe the disease burden in Canadian adults aged ≥50 years hospitalized with RSV. Methods: Using administrative data and nasopharyngeal swabs collected from active surveillance among adults aged ≥50 years hospitalized with an acute respiratory illness (ARI) during the 2012-2013, 2013-2014, and 2014-2015 influenza seasons, RSV was identified using a respiratory virus multiplex polymerase chain reaction test to describe the associated disease burden, incidence, and healthcare costs. Results: Of 7797 patients tested, 371 (4.8%) were RSV positive (2.2% RSV-A and 2.6% RSV-B). RSV prevalence varied by season from 4.2% to 6.2%. Respiratory virus coinfection was observed in 11.6% (43/371) of RSV cases, with influenza A being the most common. RSV hospitalization rates varied between seasons and increased with age, from 8-12 per 100 000 population in adults aged 50-59 years to 174-487 per 100 000 in adults aged ≥80 years. The median age of RSV cases was 74.9 years, 63.7% were female, and 98.1% of cases had ≥1 comorbidity. Among RSV cases, the mean length of hospital stay was 10.6 days, 13.7% were admitted to the intensive care unit, 6.4% required mechanical ventilation, and 6.1% died. The mean cost per RSV case was $13 602 (Canadian dollars) but varied by age and Canadian province. Conclusions: This study adds to the growing literature on adult RSV burden by showing considerable morbidity, mortality, and healthcare costs in hospitalized adults aged ≥50 years with ARIs such as influenza.

Evaluating the effectiveness of lockdowns and restrictions during SARS-CoV-2 variant waves in the Canadian province of Nova Scotia.

Introduction: After the initial onset of the SARS-CoV-2 pandemic, the government of Canada and provincial health authorities imposed restrictive policies to limit virus transmission and mitigate disease burden. In this study, the pandemic implications in the Canadian province of Nova Scotia (NS) were evaluated as a function of the movement of people and governmental restrictions during successive SARS-CoV-2 variant waves (i.e., Alpha through Omicron). Methods: Publicly available data obtained from community mobility reports (Google), the Bank of Canada Stringency Index, the "COVID-19 Tracker" service, including cases, hospitalizations, deaths, and vaccines, population mobility trends, and governmental response data were used to relate the effectiveness of policies in controlling movement and containing multiple waves of SARS-CoV-2. Results: Our results indicate that the SARS-CoV-2 pandemic inflicted low burden in NS in the initial 2 years of the pandemic. In this period, we identified reduced mobility patterns in the population. We also observed a negative correlation between public transport (-0.78), workplace (-0.69), retail and recreation (-0.68) and governmental restrictions, indicating a tight governmental control of these movement patterns. During the initial 2 years, governmental restrictions were high and the movement of people low, characterizing a 'seek-and-destroy' approach. Following this phase, the highly transmissible Omicron (B.1.1.529) variant began circulating in NS at the end of the second year, leading to increased cases, hospitalizations, and deaths. During this Omicron period, unsustainable governmental restrictions and waning public adherence led to increased population mobility, despite increased transmissibility (26.41-fold increase) and lethality (9.62-fold increase) of the novel variant. Discussion: These findings suggest that the low initial burden caused by the SARS-CoV-2 pandemic was likely a result of enhanced restrictions to contain the movement of people and consequently, the spread of the disease. Easing public health restrictions (as measured by a decline in the BOC index) during periods of high transmissibility of circulating COVID-19 variants contributed to community spread, despite high levels of immunization in NS.

Simultaneous detection of SARS-CoV-2, influenza A, respiratory syncytial virus, and measles in wastewater by multiplex RT-qPCR.

A multiplex quantitative reverse transcription polymerase chain reaction (RT-qPCR)-based method was designed for the simultaneous detection of influenza A, SARS-CoV-2, respiratory syncytial virus, and measles virus. The performance of the multiplex assay was compared to four monoplex assays for relative quantification using standard quantification curves. Results showed that the multiplex assay had comparable linearity and analytical sensitivity to the monoplex assays, and the quantification parameters of both assays demonstrated minimal differences. Viral reporting recommendations for the multiplex method were estimated based on the corresponding limit of quantification (LOQ) and the limit of detection at 95 % confidence interval (LOD) values for each viral target. The LOQ was determined by the lowest nominal RNA concentrations where %CV values were ≤35 %. Corresponding LOD values for each viral target were between 15 and 25 gene copies per reaction (GC/rxn), and LOQ values were within 10 to 15 GC/rxn. The detection performance of a new multiplex assay was validated in the field by collecting composite wastewater samples from a local treatment facility and passive samples from three sewer shed locations. Results indicated that the assay could accurately estimate viral loads from various sample types, with samples collected from passive samplers showing a greater range of detectable viral concentrations than composite wastewater samples. This suggests that the sensitivity of the multiplex method may be improved when paired with more sensitive sampling methods. Laboratory and field results demonstrate the robustness and sensitivity of the multiplex assay and its applicability to detect the relative abundance of four viral targets among wastewater samples. Conventional monoplex RT-qPCR assays are suitable for diagnosing viral infections. However, multiplex analysis using wastewater provides a fast and cost-effective way to monitor viral diseases in a population or environment.

Optimizing Treatment of Staphylococcus aureus Bloodstream Infections Following Rapid Molecular Diagnostic Testing and an Antimicrobial Stewardship Program Intervention.

Pending antibiotic susceptibility results, vancomycin is often used for bloodstream infections (BSIs) to ensure treatment of methicillin-resistant Staphylococcus aureus (MRSA). As rapid discrimination of methicillin-susceptible S. aureus (MSSA) from MRSA in BSIs could decrease vancomycin use and allow early optimization of beta-lactam therapy, this study evaluated the impact of the use of rapid molecular testing for MSSA and MRSA coupled with an antimicrobial stewardship program (ASP) intervention. Between January and July 2020, the Cepheid Xpert MRSA/SA blood culture assay was performed on blood cultures with Gram-positive cocci in clusters that were identified as S. aureus using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The ASP team member then consulted with the treating physician. The time to optimal therapy (TTOT) and clinical outcomes, including length of hospital stay (LOS), were compared between the intervention (n = 29) and historical (n = 27) cohorts. TTOT was defined as the time from the first blood culture draw to the use of appropriately dosed antistaphylococcal beta-lactam monotherapy without vancomycin. Molecular testing significantly reduced the median time to MSSA and MRSA discrimination to 7.8 h, compared to 24.3 h with culture-based methods (P < 0.001). Compared to the control group, the median TTOT in the ASP intervention group was significantly shorter (P = 0.041) at 38.0 h (versus 50.1 h). Rapid discrimination between MRSA and MSSA using molecular testing, paired with an ASP intervention, significantly reduced the TTOT in patients with MSSA BSIs. IMPORTANCE Our research shows that time to optimal antibiotic treatment for serious bloodstream infections can be improved with rapid molecular sensitivity testing and feedback to prescribers. This can be implemented in laboratories without full microbiology services or training to improve patient outcomes by improving antimicrobial use.

The DataHarmonizer: a tool for faster data harmonization, validation, aggregation and analysis of pathogen genomics contextual information.

Pathogen genomics is a critical tool for public health surveillance, infection control, outbreak investigations as well as research. In order to make use of pathogen genomics data, they must be interpreted using contextual data (metadata). Contextual data include sample metadata, laboratory methods, patient demographics, clinical outcomes and epidemiological information. However, the variability in how contextual information is captured by different authorities and how it is encoded in different databases poses challenges for data interpretation, integration and their use/re-use. The DataHarmonizer is a template-driven spreadsheet application for harmonizing, validating and transforming genomics contextual data into submission-ready formats for public or private repositories. The tool's web browser-based JavaScript environment enables validation and its offline functionality and local installation increases data security. The DataHarmonizer was developed to address the data sharing needs that arose during the COVID-19 pandemic, and was used by members of the Canadian COVID Genomics Network (CanCOGeN) to harmonize SARS-CoV-2 contextual data for national surveillance and for public repository submission. In order to support coordination of international surveillance efforts, we have partnered with the Public Health Alliance for Genomic Epidemiology to also provide a template conforming to its SARS-CoV-2 contextual data specification for use worldwide. Templates are also being developed for One Health and foodborne pathogens. Overall, the DataHarmonizer tool improves the effectiveness and fidelity of contextual data capture as well as its subsequent usability. Harmonization of contextual information across authorities, platforms and systems globally improves interoperability and reusability of data for concerted public health and research initiatives to fight the current pandemic and future public health emergencies. While initially developed for the COVID-19 pandemic, its expansion to other data management applications and pathogens is already underway.

Hunting for mpox (monkeypox) mimickers: Use of the Biofire meningitis/encephalitis panel on lesion swabs to support alternative viral diagnoses.

BACKGROUND: Mpox (formerly monkeypox) is an emerging zoonotic disease of public health concern that presents as a rash mimicking other common viral exanthems. Unlike traditional testing algorithms relying on several assays, the BioFire FilmArray meningitis/encephalitis (ME) panel simultaneously detects common viruses causing rashes; however, Biofire ME is only licensed for testing on cerebral spinal fluid. OBJECTIVES: This study evaluated use of the Biofire ME panel for detection and discrimination of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), human herpesviruses type 6 (HHV-6), enteroviruses (EVs), and human paraechoviruses (HPeVs) from a dermal or mucocutaneous swabs collected in universal transport media (UTM). STUDY DESIGN: Results of the BioFire ME panel were compared against methods used during clinical testing. Ten-fold serial dilutions in UTM of cultured viruses were used to compare analytical sensitivity, and analytical specificity was assessed using panels of microorganisms in UTM. Clinical sensitivity and specificity were assessed using 20 positive specimens each for HHV-1, HHV-2, HHV-6, VZV, EVs, and HPeV, as well as 35 known negative specimens that included 15 mpox-positive specimens. RESULTS: Biofire ME was as sensitive as comparator methods, and correctly discriminated all HSV-1, HSV-2, VZV, HHV-6, EVs, and HPeVs from mpox and mpox-mimickers. Cross-reaction between EV and rhinoviruses A, B, and C were noted in the specificity panel. CONCLUSIONS: Swabs in UTM collected for mpox testing are suitable for use on the Biofire ME panel, allowing more streamlined diagnostic testing for viral exanthems in patients under investigation for mpox infection.

Using Serum Specimens for Real-Time PCR-Based Diagnosis of Human Granulocytic Anaplasmosis, Canada.

Whole blood is the optimal specimen for anaplasmosis diagnosis but might not be available in all cases. We PCR tested serum samples collected in Canada for Anaplasma serology and found 84.8%-95.8% sensitivity and 2.8 average cycle threshold elevation. Serum can be acceptable for detecting Anaplasma spp. when whole blood is unavailable.

Factors contributing to a coronavirus disease 2019 (COVID-19) outbreak on a mixed medical-surgical unit in a Canadian acute-care hospital.

Objective: To identify preventable factors that contribute to the cross transmission of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) to patients in healthcare facilities. Design: A case-control study was conducted among inpatients on a coronavirus disease 2019 (COVID-19) outbreak unit. Setting: This study was conducted in a medical-surgical unit of a tertiary-care hospital in Nova Scotia in May 2021. Patients: Patients hospitalized on the unit for at least 12 hours and healthcare workers (HCW) working on the unit within 2 weeks of outbreak declaration were included. Methods: Risk factors for SARS-CoV-2 infection were analyzed using simple and multiple logistic regression. Whole-genome sequencing (WGS) was performed to identify SARS-CoV-2 strain relatedness. Network analysis was used to describe patient accommodation. Results: SARS-CoV-2 infections were identified in 21 patients (29.6%) and 11 HCWs (6.6%). WGS data revealed 4 distinct clades of related sequences. Several factors likely contributed to the outbreak, including failure to identify SARS-CoV-2, a largely incomplete or unvaccinated population, and patient wandering behaviors. The most significant risk factor for SARS-CoV-2 infection was room sharing with an infectious patient, which was the only factor that remained statistically significant following multivariate analysis (odds ratio [OR], 9.2l; 95% confidence interval [CI], 2.04-41.67; P = .004). Conclusions: This outbreak likely resulted from admission of 2 patients with COVID-19, with subsequent transmissions to 17 patients and 11 staff. WGS and bioinformatics analyses were critical to identifying previously unrecognized nosocomial transmissions of SARS-CoV-2. This study supports strategies to reduce nosocomial transmissions of SARS-CoV-2, such as single-patient rooms, promotion of COVID-19 vaccination, and infection prevention and control measures including management of wandering behaviors.

Impact of respiratory viral infections on mortality and critical illness among hospitalized patients with chronic obstructive pulmonary disease.

BACKGROUND: Seasonal respiratory viral infections are associated with exacerbations and morbidity among patients with COPD. The real-world clinical outcomes associated with seasonal viral infections are less well established among hospitalized patients. RESEARCH QUESTION: To estimate the association between seasonal respiratory viral infections, 30-day mortality, and intensive care unit (ICU) admission among hospitalized COPD patients. STUDY DESIGN AND METHODS: We conducted an analysis of a national prospective multicenter cohort of COPD patients hospitalized with acute respiratory illness during winter seasons (2011-2015) in Canada. Nasopharyngeal swabs were performed on all patients at the onset of hospital admission for diagnosis of viral infection. Primary outcomes were 30-day mortality and ICU admissions. Secondary outcomes included invasive/non-invasive ventilation use. RESULTS: Among 3931 hospitalized patients with COPD, 28.5% (1122/3931) were diagnosed with seasonal respiratory viral infection. Viral infection was associated with increased admission to ICU (OR 1.5, 95% CI 1.2-1.9) and need for mechanical ventilation (OR 1.9, 95% CI 1.4-2.5), but was not associated with mortality (OR 1.1, 95% CI 0.8-1.4). Patients with respiratory syncytial virus (RSV) were equally likely to require ICU admission (OR 1.09, 95% CI 0.67-1.78), and more likely to need non-invasive ventilation (OR 3.1; 95% CI 1.8-5.1) compared to patients with influenza. INTERPRETATION: Our results suggest COPD patients requiring hospitalization for respiratory symptoms should routinely receive viral testing at admission, especially for RSV and influenza, to inform prognosis, clinical management, and infection control practices during winter seasons. Patients with COPD will be an important target population for newly developed RSV therapeutics. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT01517191.

Modified Two-Tiered Testing Enzyme Immunoassay Algorithm for Serologic Diagnosis of Lyme Disease.

The modified 2-tier testing algorithm (MTTT) for Lyme disease (LD) has been approved by the US Food and Drug Administration. In this study, we show that the MTTT detected 28% more cases of early infection compared with the standard 2-tier algorithm while retaining high specificity in a region with a high incidence of LD.

Avoiding False-Positive SARS-CoV-2 Rapid Antigen Test Results with Point-of-Care Molecular Testing on Residual Test Buffer.

Antigen-based rapid diagnostic tests (Ag-RDTs) have been widely used for the detection of SARS-CoV-2 during the coronavirus disease 2019 (COVID-19) pandemic. In settings of low disease prevalence, such as asymptomatic community testing, national guidelines recommend confirmation of positive Ag-RDT results with a nucleic acid amplification test (NAAT). This often requires patients to be recalled for repeat specimen recollection and subsequent testing in reference laboratories. This project assessed the use of a point-of-care molecular NAAT for SARS-CoV-2 detection (i.e., ID NOW), which was performed on-site at a volunteer-led asymptomatic community testing site on the residual test buffer (RTB) from positive Ag-RDTs. The ID NOW NAAT assay was performed on RTB from two Ag-RDTs: the Abbott Panbio and BTNX Rapid Response assays. Results of ID NOW were compared to real-time RT-PCR at a reference laboratory. Along with investigations into the clinical performance of ID NOW on RTB, analytical specificity was assessed with a panel of various respiratory organisms. Of the Ag-RDTs results evaluated, all 354 Ag-RDTs results characterized as true positives by RT-PCR were accurately identified with ID NOW testing of RTB. No SARS-CoV-2 detections by ID NOW were observed from 10 specimens characterized as false-positive Ag-RDTs, or from contrived specimens with various respiratory organisms. The use of on-site molecular testing on RTB provides a suitable option for rapid confirmatory testing of positive Ag-RDTs, thereby obviating the need for specimen recollection for molecular testing at local reference laboratories. IMPORTANCE During the COVID-19 pandemic, rapid antigen tests have been widely used for the detection of SARS-CoV-2. These simple devices allow rapid test results. However, false-positive results may occur. As such, individuals with positive rapid tests often must return to testing centers to have a second swab collected, which is then transported to a specialized laboratory for confirmation using molecular tests. As an alternative to requiring a repeat visit and a prolonged turn-around time for result confirmation, this project evaluated whether the leftover material from rapid antigen tests could be confirmed directly on a portable point-of-care molecular instrument. Using this approach, molecular confirmation of positive antigen tests could be performed in less than 15 min, and the results were equivalent to laboratory-based confirmation. This procedure eliminates the need for individuals to return to testing centers following a positive rapid antigen test and ensures accurate antigen test results through on-site confirmation.

Combined oropharyngeal/nares and nasopharyngeal swab sampling remain effective for molecular detection of SARS-CoV-2 Omicron variant.

The world has experienced several waves of SARS-CoV-2 variants of concern (VoCs) throughout the COVID-19 pandemic since the first cases in December 2019. The Omicron VoC has increased transmission, compared to its predecessors, and can present with sore throat and other cold-like symptoms. Given the predominance of throat symptoms, and previous work demonstrating better sensitivity using antigen-based rapid detection tests when a throat swab is included in the standard nasal sampling, this quality improvement project sought to ensure ongoing suitability of both combined oropharyngeal/nares (OPN) and nasopharyngeal (NP) swab sampling used throughout the pandemic. Consenting participants meeting Public Health testing criteria (mostly symptomatic or a close contact of a known case) were enrolled, and paired NP and OPN swabs were subjected to nucleic acid amplification testing (NAAT). Comparing paired specimens from 392 participants sensitivity of NP swabs was 89.1 % (95 % CI, 78.8-94.9), and that of OPN was 98.4 % (95 % CI: 90.9->99.9) (P-value 0.052). This project demonstrated that both NP and combined OPN swabs detected the Omicron variant with similar sensitivity by NAAT, supporting the continued use of either swab collection for SARS-CoV-2 molecular detection.

Older Age and Frailty are Associated with Higher Mortality but Lower ICU Admission with COVID-19.

Background: We report characteristics and outcomes of adults admitted to Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS) Network hospitals with COVID-19 in 2020. Methods: Patients with laboratory-confirmed COVID-19 admitted to 11 sites in Ontario, Quebec, Alberta, and Nova Scotia up to December 31, 2020 were enrolled in this prospective observational cohort study. Measures included age, sex, demographics, housing, exposures, Clinical Frailty Scale, comorbidities; in addition, length of stay, intensive care unit (ICU) admission, mechanical ventilation, and survival were assessed. Descriptive analyses and multivariable logistic regressions were conducted. Results: Among 2,011 patients, mean age was 71.0 (range 19-105) years. 29.7% were admitted from assisted living or long-term care facilities. The full spectrum of frailty was represented in both younger and older age groups. 81.8% had at least one underlying comorbidity and 27.2% had obesity. Mortality was 14.3% without ICU admission, and 24.6% for those admitted to ICU. Older age and frailty were independent predictors of lower ICU use and higher mortality; accounting for frailty, obesity was not an independent predictor of mortality, and associations of comorbidities with mortality were weakened. Conclusions: Frailty is a critical clinical factor in predicting outcomes of COVID-19, which should be considered in research and clinical settings.