Variation in SARS-CoV-2 molecular test sensitivity by specimen types in a large sample of emergency department patients.

BACKGROUND: Provider-collected nasopharyngeal specimens for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) molecular testing are the standard of care in many clinical settings, but patient-collected saliva and anterior nares specimens are less invasive and more flexible alternatives. Prior studies comparing specimen types for SARS-CoV-2 molecular testing have been limited by small sample sizes and low pretest probability. We conducted a large observational study among symptomatic adults at 7 emergency departments of Kaiser Permanente Southern California to examine sensitivity of SARS-CoV-2 molecular tests by specimen type and patient characteristics. METHODS: Provider-collected nasopharyngeal/oropharyngeal (NP/OP) specimens and patient-collected saliva and anterior nares specimens were collected at the same visit and analyzed with the Roche cobas® SARS-CoV-2 assay. Patients were considered truly positive for SARS-CoV-2 if any of the three specimens was positive and negative if all three specimens were negative. Factors associated with discordant and missed positive results were examined with multivariable logistic regression. RESULTS: Of 2112 patients, 350 (16.6%) were positive for SARS-CoV-2. Sensitivity of NP/OP was 93.7% (95% confidence interval [CI] 90.6%-96.0%), sensitivity of saliva was 87.7% (83.8%-91.0%), and sensitivity of anterior nares was 85.4% (81.3%-89.0%). Patients ages 18-39 years versus ≥40 years were more likely to have discordant results [adjusted odds ratio (aOR) 1.97 (1.12-3.45)], as were patients with <4 symptoms versus ≥4 [aOR 2.43 (1.39-4.25)]. Cycle threshold values were higher for saliva and anterior nares than NP/OP specimens, as well as for specimens in discordant versus concordant sets and patients with fewer symptoms. CONCLUSION: This study provides robust evidence that patient-collected saliva and anterior nares are sensitive for SARS-CoV-2 molecular testing in emergency department settings, particularly among adults ages ≥40 years and those with multiple symptoms. Higher sensitivity of provider-collected NP/OP specimens must be weighed against the benefits of patient-collected specimens in tailored strategies for SARS-CoV-2 testing.

Universal SARS-Cov-2 Screening in Women Admitted for Delivery in a Large Managed Care Organization.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has created a need for data regarding the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnant women. After implementing universal screening for COVID-19 in women admitted for delivery, we sought to describe the characteristics of COVID-19 in this large cohort of women. STUDY DESIGN: An observational study of women admitted to labor and delivery units in Kaiser Permanente Southern California (KPSC) hospitals between April 6 and May 11, 2020 who were universally offered testing for SARS-CoV-2 infection (n = 3,963). Hospital inpatient and outpatient physician encounter, and laboratory records were used to ascertain universal testing levels, test results, and medical and obstetrical histories. The prevalence of SARS-CoV-2 infection was estimated from the number of women who tested positive during labor per 100 women delivered. RESULTS: Of women delivered during the study period, 3,923 (99.0%) underwent SARS-CoV-2 testing. A total of 17 (0.43%; 95% confidence interval: 0.23-0.63%) women tested positive, and none of them were symptomatic on admission. There was no difference in terms of characteristics between SARS-CoV-2 positive and negative tested women. One woman developed a headache attributed to COVID-19 3 days postpartum. No neonates had a positive test at 24 hours of life. CONCLUSION: The findings suggest that in pregnant women admitted for delivery between April 6 and May 11, 2020 in this large integrated health care system in Southern California, prevalence of SARS-CoV-2 test positive was very low and all patients were asymptomatic on admission. KEY POINTS: · The prevalence of SARS-CoV-2 infection in a large diverse cohort of term pregnant women was 0.43%.. · 99% of women accepted SARS-CoV-2 screening on admission to labor and delivery.. · All women with positive test results were asymptomatic at the time of testing..

A Laboratory Medicine Best Practices Systematic Review and Meta-analysis of Nucleic Acid Amplification Tests (NAATs) and Algorithms Including NAATs for the Diagnosis of Clostridioides (Clostridium) difficile in Adults.

The evidence base for the optimal laboratory diagnosis of Clostridioides (Clostridium) difficile in adults is currently unresolved due to the uncertain performance characteristics and various combinations of tests. This systematic review evaluates the diagnostic accuracy of laboratory testing algorithms that include nucleic acid amplification tests (NAATs) to detect the presence of C. difficile The systematic review and meta-analysis included eligible studies (those that had PICO [population, intervention, comparison, outcome] elements) that assessed the diagnostic accuracy of NAAT alone or following glutamate dehydrogenase (GDH) enzyme immunoassays (EIAs) or GDH EIAs plus C. difficile toxin EIAs (toxin). The diagnostic yield of NAAT for repeat testing after an initial negative result was also assessed. Two hundred thirty-eight studies met inclusion criteria. Seventy-two of these studies had sufficient data for meta-analysis. The strength of evidence ranged from high to insufficient. The uses of NAAT only, GDH-positive EIA followed by NAAT, and GDH-positive/toxin-negative EIA followed by NAAT are all recommended as American Society for Microbiology (ASM) best practices for the detection of the C. difficile toxin gene or organism. Meta-analysis of published evidence supports the use of testing algorithms that use NAAT alone or in combination with GDH or GDH plus toxin EIA to detect the presence of C. difficile in adults. There is insufficient evidence to recommend against repeat testing of the sample using NAAT after an initial negative result due to a lack of evidence of harm (i.e., financial, length of stay, or delay of treatment) as specified by the Laboratory Medicine Best Practices (LMBP) systematic review method in making such an assessment. Findings from this systematic review provide clarity to diagnostic testing strategies and highlight gaps, such as low numbers of GDH/toxin/PCR studies, in existing evidence on diagnostic performance, which can be used to guide future clinical research studies.

Diagnostic Importance of Hyphae on Heart Valve Tissue in Histoplasma Endocarditis and Treatment With Isavuconazole.

A patient who never resided in an endemic area for dimorphic fungi was diagnosed with Histoplasma capsulatum endocarditis. His diagnosis was suggested by yeast and hyphae on cardiac valve tissue pathology. Isavuconazole was an optimal therapeutic option due to renal dysfunction and anticoagulation with warfarin for mechanical valve replacement.

Quantitative nucleic acid amplification methods for viral infections.

BACKGROUND: Over the past 2 decades there have been substantial improvements in the methods used to quantify viral nucleic acid in body fluids and in our understanding of how to use viral load measurements in the diagnosis and management of patients with a number of viral infections. These methods are now integrated into a wide range of diagnostic and treatment guidelines and commonly deployed in a variety of clinical settings. CONTENT: Quantitative nucleic acid amplification methods that are used to measure viral load are described along with key issues and important variables that affect their performance. Particular emphasis is placed on those methods used in clinical laboratories as US Food and Drug Administration-cleared or laboratory-developed tests. We discuss the clinical applications of these methods in patients with HIV-1, hepatitis C virus, hepatitis B virus, cytomegalovirus, Epstein-Barr virus, and BK polyomavirus infections. Finally, the current challenges and future directions of viral load testing are examined. SUMMARY: Quantitative nucleic acid amplification tests provide important information that can be used to predict disease progression, distinguish symptomatic from asymptomatic infection, and assess the efficacy of antiviral therapy. Despite the advances in technology, large challenges remain for viral testing related to accuracy, precision, and standardization. Digital PCR, a direct method of quantification of nucleic acids that does not rely on rate-based measurements or calibration curves, may address many of the current challenges.

A biomechanical comparison of back and front squats in healthy trained individuals.

The strength and stability of the knee plays an integral role in athletics and activities of daily living. A better understanding of knee joint biomechanics while performing variations of the squat would be useful in rehabilitation and exercise prescription. We quantified and compared tibiofemoral joint kinetics as well as muscle activity while executing front and back squats. Because of the inherent change in the position of the center of mass of the bar between the front and back squat lifts, we hypothesized that the back squat would result in increased loads on the knee joint and that the front squat would result in increased knee extensor and decreased back extensor muscle activity. A crossover study design was used. To assess the net force and torque placed on the knee and muscle activation levels, a combination of video and force data, as well as surface electromyographic data, were collected from 15 healthy trained individuals. The back squat resulted in significantly higher compressive forces and knee extensor moments than the front squat. Shear forces at the knee were small in magnitude, posteriorly directed, and did not vary between the squat variations. Although bar position did not influence muscle activity, muscle activation during the ascending phase was significantly greater than during the descending phase. The front squat was as effective as the back squat in terms of overall muscle recruitment, with significantly less compressive forces and extensor moments. The results suggest that front squats may be advantageous compared with back squats for individuals with knee problems such as meniscus tears, and for long-term joint health.