Assessing Vulnerability to COVID-19 in High-Risk Populations: The Role of SARS-CoV-2 Spike-Targeted Serology.

Individuals at increased risk for severe coronavirus disease-2019 (COVID-19) outcomes, due to compromised immunity or other risk factors, would benefit from objective measures of vulnerability to infection based on vaccination or prior infection. The authors reviewed published data to identify a specific role and interpretation of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike-targeted serology testing. Specific recommendations are provided for an evidence-based and clinically-useful interpretation of SARS-CoV-2 spike-targeted serology to identify vulnerability to infection and potential subsequent adverse outcomes. Decreased vaccine effectiveness among immunocompromised individuals is linked to correspondingly high rates of breakthrough infections. Negative results on SARS-CoV-2 antibody tests are associated with increased risk for subsequent infection. "Low-positive" results on semiquantitative SARS-CoV-2 spike-targeted antibody tests may help identify persons at increased risk as well. Standardized SARS-CoV-2 spike-targeted antibody tests may provide objective information on the risk of SARS-CoV-2 infection and associated adverse outcomes. This holds especially for high-risk populations that demonstrate a relatively high rate of seronegativity. The widespread availability of such tests presents an opportunity to refine risk assessment for individuals with suboptimal SARS-CoV-2 antibody levels and to promote effective interventions. Interim federal guidance would support physicians and patients while additional investigations are pursued.

Outpatient Antibiotic Resistance Patterns of Escherichia coli Urinary Isolates Differ by Specialty Type.

Antibiotic-resistant E. coli infections represent a major cause of morbidity and mortality and pose a challenge to antibiotic stewardship. We analyzed a large outpatient data set of E. coli urinary isolates to determine whether resistance patterns vary between types of outpatient practices. Using deidentified data from a clinical reference laboratory over 5 years and logistic regression, we examined the association of antibiotic resistance with outpatient practice type, controlling for testing year, patient sex, and patient age. The odds of antibiotic resistance were significantly higher in urology/nephrology practices for ampicillin (odds ratio [OR] 1.36; 95% CI, 1.10 to 1.69), ciprofloxacin (OR 2.29; 95% CI, 1.77 to 2.94), trimethoprim-sulfamethoxazole (OR 1.52; 95% CI, 1.18 to 1.94), and gentamicin (OR 1.72; 95% CI, 1.16 to 2.46). Odds of resistance were also higher for ciprofloxacin in oncology practices (OR 1.54; 95% CI, 1.08 to 2.15) and "all other specialties" (OR 1.33; 95% CI, 1.13 to 1.56). In contrast, specimens from obstetrics and gynecology practices had lower odds of having resistance to ampicillin (OR 0.90; 95% CI, 0.82 to 0.99) and trimethoprim-sulfa (OR 0.83; 95% CI, 0.73 to 0.93) but higher odds of having resistance to nitrofurantoin (OR 1.33; 95% CI, 1.03 to 1.70). Other findings included lower odds of having resistance to trimethoprim-sulfa in pediatric practices (OR 0.78; 95% CI, 0.64 to 0.94) and lower odds of having resistance to gentamicin in isolates from internal medicine practices (OR 0.66; 95% CI, 0.51 to 0.84) (all P < 0.05). IMPORTANCE Patterns of antibiotic resistance in E. coli urinary isolates can vary between outpatient specialties. The use of clinical data to create practice and specialty-specific antibiograms in outpatient settings may improve antibiotic stewardship.

Contributions of Glucose and Hemoglobin A1c Measurements in Diabetes Screening.

OBJECTIVES: Given the long-term consequences of untreated diabetes, patients benefit from timely diagnoses. Payer policies often recognize glucose but not hemoglobin A1c (HbA1c) for diabetes screening. This study evaluates the different information that glucose and HbA1c provide for diabetes screening. METHODS: We conducted a retrospective review of national clinical laboratory testing during 2020 when glucose and HbA1c were ordered for routine diabetes screening, excluding patients with known diabetes, out-of-range glucose, or metabolic syndrome. RESULTS: Of 15.47 million glucose and HbA1c tests ordered simultaneously, 672,467 (4.35%) met screening inclusion criteria; 116,585 (17.3%) were excluded because of diabetes-related conditions or the specimen was nonfasting, leaving 555,882 result pairs. More than 1 in 4 patients 60 years of age or older with glucose within range had an elevated HbA1c level. HbA1c claims were denied more often for Medicare beneficiaries (38,918/65,273 [59.6%]) than for other health plans combined (23,234/291,764 [8.0%]). CONCLUSIONS: Although many health plans do not cover HbA1c testing for diabetes screening, more than 1 in 4 glucose screening patients 60 years of age or older with an in-range glucose result had a concurrent elevated HbA1c result. Guideline developers and health plans should explicitly recognize that glucose and HbA1c provide complementary information and together offer improved clinical utility for diabetes screening.

Association of changes in lipid levels with changes in vitamin D levels in a real-world setting.

In clinical trials, vitamin D supplementation has been reported to reduce serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) but not high-density lipoprotein cholesterol (HDL-C). In this cohort study we evaluated the association between changes in vitamin D (25-hydroxyvitamin D) and changes in lipid levels in a real-world setting. Changes in lipid levels over a 1-year period were evaluated among individuals whose vitamin D levels increased (group 1) or decreased (group 2) by ≥ 10 ng/mL in year 2018 versus 2017 (cohort 1; n = 5580), in 2019 versus 2018 (cohort 2, n = 6057), or in 2020 versus 2019 (cohort 3, n = 7249). In each cohort, levels of TC, LDL-C, and TG decreased in group 1 and increased in group 2. Between-group differences in average changes in the 3 cohorts ranged from 10.71 to 12.02 mg/dL for TC, from 7.42 to 8.95 mg/dL for LDL-C, and from 21.59 to 28.09 mg/dL for TG. These differences were significant after adjusting for age, sex, race, education, body mass index, blood pressure, smoking status, geographical location, and baseline levels of vitamin D and lipids (P < 0.001). Changes in vitamin D levels were not significantly associated with changes in HDL-C levels.

Patterns of Prostate-Specific Antigen Testing and Prostate Biopsies During the COVID-19 Pandemic.

PURPOSE: This study examined changes in prostate disease screening (prostatic-specific antigen [PSA] testing), prostate biopsy testing, and prostate cancer diagnoses during the COVID-19 pandemic through December 2020. MATERIALS AND METHODS: This analysis included test results from men ≥ 40 years, without prior International Classification of Diseases-10 record of prostate cancer since January 2016, who received PSA or prostate biopsy testing at Quest Diagnostics during January 2018-December 2020. Monthly trends were evaluated for three periods: prepandemic (January 2018-February 2020), early-pandemic (March-May 2020), and late-pandemic (June-December 2020). RESULTS: Meeting inclusion criteria were 16,365,833 PSA and 48,819 prostate biopsy results. The average monthly number of PSA tests declined from 465,187 prepandemic to 295,786 early-pandemic (36.4% decrease; P = .01) before rebounding to 483,374 (3.9% increase; P = .23) late-pandemic. The monthly average number of PSA results ≥ 50 ng/mL (23,356; 0.14% of all PSA results) dipped from 659 prepandemic to 506 early-pandemic (23.2% decrease; P = .02) and rebounded to 674 late-pandemic (2.3% increase; P = .65). The average monthly number of prostate biopsy results decreased from 1,453 prepandemic to 903 early-pandemic (37.9% decrease; P = .01) before rebounding to 1,190 late-pandemic (18.1% decrease; P = .01). The average monthly number for Gleason score ≥ 8 (6,241; 12.8% of all prostate biopsies) declined from 182 prepandemic to 130 early-pandemic (28.6% decrease; P = .02) and decreased to 161 late-pandemic (11.5% decrease; P = .02). CONCLUSION: The findings suggest that a substantial number of prostate screening opportunities and cancer diagnoses have been missed. Efforts are needed to bring such patients back for screening and diagnostic testing and to restore appropriate care for non-COVID-19-related medical conditions.

Antimicrobial Resistance Patterns of Urinary Escherichia coli Among Outpatients in Washington State, 2013-2017: Associations With Age and Sex.

BACKGROUND: Management of acute, uncomplicated cystitis in outpatients benefits from knowledge of drug resistance patterns in the population. However, antibiograms are often not available for the outpatient setting, and the role of host factors such as sex and age in assessing the likelihood of resistance are not well understood. We investigated whether antibiotic resistance patterns of outpatient urinary Escherichia coli isolates vary by age group and sex in a large database of antibiotic susceptibility test (AST) results from Washington State. METHODS: We retrospectively analyzed AST data for outpatient urinary E. coli isolates in Washington State tested at a clinical reference laboratory from 2013 to 2017. In logistic regression models stratified by sex, we tested the associations of antibiotic resistance with patient age. RESULTS: We found females >50 years had greater odds than females younger than 19 for resistance to amoxicillin-clavulanate (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.22-1.69), ciprofloxacin (OR, 3.04; 95% CI, 2.48-3.74), ceftriaxone (OR, 2.58; 95% CI, 1.77-3.92), and gentamicin (OR, 1.62; 95% CI, 1.27-2.08) (all P < .001). Compared to males younger than 19, males >50 years had greater odds of resistance to ciprofloxacin (OR, 2.59; 95% CI, 1.18-5.69) and lower odds of resistance to amoxicillin-clavulanate (OR, 0.56; 95% CI, .34-.96) (all P < .05). CONCLUSIONS: These findings demonstrate that age and sex are associated with variability in antibiotic resistance patterns in the outpatient setting. Availability of outpatient antibiotic resistance data based on sex and age may be useful to inform empiric prescribing for outpatient UTIs and to support antibiotic stewardship efforts.

Evolution of Specimen Self-Collection in the COVID-19 Era: Implications for Population Health Management of Infectious Disease.

Laboratory testing is an important component in the diagnosis of respiratory tract infections such as with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, specimen collection not only risks exposure of health care workers and other patients to infection, but also necessitates use of personal protective equipment that may be in short supply during periods of heightened disease activity. Self-collection of nasal or oropharyngeal swabs offers an alternative to address these drawbacks. Although studies in the past decade have demonstrated the utility of this approach for respiratory infections, it has not been widely adopted in routine clinical practice. The rapid spread of coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has focused attention on the need for safe, convenient, timely, and scalable methods for collecting upper respiratory specimens for testing. The goals of this article are to highlight the literature regarding self-collected nasal or oropharyngeal specimens for respiratory pathogen testing; discuss the role of self-collection in helping prevent the spread of the COVID-19 disease from infected patients and facilitating a shift toward "virtual" medicine or telemedicine; and describe the current and future state of self-collection for infectious agents, and the impacts these approaches can have on population health management and disease diagnosis and prevention.

Model for Mitigation of Workplace Transmission of COVID-19 Through Population-Based Testing and Surveillance.

The coronavirus disease-2019 (COVID-19) pandemic is having a widespread impact on societies across the globe. As part of the effort to control transmission in the United States, many businesses either closed or instituted nonpharmaceutical control measures and allowed only essential workers on-site. During summer and fall of 2020, employers began formulating "return to work" strategies designed to mitigate the risk of transmission among employees. On a population level, several countries implemented national testing and surveillance strategies that proved effective in mitigating citizen-to-citizen transmission and contributed to suppressing COVID-19. A crucial component of many such strategies is population-based testing to identify and engage individuals with asymptomatic or presymptomatic infection, which also is relevant to return-to-work strategies. The authors describe an approach that multisite employers might use to help mitigate transmission of COVID-19 in the workplace. This approach leverages a bioinformatics platform informed by real-time PCR test data at the county and subcounty (eg, Public Use Microdata Area) level, allowing for population-based testing to be selectively targeted for employees in geographies with elevated SARS-CoV-2 positivity. A "Command Center" application integrates data from multiple sources (eg, local infection trends, employee symptom diaries, Bluetooth thermometers) in real time, which can be used to inform decisions regarding surveillance and employee self-isolation or quarantine; a mobile phone-based application provides for rapid, secure communication with employees. This overview is based on peer-reviewed literature and the early experience of a large employer with implementing bioinformatics tools to mitigate the impact of the pandemic on the workplace.

The Opioid Epidemic Within the COVID-19 Pandemic: Drug Testing in 2020.

The convergence of the opioid epidemic and the coronavirus disease 2019 (COVID-19) pandemic has created new health care challenges. The authors analyzed changes in clinical drug testing patterns and results at a national clinical laboratory, comparing data obtained before and during the pandemic. Testing for prescription and illicit drugs declined rapidly during the pandemic, with weekly test volumes falling by approximately 70% from the baseline period to the trough (the week beginning March 29) before rising in subsequent weeks. Among individuals tested, positivity increased by 35% for non-prescribed fentanyl and 44% for heroin during the pandemic. Positivity for non-prescribed fentanyl increased significantly among patients positive for other drugs: by 89% for specimens positive for amphetamines; 48% for benzodiazepines; 34% for cocaine; and 39% for opiates (P < 0.01 for all comparisons). These findings suggest significant increases in dangerous drug combinations. Positivity for non-prescribed use of many other drugs remained consistent or declined for some drugs, relative to pre-pandemic patterns. Models adjusting for potential confounding variables, including medication-assisted treatment and treatment at a substance use disorder facility indicated that the risk for non-prescribed fentanyl positivity rose by more than 50% during the pandemic. In summary, these findings demonstrate decreased drug testing overall, with increased positivity for high-risk drugs and dangerous drug combinations. The convergence of the drug abuse epidemic and COVID-19 pandemic has led to an increased need for health care and public health resources dedicated to supporting vulnerable patients and addressing the underlying causes of these disturbing trends.

Effects of platforms, size filter cutoffs, and targeted regions of cytogenomic microarray on detection of copy number variants and uniparental disomy in prenatal diagnosis: Results from 5026 pregnancies.

OBJECTIVE: We evaluated the effects of platforms, size filter cutoffs, and targeted regions of cytogenomic microarray (CMA) on the detection of copy number variants (CNVs) and uniparental disomy (UPD) in prenatal diagnosis. METHODS: Five thousand twenty-six consecutive prenatal specimens (>98% high-risk pregnancy) were studied by high-resolution CMA, with cutoffs of 50 kb for losses and 200 kb for gains in nontargeted regions and 20 kb for losses and 100 kb for gains in targeted regions. We assessed actual detection rates using the current assay as well as hypothetical detection rates using platforms with the same or lower resolution and smaller or larger cutoffs. RESULTS: The detection rate of our current assay was 11.2% (562 of 5026), including abnormal findings in 543 cases and likely pathogenic variants in 19. The hypothetical decrease in the overall detection of variants (excluding likely benign) and UPD ranged from 3.8% to 23.0%. For the subgroup of pathogenic and likely pathogenic CNVs < 1 Mb, the decrease of detection ranged from 2.7% to 24.3%. CONCLUSIONS: These findings underscore the significant effects of chosen CMA platform, as well as size filter cutoffs and targeted regions used in data analysis, on detection of CNVs and UPDs in a cohort of prenatal cases.

Q fever: an under-reported reportable communicable disease.

The objective of this study was to provide real-world clinical laboratory-based data to supplement Centers for Disease Control and Prevention (CDC) reporting of Q fever. We analysed titre results of specimens submitted to a large US clinical laboratory for Coxiella burnetii IgG antibody testing from 2010 through 2016. Presumptive Q fever was defined as acute (phase II IgG titre ⩾1:128, phase I titre <1:1024) or chronic (phase I IgG titre ⩾1:1024), based on the results from a single serum specimen. During 2010-2016, an average of 328 presumptive acute Q fever cases were identified at Quest each year, nearly three times the annual average reported to the CDC (122). During the same period, the number of chronic cases identified annually at Quest Diagnostics (34) was similar to that reported to the CDC (29). These findings suggest that CDC data may underestimate the incidence of acute Q fever.