Spike Protein Antibodies Research Articles

Humoral COVID-19 vaccine response in patients with NMOSD/MOGAD during anti-IL-6 receptor therapy compared to other immunotherapies

Background: Data on the humoral vaccine response in patients on anti-interleukin-6 (IL-6) receptor therapy remain scarce. Objective: The main objective of our study was to investigate the humoral response after vaccination against SARS-CoV-2 in neuromyelitis optica spectrum disorder (NMOSD)/myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) patients treated with anti-IL-6 receptor therapy. Secondarily, we analyzed relapse activity timely associated with vaccination. Methods: In this retrospective cross-sectional multicenter study, we included 15 healthy controls and 48 adult NMOSD/MOGAD patients without previous COVID-19 infection. SARS-CoV-2 spike protein antibody titers during anti-IL-6 receptor therapy were compared to anti-CD20 antibody therapy, oral immunosuppressants, and to nonimmunosuppressed individuals. Results: We observed 100% seroconversion in the anti-IL-6 receptor treatment group. Titers of SARS-CoV-2 spike protein antibodies were lower compared to healthy controls (720 vs 2500 binding antibody units (BAU)/mL, p = 0.004), but higher than in the anti-CD20 (720 vs 0.4 BAU/mL, p < 0.001) and comparable to the oral immunosuppressant group (720 vs 795 BAU/mL, p = 1.0). We found no association between mRNA-based vaccines and relapse activity in patients with or without immunotherapy. Conclusions: Despite being lower than in healthy controls, the humoral vaccine response during anti-IL-6 receptor therapy was evident in all patients and substantially stronger compared to anti-CD20 treatment. No relevant disease activity occurred after mRNA vaccination against SARS-CoV-2.

P755 Impaired antibody seroconversion after COVID-19 vaccination and negative impact of immunosuppressive treatment in Inflammatory Bowel Disease. Results from a multicentre, prospective study of GETECCU (VACOVEII)

Abstract Background COVID-19 vaccination has been suggested as very effective in patients with Inflammatory Bowel Disease (IBD), but most studies assess antibody levels within a few weeks after vaccination and do not use the most recent recommendations as seroconversion cut-off. The objective of VACOVEII study is to evaluate the antibody response to vaccination at 6 months using these recommendations, the improvement after a booster dose and the effect of the immunosuppressive therapy (IST). We present the intermediate results of the study. Methods Spanish multicentre, prospective and case-control study. 18 years or older IBD patients fully vaccinated against COVID-19 were included. Those with previous COVID infection were not included, but not excluded for the next analyses if the infection was subsequent. Main outcomes were anti-SARS-CoV-2 spike protein antibody (anti S) concentrations and rate of seroconversion (defined above the protection threshold of 260 BAU/mL), measured 6 months after vaccination at a single centralized laboratory. The effect of IST on the main outcomes was analysed, adjusted by age, vaccine type and COVID infection. Groups of treatment considered for the analysis were: patients without IST (without treatment or under salicylates alone), anti-TNF in combination with immunomodulators (IMM), anti-TNF in monotherapy, IMM in monotherapy, ustekinumab and anti-integrin. Results We included 313 patients with IBD (46.5% ulcerative colitis and 52.3% Crohn’s disease, median age 49 years) vaccinated either with non-mRNA vaccines (14%) or mRNA vaccines (86%). Baseline therapy was: 124 patients without IST, 21 with anti-TNF plus IMM, 67 with anti-TNF in monotherapy, 54 with IMM in monotherapy, 28 with ustekinumab and 19 with anti-integrin. Mean anti S concentrations were significant lower in patients with anti-TNF compared with patients without IST (Figure 1). In multivariable analysis, lower antibody concentrations were independently associated with anti-TNF treatment, non-mRNA vaccines and older age. Within the patients with no COVID infection during the follow-up, we found very low rates of seroconversion in patients with anti-TNF (14.1%), ustekinumab (30.8%) and IMM in monotherapy (34.9%), compared with patients without IST (51.5%) (Table 1). In multivariable analysis, anti-TNF treatment, non-mRNA vaccines and older age were independently associated with lower rates of seroconversion, as well as ustekinumab and IMM in monotherapy (Table 2). Conclusion COVID-19 vaccine-induced antibody seroconversion in patients with IBD, measured at 6 months and according to &amp;gt;260 BAU as protection threshold, is clearly lower than previously reported, with a profound impact by some IST therapies, mainly anti-TNF, besides age and type of vaccine.

Lack of seroresponse to SARS-CoV-2 booster vaccines given early post-transplant in patients primed pre-transplantation.

SARS-CoV-2 vaccines are recommended pre-transplantation, however, waning immunity and evolving variants mandate booster doses. Currently there no data to inform the optimal timing of booster doses post-transplant, in patients primed pre-transplant. We investigated serial serological samples in 204 transplant recipients who received 2 or 3 SARS-CoV-2 vaccines pre-transplant. Spike protein antibody concentrations, [anti-S], were measured on the day of transplantation and following booster doses post-transplant. In infection-naïve patients, post-booster [anti-S] did not change when V3 (1st booster) was given at 116(78-150) days post-transplant, falling from 122(32-574) to 111(34-682) BAU/ml, p=0.78. Similarly, in infection-experienced patients, [anti-S] on Day-0 and post-V3 were 1090(133-3667) and 2207(650-5618) BAU/ml respectively, p=0.26. In patients remaining infection-naïve, [anti-S] increased post-V4 (as 2nd booster) when given at 226(208-295) days post-transplant, rising from 97(34-1074) to 5134(229-5680) BAU/ml, p=0.0016. Whilst in patients who had 3 vaccines pre-transplant, who received V4 (as 1st booster) at 82(49-101) days post-transplant, [anti-S] did not change, falling from 981(396-2666) to 871(242-2092) BAU/ml, p=0.62. Overall, infection pre-transplant and [anti-S] at the time of transplantation predicted post-transplant infection risk. As [Anti-S] fail to respond to SARS-CoV-2 booster vaccines given early post-transplant, passive immunity may be beneficial to protect patients during this period.

SARS-CoV-2 delta (B.1.617.2) spike protein adjuvanted with Alum-3M-052 enhances antibody production and neutralization ability.

Optimizing adjuvant is one of the critical methods to improve the vaccine. 3M-052, a novel TLR7/8 agonist which was designed for slow dissemination at the injection site, has a potential as adjuvant, but its performance as a vaccine adjuvant for SARS-CoV-2 (B.1.617.2) spike protein has not been studied. The present study aimed to evaluate the effect of Alum-3M-052 as an adjuvant to improve mice serum antibody titers and pseudovirus neutralization efficiency. Female Balb/c mice were immunized 3 times at day 0, 7 and 21 intramuscularly with SARS-CoV-2 (B.1.617.2) spike protein and adjuvant (Alum or Alum-3M-052). Mice serum was collected weekly since day 7. Antibody titers of mice serum anti-SARS-CoV-2 (B.1.617.2) IgG and IgM were detected by ELISA. Inhibition rates of mice serum blocking SARS-CoV-2 (B.1.617.2) spike protein binding to ACE2 were detected by SARS-CoV-2 (B.1.617.2) Inhibitor Screening Kit. Neutralization efficiencies of mice serum against both SARS-CoV-2 (BA.2.12.1) pseudovirus and SARS-CoV-2 (B.1.617.2) pseudovirus were detected by pseudovirus neutralizing assay. Serum of mice immunized by SARS-CoV-2 (B.1.617.2) spike protein adjuvanted with Alum-3M-052 had highest antibody titers and higher neutralization efficiency against both SARS-CoV-2 (BA.2.12.1) pseudovirus and SARS-CoV-2 (B.1.617.2) pseudovirus. Besides, neutralization efficiency of anti-SARS-CoV-2 (B.1.617.2) spike protein antibody against SARS-CoV-2 (BA.2.12.1) pseudovirus was lower than that of SARS-CoV-2 (B.1.617.2) pseudovirus. Alum-3M-052 rapidly increased the titer of anti-SARS-CoV-2 (B.1.617.2) spike protein neutralizing antibodies and enhanced the neutralization ability against pseudoviruses and variants. This study provided evidence for the application of Alum-3M-052 as an adjuvant in COVID-19 vaccines production.

Differences in BNT126b2 and ChAdOx1 Homologous Vaccination Antibody Response among Teachers in Poznan, Poland

Children are among the best vectors to spread respiratory viruses, including emerging variants of SARS-CoV-2 due to the asymptomatic or relatively mild course of infection and simultaneously high titres of pathogens in the respiratory tract. Therefore, individuals who have constant contact with children, e.g., teachers should be vaccinated against COVID-19 as essential workers within the first phases of a vaccination campaign. In Poland, primary and secondary school teachers were vaccinated with ChAdOx1 from February 2021 with a three month interval between the two doses, while lecturers at medical universities, who are simultaneously healthcare workers, received the BNT126b2 vaccine from December 2020 with three weeks between the first and second doses. The aim of this study was to compare the antibody responses at two weeks and three months after vaccination and to estimate the vaccine effectiveness against COVID-19 among infection-naïve teachers vaccinated with mRNA and a vector vaccine. We found that the anti-SARS-CoV-2 spike protein antibodies were significantly higher among the lecturers but antibody waning was slower among the schoolteachers. However, those vaccinated with ChAdOx1 complained significantly more often of vaccine side effects. In addition, during the three months after the second vaccine dose no study participants were infected with SARS-CoV-2. The BNT126b2 vaccine gave higher antibody titres in comparison with ChAdOx1 but protection against COVID-19 in both cases was similar. Moreover, we did not find any anti-SARS-CoV-2 nucleoprotein antibodies at two weeks as well as at three months after vaccination among the study participants, which shows a very high vaccine effectiveness in the occupational group with a high SARS-CoV-2-infection risk.

Augmented humoral and cellular immunity against severe acute respiratory syndrome coronavirus 2 after breakthrough infection in kidney transplant recipients who received 3 doses of coronavirus disease 2019 vaccine

Diminished immune response to coronavirus disease 2019 (COVID-19) vaccines and breakthrough infection (BI) is a major concern for solid organ transplant recipients. Humoral and cellular immune responses of kidney transplant (KT) recipients after a third COVID-19 vaccination were investigated compared to matched health care workers. Anti–severe acute respiratory syndrome coronavirus 2 spike protein antibody and severe acute respiratory syndrome coronavirus 2 specific interferon-gamma releasing assay (IGRA) were assessed. A total of 38 KT recipients, including 20 BI and 18 noninfection, were evaluated. In the KT BI group, antibody titers were significantly increased (median 5 to 724, binding antibody units/mL (P = 0.002) after the third vaccination, but IGRA responses were negligible. After BI, antibody titers increased (median 11 355 binding antibody unit/mL; P < 0.001) and there was a significant increase of IGRA responses to spike proteins (Spike1-Nil, median 0.05 to 0.41 IU/mL; P = 0.009). Antibody titers and IGRA responses were significantly higher in the BI than in the noninfection group after 6 months. Immune responses were stronger in the health care worker than in the KT cohort, but the gap became narrower after BI. In conclusion, KT recipients who experienced BI after 3 COVID-19 vaccinations acquired augmented humoral and cellular immune responses.

Demonstration of Antibodies Against SARS-CoV-2, Neutralizing or Binding, in Seroconversion Panels After mRNA-1273, BNT-162b2, and Ad26.COV2.S Vaccine Administration

Vaccines are an important tool in combating the COVID-19 pandemic. Two mRNA vaccines (mRNA-1273 and BNT-162b2) and an adenovirus vector vaccine (Ad26.COV2.S) were among the first vaccines to be approved by global regulatory authorities. The aim of this observational study was to characterize the levels and time course of the generation of anti-SARS-CoV-2 spike protein antibodies after vaccination with 3 different vaccines and the neutralizing activity of these antibodies. Seroconversion panels were generated from blood samples collected before and after vaccination with 3 COVID-19 vaccines: mRNA-1273, BNT-162b2, and Ad26.COV2.S. The seroconversion panels were tested for antibody activity by chemiluminescent immunoassay or enzyme-linked immunosorbent assay (ELISA), and 1 panel was tested for neutralization activity in a pseudovirus assay. Participants positive for anti-SARS-CoV-2 antibodies before vaccination (18.6%) had a higher response to the first dose than participants who tested negative. For 2-dose vaccines, older participants showed a lower response to the first dose than younger participants. All participants showed positive responses after the second vaccine. For the adenovirus vector vaccine, 2 participants did not generate antibody responses after vaccination. Four participants were negative at 2 weeks but positive at 2 months. Pseudovirus neutralization showed good correlation with antibody activity (correlation coefficient = 0.78, P &lt; .0001). Antibody responses in participants over 45 years old tended to be less robust. Participants that had been infected with SARS-CoV-2 and had antibodies prior to vaccination showed a more robust response to initial vaccination. Older participants (&gt;45 years) showed less robust responses to both types of vaccine. All participants receiving full mRNA vaccination showed positive antibody responses. Some participants receiving the adenovirus vaccine did not respond. Antibody responses correlated well with neutralization activity. Seroconversion panels can be useful in the development of antibody assays and in investigating their effectiveness against new SARS-CoV-2 variants.

Antibody Response to Inactive SARS-CoV-2 Vaccination in a Cohort of Elderly Patients Living with Obesity

Introduction: Obesity and aging negatively affect the immune system and host defense mechanisms, increasing vulnerability to and worsening prognosis of infectious diseases, leading to vaccine failure. Our aim was to investigate the antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antigens and the risk factors affecting antibody levels in elderly patients living with obesity (PwO) after inactive SARS-CoV-2 vaccine (CoronaVac) administration. Methods: One hundred twenty-three consecutive elderly patients with obesity (age ≥65 years, body mass index [BMI] ≥30 kg/m²) and 47 adults with obesity (age 18–64 years, BMI ≥30 kg/m²) admitted between August and November 2021 were enrolled. Seventy-five nonobese elderly people (age ≥65 years, BMI 18.5–29.9 kg/m²) and 105 nonobese adults (age 18–64 years, BMI 18.5–29.9 kg/m²) were recruited from subjects who visited the Vaccination Unit. SARS-CoV-2 spike protein antibody titers were measured in patients with obesity and nonobese controls who received two doses of CoronaVac. Results: SARS-CoV-2 levels of patients with obesity were found to be significantly lower than those of nonobese elderly individuals who had non-prior infection. There was no difference in SARS-CoV-2 levels between patients with obesity and nonobese individuals with prior infection. Age and SARS-CoV-2 level were found to be highly correlated in the correlation analysis in the group of elderly individuals (r: −0.184). In multivariate regression analysis, when SARS-CoV-2 immunoglobulin class G (IgG) was regressed on age, sex, BMI, type 2 diabetes mellitus, and hypertension (HT), HT was found to be an independent factor of the SARS-CoV-2 level (β: −2,730). Conclusion: In the non-prior infection group, elderly patients with obesity generated significantly reduced antibody titers against SARS-CoV-2 spike antigen after CoronaVac vaccine compared to nonobese people. It is anticipated that the results obtained will provide invaluable information about SARS-CoV-2 vaccination strategies in this vulnerable population. Antibody titers may be measured, and booster doses should be delivered accordingly in elderly PwO for optimal protection.

Positive Predictive Value of SARS-CoV-2 Spike Protein Antibody Test after COVID-19 Vaccination Policies.

Positive Predictive Value of SARS-CoV-2 Spike Protein Antibody Test after COVID-19 Vaccination Policies.

The Levels of Anti-SARS-CoV-2 Spike Protein IgG Antibodies Before and After the Third Dose of Vaccination Against COVID-19.

The COVID-19 pandemic has been going on for almost three years, and so far, many preventive and therapeutic strategies have been developed. The issue of subsequent booster vaccinations is currently being discussed. We aimed to analyze how the third dose of vaccination against COVID-19 correlates with the dynamics of IgG anti-SARS-CoV-2 spike protein antibody levels in a group of healthy people. The prospective study included 93 participants before and after a second booster of COVID-19 vaccination, from whom 4 blood samples were collected at intervals. The levels of IgG anti-SARS-CoV-2 in serum were identified using the chemiluminescent immunoassay specific for the receptor-binding domain (RBD) of the S1 protein. The analysis of the results was performed using appropriate statistical methods, considering p <0.05 as a statistically significant value. The IgG levels were significantly higher and less diverse after the same follow-up time from the second booster vaccination compared to the first booster. The antibody levels were positively correlated with female, healthcare workers, the elderly and participants with a negative COVID-19 history. Furthermore, the increase in IgG antibodies after the second booster vaccination correlated inversely with the baseline level of antibodies before the vaccination. The latest results showed that antibody levels dropped 1.5-fold after approx. 10 months from the second booster vaccination but still remained at a protective level. Booster vaccinations seem to better stimulate immune memory, and in the case of borderline IgG level induces the greatest increase in antibodies. It is worth considering the individual parameters of patients and measuring antibodies before vaccination.

Association of SARS-CoV-2 Spike Protein Antibody Vaccine Response With Infection Severity in Patients With Cancer

Accurate identification of patient groups with the lowest level of protection following COVID-19 vaccination is important to better target resources and interventions for the most vulnerable populations. It is not known whether SARS-CoV-2 antibody testing has clinical utility for high-risk groups, such as people with cancer. To evaluate whether spike protein antibody vaccine response (COV-S) following COVID-19 vaccination is associated with the risk of SARS-CoV-2 breakthrough infection or hospitalization among patients with cancer. This was a population-based cross-sectional study of patients with cancer from the UK as part of the National COVID Cancer Antibody Survey. Adults with a known or reported cancer diagnosis who had completed their primary SARS-CoV-2 vaccination schedule were included. This analysis ran from September 1, 2021, to March 4, 2022, a period covering the expansion of the UK's third-dose vaccination booster program. Anti-SARS-CoV-2 COV-S antibody test (Elecsys; Roche). Odds of SARS-CoV-2 breakthrough infection and COVID-19 hospitalization. The evaluation comprised 4249 antibody test results from 3555 patients with cancer and 294 230 test results from 225 272 individuals in the noncancer population. The overall cohort of 228 827 individuals (patients with cancer and the noncancer population) comprised 298 479 antibody tests. The median age of the cohort was in the age band of 40 and 49 years and included 182 741 test results (61.22%) from women and 115 737 (38.78%) from men. There were 279 721 tests (93.72%) taken by individuals identifying as White or White British. Patients with cancer were more likely to have undetectable anti-S antibody responses than the general population (199 of 4249 test results [4.68%] vs 376 of 294 230 [0.13%]; P < .001). Patients with leukemia or lymphoma had the lowest antibody titers. In the cancer cohort, following multivariable correction, patients who had an undetectable antibody response were at much greater risk for SARS-CoV-2 breakthrough infection (odds ratio [OR], 3.05; 95% CI, 1.96-4.72; P < .001) and SARS-CoV-2-related hospitalization (OR, 6.48; 95% CI, 3.31-12.67; P < .001) than individuals who had a positive antibody response. The findings of this cross-sectional study suggest that COV-S antibody testing allows the identification of patients with cancer who have the lowest level of antibody-derived protection from COVID-19. This study supports larger evaluations of SARS-CoV-2 antibody testing. Prevention of SARS-CoV-2 transmission to patients with cancer should be prioritized to minimize impact on cancer treatments and maximize quality of life for individuals with cancer during the ongoing pandemic.

Cross-Clade Memory Immunity in Adults Following SARS-CoV-1 Infection in 2003

Knowledge of the longevity and breath of immune response to coronavirus infection is crucial for the development of next-generation vaccines to control the COVID-19 pandemic. To determine the profile of SARS-CoV-2 antibodies among persons infected with the closely related virus, SARS-CoV-1, in 2003 (SARS03 survivors) and to characterize their antibody response soon after the first and second doses of COVID-19 vaccines. This prospective cohort study examined SARS-CoV-2 antibodies among SARS03 survivors compared with sex- and age-matched infection-naive controls. Participants received the COVID-19 vaccines between March 1 and September 30, 2021. One of the 2 COVID-19 vaccines (inactivated [CoronaVac] or messenger RNA [BNT162b2]) available in Hong Kong. Two doses were given according to the recommended schedule. The vaccine type administered was known to both participants and observers. SARS-CoV-2 antibodies were measured prevaccination, 7 days after the first dose, and 14 days after the second dose. Eighteen SARS03 adult survivors (15 women and 3 men; median age, 46.5 [IQR, 40.0-54.3] years) underwent prevaccination serologic examination. The vast majority retained a detectable level of antibodies that cross-reacted with SARS-CoV-2 (16 of 18 [88.9%] with nucleocapsid protein antibodies and 17 of 18 [94.4%] with receptor-binding domain of spike protein antibodies); a substantial proportion (11 of 18 [61.1%]) had detectable cross-neutralizing antibodies. Twelve SARS03 adult survivors (10 women and 2 men) underwent postvaccination serologic examination. At 7 days after the first dose of vaccine, SARS03 survivors mounted significantly higher levels of neutralizing antibodies compared with controls (median inhibition: 89.5% [IQR, 77.1%-93.7%] vs 13.9% [IQR, 11.8%-16.1%] for BNT162b2; 64.9% [IQR, 60.8%-69.5%] vs 13.4% [IQR, 9.5%-16.8%] for CoronaVac; P < .001 for both). At 14 days after the second dose, SARS03 survivors generated a broader antibody response with significantly higher levels of neutralizing antibodies against variants of concern compared with controls (eg, median inhibition against Omicron variant, 52.1% [IQR, 35.8%-66.0%] vs 14.7% [IQR, 2.5%-20.7%]; P < .001). The findings of this prospective cohort study suggest that infection with SARS-CoV-1 was associated with detectable levels of antibodies that cross-react and cross-neutralize SARS-CoV-2, which belongs to a distinct clade under the same subgenus Sarbecovirus. These findings support the development of broadly protective vaccines to cover sarbecoviruses that caused 2 devastating zoonotic outbreaks in humans over the last 2 decades.

302. Using Severe Acute Respiratory Syndrome Coronavirus-2 Spike Protein Antibody Serology in addition to the ISARIC 4C Risk Score to Better Discriminate Adverse Clinical Outcomes in Hospitalized Patients with Coronavirus Disease 2019.

Abstract Background The Coronavirus disease 2019 (COVID-19) pandemic continues to threaten many countries globally. Large-scale vaccination exercises have helped to reduce transmission and severity of disease. We sought to modify an existing clinical score (the ISARIC-4C mortality score) to include serological status to better prognosticate hospitalized patients with COVID-19. Methods We examined the first 1781 consecutive hospitalized patients with polymerase chain reaction (PCR) confirmed COVID-19 in a tertiary academic centre. We divided the study population into those requiring intensive care and those who did not require throughout their inpatient stay. Baseline characteristics examined include medical comorbidities, vaccination status, SARS-CoV-2 serology spike protein, duration of fever and haemodynamics were compared. Adverse outcomes were defined as patients who required intensive care or mortality. Performance of the risk scores were measured by the area under receiver operating characteristic curves (AUC) in predicting adverse outcomes. Results The 55 patients requiring intensive care during their inpatient stay tended to have persistent fever beyond 72 hours and had lower titres of spike protein antibodies. (58.9 (±105.3) U/mL vs 144.2 (±116.2) U/mL, p = 0.007). A high spike protein antibody titre &amp;gt;75 U/mL was independently protective for adverse outcomes (adjusted OR 0.15, 95% CI 0.04-0.53), even after adjusting for the ISARIC-4C score and the presence of persistent fever. Adding the serological status and presence of persistent fever to the ISARIC-4C score improved its performance in predicting adverse outcomes (AUC 0.84, 95% CI 0.78-0.89). Conclusion Addition of the SARS-CoV-2 serology spike protein titre and prolonged fever to the ISARIC-4C mortality score helps to better prognosticate adverse clinical outcomes in hospitalized patients with COVID-19. Disclosures All Authors: No reported disclosures.

B Cell Reconstitution is Associated With COVID-19 Booster Vaccine Responsiveness in Patients Previously Seronegative Treated With Rituximab.

To assess factors associated with serologic response to the coronavirus 2019 (COVID-19) booster vaccine in patients with autoimmune rheumatic diseases treated with rituximab (RTX) who were previously serologically unresponsive to the initial vaccine series. A retrospective chart review of patients treated with RTX who failed to demonstrate a serologic response to the first SARS-CoV-2 vaccination series and subsequently received an mRNA vaccine booster was performed. Serologic response ≥ 4 weeks after the booster was the primary outcome. Fisher exact tests, t tests, and Wilcoxon rank-sum tests were used for comparisons. In 31 patients who were previously seronegative, 68% seroconverted following a booster of the COVID-19 vaccine. B cell reconstitution was significantly different between those with positive (median 1.79, IQR 0.65-3.00) and negative (median 0, IQR 0-0) serologic responses to the booster. The days from last RTX dose were also statistically different among seroconverters (median 301, IQR 251-368) vs nonseroconverters (median 188, IQR 169-245). Demographic characteristics were not associated with serologic positivity. Positive predictive value of B cell presence was 90.9% (95% CI 70.8-98.9) and negative predictive value was 100% (95% CI 59-100) for serologic response to the mRNA booster vaccine. Positive predictive value of time ≥ 6 months from last RTX dose to booster was 78.3% (95% CI 56.3-92.5) and the negative predictive value was 62.5% (95% CI 24.5-91.5). Detectable B cells and longer time from last RTX exposure were associated with the development of anti-SARS-CoV-2 spike protein antibodies following the booster vaccine. These findings should be considered in timing boosters in patients treated with RTX.

Anti-spike antibody response to the COVID vaccine in lymphoma patients.

Patients with hematologic malignancies have poor outcomes from COVID infection and are less likely to mount an antibody response after COVID infection. This is a retrospective study of adult lymphoma patients who received the COVID vaccine between 12/1/2020 and 11/30/2021. The primary endpoint was a positive anti-COVID spike protein antibody level following the primary COVID vaccination series. The primary vaccination series was defined as 2 doses of the COVID mRNA vaccines or 1 dose of the COVID adenovirus vaccine. Subgroups were compared using Fisher's exact test, and unadjusted and adjusted logistic regression models were used for univariate and multivariate analyses. A total of 243 patients were included in this study; 72 patients (30%) with indolent lymphomas; 56 patients (23%) with Burkitt's, diffuse large B-cell lymphoma (DLBCL), and primary mediastinal B-cell lymphoma (PMBL) combined; 55 patients (22%) with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL); 44 patients (18%) with Hodgkin and T-cell lymphomas (HL/TCL) combined; 12 patients (5%) with mantle cell lymphoma; and 4 patients (2%) with other lymphoma types. One-hundred fifty-eight patients (65%) developed anti-COVID spike protein antibodies after completing the primary COVID vaccination series. Thirty-eight of 46 (83%) patients who received an additional primary shot and had resultant levels produced anti-COVID spike protein antibodies. When compared to other lymphoma types, patients with CLL/SLL had a numerically lower seroconversion rate of 51% following the primary vaccination series whereas patients with HL/TCL appeared to have a robust antibody response with a seropositivity rate of 77% (p = 0.04). Lymphoma patients are capable of mounting a humoral response to the COVID vaccines. Further studies are required to confirm our findings, including whether T-cell immunity would be of clinical relevance in this patient population.

Humoral immunogenicity of COVID-19 vaccines in patients with coeliac disease and other noncoeliac enteropathies compared to healthy controls.

Data are lacking on the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients affected by coeliac disease, Whipple's disease and other noncoeliac enteropathies (NCE), characterised by primary or drug-related immunosuppression. We aimed to assess humoral response to SARS-CoV-2 vaccination in these patients compared to controls. Between December 2021 and January 2022, IgG anti-SARS-CoV-2 spike protein antibodies were measured in serum samples of coeliac disease, Whipple's disease and NCE patients attending our gastroenterology outpatient clinic for follow-up, who had received their first SARS-CoV-2 vaccination dose 3-6-9 (±1) months prior. Humoral response was compared with healthy controls (vaccinated healthcare workers undergoing serological screening), matched for gender, age, and time from first vaccine dose at sample collection. A total of 120 patients [107 coeliac disease; 10 Whipple's disease; 2 common-variable immunodeficiency (CVID); 1 idiopathic villous atrophy; 77 F, 42 ± 16 years] and 240 matched controls (154 F, 43 ± 14 years) were enrolled. At 3, 6 and 9 months, humoral response in coeliac patients was not impaired compared to controls. Inadequate humoral response to vaccination was significantly more common among Whipple's disease patients than controls ( P < 0.001). Patients on immunosuppressive therapy had markedly lower IgG anti-SARS-CoV-2 antibody titres (median 14 vs. 520 BAU/mL, P < 0.001). As expected, patients with CVID showed no humoral response to vaccination. Humoral immunogenicity of SARS-CoV-2 vaccines was not reduced in coeliac disease patients compared to controls, although it was in Whipple's disease and CVID patients. Post-vaccination humoral response should be monitored in patients with Whipple's disease and chronic enteropathies on immunosuppressive therapy in order to schedule vaccine booster doses.

Antibody Titer Correlates with Omicron Infection in Vaccinated Healthcare Workers.

The advent of vaccines against SARS-CoV-2 has drastically reduced the level of hospitalization with severe COVID-19 disease in infected individuals. However, the diffusion of variants of concern still challenge the protection conferred by vaccines raised against the wild-type form of the virus. Here, we have characterized the antibody response to the BNT162b2 (Comirnaty) mRNA vaccine in patients infected with the Omicron variant. We analyzed a population of 4354 vaccinated healthcare workers (HCW) from 7 different hospitals in Italy and monitored infection with SARS-CoV-2 Omicron. We correlated infection with the antibody response after vaccination. We found that a lower level of IgG, younger age, and the presence of allergies correlate with increased infection during the Omicron wave, and that infections correlate with wild-type spike protein antibody titers below 350 BAU/mL. These results support the necessity of a fourth booster dose, particularly for individuals with lower levels of antibodies.

Changes in spike protein antibody titer over 90 days after the second dose of SARS-CoV-2 vaccine in Japanese dialysis patients

ObjectivesThere is no report on antibody titers after vaccination against SARS-CoV-2 in Japanese dialysis patients. As dialysis is different between Japan and other countries, changes in antibody titers were examined.MethodsBaseline characteristics and anti-spike protein antibody titers (Roche) over 90 days after administration of the BNT162b2 messenger RNA vaccine were investigated in dialysis patients.ResultsThe maximum anti-spike protein antibody titer after the second dose was 738 (327 to 1143) U/mL and was reached at 19 (17 to 24) days after the second dose. Antibody titers decreased over time, with titers of 770 (316 to 1089) U/mL at 15 days, 385 (203 to 690) U/mL at 30 days, 254 (138 to 423) U/mL at 60 days, and 208 (107 to 375) U/mL at 90 days after the second dose. When an antibody titer of 137 U/mL was assumed to be a measure related to breakthrough infection, the proportion of subjects with antibody titers exceeding this level was 90.1% at 15 days, 85.3% at 30 days, 75.0% at 60 days, and 65.4% at 90 days after the second dose. When a decrease in antibody titers below the assumed breakthrough level was defined as an event, subjects with a pre-dialysis albumin ≥ 3.5 g/dL were significantly less likely to experience an event than subjects with a pre-dialysis albumin < 3.5 g/dL.ConclusionsThe presence of anti-spike protein levels ≥ 313 U/mL at 30 days after the second vaccine dose might be a factor in maintaining enough antibody titers at 90 days after. Whether an additional vaccine dose is needed should be determined based on indicators serving as factors in maintaining antibody titers as well as the status of the spread of infection.

Fluctuations of SARS-CoV-2 Antibody Concentrations with Age in Vaccine Naïve Population with SARS-CoV- 2 Infection

Abstract Introduction/Objective Notable differences have been observed in the severity of COVID-19 disease across age groups. This study’s aim was to investigate the antibody dynamics in children versus adults after natural infection with SARS-CoV-2. Methods/Case Report Charts of patients who had SARS-CoV-2 spike protein antibody (SPA) testing at our institution were reviewed. Patients with positive SPA and no documented evidence of SARS-CoV-2 vaccination were selected. SARS-CoV-2 nucleocapsid antibody (NA) testing was performed on the same SPA positive blood specimens to confirm that positive SPA was due to SARS-CoV-2 infection. In cases where NA testing could not be performed, SARS-CoV-2 polymerase chain reaction results were used to confirm previous infection. Patterns involving age, NA, and SPA concentrations were detected using scatter and box-and-whisker plots. Wilcoxon signed-rank tests were subsequently used to assess for statistical significance in the different age groups. This study was approved by our institution's IRB. Results (if a Case Study enter NA) There were 372 patients who had SPA testing and previous SARS-CoV-2 infection. SPA concentrations were not uniformly distributed but showed significantly higher concentrations in younger patients with a visually determined inflection point of around 20 years old. This was statistically confirmed by binning ages by decade of life and comparing their medians (p-value&amp;lt;0.05). Within the cohort, 107 patients were 20 years old or younger while 265 were older. Patients 0-20 years old had higher median SPA levels (262.9 U/mL vs. 108.2 U/mL, p-value&amp;lt;0.05) and significantly more variation (interquartile range 535 U/mL vs. 235 U/mL). NA levels showed a similar pattern in the overall distribution, but there was no statistically significant difference between the age groups (medians 45.835 U/mL vs. 30.3 U/mL, p-value=0.44). Conclusion These findings suggest that patients up to 20 years old have significantly higher SPA levels following SARS-CoV-2 infection, which may explain the milder symptoms of COVID-19 disease in children.

Association of Systemic Adverse Reactions and Serum SARS-CoV-2 Spike Protein Antibody Levels after Administration of BNT162b2 mRNA COVID-19 Vaccine.

Objectives The influential factors for anti-severe acute respiratory syndrome coronavirus 2 spike protein antibody (S-ab) levels were assessed after the administration of BNT162b2 mRNA coronavirus disease-2019 (COVID-19) vaccine at short and medium terms. Methods A total of 470 healthcare workers (118 males, mean age 41.0±11.9 years) underwent serum S-ab level measurement at 3 and 8 months after two inoculations of BNT162b2 vaccine given 3 weeks apart, who had no history of COVID-19 were enrolled in this study. The changes and differences after vaccination due to gender and adverse reactions of S-ab were analyzed. Results Systemic adverse reactions incidence (48%) was significantly higher after the second dose than after the first dose (8%). S-ab levels decreased as the age increased (from the 20s to 60s) in both measurements. S-ab level 8 months after the second inoculation [median 476.3 (interquartile range (IQR) 322.4-750.6) U/mL] was significantly lower than that after 3 months [977.5 (637.2-1,409.0) U/mL; p<0.001]. The median decrease rate of S-ab levels in 5 months was 50.3% (IQR 40.3-62.6) and those differences were not observed among all generations. Gender-associated differences in S-ab levels were not observed; however, a significant relationship between higher S-ab levels and the systemic adverse reactions was observed at both measurements. Conclusions The systemic adverse reaction is an independent factor for higher S-ab levels at short and medium terms after BNT162b2 vaccination as demonstrated in our data.