Immune and behavioral correlates of protection against symptomatic post-vaccination SARS-CoV-2 infection.

Introduction: We sought to determine pre-infection correlates of protection against SARS-CoV-2 post-vaccine inzfections (PVI) acquired during the first Omicron wave in the United States. Methods: Serum and saliva samples from 176 vaccinated adults were collected from October to December of 2021, immediately before the Omicron wave, and assessed for SARS-CoV-2 Spike-specific IgG and IgA binding antibodies (bAb). Sera were also assessed for bAb using commercial assays, and for neutralization activity against several SARS-CoV-2 variants. PVI duration and severity, as well as risk and precautionary behaviors, were assessed by questionnaires. Results: Serum anti-Spike IgG levels assessed by research assay, neutralization titers against Omicron subvariants, and low home risk scores correlated with protection against PVIs after multivariable regression analysis. Commercial assays did not perform as well as research assay, likely due to their lower dynamic range. Discussion: In the 32 participants that developed PVI, anti-Spike IgG bAbs correlated with lower disease severity and shorter duration of illness.

Humoral and cellular immune responses against SARS-CoV-2 post-vaccination in immunocompetent and immunocompromised cancer populations.

Cancer patients are at risk for severe coronavirus disease 2019 (COVID-19) outcomes due to impaired immune responses. However, the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is inadequately characterized in this population. We hypothesized that cancer vs non-cancer individuals would mount less robust humoral and/or cellular vaccine-induced immune SARS-CoV-2 responses. Receptor binding domain (RBD) and SARS-CoV-2 spike protein antibody levels and T-cell responses were assessed in immunocompetent individuals with no underlying disorders (n = 479) and immunocompromised individuals (n = 115). All 594 individuals were vaccinated and of varying COVID-19 statuses (i.e., not known to have been infected, previously infected, or "Long-COVID"). Among immunocompromised individuals, 59% (n = 68) had an underlying hematologic malignancy; of those, 46% (n = 31) of individuals received cancer treatment <30 days prior to study blood collection. Ninety-eight percentage (n = 469) of immunocompetent and 81% (n = 93) of immunocompromised individuals had elevated RBD antibody titers (>1,000 U/mL), and of these, 60% (n = 281) and 44% (n = 41), respectively, also had elevated T-cell responses. Composite T-cell responses were higher in individuals previously infected with SARS-CoV-2 or those diagnosed with Long-COVID compared to uninfected individuals. T-cell responses varied between immunocompetent vs carcinoma (n = 12) cohorts (P < 0.01) but not in immunocompetent vs hematologic malignancy cohorts. Most SARS-CoV-2 vaccinated individuals mounted robust cellular and/or humoral responses, though higher immunogenicity was observed among the immunocompetent compared to cancer populations. The study suggests B-cell targeted therapies suppress antibody responses, but not T-cell responses, to SARS-CoV-2 vaccination. Thus, vaccination continues to be an effective way to induce humoral and cellular immune responses as a likely key preventive measure against infection and/or subsequent more severe adverse outcomes. IMPORTANCE: The study was prompted by a desire to better assess the immune status of patients among our cancer host cohort, one of the largest in the New York metropolitan region. Hackensack Meridian Health is the largest healthcare system in New Jersey and cared for more than 75,000 coronavirus disease 2019 patients in its hospitals. The John Theurer Cancer Center sees more than 35,000 new cancer patients a year and performs more than 500 hematopoietic stem cell transplants. As a result, the work was undertaken to assess the effectiveness of vaccination in inducing humoral and cellular responses within this demographic.

Hepatitis C Virus Testing, Infection, and Cases Reported Through Public Health Surveillance During Expanded Screening Recommendations, United States, 2013-2021.

OBJECTIVES: Hepatitis C virus (HCV) infection is the most common bloodborne infection in the United States. We assessed trends in HCV testing, infection, and surveillance cases among US adults. METHODS: We used Quest Diagnostics data from 2013-2021 to assess trends in the numbers tested for HCV antibody and proportion of positivity for HCV antibody and HCV RNA. We also assessed National Notifiable Diseases Surveillance System 2013-2020 data for trends in the number and proportion of hepatitis C cases. We applied joinpoint regression for trends testing. RESULTS: Annual HCV antibody testing increased from 1.7 million to 4.8 million from 2013 to 2021, and the positivity proportion declined (average, 0.2% per year) from 5.5% to 3.7%. The greatest percentage-point increase in HCV antibody testing occurred in hospitals and substance use disorder treatment facilities and among addiction medicine providers. HCV RNA positivity was stable at about 60% in 2013-2015 and declined to 41.0% in 2021 (2015-2021 average, -3.2% per year). Age-specific HCV RNA positivity was highest among people aged 40-59 years during 2013-2015 and among people aged 18-39 years during 2016-2021. The number of reported hepatitis C cases (acute and chronic) declined from 179 341 in 2015 to 105 504 in 2020 (average decline, -13 177 per year). The proportion of hepatitis C cases among those aged 18-39 years increased by an average of 1.4% per year during 2013-2020; among individuals aged 40-59 years, it decreased by an average of 2.3% per year during 2013-2018. CONCLUSIONS: HCV testing increased, suggesting improved universal screening. Various data sources are valuable for monitoring elimination progress.

Nucleocapsid and Spike Protein-Based Anti-SARS-CoV-2 Assay Performance in the Minority and Rural Coronavirus Insights Study: Characteristics of Socioeconomically Disadvantaged Populations with Health Disparities.

BACKGROUND: COVID-19 has had a devastating impact on Black, Hispanic, and other underserved, disadvantaged populations. Here anti-SARS-CoV-2 tests are characterized in disadvantaged patients to examine equivalence in US populations. METHODS: Underserved participant adults (age > 18 years) were enrolled before the availability of SARS-CoV-2 vaccines in Federal Qualified Health Centers in California, Florida, Louisiana, Illinois, and Ohio and contributed samples to the Minority and Rural Coronavirus Insights Study (MRCIS). A subset coined the MRCIS SARS-CoV-2 Antibody Cohort of 2365 participants was tested with the Roche Anti-SARS-CoV-2 assay (Cobas e601). Five hundred ninety-five of these were also tested with the Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 IgG assay (VITROS-5600); 1770 were also tested with the Abbott ARCHITECT SARS-CoV-2 IgG assay (ARCHITECT-2000). Assay-specific cutoffs classified negative/positive results. RESULTS: Eight point four percent (199/2365) of the MRCIS SARS-CoV-2 Antibody Cohort was SARS-CoV-2 RNA positive at enrollment. Agreement between the Ortho/Roche and the Abbott/Roche antibody testing did not vary by enrollment RNA status. The Ortho (anti-spike protein) vs Roche (anti-nucleocapsid protein) comparison agreed substantially: kappa = 0.63 (95% CI: 0.57-0.69); overall agreement, 83%. However, agreement was even better for the Abbott vs Roche assays (both anti-nucleocapsid protein tests): kappa = 0.85 (95% CI: 0.81-0.87); overall agreement, 95%. Anti-SARS-CoV-2 comparisons stratified by demographic criteria demonstrated no significant variability in agreement by sex, race/ethnicity, or age. CONCLUSIONS: Analytical agreement is 96.4% for anti-spike-protein vs anti-nucleocapsid-protein comparisons. Physiologically, seroreversion of anti-nucleocapsid reactivity after infection occurred in the disadvantaged population similarly to general populations. No anti-SARS-CoV-2 assays included demonstrated a clinically significant difference due to the demographics of the disadvantaged MRCIS SARS-CoV-2 Antibody Cohort.

The Minority and Rural Coronavirus Insights Study: Design and Baseline Characteristics of a Minority Cohort.

The Minority and Rural Coronavirus Insights Study (MRCIS) is an ongoing prospective cohort study examining health disparities associated with SARS-CoV-2 infection among medically underserved populations. This report describes procedures implemented to establish the MRCIS cohort and examines the factors associated with the molecular and serological assessment of SARS-CoV-2 infection status at participant enrollment. Participants were recruited from 5 geographically dispersed federally qualified health centers between November 2020 and April 2021. At baseline, participants completed a detailed demographic survey and biological samples were collected for testing. SARS-CoV-2 infection status was determined based on the combined molecular and serological test results. Chi-squared and logistic regression analyses were conducted to examine associations between sociodemographic factors, COVID-19 safety measures, existing comorbidities, and SARS-CoV-2 infection status. The final cohort included 3238 participants. The mean age of participants was 50.2 ± 15.8 years. Most participants identified as female (60.0%), heterosexual or straight (93.0%), White (47.6%), and Hispanic or Latino (49.1%). Approximately 26.1% of participants had at least one positive SARS-CoV-2 test result. The main effect model included age, sex, and race/ethnicity. Compared with adults ≥65 years, participants in all other age groups had ∼2 times increased odds of a positive SARS-CoV-2 test result. In addition, racial/ethnic minorities had ∼2 times increased odds of a positive SARS-CoV-2 infection status compared with non-Hispanic Whites. A unique cohort of a traditionally medically underserved minority population was established. Significant racial and ethnic disparities in SARS-CoV-2 infection status at baseline were discovered.

SARS-CoV-2 spike-protein targeted serology test results and their association with subsequent COVID-19-related outcomes.

Importance: In the absence of evidence of clinical utility, the United States' Centers for Disease Control and Prevention does not currently recommend the assessment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike-protein antibody levels. Clinicians and their patients, especially immunocompromised patients, may benefit from an adjunctive objective clinical laboratory measure of risk, using SARS-CoV-2 serology. Objective: The aim of this study is to estimate the association between SARS-CoV-2 spike-protein targeted antibody levels and clinically relevant outcomes overall and among clinically relevant subgroups, such as vaccine and immunocompetency statuses. Design: A retrospective cohort study was conducted using laboratory-based data containing SARS-CoV-2 antibody testing results, as well as medical and pharmacy claim data. SARS-CoV-2 testing was performed by two large United States-based reference clinical laboratories, Labcorp® and Quest Diagnostics, and was linked to medical insurance claims, including vaccination receipt, through the HealthVerity Marketplace. Follow-up for outcomes began after each eligible individual's first SARS-CoV-2 semiquantitative spike-protein targeted antibody test, from 16 November 2020 to 30 December 2021. Exposures: Exposure is defined as having SARS-CoV-2 spike-protein targeted antibody testing. Main outcomes and measures: Study outcomes were SARS-CoV-2 infection and a serious composite outcome (hospitalization with an associated SARS-CoV-2 infection or all-cause death). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Propensity score matching was used for confounding covariate control. Results: In total, 143,091 (73.2%) and 52,355 (26.8%) eligible individuals had detectable and non-detectable levels of SARS-CoV-2 spike-protein targeted antibodies, respectively. In the overall population, having detectable vs. non-detectable antibodies was associated with an estimated 44% relative reduction in SARS-CoV-2 subsequent infection risk (HR, 0.56; 95% CI 0.53-0.59) and an 80% relative reduction in the risk of serious composite outcomes (HR 0.20; 95% CI 0.15-0.26). Relative risk reductions were observed across subgroups, including among immunocompromised persons. Conclusion and relevance: Individuals with detectable SARS-CoV-2 spike-protein targeted antibody levels had fewer associated subsequent SARS-CoV-2 infections and serious adverse clinical outcomes. Policymakers and clinicians may find SARS-CoV-2 spike-protein targeted serology testing to be a useful adjunct in counseling patients with non-detectable antibody levels about adverse risks and reinforcing appropriate actions to mitigate such risks.

Hepatitis C Virus Clearance Cascade - United States, 2013-2022.

Approximately 2.4 million adults were estimated to have hepatitis C virus (HCV) infection in the United States during 2013-2016 (1). Untreated, hepatitis C can lead to advanced liver disease, liver cancer, and death (2). The Viral Hepatitis National Strategic Plan for the United States calls for ≥80% of persons with hepatitis C to achieve viral clearance by 2030 (3). Characterizing the steps that follow a person's progression from testing to viral clearance and subsequent infection (clearance cascade) is critical for monitoring progress toward national elimination goals. Following CDC guidance (4), a simplified national laboratory results-based HCV five-step clearance cascade was developed using longitudinal data from a large national commercial laboratory throughout the decade since highly effective hepatitis C treatments became available. During January 1, 2013-December 31, 2021, a total of 1,719,493 persons were identified as ever having been infected with HCV. During January 1, 2013-December 31, 2022, 88% of those ever infected were classified as having received viral testing; among those who received viral testing, 69% were classified as having initial infection; among those with initial infection, 34% were classified as cured or cleared (treatment-induced or spontaneous); and among those persons, 7% were categorized as having persistent infection or reinfection. Among the 1.0 million persons with evidence of initial infection, approximately one third had evidence of viral clearance (cured or cleared). This simplified national HCV clearance cascade identifies substantial gaps in cure nearly a decade since highly effective direct-acting antiviral (DAA) agents became available and will facilitate the process of monitoring progress toward national elimination goals. It is essential that increased access to diagnosis, treatment, and prevention services for persons with hepatitis C be addressed to prevent progression of disease and ongoing transmission and achieve national hepatitis C elimination goals.

Risk of and duration of protection from SARS-CoV-2 reinfection assessed with real-world data.

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.

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.

Estimated SARS-CoV-2 antibody seroprevalence trends and relationship to reported case prevalence from a repeated, cross-sectional study in the 50 states and the District of Columbia, United States-October 25, 2020-February 26, 2022.

Background: Sero-surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can reveal trends and differences in subgroups and capture undetected or unreported infections that are not included in case-based surveillance systems. Methods: Cross-sectional, convenience samples of remnant sera from clinical laboratories from 51 U.S. jurisdictions were assayed for infection-induced SARS-CoV-2 antibodies biweekly from October 25, 2020, to July 11, 2021, and monthly from September 6, 2021, to February 26, 2022. Test results were analyzed for trends in infection-induced, nucleocapsid-protein seroprevalence using mixed effects models that adjusted for demographic variables and assay type. Findings: Analyses of 1,469,792 serum specimens revealed U.S. infection-induced SARS-CoV-2 seroprevalence increased from 8.0% (95% confidence interval (CI): 7.9%-8.1%) in November 2020 to 58.2% (CI: 57.4%-58.9%) in February 2022. The U.S. ratio of the change in estimated seroprevalence to the change in reported case prevalence was 2.8 (CI: 2.8-2.9) during winter 2020-2021, 2.3 (CI: 2.0-2.5) during summer 2021, and 3.1 (CI: 3.0-3.3) during winter 2021-2022. Change in seroprevalence to change in case prevalence ratios ranged from 2.6 (CI: 2.3-2.8) to 3.5 (CI: 3.3-3.7) by region in winter 2021-2022. Interpretation: Ratios of the change in seroprevalence to the change in case prevalence suggest a high proportion of infections were not detected by case-based surveillance during periods of increased transmission. The largest increases in the seroprevalence to case prevalence ratios coincided with the spread of the B.1.1.529 (Omicron) variant and with increased accessibility of home testing. Ratios varied by region and season with the highest ratios in the midwestern and southern United States during winter 2021-2022. Our results demonstrate that reported case counts did not fully capture differing underlying infection rates and demonstrate the value of sero-surveillance in understanding the full burden of infection. Levels of infection-induced antibody seroprevalence, particularly spikes during periods of increased transmission, are important to contextualize vaccine effectiveness data as the susceptibility to infection of the U.S. population changes. Funding: This work was supported by the Centers for Disease Control and Prevention, Atlanta, Georgia.

Prevalence of Hepatitis B Virus and Latent Tuberculosis Coinfection in the United States.

CONTEXT: 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. OBJECTIVE: To evaluate patterns of HBV and LTBI testing and prevalence of HBV-LTBI coinfection in the United States. DESIGN: Retrospective cohort study. SETTING: Quest Diagnostics clinical laboratory data, 2014-2020. PATIENTS: 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. MAIN OUTCOME MEASUREMENTS: 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. RESULTS: 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. LIMITATIONS: The HBV-LTBI coinfection prevalence was likely underestimated because of suboptimal awareness and testing among at-risk populations. CONCLUSION: 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.

Hepatitis C Virus Testing During Pregnancy After Universal Screening Recommendations.

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.

Crabgrass as an equine pasture forage: impact of establishment method on yield, nutrient composition, and horse preference.

Warm-season grasses (WSG) incorporated into traditional cool-season rotational grazing systems to increase summer yields are typically established in monoculture in separate pasture areas. Few studies have evaluated alternative interseeded establishment of WSG, despite potential benefits for improving biodiversity and land-use efficiency. The objective of this study was to determine the impact of establishment method (monoculture vs. interseeded) on crabgrass pasture forage yield, nutritive value, and preference under equine grazing. Three adult standardbred mares grazed two main plots on two consecutive days (8 hr/d) for three grazing events in 2019: Jul 28/29 (GRAZE 1), Aug 20/30 (GRAZE 2), Oct 1/2 (GRAZE 3). Each main plot contained four replicates of three treatments: mixed cool-season grass (CSG); Quick-N-Big crabgrass (CRB) [Digitaria sanguinalis (L.) Scop.] interseeded into existing cool-season grass (INT), and CRB established as a monoculture (MON). The cool-season grass mix included Inavale orchardgrass [Dactylis glomerata (L.)], Tower tall fescue [Lolium arundinaceum (Schreb.) Darbysh.], and Argyle Kentucky bluegrass [Poa pratensis (L.)]. Herbage mass (HM) and sward height (SH) were measured prior to each grazing event and samples were collected (0800-1000 h) for chemical composition analysis. Observed grazing time (GT) in each sub-plot as determined by 5-min scan sampling was utilized as marker of horse preference. Forage HM was greater in MON (8043 ± 1220 kg/ha) than CSG (5001 ± 1308 kg/ha; P = 0.003), with a trend for greater total HM in MON vs. INT (6582 ± 1220 kg/ha: P = 0.06), but HM did not differ between INT and CSG. The SH was also greatest for MON (28 ± 1.11; INT: 23.6 ± 1.11; CSG: 19.7 ± 1.37 cm; P < 0.003). Forage nutrients (digestible energy and crude protein) were largely similar across treatments and met requirements of horses at maintenance. Horse GT was lower in MON (22.6 ± 3.77 min/sub-plot) than in INT (31.9 ± 3.79 min/sub-plot; P = 0.003) and there was a trend for lower GT in MON vs. CSG (29.9 ± 4.17 min/sub-plot: P = 0.07). These results indicate interseeding CRB would not effectively increase yields of traditional cool-season grass equine rotational grazing systems and would not supply similar levels of summer forage provided by monoculture establishment. Results of this study also suggest horses may prefer cool-season grass pasture forage over warm-season crabgrass.

Duration of Protection Against SARS-CoV-2 Reinfection and Associated Risk of Reinfection Assessed with Real-World Data.

IMPORTANCE: Better understanding of the protective duration of prior SARS-CoV-2 infection against reinfection is needed. OBJECTIVE: Primary: 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 SETTING: Retrospective observational study of HealthVerity data among 144,678,382 individuals, during the pandemic era through April 2021. PARTICIPANTS: Individuals 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 OUTCOMES AND MEASURES: 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. RESULTS: Among 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 RELEVANCE: This 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 POINTS: Question: How long does prior SARS-CoV-2 infection provide protection against SARS-CoV-2 reinfection?Finding: Among >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.Meaning: Prior SARS-CoV-2 infection provides a durable, high relative degree of protection against reinfection.

Insights into HIV-1 Transmission Dynamics Using Routinely Collected Data in the Mid-Atlantic United States.

Background: Molecular epidemiological approaches provide opportunities to characterize HIV transmission dynamics. We analyzed HIV sequences and virus load (VL) results obtained during routine clinical care, and individual's zip-code location to determine utility of this approach. Methods: HIV-1 pol sequences aligned using ClustalW were subtyped using REGA. A maximum likelihood (ML) tree was generated using IQTree. Transmission clusters with ≤3% genetic distance (GD) and ≥90% bootstrap support were identified using ClusterPicker. We conducted Bayesian analysis using BEAST to confirm transmission clusters. The proportion of nucleotides with ambiguity ≤0.5% was considered indicative of early infection. Descriptive statistics were applied to characterize clusters and group comparisons were performed using chi-square or t-test. Results: Among 2775 adults with data from 2014−2015, 2589 (93%) had subtype B HIV-1, mean age was 44 years (SD 12.7), 66.4% were male, and 25% had nucleotide ambiguity ≤0.5. There were 456 individuals in 193 clusters: 149 dyads, 32 triads, and 12 groups with ≥ four individuals per cluster. More commonly in clusters were males than females, 349 (76.5%) vs. 107 (23.5%), p < 0.0001; younger individuals, 35.3 years (SD 12.1) vs. 44.7 (SD 12.3), p < 0.0001; and those with early HIV-1 infection by nucleotide ambiguity, 202/456 (44.3%) vs. 442/2133 (20.7%), p < 0.0001. Members of 43/193 (22.3%) of clusters included individuals in different jurisdictions. Clusters ≥ four individuals were similarly found using BEAST. HIV-1 viral load (VL) ≥3.0 log10 c/mL was most common among individuals in clusters ≥ four, 18/21, (85.7%) compared to 137/208 (65.8%) in clusters sized 2−3, and 927/1169 (79.3%) who were not in a cluster (p < 0.0001). Discussion: HIV sequence data obtained for HIV clinical management provide insights into regional transmission dynamics. Our findings demonstrate the additional utility of HIV-1 VL data in combination with phylogenetic inferences as an enhanced contact tracing tool to direct HIV treatment and prevention services. Trans-jurisdictional approaches are needed to optimize efforts to end the HIV epidemic.

Diurnal Variation in Forage Nutrient Composition of Mixed Cool-Season Grass, Crabgrass, and Bermudagrass Pastures.

Warm-season grasses have been suggested as alternative low non-structural carbohydrate (NSC) pasture forages. The purpose of this study was to evaluate nutrient composition and diurnal changes in soluble carbohydrates for the warm-season annual 'Quick-N-Big' crabgrass [CRB; Digitaria sanguinalis (L.) Scop.] and the warm-season perennial 'Wrangler' bermudagrass [BER; Cynodon dactylon (L.) Pers] in comparison to mixed cool-season grass [CSG; 'Inavale' orchardgrass (Dactylis glomerata [L.]), 'Tower' tall fescue (Lolium arundinaceum [Schreb.] Darbysh.), and 'Argyle' Kentucky bluegrass (Poa pratensis [L.])]. Samples were collected at 4-hour intervals over 3 d when each forage reached the boot stage of maturity. Digestible energy was greatest for CSG (2.29 ± 0.34 Mcal/kg) and lowest for BER (2.13 ± 0.34 Mcal/kg), while crude protein was lowest for CSG (16.1 ± 0.29%) and neutral detergent fiber was greatest for BER (60.0 ± 0.41; P ≤ .0008). Non-structural carbohydrates were greater for CSG (17.6% ± 0.26%) compared to BER (10.6% ± 0.26%) or CRB (10.9% ± 0.26%; P < .0001). Overall, NSC was greatest in the afternoon and evening (14.5-14.9 ± 0.60%) and lowest in the early morning (11.2-11.4 ± 0.60%; P ≤ .04), but diurnal variation was most pronounced in CSG versus either Warm-season grasses. Results of this study provide needed data on nutritional composition of CRB and BER and demonstrate that these grasses may serve as pasture forages for horses where NSC intake is of concern. Results also support recommendations for restricting grazing to early morning to limit NSC consumption, particularly in CSG pastures.

Yield, nutrient composition, and horse condition in integrated crabgrass and cool-season grass rotational grazing pasture systems.

Integration of warm-season grasses into traditional cool-season pastures can increase summer forage for grazing cattle. The aim of this study was to determine impacts of this practice on yield and nutrient composition of equine rotational pasture systems as well as horse body condition. Two 1.5 ha rotational systems (6 to 0.25 ha sections/system) were evaluated: a control system (CON) (all sections mixed cool-season grass [CSG-CON]) and an integrated rotational grazing system (IRS) (three CSG sections [CSG-IRS] and three Quick-N-Big crabgrass [Digitaria sanguinalis (L.) Scop.; CRB-IRS]). Three horses per system grazed in three periods: EARLY (mid-May to mid-July), SLUMP (mid-July to mid-September), and LATE (mid-September to mid-November). Herbage mass (HM) was measured prior to each rotation and samples were collected (0800 to 1000 h) for nutrient analysis. Grazing days were tracked to calculate carrying capacity (CC). Horse condition measures were assessed monthly. Over the full grazing season, 9,125 kg of forage was available for grazing in IRS versus 6,335 kg in CON. The CC was 390 horse d for IRS, while only 276 horse d for CON. Total HM/section did not differ during EARLY when CRB was not available (CSG-IRS: 2,537 ± 605; CSG-CON: 3,783 ± 856 kg/ha), but CC was greater in CSG-IRS (220 ± 37 horse d/ha) than CSG-CON (92 ± 26 horse d/ha; P = 0.03). In SLUMP, both HM and CC were greater in CRB-IRS (HM: 4,758 ± 698 kg/ha; CC: 196 ± 31 horse d/ha) than CSG-IRS (HM: 1,086 ± 698 kg/ha; CC: 32 ± 31 horse d/ha) or CON (HM: 970 ± 493 kg/ha; CC: 46 ± 22 horse d/ha; P < 0.02). While HM did not differ by section type in LATE (1,284 ± 158 kg/ha), CC was greater in CSG-CON (84 ± 9 horse d/ha) versus CRB-IRS (32 ± 13 horse d/ha; P = 0.03) and CSG-IRS (40 ± 13 horse d/ha; P = 0.06). During SLUMP, water-soluble carbohydrates (WSC) were lower in CRB-IRS (4.46% ± 0.80%) than CSG-CON (7.92% ± 0.90%; P < 0.04), but not CSG-IRS (5.93% ± 1.04%); however, non-structural carbohydrates (NSC) did not differ (7.05% ± 0.62%). There were no differences in WSC (6.46% ± 0.54%) or NSC (7.65% ± 0.54%) by section type in LATE. Horses in IRS maintained a body condition score (BCS) of 5.78 ± 0.48, but BCS did not differ by system (CON: 6.11 ± 0.48). Thus, integrated grazing increased summer pasture yield and provided adequate nutrition to maintain horse condition, but further research is needed to improve late-season production. Integrated grazing may not, however, provide an advantage in limiting dietary NSC, as NSC remained low for all pasture sections.

Retrospective Performance Analyses of over Two Million U.S. QuantiFERON Blood Sample Results.

Both the QuantiFERON-TB Gold Plus (QFT-Plus) and the QuantiFERON-TB Gold In-Tube (QFT-GIT) tests are interferon gamma (IFN-γ) release assays (IGRAs) intended to detect in vitro cell-mediated immune responses to Mycobacterium tuberculosis antigens. In this study, we retrospectively analyzed performance data for both the QFT-GIT and QFT-Plus test systems from over 2 million samples. QFT-Plus and QFT-GIT testing was performed as specified in the respective package inserts at 23 Quest Diagnostics sites. Blood specimens were collected from individuals in all 50 states from November 2018 through December 2019. Retrospective analyses compared the proportion of positive, indeterminate, and conversion/reversion results. The overall proportion of QFT-positive results was 7% for both the QFT-Plus and QFT-GIT. The proportion of positive results was highest for QFT-GIT (7.5%) followed by the heparin 1-tube QFT-Plus (7.2%); a lower proportion of positives was observed with the 4-tube (all four QFT tubes were used in blood collection) QFT-Plus (6.0%). The proportions of indeterminate results for the 1-tube (heparin-only tube collection) and 4-tube QFT-Plus methods were less than 1% and 4%, respectively. This study indicates a higher proportion of positive results for M. tuberculosis than data from other studies. Additionally, the proportion of indeterminate QFT results were markedly lower when the sample was transported in one lithium-heparin tube instead of direct inoculation into 4 QFT-Plus tubes at the site of blood collection. IMPORTANCE In this study, we retrospectively analyzed results from both the QFT-GIT and QFT-Plus test systems from over 2 million blood specimens. The variables analyzed were (i) QFT positivity rates among various U.S. populations, (ii) indeterminate rates among various types of blood draws and how often an indeterminate result was resolved within 30 days after the initial draw, and (iii) the association of TB1 and TB2 antigen tubes with IGRA reversion and conversion events from serial QFT testing. This is, to our knowledge, the largest QFT study representing patients from an extensive geographic coverage across the United States and U.S. territories.

Decreases in Hepatitis C Testing and Treatment During the COVID-19 Pandemic.

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.

Association of SARS-CoV-2 Seropositive Antibody Test With Risk of Future Infection.

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.