Sex: M
Vaccine: COVID19, UNK
Symptoms: Off label use, Protein urine
Clinical narrative: B-cells measured at the time of the booster dose showed B-cell depletion; Vaccine types: JNJ and then Pfizer-BioNtech series; Vaccine types: JNJ and then Pfizer-BioNtech series; This is a literature report. This author reported similar events for seven patients. This is second of seven reports.  Three patients with AAV received booster doses of the COVID-19 vaccine. The age range was 67-80 years, with 2 being female and all (Race name) ethnicities. Two patients each had microscopic polyangiitis phenotype and received rituximab as induction therapy, whereas all patents were on rituximab maintenance. Only 1 patient was on steroid maintenance therapy (prednisone, 2.5 mg once a day). The duration that elapsed between the last dose of rituximab and the first dose of vaccine ranged between 3 and 5 months. Two patients with B cells measured at the time of the booster dose showed B-cell depletion, and in the third patient, B-cell measurement 8 weeks before the vaccine administration demonstrated B-cell depletion. Among 2 patients who received the Johnson & Johnson vaccine first devoid of any resultant antibody response, the booster dose was associated with humoral response in 1 patient, whereas the other patient did not mount an antibody response. The third patient initially received 2 doses of the Pfizer-BioNTech vaccine and received a third dose of Johnson & Johnson vaccine and did not mount a humoral response. None of the patients had previous COVID-19 infection or required dialysis during periods of vaccination. Patient characteristics, immunosuppressive regimen, immunologic data, and vaccine administration de tails are presented. In the series, the booster dose resulted in a humoral response in 1 of 3 patients. Patients with AAV receiving rituximab have been shown to have a suboptimal response to the vaccine, with duration elapsed between rituximab and vaccine administration having a significant bearing on eventually developing antibodies. It has been previously suggested that a delay in vaccine administration for at least 6 months after rituximab administration or B-cell reconstitution should be considered to maximize efficacy of vaccines. Another pertinent aspect that warrants discussion is the immunogenicity of viral vector-based COVID-19 vaccines. In accordance with the series, the antibody response after viral vector COVID-19 vaccines may be suboptimal for immunocompromised patients, as has been demonstrated in a previous study. This finding does require more robust investigation to clarify which type of COVID-19 vaccine yields the most efficacious immune response. Although the focus of the medical community is to enhance the immunogenicity of the vaccines to aid in the protection of this vulnerable population, the effect of immunosuppression on patients with established generation of SARS-CoV-2 antibodies is unknown. In addition, rituximab has been known to be associated with reduced humoral response to pneumococcal and influenza vaccines. To the knowledge, this is the first elucidation of the effect of rituximab on SARS-CoV-2 antibodies in vaccinated patients with AAV, demonstrating a precipitous decline in antibodies 1 month after administration of the drug. This finding, albeit preliminary and in a small subset of patients, may be of significance to a large number of patients with auto-immune disease, given rituximab is one of the most widely prescribed disease-modifying therapies. Because neutralizing antibody titers against SARS-CoV-2 correlate with reduced risk of break-through infections, it may be important to continue personal protective measures in the immediate period after rituximab administration, despite previous evidence of robust antibody response to vaccines, given the demonstrated decline in antibody titer. To the knowledge, these data are the first demonstration of antibody development after a booster dose of the COVID-19 vaccine in patients with AAV on rituximab maintenance therapy. It is of paramount importance that larger studies be convened to investigate the effects of the administration of a booster dose of the vaccine to this vulnerable population. This intervention may have far-reaching effects in alleviating morbidity and mortality arising from COVID-19, the biggest public health crisis of the generation. In addition, future studies assessing immunogenicity of vaccines in patients who are immunocompromised should consider incorporating this aspect of decline of antibody titers and measure T-cell and memory B-cell responses, because generation of antibodies may not be the only paradigm that determines durable success of the vaccine in this population.  The Patient characteristics, immunosuppressive regimen, immunologic data, and details of vaccine administration.  Patient no. 1; Age: 67 years; Gender: Male; Ethnicity: (Race name); Disease phenotype: GPA (granulomatosis with polyangiitis); ANCA type (anti-neutrophil cytoplasmic antibody) and titer at the time of booster, U.ml: PR3 (30.8); Estimated GFR (glomerular filtration rate); at the time of booster, ml/min per 1.73 m2 : 68; Proteinuria at the time of booster. mg: 91; Induction IS: RTX+STEROIDS; maintenance is : RTX; Cumulative RTX (rituximab) dose, g: 8.2; Interval between last RTX and first vaccine dose, mo : 4; CD19 count, cells/ml (%): Less than 20(0); Time point of CD19 measurement: 2 wk before second vaccine dose; Vaccine types: JNJ and then Pfizer-BioNtech series; SARS-CoV-2 spike protein gG titer (immunoassay) AU: greater than 12.   Pfizer is a marketing authorization holder of rituximab in the country of incidence. This may be a duplicate report if another marketing authorization holder of rituximab has submitted the same report to the regulatory authorities.; Sender's Comments: Based on the information provided, known drug safety profile and plausible temporal association, the causality between the suspect drugs and the serious event cannot be excluded. The impact of this report on the benefit-risk profile of the Pfizer product and on the conduct of the study is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to regulatory authorities, ethics committees. and investigators, as appropriate.,Linked Report(s) : US-PFIZER INC-202101324284 Same drug/event and different patient