Low Seropositive Rate Research Articles

A community study of neutralizing antibodies against SARS-CoV-2 in China.

The immune background of the overall population before and after the outbreak of SARS-CoV-2 in China remains unexplored. And the level of neutralizing antibodies is a reliable indicator of individual immunity. This study aimed to assess the immune levels of different population groups during a viral outbreak and identify the factors influencing these levels. We measured the levels of neutralizing antibodies in 12,137 participants using the COVID19 Neutralizing Antibody Detection kit. The dynamics of neutralizing antibodies were analyzed using a generalized additive model, while a generalized linear model and multi-factor analysis of variance were employed to investigate the influencing factors. Additionally, statistical methods were used to compare neutralizing antibody levels among subgroups of the real-world population. Participants who received booster doses exhibited significantly higher levels of neutralizing antibodies compared to those who received only one or two doses (p<0.001). Both elderly [22.55 (5.12, 62.03) IU/mL, 55%] and minors [21.41 (8.15, 45.06) IU/mL, 56%] showed lower positivity rates and neutralizing antibody levels compared to young adults [29.30 (9.82, 188.08) IU/mL, 62%] (p<0.001). Furthermore, the HIV-positive group demonstrated a slightly lower seropositivity rate compared to the healthy group across the three vaccination time points. Notably, three months after the large-scale infection, both the neutralizing antibody level and positivity rate in real-world populations were higher than the previous record [300 (300, 300) IU/mL, 89%; 27.10 (8.77, 139.28) IU/mL, 60%], and this difference was statistically significant. Increasing vaccine dosage enhances neutralizing antibody levels, resulting in greater and longer-lasting immunity. Monitoring immune levels in older individuals and those with AIDS is crucial. Additionally, the neutralizing antibodies generated from vaccination have not yet reached the threshold for achieving herd immunity, while individuals exhibit higher immune levels following a large-scale infection. These findings provide valuable insights for guiding new strategies in vaccine administration.

Effective Neutralizing Antibody Response Against SARS-CoV-2 Virus and Its Omicron BA.1 Variant in Fully Vaccinated Hematological Patients

SARS-CoV-2 and its variants cause CoronaVIrus Disease 19 (COVID-19), a pandemic disease. Hematological malignancies increase susceptibility to severe COVID-19 due to immunosuppression. Anti-SARS-CoV-2 neutralizing antibodies protect against severe COVID-19. This retrospective real-life study aimed to evaluate seropositivity and neutralizing antibody rates against SARS-CoV-2 and its Omicron BA.1 variant in hematological patients. A total of 106 patients with different hematologic malignancies, who have mostly received three or more vaccine doses (73%), were included in this study. Serum was collected between May and June 2022. The primary endpoint was anti-SARS-CoV-2 antibody response against ancestral (wild type; wt) and Omicron BA.1 virus, defined as a neutralizing antibody titer ≥ 1:10. Adequate neutralizing antibody response was observed in 75 (71%) and 87 (82%) of patients for wt and Omicron BA.1 variants, respectively.However, patients with B-cell lymphoproliferative disorders and/or those treated with anti-CD20 monoclonal antibodies in the prior 12 months showed a lower seropositivity rate compared to other patients against both Omicron BA.1 variant (73% vs 91%; P = 0.02) and wt virus (64% vs 78%; P = 0.16). Our real-life experience confirmed that full vaccination against SARS-CoV-2 induces adequate neutralizing antibody protection for both the wt virus and Omicron BA.1 variants, even in hematological frail patients. However, protective measures should be maintained in hematological patients, especially those with B-cell lymphoproliferative diseases treated with anti-CD20 monoclonal antibodies, because these subjects could have a reduced neutralizing antibody production.

#2765 EVALUATION OF ANTIBODY RESPONSES TO SARS-COV-2 VACCINES IN PATIENTS WITH CKD

Abstract Background and Aims Patients with CKD are highly vulnerable to the serious complications of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infections and thus stand to benefit from vaccination. Therefore, our aim is to evaluate the effectiveness of available COVID-19 vaccines in patients with CKD. Method A total of 198 consecutive adult CKD patients in a single center in Uzbekistan were evaluated. Patients were divided into four cohorts: haemodialysis (HD) (n=116), peritoneal dialysis (PD) (n=11), kidney transplant (KT) recipients (n=22) and non-dialysis CKD (stages 4 and 5, eGFR &amp;lt;30 mL/min/1.73 m2) (n=49) patients (Fig. 1). All the screened participants received the complete vaccination with any of the available vaccines: Pfizer-BioNTech®, Moderna®, AstraZeneca®, Sputnik V®, ZF-UZ-VAC2001®. At baseline and on day 28 after the last vaccine dose, antibodies were measured and compared between cohorts. Factors associated with development of antibodies were analyzed. Results Among the 198 participants in screened group, 109 (55%) were male and the mean age was 54.3 ± 11.2 years. Vaccine distribution was as follows: 25 patients (12.6%) received Pfizer-BioNTech, 42 (21.2%) Moderna, 28 (14.1%) AstraZeneca, 36 (18.2%) Sputnik V and 67 (33.9%) ZF-UZ-VAC2001 vaccines. The distribution of the different types of vaccines differed between groups (Table 1). Development of antibody responses at 28 days after completing vaccination has been tested in 155 patients (97 HD, 8 PD, 16 KT recipients, 34 non-dialysis CKD patients). After the 28 days of completing vaccination, 137 patients (88%) presented antibody responses, 3 (2%) were doubtful and 15 (10%) had a negative result. Patients that did not develop antibody responses after vaccination included: 3 (2%) HD patients, 2 (1%) PD patients, 2 (1%) non-dialysis CKD patients and 8 (6%) KT recipients (P &amp;lt; 0.01). Patients receiving Pfizer-BioNTech, Moderna and AstraZeneca developed higher antibody titres than those receiving Sputnik V and ZF-UZ-VAC2001 vaccines (P &amp;lt; 0.01). These differences were significant in all cohort of patients. Factors associated with negative antibody response were also increasing age (p&amp;lt;0.01), history of CVD (p = 0.02), lower eGFR (P &amp;lt; 0.05). Previous COVID-19 infection was associated with higher antibody titres at 28 days (P &amp;lt; 0.05). We did not find significant association between antibody response and gender, ethnicity, BMI, diabetes and donor type. Conclusion Our study has shown a much lower seropositivity rate among the KT recipients after of SARS-COV-2 vaccine than other cohort of CKD patients, suggesting that KT patients require persistent isolation measures and booster doses of a COVID-19 vaccine. Increasing age, history of CVD and lower eGFR were factors associated with a non-response. Potential differences between COVID-19 vaccines should be explored in prospective long-term follow-up studies. These findings complement those of earlier studies and highlight the need for a tailored approach to the vaccination.

One-Year Follow-Up of Seroprevalence of SARS-CoV-2 Infection and Anxiety among Health Workers of a French Cancer Center: The PRO-SERO-COV Study.

Infection of SARS-CoV-2 among health workers (HWs) in contact with cancer patients has been a major issue since the beginning of the pandemic. We aimed to assess the serological immune status of SARS-CoV-2 infection among these HWs. A prospective cohort study was initiated in the comprehensive cancer center of the Nouvelle-Aquitaine region (NA, France). Volunteer HWs working on March 2020 without active infection or symptoms of COVID-19 completed a self-questionnaire and had a blood test at inclusion, at 3 and 12 months. Positive serological status of SARS-CoV-2 infection was defined by anti-nucleocapsid antibodies and/or IgG anti-spike antibodies, except at 12 months due to vaccine. Half of the HWs were included (N = 517) and 89% were followed for three months (N = 500) and one year (N = 462). Seroprevalence of SARS-CoV-2 infection was 3.5% (95% CI: 1.9-5.1), 6.2% (95% CI: 4.1-8.3), and 10% (95% CI: 7.2-12.7) on June-September 2020, September 2020-January 2021, and June-October 2021, respectively. At 12 months, 93.3% had detectable antibodies with 80% vaccinated in the first three months of vaccine availability. The COVID-19-free policy of the institution, respect for barrier gestures, high and early vaccination of HWs, and low prevalence of SARS-CoV-2 in NA may explain the low rate of seropositivity among the HWs of the Institut Bergonié.

Low Measles Seropositivity Rate among Thai Adolescents in the Thai National Immunization Program.

To achieve the goal of measles elimination, herd immunity with 95% seroprotection in the community is required. This study aimed to describe the measles seropositivity rate among Thai children and adolescents. A cross-sectional study was conducted among children aged 3–18 years in Bangkok and its suburbs. Measles IgG antibodies were measured using a EUROIMMUN enzyme-linked immunosorbent assay kit. Seropositivity is defined as a measles IgG titer of ≥200 IU/L, due to a correlation with a >85% positive rate with a plaque reduction neutralizing titer of >120. Factors associated with seropositivity were analyzed using logistic regression analysis. From May to July 2020, 570 children with a median (IQR) age of 11.7 (9.4–14.8) years were enrolled. The geometric mean titer (GMT) of anti-measles IgG was 281 IU/L (95% CI; 257–306). The proportion of children with seropositivity was inversely correlated with age; 3–5 years 85.3%, 6–9 years 72.5%, 10–14 years 50.7%, and 15–18 years 56.3%. Adolescents aged 10–18 years had a lower measles seropositivity rate compared with young children; aOR 0.29 (95% CI 0.17–0.48). Only half of the adolescents who received two doses of measles-containing vaccine maintained measles IgG above the seropositive level. A measles booster dose for young adults may be needed to achieve the measles elimination goal.

Blunted Post-COVID-19 Humoral Immunity in Patients With CNS Demyelinating Disorders on Anti-CD20 Treatments.

With unclear characteristics of post-infection and post-vaccination immunity, the multiple sclerosis community lacks evidence to guide patients on their continued coronavirus disease 2019 (COVID-19) infection risk. As disease modifying treatments all modulate the immune system, we expect their use to alter acquired immunity to COVID-19, but the specific impact of individual treatments is unclear. To address this, we analyzed the patient and COVID-19 specific characteristics associated with post-infection humoral immunity in 58 patients with central nervous system (CNS) demyelinating disorders in the Boston metropolitan area. Univariate analysis of variance was performed using Mann Whitney U test for continuous variables, and Chi Square or Fisher Exact test for nominal variables. Univariate and stepwise multivariate nominal logistic regression identified clinical characteristics associated with COVID-19 specific nucleocapsid IgG antibody formation post-infection. Our cohort demonstrated a 42% post-infection seropositive rate with a significantly higher rate observed with shorter duration between infection and antibody collection and use of natalizumab over no/other treatment. Use of anti-CD20 treatments compared to no/other treatment was associated with a significantly lower rate of seropositivity. However, only shorter duration between infection and antibody collection as well as use of no/other treatment compared to anti-CD20 treatment were found to be independently associated with increased likelihood of post-infection seropositivity. Additionally, we demonstrate durability of antibody response up to 9 months in a small subset of patients. Thus, our data supports that patients with CNS demyelinating disorders regardless of DMT are able to form a measurable antibody response after COVID-19 infection, and that patients on anti-CD20 treatments form less robust immunity after COVID-19 infection.

Humoral antibody kinetics with ChAdOx1-nCOV (Covishield™) and BBV-152 (Covaxin™) vaccine among Indian Healthcare workers: A 6-month longitudinal cross-sectional Coronavirus Vaccine-induced antibody titre (COVAT) study

Background and aimsThere is limited data available on longitudinal humoral antibody dynamics following two doses of ChAdOx1-nCOV (Covishield™) and BBV-152 (Covaxin™) vaccine against SARS-CoV-2 among Indians. MethodsWe conducted a 6-month longitudinal study in vaccinated healthcare workers by serially measuring quantitative anti-spike antibody at 3-weeks, 3-months and 6-months after the completion of second dose. Geometric mean titer (GMT) and linear mixed models were used to assess the dynamics of antibody levels at 6 months. ResultsOf the 481 participants, GMT of anti-spike antibody decreased by 56% at 6-months regardless of age, gender, blood group, body-mass index and comorbidities in 360 SARS-CoV-2 naive individuals but significantly more in hypertensives. Participants with past infection had significantly higher GMT at all time points compared to the naive individuals. Among SARS-CoV-2 naive cohorts, a significantly higher GMT was noted amongst the Covishield recipients at all time points, but there was a 44% decline in GMT at 6-month compared to the peak titer period. Decline in GMT was insignificant (8%) in Covaxin recipients at 6-month despite a lower GMT at all time points vs. Covishield. There was 5.6-fold decrease in seropositivity rate at 6-month with both vaccines. Participants with type 2 diabetes mellitus have a lower seropositivity rate at all the time points. Seropositivity rate was significantly higher with Covishield vs. Covaxin at all time points except at 6-month where Covaxin recipients had a higher seropositivity rate but no difference noted in propensity-matched analysis. ConclusionsThere is waning humoral antibody response following two doses of either vaccine at six months. Covishield recipients had a higher anti-spike antibody GMT compared with Covaxin at all-time points, however a significant decline in antibody titers was seen with Covishield but not with Covaxin at 6-months.

SARS-CoV2 anti-spike IgG response following COVID-19 mRNA vaccination (BNT162b2) in patients with hematological disorders

This is a prospective study conducted to determine the level of anti-spike IgG to SARS-CoV-2 2-6 weeks following the BNT162b2 vaccination in 125 patients with hematological disorders. Compared with healthy controls, patients with malignant lymphoma had lower rates of seropositivity and lower levels of antibody titer. Furthermore, patients who received rituximab (R)-containing chemotherapy had lower antibody titers than those who were not treated with R or who had completed R-containing chemotherapy more than 9 months earlier. Despite having 71% IgG-seropositivity, patients with multiple myeloma had lower antibody titers than the control group. Furthermore, patients receiving daratumumab-containing chemotherapy had lower antibody titers than those not receiving treatment. Moreover, patients with acute myeloid leukemia or myelodysplastic syndrome had lower antibody titers than the control group. Overall, the number of peripheral blood lymphocytes was significantly correlated with IgG titers, with seropositive patients having more peripheral blood lymphocytes than seronegative patients. Patients with severe immunosuppression, such as those with hematological disorders, often have impaired seroconversion with COVID-19 vaccination that should be taken into consideration by clinicians.

A comparative study of antibody response, virus neutralization efficiency & metabolites in SARS-CoV-2-infected adults & children.

COVID-19 has been a global pandemic since early 2020. It has diverse clinical manifestations, but consistent immunological and metabolic correlates of disease severity and protection are not clear. This study was undertaken to compare seropositivity rate, antibody levels against nucleocapsid and spike proteins, virus neutralization and metabolites between adult and child COVID-19 patients. Plasma samples from naïve control (n=14) and reverse transcription (RT)-PCR positive COVID-19 participants (n=132) were tested for reactivity with nucleocapsid and spike proteins by ELISA, neutralization of SARS-CoV-2 infectivity in Vero cells and metabolites by [1]H nuclear magnetic resonance (NMR) spectroscopy. An ELISA platform was developed using nucleocapsid and spike proteins for COVID-19 serosurvey. The participants showed greater seropositivity for nucleocapsid (72%) than spike (55.3%), and males showed higher seropositivity than females for both the proteins. Antibody levels to both the proteins were higher in intensive care unit (ICU) than ward patients. Children showed lower seropositivity and antibody levels than adults. In contrast to ICU adults (81.3%), ICU children (33.3%) showed lower seropositivity for spike. Notably, the neutralization efficiency correlated with levels of anti-nucleocapsid antibodies. The levels of plasma metabolites were perturbed differentially in COVID-19 patients as compared with the naive controls. Our results reflect the complexity of human immune response and metabolome to SARS-CoV-2 infection. While innate and cellular immune responses are likely to be a major determinant of disease severity and protection, antibodies to multiple viral proteins likely affect COVID-19 pathogenesis. In children, not adults, lower seropositivity rate for spike was associated with disease severity.

SARS-CoV-2 Seroprevalence in Germany.

Until now, information on the spread of SARS-CoV-2 infections in Germany has been based mainly on data from the public health offices. It may be assumed that these data do not include many cases of asymptomatic and mild infection. We determined seroprevalence over the course of the pandemic in a sequential, multilocal seroprevalence study (MuSPAD). Study participants were recruited at random in seven administrative districts (Kreise) in Germany from July 2020 onward; each participant was tested at two different times 3-5 months apart. Test findings on blood samples were used to determine the missed-case rate of reported infections, the infection fatality rate (IFR), and the association between seropositivity and demographic, socio-economic, and health-related factors, as well as to evaluate the self-reported results of PCR and antigenic tests. The registration number of this study is DRKS00022335. Among non-vaccinated persons, the seroprevalence from July to December 2020 was 1.3-2.8% and rose between February and May 2021 to 4.1-13.1%. In July 2021, 35% of tested persons in Chemnitz were not vaccinated, and the seroprevalence among these persons was 32.4% (07/2021). The surveillance detection ratio (SDR), i.e., the ratio between the true number of infections estimated from seroprevalence and the actual number or reported infections, varied among the districts included in the study from 2.2 to 5.1 up to December 2020 and from 1.3 to 2.9 up to June 2021, and subsequently declined. The IFR was in the range of 0.8% to 2.4% in all regions except Magdeburg, where a value of 0.3% was calculated for November 2020. A lower educational level was associated with a higher seropositivity rate, smoking with a lower seropositivity rate. On average, 1 person was infected for every 8.5 persons in quarantine. Seroprevalence was low after the first wave of the pandemic but rose markedly during the second and third waves. The missed-case rate trended downward over the course of the pandemic.

Seroepidemiology of enterovirus D68 infection in Kuala Lumpur, Malaysia between 2013 and 2015.

Enterovirus D68 (EV-D68) is an emerging respiratory pathogen since the 2014 outbreak in the United States. A low level of virus circulation has been reported in Kuala Lumpur, Malaysia, in the past. However, the extent of the infection in Malaysia is not known. In the present study, we determine the seroepidemiology of EV-D68 in Kuala Lumpur, Malaysia, before and after the United Statesoutbreak in August 2014. A luciferase-based seroneutralization test was developed using a clone-derived prototype Fermon strain carrying a nanoluciferase marker. We screened the neutralization capacity of 450 serum samples from children and adults (1-89 years old) collected between 2013 and 2015. EV-D68 seropositivity increased with age, with children aged 1-3 showing significantly lower seroprevalence compared to adults. Multivariate analysis showed that older age groups 13-49 years (odds ratio [OR] = 4.78; 95% confidence interval [CI] = 2.69-8.49; p < 0.0001) and ≥50 years (OR = 3.83; 95% CI = 2.19-6.68; p < 0.0001) were more likely to be EV-D68 seropositive than children <13 years. Sampling post-September 2014 compared to pre-Sept2014 also predicted seropositivity (OR = 1.66; 95% CI = 1.04-2.65). The presence of neutralizing antibodies against EV-D68 in the study population suggests that EV-D68 was circulating before 2014. A higher seropositivity post-September 2014 suggests that Malaysia also experienced an upsurge in EV-D68 infections after the United Statesoutbreaks in August 2014. A low seropositivity rate observed in children, especially those aged 1-3 years old, suggests that they are at risk and should be prioritized for future vaccination.

SARS-CoV-2 seroprevalence in a high-altitude setting in Peru: adult population-based cross-sectional study.

BackgroundThere are several ecological studies, but few studies of the prevalence of SARS-COV-2 at high altitude. We aimed to estimate the population-based seroprevalence of SARS-COV-2 in three settings of Cusco at the end of the first wave among adults.MethodsA population-based survey was conducted in September 2020, in three settings in the region of Cusco: (1) Cusco city at 3,300 meters above the sea level (m.a.s.l.), (2) the periphery of Cusco (Santiago, San Jerónimo, San Sebastián, and Wanchaq) at 3,300 m.a.s.l., and (3) Quillabamba city, located at 1,050 m.a.s.l. People aged ≥ 18 years within a family unit were included. The diagnosis of SARS-CoV-2 infection was based on identifying anti- SARS-CoV-2 total antibodies (IgM and IgG) in serum using the Elecsys Anti-SARS-CoV-2 chemiluminescence test.ResultsWe enrolled 1924 participants from 712 families. Of the total, 637 participants were anti-SARS-CoV-2 seropositive. Seroprevalence was 38.8% (95% CI [33.4%–44.9%]) in Cusco city, 34.9% (95% CI [30.4%–40.1%]) in the periphery of Cusco, and 20.3% (95% CI [16.2%–25.6%]) in Quillabamba. In 141 families (19.8%; 95% CI [17.0%–22.8%]) the whole members were positive to the test. Living with more than three persons in the same house, a positive COVID-19 case at home, and a member who died in the last five months were factors associated with SARS-COV-2 seropositivity. Dysgeusia/dysosmia was the symptom most associated with seropositivity (aPR = 2.74, 95% CI [2.41–3.12]); whereas always wearing a face shield (aPR = 0. 73; 95% CI [0.60–0.89]) or a facial mask (aPR = 0.76, 95% CI [0.63–0. 92) reduced that probability.ConclusionsA great proportion of Cusco’s city inhabitants presented anti-SARS-CoV-2 antibodies at the end of the first wave, with significant differences between settings. Wearing masks and face shields were associated with lower rate of seropositivity; however, efforts must be made to sustain them over time since there is still a high proportion of susceptible people.

An international seroprevalence survey of the IgE sensitisation to the Dermatophagoides farinae house dust mite and two of its major allergens (Der f 2, Zen 1) in atopic dogs.

BackgroundDogs with atopic dermatitis are often immunoglobulin (Ig)E‐sensitised to Dermatophagoides farinae (Df) house dust mites, yet limited data exist on the sensitisation rates to the individual Df allergens, Der f 2 and Zen 1.ObjectivesTo determine the IgE sensitisation rates to Df, Der f 2 and Zen 1 in atopic dogs from geographically diverse countries.AnimalsSerum was collected from 32 laboratory dogs in Japan, and 837 atopic dogs from 11 countries from five continents: Asia (Japan, Thailand, Taiwan), Europe (Italy, Latvia, the Netherlands, UK), North America (USA), South America (Argentina, Brazil) and Africa (South Africa).Methods and materialsWe determined Df‐, Der f 2‐ and Zen 1‐specific IgE levels by ELISA. Correlations between the IgE values for these three allergens were calculated.ResultsThe IgE seropositivity rates for Df varied between 74% (Argentina) and 100% (the Netherlands, Thailand, South Africa), those for Der f 2 between 12% (Argentina) and 88% (South Africa), and for Zen 1 between 70% (Argentina) and 100% (the Netherlands). Apart from the especially low seropositivity rate for Der f 2‐specific IgE in Argentina, the percentage of IgE sensitisation varied little between countries. There was significant correlation between the IgE levels to these three allergens which was highest between Df and Zen 1, and lowest between Zen 1 and Der f 2.Conclusions and clinical relevanceThe IgE sensitisation to Df is geographically widespread. Der f 2 and Zen 1 are major allergens for dogs in almost all countries where this was evaluated.

Immunological features and factors associated with mucocutaneous bullous pemphigoid - a retrospective cohort study.

The features of bullous pemphigoid (BP) patients presenting with mucosal lesions are not established. We aimed to elucidate the clinical and immunological features of BP patients with mucosal involvement, and to identify factors associated with mucosal lesions. A retrospective study encompassing all consecutive patients diagnosed with BP throughout the years 2009-2019 in a tertiary referral center. The study encompassed 273 patients with BP, of whom 31 (11.4%) presented with mucosal lesions. The oral mucosa was the most frequently affected mucosal surface (71.0%), followed by the genital (25.8%) and the nasal (22.6%) mucosae. Relative to other patients with BP, patients with mucosal involvement had a more prominent palmoplantar involvement (67.7% vs. 37.2%; P=0.001); lower seropositivity rate (18.2% vs. 54.2%; P=0.027) and lower levels (29.3 ±64.5 vs. 129.5 ±304.4U/ml; P=0.016) of anti-BP230 autoantibodies; and decreased peripheral eosinophil counts (760.0 ±638.6 vs. 1296.3 ±1013.7; P<0.001). Absence of anti-BP230 autoantibodies (OR, 5.32; 95% CI, 1.07-26.32; P=0.026) and lack of peripheral eosinophilia (OR, 4.31; 95% CI, 1.14-16.39; P=0.021) were associated with the presence of mucosal involvement in BP. Mucosal involvement is present in a notable subgroup of patients with BP and is associated with the absence of both anti-BP230 antibodies and peripheral eosinophilia.

MO877PREVALENCE AND PERSISTENCE OF COVID-19 ANTIBODIES IN NEW YORK CITY HEMODIALYSIS CLINIC

Background and AimsDialysis patients are at higher risk for severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. Longevity of antibody response to SARS-CoV-2 infection remains unclear. It is reported that maintenance hemodialysis (MHD) patients can mount an antibody response that is similar in intensity and timing to the non-dialysis population. We aim to investigate the prevalence and persistence of antibodies in hemodialysis patients.MethodWe measured IgG and IgM antibodies in MHD patients as part of a quality improvement project. Four New York City dialysis clinics participated in this study. Strict policy of RT-PCR testing was implemented in clinics for patients with signs and symptoms of Coronavirus Disease 2019 (COVID-19). Initial antibody testing was done on June 10 and July 13, 2020 (phase 1) and retesting was done for previously positive patients between December 9 and 17, 2020 (phase 2). Upon obtaining verbal consent, 3.5 ml of pre-dialysis blood samples were taken via vascular access. SARS-CoV-2 antibodies were determined using the emergency use authorized Diazyme DZ-Lite SARS-CoV-2 IgM / IgG CLIA assays with 100% sensitivity and 98% specificity. Detection of formed immune-complexes is achieved with N-(4-amino-butyl)-N-ethyl-isoluminol; the luminescence signal is reported as units per ml (AU/ml), values ≥ 1.00 AU/ml are considered as “reactive” and < 1.00 AU/ml as “non-reactive.”ResultsA total of 429 MHD patients were studied in phase 1. Antibodies were present in 130 (30.3%) and only 55 patients with Covid-19 diagnosis confirmed by RT-PCR test were reactive for IgG antibodies. The time to antibody testing was 73 days (median 77; range 30-111) days. In the phase 2 antibody testing, IgG antibodies were only detected in 47 patients (85.5%) 242 days (median 245, range 204 to 268) after clinical diagnosis of Covid-19. Between the two phases of antibody testing, the luminescence signal declined by 40.9 AU/mL (95% confidence interval 31.5 to 50.3) from 54.1±45.3 to 13.2±20.9 AU/mL (P<0.0001 by paired t-test; Figure 1). In univariate logistic regression, a higher number of days between clinical diagnosis of COVID-19 and the second antibody measurement was associated with a lower seropositivity rate (odds ratio 0.929, 95% confidence interval 0.864 to 0.998, P=0.044). Antibody persistence was not associated with age, gender, race, and ethnicity.MO877 Figure 1: Quantitative change of IgG antibodies over time.The antibody tests were done on average 171 days (range 154 to 189) apart. The quantitative luminescence signal declined by 40.9 AU/mL (95% confidence interval 31.5 to 50.3) from 54.1±45.3 to 13.2±20.9 AU/mL (P<0.0001 by paired t-test).ConclusionWe observed that about 6 out of 7 MHD patients maintain SARS-CoV-2 antibodies over 6-9 months but there is a significant decline of IgG level. The time between clinical diagnosis and IgG testing was associated with IgG decline. Follow up study to understand antibody dynamics in MHD population is a crucial step once vaccines become available.

P341 Perceived risks and psychosocial burden during the COVID-19 pandemic in a large cohort of pediatric and adult patients with Inflammatory Bowel Disease

BackgroundThe COVID-19 pandemic induced restrictions in daily life and anxiety especially in vulnerable parts of the population. We investigated the psycho-social burden of the pandemic and self-perceived risk and harm in a large IBD cohort.MethodsIn this monocentric prospective observational study, pediatric (pIBD) and adult patients completed questionnaires related to their IBD (phenotype, disease activity, treatment), comorbidities, demographic and socioeconomic factors, validated tools on Perceived Stress (PSQ) and quality of life (sIBDQ). They judged perception of harm in case of acquiring COVID-19 using ratings from 1 to 7. We used number and type of established conditions for severe COVID-19 outcome to categorize patients in 5 risk groups. SARS-CoV2 antibodies were determined by Elecsys Roche anti-N pan-Ig. All comparisons were made by using t-test, Mann-Whitney-U-test or Chi-square-test where applicable with 2-sided significance levels of 5%. Univariate and multiple logistic regression was performed to determine associations between factors and perceived harm.ResultsBetween mid-July to mid-October, 504 (62%) of 820 invited IBD patients and 86 pIBD parents completed the survey. Age ranged from 6-85 years, 80% received mono- or combo-therapy with immunomodulator, biologic, JAK-inhibitor or corticosteroids. Remission, mild, moderate and severe disease activity were reported by 46, 39, 12 and 3%, respectively. High harm of potential COVID-19 (>3) was perceived by 75.4%, rates increased with age (p=0.0019). After adjusting for age and gender, high perceived harm was significantly associated with immunosuppressive drugs, number/type of comorbidities, sleep disturbance, unintended gain or loss of weight, higher PSQ and lower sIBDQ scores. PSQ scored lower in males >60 years vs age matched females or younger adults, and in patients in remission vs active disease. PIBD mothers’ total PSQ was similar with even higher subscores for demands (P=0.0004) as adults with moderate/severe disease. Compared to pre-pandemic, 58-93% of pIBD decreased physical activities (at home, sports, outdoor) with minor changes in adults. SARS-CoV-2 serology was positive in 0.4% of IBD patients compared to 2% of our city population. ConclusionPrior to 2nd infection wave, even IBD patients aged <40 years suffer from a high degree of worries, stress and perceived harm for potential COVID-19. Most elderly patients and those with comorbidities adequately estimate their risks. In pIBD, pandemic restrictions substantially impacted on physical activity. The low seropositivity rate indicates high adherence to social distancing or altered immune response due to IBD drugs. Results of the follow up survey in March 21 are underway.

LB0003 IMMUNOGENICITY AND SAFETY OF THE BNT162b2 mRNA COVID-19 VACCINE IN ADULT PATIENTS WITH AUTOIMMUNE INFLAMMATORY RHEUMATIC DISEASES AND GENERAL POPULATION: A MULTICENTER STUDY

Background:Vaccination represents a cornerstone in mastering the COVID-19 pandemic. Data on immunogenicity, efficacy, and safety of the novel BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases (AIIRD) are limited.Objectives:To investigate the immunogenicity, efficacy, and safety of the BNT162b2 mRNA vaccine in patients with AIIRD compared to the general population.Methods:A prospective multicenter study investigated immunogenicity, efficacy, and safety of the two-dose regimen BNT162b2 mRNA vaccine in adult patients with AIIRD including rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthropathy (axSpA), systemic lupus erythematosus (SLE), connective tissues diseases (CTD), systemic vasculitides, and idiopathic inflammatory myositis (IIM), compared to control subjects without rheumatic diseases or immunosuppressive therapies. Serum IgG antibody levels against SARS-CoV-2 spike S1/S2 proteins were measured 2 - 6 weeks after the second vaccine dose. Seropositivity was defined as IgG ≥15 binding antibody units (BAU)/ml. Post-vaccination efficacy defined as post-vaccination COVID-19 infection and safety were assessed. Pre- and post- vaccination disease activity indices were assessed as appropriate for each disease.Results:A total of 686 AIIRD patients and 121 controls participated into the study. AIIRD patients were significantly older than controls, mean age±SD 56.76±14.88 vs 50.76±14.68, respectively, p&lt;0.0001. A total of 95.2% (n=653) AIIRD patients were treated with immunomodulatory medications.The seropositivity rate was 86% (n=590) in patients with AIIRD compared to 100% in controls (p &lt;0.0001) The level of the S1/S2 antibodies was significantly reduced in AIIRD patients compared to controls (mean± SD 132.9±91.7 vs 218.6±82.06, P&lt;0.0001). In patients with PsA, AxSpA, SLE, and LVV, the seropositive rate was above 90%. In RA, the seropositive rate was 82.1% and the lowest seropositive rate (&lt;40%) was observed in patients with AAV and IIM.Anti-CD20 significantly impaired the vaccine’s immunogenicity, with the lowest seropositivity rate of 39%. The use of GC, mycophenolate mofetil (MMF), and abatacept was associated with a significantly lower rate of seropositivity (Figure 1). MTX significantly reduced the seropositivity in patients treated with MTX monotherapy and in combinations with other treatments (92% and 84%, respectively), although at a lesser magnitude than anti-CD20, MMF, and abatacept. More than 97% of patients treated with anti-cytokine therapies including TNFi, interleukin-17 and interleukin-6 inhibitors had an appropriate immunogenic response when used as monotherapy. The combination of TNFi with MTX significantly reduced the rate of seropositivity to 93%, p=0.04. Age over 65 years, a diagnosis of RA, IIM, ANCA-associated vascilitis, and treatment with GC, MMF, anti-CD20, and abatacept were associated with a reduced likelihood of seropositivity.Figure 1.Seropositivity rate by immunosuppressive treatment.There were no post-vaccination symptomatic cases of COVID-19 among AIIRD patients and one mild case in the control group. Major adverse events in AIIRD patients included death (n=2) several weeks after the second vaccine dose, non-disseminated herpes zoster (n=6), uveitis (n=2), and pericarditis (n=1). Post-vaccination disease activity remained stable in the majority of patients.Conclusion:Vaccination with the BNTb262 vaccine resulted in an adequate immunogenic response with an acceptable safety profile in the majority of patients with AIIRD. Treatment with GC, rituximab, MMF, and abatacept may impair BNT162b2-induced immunogenicity. Postponing administration of rituximab, when clinically feasible, seems to be reasonable to improve vaccine-induced immunogenicity. Holding treatment with abatacept and MMF may be considered on an individual basis.Disclosure of Interests:None declared

Serum biomarker profile orchestrating the seroconversion status of patients with autoimmune diseases upon planned primary 17DD Yellow fever vaccination

The present study aimed to investigate whether the serum biomarkers of immune response orchestrate the seroconversion status in patients with autoimmune diseases (AID) upon planned primary 17DD-YF vaccination. For this purpose a total of 161 individuals were enrolled in a prospective study, including patients with Rheumatoid Arthritis (RA = 38), Spondyloarthritis (SpA = 51), Systemic Lupus Erythematosus (SLE = 21) and Sjögren’s Syndrome (SS = 30) along with a group of healthy controls (HC = 21). Analysis of plaque reduction neutralization test (PRNT) titers and seropositivity rates along with the 17DD-YF viremia and serum biomarkers were carried out at distinct time points (D0/D3–4/D5–6/D7/D14–28). The results demonstrated an overall lower PRNT titer and seropositivity rate (170 vs. 448; 77 vs. 95%) in AID as compared to HC, especially in SpA and SLE subgroups. No significant differences were observed in the viremia levels amongst groups. In general, a more prominent serum biomarker response was observed in AID as compared to HC, throughout the timeline kinetics. Remarkably, AID/PRNT(−) exhibited higher levels of several biomarkers at baseline as compared to AID/PRNT+. Moreover, while AID/PRNT(+) exhibited earlier increase in serum biomarkers at D3–4/D5–6, the AID/PRNT(−) displayed higher response at later time points (D7/D14–D28). Of note, a synchronic increase of IFN-γ at the peak of viremia (D5–6) was observed in HC and AID/PRNT(+) groups, whereas a later asynchronous IFN-γ response was reported for AID/PRNT(−) at D7. The biomarker profile tends to deflate at post-vaccination timeline, highlighting a putative immunomodulatory effect of live attenuated 17DD-YF vaccine in AID/PRNT(+), but not in AID/PRNT(−). Altogether these data suggested that inflammatory status prior vaccination, low IFN-γ at viremia peak and the occurrence of asynchronous biomarker storm after 17DD-YF vaccination may orchestrate the lack of neutralizing antibody response γ.

Impact of Coinfection with Schistosoma mansoni on the Antibody Response to Helicobacter pylori.

In many tropical areas, the coinfection of Schistosoma spp. and other pathogens is frequent. The impact of schistosomiasis on other infections has been demonstrated for several organisms. Infection with the widely spread bacterium, Helicobacter pylori, has been linked to ulcers and tumors of the digestive system with the humoral immune response playing possible modulatory roles. The present study investigated the impact of patent S. mansoni infection on the antibody response to H. pylori. A total of 100 participants from a schistosomiasis endemic area in Egypt were enrolled in the study. Based on the detection of S. mansoni eggs and H. pylori coproantigen in fecal samples, they were equally divided into four groups: schistosomiasis, concomitant S. mansoni and H. pylori infection, H. pylori infection alone, and healthy controls. Anti-H. pylori IgG and IgA were determined in serum samples using ELISA. A significantly lower IgA seropositivity rate and significantly lower IgG levels were found in patients with concomitant schistosomiasis (Gp2) compared to those infected only with H. pylori (Gp1). Concomitant S. mansoni infection with light to moderate intensity alters serological responses to H. pylori. In schistosomiasis endemic areas, the routine examination for H. pylori infection should, therefore, rely on coproantigen level rather than antibody levels. Further studies should investigate histopathological changes and other immunological parameters in coinfection.

HEPATITIS VACCINATION AND ANTIBODY STATUS AMONG U.S. ADULTS WITH INFLAMMATORY BOWEL DISEASE

Abstract Background It is difficult to predict when inflammatory bowel disease (IBD) patients will need to receive immunosuppressive therapy. The use of immunosuppressants increases the risks of opportunistic infection and re-activation of viral replication. Hepatitis A (HAV) and B (HBV) are still endemic in certain areas of the world, and the latter has the potential to induce fulminant hepatitis with hepatic failure in the immunocompromised. Thus, it is important to routinely screen IBD patients for hepatitis and recommend appropriate vaccinations for those who are seronegative for antibodies. Methods We performed a retrospective analysis with data from the National Health and Nutrition Survey (NHANES) from 2009 to 2010. We identified participants who reported whether they were told by a doctor or other health professional that they have IBD. We excluded those who did not provide pertinent information and those who did not know their vaccination status. For the purpose of statistical analysis, vaccination status was stratified as either complete or incomplete. Complete vaccination for HAV was defined as at least 2 doses, and that for HBV was defined as 3 doses. Incomplete vaccination was defined as the aggregate of inadequate doses, no doses, and refusal. Results HAV vaccination data was available in 48 IBD and 4303 non-IBD participants. Complete HAV vaccination was 14.6% among IBD patients, compared to 26.4% for non-IBD participants (odds ratio [OR] 0.47; 95% confidence interval [CI], 0.21–1.06). There were 55 IBD and 4443 non-IBD participants with known anti-HAV antibody status, and seropositivity was similar for both groups (41.8% vs. 42.4%, p=0.93). HBV vaccination data was available in 50 IBD and 4349 non-IBD participants. Complete HBV vaccination was 26.0% among IBD participants, compared to 34.4% among non-IBD participants (OR 0.67; 95% CI, 0.35–1.26). The presence of anti-HBV surface antibody was reported in 58 IBD and 4666 non-IBD participants, and seropositivity in the IBD group was less than the non-IBD group (17.2% vs. 23.5%, p=0.26). Conclusion Patients with IBD have lower rates of hepatitis vaccination and lower seropositivity for hepatitis antibodies. The current American College of Gastroenterology guidelines recommend the assessment and completion of HBV vaccination schedule prior to initiating biologic therapy. The European Crohn’s and Colitis Organisation is stricter on the timing of these preemptive measures and recommends doing so at the time of IBD diagnosis. A small number of studies have suggested that seroconversion following vaccination may be reduced in IBD patients, but even so, the vaccination rates need to be improved greatly. To do so, gastroenterologists and primary care physicians should systematically educate IBD patients on the importance of hepatitis vaccination and recommend routine testing for seronegative patients.