Glial fibrillary acidic protein astrocytopathy in a patient with recent mRNA SARS-CoV-2 vaccination: COVERSHEET

Background: Literature describing triggers of GFAP astrocytopathy (GFAP-A) is limited. We report a case of GFAP-A in a patient with recent messenger ribonucleic acid (mRNA) severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) vaccination and discuss the possible pathogenesis. Case description: A 45-year-old gentleman presented with features of meningoencephalitis 31 days after the first dose and 4 days after the second dose of mRNA SARS-CoV-2 vaccination. He sequentially developed brainstem/cerebellar, autonomic and cord dysfunction. Cerebrospinal fluid was positive for GFAP autoantibody. Clinical improvement occurred after intravenous methylprednisolone and immunoglobulins. Conclusion(s): Although we are uncertain of a causal link of GFAP-A to mRNA vaccine, indirect activation of an underlying dysregulated immune milieu is plausible.Copyright © 2021 The Author(s)

SARS-CoV-2 infection among healthcare workers whom already received booster vaccination during epidemic outbreak of omicron variant in Taiwan.

BACKGROUND/PURPOSE: Healthcare workers (HCWs) are at risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection due to occupational exposure. We aim to investigate the prevalence and risk factors of SARS-CoV-2 infection among HCWs during epidemic outbreak of omicron variant in Taiwan. METHODS: Sequential reserved serum samples collected from our previous study during December 2021 and July 2022 were tested for antibodies against SARS-CoV-2 nucleocapsid protein (NP). Diagnosis of SARS-CoV-2 infection was defined as positive either of anti-SARS-CoV-2 nucleoprotein, rapid antigen test or polymerase chain reaction. Retrospective chart review and a questionnaire were used to access the symptoms and risk factors for SARS-CoV-2 infection. RESULTS: Totally 300 participants (69.3% female) with a median age of 37.9 years were enrolled. A significant increase incidence of SARS-CoV-2 infection was found before and during community outbreak (11.91 versus 230.93 per 100,000 person-days, P < 0.001), which was a trend paralleling that observed in the general population. For 61 SARS-CoV-2 infected participants, nine (14.8%) were asymptomatic. Multivariate analysis revealed recent contact with a SARS-CoV-2 infected household (odds ratio [OR], 7.01; 95% confidence interval [95% CI], 3.70-13.30; P < 0.001) and co-existed underlying autoimmune diseases (OR, 4.46; 95% CI, 1.28-15.51; P = 0.019) were significant risk factors associated with acquisition of SARS-CoV-2 infection among HCWs. CONCLUSION: Community factors, such as closely contact with SARS-CoV-2 infected individuals and underlying immune suppression status, were significant factors for acquisition of SARS-CoV-2 infection among HCWs. We suggest the application of appropriate infection control measures for HCWs should be maintained to reduce risk of SARS-CoV-2 infection.

Endogenous antibody response to SARS-CoV-2 in patients who received monoclonal antibodies against COVID-19: A systematic review

Passive immunization with mAbs has been employed in COVID-19. We performed a systematic review of the literature assessing the endogenous humoral immune response against SARS-CoV-2 in patients treated with mAbs. Administration of mAbs in seronegative patients led to a reduction in both antibody titres and neutralizing activity against the virus.Copyright © 2022

Impact of immunomodulating treatment modalities, active smoking and (repeated) COVID19 vaccination on S-antibody seroconversion in IMID patients. Results of the BELCOMID study: BELgian Cohort study of COVID-19 in Immune Mediated Inflammatory Diseases (IMID)

Background: Targeted Immune-Modulating Therapies (TIMT) and immunomodulators (IMM) for Immune Mediated Inflammatory diseases (IMID) theoretically interfere with humoral responses against COVID19. However, IMID patients and particularly patients receiving immunosuppressive treatment were excluded from phase-3 COVID19 vaccination efficacy trials. Real-world observational data is therefore required to provide more insight into the efficacy of COVID19 vaccination in IMID patients. Method(s): The BELCOMID study is a multidisciplinary, prospective observational cohort study performed at two university hospitals and set up with the intention to explore the interaction between IMIDs, immune-modulating treatment modalities and SARS-CoV-2 infection and vaccination in a real-life patient cohort. Consecutive patients seen between 17/12/2020 and 28/02/2021 during routine follow-up for IMIDs of the gut, joints and skin were invited to participate. Both patient data and serological samples were collected at 3 predefined periods (Figure 1: Before vaccination, after start of the national vaccination campaign before booster vaccination, after booster vaccination). Spike (S) protein antibodies were analysed with the Abbott ArchitectTM assay. R version 4.0.2 was used to perform analyses. Result(s): At inclusion period 2, 2065 patients (Table 1) participated of whom 1547 had received complete baseline vaccination (2 doses mRNA-1273, BNT162b2, ChadOx1 nCoV-19 or 1 dose JN78436735). S-antibody seroconversion rate was 91.2%. At inclusion period 3, data was available for 1566 patients of whom 74.7% had received 1 booster (BNT162b2 or mRNA-1273) vaccination leading to a S-antibody seroconversion rate of 98.3%. In 130 patients who had received 2 boosters, S-antibody seroconversion rate was 100%. At period 3, 37 patients had refused all vaccinations. Although 23 of these had experienced confirmed COVID19 since previous inquiry, no S-antibody seroconversion was found in 15 of them. Logistic regression analyses revealed that the odds of no S-antibody seroconversion were significantly higher in IMID patients treated with IMM, combination of IMM+TIMT, systemic steroids and smoking patients at both inclusion periods (Table 2). TIMT monotherapy did not influence seroconversion rates at inclusion period 3 but was associated with higher odds of the lowest S-antibody titre quartile (OR2.32, P<0.001). Among TIMT options, rituximab had higher odds of S-seronegativity. Conclusion(s): S-antibody seroconversion rate in this real-life IMID population was high after baseline vaccination and increased further proportionally with booster vaccination, highlighting the value of repeated vaccination. However, the serologic response may be blunted due to different IMID treatment modalities and smoking.

Transient optic neuritis and perineuritis associated with anti-MOG antibody after SARS-CoV-2 mRNA vaccination

Backgrounds: To report the first case of left optic neuritis and perineuritis associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BNT162b2 mRNA vaccination. Case presentation: A 39-year-old woman was referred and admitted to our hospital due to transient left visual field abnormality with left ophthalmalgia and headache 12 days after the first vaccination dose of SARS-CoV-2 (BNT162b2). On admission (Day 2), she presented with left ophthalmalgia and headache without any other neurological deficits including the movement of eyeballs, visual field, visual acuity, or nystagmus. MRI on Day 2 suggested slight left optic neural swelling;Gadolinium-enhanced MRI on Day 4 revealed left optic perineuritis. Test for serum anti-aquaporin 4 antibody was negative, whereas anti-myelin oligodendrocyte glycoprotein (MOG) antibody was positive. She was diagnosed with left optic perineuritis after SARS-CoV-2 mRNA vaccination. Her visual disturbance never recurred and her ophthalmalgia and headache subsided only with anti-inflammatory agents. Discussion(s): Many cases of optic neuritis associated with vaccinations have been reported except for SARS-CoV-2 BNT162b2 mRNA. To our knowledge, only one neuromyelitis optica case was associated with anti-MOG antibody. Therefore, we propose that SARS-CoV-2 mRNA vaccination may induce transient optic neuritis and perineuritis, associated with anti-MOG antibody in the present case. Conclusion(s): This is the first case of left optic neuritis and perineuritis associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BNT162b2 mRNA vaccination.Copyright © 2022

Colorimetric and Raman dual-mode lateral flow immunoassay detection of SARS-CoV-2 N protein antibody based on Ag nanoparticles with ultrathin Au shell assembled onto Fe3O4 nanoparticles.

Serological antibody tests are useful complements of nuclei acid detection for SARS-CoV-2 diagnosis, which can significantly improve diagnostic accuracy. However, antibody detection in serum or plasma remains challenging to do with high sensitivity. In this study, Ag nanoparticles with ultra-thin Au shells embedded with 4-mercaptobenzoic acid (MBA) (AgMBA@Au) were manufactured and then assembled onto Fe3O4 surface by electrostatic interaction to construct the Fe3O4-AgMBA@Au nanoparticles (NPs) with magnetic-Raman-colorimetric properties. Based on the composite nanoparticles, a colorimetric and Raman dual-mode lateral flow immunoassay (LFIA) for ultrasensitive identification of SARS-CoV-2 nucleocapsid (N) protein antibody was constructed. The magnetic nanoparticles (Fe3O4 NPs) were acted as the core and coated a layer of AgMBA@Au particles on the surface by electrostatic interaction to prepare Fe3O4-AgMBA@Au NPs, which can amplify the SERS signal due to multiple AgMBA@Au particles concentrated on a single magnetic nanoparticle. Moreover, the Fe3O4-AgMBA@Au NPs facilitated pre-purifying sample using magnetic separation, and complex matrix interference would be greatly decreased in the detection. The Fe3O4-AgMBA@Au NPs modified with N protein recognized and bound with N protein antibodies, which were trapped on the T-line, forming color band for observing detection. Under optimal conditions, the N protein antibodies could be qualitatively detected in colorimetric mode with the visual limit of 10-8 mg/mL and quantitatively detected by SERS signals between 10-6 and 10-10 mg /mL with 0.08 pg/mL detection limit. The coefficients variations (CV) of intra-assay was 8.0%, whereas of inter-assay was 11.7%, confirming of good reproducibility. Finally, this approach was able to discriminate between positive, negative, and weakly positive samples when detecting 107 clinical serum samples. The process enables highly sensitive quantitative assays that are valuable for evaluating disease processes and guiding treatment. Colorimetric and Raman dual-mode LFIA detection of SARS-CoV-2 N protein antibody based on Fe3O4-AgMBA@Au nanoparticles.

COVID-19 Booster Vaccine: is it an absolute need?

Booster vaccine doses are meant to revive the fading immunity created by prior exposure to an immunizing antigen. They stabilize the antibody response ultimately leading to longer and higher protection against pathogens. Immunological studies done for COVID-19 vaccines have documented a steady decrease in antibody levels among vaccinated individuals and evidence of breakthrough infections over a course of time. With an emerging science behind the need for COVID-19 vaccine booster shots, there equally is a contrasting idea regarding its absolute necessity. Copyright © 2021, Kathmandu University. All rights reserved.

International Practices on COVID-19 Vaccine Mandates for Transplant Candidates

Purpose: The coronavirus disease 2019 (COVID-19) pandemic has created unprecedented challenges and there are practice differences for solid organ transplant programs worldwide. We sought to assess an international perspective on COVID-19 vaccine mandates and rationales for or against a mandate policy. Method(s): We administered an electronic survey instrument to staff at transplant programs outside the United States (October-November 2021) that comprised of 23 questions addressing the reasons cited by centers for or against implementing a vaccine mandate. Each responding transplant program was represented once in the analysis. Result(s): Respondents (n=63) represented 19 countries on 5 continents. More than half (52.6%) of centers reported implementing a vaccine mandate, however 37.2% reported that their center has not considered (27.1%) or unsure (10.2%) on vaccination requirement. The main rationale for centers not implementing a vaccine mandate were concerns for undue pressure to transplant candidates, equity and legal considerations. (Fig. 1) The main rationale for centers with a vaccine mandate were efficacy of pre-transplant vaccination then post-transplant, importance for public health and minimizing exposure of other patients. (Fig. 2) The majority (79%) of the centers mandate vaccine regardless of prior SARS-CoV-2 infection status, and regardless of pre-vaccination spike-protein antibody titer or other markers or prior infection. Only 24.4% of centers with a vaccine mandate for transplant candidates also extended a vaccine requirement to potential living donors. Conclusion(s): The approach to pre-transplant COVID-19 vaccination mandate is heterogeneous across different countries and centers. More than one third of centers are reluctant to consider vaccine mandates for a varies of reasons including ethical, legal and equity concerns. (Figure Presented).

Correlation of Serum and Fingerstick Blood Collection for Monitoring Sars-Cov-2 Spike and Nucleocapsid Antibodies

Background: The rapid spread and recurrent infections of SARS-CoV-2 has led to increased use and availability of at-home antigen testing, but widespread testing of antibodies against spike and nucleocapsid to monitor vaccine-induced immunity and exposure to the virus is lacking. Most serological tests require a serum sample from a venous blood draw, increasing risk of exposure to COVID-19 and limiting availability and scalability of testing for many patients. This is especially the case for individuals who are immunocompromised, such as those with inflammatory bowel diseases (IBD), which are frequently on medications that might alter their immune response and impact vulnerability to SARS-CoV-2. Use of easily acquired and stably stored dried fingerstick blood serves a promising specimen source for at-home, remote testing for SARS-CoV-2 antibodies. Aim(s): Validate the use of fingerstick blood (dried and then eluted) versus serum as a specimen for the measurement of quantitative spike and nucleocapsid antibodies to SARS-CoV-2 in a diverse cohort of healthy and immunocompromised patients. Method(s): Patients were consented and enrolled into the Pediatric Gastrointestinal Tissue, Stool, Saliva and Blood Registry prior to having an endoscopic procedure. Five mL of blood was obtained by venipuncture and 10 muL of fingerstick blood was collected and dried on a Neoteryx Mitra device. Blood was eluted from the Neoteryx Mitra samples in 200 muL of dilution buffer (1% BSA, 0.05% Tween-20, 140 mM NaCl, 50 mM Tris (pH 8.0), 0.025% sodium azide) and placed on an orbital shaker at a speed of 500 RPM for 3 h. Paired serum and fingerstick blood eluate specimens were run on the quantitative Roche Elecsys SARS-CoV-2 spike antibody assay and the qualitative Roche Elecsys SARS-CoV-2 nucleocapsid antibody assay. Linear regression were performed on each assay with exclusion of values that were above the upper limit of detection of the assay. Result(s): We observed an excellent correlation in both SARS-CoV-2 antibody assays when comparing fingerstick blood eluates and serum. The linear regression for the nucleocapsid antibody assay had a slope of 15.5, intercept of 4.05, and R2 of 0.92, indicating that a Neoteryx value of 1.00 COI (cut-off index) equates to a serum value of 19.6 COI. The linear regression for the spike assay had a slope of 13.6, intercept of 953, and R2 of 0.95, indicating that a value of 1,000 U/mL from a fingerstick sample equates to a serum value of 14,544 U/mL. Conclusion(s): These data demonstrate that fingerstick blood collected on Neoteryx Mitra devices can be used as a specimen source in Roche Elecsys SARS-CoV-2 antibody assays to calculate the serum levels of spike and nucleocapsid antibodies. This can serve as a platform to remotely and reliably monitor the durability of antibody responses to natural infection with and immunization against SARS-CoV-2 in patients. Chart comparisons of nucleocapsid (top) and spike (bottom) protein antibody levels detected via remote fingerstick collection (Neoteryx, x-axis) and venous blood serum (y-axis).

The Waxing, Waning, and Predictors of Humoral Responses to Vector-Based SARS-CoV-2 Vaccine in Hemodialysis Patients.

Hemodialysis (HD) patients are vulnerable to coronavirus disease 2019 (COVID-19) and have a high mortality rate. We evaluated the anti-SARS-CoV-2 spike protein antibody (ACOV2S) levels in 385 HD patients before and 4 and 8 weeks after the second dose of vector-based ChAdOx1 nCoV-19 vaccine. For study control, week 4 ACOV2S levels after the second vaccination dose were measured in 66 healthcare workers (HCWs). The seroconversion rate of HD patients was 98.96% 4 weeks after the second vaccination. Despite low antibody levels before the second dose (week 0), week 4 ACOV2S levels after the second vaccine dose in HD patients increased prominently and were compatible with those in HCWs (p = 0.814 for HCWs vs. HD patients). The ACOV2S levels in HD patients waned significantly 8 weeks after the second vaccination dose (p < 0.001 at week 8 vs. 4). Older age and immunosuppressant use were negative predictors, while higher C-reactive protein (CRP) levels were positive predictors of ACOV2S waxing after the second vaccine dose in HD patients. Higher CRP levels and platelet counts were independently associated with decreased ACOV2S waning. The ChAdOx1 nCoV-19 vaccine is effective and safe for primary vaccination in HD patients and a booster dose is necessary.

Age- and sex-based changes in spike protein antibody status after SARS-CoV-2 vaccination and effect of past-infection in healthcare workers in Osaka.

OBJECTIVE: We aimed to compare the changes in SARS-CoV-2 spike protein antibody titres based on age group and sex using paired blood sampling after vaccination in association with the presence of nucleocapsid protein antibody. METHODS: All participants were healthcare workers at Yao Municipal Hospital in Osaka who voluntarily provided peripheral blood samples (n = 636, men/women 151/485, mean age 45 years). We investigated the serial changes in SARS-CoV-2 spike protein antibody titres at 1 and 7 months after the second vaccination regarding their relationship with sex and age group. At 7 months, we also examined anti-nucleocapsid assays. Antibody titres were shown as logarithmic values and the differences were assessed using a paired or unpaired student's t-test as appropriate. RESULTS: Among participants younger than 30 years, the antibody titres of spike protein were significantly higher in women one (p = 0.005) and seven (p = 0.038) months after vaccination. However, among those aged 30-49 years, the antibody titres were not different between the sexes at either follow-up time point. In contrast, among those aged 50-59 years, between-sex differences in antibody titres were observed only at 7 months, which was associated with a significant reduction in men. A significant negative correlation was observed between the antibody titres for spike protein at both time points in participants with positive nucleocapsid protein antibody at 7 months (r = - 0.467, p = 0.043), although a significant positive correlation was observed in those with negative results (r = 0.645, p < 0.001), CONCLUSIONS: Between-sex differences in SARS-CoV-2 spike protein antibody titres by paired blood sampling at different time points after vaccination depended on age group. The presence of nucleocapsid protein antibody was associated with changes in spike protein antibody titres after vaccination.

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.

[SARS-CoV-2 antibody response to the second COVID-19 vaccination in neuromuscular disease patients under immune modulating treatment]. / SARS-CoV-2-Antikörper-Antwort auf die zweite COVID-19-Impfung bei neuromuskulären Patienten unter immunmodulierender Therapie.

Successful vaccination (adequate elevation of anti-spike protein antibodies) is attributed with sufficient protection against a severe course of coronavirus disease 2019 (COVID-19). For patients with chronic inflammatory diseases (CID) and immunosuppression the success of vaccination is an ongoing scientific discourse. Therefore, we evaluated the antibody titer against the S1 antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 2 weeks after complete immunization in patients with an underlying neuromuscular disease (NMD), who presented to our neurological day clinic and outpatient department for regular infusions of immunoglobulins. The data show that patients with chronic autoimmune NMD and simultaneous immunosuppressive or immune modulating treatment show an antibody response after vaccination with both mRNA and vector vaccines. In comparison to healthy subjects there is a comparable number of seroconversions due to the vaccination. A correlation between immunoglobulin dose and vaccination response could not be found; however, in contrast, there was a significant reduction of specific antibody synthesis, especially for the combination of mycophenolate mofetil (MMF) and prednisolone.

HUMORAL AND T CELL RESPONSES TO COVID-19 VACCINATION IN INFLAMMATORY BOWEL DISEASE

BACKGROUND: The characteristics of SARS-CoV-2 vaccine-induced immunity in inflammatory bowel disease (IBD) patients on immune modifying agents has not been clearly defined due to their exclusion in vaccine trials. Emerging results suggest infliximab impairs antibody response compared to vedolizumab. However there has not been direct comparison to controls. We evaluated this with both humoral and T cell response in IBD patients. METHODS: Antibody and T cell response were analysed in IBD patients who received BNT162b2 (Pfizer–BioNTech) or ChAdOx1 nCoV-19 (Oxford–AstraZeneca) vaccination from a single Australian centre. The control group were healthcare workers (HCW) without IBD. Blood samples were taken at 4 time points: at baseline V0 (before vaccination);V1 (7- 14 days after vaccine 1);V2 (7-14 days after vaccine 2);V3 (21-42 days after vaccine 2). Antibodies to the S1/2 IgG subunit and receptor-binding protein (RBD) were measured and reported here. RESULTS: 88 (28 ulcerative colitis, 50 Crohn's disease) IBD patients were included and compared to 53 healthy controls (Table 1). IBD patients medications included 6 5ASA (6.8%), 6 immunomodulator monotherapy (6.8%), 14 anti-TNF monotherapy (15.9%), 32 anti-TNF combination therapy with immunomodulator (36%), 16 IL12/23 (18%) and 13 vedolizumab (14%). Pre-vaccine baseline sera showed absence of anti-RBD antibodies in all participants. 84 patients (87%) received BNT162b2 and 4 (4.5%) received ChAdOx1 nCoV-19 vaccines. Geometric mean [SD] anti-S1/2 antibody concentrations at 4 weeks after second vaccination (V3) were significantly lower in IBD TNF treated patients (162.6[1.7]) compared to IBD non TNF treated patients (325.2[1.3]), and healthy controls (325.2[1.3]), p<0.0001 (Figure 1). There was no difference between non-TNF treated patients including those on vedolizumab or IL12/23 compared to controls. Similarly there was a significant difference between anti-RBD IgG titres between TNF and non-TNF IBD patients at V3 but not when compared to controls. There was no difference in RBD IgG and anti-S1/2 antibodies between anti-TNF monotherapy and combination therapy. All healthy controls and most IBD patients seroconverted at V3. 2 patients that failed to seroconvert were on steroid. CONCLUSION: TNF agents influence SARS-CoV-2 vaccine-induced antibody response in IBD patients, with lower anti-S1/2 IgG concentrations compared to non-TNF IBD patients and healthy controls. However, there was no difference in RBD IgG concentrations. It is unclear whether these subtle differences in antibody response in IBD patients on TNF agents is biologically meaningful, as most seroconverted after second dose vaccination. They may translate to differences in antibody longevity, but this is yet to be demonstrated. Neutralising antibody and T cell (CD4+/CD8+/follicular T cell) data from this study to come. (Table Presented) (Figure Presented)

CASIRIVIMAB/IMDEVIMAB IN VACCINATED CHRONIC HAEMODIALYZED PATIENTS WITH ACUTE MILD COVID-19: SAFETY AND EFFICIENCY

BACKGROUND AND AIMS: Casirivimab/imdevimab (C/I) is a combination of two neutralizing human monoclonal antibodies against the SARS-CoV-2. It has been approved for primary prophylaxis or acute SARS-CoV-2 infection in patients with a poor vaccine response. Chronic haemodialyzed (CHD) patients are a high-risk population for both severe COVID-19 and impaired vaccine response. We herein report the safety and efficiency of C/I in CHD patients with acute mild COVID-19. METHOD: In a single-centre haemodialysis facility, all 56 CHD patients received 3 injections of anti-COVID-19 mRNA BNT162b2 vaccine, with anti-S protein antibodies response assessed 7 months after the last injection. During follow-up, patients who presented an acute mild SARS-CoV-2 infection without the need for oxygen therapy and a poor vaccine response received within 5 days after diagnosis 600mg/600mg of C/I. The combination of monoclonal antibodies was infused only once after the end of the dialysis session during 20 min. Patients were kept under surveillance during 1 h before discharge. Efficiency was assessed by RT-PCR 7 days after C/I infusion and clinical evaluation. RESULTS: Six CHD patients had an acute COVID-19 without oxygen therapy requirement and four had a vaccine response < 264 BAU/mL. Among them three had the Delta variant (L452R mutation), and received C/I. Two of them had the opportunity to have a fourth vaccine injection, but got infected within 2 weeks after the boost. Clinical data are summarized in Table 1. No patient presented any adverse effect within the time in the dialysis facility. During follow-up, all patients remained asymptomatic and all control RT-PCR performed 7 days after infusion were negative. CONCLUSION: 600 mg/600 mg of C/I is a safe and efficient treatment for CHD patients with a poor vaccine humoral response presenting mild acute Delta variant COVID-19 without oxygen requirement.

Aquaporin-4 protein antibody-associated optic neuritis related to neuroendocrine tumor after receiving an inactive COVID-19 vaccine.

Neuromyelitis optica (NMO), also known as Devic's disease, is a rare, autoimmune, and recurrent demyelinating disorder that primarily affects the spinal cord and optic nerve. We report a case with recurrent optic neuritis caused by the paraneoplastic NMO spectrum disorder in the setting of a gastric neuroendocrine tumor 2 weeks after receiving an inactive COVID-19 vaccine.

Immunogenicity of SARS-CoV-2 vaccination in subjects on active treatment for breast cancer

Background: Infection with SARS-CoV-2 has led to a global pandemic and has significantly impacted the care of cancer patients. Breast cancer patients receiving active systemic therapy need protection against COVID19 but the efficacy of vaccines in this population is unknown. Although specific biomarkers associated with protection from SARS-CoV-2 infection have yet to be identified, measurement of serum antibody activity is generally accepted as a surrogate of in vivo humoral response to vaccine. This study evaluates the efficiency and durability of binding antibodies to SARS-CoV-2 spike (S) protein in response to COVID19 vaccine in breast cancer patients receiving systemic treatment. Methods: Breast cancer patients, who were unvaccinated, partially or fully vaccinated with Pfizer-BioNTech BNT162b2 (PF), Moderna mRNA-1273 (Mod) or Johnson & Johnson AD26.COV2.S (J&J) were enrolled in this prospective longitudinal study. Eligible patients were on systemic treatment with cytotoxic chemotherapy, chemotherapy plus a checkpoint inhibitor (CPI), CPI alone or a CDK 4/6 inhibitor. Longitudinal blood samples are being collected at baseline, prior to vaccination in unvaccinated patients (T0), 2 weeks after the first vaccine dose and before Sthe second dose for the mRNA vaccines (T1), 1 month (T2), 3 months (T3), 6 months (T4) and 12 month post vaccination. For J&J, there was no T1 timepoint. Roche Elecsys® Anti-SARS-CoV-2 S receptor binding domain (RBD) antibody immunoassay was used to measure antibody titers (range 0.4 to 250 U/mL). Cut points of <0.8 U/mL = negative, ≥0.8 U/mL = seropositive, were based on validated product specifications. Results: Of the 84 breast cancer patients enrolled, 9 had documented COVID infection at baseline and were excluded from analysis. Mean age was 58 years;99% were female, 85% were Caucasian, 49% had early stage disease and 51% had metastatic breast cancer. 67% were receiving cytotoxic chemotherapy, 20% a CKD 4/6 inhibitor, 13% a CPI with or without chemotherapy. 61.2% were vaccinated with PF, 34.3% with Mod and 4.5% with J&J vaccines. Seropositivity rate for the entire group was 10% at T0, 78% at T1, 98% at T2 and 100% at T3. Seropositivity rates of all cohorts at different timepoints are shown in the table. Mean titers for all patients were 12.6 U/mL at T0, 102.3 U/mL at T1, 204.4 U/mL at T2 and 214.6 U/mL at T3 timepoints. Similar incremental increase in antibody levels was observed in all cohorts (Table). Conclusions: 78% of the patients with breast cancer on active systemic treatment were seropositive after the first dose of COVID19 vaccine and 98% after the second dose. The antibody response was maintained at 3 months, with 100% seropositivity rate. 6-month antibody response will be available at the time of presentation. Durability of antibody response at 6 and 12 months will help determine the timing of additional vaccine booster doses in this population. Importantly, this study has found that active treatment with chemotherapy, immunotherapy or CDK4/6 inhibitor therapy does not impact antibody response to SARS-CoV-2 vaccination in patients with breast cancer. Table: Seropositivity rate and mean Anti-S protein antibody levels by cohort at each time point. T0= baseline, T1=after first vaccine dose (mRNA vaccines), T2= 4 weeks after 2 doses of mRNA vaccine or after single dose of J&J vaccine, T3=3 months after the first dose of vaccine.

Anti-spike protein antibody titer at the time of breakthrough infection of SARS-CoV-2 omicron.

By December 2021, about 80% of people over the age of 12 had been vaccinated in Japan, and almost all people were vaccinated with the mRNA vaccine. We investigated here the anti-spike protein antibody titer at the time of breakthrough infection of SARS-CoV-2 omicron. A total of 32 SARS-CoV2 omicron breakthrough infection was included in the study. The median antibody titer at breakthrough infection was 776 AU/mL overall, of which the median antibody titer of BNT162b2 vaccinated was 633 AU/mL and that of mRNA-1273 vaccinated was 9416 AU/mL. This result suggests that low levels of antibody titers 6 months after vaccination do not provide sufficient antibodies to prevent the omicron variant breakthrough infection, which may occur with a higher anti-spike antibody titer after vaccination with mRNA-1273. However, antibody titers in some patients were comparable to those immediately after the second vaccination with either mRNA vaccine.

Evolution of COVID19 serology in a real-life population of IMID patients. Results of the BELCOMID study: BELgian Cohort study of COVID-19 in Immune Mediated Inflammatory Diseases (IMID)

Background: Immunomodulators (IMM) and Targeted Immune-Modulating Therapies (TIMT) such as anti-TNF, anti-interleukins and Janus Kinase inhibitors, for treatment of Immune Mediated Inflammatory diseases (IMID) could theoretically interfere with the cytokine storm and humoral immune response against COVID19 infection and vaccination. We investigate seroprevalence and evolution of SARS-CoV2 antibodies in relation to previous vaccination and/or exposure to COVID19 and ongoing IMID-treatment in a Belgian, reallife population of IMID patients. Methods: A cross-disciplinary, prospective, observational cohort study was set up at two university hospitals. All patients with IMIDs of the gut (Crohn's disease, ulcerative colitis), joints (rheumatoid, psoriatic or spondyloarthritis) and skin (psoriasis, hidradenitis suppurativa, atopic dermatitis) visiting the respective clinics were asked to participate. Patients had to fill out an electronic survey (REDCap®, based on WHO-ISARIC) and blood samples were drawn for serology testing (anti-Spike(S) and antiviral Nucleocapsid(N) protein antibody IgG, Abbott). Results at baseline, prior to the national vaccination program and at 6 months follow-up are presented. R version 4.0.2 was used for statistical analyses. Results: At baseline 2165 IMID patients consented to take part. In 3.2% SARS-CoV2 anti-N seroconversion was confirmed. Of the anti-N seroconverted patients 72.9% reported a positive PCR test prior to inclusion. At 6-months follow-up, data of 1853 IMID patients was collected. Of these, 81.7% were fully and 14.4% partially vaccinated. Seroconversion for anti-N antibodies was confirmed in 2.5% of all participants and seroconversion for anti-S antibodies in 90.8%. In 5.1% (61/1483) of fully vaccinated IMID patients no seroconversion in anti-N nor anti-S antibodies was found. Chi Square analyses show, at 6-months follow-up, no significant association between anti-S seroconversion rate and treatment with systemic steroids (RiskRatio 1.22, 95%CI 0.38-3.9, P=0.99), TIMT (RiskRatio 0.57, 95% CI 0.3-1.1, P=0.12), IMM (RiskRatio 1.65, 95% CI 0.85- 3.19, P=0.19) or combination treatment IMM/TIMT (RiskRatio 1.60, 95% CI 0.75-3.4, P=0.32). Appearance of COVID19 symptoms followed the epidemiological curve in Belgium (Fig1). Conclusion: In this real-life IMID cohort, the number of COVID19 cases confirmed by PCR prior to vaccination was low. Seroconversion rate for anti-N antibodies was lower at 6-months follow-up, suggesting decrease in antibody titre over time. Full COVID19 vaccination led to a high anti-S antibody seroconversion rate. Nonetheless, 5.1% of fully vaccinated patients showed no antibody seroconversion. So far, no significant association between anti-S antibody seroconversion and IMID treatment was noted.

Humoral and T cell responses to COVID-19 vaccination in IBD

Background: The characteristics of SARS-CoV-2 vaccine-induced immunity in inflammatory bowel disease (IBD) patients on immune modifying agents has not been clearly defined due to their exclusion in vaccine trials. Emerging results suggest infliximab impairs antibody response compared to vedolizumab. However there has not been direct comparison to controls. We evaluated this with both humoral and T cell response in IBD patients. Methods: Antibody and T cell response were analysed in IBD patients who received BNT162b2 (Pfizer-BioNTech) or ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccination from a single Australian centre. The control group were healthcare workers (HCW) without IBD. Blood samples were taken at 4 time points: at baseline V0 (before vaccination);V1 (7-14 days after vaccine 1);V2 (7-14 days after vaccine 2);V3 (21-42 days after vaccine 2). Antibodies to the S1/2 IgG subunit and receptor-binding protein (RBD) were measured and reported here. Results: 88 (28 ulcerative colitis, 50 Crohn's disease) IBD patients were included and compared to 53 healthy controls (Table 1). IBD patients medications included 6 5ASA (6.8%), 6 immunomodulator monotherapy (6.8%), 14 anti-TNF monotherapy (15.9%), 32 anti- TNF combination therapy with immunomodulator (36%), 16 IL12/23 (18%) and 13 vedolizumab (14%). Pre-vaccine baseline sera showed absence of anti-RBD antibodies in all participants. 84 patients (87%) received BNT162b2 and 4 (4.5%) received ChAdOx1 nCoV-19 vaccines. Geometric mean [SD] anti-S1/2 antibody concentrations at 4 weeks after second vaccination (V3) were significantly lower in IBD TNF treated patients (162.6[1.7]) compared to IBD non TNF treated patients (325.2[1.3]), and healthy controls (325.2[1.3]), p<0.0001 (Figure 1). There was no difference between non-TNF treated patients including those on vedolizumab or IL12/23 compared to controls. Similarly there was a significant difference between anti-RBD IgG titres between TNF and non-TNF IBD patients at V3 but not when compared to controls (Figure 2). There was no difference in RBD IgG and anti-S1/2 antibodies between anti-TNF monotherapy and combination anti-TNF with immunomodulator. All IBD and healthy controls seroconverted at V3 (Figure 3). Conclusion: TNF agents influence SARS-CoV-2 vaccine-induced antibody response in IBD patients, with lower anti-S1/2 IgG concentrations compared to non-TNF IBD patients and healthy controls. However, there was no difference in RBD IgG titres between controls and IBD patients overall. It is unclear whether these subtle differences in antibody response in IBD patients on TNF agents is biologically meaningful, as all groups seroconverted after second dose vaccination. Neutralising antibody and T cell data (CD4+/CD8+) from this study to come.