Sex: F
Vaccine: COVID19
Symptoms: SARS-CoV-2 antibody test, SARS-CoV-2 antibody test negative
Clinical narrative: Despite delaying vaccination until 14 weeks after her last rituximab dose, the case patient did not produce a detectable antibody response; Despite delaying vaccination until 14 weeks after her last rituximab dose, the case patient did not produce a detectable antibody response; This is a literature report  We have demonstrated high IGRA (Interferon-gamma release assay) sensitivity in convalescent patients in the weeks following COVID-19, which remains sensitive up to 7 months post infection. The SARS-CoV-2 IGRA is offered as a laboratory-developed test at laboratories. This test uses a combination of four peptide pools, which includes the corresponding peptides to spike protein, to stimulate CD4+ and CD8+ T cells and assess IFN-y concentration by auto mated enzyme-linked immunosorbent assay (ELISA) with a cutoff value of 0.35 IU/ml. In addition to using the SARS-CoV-2 IGRA to assess for past infection, the SARS-CoV-2 IGRA can also be used to assess the cellular immune response post vaccination. We present the case of a 44-year-old female patient whose medical history was notable only for multiple sclerosis that was well controlled on rituximab administered at a dose of 500 mg every 6 months for the past 3 years, with no prior multiple sclerosis therapies. She had had no symptoms of respiratory infection between April 2020 and January 2021 and no known exposures to SARS-CoV-2. Rituximab (Rituxan) 500mg was last administered as an intravenous infusion 14 weeks (98 day) prior to her first dose of Pfizer/BNT vaccine, with two doses given 21 days apart. Lymphocyte subsets 18 weeks (126 day) prior to first vaccine and 19 days after the second vaccine dose demonstrated zero B cells. SARS-CoV-2-specific antibodies were not evaluated prior to vaccination. Eighteen days after the second vaccine dose, SARSCoV-2-specific IgG/IgM levels were undetectable, identified by Siemens and Diasorin spike protein assays. Nineteen days after second vaccine dose, the SARS-CoV-2 IGRA was strongly positive: antigen minus nil = 8.39 IU/ml, with reference range (less than 0.35IU/ml). The nitogen nil results was 9.98 IU/ml. It is expected that patients receiving B cell depleting agents such as rituximab will have an impaired antibody response to COVID-19 vaccine, as in this case. Despite delaying vaccination until 14 weeks after her last rituximab dose, the case patient did not produce a detectable antibody response. More notably, this patient readily produced an antigen-specific T cell response detectable 19 days after completed vaccination despite having no B cells. The SARS-CoV-2 IGRA provided evidence that this patient mounted a robust cellular immune response after vaccination, similar to findings by others. Currently, although humoral and cellular immune responses may together reduce disease severity, we do not yet know whether a vaccine-generated T cell response in the absence of antibody production provides protection against COVID-19. Although current guidance recommends temporarily pausing rituximab and other immunosuppression pending COVID-19 vaccination, it is not known whether this practice improves the immunological response. This is an important factor to discuss with patients if delaying therapy could incur risks of disease reactivation and need for corticosteroids, which impair both humoral and cellular immunity. In weighing the risks and benefits of reducing or delaying disease-modifying agents, the benefits are not yet de fined. There are several limitations in interpreting this case. Without pre-vaccination testing, we cannot rule out that the patient had had a prior undetected SARS-CoV-2 infection producing the positive IGRA. This specific IGRA showed a 10% background positive rate in healthy individuals, reflecting either false-positive results, asymptomatic SARS-CoV-2 exposure, or cross-reactivity with seasonal coronaviruses. The findings of positive SARS-CoV-2 IGRA post-vaccination with negative antibodies in this patient on rituximab with zero B cells, suggests that the IGRA should be studied as a possible correlate of protection after COVID-19 mRNA vaccines in patients on immunosuppressive medications.; Sender's Comments: Based on the known safety profile of the vaccine BNT162B2, a temporal relation between the events (Drug interaction,SARS-CoV-2 antibody test negative) and the administration of the vaccine cannot be excluded. The impact of this report on the benefit/risk profile of the Pfizer product 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.