Anti-nucleocapsid Antibodies Research Articles

The Trajectory of Antibody Responses One Year Following SARS-CoV-2 Infection among Indigenous Individuals in the Southwest United States

SARS-CoV-2 antibody kinetics based on immunologic history is not fully understood. We analyzed anti-spike and anti-nucleocapsid antibody responses following acute infection in a cohort of Indigenous persons. The models of peak concentrations and decay rates estimated that one year after infection, participants would serorevert for anti-nucleocapsid antibodies and remain seropositive for anti-spike antibodies. The peak anti-spike concentrations were higher for individuals vaccinated prior to infection, but the decay rates were similar across immunologic status groups. Children had significantly lower peak anti-spike concentrations than adults. This study affirms the importance of continued vaccination to maintain high levels of immunity in the face of waning immunity.

B-087 Sars-cov-2 Nt Chip test performance: a novel microarray-based enzymatic immunoassay for in vitro identification of neutralizing antibodies against emerging variants

Abstract Background The COVID-19 pandemic has created a need for reliable and adaptable diagnostic tools to detect exposure and neutralizing antibodies to emerging SARS-CoV-2 variants. To address this need, we evaluated the performance of the SARS-CoV-2 NT Chip Test, an ELISA-like immunoblot assay that incorporates a customizable panel of purified antigens from the variants of interest. This assay detects antibodies that neutralize the interaction between the receptor-binding domain (RBD) of the Wuhan strain and the Omicron BA1 variant with the cellular ACE-2 receptor and provides a marker of prior infection through the nucleocapsid protein. Methods We analyzed 73 clinical samples from six distinct groups: GROUP 1: Pre-pandemic samples (33); GROUP 2: Samples from children naive to Wuhan and infected with the Omicron variant (10); GROUP 3: Samples from individuals infected only with the original Wuhan strain (10); GROUP 4: Samples from individuals vaccinated and/or infected with the Wuhan strain and the Omicron variant (10); GROUP 5: Samples collected from individuals with 0-2 days after Omicron BA.1 infection (5) and GROUP 6: Samples collected from the same individuals 10 days after Omicron BA.1 infection (5). Evaluation utilized a proprietary non-numerical (qualitative) validation spreadsheet. Performance metrics included sensitivity, specificity, observed agreement (≥90%), and kappa index (≥0.70). Results were compared against the manufacturer's validation using the PRNT viral neutralization assay. Results Our comparative evaluation showed the following results for each parameter: 1) Wuhan neutralizing antibodies (sensitivity and specificity of 92%, agreement of 92%, and kappa index of 0.84); 2) Omicron neutralizing antibodies (sensitivity and specificity of 100%, agreement of 100%, and kappa index of 1.00); 3) Anti-nucleocapsid antibodies (sensitivity of 97%, specificity of 98%, agreement of 97%, and kappa index of 0.94). Three samples from GROUP 1 showed positive results for Wuhan RBD and one for Nucleocapsid, all close to the cutoff value. Four samples from GROUP 2 showed positive results for Wuhan RBD, which may be attributed to maternal antibodies. Three samples from GROUP 3 and three samples from GROUP 4, showed negative results for nucleocapsid, agreeing with the manufacturer's validation. Samples from GROUP 5 and GROUP 6 showed expected results, with Omicron RDB negative in GROUP 5, becoming positive in GROUP 6. Conclusions The test showed excellent performance in the verification of the three parameters in the populations studied, being approved in our laboratory. Due to its ability to incorporate antigens from emerging variants, it enables sensitive tracking of changes in neutralizing antibody profiles over time. The automated and customizable nature of the test provides an important tool for both public health epidemiological studies, monitoring changes in humoral immunity as this virus evolves, and for individual diagnostics, revealing the level of humoral protection of a patient against circulating strains in a timely manner to guide care. Although further studies are still warranted, the assay's ability to map evolving strain-specific serological immunity may offer valuable insights.

Anti-SARS-CoV-2 Nucleocapsid Antibody Positivity Three Years after COVID-19.

The accurate identification of individuals without prior infection with severe acute respiratory syndrome coronavirus 2 is pivotal for seroepidemiological studies and vaccine trials. Owing to widespread vaccination against coronavirus disease 2019 (COVID-19), the anti-nucleocapsid antibody continues to serve as a valuable marker for individuals without a history of COVID-19. This study aimed to comprehensively assess anti-nucleocapsid antibody positivity using diverse commercial and in-house immunoassays among individuals who contracted COVID-19 more than three years earlier. We enrolled 44 participants with laboratory-confirmed COVID-19 between January and May 2020 from the Seoul National University Hospital and its community treatment centers. The results showed anti-nucleocapsid antibody positivity ranging from 45.5% to 87.9%, depending on the immunoassay. This study highlights the importance of considering the limited anti-nucleocapsid antibody positivity in individuals, with a history of distant COVID-19, in seroepidemiological or vaccine research.

Understanding the Omicron Variant Impact in Healthcare Workers: Insights from the Prospective COVID-19 Post-Immunization Serological Cohort in Munich (KoCo-Impf) on Risk Factors for Breakthrough and Reinfections.

This study analyzes immune responses to SARS-CoV-2 vaccination and infection, including asymptomatic cases, focusing on infection risks during the Omicron wave, particularly among high-risk healthcare workers. In the KoCo-Impf study, we monitored 6088 vaccinated participants in Munich aged 18 and above. From 13 May to 31 July 2022, 2351 participants were follow-uped. Logistic regression models evaluated primary, secondary, and breakthrough infections (BTIs). Roche Elecsys® Anti-SARS-CoV-2 assays detected prior infections (via anti-Nucleocapsid antibodies) and assessed vaccination/infection impact (via anti-Spike antibodies) using dried blood spots. Our findings revealed an anti-Nucleocapsid seroprevalence of 44.1%. BTIs occurred in 38.8% of participants, with reinfections in 48.0%. Follow-up participation was inversely associated with current smoking and non-vaccination, while significantly increasing with age and receipt of three vaccine doses. Larger household sizes and younger age increased infection risks, whereas multiple vaccinations and older age reduced them. Household size and specific institutional subgroups were risk factors for BTIs. The anti-Nucleocapsid value prior to the second infection was significantly associated with reinfection risk. Institutional subgroups influenced all models, underscoring the importance of tailored outbreak responses. The KoCo-Impf study underscores the importance of vaccination, demographic factors, and institutional settings in understanding SARS-CoV-2 infection risks during the Omicron wave.

Association between humoral serological markers levels and risk of SARS-CoV-2 infection after the primary COVID-19 vaccine course among ANRS0001S COV-POPART cohort participants

BackgroundWe assessed the prognostic value of serological humoral markers measured one month after the last dose of the primary COVID-19 vaccine course for predicting the risk of severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 infection over the following six months in specific populations.MethodsANRS0001SCOV-POPART is a French nationwide multicenter prospective observational cohort study assessing the immune response to Covid-19 vaccines routinely administered to 11 subgroups of patients with chronic disease and a control group. Participants from the ANRS0001S COV-POPART were included if they received at least two doses of Covid-19 vaccine for the primary vaccine course, had measurements of anti-Spike, anti-receptor binding domain (RBD) IgG-specific or neutralizing antibodies one month after the end of the primary vaccine course, without being infected by SARS-CoV-2 before the measurement. SARS-CoV-2 infections defined by a positive PCR/antigenic test or seroconversion to detectable anti nucleocapsid antibodies were evaluated until the first COVID-19 booster injection. Cox proportional hazards models taking into account interval-censored data were implemented to estimate the association between each antibody level and the risk of SARS-CoV-2 infection. Predictive performances were evaluated by the area under the receiving operating characteristic curve (AUROC).ResultsTwo thousand five hundred seventy adults from a specific population and 1,123 from the control group were included. The cumulative probabilities of SARS-CoV-2 infections at five months after serological measurement were 6.0% 95% confidence interval: [5.0; 7.9] and 10.1% 95% confidence interval: [8.3; 11.9], respectively. Higher levels of anti-Spike IgG antibody were associated with a lower risk of SARS-CoV-2 infections in the control group, but not in the specific populations. Among the specific populations, AUROC were 74.5%, 74.9%, and 72.4% for anti-Spike IgG, anti-RBD IgG, and neutralizing antibodies, respectively. AUROC were superior in the specific populations, 82.0%, 81.2%, and 81.4% for anti-Spike IgG, anti-RBD IgG, and neutralizing antibodies, respectively.ConclusionsVaccine-induced antibody response after the primary course of Covid-19 infection only moderately discriminated between participants developing a SARS-CoV-2 infection during the Omicron wave.Trial registrationNCT04824651 (first posted: 2021-04-01).

Dynamics of anti-SARS-CoV-2 antibodies in the Albanian population: Impact of infection- and vaccine-induced immunity during the COVID-19 pandemic

ObjectivesUnderstanding immune response dynamics during the COVID-19 pandemic is crucial for optimizing future vaccine strategies. This study investigated the infection- and vaccine-induced SARS-CoV-2 antibody responses in the Albanian population from August 2021 to August 2022. MethodsThis used a cross-sectional approach, analyzing two independent, randomly selected population samples over 1 year. Participants’ demographic, health, vaccination, and COVID-19 data were collected, with blood samples assessed via enzyme linked immunosorbent assay for immunoglobulin G class anti-spike and anti-nucleocapsid antibodies. ResultsBy August 2022, all individuals receiving one vaccine dose achieved antibody levels comparable to those receiving two doses (median 7.71 index ratio [IR] vs 7.00 IR). In August 2021, those with previous COVID-19 infection receiving one vaccine dose showed median anti-spike immunoglobulin G levels of 7.22 IR compared with 4.84 IR in those without previous infection receiving two doses. However, individuals aged ≥61 years required two vaccine doses to achieve similar immune responses as younger individuals with one dose. ConclusionsThese findings underscore the importance of hybrid immunity, suggesting one vaccine dose may suffice for individuals with previous COVID-19 infection, whereas older adults require additional doses for optimal protection. This study provides insights into humoral immune response dynamics, which is crucial for refining COVID-19 vaccination strategies in middle-income countries with low vaccination coverage and high infection rates.

Transfusion safety concerns during the COVID-19 pandemic in Taiwan: Altered by evolving control strategies

BackgroundIn 2022, the SARS-CoV-2 Omicron surge affected 8.8 million people in Taiwan. This study delves into how the transition from containment to mitigation strategies in COVID-19 control has altered concerns regarding transfusion safety. MethodsBlood donations during 2020–2022 in Taiwan were included. Donation details and post-donation information (PDI) were retrieved to assess donation fluctuations and incidences of various PDI. The main effects of PDI reporting were assessed using chi-square test and logistic regression. Additionally, from April to August 2022, we collected disease information from COVID-19 donors, and tested their repository specimens for SARS-CoV-2 RNA and antibodies. ResultsBefore 2022, when containment measures were in place, only 8 blood donors with COVID-19 reported PDI. However, by mid-2021, there was a significant decrease in blood donations. In 2022, with mitigation strategies implemented, a total of 3483 donations reported COVID-19 PDI. The incidence of all cause PDI increased from 10.5 per 10,000 donations in 2020–2021 to 29.9 per 10,000 in 2022, with nearly 70% of PDI being related to COVID-19. Female donors reported more PDI events. Additionally, the incidence significantly decreased with age. A total of 1148 repository specimens from COVID-19 donor were tested, revealing no detection of SARS-CoV-2 RNA. The seroprevalence rates of anti-nucleocapsid(N) and anti-spike(S) antibodies were 0.61% and 98.4%, respectively. ConclusionTransfusion safety concerns in Taiwan progressed alongside the evolution of control strategies, with a one-year delay following the pandemic started. The absence of RNAemia among COVID-19 donors indicates that precautionary measures were commensurate with the risk.

Interim safety and immunogenicity analysis of the EuCorVac-19 COVID-19 vaccine in a Phase 3 randomized, observer-blind, immunobridging trial in the Philippines.

EuCorVac-19 (ECV-19) is a recombinant receptor binding domain (RBD) COVID-19 vaccine that displays the RBD (derived from the SARS-CoV-2 Wuhan strain) on immunogenic liposomes. This study compares the safety and immunogenicity of ECV-19 to the COVISHIELDTM (CS) adenoviral-vectored vaccine. Interim analysis is presented of a randomized, observer-blind, immunobridging Phase 3 trial in the Philippines in 2600 subjects, with treatment and biospecimen collection between October 2022 and January 2023. Healthy male and female adults who received investigational vaccines were 18 years and older, and randomly assigned to ECV-19 (n = 2004) or CS (n = 596) groups. Immunization followed a two-injection, intramuscular regimen with 4 weeks between prime and boost vaccination. Safety endpoints were assessed in all participants and immunogenicity analysis was carried out in a subset (n = 585 in ECV-19 and n = 290 in CS groups). The primary immunological endpoints were superiority of neutralizing antibody response, as well as noninferiority in seroresponse rate (defined as a 4-fold increase in RBD antibody titers from baseline). After prime vaccination, ECV-19 had a lower incidence of local solicited adverse events (AEs) (12.0% vs. 15.8%, p < 0.01), and solicited systemic AEs (13.1 vs. 17.4%, p < 0.01) relative to CS. After the second injection, both ECV-19 and CS had lower overall solicited AEs (7.8% vs. 7.6%). For immunological assessment, 98% of participants had prior COVID-19 exposure (based on the presence of anti-nucleocapsid antibodies) at the time of the initial immunization, without differing baseline antibody levels or microneutralization (MN) titers against the Wuhan strain in the two groups. After prime vaccination, ECV-19 induced higher anti-RBD IgG relative to CS (1,464 vs. 355 BAU/mL, p < 0.001) and higher neutralizing antibody response (1,303 vs. 494 MN titer, p < 0.001). After boost vaccination, ECV-19 and CS maintained those levels of anti-RBD IgG (1367 vs. 344 BAU/mL, p < 0.001) and neutralizing antibodies (1128 vs. 469 MN titer, p < 0.001). ECV-19 also elicited antibodies that better neutralized the Omicron variant, compared to CS (763 vs. 373 MN titer, p < 0.001). Women displayed higher responses to both vaccines than men. The ECV-19 group had a greater seroresponse rate compared to CS (83% vs. 30%, p < 0.001). In summary, both ECV-19 and CS had favorable safety profiles, with ECV-19 showing diminished local and systemic solicited AE after prime immunization. ECV-19 had significantly greater immunogenicity in terms of anti-RBD IgG, neutralizing antibodies, and seroresponse rate. These data establish a relatively favorable safety and immunogenicity profile for ECV-19. The trial is registered on ClinicalTrials.gov (NCT05572879).

SARS-COV-2 breakthrough infection and its covariates among healthcare providers of a hospital in Bangladesh during the omicron wave

IntroductionBreakthrough infection by SARS-COV-2 virus among vaccinated individuals has been reported from all over the world and it has created a substantial challenge in designing strategies to live with the virus in the post-pandemic era. Factors affecting the extent and nature of breakthrough infection are still not fully understood and those are known to vary depending on host and agent factors. Health Care Workers (HCWs), especially in hospital settings, are front-liners in combating the epidemic and, consequently, they are more vulnerable to breakthrough infection by SARS-COV-2. Like most of the countries of the world, Bangladesh went through several waves of COVID-19 and the last (3rd wave) was the widespread Omicron wave during the winter of 2022. HCWs in Bangladesh have been disproportionately affected by the virus. Under this context, the aim of the present study was to explore breakthrough infection (BTI) and its host-related covariates among HCWs of a COVID-dedicated city-based hospital during the Omicron wave in Bangladesh. Materials and methodsAn observational cross-sectional study was conducted on 267 HCWs of the Narayanganj Tertiary (300-bed) hospital during February–March 2022 which coincided with the terminal part of the 3rd wave. Data were collected by trained Field Assistants using Interviewer-administered Data Collection Forms with Questionnaires as instruments. Previous COVID-19 status (any time after the onset of the pandemic and within last 3 months) was explored by the history of specific symptoms as well as by the confirmatory rtPCR test reports from DGHS approved laboratories Anti-nucleocapsid antibody (Anti-N-Ab) in venous blood samples, assayed by a chemiluminescent ELISA technique, was used as a seroprevalence-based marker of breakthrough infection during the preceding few months. Data were analyzed by bivariate as well as multivariate statistics using the IBM-SPSS software. ResultsThe median age (range) of the HCWs was 38 (21–65) years; Body Mass Index (BMI, kg/m2) 25 (15–49); and Waist-Hip Ratio (WHR) was 0.92 (0.46–1.21). The male subjects had significantly higher median age (p = 0.01) and higher WHR (p = 0.001) as compared to the female subjects. As per the BMI category, subjects with overweight and obesity constituted 83.3 % of the male subjects as compared to 61.6 % of the female subjects (p = 0.001). The time lapse between receiving of 3rd dose and blood sampling was significantly higher among females compared to males (median days 60 vs 49, p < 0.02) indicating earlier vaccination with 1st booster dose among females. A proportion of 51.85 % male and 49.68 % female subjects showed Anti-N-Ab positivity; there was no significant difference between the gender groups. Also, there was no significant difference among male and female subjects regarding the Ab levels. On Spearman correlation analysis, a tendency of association of WHR with Ab level was observed among the male subjects; however, the association did not show statistical significance (p = 0.09). On binary logistic regression Ab positivity was found to be independently associated with WHR (p = 0.03), and prior SARS-COV-2 infection within the last 3 months (p = 0.02) among males. When all the subjects were considered together, COVID symptom positivity during the last 3 months (p = 0.067) and receiving the 1st booster dose (p = 0.07) showed a tendency of association with Ab positivity. On multiple regression analysis, Ab levels showed a negative association with WHR (p = 0.035) among males. ConclusionsMore than 50 % of the vaccinated hospital-based HCWs in Bangladesh suffered from BTI during the winter of 2022 when the Omicron wave (the 3rd wave) of COVID-19 was at its peak. The data also indicate that overweight and obesity are major host-related risk factors underlying BTI. Inadequate coverage by a booster dose seems to be another determinant of BTI and the level of immune response in this population.

Early warning COVID-19 outbreak in long-term care facilities using wastewater surveillance: correlation, prediction, and interaction with clinical and serological statuses

The unprecedented COVID-19 pandemic has highlighted the strategic value of wastewater-based surveillance (WBS) of SARS-CoV-2. This multisite 28-month-long study focused on WBS for older residents in 12long-term care facilities (LTCFs) in Edmonton (AB, Canada) by assessing relationships between COVID-19, WBS, and serostatus during the pandemic. Wastewater samples collected two to three times per week were tested for SARS-CoV-2 using RT-quantitative PCR. Theserostatus of antibodies was examined using immunoassays. The data of clinical COVID-19 outbreaks based on extensive testing were obtained from local public health officials. Analyses included calculating correlations between 7-day rolling averages for WBS and COVID-19 cases and investigating whether WBS led or lagged confirmed outbreaks using a multinomial test. Wastewater results correlated well with clinical COVID-19 infections and outbreaks at participating LTCFs. 1058 (36·0%) of 2936collected wastewater samples were SARS-CoV-2 positive, compared with 1247people (resident n=671, staff n=572, and unknown n=4) reporting positive test results of 21 673clinical samples assessed (5·8%). WBS led clinical testing in 32 (60·4%) confirmed outbreaks, which was significantly different from WBS lagged (12outbreaks [22·6%, 95% CI 11·3-33·7]). Non-detection of WBS SARS-CoV-2 served as a negative predictor for outbreaks. WBS results attested protective immunity in vaccinated individuals before the omicron wave. Aparallel increase in the proportions of positive WBS SARS-CoV-2 and anti-nucleocapsid antibodies underlined that omicron was an immunity-evading variant despite high seropositivity of neutralising antibodies after multiple doses of vaccine. Implementation of WBS could enable targeted clinical investigations and improve cost-effectiveness of COVID-19 outbreak management in LTCFs. WBS and serostatus provided informed dynamic changes of infections and immunity. Critical evidence was that LTCF WBS is an effective early warning system to support rapid public health outbreak management and protect vulnerable older populations. Canadian Immunity Task Force for COVID-19 and Alberta Health.

Detection and comparison of SARS-CoV-2 antibody produced in naturally infected patients and vaccinated individuals in Addis Ababa, Ethiopia: multicenter cross-sectional study

BackgroundNatural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or vaccination triggers antibody production against key viral antigens. However, there is limited evidence on the levels of antibodies produced in naturally infected individuals compared to those vaccinated in Ethiopia. Therefore, we aimed to detect and compare SARS-CoV-2 antibodies produced by naturally infected and vaccinated individuals.Materials and methodsWe conducted a multicenter cross-sectional study among a total of 355 naturally infected and 355 vaccinated individuals from November 2022 to April 2023 at 10 selected health facilities in Addis Ababa, Ethiopia. We enrolled the participants consecutively upon their arrival at health facilities until the required sample size was achieved. We used a structured questionnaire to collect data on the demographic and clinical characteristics of the participants. We also collected 3–5 ml of blood samples from all participants and tested for anti-Spike (anti-S) and anti-nucleocapsid (anti-N) antibodies using Cobas 6000. We utilized frequency, mean, or median to describe the data, the Mann-Whitney U test to compare groups, and a generalized linear regression model to assess factors associated with anti-S antibody concentration. We analyzed the data with SPSS version 26, and the level of significance was set at P-value < 0.05.ResultsOf the naturally infected participants, 352 (99.5%) had anti-S antibodies and all (100%) had anti-N antibodies, whereas among vaccinated participants, all (100%) had anti-S antibodies, while 323 (91.6%) had anti-N antibodies. Anti-S antibodies produced by vaccinated individuals were significantly (P < 0.001) higher than those produced as a result of natural infection. Being young (P = 0.004), having hypertension (P < 0.001), and having diabetes (P < 0.001) were significantly associated with lower anti-S antibody levels, while being recently vaccinated and having a higher number of vaccine doses were significantly associated with higher anti-S antibody concentrations in vaccinated participants. Having diabetes (P < 0.001) were significantly associated with lower anti-S concentrations in participants who were naturally infected.ConclusionThere is a high seropositivity rate in both naturally infected and vaccinated individuals. However, vaccinated individuals had higher levels of SARS-CoV-2 antibodies than those who were naturally infected, which highlights the significant contribution of vaccination in increasing the protection of COVID-19 in Ethiopia.

SARS-CoV-2 seroepidemiology in Cape Town, South Africa, and implications for future outbreaks in low-income communities.

In low- and middle-income countries where SARS-CoV-2 testing is limited, seroprevalence studies can help describe and characterise the extent of the pandemic, as well as elucidate protection conferred by prior exposure. We conducted repeated cross-sectional serosurveys (July 2020 -November 2021) using residual samples from patients from Cape Town, South Africa, sent for routine laboratory studies for non-COVID-19 conditions. SARS-CoV-2 anti-nucleocapsid antibodies and linked clinical information were used to investigate: (1) seroprevalence over time and risk factors associated with seropositivity, (2) ecological comparison of seroprevalence between subdistricts, (3) case ascertainment rates, and (4) the relative protection against COVID-19 associated with seropositivity and vaccination statuses. Among the subset sampled, seroprevalence of SARS-CoV-2 in Cape Town increased from 39.19% (95% confidence interval [CI] 37.23-41.19) in July 2020 to 67.8% (95%CI 66.31-69.25) in November 2021. Poorer communities had both higher seroprevalence and COVID-19 mortality. Only 10% of seropositive individuals had a recorded positive SARS-CoV-2 test. Using COVID-19 hospital admission and death data at the Provincial Health Data Centre, antibody positivity before the start of the Omicron BA.1 wave (28 November 2021) was strongly protective for severe disease (adjusted odds ratio [aOR] 0.15; 95%CI 0.05-0.46), with additional benefit in those who were also vaccinated (aOR 0.07, 95%CI 0.01-0.35). The high population seroprevalence in Cape Town was attained at the cost of substantial COVID-19 mortality. At the individual level, seropositivity was highly protective against subsequent infections and severe COVID-19 disease. In low-income communities, where diagnostic testing capacity is often limited, surveillance systems dependent on them will underestimate the true extent of an outbreak. Rapidly conducted seroprevalence studies can play an important role in addressing this.

Comparison of SARS-CoV-2 seroprevalence estimates between commercial lab serum specimens and blood donor specimens, United States, September-December 2021.

This study was the first systematic comparison between two nationwide severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) studies which estimated seroprevalence, or the proportion of the population with antibodies to the virus, using differing convenience sample populations. One study tested blood donor specimens; the other study tested specimens left over from clinical blood tests. The seroprevalence of anti-nucleocapsid and anti-spike antibodies was compared in the same states during the same months with statistical adjustments based on state demographics. Similar anti-nucleocapsid antibody seroprevalence estimates produced by two independent studies using differing convenience samples build confidence in the generalizability of their anti-nucleocapsid findings. Due to high blood donor vaccine rates, blood donor SARS-CoV-2 anti-spike antibody estimates might overestimate general population seroprevalence, an important consideration for interpreting national seroprevalence study results. Furthermore, because laboratory residuals and blood donations are two common sources of specimens for seroprevalence studies, study findings may be informative for other respiratory virus seroepidemiology studies.

Anti-Spike IgG antibodies as correlates of protection against SARS-CoV-2 infection in the pre-Omicron and Omicron era.

Anti-Spike IgG antibodies against SARS-CoV-2, which are elicited by vaccination and infection, are correlates of protection against infection with pre-Omicron variants. Whether this association can be generalized to infections with Omicron variants is unclear. We conducted a retrospective cohort study with 8457 blood donors in Tyrol, Austria, analyzing 15,340 anti-Spike IgG antibody measurements from March 2021 to December 2022 assessed by Abbott SARS-CoV-2 IgG II chemiluminescent microparticle immunoassay. Using a Bayesian joint model, we estimated antibody trajectories and adjusted hazard ratios for incident SARS-CoV-2 infection ascertained by self-report or seroconversion of anti-Nucleocapsid antibodies. At the time of their earliest available anti-Spike IgG antibody measurement (median November 23, 2021), participants had a median age of 46.0 years (IQR 32.8-55.2), with 45.3% being female, 41.3% having a prior SARS-CoV-2 infection, and 75.5% having received at least one dose of a COVID-19 vaccine. Among 6159 participants with endpoint data, 3700 incident SARS-CoV-2 infections with predominantly Omicron sublineages were recorded over a median of 8.8 months (IQR 5.7-12.4). The age- and sex-adjusted hazard ratio for SARS-CoV-2 associated with having twice the anti-Spike IgG antibody titer was 0.875 (95% credible interval 0.868-0.881) overall, 0.842 (0.827-0.856) during 2021, and 0.884 (0.877-0.891) during 2022 (all p < 0.001). The associations were similar in females and males (Pinteraction = 0.673) and across age (Pinteraction = 0.590). Higher anti-Spike IgG antibody titers were associated with reduced risk of incident SARS-CoV-2 infection across the entire observation period. While the magnitude of association was slightly weakened in the Omicron era, anti-Spike IgG antibody continues to be a suitable correlate of protection against newer SARS-CoV-2 variants.

Overcoming the age-dependent SARS-CoV-2 vaccine response through hybrid immunity: analysis of humoral and cellular immunity with mass cytometry profiling

BackgroundAge-dependent immune responses to coronavirus disease 2019 (COVID-19) vaccinations and breakthrough infections (BIs) in young and middle-aged individuals are unclear.MethodsThis nationwide multicenter prospective cohort study analyzed immune responses in participants of the ChAdOx1 (ChAd)-ChAd-mRNA vaccine group using cytometry by time-of-flight, anti-spike protein antibody (Sab) and anti-nucleocapsid antibody (Nab) titers, plaque reduction neutralization tests (PRNTs), and interferon-gamma (IFN-γ) release assays at various time points.ResultsWe evaluated 347 participants with an average age of 38.9 ± 9.4 years (range: 21–63). There was a significant inverse correlation between age and Sab levels after the second dose (slope − 14.96, P = 0.032), and this was more pronounced after the third dose (slope − 208.9, P < 0.001). After BIs, older participants showed significantly higher Sab titers (slope 398.8, P = 0.001), reversing the age-related decline observed post-vaccination. This reversal was also observed in PRNTs against wild-type SARS-CoV-2 and the BA.1 and BA.5 variants. IFN-γ responses increased markedly after the third dose and Bis, but showed a weak positive correlation with age, without statistical significance. Immune cell profiling revealed an age-dependent decrease in the proportions of B-cell lineage cells. The proportions of naive CD4+ and CD8+ T cells were inversely correlated with age, whereas the proportions of mature T cell subsets with memory function, including memory CD4+ T, CD8+ TEM, CD8+ TEMRA, and TFH cells, increased with age.ConclusionsAge-dependent waning of the serologic response to COVID-19 vaccines occurred even in middle-aged individuals, but was reversed after BIs. IFN-γ responses were preserved, compensating for the decrease in naive T cell populations, with an increase in memory T cell populations.

Development of a unit conversion tool for five quantitative anti-spike assays and agreement analysis of three qualitative anti-nucleocapsid assays for SARS-CoV-2.

Commercially available assays for measuring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike (S) or anti-nucleocapsid (N) antibodies differ in units, making results comparisons challenging. This study aimed to develop conversion equations between five quantitative anti-S antibody tests and to assess the agreement over time between three qualitative anti-N antibody tests. Blood samples from 24 216 vaccinated healthcare workers in Hiroshima Prefecture, Japan, were analyzed for anti-S antibodies using five quantitative tests (Abbott, Fujirebio, Ortho, Sysmex, Roche) and for anti-N antibodies using three qualitative tests (Abbott, Sysmex, Roche). Geometric mean regression was performed to establish equations for converting measured values between the five quantitative tests. Fleiss κ statistic was used to assess the agreement between the three qualitative tests. A strong correlation (Pearson's coefficient r > 0.9) was found for each pair of the five quantitative tests measuring anti-S antibodies, enabling the development of equations to convert values between each pair. Using these equations, which are based on the original output unit of each test, values obtained from one test can be transformed to be equivalent to the corresponding values in another test. For the three tests for anti-N antibodies, the agreement was substantial in the total sample (Fleiss' κ, 0.74) and moderate among those with self-reported past coronavirus disease 2019 (COVID-19) infection (Fleiss' κ, 0.39). The agreement decreased with time after infection. Reduced agreement between anti-N antibodies tests over time suggests caution in comparing seroepidemiological studies of COVID-19 exposure based on anti-N antibodies measurement. The findings could help improve antibody measurement systems and inform public health decision-makers.

Characteristics of Lung Cancer Patients With Asymptomatic or Undiagnosed SARS-CoV-2 Infections

IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be spread by individuals unaware they are infected. Such dissemination has heightened ramifications in cancer patients, who may need to visit healthcare facilities frequently, be exposed to immune-compromising therapies, and face greater morbidity from coronavirus disease 2019 (COVID-19). We determined characteristics of (1) asymptomatic, clinically diagnosed, and (2) serologically documented but clinically undiagnosed SARS-CoV-2 infection among individuals with lung cancer. Patients and methodsIn a multicenter registry, individuals with lung cancer (regardless of prior SARS-CoV-2 vaccination or documented infection) underwent collection of clinical data and serial blood samples, which were tested for antinucleocapsid protein antibody (anti-N Ab) or IgG (N) levels. We used multivariable logistic regression models to investigate clinical characteristics associated with the presence or absence of symptoms and the presence or absence of a clinical diagnosis among patients with their first SARS-CoV-2 infection. ResultsAmong patients with serologic evidence or clinically documented SARS-CoV-2 infection, 80/142 (56%) had no reported symptoms at their first infection, and 61/149 (40%) were never diagnosed. Asymptomatic infection was more common among older individuals and earlier-stage lung cancer. In multivariable analysis, non-white individuals with SARS-CoV-2 serologic positivity were 70% less likely ever to be clinically diagnosed (P = .002). ConclusionsIn a multicenter lung cancer population, a substantial proportion of SARS-CoV-2 infections had no associated symptoms or were never clinically diagnosed. Because such cases appear to occur more frequently in populations that may face greater COVID-19-associated morbidity, measures to limit disease spread and severity remain critical.

SARS-CoV-2 antibody vaccine response in Inflammatory Bowel Disease patients with positive anti-nucleocapsid serology or history of COVID-19 infection.

Previous history of COVID-19 infection is a natural booster of the vaccine response in the general population. The response to COVID-19 vaccines is lessened in Inflammatory Bowel Disease patients on selected class of immunosuppressive treatments. The study was to assess anti-SARS-CoV-2 spike-specific IgG antibody response in Inflammatory Bowel Disease patients with a history of COVID-19 infection. This single-center prospective study involved 504 Inflammatory Bowel Disease patients. Demographic data and clinical data were gathered through questionnaires and patient charts. Anti-SARS-CoV-2 spike-specific and antinucleocapsid antibody levels were measured at T1, T2 (after the 2-dose series), and T3 or T4 (booster vaccine). This study included 504 Inflammatory Bowel Disease patients, and 234 completed one year follow-up with blood tests. Positive anti-nucleocapsid serology or history of COVID-19 infection was significantly associated with increased median anti- SARS-CoV-2 spike-specific IgG titers after the 2-dose series (1930 BAU/mL vs. 521 BAU/mL p < 0.0001) and the booster vaccine (4390 BAU/mL vs. 2160 BAU/mL, p = 0.0156). Multivariate analysis showed that higher anti-SARS-CoV-2 spike-specific IgG levels were independently associated with anti-nucleocapsid antibodies at T2 (OR=2.23, p < 0.0001) and T3 (OR=1.72, p = 0.00011). Immunosuppressive treatments did not impact the antibody response or levels in patients with a history of COVID-19 infection or positive anti-nucleocapsid serology. In Inflammatory Bowel Disease, prior COVID-19 infection or positive anti-nucleocapsid serology leads to increased anti-SARS-CoV-2 spike-specific IgG levels after vaccination, regardless of immunosuppressive treatments. This emphasizes the significance of accounting for previous infection in vaccination approaches.

SARS-CoV-2 Vaccination is Not Associated With Involuntary Childlessness in Female Healthcare Workers: A Multicenter Cohort Study.

There is debate about the causes of the recent birth rate decline in high-income countries worldwide. During the pandemic, concern about the effects on reproductive health has caused vaccine hesitancy. We investigated the association of SARS-CoV-2 vaccination and infection with involuntary childlessness. Females in fertility age within a prospective multicenter cohort of healthcare workers (HCW) were followed since August 2020. Data on baseline health, SARS-CoV-2-infection, and vaccination were obtained and regularly updated, in which serum samples were collected repetitively and screened for anti-nucleocapsid and anti-spike antibodies. In October 2023, participants indicated the presence of involuntary childlessness with onset during the pandemic, whereas those indicating an onset before the pandemic were excluded. The association of involuntary childlessness and SARS-CoV-2-vaccination and infection was investigated using univariable and multivariable analysis. Sensitivity analysis was performed to compare those reporting involuntary childlessness with those birthing a child since 2020. Of 798 participants, 26 (3.2%) reported involuntary childlessness starting since the pandemic. Of the involuntary childless women, 73.1% (19/26) were vaccinated compared to 86.0% (664/772) without involuntary childlessness (p = 0.73). SARS-CoV-2 infection was reported by 76.9% (20/26) compared to 72.4% (559/772) of controls (p = 0.64). Neither SARS-CoV-2 vaccination (aOR 0.91 per dose, 95%CI 0.67-1.26) nor infection (aOR per infection 1.05, 95%CI 0.62-1.71) was associated with involuntary childlessness. Sensitivity analysis confirmed these results. Among female HCW of fertility age, 3.2% indicated involuntary childlessness, which is comparable to pre-pandemic data. No association between involuntary childlessness and SARS-CoV-2 vaccination or infection was found.

Kinetics of SARS-CoV-2 infection biomarkers in a household transmission study

SARS-CoV-2 is the causative agent of COVID-19. Timely and accurate diagnostic testing is vital to contain the spread of infection, reduce delays in treatment and care, and inform patient management. Optimal specimen type (e.g. nasal swabs or saliva), timing of sampling, viral marker assayed (RNA or antigen), and correlation with viral infectivity and COVID-19 symptoms severity remain incompletely defined. We conducted a field study to evaluate SARS-CoV-2 viral marker kinetics starting from very early times after infection. We measured RNA and antigen levels in nasal swabs and saliva, virus outgrowth in cell culture from nasal swabs, and antibody levels in blood in a cohort of 30 households. Nine household contacts (HHC) became infected with SARS-CoV-2 during the study. Viral RNA was detected in saliva specimens approximately 1–2 days before nasal swabs in six HHC. Detection of RNA was more sensitive than of antigen, but antigen detection was better correlated with culture positivity, a proxy for contagiousness. Anti-nucleocapsid antibodies peaked one to three weeks post-infection. Viral RNA and antigen levels were higher in specimens yielding replication competent virus in cell culture. This study provides important data that can inform how to optimally interpret SARS-CoV-2 diagnostic test results.