Project description:Multiple myeloma (MM) patients are at higher risk for severe COVID-19. Their mRNA vaccination response against SARS-CoV-2 is unknown. Thus, we analyzed responses to mRNA vaccination against COVID-19 among these patients. Using an ELISA-based assay that detects IgG antibodies to SARS-CoV-2 spike protein, we determined serum antibody levels prior to immunization and 12-21 and 14-21 days following the first and second vaccinations, respectively, with mRNA-1273 (Moderna) or BNT162b2 (Pfizer/BioNTech) among 103 MM patients (96 and 7 with active and smoldering disease, respectively). We stratified patients into clinically relevant responders (>250 IU/mL), partial responders (50-250 IU/mL, which was above pre-COVID-19 background), and nonresponders (<50 IU/mL). Smoldering MM patients responded better than those with active disease. Only 45% of active MM patients developed an adequate response, while 22% had a partial response. Lower spike antibody levels were associated with older age, impaired renal function, low lymphocyte counts, reduced uninvolved immunoglobulin levels, > second line of treatment, and among those not in complete remission. Patients who received mRNA-1273 vaccine had higher anti-spike antibody levels than those who were vaccinated with BNT162b2. Thus, most MM patients have impaired responses to mRNA vaccination against COVID-19, and specific clinical and myeloma-related characteristics predict vaccine responsiveness.
Project description:Background & aimPatients with inflammatory bowel diseases (IBD), specifically those treated with anti-tumor necrosis factor (TNF)α biologics, are at high risk for vaccine-preventable infections. Their ability to mount adequate vaccine responses is unclear. The aim of the study was to assess serologic responses to messenger RNA-Coronavirus Disease 2019 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared with healthy controls (HCs).MethodsProspective, controlled, multicenter Israeli study. Subjects enrolled received 2 BNT162b2 (Pfizer/BioNTech) doses. Anti-spike antibody levels and functional activity, anti-TNFα levels and adverse events (AEs) were detected longitudinally.ResultsOverall, 258 subjects: 185 IBD (67 treated with anti-TNFα, 118 non-anti-TNFα), and 73 HCs. After the first vaccine dose, all HCs were seropositive, whereas ∼7% of patients with IBD, regardless of treatment, remained seronegative. After the second dose, all subjects were seropositive, however anti-spike levels were significantly lower in anti-TNFα treated compared with non-anti-TNFα treated patients, and HCs (both P < .001). Neutralizing and inhibitory functions were both lower in anti-TNFα treated compared with non-anti-TNFα treated patients, and HCs (P < .03; P < .0001, respectively). Anti-TNFα drug levels and vaccine responses did not affect anti-spike levels. Infection rate (∼2%) and AEs were comparable in all groups. IBD activity was unaffected by BNT162b2.ConclusionsIn this prospective study in patients with IBD stratified according to treatment, all patients mounted serologic response to 2 doses of BNT162b2; however, its magnitude was significantly lower in patients treated with anti-TNFα, regardless of administration timing and drug levels. Vaccine was safe. As vaccine serologic response longevity in this group may be limited, vaccine booster dose should be considered.
Project description:Vaccination guidelines for patients treated for hematological diseases are typically conservative. Given their high risk for severe COVID-19, it is important to identify those patients that benefit from vaccination. We prospectively quantified serum immunoglobulin G (IgG) antibodies to spike subunit 1 (S1) antigens during and after 2-dose mRNA-1273 (Spikevax/Moderna) vaccination in hematology patients. Obtaining S1 IgG ≥ 300 binding antibody units (BAUs)/mL was considered adequate as it represents the lower level of S1 IgG concentration obtained in healthy individuals, and it correlates with potent virus neutralization. Selected patients (n = 723) were severely immunocompromised owing to their disease or treatment thereof. Nevertheless, >50% of patients obtained S1 IgG ≥ 300 BAUs/mL after 2-dose mRNA-1273. All patients with sickle cell disease or chronic myeloid leukemia obtained adequate antibody concentrations. Around 70% of patients with chronic graft-versus-host disease (cGVHD), multiple myeloma, or untreated chronic lymphocytic leukemia (CLL) obtained S1 IgG ≥ 300 BAUs/mL. Ruxolitinib or hypomethylating therapy but not high-dose chemotherapy blunted responses in myeloid malignancies. Responses in patients with lymphoma, patients with CLL on ibrutinib, and chimeric antigen receptor T-cell recipients were low. The minimal time interval after autologous hematopoietic cell transplantation (HCT) to reach adequate concentrations was <2 months for multiple myeloma, 8 months for lymphoma, and 4 to 6 months after allogeneic HCT. Serum IgG4, absolute B- and natural killer-cell number, and number of immunosuppressants predicted S1 IgG ≥ 300 BAUs/mL. Hematology patients on chemotherapy, shortly after HCT, or with cGVHD should not be precluded from vaccination. This trial was registered at Netherlands Trial Register as #NL9553.
Project description:RNA was extracted from whole blood of subjects collected in Tempus tubes prior to COVID-19 mRNA booster vaccination. D01 and D21 correspond to samples collected at pre-dose 1 and pre-dose 2 respectively. RNA was also extracted from blood collected at indicated time points post-vaccination. DB1, DB2, DB4 and DB7 correspond to booster day 1 (pre-booster), booster day 2, booster day 4 and booster day 7 respectively. The case subject experienced cardiac complication following mRNA booster vaccination. We performed gene expression analysis of case versus controls over time.
Project description:Abstract Messenger RNA vaccines are the main COVID-19 vaccines authorized for use in the United States. Side effects are typically minor and transient. We report a case series of four subjects with an acute myocarditis-like illness following mRNA COVID-19 vaccination who were hospitalized at our hospital in Lubbock, Texas. Three patients were young men who presented with acute chest pain after the second dose of the mRNA-1273 vaccine. Another patient was a 53-year-old white woman who presented with acute left arm pain 3 days after the first dose of the mRNA-1273 vaccine. She was later found to have acute decompensated heart failure, and endomyocardial biopsy revealed eosinophilic injury–mediated myocarditis.
Project description:BackgroundClinical trials of the BNT162b2 vaccine, revealed efficacy and safety. We report six cases of myocarditis, which occurred shortly after BNT162b2 vaccination.MethodsPatients were identified upon presentation to the emergency department with symptoms of chest pain/discomfort. In all study patients, we excluded past and current COVID-19. Routine clinical and laboratory investigations for common etiologies of myocarditis were performed. Laboratory tests also included troponin and C-reactive protein levels. The diagnosis of myocarditis was established after cardiac MRI.FindingsFive patients presented after the second and one after the first dose of the vaccine. All patients were males with a median age of 23 years. Myocarditis was diagnosed in all patients, there was no evidence of COVID-19 infection. Laboratory assays excluded concomitant infection; autoimmune disorder was considered unlikely. All patients responded to the BNT162b2 vaccine. The clinical course was mild in all six patients.InterpretationOur report of myocarditis after BNT162b2 vaccination may be possibly considered as an adverse reaction following immunization. We believe our information should be interpreted with caution and further surveillance is warranted.
Project description:BackgroundPeople living with chronic kidney disease (CKD) have been disproportionately affected by the coronavirus disease 2019 (COVID-19) pandemic, including higher rates of infection, hospitalization, and death. Data on responsiveness to COVID-19 vaccination strategies and immunogenicity are limited, yet required to inform vaccination strategies in this at-risk population.ObjectiveThe objective of this study is to characterize the longitudinal serologic response to COVID-19 vaccination.DesignThis is a prospective observational cohort study.SettingParticipating outpatient kidney programs within Ontario and British Columbia.PatientsUp to 2500 participants with CKD G3b-5D receiving COVID-19 vaccination, including participants receiving dialysis and kidney transplant recipients (CKD G1T-5T).MeasurementsThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibodies (anti-spike, anti-receptor binding domain, anti-nucleocapsid) will be detected by ELISA (enzyme-linked immunosorbent assay) from serum or dried blood spot testing. In a subset of participants, neutralizing antibodies against novel variants of concern will be evaluated. Peripheral blood mononuclear cells will be collected for exploratory immune profiling of SARS-CoV-2 specific cellular immunity.MethodsParticipants will be recruited prior to or following any COVID-19 vaccine dose and have blood sampled for serological testing at multiple timepoints: 1, 3, 6, 9, and 12 months post vaccination. When possible, samples will be collected prior to a dose or booster. Participants will remain in the study for at least 1 year following their last COVID-19 vaccine dose.Strengths and limitationsThe adaptive design of this study allows for planned modification based on emerging evidence or rapid changes in public health policy surrounding vaccination. Limitations include incomplete earlier timepoints for blood collection due to rapid vaccination of the population.ConclusionsThis large multicenter serologic study of participants living with kidney disease will generate data on the kinetics of SARS-CoV-2 immune response to vaccination across the spectrum of CKD, providing insights into the amplitude and duration of immunity conferred by COVID-19 vaccination and allowing for characterization of factors associated with immune response. The results of this study may be used to inform immunization guidelines and public health recommendations for the 4 million Canadians living with CKD.
Project description:BackgroundTrials of the Pfizer-BioNTech BNT162b2 mRNA vaccine showed 95% efficacy in preventing symptomatic disease; however, the trials excluded immunocompromised patients (ICPs). We aim at analyzing antibody response in ICPs.MethodsA prospective cohort study was conducted at Sheba Medical Center, Israel, between January and April 2020, in 1274 participants who received the vaccine, including 1002 ICPs and 272 immunocompetent healthcare workers (HCWs). Antibodies were measured two-four weeks after vaccination by SARS-CoV-2 anti-receptor binding domain IgG antibodies (RBD IgG) and pseudo-virus neutralization assays. Multivariable logistic regression analyses were used to identify factors associated with vaccine-induced antibody response. Adverse events (AEs) were monitored.FindingsRBD-IgG antibodies were detected in 154/156 (98.7%) of patients with HIV, 75/90 (83.3%) with solid malignancies, 149/187 (79.7%) with myeloma, 83/111 (74.8%) following hematopoietic stem cell transplants, 25/36 (69.4%) following liver transplantation, 26/43 (60.5%) with myelodysplastic syndrome, 96/188 (51.0%) with chronic lymphocytic leukemia/non-Hodgkin's lymphoma, 50/110 (45.5%) following kidney transplantation, 15/80 (18.8%) following heart transplantation, and 269/272 (98.9%) in controls. There was a significant correlation r = 0.74 (95%CI 0.69,0.78) between RBD-binding IgG and neutralizing antibodies in all groups. Multivariate logistic regression analysis showed that age > 65 years (OR 0.41,95%CI 0.30,0.57) and underlying immunosuppression (OR 0.02,95%CI 0.01,0.07) were significantly associated with a non-reactive response of IgG antibodies. HIV patients showed a similar immunological response as healthy adults. The vaccine was safe without any episodes of rejection, graft-versus-host disease (GVHD) or allergy. Immunocompetent HCWs experienced significantly more AEs than ICPs.InterpretationAntibody response to the Pfizer-BioNTech vaccine was highly variable among different ICPs; thus, individual recommendations should be provided for the different immunosuppression states.