Median Titer Research Articles

Long term follow-up of humoral and cellular response to mRNA-based vaccines for SARS-CoV-2 in patients with active multiple myeloma.

Long-term kinetics of antibody (Ab) and cell-mediated immune (CMI) response to full anti-SARS-CoV-2 vaccine schedule and booster doses in Multiple Myeloma (MM) patients remain unclear. We prospectively evaluated Ab and CMI response to mRNA vaccines in 103 SARS-CoV-2-naïve MM patients (median age 66, 1 median prior line of therapy) and 63 health-workers. Anti-S-RBD IgG (Elecsys®assay) were measured before vaccination and after 1 (T1), 3 (T3), 6 (T6), 9 (T9) and 12 (T12) months from second dose (D2) and 1 month after the introduction of the booster dose (T1D3). CMI response (IGRA test) was evaluated at T3 and T12. Fully vaccinated MM patients displayed high seropositivity rate (88.2%), but low CMI response (36.2%). At T6 the median serological titer was halved (p=0.0391) in MM patients and 35% reduced (p=0.0026) in controls. D3 (94 patients) increased the seroconversion rate to 99% in MM patients and the median IgG titer in both groups (up to 2500 U/mL), maintained at T12. 47% of MM patients displayed a positive CMI at T12 and double-negativity for humoral and CMI (9.6% at T3) decreased to 1%. Anti-S-RBD IgG level ≥346 U/mL showed 20-times higher probability of positive CMI response (OR 20.6, p<0.0001). Hematological response ≥CR and ongoing lenalidomide maintenance enhanced response to vaccination, hindered by proteasome inhibitors/anti-CD38 monoclonal antibodies. In conclusion, MM elicited excellent humoral, but insufficient cellular responses to anti-SARS-CoV-2 mRNA vaccines. Third dose improved immunogenicity renewal, even when undetectable after D2. Hematological response and ongoing treatment at vaccination were the main predictive factors of vaccine immunogenicity, emphasizing the role of vaccine response assessment to identify patients requiring salvage approaches.

Immunogenicity of Anti-SARS-CoV-2 Vaccination After Kidney Transplantation in Kidney Transplant Recipients Vaccinated Before Transplantation.

Solid-organ transplant patients, including kidney transplant recipients (KTRs) are at high risk of severe forms of coronavirus disease 2019 (COVID-19) infection1 and fail to mount a robust and sustained humoral response to COVID-19 vaccines,2 despite reinforced schemes (Reference S1, SDC, https://links.lww.com/TP/C770).3 In this context, the use of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies, because preexposure prophylactic strategy has been dramatically helpful to provide passive protection against COVID-19. However, currently available monoclonal antibodies are no longer effective at neutralizing the most recent Omicron variants of SARS-CoV-2.4,5 Hence, vaccination is the unique remaining prophylactic tool against COVID-19 in vulnerable individuals. Unlike KTRs, patients with chronic kidney disease, including those undergoing long-term dialysis, have shown potent vaccine responses against SARS-Cov-2, reaching antibody levels close to those observed in the general population (Reference S3, SDC, https://links.lww.com/TP/C770). Whether a pretransplant vaccination improves the response to subsequent doses after transplantation has yet to be established. To address this important question, we aimed to investigate the trajectory of the SARS-CoV-2-specific humoral immune response following a booster dose in KTRs who had received at least 2 vaccine shots before the transplantation. This retrospective single-center study (Necker Hospital, Paris, France) enrolled all consecutive patients, transplanted between June and December 2021, following a minimum of 2 vaccine doses before the kidney transplantation (KT), in the absence of concurrent immunosuppressive therapy. Forty-nine patients (25 men [51.0%], median age of 57.2 y, interquartile range 42.9–68.1) were enrolled (Table S1 and Material S1, SDC, https://links.lww.com/TP/C770). At time of KT, most patients (93.6%) displayed a positive SARS-CoV-2 serology and 66% showed an anti-Spike IgG titer >264 binding antibody unit (BAU)/mL (median titer of 809 [128.5–3210.0]). In the 26 KTRs who did not receive an additional vaccine shot after transplantation, antibody titers decreased to 131 BAU/mL at M3 and to 136 BAU/mL (24.5–662.5) at the last follow-up, after a median posttransplant time of 5.0 (3.0–6.9) mo (Table S1, SDC, https://links.lww.com/TP/C770). Twenty-three KTRs (46.9%) received a booster dose of messenger RNA COVID-19 vaccine after KT. The median time between KT and first dose was 13.4 wk (11.1–22.1). Nineteen (82.6%) received only 1 posttransplant dose, while 4 patients (17.4%) received an additional one. Most patients exhibited a strong postvaccinal humoral response after one injection: 20 patients (90.9%) showed a postvaccinal anti-Spike titer > 264 BAU/mL (versus 10 before vaccine) and anti-Spike IgG titers increased significantly from 172.0 (48.0–698.5) to 1220.0 (583.8–3299.5), P = 0.0004 (Figure 1). Compared to responders, the nonresponders (to one posttransplant dose) were significantly older, were given more frequently rituximab at induction, and had received a greater number of vaccine doses before KT (Table S2, SDC, https://links.lww.com/TP/C770). One of the nonresponders after the first dose developed an effective response after the second. Interestingly, a strong recall humoral response also occurred in KTRs treated with belatacept after one vaccine dose (anti-Spike IgG titers increased from 590.5 [118.3–987] to 3641.5 BAU/mL [2898.5–3819]), whereas belatacept was found to dramatically hamper the antibody response to COVID-19 vaccine in patients who were vaccine-naive at the time of transplantation (Reference S1, SDC, https://links.lww.com/TP/C770).2Figure 1.: Evolution of anti-SARS-CoV-2 spike IgG at day 0 postkidney transplantation, before and after 1 injection of anti-SARS-CoV-2 mRNA vaccination in 23 KTRs who received anti-SARS-CoV-2 vaccination before transplantation. BAU, binding antibody unit; KT, kidney transplantation; KTR, kidney transplant recipient; mRNA, messenger RNA; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.Eleven patients (22.4%) experienced COVID-19 after KT, including 2 breakthrough infections following posttransplant dose. All but one cases were infected with the Omicron variants (Delta variant in one case). Three patients were admitted to hospital, two of whom experienced a severe infection requiring intensive care unit and eventually died. These latter were infected with the Omicron variants, displayed a weak anti-spike response and were not administered preventive mAbs before COVID-19. Our study is limited by its retrospective nature, by the relatively small number of patients and the lack of data about neutralizing antibodies (which are a better measure of protection than the commercially available anti-spike antibody assay) and vaccine-specific cellular response. However, it clearly demonstrates that a pretransplant vaccination against COVID-19 before KT significantly improves the response to vaccine after KT. Anti-SARS-CoV-2 vaccination is recommended in dialysis patients, who are exposed to severe forms of COVID-19 (Reference S6, SDC, https://links.lww.com/TP/C770). Our data further stress the importance of vaccination in patients on the waiting list for solid-organ transplantation. Pretransplant priming of vaccine-specific responses can dramatically improve the posttransplant vaccine response through the recall stimulation of a preexisting memory response.

A third dose of the BNT162b2 mRNA vaccine sufficiently improves the neutralizing activity against SARS-CoV-2 variants in liver transplant recipients.

We examined the neutralizing antibody production efficiency of the second and third severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine doses (2nd- and 3rd-dose) and neutralizing activity on mutant strains, including, the Ancestral, Beta and Omicron strains using green fluorescent protein-carrying recombinant SARS-CoV-2, in living-donor liver transplantation (LDLT) recipients. The patients who were administered vaccines other than Pfizer- BioNTechBNT162b2 and who had coronavirus disease 2019 in this study period were excluded. We enrolled 154 LDLT recipients and 50 healthy controls. The median time were 21 days (between 1st and 2nd vaccination) and 244 days (between 2nd and 3rd vaccination). The median neutralizing antibody titer after 2nd-dose was lower in LDLT recipients than in controls (0.46 vs 1.00, P<0.0001). All controls had SARS-CoV-2 neutralizing antibodies, whereas 39 LDLT recipients (25.3%) had no neutralizing antibodies after 2nd-dose; age at vaccination, presence of ascites, multiple immunosuppressive treatments, and mycophenolate mofetil treatment were significant risk factors for nonresponder. The neutralizing activities of recipient sera were approximately 3-fold and 5-fold lower than those of control sera against the Ancestral and Beta strains, respectively. The median antibody titer after 3rd-dose was not significantly different between recipients and controls (1.02 vs 1.22, p=0.0758); only 5% recipients was non-responder. The neutralizing activity after third dose to Omicron strains were enhanced and had no significant difference between two groups. Only the 2nd-dose was not sufficiently effective in recipients; however, 3rd-dose had sufficient neutralizing activity against the mutant strain and was as effective as that in healthy controls.

Effectiveness of oral levamisole as an adjuvant to hepatitis B vaccination in healthcare workers non-responsive to previous vaccination: A randomized controlled trial

BackgroundHealthcare workers are at risk for HBV infection through percutaneous or mucosal contact with infected blood, body secretions, or blood products or via sharps injury. Hepatitis B vaccination, despite immunogenicity, may not induce a proper immune response in 5–10% of the general adult population. Increased immune response in healthcare providers that do not respond properly to conventional hepatitis B vaccination is an important health challenge. Therefore, the aim of the present study was to evaluate the effectiveness of hepatitis B vaccination plus oral levamisole as adjuvant in healthcare providers non-responsive to routine vaccination. Materials and methodsThe healthcare workers that were non-responsive to previous hepatitis B vaccination were enrolled in a double-blind randomized placebo-controlled clinical trial. The participants were then randomized to two groups including hepatitis B vaccination (as a three-dose series on a 0, 1, and 2-month schedule in the deltoid muscle) plus levamisole (levamisole group) and hepatitis B vaccination plus placebo (placebo group) at a 1:1 ratio. The outcome measure was the HBs antibody titer one month after receiving each dose as well as the seroprotection ratio. The side effects were also evaluated in all participants. ResultsIn total, 22 subjects finished the trial (11 individual in per group). The median antibody titer one month after receiving the first and third doses increased more in the levamisole group compared to the placebo group but the difference was not significant (p ​= ​0.34, p ​= ​0.66, respectively).The seroprotection ratio after three doses was similarly high in both groups (90.9% in per group). Furthermore, the seroprotection ratio and median antibody titer had no significant correlation with age, sex, BMI, and history of smoking in intervention and control groups (p>0.05). No serious side effects were noted in both groups. ConclusionsRe-vaccination can boost the immune response in healthcare professionals that were non-responsive to previous vaccination although the mean antibody titer was higher in the levamisole group.

Optimizing COVID-19 Vaccination Strategy in Pediatric Kidney Transplant Recipients: Humoral and Cellular Response to SARS-CoV-2 mRNA Vaccination.

In this retrospective cohort study, we analyze the early humoral and cellular response in 64 adolescents KTx recipients, after two or three doses of mRNA vaccine BNT162b2 against different variants of COVID-19. After 2 doses, 77.8% % of children with no history of infection had a positive humoral response with a median anti-S IgG level of 1107 (IQR, 593-2,658) BAU/mL. All the patients with a history of infection responded with a higher median IgG level (3,265 (IQR, 1,492-8,178) BAU/mL). In non-responders after 2 doses, 75% responded after a third dose with a median Ab titer at 355 (IQR, 140-3,865BAU/mL). Neutralizing activity was significantly lower against the delta and the omicron variants compared to the wild-type strain and did not improve after a 3rd dose, while infection did provide higher levels of neutralizations against the variants. T cell specific response correlated with humoral response and no patient displayed a cellular response without a humoral response. Adolescent KTx recipients exhibit a high seroconversion rate after only two doses. A third injection, induces a response in the majority of the non-responders patients but did not counterbalance the strong decrease in neutralizing antibody activities against variants highlighting the need for boosters with specific vaccines.

Kinetics of cellular and humoral immunogenicity and effectiveness of SARS-CoV-2 booster vaccination in hematologic neoplasms.

Data on the effect of booster SARS-CoV-2 vaccination are mainly focused on humoral immunogenicity, while the kinetics of vaccine-induced cellular response and its correlation with effectiveness in hematologic patients are less explored. Our aim was to evaluate the longitudinal cellular and humoral immunogenicity induced by two and three doses of the mRNA-1273 SARS-CoV-2 vaccine in 270 patients with hematologic malignancies, and its relationship with the severity of breakthrough SARS-CoV-2 infection. Results indicate that at 23 weeks after the second dose, the seroconversion rate declined from 68.5% to 59.3%, with a reduction in median anti-S titers from 1577 to 456 BAU/mL, mainly in patients over 65 years of age or chronic lymphocytic leukemia (CLL) patients undergoing active therapy. Cellular immunogenicity, however, remained positive in 84.4% of cases. A third vaccine dose seroconverted 42.7% (41/96) and triggered cellular response in 36.7% (11/30) of previously negative patients. Notably, only 7.2% (15/209) of patients failed to develop both humoral and cellular response. Active therapy, anti-CD20 antibodies, lymphopenia, hypogammaglobulinemia, and low CD19+ cell count were associated with poor humoral response, while active disease, GvHD immunosuppressive therapy, lymphopenia, and low CD3+ , CD4+ , CD56+ cell count determined an impaired cellular response. After 13.8 months of follow-up, the incidence of SARS-CoV-2 infection was 24.8% (67/270), including 6 (9%) severe/critical cases associated with a weaker cellular (median interferon gamma (IFN-γ) 0.19 vs. 0.35 IU/mL) and humoral response (median anti-S titer <4.81 vs. 788 BAU/mL) than asymptomatic/mild cases. In conclusion, SARS-CoV-2 booster vaccination improves humoral response and COVID-19 severity is associated with impaired vaccine-induced immunogenicity.

Epidemiology of Antibody-positive Myasthenia Gravis in Sardinia, Italy (P2-5.027)

<h3>Objective:</h3> To determine the incidence and prevalence of myasthenia gravis (MG) associated with acetylcholine receptor (AchR)-IgG and muscle tyrosine kinase (MuSK)-IgG in the district of Sassari (Sardinia; Italy). <h3>Background:</h3> The global mean incidence and prevalence of MG have been assessed at ≈15 (range, 4–29)/million and 20 (range, 2–37)/100,000, respectively. The island of Sardinia is a recognized area at higher risk for different immune-mediated disorders (<i>e.g</i>., multiple sclerosis), but the epidemiology of MG remains unclear. <h3>Design/Methods:</h3> From the Neurochemistry Laboratory of the University-Hospital of Sassari (reference laboratory for AchR-IgG/MuSK-IgG testing in the island since 1998) we retrospectively identified patients with: 1) AchR-IgG (titer ≥0.5 nmol/L) and/or MuSK-IgG (titer ≥100 pg/ml) positivity by radioimmunoprecipitation assay; 2) available medical records; and 3) residence within the district of Sassari. Incidence (January 2010-December 2019) and prevalence (on January 1, 2020; population 325,288) were calculated. <h3>Results:</h3> Among 517 antibody-positive patients identified, 183 were included (incident, 97; prevalent, 165). We excluded 334 patients due to: 1) missing clinical information (n=65); 2) residency outside the Sassari district (n=168); 3) not classifiable as incident or prevalent (n=56); and 4) clinical phenotype not consistent with MG (n=45; median AchR-IgG titer, 0.7 [range, 0.5–5.5] nmol/L). The crude MG prevalence was 50.7/100,000 (95% CI, 43.4–58.9), whereas incidence was 29.8/1,000,000 person-years (95% CI, 24.3–36.2). Antibody specificities were AchR in 170 (92.9%; median titer 5.7 [range, 0.5–22]) and MuSK in 13 (7.1%; median titer 1,255 [range, 136–1,730]). Among incidence cases, age at disease onset was distributed as: &lt;18 years (n=2; 2%); 18–50 years (n=14; 14.4%); 51–65 years (n=25; 25.8%); and &gt;65 years (n=56; 57.7%). In 45 (46.4%) incident cases, MG was initially restricted to ocular muscles. <h3>Conclusions:</h3> We report the highest incidence and prevalence of MG worldwide. The environmental and genetic determinants of MG risk in the Sardinian population need to be investigated. <b>Disclosure:</b> Dr. Zara has nothing to disclose. Dr. DEIANA has nothing to disclose. Prof. Sotgiu has nothing to disclose. Dr. Ortu has nothing to disclose. Stefano Sotgiu has nothing to disclose. Gregorio Spagni has nothing to disclose. Dr. Damato has nothing to disclose. Dr. Solla has nothing to disclose. Dr. Sechi has nothing to disclose.

Age and Sex Distributions of MOG-IgG and AQP4-IgG Positive Sera from a Large Neuroimmunology Laboratory Database (P2-5.028)

Age and Sex Distributions of MOG-IgG and AQP4-IgG Positive Sera from a Large Neuroimmunology Laboratory Database (P2-5.028)

Outcomes of Surgical Resection and VNS in Patients with Medically Refractory Epilepsy and GAD65 Antibody Positivity (S40.004)

<h3>Objective:</h3> To determine effectiveness of vagus nerve stimulator (VNS) and surgical resection in patients with drug-resistant epilepsy associated with glutamic acid decarboxylase 65 (GAD65) antibodies. <h3>Background:</h3> Epilepsy associated with high-titer GAD65 antibodies is often refractory to immunotherapies and antiseizure medications (ASMs), underscoring the need for alternate treatment strategies. <h3>Design/Methods:</h3> We retrospectively identified Mayo Clinic Rochester patients (January 2003 – April 2022) with drug-resistant epilepsy and high serum GAD65-antibody titers (&gt;20 nnmol/L) who underwent surgical resection and/or VNS implantation. A “favorable” surgical outcome was defined as Engel I-II, and a responder to VNS was defined as a &gt;50% reduction in seizure frequency from baseline. <h3>Results:</h3> We identified 15 patients (13 females, 86.7%) who underwent surgical resection (n=7), VNS implantation (n=6), and both (n=2). Patients had failed a median of 5.5 anti-seizure medications. Twelve patients had GAD65 tested in the CSF, all were positive (median titer 3.8). Of the nine patients who underwent surgical intervention (all involving the temporal region), three (33.3%) had a favorable outcome, which was sustained for at least 3.5 years in one, 10 years in another, and the third was lost to follow-up after 1 year. Pathology was available in four patients, only one had evidence of inflammation. Of the 8 patients who underwent VNS implantation, 3 (37.5%) were initially considered a responder, but this was not sustained in two of the three. No clinical factors were statistically associated with favorable surgical or VNS outcomes. <h3>Conclusions:</h3> Temporal surgical resection and VNS are not highly effective in drug-resistant autoimmune-associated epilepsy related to high-titer GAD65 antibodies. Additional therapies are greatly needed for this challenging clinical scenario. <b>Disclosure:</b> Dr. Zhao-Fleming has nothing to disclose. Dr. Britton has received personal compensation in the range of $0-$499 for serving as a Online course with American Clinical Neurophysiology Society. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. The institution of Dr. Dubey has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Astellas. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. Dr. Dubey has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for AGRIMS. Dr. Dubey has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Advances in Neurology . Dr. Dubey has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Moffit Cancer Center . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. The institution of Dr. Smith has received research support from CURE Epilepsy.

Anti-HMGCR myopathy frequently coexists with other myositis-specific autoantibodies in Korean patients (P9-8.012)

<h3>Objective:</h3> To understand the characteristics of Korean patients with anti-HMGCR myopathy, we measured anti-HMGCR antibodies and analyzed clinical, radiological, and pathological features. <h3>Background:</h3> Immune-mediated necrotizing myopathy (IMNM) is an inflammatory myopathy subgroup characterized by subacute proximal weakness and prominent myofiber necrosis with minimal inflammatory cell infiltrate on muscle biopsy. Two autoantibodies have been reported in association with IMNM: antibodies against the signal recognition particle (SRP) and 3-hydroxy-3-methylglutaryl-coenxyme A reductase (HMGCR). To date, there only have been two case reports of Korea patients with anti-HMGCR myopathy. <h3>Design/Methods:</h3> We measured titers of anti-HMGCR antibodies in the sera of 99 patients with inflammatory myopathy using the enzyme-linked immunosorbent assay. We also tested 16 myositis-specific autoantibodies (MSAs) in all patients with anti-HMGCR myopathy. <h3>Results:</h3> Postivity for the anti-HMGCR antibody was observed in 17 (4 males and 13 females) of 99 patients with inflammatory myopathy. The median age at symptom onset was 60 years. Ten (59%) of the anti-HMGCR positive patients had taken statins. The most common symptoms were proximal muscle weakness in 15 (88%), followed by myalgia in 9 (53%), neck weakness in 4 (24%), dysphagia in 3 (18%), and skin lesions in 2 (12%). The median titer of anti-HMGCR antibody was 202 U/ml. We found eight different MSAs in nine (53%) patients. The median disease duration from symptom onset to diagnosis was significantly shorter in the MSA-positive group than in the MSA-negative group (p = 0.027). <h3>Conclusions:</h3> In conclusion, our study is the first to measure anti-HMGCR antibodies with inflammatory myopathy, and identify new findings including the coexistence of other MSAs in Korean patients. <b>Disclosure:</b> Miss Lee has nothing to disclose. Ms. Oh has nothing to disclose. Kee Duk Park has nothing to disclose. Young-Chul Choi has nothing to disclose. Hyung Jun Park has nothing to disclose.

E081 Effectiveness of intravenous belimumab in patients with systemic lupus erythematosus at a UK tertiary referral centre

Abstract Background/Aims Belimumab was approved in the United Kingdom (UK) in 2016 as add-on therapy for patients with auto-antibody positive systemic lupus erythematosus (SLE) and high disease activity refractory to standard treatment. Data regarding the effectiveness of belimumab outside clinical trials has been published in worldwide SLE cohorts but not the UK. Here, we describe the efficacy of add-on belimumab therapy in SLE patients from a large London tertiary centre. Methods We performed a retrospective, intention-to-treat analysis of clinical and biochemical outcomes, at 6 and 12 months, post receipt of at least 1 infusion of belimumab in SLE patients attending Guy’s and St Thomas’ NHS Trust (April 2013-November 2021). Outcomes assessed included: the Safety of Estrogen in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI), anti-dsDNA ELISA titre, complement C3 and C4 titres, urine protein:creatinine ratio (uPCR) and daily prednisolone dose. Analyses performed using SPSS statistics 27. Results 63 patients (56 female [88.9%], median age 38 years, self-reported race/ ethnicity; 24 Black [38.1%], 24 White [38.1%], 13 Asian [20.6%]) with SLE as defined by the 1997 ACR criteria were included. An 8-point reduction in median SELENA-SLEDAI was evident at 6 months after commencing belimumab, which increased to 9 points at 12 months (n = 28, p &amp;lt; 0.001)(Table 1). Improvements in C3/ C4 titres were also observed at 6 months (0.13-point and 0.04-point increase in median C3/ C4 titres respectively, n = 45, p &amp;lt; 0.001). At 12 months, significant reductions in median anti-dsDNA titre (16.50-point reduction, n = 42, p &amp;lt; 0.001) and median daily prednisolone dose were evident (2.50mg reduction, n = 51, p &amp;lt; 0.001). No change in uPCR was noted (n = 23, p = 0.956). 40/47 (85%) patients with a SELENA-SLEDAI score recorded at 6 months achieved the National Institute for Health and Care Excellence (NICE) defined target for a &amp;gt;/= 4-point reduction in SELENA-SLEDAI. No significant associations between baseline demographic variables and SELENA-SLEDAI score at 6 months, or prednisolone dose at 12 months, were evident. Conclusion We observed a significant improvement in SLE disease activity as determined by SELENA-SLEDAI score measured at 6 and 12 months after starting belimumab, and a significant steroid-sparing effect at 12 months. These findings are similar to published worldwide data. Disclosure G. Mallett: None. C. Hession: None. M. Fernando: Other; MF has received speaker fees from GlaxoSmithKline (GSK) and Union Chimique Belge (UCB), as well as conference fees from GSK.

Trends in Antibody Titers after SARS-CoV-2 Vaccination—Insights from Self-Paid Tests at a General Internal Medicine Clinic

Background: The rise in antibody titers against the novel coronavirus (SARS-CoV-2) and its duration are considered an important indicator for confirming the effect of a COVID-19 vaccine, and self-paid tests of antibody titer are conducted in many facilities nationwide. Methods: The relationship between the number of days after the second and third dose of vaccines, age, and antibody titer was determined from the medical records of general internal medicine clinics that conducted self-paid testing of the SARS-CoV-2 antibody titer using Elecsys Anti-SARS-CoV-2 S (Roche Diagnostics); the relationship between the number of days after two or more doses of vaccines and antibody titer was also determined. We also examined the antibody titers in cases of spontaneous infection with SARS-CoV-2 after two or more doses of the vaccine. Results: Log-transformed SARS-CoV-2 antibody titers measured within 1 month from the second or third dose of vaccine showed a negative correlation with age (p < 0.05). In addition, the log-transformed antibody titers also showed a negative correlation trend with the number of days after the second dose of vaccine (p = 0.055); however, there were no significant correlations between the log-transformed antibody titers and the number of days after the third dose of vaccine. The median antibody titer after the third vaccination was 18,300 U/mL, more than 10 times the median antibody titer after the second dose of vaccine, of 1185 U/mL. There were also some cases of infection after the third or fourth dose of vaccine, with antibody titers in the tens of thousands of U/ml after infection, but the patients still received further booster vaccinations after the infection. Conclusions: The antibody titers after the third vaccination did not attenuate after a short follow-up period of one month, while they tended to attenuate after the second vaccination. It is considered that many people in Japan received further booster vaccinations after spontaneous infection, even though they already had antibody titers in the tens of thousands of U/mL due to "hybrid immunity" after spontaneous infection following two or more doses of vaccine. The clinical significance of the booster vaccination in this population still needs to be thoroughly investigated and should be prioritized for those with low SARS-CoV-2 antibody titers.

SARS-CoV-2 Neutralizing Antibodies to B.1 and to BA.5 Variant after Booster Dose of BNT162b2 Vaccine in HIV Patients COVID-Naïve and on Successful Antiretroviral Therapy.

Live virus neutralization is the gold standard to investigate immunity. This prospective observational study aimed to determine the magnitude of response against the original B.1 lineage and against the BA.5 lineage six months after the third BNT162b2 mRNA vaccine dose in patients with HIV infection on successful antiretroviral treatment and no previous SARS-CoV-2 infection. A total of 100 subjects (M/F 83/17, median age 54 years) were included in the analysis: 95 had plasma HIV RNA <40 copies/mL, the median CD4+ T cell count at the administration of the third dose was 580 cells/mm3, and the median nadir CD4+ T cell count was 258 cells/mm3. Neutralizing antibodies (NtAb) against B.1 were detectable in all the subjects, but those to BA.5 were only detected in 88 (p < 0.001). The median NtAb titer to B.1 was significantly higher than that to BA.5 (393 vs. 60, p < 0.0001), and there was a strong positive correlation between the paired measurements (p < 0.0001). Linear regression on a subset of 87 patients excluding outlier NtAb titers showed that 48% of the changes in NtAb titers to BA.5 are related to the changes in value titers to B.1. SARS-CoV-2 variants evolve rapidly, challenging the efficacy of vaccines, and data on comparative NtAb responses may help in tailoring intervals between vaccine doses and in predicting vaccine efficacy.

FLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures overlaying anti-N-methyl-D-aspartate receptor encephalitis: a case report and literature review

FLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES) has been identified increasingly frequently in recent years. However, this rare MOG antibody disease may coexist with anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARe), in an overlap syndrome with unknown clinical features and prognosis. We report a new case of this overlap syndrome and present a systematic review of similar cases in the literature to provide information on the clinical presentation, MRI features, EGG abnormalities, treatment, and prognosis of patients with this rare syndrome. A total of 12 patients were analyzed in the study. The most common clinical manifestations of FLAMES overlaid with anti-NMDARe were epilepsy (12/12), headache (11/12), and fever (10/12). Increases in intracranial pressure (median: 262.5 mmH2O, range: 150-380 mmH2O), cerebrospinal fluid (CSF) leukocyte count (median: 128×106/L, range: 1-610×106/L), and protein level (median: 0.48 g/L) were also observed. The median CSF anti-NMDAR antibody titer was 1:10 (1:1-1:32), while the median serum MOG antibody titer was 1:32 (1:10-1:1024). Seven cases exhibited unilateral cortical FLAIR hyperintensity, and five cases (42%) had bilateral cortical FLAIR hyperintensity, including four cases involving the bilateral medial frontal lobes. Of the 12 patients, five showed lesions at other sites (e.g., the brainstem, corpus callosum, or frontal orbital gyrus) before or after the development of cortical encephalitis. EEG showed slow waves in four cases, spike-slow waves in two cases, an epileptiform pattern in one case, and normal waves in two cases. The median number of relapses was two. Over a mean follow-up period of 18.5 months, only one patient experienced residual visual impairment, while the remaining 11 patients had good prognoses. FLAMES alone is difficult to distinguish from overlap syndrome based on clinical features. However, FLAMES with bilateral medial frontal lobe involvement suggests the presence of the overlap syndrome.

Serologic response to COVID-19 infection or vaccination in pediatric kidney transplant recipients compared to healthy children

BackgroundDifferences in serologic response to COVID-19 infection or vaccination were reported in adult kidney transplant recipients (KTR) compared to non-immunocompromised patients. This study aims to compare the serologic response of naturally infected or vaccinated pediatric KTR to that of controls. MethodsThirty-eight KTR and 42 healthy children were included; aged ≤18 years, with a previously confirmed COVID-19 infection or post COVID-19 vaccination. Serological response was measured by anti-spike protein IgG antibody titers. Response post third vaccine was additionally assessed in KTR. ResultsFourteen children in each group had previously confirmed infection. KTR were significantly older and developed a 2-fold higher antibody titer post-infection compared to controls [median (interquartile range [IQR]) age: 14.9 (7.8, 17.5) vs. 6.3 (4.5, 11.5) years, p = 0.02; median (IQR) titer: 1695 (982, 3520) vs. 716 (368, 976) AU/mL, p = 0.03]. Twenty-four KTR and 28 controls were vaccinated. Antibody titer was lower in KTR than in controls [median (IQR): 803 (206, 1744) vs. 8023 (3032, 30,052) AU/mL, p < 0.001]. Fourteen KTR received third vaccine. Antibody titer post booster in KTR reached similar levels to those of controls post two doses [median (IQR) 5923 (2295, 12,278) vs. 8023 (3034, 30,052) AU/mL, p = 0.37] and to KTR post natural infection [5282 AU/mL (2583, 13,257) p = 0.8]. ConclusionSerologic response to COVID-19 infection was significantly higher in KTR than in controls. Antibody level in KTR was higher in response to infection vs. vaccination, contrary to reports in the general population. Response to vaccination in KTR reached levels comparable to controls only after third vaccine.

Anti-CD20 antibodies and bendamustine attenuate humoral immunity to COVID-19 vaccination in patients with B-cell non-Hodgkin lymphoma

Serologic responses of COVID-19 vaccine are impaired in patients with B-cell lymphoma, especially those who had recently been treated with anti-CD20 monoclonal antibodies. However, it is still unclear whether those patients develop an immune response following vaccination. We investigated the efficacy of vaccination against SARS-CoV-2 in 171 patients with B-cell non-Hodgkin lymphoma (B-NHL) who received two doses of an mRNA-based COVID-19 vaccine and we compared the efficacy of vaccination to that in 166 healthy controls. Antibody titers were measured 3 months after administration of the second vaccine dose. Patients with B-NHL showed a significantly lower seroconversion rate and a lower median antibody titer than those in healthy controls. The antibody titers showed correlations with the period from the last anti-CD20 antibody treatment to vaccination, the period from the last bendamustine treatment to vaccination and serum IgM level. The serologic response rates and median antibody titers were significantly different between diffuse large B-cell lymphoma (DLBCL) patients in whom anti-CD20 antibody treatment was completed within 9 months before vaccination and follicular lymphoma (FL) patients in whom anti-CD20 antibody treatment was completed within 15 months before vaccination. Moreover, the serologic response rates and median antibody titers were significantly different among FL patients in whom bendamustine treatment was completed within 33 months before vaccination. We demonstrated that B-NHL patients who were recently treated with anti-CD20 antibodies and bendamustine had a diminished humoral response to COVID-19 vaccination. UMIN 000,045,267.

Omicron BA.4/5 Neutralization and T-Cell Responses in Organ Transplant Recipients After Booster Messenger RNA Vaccine: A Multicenter Cohort Study.

In solid organ transplant (SOT) recipients, the primary vaccination series against Coronavirus Disease 2019 is 3 doses followed by boosters. We determined whether a fourth dose booster induced Omicron BA.4/5 neutralizing antibodies (nAbs) and T cells in a large multicenter cohort study. Serum was collected 4-6 weeks post-third and post-fourth doses of messenger RNA vaccine in 222 SOT recipients. nAbs were measured using a pseudovirus neutralization assay that targeted the Omicron BA.4/5 spike protein. A subset underwent T-cell testing. The median age of the cohort was 63 years (interquartile range [IQR], 50-68) with 61.7% men. BA.4/5 nAb detection increased from 26.6% (59 of 222) post-third dose to 53.6% (119 of 222) post-fourth dose (P < .0001). In patients with breakthrough infection prior to the fourth dose (n = 27), nAbs were detected in 77.8% and median nAb titers were significantly higher compared with those with 4 vaccine doses alone (P < .0001). Factors associated with a low BA.4/5 neutralization response after the fourth dose were older age (odds ratio [OR], 0.96; 95% confidence interval [CI], .94-.99), mycophenolate use (OR, 0.39; 95% CI, .20-.77) and prednisone use (OR, 0.34; 95% CI, .18-.63), and vaccine type (OR, 0.72; 95% CI, .51-.99), while breakthrough infection prior to the fourth dose (OR, 3.6; 95% CI, 1.3-9.9) was associated with a greater nAb response. Polyfunctional BA.4/5-specific CD4+ T cells significantly increased after 4 doses and were identified in 76.9% of patients at a median frequency of 213/106 cells (IQR, 98-650). In summary, a booster significantly increases BA.4/5-specific neutralization and polyfunctional CD4+ T-cell responses, suggesting protection from severe disease even with new Omicron variants. However, SOT recipients who are older and on mycophenolate and prednisone need additional preventative strategies.

Mix-and-match COVID-19 vaccines trigger high antibody response after the third dose vaccine in Moroccan health care workers

Recent studies have shown that in individuals who have received two doses of COVID-19 vaccine, the level of IgG antibodies decreased over time. In addition, the resurgence of the epidemic due to variants has led the authorities in several countries, including Morocco, to extend the third dose to the entire adult population. In this study, we included 43 healthcare workers (HCWs) who were vaccinated with three doses. They were vaccinated with ChAdOx1 nCoV-19 for the first two doses and with BNT 162b2 or BBIBP-CorV vaccine for the third dose. Humoral response was assessed on the day of injection of the third dose of vaccine and one month after the third dose by measuring anti-receptor-binding domain (RBD) IgG levels. Seven months after the second dose, the median titer of anti-RBD IgG was higher in the group with a history of SARS-CoV-2 infection than in the group with no history of infection (1038 AU/mL vs. 76.05 AU/mL, respectively, p = 0.003). One month after the third dose, a significant increase in median level of anti-RBD in both groups was observed: from 76.05 AU/mL to 6127 AU/mL in the group with no history of infection and from 1038 AU/mL to 14,412 AU/mL in the group with history of infection. Notably, the BNT 162b2 vaccine elicits a high titer of anti-RBD antibody compared to the BBIBP-CorV vaccine. Median antibody titers were 21,991 AU/mL and 3640 AU/mL for BNT 162b2 and BBIBP-CorV vaccines, respectively (p = 0.0002). 23% of HCWs were infected with SARS-CoV-2 within the first two months after the third dose injection. However, all these patients developed mild symptoms and tested negative by RT-qPCR between 10 and 15 days after the onset of symptoms. Our findings support that the third dose of COVID-19 vaccine significantly improves the humoral response and protects against the severe disease.

SEROLOGIC RESPONSE AND ADVERSE EFFECTS OF RECOMBINANT CANINE DISTEMPER VACCINATION IN THREE AQUARIUM-HOUSED WALRUSES (ODOBENUS ROSMARUS).

Fatalities have been associated with phocine and canine distemper viruses in marine mammals, including pinnipeds. No data are available regarding distemper disease or vaccination in walruses. This study evaluates seroconversion and clinical adverse effects following administration of a canarypox-vectored recombinant distemper vaccination (two 1-ml doses, 3 wk apart) in three adult aquarium-housed walruses. Serum antibodies to distemper were measured using seroneutralization on blood samples collected under operant conditioning prior to and for 12 mon after vaccination or until titers were <32. All walruses seroconverted. Medium positive titers (64-128) were detected for 4 to 9.5 mon in two of three individuals. Interindividual variability was noted, with one individual displaying only low positive titers. Major swelling at the site of injection and lameness for a week following injection occurred in all three walruses. Further studies on dosing amount and interval are needed to make vaccine recommendations in this species.

Effect of Convalescent Plasma Therapy on COVID-19 Patients: A Retrospective Study

Background: Coronavirus disease 2019 (COVID-19) was first detected in December 2019 in Wuhan, China. Different treatments have been used to fight against the virus; however, one of the most effective and accessible is convalescent plasma therapy (CPT). Objectives: The present study investigated the effect of CPT on improving the clinical conditions of COVID-19 patients. Methods: This study was conducted on 440 individuals, including 220 COVID-19-recovered individuals as plasma donors and 220 plasma recipients, in Shiraz, Fars province, Iran, from May 2020 to February 2021 using random sampling. After complete recovery from COVID-19, patients were recalled for apheresis and plasma isolation for convalescent plasma (CP) preparation; they were referred to the blood donation centers of Shiraz. According to the hospital request, compatible and related plasma was sent for COVID-19-hospitalized patients. At the same time, hospitals were asked to send the clinical condition documents of the patients based on the medical records and the outcomes after CPT. The Iranian Blood Transfusion Organization evaluated the results. Results: The median antibody titer was 1300. Titers higher and lower than 1300 were considered high and low, respectively. Blood group O had 54 times higher antibody titers above 1300 than other blood groups (odds ratio (OR) = 54, confidence interval (CI): 19.5 - 205.3, P &lt; 0.001). Additionally, most deceased cases received plasma with antibody titers less than 1300 (OR = 0.08, CI: 0.009 - 0.36, P &lt; 0.001). Nevertheless, most discharged patients received plasma with antibody titers higher than 1300 (OR = 1.5, CI: 1.06 - 2.3, P = 0.01). Moreover, when donors’ antibody titer was higher than 1300, the chance of survival increased by 50%. In addition, the results of this study showed higher mortality in patients whose volume of received plasma was less than 387 mL (OR = 0.3, CI: 0.10 - 0.91, P = 0.018). However, patients who received more than 387 mL CP were more likely to discharge (OR = 5.7, CI: 3.7 - 8.8, P &lt; 0.001). Conclusions: Using blood group O plasma with a minimum volume of 387 mL can be very effective in improving the clinical symptoms of patients with COVID-19 and increasing the chances of survival for these patients.