A 74 year old woman was diagnosed with generalized MG 44 months prior to initial SARS-CoV-2 vaccination. Serologic testing showed elevated antibodies to acetylcholine receptors. For 18 months prior to and including the vaccine time course, treatment with 1440 mg mycophenolate sodium and prednisone 11 mg daily resulted in clinically stability. There was a remote history of ductal carcinoma in situ and Hashimoto's thyroiditis, and no history of opportunistic infection. Peripheral blood monitoring showed 8700 leukocytes and 800 lymphocytes per microliter (9%), consistent with mild lymphopenia. Three months prior to initial vaccination, the patient began treatment with eculizumab, an anti-C5 monoclonal antibody with activity in MG. Eculizumab was given weekly and then biweekly per US labelling. The indication was adjunctive therapy to bridge elective surgery, which was uneventful. Eight weeks after surgery, BNT162b2 vaccination was started and two doses were administered 21 days apart. Eculizumab administration time points included 10 days prior to dose 1 of BNT162b2 and 3 days prior to dose 2, with the last dose given 11 days later.
Blood was initially tested 71 days after the second dose of BNT162b2. The SARS-CoV-2 RBD binding antibody level (Abbott Architect IgG II) was 19 arbitrary units (AU)/ml, with values below 50 considered negative (https://www.fda.gov/media/146371/download). QuantiFERON SARS-CoV-2 RUO (Qiagen), an S-peptide-based interferon-gamma release assay (IGRA) similar to the QFT-Plus assay for Mycobacterium tuberculosis-specific T cells, was performed per the manufacturer. SARS-CoV-2 S peptide pool S1 and S2 net values of 0.02 international units (IU)/ml and 0.03 IU/ml were summed to 0.05 IU/ml to provide a single metric. Negative (nil) and positive (mitogen) control values were 0.02 IU/ml and >10 IU/ml, indicating negligible background lymphocyte activation and intact activation potential. Amongst 14 healthy controls (HC) studied a median of 58 days (range, 10-107) after completing BNT162b2 (10 persons) or M1273 (4 persons), median net summary response to S was 1.27 IU/ml (range, 0.34 IU/ml-2.60 IU/ml). HC median nil was 0.03 IU/ml (range, 0.02 IU/ml-0.06 IU/ml) and each mitogen control was >10 IU/ml.
After tests for vaccine immunogenicity returned negative, the patient sought repeat vaccination. At 85 days after completing BNT162b2, they received M1273, with a second dose 29 days later. Side effects were minimal. Immune response were tested 16 days after the second dose of M1273. The serum anti-SARS-CoV-2 RBD IgG level was 2999 AU/ml, considered positive. IGRA re-test 32 days after completing M1273 showed a net summary response to S peptides of 0.38 IU/ml IFN-gamma, with nil and mitogen responses of 0.03 IU/ml and >10 IU/ml.