BACKGROUND:The extent to which infection versus vaccination has conferred similarly durable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity during the Omicron era remains unclear. METHODS:In a cohort of 4496 adults under continued serological surveillance throughout the first year of Omicron-predominant SARS-CoV-2 transmission, we examined incidence of new infection among individuals whose last known antigenic exposure was either recent (<90 days) or remote (≥90 days) infection or vaccination. RESULTS:We adjudicated 2053 new-onset infections occurring between 15 December 2021 through 22 December 2022. In multivariable-adjusted analyses, compared to individuals whose last known exposure was remote vaccination, those with recent vaccination (odds ratio [OR], 0.82 [95% confidence interval {CI}, .73-.93]; P = .002) or recent infection (OR, 0.14 [95% CI, .05-.45]; P = .001) had lower risk for new infection within the subsequent 90-day period. Given a significant age interaction (P = .004), we found that remote infection compared to remote vaccination was associated with significantly greater new infection risk in persons aged ≥60 years (OR, 1.88 [95% CI, 1.13-3.14]; P = .015) with no difference seen in those <60 years (1.03 [95% CI, .69-1.53]; P = .88). CONCLUSIONS:During the initial year of Omicron, prior infection and vaccination both offered protection against new infection. However, remote prior infection was less protective than remote vaccination for individuals aged ≥60 years. In older adults, immunity gained from vaccination appeared more durable than immunity gained from infection.

INTRODUCTION:HCV antibody assays have been used to screen for HCV, but confirmation of acute infection is dependent on RNA or core antigen testing. The aim of the study was to compare the performance of five HCV test methods, including RNA testing, on a US emergency department population. METHODS:Clinical performance metrics were calculated on 708 consenting Johns Hopkins Emergency Department patients who self-reported an increased risk for HCV infection. Detection times of antibody, antigen, and RNA testing were compared using 89 samples from commercially available seroconversion panels. Testing was performed on the Abbott Alinity HCV Ag Next (RUO), Roche Elecsys HCV Duo, Abbott ARCHITECT Anti-HCV, and Elecsys Anti-HCV II assays. RNA testing was performed on the Abbott m2000 system. RESULTS:Overall, 21 (3.0%) participants tested positive for HCV on at least one test, 11 (52.4%) had chronic, 1 (4.8%) had an acute, and 3 (14.3%) had resolved infections. The Alinity HCV Ag Next assay demonstrated 99.43% specificity when compared to RNA testing. The Alinity HCV Ag Next assay also detected 91.67% of the active infections compared to RNA testing, while the Elecsys HCV Duo Ag assay detected only 58.33%. The seroconversion panel testing demonstrated that the Alinity HCV Ag Next assay detects an infection within 0.8 days of an RNA result. CONCLUSION:The Alinity HCV Ag Next assay demonstrated excellent concordance to RNA testing in a US urban E.D. POPULATION:This data supports the utility of Alinity HCV Ag Next in diagnosis of active HCV infections.

The prevalence of hepatitis C virus (HCV) infection in the United States has increased over the past decade despite the development of effective direct-acting antiviral treatments. To meet the World Health Organization’s (WHO) goal of eliminating HCV infection by 2030, transmission events must be reduced. Currently, infection screening relies on detection of HCV antibodies, with nucleic acid amplification testing (NAAT) used to confirm HCV viremia and monitor changes in viral load. However, the seroconversion window for detection of HCV antibodies is long, averaging 6 weeks, with delayed seroconversion common in co-infected and immunosuppressed populations. Testing for HCV core antigen, which is present approximately 5 weeks before HCV antibodies, holds promise for earlier detection of HCV infection. It may also hold promise as a cheaper, more accessible, and more rapid alternative to NAAT for infection confirmation. Here, we evaluated the agreement between a research-use HCV Core Antigen Assay and NAAT among US patients receiving clinically indicated NAAT. Among 412 specimens, the overall concordance was 97.1%, with a positive percent agreement of 95.5%. Discrepancies primarily occurred among patients with chronic HCV and low viral loads; 11/12 discrepancies showed viral loads <4,000 IU/mL. Among patients being screened for HCV infection (i.e., excluding those undergoing NAAT for serial monitoring of a previously diagnosed infection), the positive percent agreement was 97.0%. Among patients undergoing serial testing, changes in HCV Core Antigen Assay signal-to-cut-off values were generally correlated with changes in the viral load. Results suggest that the research-use HCV Core Antigen Assay studied here may reliably detect and/or confirm HCV infection. IMPORTANCE A research-use HCV Core Antigen Assay showed high concordance with nucleic acid amplification testing for the detection of current hepatitis C infection. The assay may enable more rapid and lower-cost detection and/or confirmation of hepatitis C infection.

COVID-19 has highlighted challenges in the measurement quality and comparability of serological binding and neutralization assays. Due to many different assay formats and reagents, these measurements are known to be highly variable with large uncertainties. The development of the WHO international standard (WHO IS) and other pool standards have facilitated assay comparability through normalization to a common material but does not provide assay harmonization nor uncertainty quantification. In this paper, we present the results from an interlaboratory study that led to the development of (1) a novel hierarchy of data analyses based on the thermodynamics of antibody binding and (2) a modeling framework that quantifies the probability of neutralization potential for a given binding measurement. Importantly, we introduced a precise, mathematical definition of harmonization that separates the sources of quantitative uncertainties, some of which can be corrected to enable, for the first time, assay comparability. Both the theory and experimental data confirmed that mAbs and WHO IS performed identically as a primary standard for establishing traceability and bridging across different assay platforms. The metrological anchoring of complex serological binding and neuralization assays and fast turn-around production of an mAb reference control can enable the unprecedented comparability and traceability of serological binding assay results for new variants of SARS-CoV-2 and immune responses to other viruses.

BACKGROUND AND AIMS:Patients with inflammatory bowel disease [IBD] have an attenuated response to initial COVID-19 vaccination. We sought to characterize the impact of IBD and its treatment on responses after the third vaccine against SARS-CoV-2. METHODS:This was a prospective multicentre observational study of patients with IBD [n = 202] and healthy controls [HC, n = 92]. Serological response to vaccination was assessed by quantification of anti-spike protein [SP] immunoglobulin [Ig]G levels [anti-SPIgG] and in vitro neutralization of binding to angiotensin-converting enzyme 2 [ACE2]. Peripheral blood B-cell phenotype populations were assessed by flow cytometry. SARS-CoV-2 antigen-specific B-cell responses were assessed in ex vivo culture. RESULTS:Median anti-SP IgG post-third vaccination in our IBD cohort was significantly lower than HCs [7862 vs 19 622 AU/mL, p < 0.001] as was ACE2 binding inhibition [p < 0.001]. IBD patients previously infected with COVID-19 [30%] had similar quantitative antibody response as HCs previously infected with COVID-19 [p = 0.12]. Lowest anti-SP IgG titres and neutralization were seen in IBD patients on anti-tumour necrosis factor [anti-TNF] agents, without prior COVID-19 infection, but all IBD patients show an attenuated vaccine response compared to HCs. Patients with IBD have reduced memory B-cell populations and attenuated B-cell responses to SARS-CoV-2 antigens if not previously infected with COVID-19 [p = 0.01]. Higher anti-TNF drug levels and zinc levels <65 ng/ml were associated with significantly lower serological responses. CONCLUSIONS:Patients with IBD have an attenuated response to three doses of SARS-CoV-2 vaccine. Physicians should consider patients with higher anti-TNF drug levels and/or zinc deficiency as potentially at higher risk of attenuated response to vaccination.

BackgroundIndividuals with post-acute sequelae of COVID (PASC) may have a persistence in immune activation that differentiates them from individuals who have recovered from COVID without clinical sequelae. To investigate how humoral immune activation may vary in this regard, we compared patterns of vaccine-provoked serological response in patients with PASC compared to individuals recovered from prior COVID without PASC.MethodsWe prospectively studied 245 adults clinically diagnosed with PASC and 86 adults successfully recovered from prior COVID. All participants had measures of humoral immunity to SARS-CoV-2 assayed before or after receiving their first-ever administration of COVID vaccination (either single-dose or two-dose regimen), including anti-spike (IgG-S and IgM-S) and anti-nucleocapsid (IgG-N) antibodies as well as IgG-S angiotensin-converting enzyme 2 (ACE2) binding levels. We used unadjusted and multivariable-adjusted regression analyses to examine the association of PASC compared to COVID-recovered status with post-vaccination measures of humoral immunity.ResultsIndividuals with PASC mounted consistently higher post-vaccination IgG-S antibody levels when compared to COVID-recovered (median log IgG-S 3.98 versus 3.74, P < 0.001), with similar results seen for ACE2 binding levels (median 99.1 versus 98.2, P = 0.044). The post-vaccination IgM-S response in PASC was attenuated but persistently unchanged over time (P = 0.33), compared to in COVID recovery wherein the IgM-S response expectedly decreased over time (P = 0.002). Findings remained consistent when accounting for demographic and clinical variables including indices of index infection severity and comorbidity burden.ConclusionWe found evidence of aberrant immune response distinguishing PASC from recovered COVID. This aberrancy is marked by excess IgG-S activation and ACE2 binding along with findings consistent with a delayed or dysfunctional immunoglobulin class switching, all of which is unmasked by vaccine provocation. These results suggest that measures of aberrant immune response may offer promise as tools for diagnosing and distinguishing PASC from non-PASC phenotypes, in addition to serving as potential targets for intervention.

An updated understanding of how immunity may wane or be sustained following SARS-CoV-2 vaccination is needed to guide efforts aimed at mitigating the ongoing risks from COVID. Prior studies found that greater magnitude and duration of antibody response after initial vaccination are associated with prior infection, female sex, and younger age. However, most of these earlier reports were limited to analyses conducted within a year of vaccine availability, among predominantly female healthcare workers, and without data on the effects of comorbidities [1–4].

BACKGROUND:Tixagevimab-cilgavimab (Tix-Cil) was authorized for prophylaxis against COVID-19 in immunocompromised patients from December 2021 through January 2023. Real-world effectiveness for solid organ transplant (SOT) recipients has been unclear. METHODS:We enrolled 911 SOT recipients into a longitudinal COVID-19 serology study, of whom 381 (42%) received ≥1 dose of Tix-Cil. We collected and analyzed data on incident SARS-CoV-2 infections and antibody kinetics for all patients from January 2022 to March 2023, including periods dominated by Omicron BA and BQ subvariants. RESULTS:Over 253 ± 131 days of follow-up, there were 324 new-onset SARS-CoV-2 infections: 117 (31%) in Tix-Cil treated and 207 (39%) in Tix-Cil untreated patients (p = .012). In analyses adjusting for demographic, clinical, and COVID-19 exposure factors, any Tix-Cil treatment was associated with lower infection risk (OR 0.52, 95% CI 0.27-0.96, p = .039) throughout the surveillance period including when more resistant BQ.1 and BQ.1.1 subvariants had emerged (12/1/2022 onwards). Among treated patients, receiving a Tix-Cil dose was associated with substantial and sustained increase in anti-spike IgG antibody and angiotensin-converting enzyme 2 binding inhibition levels (Abbott Architect assay) that together also demonstrated association with lower infection risk (p = .042). During the full surveillance period, the frequency of infections requiring hospitalization was low overall (N = 26, 2.9% of the total cohort) and not significantly different between Tix-Cil recipients (N = 12, 3.2% of treated patients) and non-Tix-Cil recipients (N = 14, 2.6% of untreated patients) with unadjusted p = .31 for between-group difference. CONCLUSION:In a large cohort of SOT recipients, we found that Tix-Cil reduced infection risk even amidst emergent Omicron subvariants. Additionally, the extent of measurable humoral response to Tix-Cil may indicate relative effectiveness. Pre-exposure monoclonal antibody therapy may represent a strategy that will continue to offer clinical benefit for immunocompromised persons who are known to derive limited protection from vaccinations.

Abstract Background Serological testing for SARS-CoV-2 is integral for understanding prevalence of disease, tracking of infections, confirming humoral response to vaccines, and determining timing and efficacy of boosters. The study objective was to compare the specificity of serology assays in emergency department populations across the United States in 2019 (pre-pandemic) and early 2020, incorporating an automated confirmatory assay. Methods Patient specimens (n = 1954) were from 4 regions in the United States: New York, NY; Milwaukee, WI; Miami, FL; and Los Angeles, CA. Specimens were tested with SARS-CoV-2 anti-spike receptor-binding domain assays: SARS-CoV-2 IgG on the Abbott Alinity i (AdviseDx SARS-Cov-2 IgG II) and Beckman Coulter Access 2 (SARS-CoV-2 IgG II), and SARS-CoV-2 IgM on the Abbott Alinity i (AdviseDx SARS-CoV-2 IgM). Reactive samples were tested with a research use only angiotensin-converting enzyme 2 binding inhibition assay (Abbott ARCHITECT) for confirmation of SARS-CoV-2 neutralizing antibodies. Assay specificity was determined and comparisons performed with Fisher’s exact test. Results Overall SARS-CoV-2 IgG specificity was 99.28% (95% confidence interval, 98.80%–99.61%), 99.39% (98.93%–99.68%), and 99.44% (98.99%–99.72%) for SARS-CoV-2 IgG by Abbott and Beckman, and SARS-CoV-2 IgM, respectively. Overall agreement for the two IgG assays was 99.28% (range for the 4 sites: 98.21% to 100%). There were no specificity differences between assays or sites. Conclusions The specificity of the serological assays evaluated in a large, diverse emergency department population was >99% and did not vary by geographical site. A confirmatory algorithm with an automated pseudo-neutralization assay allowed testing on the same specimen while reducing the false positivity rate and increasing the value of serology screening methods.

Virus-like particle (VLP) and live virus assays were used to investigate neutralizing immunity against Delta and Omicron SARS-CoV-2 variants in 259 samples from 128 vaccinated individuals. Following Delta breakthrough infection, titers against WT rose 57-fold and 3.1-fold compared with uninfected boosted and unboosted individuals, respectively, versus only a 5.8-fold increase and 3.1-fold decrease for Omicron breakthrough infection. Among immunocompetent, unboosted patients, Delta breakthrough infections induced 10.8-fold higher titers against WT compared with Omicron (p = 0.037). Decreased antibody responses in Omicron breakthrough infections relative to Delta were potentially related to a higher proportion of asymptomatic or mild breakthrough infections (55.0% versus 28.6%, respectively), which exhibited 12.3-fold lower titers against WT compared with moderate to severe infections (p = 0.020). Following either Delta or Omicron breakthrough infection, limited variant-specific cross-neutralizing immunity was observed. These results suggest that Omicron breakthrough infections are less immunogenic than Delta, thus providing reduced protection against reinfection or infection from future variants.

Background Measuring anti-viral antibody affinity in blood plasma or serum is a rational quantitative approach to assess humoral immune response and acquired protection. Three common vaccines against SARS-CoV-2—Comirnaty developed by Pfizer/BioNTech, Spikevax developed by Moderna/NIAID, and Jcovden (previously Janssen COVID-19 Vaccine) developed by Johnson & Johnson/Janssen (J&J)—induce antibodies to a variety of immunogenic epitopes including the epitopes located in the ACE2 receptor-binding domain (RBD) of the spike protein. Blocking RBD with antibodies interferes with the binding of the virus to ACE2 thus protecting against infection. Methods We perform measurements in the serum of the recipients of Pfizer, Moderna, and J&J vaccines, and we compare the apparent affinities of vaccine-induced antibodies against the RBD of the ancestral SARS-CoV-2 virus and the Delta and Omicron variants. We use our recently published method to determine the apparent affinity of anti-spike protein antibodies directly in human serum. This involves probing antibody-antigen equilibria with a small number of antigen-coated magnetic microparticles and imaging them on a fluorescence microscope. Results Recipients of two-dose Pfizer and Moderna vaccines, as well as recipients of the single-dose J&J vaccine, develop high-affinity antibodies toward RBD derived from ancestral SARS-CoV-2. Affinities of these antibodies to Delta-RBD are approximately 10 times weaker, and even more drastically reduced (∼1000-fold) toward Omicron-RBD. Conclusions Vaccine-induced antibodies against ancestral SARS-CoV-2 RBD demonstrate ~10-fold and ~1000-fold weaker affinities toward Delta- and Omicron-RBD, respectively. Our approach offers a direct means for evaluating vaccine-induced adaptive immunity and can be helpful in designing or updating vaccines.

assessed.Gender distribution varied between sites, with 28% and 68% female graduates from RST and AZ respectively, p<0.001.(Table 1) Due in part to varied gender distribution at sites, overall research time averaged 13.9 months for men and 9.9 months for women (range 6-24 months).Women who had a child during fellowship had the least dedicated research time of all groups at a mean of 9.2 months.By graduation, trainees produced 10.9 manuscripts and 13.6 abstracts on average, with men producing 29.5 total research products compared to 17.8 for women, p=0.002.When normalized to research time, there was no significant difference between total research products of men and women.(Figure 1) Men with children before fellowship were the most productive, with a mean of 30.8 scholarly products, followed by men with no children at 22.0, and men who had children during fellowship at 21.0.Women who had children during fellowship, women with children before fellowship, and women without children produced a mean of 15.1, 16.8, and 21.3 scholarly products, respectively.There were no significant differences in research productivity between groups according to parenthood among men or women.Discussion: In our study, decreased research productivity of female compared to male fellows was accounted for by decreased research time.Personal decisions regarding training site, research tracks, and sacrifices for parental leave and caretaking likely underlie the gendered discrepancy in research time and ultimately productivity.As publications continue to mark success, further efforts are needed to expand support research opportunities for women. Mo1017

Objectives We sought to understand the demographic and clinical factors associated with variations in longitudinal antibody response following completion of two-dose regiment of BNT162b2 vaccination. Design This study is a 10-month longitudinal cohort study of healthcare workers and serially measured anti-spike protein IgG (IgG-S) antibody levels using mixed linear models to examine their associations with participant characteristics. Setting A large, multisite academic medical centre in Southern California, USA. Participants A total of 843 healthcare workers met inclusion criteria including completion of an initial two-dose course of BNT162b2 vaccination, complete clinical history and at least two blood samples for analysis. Patients had an average age of 45±13 years, were 70% female and 7% with prior SARS-CoV-2 infection. Results Vaccine-induced IgG-S levels remained in the positive range for 99.6% of individuals up to 10 months after initial two-dose vaccination. Prior SARS-CoV-2 infection was the primary correlate of sustained higher postvaccination IgG-S levels (partial R 2 =0.133), with a 1.74±0.11 SD higher IgG-S response (p<0.001). Female sex (beta 0.27±0.06, p<0.001), younger age (0.01±0.00, p<0.001) and absence of hypertension (0.17±0.08, p=0.003) were also associated with persistently higher IgG-S responses. Notably, prior SARS-CoV-2 infection augmented the associations of sex (−0.42 for male sex, p=0.08) and modified the associations of hypertension (1.17, p=0.001), such that infection-naïve individuals with hypertension had persistently lower IgG-S levels whereas prior infected individuals with hypertension exhibited higher IgG-S levels that remained augmented over time. Conclusions While the IgG-S antibody response remains in the positive range for up to 10 months following initial mRNA vaccination in most adults, determinants of sustained higher antibody levels include prior SARS-CoV-2 infection, female sex, younger age and absence of hypertension. Certain determinants of the longitudinal antibody response appear significantly modified by prior infection status. These findings offer insights regarding factors that may influence the ‘hybrid’ immunity conferred by natural infection combined with vaccination.

SARS-CoV-2 mRNA vaccines have been critical to curbing pandemic COVID-19; however, a major shortcoming has been the inability to assess levels of protection after vaccination. This study assessed serologic status of breakthrough infections in vaccinated patients at a Veterans Administration medical center from June through December 2021 during a SARS-CoV-2 delta variant wave. Breakthrough occurred mostly beyond 150 days after two-dose vaccination with a mean of 239 days. Anti-SARS-CoV-2 spike (S) IgG levels were low at 0 to 2 days postsymptoms but increased in subjects presenting thereafter. Population measurements of anti-S IgG and angiotensin converting enzyme-2 receptor (ACE2-R) binding inhibition among uninfected, vaccinated patients suggested immune decay occurred after 150 days with 62% having anti-S IgG levels at or below 1,000 AU comparable with breakthrough patients at 0 to 2 days postsymptom onset. In contrast, vaccination after resolved infection conferred robust enduring anti-S IgG levels (5,000 to >50,000 AU) with >90% ACE2-R binding inhibition. However, monoclonal antibody (MAb)-treated patients did not benefit from their prior infection suggesting impaired establishment of B cell memory. Analysis of boosted patients confirmed the benefit of a third vaccine dose with most having anti-S IgG levels above 5,000 AU with >90% ACE2-R binding inhibition, but a subset had levels <5,000 AU. Anti-S IgG levels >5,000 AU were associated with >90% ACE2-R binding inhibition and no documented breakthrough infections, whereas levels falling below 5,000 AU and approaching 1,000 AU were associated with breakthrough infections. Thus, quantitative antibody measurements may provide a means to guide vaccination intervals for the individual. IMPORTANCE Currently, clinicians have no guidance for the serologic assessment of SARS-Cov-2 postvaccination status regarding protection and risk of infection. Vaccination and boosters are administered blindly without evaluation of need or outcome at the individual level. The recent development of automated quantitative assays for anti-SARS-CoV-2 spike protein IgG antibodies permits accurate measurement of humoral immunity in standardized units. Clinical studies, such as reported here, will help establish protective antibody levels allowing identification and targeted management of poor vaccine responders and vaccinated subjects undergoing immune decay.

T-cells specifically bind antigens to induce adaptive immune responses using highly specific molecular recognition, and a diverse T-cell repertoire with expansion of antigen-specific clones can indicate robust immune responses after infection or vaccination. For patients with inflammatory bowel disease (IBD), a spectrum of chronic intestinal inflammatory diseases usually requiring immunomodulatory treatment, the T-cell response has not been well characterized. Understanding the patient factors that result in strong vaccination responses is critical to guiding vaccination schedules and identifying mechanisms of T-cell responses in IBD and other immune-mediated conditions. Here we used T-cell receptor sequencing to show that T-cell responses in an IBD cohort were influenced by demographic and immune factors, relative to a control cohort of health care workers (HCWs). Subjects were sampled at the time of SARS-CoV-2 vaccination, and longitudinally afterwards; TCR Vβ gene repertoires were sequenced and analyzed for COVID-19-specific clones. We observed significant differences in the overall strength of the T-cell response by age and vaccine type. We further stratified the T-cell response into Class-I- and Class-II-specific responses, showing that Ad26.COV2.S vector vaccine induced Class-I-biased T-cell responses, whereas mRNA vaccine types led to different responses, with mRNA-1273 vaccine inducing a more Class-I-deficient T-cell response compared to BNT162b2. Finally, we showed that these T-cell patterns were consistent with antibody levels from the same patients. Our results account for the surprising success of vaccination in nominally immuno-compromised IBD patients, while suggesting that a subset of IBD patients prone to deficiencies in T-cell response may warrant enhanced booster protocols.

Importance:Some individuals who were infected by the SARS-CoV-2 Omicron variant may have been completely unaware of their infectious status while the virus was actively transmissible. Objective:To examine awareness of infectious status among individuals during the recent Omicron variant surge in a diverse and populous urban region of Los Angeles County. Design, Setting, and Participants:This cohort study analyzed the records of adult employees and patients of an academic medical center who were enrolled in a longitudinal COVID-19 serological study in Los Angeles County, California. These participants had 2 or more serial anti-nucleocapsid IgG (IgG-N) antibody measurements at least 1 month apart, with the first occurring after the end of a regional Delta variant surge (September 15, 2021) and a subsequent one occurring after the start of a regional Omicron variant surge (December 15, 2021). Adults with evidence of new SARS-CoV-2 infection occurring during the Omicron variant surge period through May 4, 2022, were included in the present study sample. Exposures:Recent Omicron variant infection as evidenced by SARS-CoV-2 seroconversion. Main Outcomes and Measures:Awareness of recent SARS-CoV-2 infection was ascertained from review of self-reported health updates, medical records, and COVID-19 testing data. Results:Of the 210 participants (median [range] age, 51 (23-84) years; 136 women [65%]) with serological evidence of recent Omicron variant infection, 44% (92) demonstrated awareness of any recent Omicron variant infection and 56% (118) reported being unaware of their infectious status. Among those who were unaware, 10% (12 of 118) reported having had any symptoms, which they attributed to a common cold or other non-SARS-CoV-2 infection. In multivariable analyses that accounted for demographic and clinical characteristics, participants who were health care employees of the medical center were more likely than nonemployees to be aware of their recent Omicron variant infection (adjusted odds ratio, 2.46; 95% CI, 1.30-4.65). Conclusions and Relevance:Results of this study suggest that more than half of adults with recent Omicron variant infection were unaware of their infectious status and that awareness was higher among health care employees than nonemployees, yet still low overall. Unawareness may be a highly prevalent factor associated with rapid person-to-person transmission within communities.

Lay Summary T-cell and antibody responses to severe acute respiratory syndrome coronavirus 2 vaccination in inflammatory bowel disease patients are poorly correlated. T-cell responses are preserved by most biologic therapies, but augmented by anti-tumor necrosis factor (anti-TNF) treatment. While anti-TNF therapy blunts the antibody response, cellular immunity after vaccination is robust.

BACKGROUND:Serological testing for SARS-CoV-2 is integral for understanding prevalence of disease, tracking of infections, confirming humoral response to vaccines, and determining timing and efficacy of boosters. The study objective was to compare the specificity of serology assays in emergency department populations across the United States in 2019 (pre-pandemic) early 2020 incorporating an automated confirmatory assay. METHODS:Patient specimens (n = 1954) were from four regions in the United States: New York, NY; Milwaukee, WI; Miami, FL; and Los Angeles, CA. Specimens were tested with SARS-CoV-2 anti-spike receptor binding domain assays: SARS-CoV-2 IgG on the Abbott Alinity i (AdviseDx SARS-Cov-2 IgG II) and Beckman Coulter Access 2 (SARS-CoV-2 IgG II), and SARS-CoV-2 IgM on the Abbott Alinity i (AdviseDx SARS-CoV-2 IgM). Reactive samples were tested with a research use only ACE2 binding inhibition assay (Abbott ARCHITECT) for confirmation of SARS-CoV-2 neutralizing antibodies. Assay specificity was determined and comparisons performed with Fisher's Exact Test. RESULTS:Overall SARS-CoV-2 IgG specificity was 99.28% (95% confidence interval: 98.80%-99.61%), 99.39% (98.93%-99.68%), and 99.44% (98.99%-99.72%) for SARS-CoV-2 IgG by Abbott and Beckman, and SARS-CoV-2 IgM, respectively. Overall agreement for the two IgG assays was 99.28% (range for the four sites: 98.21%-100%). There were no specificity differences between assays or sites. CONCLUSIONS:The specificity of the serological assays evaluated in a large diverse emergency department population was >99% and did not vary by geographical site. A confirmatory algorithm with an automated pseudo-neutralization assay allowed testing on the same specimen while reducing the false positivity rate and increasing the value of serology screening methods.