Comparison of anti-nucleocapsid antibody assays for the detection of SARS-CoV-2 Omicron vaccine breakthroughs after various intervals since the infection.

Antibody assays with the nucleocapsid (NC) protein as the target antigen can identify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections when polymerase chain reaction (PCR) analyses are unavailable. Regarding the kinetics of NC-specific antibodies, vaccine breakthroughs with Omicron subvariants may differ from infections with the ancestral wild-type virus. Therefore, we evaluated which assays have the highest sensitivity for detecting NC-specific antibodies after various intervals since breakthrough infections with an Omicron subvariant. The study included 279 samples from vaccinated subjects who experienced PCR-confirmed Omicron breakthrough infections between 21 and 266 days before sampling. The samples were comparatively assessed with the Elecsys® Anti-SARS-CoV-2 N (Roche), the Anti-SARS-CoV-2-NCP-ELISA (Euroimmun), the recomLine SARS-CoV-2 IgG (Mikrogen), and the SARS-CoV-2 ViraChip IgG assays (Viramed). In the whole cohort, the Elecsys® Anti-SARS-CoV-2 N assay displayed the highest sensitivity (93%, p < 0.0001), followed by the recomLine SARS-CoV-2 IgG assay (70%), the SARS-CoV-2 ViraChip IgG assay (41%) and the Anti-SARS-CoV-2-NCP-ELISA (35%). Although measured antibody levels and time-dependent sensitivities differed, the extent of the antibody decrease was similar among all assays. As demonstrated by this study, manufacturer-dependent differences in the sensitivities of NC-specific antibody assays should be considered when serology is applied to link previous SARS-CoV-2 infections with potential post-COVID sequelae.

Respiratory syncytial virus surge in 2022 caused by lineages already present before the COVID-19 pandemic.

In 2022, Austria experienced a severe respiratory syncytial virus (RSV) epidemic with an earlier-than-usual start (Weeks 35/2021-45/2022) and increased numbers of pediatric patients in emergency departments. This surge came 2 years after a season with no cases detected as a result of coronavirus disease 2019 nonpharmaceutical interventions. We analyzed epidemiologic patterns and the phylodynamics of RSV based on approximately 30 800 respiratory specimens collected year-round over 10 years from ambulatory and hospitalized patients from 248 locations in Austria. Genomic surveillance and phylogenetic analysis of 186 RSV-A and 187 RSV-B partial glycoprotein sequences collected from 2018 to 2022 revealed that the 2022/2023 surge was driven by RSV-B in contrast to the surge in the 2021/2022 season that was driven by RSV-A. Whole-genome sequencing and phylodynamic analysis indicated that the RSV-B strain GB5.0.6a was the predominant genotype in the 2022/2023 season and emerged in late 2019. The results provide insight into RSV evolution and epidemiology that will be applicable to future monitoring efforts with the advent of novel vaccines and therapeutics.

Three rounds of a national external quality assessment reveal a link between disharmonic anti-SARS-CoV-2 antibody quantifications and the infection stage.

OBJECTIVES: The WHO's standardized measuring unit, "binding antibody units per milliliter (BAU/mL)," should allow the harmonization of quantitative results by different commercial Anti-SARS-CoV-2 immunoassays. However, multiple studies demonstrate inter-assay discrepancies. The antigenic changes of the Omicron variant affect the performance of Spike-specific immunoassays. This study evaluated the variation of quantitative Anti-SARS-CoV-2-Spike antibody measurements among 46, 50, and 44 laboratories in three rounds of a national external quality assessment (EQA) prior to and after the emergence of the Omicron variant in a diagnostic near-to-real-life setting. METHODS: We analyzed results reported by the EQA participant laboratories from single and sequential samples from SARS-CoV-2 convalescent, acutely infected, and vaccinated individuals, including samples obtained after primary and breakthrough infections with the Omicron variant. RESULTS: The three immunoassays most commonly used by the participants displayed a low intra-assay and inter-laboratory variation with excellent reproducibility using identical samples sent to the participants in duplicates. In contrast, the inter-assay variation was very high with all samples. Notably, the ratios of BAU/mL levels quantified by different immunoassays were not equal among all samples but differed between vaccination, past, and acute infection, including primary infection with the Omicron variant. The antibody kinetics measured in vaccinated individuals strongly depended on the applied immunoassay. CONCLUSIONS: Measured BAU/mL levels are only inter-changeable among different laboratories when the same assay was used for their assessment. Highly variable ratios of BAU/mL quantifications among different immunoassays and infection stages argue against the usage of universal inter-assay conversion factors.

Using the Medical Research Council framework for development and evaluation of complex interventions in a low resource setting to develop a theory-based treatment support intervention delivered via SMS text message to improve blood pressure control.

BACKGROUND: Several frameworks now exist to guide intervention development but there remains only limited evidence of their application to health interventions based around use of mobile phones or devices, particularly in a low-resource setting. We aimed to describe our experience of using the Medical Research Council (MRC) Framework on complex interventions to develop and evaluate an adherence support intervention for high blood pressure delivered by SMS text message. We further aimed to describe the developed intervention in line with reporting guidelines for a structured and systematic description. METHODS: We used a non-sequential and flexible approach guided by the 2008 MRC Framework for the development and evaluation of complex interventions. RESULTS: We reviewed published literature and established a multi-disciplinary expert group to guide the development process. We selected health psychology theory and behaviour change techniques that have been shown to be important in adherence and persistence with chronic medications. Semi-structured interviews and focus groups with various stakeholders identified ways in which treatment adherence could be supported and also identified key features of well-regarded messages: polite tone, credible information, contextualised, and endorsed by identifiable member of primary care facility staff. Direct and indirect user testing enabled us to refine the intervention including refining use of language and testing of interactive components. CONCLUSIONS: Our experience shows that using a formal intervention development process is feasible in a low-resource multi-lingual setting. The process enabled us to pre-test assumptions about the intervention and the evaluation process, allowing the improvement of both. Describing how a multi-component intervention was developed including standardised descriptions of content aimed to support behaviour change will enable comparison with other similar interventions and support development of new interventions. Even in low-resource settings, funders and policy-makers should provide researchers with time and resources for intervention development work and encourage evaluation of the entire design and testing process. TRIAL REGISTRATION: The trial of the intervention is registered with South African National Clinical Trials Register number (SANCTR DOH-27-1212-386; 28/12/2012); Pan Africa Trial Register (PACTR201411000724141; 14/12/2013); ClinicalTrials.gov ( NCT02019823 ; 24/12/2013).

Mobile Phone Text Messages to Support Treatment Adherence in Adults With High Blood Pressure (SMS-Text Adherence Support [StAR]): A Single-Blind, Randomized Trial.

BACKGROUND: We assessed the effect of automated treatment adherence support delivered via mobile phone short message system (SMS) text messages on blood pressure. METHODS AND RESULTS: In this pragmatic, single-blind, 3-arm, randomized trial (SMS-Text Adherence Support [StAR]) undertaken in South Africa, patients treated for high blood pressure were randomly allocated in a 1:1:1 ratio to information only, interactive SMS text messaging, or usual care. The primary outcome was change in systolic blood pressure at 12 months from baseline measured with a validated oscillometric device. All trial staff were masked to treatment allocation. Analyses were intention to treat. Between June 26, 2012, and November 23, 2012, 1372 participants were randomized to receive information-only SMS text messages (n=457), interactive SMS text messages (n=458), or usual care (n=457). Primary outcome data were available for 1256 participants (92%). At 12 months, the mean adjusted change in systolic blood pressure compared with usual care was -2.2 mm Hg (95% confidence interval, -4.4 to -0.04) with information-only SMS and -1.6 mm Hg (95% confidence interval, -3.7 to 0.6) with interactive SMS. Odds ratios for the proportion of participants with a blood pressure <140/90 mm Hg were 1.42 (95% confidence interval, 1.03-1.95) for information-only messaging and 1.41 (95% confidence interval, 1.02-1.95) for interactive messaging compared with usual care. CONCLUSIONS: In this randomized trial of an automated adherence support program delivered by SMS text message in a general outpatient population of adults with high blood pressure, we found a small reduction in systolic blood pressure control compared with usual care at 12 months. There was no evidence that an interactive intervention increased this effect. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02019823. South African National Clinical Trials Register, number SANCTR DOH-27-1212-386; Pan Africa Trial Register, number PACTR201411000724141.

Efficacy of a text messaging (SMS) based intervention for adults with hypertension: protocol for the StAR (SMS Text-message Adherence suppoRt trial) randomised controlled trial.

BACKGROUND: Interventions to support people with hypertension in attending clinics and taking their medication have potential to improve outcomes, but delivery on a wide scale and at low cost is challenging. Some trials evaluating clinical interventions using short message service (SMS) text-messaging systems have shown important outcomes, although evidence is limited. We have developed a novel SMS system integrated with clinical care for use by people with hypertension in a low-resource setting. We aim to test the efficacy of the system in improving blood pressure control and treatment adherence compared to usual care. METHODS/DESIGN: The SMS Text-message Adherence suppoRt trial (StAR) is a pragmatic individually randomised three-arm parallel group trial in adults treated for hypertension at a single primary care centre in Cape Town, South Africa. The intervention is a structured programme of clinic appointment, medication pick-up reminders, medication adherence support and hypertension-related education delivered remotely using an automated system with either informational or interactive SMS text-messages. Usual care is supplemented by infrequent non-hypertension related SMS text-messages. Participants are 1:1:1 individually randomised, to usual care or to one of the two active interventions using minimisation to dynamically adjust for gender, age, baseline systolic blood pressure, years with hypertension, and previous clinic attendance. The primary outcome is the change in mean systolic blood pressure at 12-month follow-up from baseline measured with research staff blinded to trial allocation. Secondary outcomes include the proportion of patients with 80% or more of days medication available, proportion of participants achieving a systolic blood pressure less than 140 mmHg and a diastolic blood pressure less than 90 mmHg, hospital admissions, health status, retention in clinical care, satisfaction with treatment and care, and patient related quality of life. Anonymised demographic data are collected on non-participants. DISCUSSION: The StAR trial uses a novel, low cost system based on widely available mobile phone technology to deliver the SMS-based intervention, manage communication with patients, and measure clinically relevant outcomes. The results will inform implementation and wider use of mobile phone based interventions for health care delivery in a low-resource setting. TRIAL REGISTRATION: NCT02019823.

Measuring Variant-Specific Neutralizing Antibody Profiles after Bivalent SARS-CoV-2 Vaccinations Using a Multivariant Surrogate Virus Neutralization Microarray.

The capability of antibodies to neutralize different SARS-CoV-2 variants varies among individuals depending on the previous exposure to wild-type or Omicron-specific immunogens by mono- or bivalent vaccinations or infections. Such profiles of neutralizing antibodies (nAbs) usually have to be assessed via laborious live-virus neutralization tests (NTs). We therefore analyzed whether a novel multivariant surrogate-virus neutralization test (sVNT) (adapted from a commercial microarray) that quantifies the antibody-mediated inhibition between the receptor angiotensin-converting enzyme 2 (ACE2) and variant-specific receptor-binding domains (RBDs) can assess the neutralizing activity against the SARS-CoV-2 wild-type, and Delta Omicron BA.1, BA.2, and BA.5 subvariants after a booster with Omicron-adapted bivalent vaccines in a manner similar to live-virus NTs. Indeed, by using the live-virus NTs as a reference, we found a significant correlation between the variant-specific NT titers and levels of ACE2-RBD binding inhibition (p < 0.0001, r ≤ 0.78 respectively). Furthermore, the sVNTs identified higher inhibition values against BA.5 and BA.1 in individuals vaccinated with Omicron-adapted vaccines than in those with monovalent wild-type vaccines. Our data thus demonstrate the ability of sVNTs to detect variant-specific nAbs following a booster with bivalent vaccines.

A Multivariant Surrogate Virus Neutralization Test Demonstrates Distinct SARS-CoV-2-Specific Antibody Responses in People Living with HIV after a Fourth Monovalent mRNA Vaccination or an Omicron Breakthrough Infection.

While neutralizing antibodies (nAbs) induced by monovalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations are primarily directed against the wildtype (WT), subsequent exposure to the Omicron variants may increase the breadth of the antibodies' cross-neutralizing activity. Here, we analyzed the impact of an Omicron breakthrough infection (BTI) or a fourth monovalent mRNA vaccination on nAb profiles in people living with human immunodeficiency virus (PLWH). Using a multivariant surrogate virus neutralization test (sVNT), we quantified nAbs in 36 three-times vaccinated PLWH, of whom 9 acquired a serologically confirmed Omicron BTI, 8 received a fourth vaccine dose, and 19 were neither infected nor additionally vaccinated. While nAbs against WT and Delta increased after the BTI and a fourth vaccination, a significant increase against BA.1, BA.2, and BA.5 was only observed after the BTI. However, there was no significant difference in nAb concentrations between the samples obtained after the BTI and fourth vaccination. In contrast, nAb levels were significantly lower in PLWH, who were neither infected nor additionally vaccinated after three vaccinations. Thus, our study demonstrates the suitability of a multivariant sVNT to assess hybrid humoral immunity after Omicron BTIs in PLWH vaccinated against SARS-CoV-2.

Temporal decline in serum PFAS concentrations among metropolitan firefighters: Longitudinal study on post-exposure changes following PFAS foam cessation.

Firefighters are at a high risk of exposure to per- and polyfluoroalkyl substances (PFAS) due to their frequent use of PFAS-containing foams in training and emergency situations. This longitudinal study aimed to investigate the changes in serum PFAS levels among firefighters following cessation of their exposure to PFAS-containing foams. The study involved 130 firefighters from the South Australian Metropolitan Fire Services (SAMFS), and serum samples were collected at two time points: baseline in 2018-19 and follow-up in 2021-22. Along with the collection of samples, a survey questionnaire was administered to gather information on firefighters' employment and demographic characteristics. Regression models were employed to assess the association between these factors and the outcome variable (annual percentage change in serum PFAS concentration). The results indicated a decline in serum PFAS concentrations over time, with the main contaminants being perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorooctanoic acid (PFOA). The median and Interquartile Range (IQR) of total PFAS (∑PFAS) concentration reduced from 21.5 ng/ml (IQR: 11 to 53 ng/ml) at baseline to 15 ng/ml (IQR: 8 to 33 ng/ml) at follow-up. On average, there was an annual reduction of 13%, 7%, and 4.4% in serum concentrations of PFOS, PFHxS, and PFOA, respectively. Firefighters under the age of 55, those who used PFAS in the past ten years, or those who had little to no frequency of PFAS exposure in their previous employment, encountered a significantly higher annual percentage reduction (P < 0.05) in both ∑PFAS and PFOS concentrations. None of the independent variables analysed could significantly predict the annual percentage change in PFOA and PFHxS. This study provides evidence for a declining temporal trend in serum PFAS concentrations among metropolitan firefighters following workplace interventions that involved the removal of PFAS-containing foams.

Breakthrough infections with SARS-CoV-2 omicron efficiently boost antibodies from previous BNT162b2 vaccinations.

Objective: To investigate whether SARS-CoV-2 omicron breakthrough infection in individuals after three doses of wildtype-based BNT162b2 increases antibody levels measured by a commercially available wildtype-based immunoassay. Methods: 16 of 21 individuals in a BNT162b2 vaccination cohort (recruited 129 [129-135] days after dose 3) experienced a breakthrough infection (BTI) between March and September 2022. Antibodies to the receptor binding domain (RBP) of the spike protein (Anti-S) were quantified using the wildtype-based Elecsys SARS-CoV-2 S assay (Roche). Antibody responses of triple vaccinated BTI cases were compared to triple vaccinated individuals without breakthrough infection and to 16 matched individuals after primary omicron infection. Results: In the 16 individuals with primary Omicron infection, the anti-S assay returned only very low results (2.25 [0.61-5.80] U/mL). However, in individuals with BTI, Anti-S levels rose from 7,135 [5,870-17,470] U/mL to 21,705 (7,750-46,137.5) U/mL. At the same time, Anti-S concentrations decreased from 9,120 [7,480-13,480] U/mL to 3,830 (2,390-4,220) U/mL in those 5 of 21 vaccinated only. Conclusions: Our data suggest that breakthrough infection with omicron can efficiently boost wild-type antibodies in individuals vaccinated with wild-type BNT162b2.

Prediction of humoral and cellular immune response to COVID-19 mRNA vaccination by TTV load in kidney transplant recipients and hemodialysis patients.

BACKGROUND: Immunosuppressed individuals such as kidney transplant recipients (KTR) and hemodialysis patients (DP) show impaired immune responses to COVID-19 vaccination. Plasma Torque Teno Virus (TTV) DNA load is used as surrogate for the individual degree of immunosuppression. We now assessed the association of TTV load at time of COVID-19 vaccination with humoral and cellular immune response rates to vaccination in KTR, DP, and healthy medical personnel (MP). METHODS: A total of 100 KTR, 115 DP and 54 MP were included. All were SARS-CoV-2 seronegative at the time of vaccination with either BNT162b2 or mRNA-1273. Plasma TTV loads were assessed at the time of first vaccination. After two-dose vaccination, seroconversion (de novo detection of SARS-CoV-2 S1-IgA and/or IgG) was determined. In addition, cellular responses as assessed by interferon γ release and neutralizing antibodies were assessed in a subset of participants. ROC analyses were performed to define TTV load cut-offs predicting specific immune responses to vaccination. RESULTS: Plasma TTV loads at the time of first vaccination were negatively associated with seroconversion after two-dose vaccination in KTR (OR 0.87, 95% CI 0.76-0.99). TTV loads were significantly lower in KTR who developed humoral and cellular immune responses to vaccination compared to non-responders (p = 0.0411 and 0.0030, respectively). Of patients with TTV loads above 106 copies/ml, none developed cellular immune responses against SARS-CoV-2, and only 2 of 17 (12%) seroconverted in response to vaccination. CONCLUSION: Plasma TTV loads at the time of first vaccination in immunosuppressed individuals may be useful to predict individual vaccine-specific immune responses.

Bivalent COVID-19 mRNA booster vaccination (BA.1 or BA.4/BA.5) increases neutralization of matched Omicron variants.

We report SARS-CoV-2 neutralizing antibody titers in sera of triple-vaccinated individuals who received a booster dose of an original monovalent or a bivalent BA.1- or BA.4/BA.5-adapted vaccine or had a breakthrough infection with Omicron variants BA.1, BA.2 or BA.4/BA.5. A bivalent BA.4/BA.5 booster or Omicron-breakthrough infection induced increased Omicron-neutralization titers compared with the monovalent booster. The XBB.1.5 variant effectively evaded neutralizing-antibody responses elicited by current vaccines and/or infection with previous variants.

Comprehensive Comparison of Seven SARS-CoV-2-Specific Surrogate Virus Neutralization and Anti-Spike IgG Antibody Assays Using a Live-Virus Neutralization Assay as a Reference.

Neutralizing antibodies (nAbs) are considered a valuable marker for measuring humoral immunity against SARS-CoV-2. However, live-virus neutralization tests (NTs) require high-biosafety-level laboratories and are time-consuming. Therefore, surrogate virus neutralization tests (sVNTs) have been widely applied, but unlike most anti-spike (S) antibody assays, NTs and sVNTs are not harmonized, requiring further evaluation and comparative analyses. This study compared seven commercial sVNTs and anti-S-antibody assays with a live-virus NT as a reference, using a panel of 720 single and longitudinal serum samples from 666 convalescent patients after SARS-CoV-2 infection. The sensitivity of these assays for detecting antibodies ranged from 48 to 94% after PCR-confirmed infection and from 56% to 100% relative to positivity in the in-house live-virus NT. Furthermore, we performed receiver operating characteristic (ROC) curve analyses to determine which immunoassays were most suitable for assessing nAb titers exceeding a specific cutoff (NT titer, ≥80) and found that the NeutraLISA and the cPass assays reached the highest area under the curve (AUC), exceeding 0.91. In addition, when the assays were compared for their correlation with nAb kinetics over time in a set of longitudinal samples, the extent of the measured decrease of nAbs after infection varied widely among the evaluated immunoassays. Finally, in vaccinated convalescent patients, high titers of nAbs exceeded the upper limit of the evaluated assays' quantification ranges. Based on data from this study, we conclude that commercial immunoassays are acceptable substitutes for live-virus NTs, particularly when additional adapted cutoffs are employed to detect nAbs beyond a specific threshold titer. IMPORTANCE While the measurement of neutralizing antibodies is considered a valuable tool in assessing protection against SARS-CoV-2, neutralization tests employ live-virus isolates and cell culture, requiring advanced laboratory biosafety levels. Including a large sample panel (over 700 samples), this study provides adapted cutoff values calculated for seven commercial immunoassays (including four surrogate neutralization assays and a protein-based microarray) that robustly correlate with specific titers of neutralizing antibodies.

A Multivariant Surrogate Neutralization Assay Identifies Variant-Specific Neutralizing Antibody Profiles in Primary SARS-CoV-2 Omicron Infection.

Primary infection with the Omicron variant of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) can be serologically identified with distinct profiles of neutralizing antibodies (nAbs), as indicated by high titers against the Omicron variant and low titers against the ancestral wild-type (WT). Here, we evaluated whether a novel surrogate virus neutralization assay (sVNT) that simultaneously quantifies the binding inhibition of angiotensin-converting enzyme 2 (ACE2) to the proteins of the WT- and Omicron-specific receptor-binding domains (RBDs) can identify nAb profiles after primary Omicron infection with accuracy similar to that of variant-specific live-virus neutralization tests (NTs). Therefore, we comparatively tested 205 samples from individuals after primary infection with the Omicron variant and the WT, and vaccinated subjects with or without Omicron breakthrough infections. Indeed, variant-specific RBD-ACE2 binding inhibition levels significantly correlated with respective NT titers (p < 0.0001, Spearman's r = 0.92 and r = 0.80 for WT and Omicron, respectively). In addition, samples from individuals after primary Omicron infection were securely identified with the sVNT according to their distinctive nAb profiles (area under the curve = 0.99; sensitivity: 97.2%; specificity: 97.84%). Thus, when laborious live-virus NTs are not feasible, the novel sVNT we evaluated in this study may serve as an acceptable substitute for the serological identification of individuals with primary Omicron infection.

Food grown on fire stations as a potential pathway for firefighters' exposure to per- and poly-fluoroalkyl substances (PFAS).

Human exposure to per- and polyfluoroalkyl substances also known as PFAS is an ongoing occupational and environmental health problem. This study seeks to characterise multiple pathways for firefighters' exposure to PFAS. PFAS were analysed in 688 environmental samples such as eggs, fruits, vegetables, dust, soil, surface swabs, appliance washes and water obtained from fire stations. Relevant exposure pathways were identified and daily intake levels were estimated using PFAS concentrations and exposure factors relevant to firefighters. Five PFAS including perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), 6:2 fluorotelomer sulfonate (6:2 FTS), and 8:2 fluorotelomer sulfonic acid (8:2 FTS) were frequently detected in the samples. Based on the median concentrations in each sample type, PFOS was the most abundant contaminant in eggs (80%), fruits (52%), dust (81%), surface swab (66%), soil (83%) and appliance wash (31%) samples. On the other hand, PFHxS was most abundant in vegetables (77%) and 8:2 FTS in water (58%). The intake estimation results show that dietary exposure from ingestion of foods produced on fire stations was the predominant exposure pathway, representing 82% and 62% of firefighters' total PFAS intake under typical and worst-case exposure scenarios, respectively. Incidental ingestion and dermal absorption of PFAS in dust contributed 15% for typical and 34% for worst-case exposure scenarios. The relative contributions from incidental ingestion and dermal absorption of PFAS in soil and appliance washes were insignificant. Overall, the study identifies multiple exposure pathways relevant to career firefighters including consumption of food grown on fire stations, which has not previously been recognised within the occupational exposure context. The results suggest exposure control strategies that target foods produced on fire stations could substantially reduce firefighters' exposure to PFAS.

Different Neutralization Profiles After Primary SARS-CoV-2 Omicron BA.1 and BA.2 Infections.

Background and Methods: The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) Omicron (B.1.1.529) variant is the antigenically most distinct variant to date. As the heavily mutated spike protein enables neutralization escape, we studied serum-neutralizing activities of naïve and vaccinated individuals after Omicron BA.1 or BA.2 sub-lineage infections in live virus neutralization tests with Omicron BA.1, Omicron BA.2, wildtype (WT, B1.1), and Delta (B.1.617.2) strains. Serum samples obtained after WT infections and three-dose mRNA vaccinations with and without prior infection were included as controls. Results: Primary BA.1 infections yielded reduced neutralizing antibody levels against WT, Delta, and Omicron BA.2, while samples from BA.2-infected individuals showed almost no cross-neutralization against the other variants. Serum neutralization of Omicron BA.1 and BA.2 variants was detectable after three-dose mRNA vaccinations, but with reduced titers. Vaccination-breakthrough infections with either Omicron BA.1 or BA.2, however, generated equal cross-neutralizing antibody levels against all SARS-CoV-2 variants tested. Conclusions: Our study demonstrates that although Omicron variants are able to enhance cross-neutralizing antibody levels in pre-immune individuals, primary infections with BA.1 or BA.2 induced mostly variant-specific neutralizing antibodies, emphasizing the differently shaped humoral immunity induced by the two Omicron variants. These data thus contribute substantially to the understanding of antibody responses induced by primary Omicron infections or multiple exposures to different SARS-CoV-2 variants and are of particular importance for developing vaccination strategies in the light of future emerging variants.

Reduced Sensitivity of Commercial Spike-Specific Antibody Assays after Primary Infection with the SARS-CoV-2 Omicron Variant.

The SARS-CoV-2 Omicron variant is characterized by substantial changes in the antigenic structure of the Spike (S) protein. Therefore, antibodies induced by primary Omicron infection lack neutralizing activity against earlier variants. In this study, we analyzed whether these antigenic changes impact the sensitivity of commercial anti-SARS-CoV-2 antibody assays. Sera from 37 unvaccinated, convalescent individuals after putative primary Omicron infection were tested with a panel of 20 commercial anti-SARS-CoV-2 immunoassays. As controls, we used samples from 43 individuals after primary infection with the SARS-CoV-2 ancestral wild-type strain. In addition, variant-specific live-virus neutralization assays were used as a reference for the presence of SARS-CoV-2-specific antibodies in the samples. Notably, in Omicron convalescents, there was a statistically significant reduction in the sensitivity of all antibody assays containing S or its receptor-binding-domain (RBD) as antigens. Furthermore, antibody levels quantified by these assays displayed a weaker correlation with Omicron-specific neutralizing antibody titers than with those against the wild type. In contrast, the sensitivity of nucleocapsid-protein-specific immunoassays was similar in wild-type and Omicron-infected subjects. In summary, the antigenic changes in the Omicron S lead to reduced immunoreactivity in the current commercial S- and RBD-specific antibody assays, impairing their diagnostic performance. IMPORTANCE This study demonstrates that the antigenic changes of the SARS-CoV-2 Omicron variant affect test results from commercial Spike- and RBD-specific antibody assays, significantly diminishing their sensitivities and diagnostic abilities to assess neutralizing antibodies.

Internalizing symptoms linking youths' maltreatment and delinquent behavior.

This study examines internalizing mental health symptoms (depression and posttraumatic stress disorder) as potential intervening factors in the relationship between maltreatment and delinquency using data from the National Survey for Child and Adolescent Well-Being (N = 1179). Significant mediating effects indicated that youth at greater risk of maltreatment experienced higher levels of internalizing symptoms that result in increased risk for delinquent behavior, although longitudinal effects were not supported. These findings highlight internalizing mental health symptoms as an important factor to address in treating victimized children at risk of future delinquency. Implications for child welfare service provision are discussed.

Substance use and abuse trajectories across adolescence: a latent trajectory analysis of a community-recruited sample of girls.

We used data from a school-based study of 496 adolescent girls to identify qualitatively distinct substance use and substance abuse developmental trajectory groups and tested whether the problematic groups differed from the non-problematic groups on baseline and outcome validation variables. Results identified four substance use groups (late users, normative users, late-heavy users, early-heavy users) and four substance abuse groups (non-abusers, moderate-escalating abusers, moderate decreasing abusers, adolescent-limited heavy abusers). Problematic substance use and abuse trajectory groups, relative to non-problematic groups, showed elevations in baseline validation variables (age 14 delinquency, depressive symptoms, negative affectivity, parental support deficits, body dissatisfaction) and outcome validation variables (age 20 delinquency, depressive symptoms, social impairment, legal problems, school dropout, and substance abuse diagnosis), providing partial validation of this trajectory model.

Fundamental sex differences in morphine withdrawal-induced neuronal plasticity.

ABSTRACT: Withdrawal from systemic opioids can induce long-term potentiation (LTP) at spinal C-fibre synapses ("opioid-withdrawal-LTP"). This is considered to be a cellular mechanism underlying opioid withdrawal-induced hyperalgesia, which is a major symptom of the opioid withdrawal syndrome. Opioids can activate glial cells leading to the release of proinflammatory mediators. These may influence synaptic plasticity and could thus contribute to opioid-withdrawal-LTP. Here, we report a sexual dimorphism in the mechanisms of morphine-withdrawal-LTP in adult rats. We recorded C-fibre-evoked field potentials in the spinal cord dorsal horn from deeply anaesthetised male and female rats. In both sexes, we induced a robust LTP through withdrawal from systemic morphine infusion (8 mg·kg-1 bolus, followed by a 1-hour infusion at a rate of 14 mg·kg-1·h-1). This paradigm also induced mechanical hypersensitivity of similar magnitude in both sexes. In male rats, systemic but not spinal application of (-)naloxone blocked the induction of morphine-withdrawal-LTP, suggesting the involvement of descending pronociceptive pathways. Furthermore, we showed that in male rats, the induction of morphine-withdrawal-LTP required the activation of spinal astrocytes and the release of the proinflammatory cytokines tumour necrosis factor and interleukin-1. In striking contrast, in female rats, the induction of morphine-withdrawal-LTP was independent of spinal glial cells. Instead, blocking µ-opioid receptors in the spinal cord was sufficient to prevent a facilitation of synaptic strength. Our study revealed fundamental sex differences in the mechanisms underlying morphine-withdrawal-LTP at C-fibre synapses: supraspinal and gliogenic mechanisms in males and a spinal, glial cell-independent mechanism in females.