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ImportanceIndividuals at increased risk for severe outcomes from COVID-19, due to compromised immunity or other risk factors, would benefit from objective measures of vulnerability to infection based on prior infection and/or vaccination. We reviewed published data to identify a specific role and interpretation of SARS-CoV-2 spike-targeted serology testing for such individuals. We also provide real-world evidence of spike-targeted antibody test results, identifying the seronegativity rate across the United States from March 2021 through June 2022. Analysis of antibody test results were compared between post-transplant (ie, immunocompromised) and all other patients tested in the first half of 2022. Finally, specific recommendations are provided for an evidence-based and clinically useful interpretation of spike-targeted serology to identify vulnerability to infection and potential subsequent adverse outcomes.ObservationsDecreased vaccine effectiveness among immunocompromised individuals is linked to correspondingly high rates of breakthrough infections. Evidence indicates that negative results on SARS-CoV-2 antibody tests are associated with increased risk for subsequent infection. Results from widely available, laboratory-based tests do not provide a direct measure of protection but appear to correlate well with the presence of surrogate pseudovirus-neutralizing antibodies. The results of SARS-CoV-2 semiquantitative tests have also been associated with vaccine effectiveness and the likelihood of breakthrough infection. The data suggest that “low-positive” results on semiquantitative SARS-CoV-2 spike-targeted antibody tests may help identify persons at increased relative risk for breakthrough infection leading to adverse outcomes. In an analysis of data from large national laboratories during the COVID-19 Omicron-related surge in 2022, results from SARS-CoV-2 spike-targeted antibody tests were negative in 16.6% (742/4459) of solid organ transplant recipients tested compared to only 11.0% (47,552/432,481) of the remaining tested population.Conclusions and RelevanceStandardized semiquantitative and quantitative SARS-CoV-2 spike-targeted antibody tests may provide objective information on risk of SARS-CoV-2 infection and associated adverse outcomes. This holds especially for high-risk populations, including transplant recipients, who demonstrate a relatively higher 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.

Underlying chronic hepatitis B virus (HBV) infection increases the risk of drug-induced liver injury (DILI) when receiving tuberculosis therapies. Prevalence of HBV and latent tuberculosis infection (LTBI) coinfection is not well reported and no studies have evaluated testing patterns for and prevalence of HBV-LTBI coinfection in the United States.To evaluate patterns of HBV and LTBI testing and prevalence of HBV-LTBI coinfection in the United States.Retrospective cohort study.Quest Diagnostics clinical laboratory data, 2014-2020.Chronic HBV infection was defined as any combination of 2 positive HBV surface antigen, HBV e antigen, or detectable HBV DNA tests at least 6 months apart. LTBI was defined as a positive QuantiFERON-TB or T-SPOT.TB test without evidence of active tuberculosis infection.Testing patterns for chronic HBV infection and LTBI and prevalence of HBV-LTBI coinfection were evaluated from 2016 through 2020 and stratified by age, sex, and race and ethnicity.Among 89 259 patients with chronic HBV infection, 9508 (10.7%) were tested for LTBI, among whom prevalence of HBV-LTBI coinfection was 19.6%, more than twice the observed prevalence of LTBI in patients with no chronic HBV infection in our cohort. Among 394 817 LTBI patients, 127 414 (32.3%) were tested for HBV, among whom prevalence of HBV-LTBI coinfection was 1.5%, approximately 3 times higher than prevalence of HBV infection in patients with no LTBI. The HBV-LTBI coinfection prevalence was highest among Asian Americans and older individuals.The HBV-LTBI coinfection prevalence was likely underestimated because of suboptimal awareness and testing among at-risk populations.Among US individuals with chronic HBV infection or LTBI, prevalence of HBV-LTBI coinfection is substantial and highlights the need of testing for HBV-LTBI coinfection to mitigate risk of DILI associated with tuberculosis medications in patients with chronic HBV infection.

The purpose of this study was to evaluate hepatitis delta virus (HDV) testing patterns among US adults with chronic hepatitis B (CHB).HDV testing was evaluated among CHB patients using Quest Diagnostics (2016-2020) and Veterans Affairs (2010-2020) data.Among 157,333 CHB patients (Quest), 6.7% received HDV testing, among which 2.2% were positive. HDV testing was higher in male patients, younger individuals, and patients with advanced liver disease. Among 12,002 CHB patients (Veterans Affairs), 19.7% received HDV testing, among which 3.1% were positive. HDV testing was higher in younger individuals and Asians.Low HDV testing was observed among 2 large US cohorts of adults with CHB.

Background Early, sustained hepatitis B virus (HBV) DNA suppression reduces long-term risks of hepatocellular carcinoma. Chronic hepatitis B (CHB) treatment criteria are complex. Simplifying criteria will improve timely linkage to therapy. We evaluated treatment eligibility patterns among US patients with CHB and propose stepwise simplification of CHB treatment criteria. Methods Using 2016–2020 Quest Diagnostics data, we evaluated treatment eligibility among patients with CHB (2 positive HBV tests [HBV surface antigen, HBV e antigen, or HBV DNA] ≥6 months apart) using American Association for the Study of Liver Disease (AASLD), European Association for Study of the Liver (EASL), Asian Pacific Association for Study of the Liver (APASL), and Asian American Treatment Algorithm (AATA) criteria. Results Among 84 916 patients with CHB, 6.7%, 6.2%, 5.8%, and 16.4% met AASLD, EASL, APASL, and AATA criteria, respectively. Among treatment-ineligible patients with CHB, proportion with significant fibrosis (aspartate aminotransferase platelet ratio index >0.5) were 10.4%, 10.4%, 10.8%, and 7.7% based on AASLD, EASL, APASL, and AATA, respectively. In the proposed treatment simplification, the proportion of patients with CHB eligible for therapy increased from 10.3% for step 1 (HBV DNA >20 000 IU/mL, elevated alanine aminotransferase [ALT] level) to 14.1% for step 2 (HBV >2000 IU/mL, elevated ALT level), 33.5% for step 3 (HBV DNA >2000 IU/mL, any ALT level), and 87.2% for step 4 (detectable HBV DNA, any ALT level). Conclusions A large proportion of patients with CHB not meeting established treatment criteria have significant fibrosis. Simplifying criteria to treat all patients with detectable HBV DNA will reduce complexity and heterogeneity in assessing treatment eligibility, improving treatment rates and progress toward HBV elimination.

Recognizing that race is a social and not a biological construct, healthcare professionals and the public have called for removal of race in clinical algorithms. In response, the National Kidney Foundation and the American Society of Nephrology created the Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Diseases to examine the issue and provide recommendations. The final report from the Task Force recommends calculating estimated glomerular filtration rate (eGFR) without a race coefficient using the recently published CKD-EPI 2021 creatinine (cr) and creatinine-cystatin C (cr-cys) equations. The Task Force recommends immediately replacing older eGFRcr equations (MDRD Study and CKD-EPI 2009) with the new CKD-EPI 2021 equation. In a 2019 survey by the College of American Pathologists, 23% of 6200 laboratories reporting eGFRcr used an incorrect equation that is not suitable for use with standardized creatinine measurements, 34% used the CKD-EPI 2009 equation and 43% used the MDRD Study 2006 equation re-expressed for standardized creatinine measurement. Rapid transition to using the CKD-EPI 2021 equation is an opportunity for laboratories to standardize to a single equation to eliminate differences in eGFRcr due to different equations used by different laboratories, and to report eGFR without use of race. We provide guidance to laboratories for implementing the CKD-EPI 2021 equations for both eGFRcr and eGFRcr-cys.

Chlamydia trachomatis positivity and testing for both Chlamydia trachomatis and Neisseria gonorrhoeae in the United States have increased during pregnancy from 2010 to 2018, but many are not tested in accordance with guidelines., Background Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) case surveillance relies on reported positive laboratory results. Changes in reported cases may represent changes in testing practice or infection prevalence. This study evaluated changes over time for CT and NG positivity and testing rates of pregnant persons. Methods Prenatal testing results from persons aged 16 to 40 years tested by a national reference clinical laboratory were analyzed for CT and NG testing and positivity from 2010 to 2018 (n = 3,270,610). Results Testing rates increased among pregnant persons for CT (from 56.3% in 2010 to 64.1% in 2018, P < 0.001) and NG (from 55.6% to 63.2%, P < 0.001). Higher CT testing rates were found in Black non-Hispanic (adjusted odds ratio [AOR], 1.58; 95% confidence interval [CI], 1.57–1.60) and Hispanic (AOR, 1.19; 95% CI, 1.18–1.20) persons. NG and CT testing rates were virtually identical. Significant increasing trends in CT positivity were observed for each age group studied (P < 0.001 for all): 16–19 (from 11.7% to 13.0%), 20–24 (from 6.4% to 6.7%), 25–30 (from 1.9% to 2.4%), and 31–40 years (from 0.76% to 0.92%). Black non-Hispanic persons had the highest positivity for CT (AOR, 2.52; 95% CI, 2.46–2.57) and NG (AOR, 5.42; 95% CI, 5.05–5.82). Conclusions Testing and adjusted positivity for both CT and NG among pregnant persons increased from 2010 to 2018. Higher testing rates were observed in Black non-Hispanic and Hispanic persons (even in persons younger than 25 years), suggesting some testing decisions may have been based on perceived risk, in contrast to many guidelines recommending screening all pregnant persons younger than 25 years.

BACKGROUND The reported incidence of acute hepatitis C virus (HCV) infection is increasing among reproductive age persons in the United States. Infants born to pregnant persons with HCV infection are at risk for perinatal HCV acquisition. Hepatitis C testing during pregnancy was evaluated during 2015 –2019. OBJECTIVE We estimated hepatitis C testing rates in a large sample of patients with Medicaid and commercial insurance who gave birth during 2015–2019 and described demographic and risk-based factors associated with testing. METHODS Medicaid and commercial insurance claims for patients ages 15–44 years who gave birth between 2015 and 2019 were included. Birth claims were identified using procedure and diagnosis codes for vaginal or cesarean delivery. Hepatitis C testing was defined as an insurance claim during the 42 weeks before delivery. Testing rates were calculated among patients who delivered and among the subset of patients who were continuously enrolled for 42 weeks before delivery. Multivariable logistic regression was used to identify factors associated with testing. RESULTS Among 1,142,770 Medicaid patients and 1,207,132 commercially insured patients, 15.3% and 18.3% were tested for hepatitis C during pregnancy, respectively. Testing rates were 21.8% and 21.9% among continuously enrolled Medicaid and commercially insured patients, respectively. Rates increased from 2015 through 2019 among Medicaid (from 19.2% to 26.8%) and commercially insured patients (from 18.1% to 28.0%), respectively. Among Medicaid patients, non-Hispanic Black and Hispanic race/ethnicity were associated with lower odds of testing. Opioid use disorder, HIV infection, and high-risk pregnancy were associated with higher odds of testing in both Medicaid and commercially insured patients. CONCLUSIONS Hepatitis C testing during pregnancy increased from 2015 through 2019 among patients with Medicaid and commercial insurances although tremendous opportunity for improvement remains.

The study evaluates the effect of the 2020 Centers for Disease Control and Prevention and U.S. Preventive Services Task Force recommendations on hepatitis C virus (HCV) screening among pregnant persons nationally and by health insurance type. The study included 5,048,428 pregnant persons aged 15-44 years with either Medicaid or commercial health insurance who had obstetric panel testing performed by Quest Diagnostics, January 2011-June 2021. Antibody screening for HCV infection increased before and accelerated after the updated recommendations in early 2020. Disparities in HCV testing by health insurance status were substantial over the entire study period. Despite substantial progress in the proportion of pregnant persons screened for HCV infection, current testing rates fall short of universal recommendations. ispartof: OBSTETRICS AND GYNECOLOGY vol:140 issue:1 pages:99-101 ispartof: location:United States status: published

Introduction: This study aims to determine if and how the age distribution of Chlamydia trachomatis and Neisseria gonorrhoeae infections in women evolved from 2010 to 2017, given changes in sexual practices over this time. Methods: All Chlamydia trachomatis/Neisseria gonorrhoeae co-testing laboratory results from females aged 12–30 years tested at Quest Diagnostics during 2010–2017 (n=17,794,680) were evaluated to assess trends in Chlamydia trachomatis and Neisseria gonorrhoeae positivity over time. Data were collected and analyzed in November 2018. Results: Age-based positivity shifted toward older ages from 2010 to 2017 for both Chlamydia trachomatis and Neisseria gonorrhoeae. There was a declining trend in Chlamydia trachomatis positivity from 2010 to 2017 for the youngest age group (12–17 years; 17% decline, 8.9% to 7.4%, p

Summary: Background & aims: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease globally. We aim to evaluate prevalence and predictors of hepatic fibrosis among NAFLD patients, focusing on metabolic co-morbidities and dietary patterns. Methods: Quest Diagnostics laboratory data from 2017 to 2018 were used to identify NAFLD patients using a stepwise algorithm based on laboratory data and ICD-9/10 codes. Prevalence of fibrosis was assessed using a step-wise AST to platelet ratio index (APRI) algorithm. Multivariate logistic regression evaluated predictors of ≥F2 fibrosis or cirrhosis. Prevalence of fibrosis was stratified by U.S. Department of Health and Human Services geographic regions and compared with region-specific data on metabolic diseases and dietary patterns (fruit and vegetable intake) using 2017 Behavioral Risk Factor Surveillance System. Results: Among NAFLD patients, proportion of patients with APRI >2.0 was 1.58%, increasing to 3.05% (APRI > 1.5), 6.81% (APRI > 1.0), 12.67% (APRI > 0.7), and 21.87% with APRI >0.5. Increasing metabolic co-morbidities was associated with higher odds of fibrosis. Compared to patients with no metabolic co-morbidities, odds of >F2 fibrosis was OR 2.61 (95% CI 2.57–2.65, p

ImportanceBetter understanding of the protective duration of prior SARS-CoV-2 infection against reinfection is needed.ObjectivePrimary: To assess the durability of immunity to SARS-CoV-2 reinfection among initially unvaccinated individuals with previous SARS-CoV-2 infection. Secondary: Evaluate the crude SARS-CoV-2 reinfection rate and associated characteristics.Design and SettingRetrospective observational study of HealthVerity data among 144,678,382 individuals, during the pandemic era through April 2021.ParticipantsIndividuals studied had SARS-CoV-2 molecular diagnostic or antibody index test results from February 29 through December 9, 2020, with ≥365 days of pre-index continuous closed medical enrollment, claims, or electronic health record activity.Main Outcome(s) and Measure(s)Rates of reinfection among index-positive individuals were compared to rates of infection among index-negative individuals. Factors associated with reinfection were evaluated using multivariable logistic regression. For both objectives, the outcome was a subsequent positive molecular diagnostic test result.ResultsAmong 22,786,982 individuals with index SARS-CoV-2 laboratory test data (2,023,341 index positive), the crude rate of reinfection during follow-up was significantly lower (9.89/1,000-person years) than that of primary infection (78.39/1,000 person years). Consistent with prior findings, the risk of reinfection among index-positive individuals was 87% lower than the risk of infection among index-negative individuals (hazard ratio, 0.13; 95% CI, 0.13, 0.13). The cumulative incidence of reinfection among index-positive individuals and infection among index-negative individuals was 0.85% (95% CI: 0.82%, 0.88%) and 6.2% (95% CI: 6.1%, 6.3%), respectively, over follow-up of 375 days. The duration of protection against reinfection was stable over the median 5 months and up to 1-year follow-up interval. Factors associated with an increased reinfection risk included older age, comorbid immunologic conditions, and living in congregate care settings; healthcare workers had a decreased reinfection risk.Conclusions and RelevanceThis large US population-based study demonstrates that SARS-CoV-2 reinfection is uncommon among individuals with laboratory evidence of a previous infection. Protection from SARS-CoV-2 reinfection is stable up to one year. Reinfection risk was primarily associated with age 85+ years, comorbid immunologic conditions and living in congregate care settings; healthcare workers demonstrated a decreased reinfection risk. These findings suggest that infection induced immunity is durable for variants circulating prior to Delta.Key PointsQuestionHow long does prior SARS-CoV-2 infection provide protection against SARS-CoV-2 reinfection?FindingAmong >22 million individuals tested February 2020 through April 2021, the relative risk of reinfection among those with prior infection was 87% lower than the risk of infection among individuals without prior infection. This protection was durable for up to a year. Factors associated with increased likelihood of reinfection included older age (85+ years), comorbid immunologic conditions, and living in congregate care settings; healthcare workers had lower risk.MeaningPrior SARS-CoV-2 infection provides a durable, high relative degree of protection against reinfection.

This retrospective observational study aimed to gain a better understanding of the protective duration of prior SARS-CoV-2 infection against reinfection. The objectives were two-fold: to assess the durability of immunity to SARS-CoV-2 reinfection among initially unvaccinated individuals with previous SARS-CoV-2 infection, and to evaluate the crude SARS-CoV-2 reinfection rate and associated risk factors. During the pandemic era time period from February 29, 2020, through April 30, 2021, 144,678,382 individuals with SARS-CoV-2 molecular diagnostic or antibody test results were studied. Rates of reinfection among index-positive individuals were compared to rates of infection among index-negative individuals. Factors associated with reinfection were evaluated using multivariable logistic regression. For both objectives, the outcome was a subsequent positive molecular diagnostic test result. Consistent with prior findings, the risk of reinfection among index-positive individuals was 87% lower than the risk of infection among index-negative individuals. The duration of protection against reinfection was stable over the median 5 months and up to 1-year follow-up interval. Factors associated with an increased reinfection risk included older age, comorbid immunologic conditions, and living in congregate care settings; healthcare workers had a decreased reinfection risk. This large US population-based study suggests that infection induced immunity is durable for variants circulating pre-Delta predominance.

PURPOSEThis 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 METHODSThis 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).RESULTSMeeting 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).CONCLUSIONThe 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.

The clinical laboratory plays a critical role in the assessment of atherosclerotic cardiovascular disease (ASCVD)9 risk. Since the 1970s, this laboratory assessment has been primarily through tests in the lipid panel, which included cholesterol, triglycerides (TG), and HDL cholesterol (HDL-C) based on fasting serum or plasma specimens. Until the advent of direct LDL cholesterol (LDL-C) tests approximately 20 years ago, LDL-C was almost exclusively estimated by the Friedewald equation (valid when TG 150 mg/dL (>1.7 mmol/L) and at low concentrations of LDL-C (

BackgroundThe current opioid injection drug use epidemic has been associated with an increase in hepatitis C virus infections among women of childbearing age in the United States, but changes in hepatitis B virus (HBV) infections have not been studied.MethodsA retrospective analysis of HBV statuses among women of childbearing age nationally and by state was conducted, utilizing the Quest Diagnostics database. Rates of HBV in women born before and after the implementation of universal HBV vaccination recommendations were determined.ResultsWe identified 8 871 965 women tested for HBV from 2011–2017. Nationally, the annual rate of acute HBV infections was stable, but rates increased in Kentucky, Alabama, and Indiana (P < .03). The national prevalence of new, chronic HBV diagnoses decreased significantly, from 0.83% in 2011 to 0.19% in 2017 (P < .0001), but increased in Mississippi, Kentucky, and West Virginia (P ≤ .05). A declining prevalence of HBV seroprotection was evident over time, especially within the birth-dose cohort (which dropped from 48.5% to 38.5%; P < .0001).ConclusionsNational rates of newly diagnosed acute and chronic HBV infections declined or were stable overall, but increased significantly in specific Appalachian states. The HBV vaccine is effective in decreasing infections, but seroprotection wanes over time. These trends in new infections may be related to increased injection drug use and highlight potential gaps in HBV vaccine protection.

Trends in resistance to antiretroviral drugs for HIV-1 may inform clinical support and drug development. We evaluated drug resistance mutation (DRM) trends for nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), protease inhibitor (PI), and integrase strand transfer inhibitor (INSTI) in a large U.S. reference laboratory database. DRMs with a Stanford HIV Drug Resistance Database mutation score ≥10 from deidentified subtype B NRTI/NNRTI/PI specimens (2006-2017;10,000/year) and INSTI specimens (2010-2017;1,000/year) were evaluated. Sequences with NRTI, NNRTI, or PI single- or multiclass DRMs declined from 48.9% to 39.3%. High-level dual- and triple-class resistance declined from 43.3% (2006) to 17.1% (2017), while sequences with only single-class DRMs increased from 40.0% to 52.9%. The prevalence of DRMs associated with earlier treatment regimens declined, while prevalence of some DRMs associated with newer regimens increased. M184V/I decreased from 48.3% to 29.4%. K103N/S/T declined from 42.5% in 2012 to 36.4% in 2017. Rilpivirine and etravirine DRMs E138A/Q/R and E138K increased from 4.9% and 0.4% to 9.7% and 1.7%, respectively. Sequences with ≥1 darunavir DRM declined from 18.1% to 4.8% by 2017. INSTI DRM Q148H/K/R declined from 39.3% (2010) to 13.8% (2017). Prevalence of elvitegravir-associated DRMs T66A/I/K, E92Q, S147G, and the dolutegravir-associated DRM R263K increased. For a subset of patients with serial testing, 50% (2,646/5,290) of those who initially had no reportable DRM subsequently developed ≥1 DRM for NRTI/NNRTI/PI and 49.7% (159/320) for INSTI. These trends may inform the need for baseline genotypic resistance testing. The detection of treatment-emergent DRMs in serially tested patients confirms the value of genotypic testing following virologic failure.

Objectives Two epidemics in the United States are related: opioid drug injection and hepatitis C virus (HCV) infection. This study quantifies the relationship between illicit/prescription drug misuse and HCV infection in 3 population generations: baby boomers (born 1945-1965, inclusive), pre-baby boomers, and post-baby boomers. Methods This retrospective study included prescription drug consistency (March-December 2015) and HCV (2011-2015) patient test results performed at a large national clinical reference laboratory. HCV positivity, drug use consistency/inconsistency with prescribed drug information, type of inconsistent use, and inconsistent use of individual drug classes were assessed. Results This study evaluated 39,231 prescription drug monitoring and HCV sets of test results from 18,410 patients. Of these patients, 25.1% tested positive for HCV and 57.3% demonstrated drug test results that were inconsistent with the prescribed medication(s). The types of drug test inconsistency differed substantially between HCV-positive and -negative patients, particularly testing positive for both non-prescribed drugs and prescribed drugs. Specimens from HCV-positive baby boomer and post-baby boomers demonstrated non-prescribed use of opioids and many other drug classes more often than from HCV-negative patients. Conclusions The rates of inconsistent drug test results and types of drugs misused suggest that HCV-positive patients are more likely than HCV-negative patients to display high-risk behavior, even beyond opioid use. This difference is most pronounced in the post-baby boomer generation. Healthcare professionals should consider these patterns and how they differ by generation when monitoring for both prescription and illicit drugs, the results of which can impact treatment decisions including prescribing analgesics.

Introduction The COVID-19 pandemic has disrupted healthcare services, reducing opportunities to conduct routine hepatitis C virus antibody screening, clinical care, and treatment. Therefore, people living with undiagnosed hepatitis C virus during the pandemic may later become identified at more advanced stages of the disease, leading to higher morbidity and mortality rates. Further, unidentified hepatitis C virus–infected individuals may continue to unknowingly transmit the virus to others. Methods To assess the impact of the COVID-19 pandemic, data were evaluated from a large national reference clinical laboratory and from national estimates of dispensed prescriptions for hepatitis C virus treatment. Investigators estimated the average number of hepatitis C virus antibody tests, hepatitis C virus antibody–positive test results, and hepatitis C virus RNA–positive test results by month in January–July for 2018 and 2019, compared with the same months in 2020. To assess the impact of hepatitis C virus treatment, dispensed hepatitis C virus direct-acting antiretroviral medications were examined for the same time periods. Statistical analyses of trends were performed using negative binomial models. Results Compared with the 2018 and 2019 months, hepatitis C virus antibody testing volume decreased 59% during April 2020 and rebounded to a 6% reduction in July 2020. The number of hepatitis C virus RNA–positive results fell by 62% in March 2020 and remained 39% below the baseline by July 2020. For hepatitis C virus treatment, prescriptions decreased 43% in May, 37% in June, and 38% in July relative to the corresponding months in 2018 and 2019. Conclusions During the COVID-19 pandemic, continued public health messaging, interventions and outreach programs to restore hepatitis C virus testing and treatment to prepandemic levels, and maintenance of public health efforts to eliminate hepatitis C infections remain important.

Introduction This study evaluates the impact of the COVID-19 pandemic on testing for common sexually transmitted infections. Specifically, changes are measured in chlamydia and gonorrhea testing and case detection among patients aged 14–49 years during the COVID-19 pandemic. Methods U.S. chlamydia and gonorrhea testing and positivity were analyzed on the basis of >18.6 million tests (13.6 million tests for female patients and 4.7 million tests for male patients) performed by a national reference clinical laboratory from January 2019 through June 2020. Results Chlamydia and gonorrhea testing reached a nadir in early April 2020, with decreases (relative to the baseline level) of 59% for female patients and 63% for male patients. Declines in testing were strongly associated with increases in weekly positivity rates for chlamydia (R2=0.96) and gonorrhea (R2=0.85). From March 2020 through June 2020, an expected 27,659 (26.4%) chlamydia and 5,577 (16.5%) gonorrhea cases were potentially missed. Conclusions The COVID-19 pandemic impacted routine sexually transmitted infection services, suggesting an increase in syndromic sexually transmitted infection testing and missed asymptomatic cases. Follow-up analyses will be needed to assess the long-term implications of missed screening opportunities. These findings should serve as a warning for the potential sexual and reproductive health implications that can be expected from the overall decline in testing and potential missed cases.

Importance Understanding the effect of serum antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on susceptibility to infection is important for identifying at-risk populations and could have implications for vaccine deployment. Objective The study purpose was to evaluate evidence of SARS-CoV-2 infection based on diagnostic nucleic acid amplification test (NAAT) among patients with positive vs negative test results for antibodies in an observational descriptive cohort study of clinical laboratory and linked claims data. Design, Setting, and Participants The study created cohorts from a deidentified data set composed of commercial laboratory tests, medical and pharmacy claims, electronic health records, and hospital chargemaster data. Patients were categorized as antibody-positive or antibody-negative according to their first SARS-CoV-2 antibody test in the database. Main Outcomes and Measures Primary end points were post-index diagnostic NAAT results, with infection defined as a positive diagnostic test post-index, measured in 30-day intervals (0-30, 31-60, 61-90, >90 days). Additional measures included demographic, geographic, and clinical characteristics at the time of the index antibody test, including recorded signs and symptoms or prior evidence of coronavirus 2019 (COVID) diagnoses or positive NAAT results and recorded comorbidities. Results The cohort included 3 257 478 unique patients with an index antibody test; 56% were female with a median (SD) age of 48 (20) years. Of these, 2 876 773 (88.3%) had a negative index antibody result, and 378 606 (11.6%) had a positive index antibody result. Patients with a negative antibody test result were older than those with a positive result (mean age 48 vs 44 years). Of index-positive patients, 18.4% converted to seronegative over the follow-up period. During the follow-up periods, the ratio (95% CI) of positive NAAT results among individuals who had a positive antibody test at index vs those with a negative antibody test at index was 2.85 (95% CI, 2.73-2.97) at 0 to 30 days, 0.67 (95% CI, 0.6-0.74) at 31 to 60 days, 0.29 (95% CI, 0.24-0.35) at 61 to 90 days, and 0.10 (95% CI, 0.05-0.19) at more than 90 days. Conclusions and Relevance In this cohort study, patients with positive antibody test results were initially more likely to have positive NAAT results, consistent with prolonged RNA shedding, but became markedly less likely to have positive NAAT results over time, suggesting that seropositivity is associated with protection from infection. The duration of protection is unknown, and protection may wane over time.

Numerous reports indicate that African Americans and Latinos are being affected disproportionately by coronavirus disease 2019 (COVID-19). Positivity rates have not been analyzed on scale because only 4 states report race/ethnicity as part of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. Previous studies also have had little ability to control for many known risk factors to better identify the effects of COVID-19 on racial and ethnic communities. Using test results from a large national reference laboratory database that included patients from all 50 states and the District of Columbia, this study compared positivity rates for SARS-CoV-2 nucleic acid amplification tests (NAAT) among various race/ethnicity groups by linking zip code-based race/ethnicity proportions from US Census data. Analysis of 2,331,175 unique patients tested March-May 2020 demonstrated an increasing trend in SARS-CoV-2 NAAT positivity across Black non-Hispanic community progressive quintiles (from 7.8% to 17.2%, P

Serologic tests for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) provide information on past infection and immune response. To better understand the persistence of immune response and the proportion of the population who can develop one, the authors assessed patterns of immunoglobulin G (IgG) positivity over time in individuals tested for SARS-CoV-2 RNA or IgG at a large national reference laboratory. More than 2.4 million SARS-CoV-2 IgG serology (initiated April 21, 2020) and 6.6 million nucleic acid amplification testing (NAAT) (initiated March 9, 2020) results on persons from across the United States as of July 10, 2020 were analyzed. Additional IgG serology results through August 11, 2020 were used for one household analysis. SARS-CoV-2 IgG positivity was observed in 91% (19,434/21,452) of individuals tested after a positive NAAT result and in 10% (7,831/80,968) after a negative NAAT result. Factors associated with seropositivity include age, region of patient residence, and interval between NAAT and IgG serology. The probability of persistent IgG seropositivity declined from 98.6% after 1 week to 74.3% after 2 months, less so in individuals ages ≥55 years than in younger groups. Specimens within 2 days from pairs of same-household members showed 92% IgG antibody concordance. Household adults were more frequently IgG positive prior to household children testing positive (36% versus 8%). IgG serology testing can identify an immune response to SARS-CoV-2 that varies based on age, sex, and duration since exposure. Loss of detectable IgG seropositivity occurs, in some patients, over weeks or months. Adults may be infecting household children.

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.

Reports suggested an association between SARS-CoV-2 infection and GBS, but subsequent studies produced conflicting results regarding the incidence of GBS during the pandemic. This study assessed positivity rates for GQ1b, GM-1, GD1a, and GD1b for tests performed January 2016, through March 2021, at a national laboratory. Relative to pre-pandemic levels, positivity rates during the pandemic declined by 61% for GQ1b and 24% for GM-1, while unchanged for GD1a and GD1b. These findings suggest heterogeneity with positivity rates of GBS-associated ganglioside antibodies during the COVID-19 pandemic. Mitigation strategies during the pandemic may have reduced the frequency of certain forms of GBS.

ImportanceThere is limited evidence regarding whether the presence of serum antibodies to SARS-CoV-2 is associated with a decreased risk of future infection. Understanding susceptibility to infection and the role of immune memory is important for identifying at-risk populations and could have implications for vaccine deployment.ObjectiveThe purpose of this study was to evaluate subsequent evidence of SARS-CoV-2 infection based on diagnostic nucleic acid amplification test (NAAT) among individuals who are antibody-positive compared with those who are antibody-negative, using real-world data.DesignThis was an observational descriptive cohort study.ParticipantsThe study utilized a national sample to create cohorts from a de-identified dataset composed of commercial laboratory test results, open and closed medical and pharmacy claims, electronic health records, hospital billing (chargemaster) data, and payer enrollment files from the United States. Patients were indexed as antibody-positive or antibody-negative according to their first SARS-CoV-2 antibody test recorded in the database. Patients with more than 1 antibody test on the index date where results were discordant were excluded.Main Outcomes/MeasuresPrimary endpoints were index antibody test results and post-index diagnostic NAAT results, with infection defined as a positive diagnostic test post-index, as measured in 30-day intervals (0-30, 31-60, 61-90, >90 days). Additional measures included demographic, geographic, and clinical characteristics at the time of the index antibody test, such as recorded signs and symptoms or prior evidence of COVID-19 (diagnoses or NAAT+) and recorded comorbidities.ResultsWe included 3,257,478 unique patients with an index antibody test. Of these, 2,876,773 (88.3%) had a negative index antibody result, 378,606 (11.6%) had a positive index antibody result, and 2,099 (0.1%) had an inconclusive index antibody result. Patients with a negative antibody test were somewhat older at index than those with a positive result (mean of 48 versus 44 years). A fraction (18.4%) of individuals who were initially seropositive converted to seronegative over the follow up period. During the follow-up periods, the ratio (CI) of positive NAAT results among individuals who had a positive antibody test at index versus those with a negative antibody test at index was 2.85 (2.73 - 2.97) at 0-30 days, 0.67 (0.6 - 0.74) at 31-60 days, 0.29 (0.24 - 0.35) at 61-90 days), and 0.10 (0.05 - 0.19) at >90 days.ConclusionsPatients who display positive antibody tests are initially more likely to have a positive NAAT, consistent with prolonged RNA shedding, but over time become markedly less likely to have a positive NAAT. This result suggests seropositivity using commercially available assays is associated with protection from infection. The duration of protection is unknown and may wane over time; this parameter will need to be addressed in a study with extended duration of follow up.Key PointsQuestionCan real-world data be used to evaluate the comparative risk of SARS-CoV-2 infection for individuals who are antibody-positive versus antibody-negative?FindingOf patients indexed on a positive antibody test, 10 of 3,226 with a NAAT (0.3%) had evidence of a positive NAAT > 90 days after index, compared with 491 of 16,157 (3.0%) indexed on a negative antibody test.MeaningIndividuals who are seropositive for SARS-CoV-2 based on commercial assays may be at decreased future risk of SARS-CoV-2 infection.

Objective: The Centers for Disease Control and Prevention (CDC) recommend that clinicians prescribing opioids for chronic pain should consider at least annual urine drug testing (UDT). We evaluated whether shorter intervals for repeat UDT are associated with decreased rates of drug misuse. Design: Retrospective analysis of deidentified serial UDT and matched prescribing data. Setting: We analyzed Quest Diagnostics 2016-2017 UDT results from new patients being monitored for prescription drug adherence, in nonsubstance use disorder (SUD) treatment environments. Main Outcome Measures: Drug misuse was defined as the absence of a prescribed substance or the presence of a nonprescribed substance. Patients with ≥ 3 sets of the UDT results were included. Results: UDT results from 49,601 patients (148,803 specimens) were tested. Declines in misuse between the first and second UDT were highest for those tested at the shortest intervals: approximately weekly, 19 percent; monthly, 15 percent; bimonthly, 12 percent; quarterly, 9 percent; semiannually, 3 percent; misuse rates increased by 1 percent for patients tested annually. Declines in misuse were more pronounced for opioids than other drug groups. Substantial declines in positivity were noted for heroin (32 percent) and nonprescribed fentanyl (10 percent). Declines in misuse between the second and third UDT followed a similar pattern. Conclusions: UDT intervals of ≤ quarterly were associated with marked declines, but testing annually or semiannually was not associated with consistent decreases. Our findings suggest that clinical strategies that include serial testing conducted quarterly or sooner may be instrumental in decreasing drug misuse. Testing more frequently than “at least once annually” should be considered by clinicians monitoring potential drug misuse.

Background Nucleic acid amplification testing is a critical tool for addressing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Specimen pooling can increase throughput and conserve testing resources but requires validation to ensure that reduced sensitivity does not increase the false-negative rate. We evaluated the performance of a real-time reverse transcription polymerase chain reaction (RT-PCR) test authorized by the US Food and Drug Administration (FDA) for emergency use for pooled testing of upper respiratory specimens. Methods Positive specimens were selected from 3 prevalence groups, 1%–3%, >3%–6%, and >6%–10%. Positive percent agreement (PPA) was assessed by pooling single-positive specimens with 3 negative specimens; performance was assessed using Passing-Bablok regression. Additionally, we assessed the distributions of RT-PCR cycle threshold (Ct) values for 3091 positive specimens. Results PPA was 100% for the 101 pooled specimens. There was a linear relationship between Ct values for pooled and single-tested specimens (r = 0.96–0.99; slope ≈ 1). The mean pooled Ct shifts at 40 cycles were 2.38 and 1.90, respectively, for the N1 and N3 targets. The median Cts for 3091 positive specimens were 25.9 (N1) and 24.7 (N3). The percentage of positive specimens with Cts between 40 and the shifted Ct was 1.42% (N1) and 0.0% (N3). Conclusions Pooled and individual testing of specimens positive for SARS-CoV-2 demonstrated 100% agreement, which demonstrates the viability of pooled specimens for SARS-COV-2 testing using a dual-target RT-PCR system. Pooled specimen testing can help increase testing capacity for SARS-CoV-2 with a low risk of false-negative results.

This cross-sectional study examines changes in the number of patients with newly identified cancer before and during the coronavirus disease 2019 (COVID-19) pandemic in the United States.

ObjectivesGiven the recent debate challenging the contribution of cytology in cervical screening, we evaluated results of liquid-based cytology (LBC) and human papillomavirus (HPV) testing in cotesting preceding cervical cancer (CxCa) and precancer diagnoses in a national, heterogeneous population.MethodsWe assessed the results of cotesting, performed by Quest Diagnostics, in 13,633,071 women 30 years and older, tested 2010 to 2018. Cotest results preceding CxCa or precancer diagnoses were analyzed and stratified by histopathology.ResultsAmong all screening results, 1,615 cotests preceded 1,259 CxCa diagnoses, and 11,164 cotests preceded 8,048 cervical precancer diagnoses. More women who were subsequently diagnosed with CxCa within 1 year were identified by the LBC result than by the HPV result (85.1%, 1,015/1,193 vs 77.5%, 925/1,193). Among all women with CxCa, the overall rate of nondetection was 13.1% (212/1,615) for cotesting results (LBC negative/HPV negative) and this rate increased substantially when testing exceeded 12 months compared to within 1 year prediagnosis of either CxCa or precancer.ConclusionsAnalysis of 9-year cotest results from a national reference laboratory confirms the value of LBC element in cotesting. This supports that LBC/HPV cotesting enhances screening for the identification of CxCa in women 30 years and older, more so than LBC or HPV alone within cotesting.

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

IMPORTANCE: No safe level of exposure to lead has been identified. OBJECTIVE: To evaluate individual- and community-level factors associated with detectable and elevated blood lead levels (BLLs) in children. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional, retrospective study analyzed deidentified results from blood lead tests performed at a large clinical laboratory from October 1, 2018, to February 29, 2020. Participants were 1 141 441 children younger than 6 years living in all 50 US states and the District of Columbia who underwent blood lead testing during the study period. Children who underwent lead testing of unknown source and those with elevated BLLs who received capillary blood lead testing without confirmatory venous testing were excluded. EXPOSURES: Individual demographic categories included sex, age, and insurance type; community-level demographic categories included pre-1950s housing, poverty, predominant race and ethnicity, and geographical regions. MAIN OUTCOMES AND MEASURES: Proportions of children with detectable (≥1.0 μg/dL) and elevated (≥5.0 μg/dL) BLLs, by exposure category. RESULTS: Of the 1 141 441 children (586 703 boys [51.4%]; mean [SD] age, 2.3 [1.4] years) in the study, more than half of the children tested (576 092 [50.5%; 95% CI, 50.4%-50.6%]) had detectable BLLs, and 21 172 children (1.9% [95% CI, 1.8%-1.9%]) had BLLs of 5.0 μg/dL or more. In multivariable analyses, children with public insurance had greater odds of having detectable BLLs (adjusted odds ratio [AOR], 2.01 [95% CI, 1.99-2.04]) and elevated BLLs (AOR, 1.08 [95% CI, 1.04-1.12]). The proportion of children with detectable and elevated BLLs increased significantly for progressive pre-1950s housing and poverty quintiles (P

Objectives Recently, more than 63% of the 52,404 drug overdose deaths in the United States involved heroin and opioid pain medications. More than 30% of opioid-related deaths also involved benzodiazepines. Previous studies examining the extent of concurrent opioid and benzodiazepine use have relied on prescription data. To gain fuller insight into the extent of the concurrent use problem, we analyzed opioid and benzodiazepine prescription patterns in the context of drug testing results. Methods All specimens from patients that were prescribed at least 1 drug and were tested for both opioids and benzodiazepines by a national reference laboratory were included. This resulted in an analytical set of 231,228 sets of test results from 144,535 patients with diverse demographic factors being tested in a variety of health care settings. Results Laboratory test results indicated concurrent use of opioids and benzodiazepines in over 25% of patients. In 52% of test results with evidence of concurrent use, 1 drug class was prescribed and the other was non-prescribed. Nearly 1 in 5 specimens (19%) testing positive for prescribed opioids also tested positive for non-prescribed benzodiazepines. Over 15% of specimens with prescribed benzodiazepines also demonstrated non-prescribed opioid use. Conclusions The extent of concurrent use of benzodiazepines and opioids, particularly non-prescribed use, suggests the need for more effective clinician assessment and intervention. The results support the Centers for Disease Control and Prevention opioid prescribing guidelines that drug testing occur before and periodically throughout opioid use and suggest that this testing should be extended to patients prescribed benzodiazepines as well.