Development, study, and comparison of models of cross-immunity to the influenza virus using statistical methods and machine learning.

INTRODUCTION: The World Health Organization considers the values of antibody titers in the hemagglutination inhibition assay as one of the most important criteria for assessing successful vaccination. Mathematical modeling of cross-immunity allows for identification on a real-time basis of new antigenic variants, which is of paramount importance for human health. MATERIALS AND METHODS: This study uses statistical methods and machine learning techniques from simple to complex: logistic regression model, random forest method, and gradient boosting. The calculations used the AAindex matrices in parallel to the Hamming distance. The calculations were carried out with different types and values of antigenic escape thresholds, on four data sets. The results were compared using common binary classification metrics. RESULTS: Significant differentiation is shown depending on the data sets used. The best results were demonstrated by all three models for the forecast autumn season of 2022, which were preliminary trained on the February season of the same year (Auroc 0.934; 0.958; 0.956, respectively). The lowest results were obtained for the entire forecast year 2023, they were set up on data from two seasons of 2022 (Aucroc 0.614; 0.658; 0.775). The dependence of the results on the types of thresholds used and their values turned out to be insignificant. The additional use of AAindex matrices did not significantly improve the results of the models without introducing significant deterioration. CONCLUSION: More complex models show better results. When developing cross-immunity models, testing on a variety of data sets is important to make strong claims about their prognostic robustness.

Seroprotection achieved with standard four-dose schedule of hepatitis B vaccine in people with chronic kidney disease: A real-life data.

BACKGROUND AND OBJECTIVES: Hepatitis B virus (HBV) infection is common in people with chronic kidney diseases (CKD). The guidelines recommend four doses, 2.0 mL each, of HBV vaccine, given at zero, one, two and six months in these patients. However, real-life data on the effectiveness of this schedule are limited. We retrospectively reviewed the HBV vaccine response in the CKD population. METHODS: The study included adult (≥ 18 years) patients with glomerular filtration rate < 60 mL/min, if they had received four doses (each of 2.0 mL volume) of HBV vaccine and anti-HBs titer was measured at ≥ 1 month of the last dose of vaccine. Participants with hepatitis C or human immunodeficiency virus (HIV) coinfection, organ transplant recipients, active or remote malignancy or use of immunosuppressive medication were excluded. Anti-HBs antibody was measured with two different assays with their limits of detection up to 500 mIU/mL and 1000 mIU/mL. The presence of detectable anti-HBs antibody and anti-HBs titer ≥ 10 mIU/mL defined seroconversion and seroprotection, respectively. RESULTS: The study included 208 patients (71.9% males; age 44 [33-55] years; CKD stage II/III/IV/V in 1.4%/7.2%/26.4%/64.9%; 46% on maintenance hemodialysis [MHD]). Overall, seroconversion and seroprotection were achieved in 174 (83.7%) and 161 (77.4%) participants and anti-HBs titer, measured three (2-8) months after the fourth dose, was 124 (12-500) mIU/mL. The median anti-HBs antibody levels at ≤ 6, 7-12, 13-24 and 24 months after the fourth doses were 116, 478, 43 and 70 mIU/mL, respectively. Age, body mass index, stage of CKD, serum albumin and dialysis status were not associated with seroprotection (p < 0.05). CONCLUSION: A standard vaccination schedule of four 2.0 mL doses of HBV vaccine in CKD patients induces reasonably good and sustained seroprotection.

SARS-CoV-2 spike protein antibody titers after the fourth dose of BNT162b2 vaccine among Japanese patients undergoing hemodialysis: a single-center study.

Patients undergoing hemodialysis are particularly vulnerable to severe outcomes of SARS-CoV-2 infection, with mortality rates higher than that of the general population. Vaccination reduces the risk of adverse outcomes, with booster doses being particularly beneficial. However, limited data are available on the effectiveness of subsequent vaccinations or their effect on increasing antibody levels. This single-center study aimed to investigate changes in SARS-CoV-2 IgG antibody titers following the fourth vaccination among 28 patients undergoing hemodialysis. Blood tests were conducted at various intervals post-vaccination, with a focus on identifying factors associated with antibody levels. The IgG antibody levels rapidly increased by Day 7 post-vaccination, with a median time to peak of 11 days. Antibody titers tended to be higher in male patients than in female patients. This study sheds light on the immune response to the fourth vaccination in patients undergoing hemodialysis. As this study included a small sample size, with a short observation period, further research is warranted to comprehensively understand the effectiveness of vaccination and the benefits of additional doses of vaccine.

An Analytical Protocol for Detecting Antibody Titer Levels in Serum/Saliva by Indirect Enzyme-Linked Immunosorbent Assay (ELISA).

Enzyme-linked immunosorbent assay (ELISA) detects qualitatively and quantitatively the presence of antibodies or antigens in a sample. Due to its simplicity, high sensitivity, and user-friendliness, the test is widely used in laboratory research, clinical diagnoses, and food testing. This chapter describes the indirect semiquantitative ELISA protocol used to monitor antibody levels in animals and analyze the titer levels of specific antibodies against a target antigen in serum and saliva.

Antibody Titers and the Risk of Infection During the SARS-CoV-2 Omicron Phase in Bizen City, Japan.

BACKGROUND: Understanding the association between the immune response and the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has implications for forthcoming prevention strategies. We evaluated the association between antibody titers and the risk of infection for the general population during the Omicron-dominant phase. METHODS: This was a prospective cohort study of residents or people affiliated with institutions in Bizen City, which included 1899 participants. We measured the titers of antibodies against SARS-CoV-2 repeatedly every 2 months from June 2022 to March 2023. Infection status was obtained from self-reported questionnaires and the official registry. We estimated risk ratios (RRs) for infection within 2 months of the date of each antibody measurement with 95% confidence intervals (CIs) based on antibody titer categories and spline functions. RESULTS: Compared with the <2500 arbitrary unit (AU)/mL category, the 2500-5000, 5000-10 000, and ≥10 000 AU/mL categories had adjusted RRs of 0.81 (95% CI, .61-1.08), 0.51 (95% CI, .36-.72), and 0.41 (95% CI, .31-.54), respectively. The spline function showed a nonlinear relationship between antibody titer and risk. CONCLUSIONS: Higher antibody titers were associated with a lower risk. We demonstrate the usefulness of measuring an antibody titers to determine the appropriate timing for future prevention strategies.

Silent Infections are not So Silent: The Emerging Role of Combined Infections, Inflammation, and Vitamin Levels in OCD.

Objective: Recent evidence highlights that different agents may trigger immune-mediated processes involved in the pathophysiology of different neuropsychiatric conditions. Given the limited information on obsessive-compulsive disorder (OCD), the present study aimed at assessing current/past infections and plasma levels of vitamin D, vitamin B12, folic acid, homocysteine and common peripheral inflammatory markers in a group of OCD outpatients. Method: The sample included 217 adult outpatients with an OCD diagnosis according to the DSM-5 criteria. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used to assess the clinical phenotype and symptom severity. Laboratory blood tests measured levels of vitamin D, vitamin B12, folic acid, homocysteine, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), blood count and antibodies titers for cytomegalovirus (CMV), Epstein Barr virus (EBV), Toxoplasma gondii and antistreptolysin titer. Results: Sixty-one patients had a previous EBV infection, 46 were seropositive for CMV IgG, 24 showed positive antistreptolysin titer, 14 were seropositive for Toxoplasma gondii IgG, and four for CMV IgM. More than a half of patients showed vitamin D insufficiency. Compared to seronegative patients, patients with a past EBV infection displayed significantly higher scores on the Y-BOCS total score and compulsion subscale, and other symptoms. Vitamin D was negatively correlated with both the Y-BOCS total score and the subscales scores. Folic acid was negatively correlated with the Y-BOCS total and obsessions subscale score. Conclusions: The findings of our study show an association between Epstein-Barr infection and hypovitaminosis D and the overall severity and specific symptom patterns of OCD. The laboratory measures used in this study are useful, cheap and easy parameters that should be routinely assessed in patients with OCD. Further studies are needed to clarify their role in OCD pathophysiology and outcomes, as well as the potential therapeutic impact of vitamins and antibiotics/immunomodulatory agents in OCD and other psychiatric conditions.

Immediate Adverse Reaction and SARS-CoV-2 Anti-Spike Receptor Binding Domain IgG of COVID-19 Vaccines Among Health Staffs.

OBJECTIVE: To contain the spread of coronavirus disease 2019 (COVID-19), several vaccines have been developed. This study is intended to elucidate the level of anti-severe acute respiratory syndrome coronavirus 2 immunoglobulin G (anti-SARS-CoV-2-IgG) antibodies for COVID-19 vaccines (Pfizer BioNTech [BNT162b2], Oxford/AstraZeneca [ChAdOx1], and Sinopharm [BBIBP-CorV]) among health staff from health facilities in Duhok province, and it explored the immediate adverse reactions of COVID-19 vaccines among participants. METHODS: A longitudinal study was conducted from June 1, 2021, to June 30, 2022, and 300 participants were included through simple random sampling. RESULTS: The immune response 1 mo after the second dose was significantly higher than the sustained immune after 5 and 9 mo as results revealed that, in 100% of study samples who had (ChAdOx1) vaccine, their antibody titers exceeded the positivity threshold of 1 AU/m, while 96% for (BNT162b2) and 90% for (BBIBP-CorV) for the first test after 1 mo from the second dose of the COVID-19 vaccine, and these rates were reduced to 94.6% for (ChAdOx1), 97.8% for (BNT162b2), and 81.9% for (BBIBP-CorV) at 5 mo after the second dose, while simultaneously the seropositivity rates were more reduced at 9 mo to 46.5% for (ChAdOx1), 67.5% for (BNT162b2), and 9.20% for (BBIBP-CorV). In terms of adverse reactionsss, fever was reported as the most prevalent after the first dose in 58% for ChAdOx1, 43% for BNT162b2, and 23% for BBIBP-CorV, followed by muscle pain, joint pain, and shoulder pain for both doses. CONCLUSIONS: The implications of the findings from this study are that higher and potentially longer antibody responses can be obtained if the BNT162b2 is given as compared with the other 2 vaccines. Moreover, the booster doses of the COVID-19 vaccine are highly recommended because more than 50% of the participants either have become anti-spike protein negative or have a deficient level of anti-spike protein against COVD-19 vaccines.

Enhancing effects of Aloe vera gel extracts on the humoral and cellular immune response and growth performance in broiler chickens.

Objective: The experiment evaluated how Aloe vera gel (AVG) extract supplementation affected immune responses and physiological performances in broiler chickens. Materials and Methods: 90-day-old Cobb 500 broiler chicks were reared for 38 days without the addition of antibiotics, either through feed or water. At 10 days, chicks were allocated into three groups: A, B, and C (n = 30). Group A served as non-supplemented control. Groups B and C were administered aqueous extracts of AVG at 1.0% and 2.0%, respectively, with drinking water. Results: The supplementation of AVG potentiated the chicken immune response to Newcastle disease-vaccinated birds and sheep red blood cell-treated birds, which detected the highest antibody titers against Newcastle disease virus and sRBC. The cellular immune response evaluated through a cutaneous basophilic hypersensitivity test using phytohemagglutinin-P demonstrated a significant increase in skin thickness in AVG-supplemented birds. The relative sizes of lymphoid organs (bursa, spleen, and thymus) were significantly enhanced (p < 0.05) among the groups. Broilers given AVG-1 and AVG-2 exhibited significantly greater (p < 0.01) live body weight, dressing percentages, and serum protein and serum albumin levels. The supplemented groups experienced a significant reduction in total serum cholesterol, triglycerides, and low-density lipoprotein-cholesterol values, while the levels of high-density lipoprotein-cholesterol remained unchanged. The dietary aqueous extracts of AVG are effective in enhancing innate and specific immunity. Conclusion: This work strengthens the perspective of the use of AVG as an immune stimulant to facilitate recovery from immune suppression states, enhance innate and specific immunity, and improve broiler growth performance.

A Pseudovirus-Based Neutralization Assay for SARS-CoV-2 Variants: A Rapid, Cost-Effective, BSL-2-Based High-Throughput Assay Useful for Vaccine Immunogenicity Evaluation.

Neutralizing antibody responses from COVID-19 vaccines are pivotal in conferring protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Effective COVID-19 vaccines and assays measuring neutralizing antibodies against emerging variants (i.e., XBB.1.5, XBB.1.16, and XBB.2.3) are needed. The use of biosafety level (BSL)-3 laboratories for live virus assays results in higher costs and a longer turnaround time; therefore, a BSL-2-based pseudovirus neutralization assay (PNT) was developed. The pseudoviruses were produced by cotransfecting cells with plasmids encoding a lentiviral backbone-expressing luciferase reporter; non-surface proteins for lentiviral production; and ancestral or Omicron (BA.1 and BA.5) SARS-CoV-2 spike (S) proteins. The PNT was developed and optimized in dose and kinetics experiments. The representative serum samples (COVID-19-convalescent or NVX-CoV2373-vaccinated participants enrolled in the 2019nCoV-101 trial) demonstrated a wide dynamic range. The neutralization data showed robust correlation with validated anti-recombinant spike IgG levels and angiotensin-converting enzyme 2 inhibition titers (ancestral). This assay is suitable for measurement of the neutralization ability in clinical samples from individuals infected with SARS-CoV-2 or immunized with a COVID-19 vaccine. The results suggest that this PNT provides a lower cost, high-throughput, rapid turnaround alternative to BSL-3-based microneutralization assays and enables the discovery and development of effective vaccines against emerging variants.

Contribution of cerebrospinal fluid antibody titers and sex to acute cerebral blood flow in patients with anti-NMDAR autoimmune encephalitis.

Objective: The objective of this study was to elucidate the contribution of cerebrospinal fluid (CSF) antibody titers (AT) and sex to acute cerebral blood flow (CBF) in patients diagnosed with anti-N-methyl-d-aspartate receptor autoimmune encephalitis (NMDAR AE). Methods: Forty-five patients diagnosed with NMDAR AE were recruited from December 2016 to January 2023. The acute CBF in patients with NMDAR AE at the early stage of the disease was analyzed using arterial spin labeling. The groups were compared based on CSF AT and sex. The connectivity of the CBF in the region of interest was also compared between groups. Results: The patients with different CSF AT exhibited varied brain regions with CBF abnormalities compared to the healthy subjects (p = 0.001, cluster-level FWE corrected). High antibody titers (HAT) in CSF contributed to more brain regions with CBF alterations in female patients than in female patients with low antibody titers (LAT) in CSF (p = 0.001, cluster-level FWE corrected). Female patients with HAT in CSF displayed more decreased CBF in the left post cingulum gyrus, left precuneus, left calcarine, and left middle cingulum gyrus than the male patients with the same AT in CSF (p = 0.001, cluster-level FWE corrected). All patients with NMDAR AE showed increased CBF in the left putamen (Putamen_L) and left amygdala (Amygdala_L) and decreased CBF in the right precuneus (Precuneus_R), which suggests that these are diagnostic CBF markers for NMDAR AE. Conclusion: CSF AT and sex contributed to CBF abnormalities in the patients diagnosed with NMDAR AE. Altered CBF might potentially serve as the diagnostic marker for NMDAR AE.

Monitoring Memory B Cells by Next-Generation ImmunoSpot® Provides Insights into Humoral Immunity that Measurements of Circulating Antibodies Do Not Reveal.

Memory B cells (Bmem) provide the second wall of adaptive humoral host defense upon specific antigen rechallenge when the first wall, consisting of preformed antibodies originating from a preceding antibody response, fails. This is the case, as recently experienced with SARS-CoV-2 infections and previously with seasonal influenza, when levels of neutralizing antibodies decline or when variant viruses arise that evade such. While in these instances, reinfection can occur, in both scenarios, the rapid engagement of preexisting Bmem into the recall response can still confer immune protection. Bmem are known to play a critical role in host defense, yet their assessment has not become part of the standard immune monitoring repertoire. Here we describe a new generation of B cell ELISPOT/FluoroSpot (collectively ImmunoSpot®) approaches suited to dissect, at single-cell resolution, the Bmem repertoire ex vivo, revealing its immunoglobulin class/subclass utilization, and its affinity distribution for the original, and for variant viruses/antigens. Because such comprehensive B cell ImmunoSpot® tests can be performed with minimal cell material, are scalable, and robust, they promise to be well-suited for routine immune monitoring.

Assessing the Affinity Spectrum of the Antigen-Specific B Cell Repertoire via ImmunoSpot®.

The affinity distribution of the antigen-specific memory B cell (Bmem) repertoire in the body is a critical variable that defines an individual's ability to rapidly generate high-affinity protective antibody specificities. Detailed measurement of antibody affinity so far has largely been confined to studies of monoclonal antibodies (mAbs) and are laborious since each individual mAb needs to be evaluated in isolation. Here, we introduce two variants of the B cell ImmunoSpot® assay that are suitable for simultaneously assessing the affinity distribution of hundreds of individual B cells within a test sample at single-cell resolution using relatively little labor and with high-throughput capacity. First, we experimentally validated that both ImmunoSpot® assay variants are suitable for establishing functional affinity hierarchies using B cell hybridoma lines as model antibody-secreting cells (ASC), each producing mAb with known affinity for a defined antigen. We then leveraged both ImmunoSpot® variants for characterizing the affinity distribution of SARS-CoV-2 Spike-specific ASC in PBMC following COVID-19 mRNA vaccination. Such ImmunoSpot® assays promise to offer tremendous value for future B cell immune monitoring efforts, owing to their ease of implementation, applicability to essentially any antigenic system, economy of PBMC utilization, high-throughput capacity, and suitability for regulated testing.

Serial Evaluation of Preimmunization Antibody Titers in Lymphoma Patients Receiving Chimeric Antigen Receptor T Cell Therapy.

Antibody titers and the potential need for immunization have not been formally studied in recipients of chimeric antigen receptor T cell therapy (CAR-T). Prior studies have shown that CD19-targeted CAR-T can induce persistent B cell aplasia but preserve plasma cells for humoral response. Aiming to assess the immune repertoire and antibody titer status of CAR-T recipients, we conducted a retrospective study of immune cell recovery and antibody titers to vaccines in anti-CD19 CAR-T recipients at Mayo Clinic, Rochester. In our cohort of 95 CAR-T recipients, almost one-half had low CD4 T and B cell counts prior to CAR-T that remained persistently low post-CAR-T. Prior to CAR-T, the seronegative rate was lowest for tetanus and highest for pneumococcus irrespective of prior transplantation status (within 2 years of CAR-T). At 3 months post-CAR-T, overall seronegativity rates were similar to pre-CAR-T rates for the prior transplantation and no prior transplantation groups. For patients who received IVIG, loss of seropositivity was seen for hepatitis A (1 of 7; 14%). No seroconversion was noted for pneumococcus. For patients who did not receive IVIG, loss of seropositivity was seen for pneumococcus (2 of 5; 40%) and hepatitis A (1 of 4; 25%). CAR-T recipients commonly experience T cell and B cell lymphopenia and might not have adequate antibody titers against vaccine-preventable diseases despite IVIG supplementation. Loss of antibody titers post-CAR-T is possible, highlighting the need for revaccination. Additional studies with long-term follow-up are needed to inform the optimal timing of immunization post-CAR-T.

Deciphering the clinical significance of longitudinal antiphospholipid antibody titers.

In antiphospholipid syndrome (APS), the risk of clinical manifestations increases with higher titers of antiphospholipid antibodies (aPL). Despite the adoption of aPL titers in the classification approach to aPL-positive subjects, the value of longitudinal monitoring of those titers in the follow-up is still debated, being well studied only in systemic lupus erythematosus (SLE). The literature suggests that the rate of aPL positivity decreases during follow-up in primary APS, estimating that seroconversion occurs in between 8.9 and 59% of patients over time. Negativisation of aPL occurs more frequently in asymptomatic aPL carriers than in patients with full-blown APS as well as in subjects with single aPL positivity or low aPL antibody titers. In patients with SLE, aPL typically behave fluctuating from positive to negative and back again in the course of follow-up. The few studies assessing the longitudinal course of aPL positivity with no associated systemic connective tissue disease reported a progressive decrement of aPL titers over time, in particular of antibodies against ß2 glycoprotein I (antiß2GPI) and cardiolipin (aCL) of IgG isotype. After a thrombotic event, aPL titers tend to decrease, as emerged from cohorts of both primary and secondary APS. Hydroxychloroquine has been identified as the most effective pharmacological agent to reduce aPL titers, with multiple studies demonstrating a parallel reduction in thrombosis rate. This review addresses available evidence on the significance of aPL titer fluctuation from clinical, therapeutic and pathogenic perspectives.

Association between use of antipyretics and antibody titers after two doses of the BNT162b2 SARS-CoV-2 vaccine in adolescents and young adults with underlying diseases.

There are few reports on the association between antipyretic use and antibody titers in adolescents and young adults following SARS-CoV-2 vaccination. Multivariable linear regression analyses were performed to examine the association between antipyretic use and antibody titers. The use of antipyretics was not associated with antibody titers (ß coefficient [95% CI] = -0.107 [-0.438 to 0.224]).

Review of a Series of Surveys on Adverse Reactions to the COVID-19 mRNA-1273 Vaccine at Okayama University.

This paper presents the results of a series of surveys conducted from July 2021 to March 2023 to investigate the post-vaccination adverse reactions to the mRNA-1273 (Moderna) vaccine among faculty, staff, and students at Okayama University. These studies complement the official surveys conducted by the Ministry of Health, Labour and Welfare (MHLW) and provide a more representative picture of adverse reactions in the general population including large numbers of healthy young people. Pain, swelling, redness at the injection site, fever, headache, and malaise were the main adverse reactions reported. The proportion of adverse reactions was generally higher after the second vaccination and decreased with each additional vaccination. No statistically significant differences in the adverse reactions were found for males and females and those with/without a history of allergy, but a lower proportion of fever was observed in older participants and those with underlying medical conditions. We also evaluated the association between adverse reactions and antibody titers after the third vaccination and found no significant differences in antibody levels one month after vaccination. This series of studies highlights the importance of conducting surveys in diverse populations to provide a more representative picture of post-vaccination adverse reactions during a pandemic.

Serum Anti-Spike Antibodies Are Not Affected by Immunosuppressants in SARS-CoV-2 Vaccinations Given to Brazilian Patients with Inflammatory Bowel Disease.

This study aimed to evaluate humoral responses after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of patients with inflammatory bowel disease (IBD). Patients with IBD enrolled in a tertiary outpatient unit were followed up between September 2021 and September 2022 via serial blood collection. Immunoglobulin G antibody titers against SARS-CoV-2 were measured before administration and 1 and 6 months after the administration of two doses of different vaccination regimens. The results were compared with those of a healthy control group obtained during the same period. The mean pre-vaccination antibody titers were 452.0 and 93.3 AU/mL in the IBD (n = 42) and control (n = 89) groups, respectively. After two doses of the vaccine, the titers significantly increased in both groups (IBD, 8568.0 AU/mL; control, 7471.0 AU/mL; p < 0.001). One month after the second dose, no significant differences were observed between the two groups (p = 0.955). Significant differences between vaccination schemes in the IBD group were observed, with higher titers in those who received Pfizer, younger patients (p < 0.005), and those with a previous coronavirus disease 2019 (COVID-19) infection (p < 0.012). The use of immunosuppressants and immunobiologicals did not affect the overall humoral response to COVID-19 vaccine in patients with IBD, but specific vaccine regimens, age, and previous coronavirus infection significantly did. This study reinforces the positive impact of booster doses and the safety of SARS-CoV-2 vaccination.

Adeno-associated virus serotype 9 antibody seroprevalence for patients in the United States with spinal muscular atrophy.

Onasemnogene abeparvovec is a recombinant adeno-associated virus serotype 9 (AAV9) vector-based gene therapy for spinal muscular atrophy (SMA). Patients with elevated titers of anti-AAV9 antibodies (AAV9-Ab) should not receive onasemnogene abeparvovec because of potential safety and efficacy implications. We conducted a retrospective study to describe the seroprevalence of anti-AAV9 binding antibodies for pediatric patients with SMA in the United States. At initial testing, 13.0% (115 of 882) of patients (mean [SD] age, 26.29 [33.66] weeks) had elevated AAV9-Ab titers. The prevalence of elevated titers decreased as age increased, with 18.2% (92 of 507) of patients ≤3 months old but only 1.1% (1 of 92) of patients ≥21 months old having elevated titers. This suggests transplacental maternal transfer of antibodies. No patterns of geographic variations in AAV9-Ab prevalence were confirmed. Elevated AAV9-Ab titers in children <6 weeks old decreased in all circumstances. Lower magnitudes of elevated titers declined more rapidly than greater magnitudes. Retesting was completed at the discretion of the treating clinician, so age at testing and time between tests varied. AAV9-Ab retesting should be considered when patients have elevated titers, and elevations at a young age are not a deterrent to eventual onasemnogene abeparvovec administration. Early disease-modifying treatment for SMA leads to optimal outcomes.

Decreased rate of blood donors with high ABO antibody titers in Japan and the underlying factors: Comparisons between 2010 and 2021.

BACKGROUND AND OBJECTIVES: Previously (2007), it was reported that ABO antibody titers in Japanese blood donors had decreased significantly compared to 20 years before. Here we evaluated whether further decrease of antibody titers had occurred in recent years, and the potential factors associated with changes in antibody titers. MATERIALS AND METHODS: Serum/plasma from random blood donors in 2010 and 2021 (2010: 3369, 2021: 5796 donors) was classified into low, middle, and high ABO antibody titers according to the reactivity of diluted serum/plasma (2.5-fold and 20-fold) by an automated microplate system. The rates of low/high titer in the two periods were compared. Logistic regression and age-gender-BMI subgroup analyses were conducted to identify the factors that contributed to changes in antibody titers. RESULTS: Compared to 2010, the rate of donors with high ABO antibody titers was　decreased in 2021 for both anti-A and anti-B (anti-A, 2010: 23.8%, 2021: 19.3%; anti-B, 2010: 23.8%, 2021: 16.4%). In logistic regression analysis, age was found to significantly affect both anti-A and anti-B antibody titers (anti-A, adjusted odds ratio 0.36, 95% CI 0.31-0.41; anti-B, 0.42, 0.37-0.47), and BMI (0.82, 0.73-0.92) and other time-related factors (0.79, 0.71-0.88) significantly affect anti-B antibody titers. Subgroup analysis revealed decreased rate of high anti-B titers in the higher age group in 2021. CONCLUSION: The rate of high ABO antibody titers, especially high anti-B titers, was significantly decreased in 2021, and our results suggested an association with aging and obesity of blood donors as well as other time-related factors.

Long-term antibody titers variation in unvaccinated patients receiving convalescent plasma or placebo for severe SARS-CoV-2 pulmonary infection.

BACKGROUND: Convalescent plasma (CP) became a prominent treatment in the early stages of the SARS-CoV-2 pandemic. In Argentina, a randomized clinical trial was executed to compare the use of CP in inpatients with severe COVID-19 pneumonia versus placebo. No differences in clinical outcomes or overall mortality between groups were observed. We conducted a cohort study in outpatients enrolled in the trial to describe long-term antibody titer variations between CP and placebo recipients. METHODS: Patients' total SARS-CoV-2 IgG antibodies against spike protein were collected 3, 6 and 12 months after hospital discharge from August 2020 to December 2021. In addition, reinfections, deaths and vaccination status were retrieved. Statistical analysis was performed using antibody geometric mean titers (GMT). All estimations were made considering the date of the trial infusion (placebo or CP) as time 0. RESULTS: From the 93 patients included in the follow-up, 64 had received CP and 29 placebo. We excluded all 12-month measurements because they were collected after the patients' vaccination date. At 90 days post-infusion, patients had an antibody GMT of 8.1 (IQR 7.4-8.1) in the CP group and 8.8 (IQR 8.1-9.1) in the placebo group. At 180 days, both groups had a GMT of 8.1 (IQR 7.4-8.1). No statistical differences in GMT were found between CP and placebo groups at 90 days (p = 0.12) and 180 days (p = 0.25). No patients registered a new COVID-19 infection; one died in the CP group from an ischemic stroke. CONCLUSIONS: No differences were observed in long-term antibody titers in unvaccinated patients that received CP or placebo after severe COVID-19 pneumonia.