Bamlanivimab decreases severe outcomes of SARS-CoV-2 infection in ANCA vasculitis patients

Abstract

Patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are more likely to have poor outcomes if infected with SARS-CoV-2. 1 B-lymphocytes play a central role in the pathogenesis of AAV. 2 Thus, rituximab therapy targeting B-cells is a first-line agent for both induction and maintenance therapy, 3 however treatment with rituximab increases mortality risk in patients with rheumatic disease infected with SARS-CoV-2. 4 Additionally, rituximab use is associated with blunted humoral and cell mediated immune responses to SARS-CoV-2 vaccine. 5 Monoclonal antibody treatment, specifically Bamlanivimab, has shown promise in reducing hospitalization and mortality rates for patients infected with SARS-CoV-2. 6 We studied the outcome of SARS-CoV-2 infection in AAV patients during the pandemic and investigated the impact of Bamlanivimab on the risk of hospitalization and death After extracting demographic and clinical information from medical records, we performed descriptive statistics and bivariate comparisons using χ2 and Fischer’s exact tests for categorical variables and t-tests and Welch unequal variances tests for continuous variables. Analyses were conducted in SAS V.9.4 (SAS Institute). Of the 20 patients with a mean age of 61 years, 75% Caucasian and 60% MPO ANCA, 12 were hospitalized and 5 died of pneumonia or sepsis. Majority (75%) were treated with rituximab (Table 1 ). The median (IQR) time from last rituximab administration to SARS-CoV-2 diagnosis in 15 rituximab treated AAV patients was 18 (13 to 30) weeks. B cells were depleted in 13 patients who had CD19 data. Four patients had received both doses of the SARS-CoV-2 vaccination with Pfizer or Moderna prior to SARS-CoV-2 diagnosis. Of these 4 vaccinated patients, 3 did not mount a humoral response, the single patient with a humoral response had subsequently received treatment with rituximab for newly diagnosed AAV. The median (IQR) time between administration of the second dose of SARS-CoV-2 vaccination and SARS-CoV-2 diagnosis was 14 weeks (8.3–23 weeks). Table 1 Demographic, co-morbidities, immunosuppressive treatment versus SARS-CoV-2 outcomes. Variable All Patients Not Hospitalized Hospitalized Prob Survived Died Prob n 20 8 12 15 5 Age (years) 0.0138 0.3913 Mean (Std Dev) 61.3 (15.4) 50.9 (14.2) 68.3 (12.2) 59.6 (4.1) 66.4 (14.0) Gender, n (col %, row %) 1.000 0.3034 Female 10 (50.0) 4 (50.0, 40.0) 6 (50.0, 60.0) 6 (40.0, 60.0) 4 (80.0, 40.0) Male 10 (50.0) 4 (50.0, 40.0) 6 (50.0, 60.0) 9 (60.0, 90.0) 1 (20.0, 10.0) BMI 0.8596 0.4263 Mean (Std Dev) 35.2 (6.2) 34.8 (8.7) 35.4 (4.2) 35.7 (6.9) 33.7 (3.5) Comorbidities, n (col %, row %) Hypertension 0.2553 1.000 No 4 (20.0) 3 (37.5, 75.0) 1 (8.33, 25.0) 3 (20.0, 75.0) 1 (20.0, 25.0) Yes 16 (80.0) 5 (62.5, 31.25) 11 (91.7, 68.8) 12 (80.0, 75.0) 4 (80.0, 25.0) Diabetes 0.2421 0.5395 No 17 (85.0) 8 (100.0, 47.1) 9 (75.0, 52.9) 12 (80.0, 70.6) 5 (100.0, 29.4) Yes 3 (15.0) 0 (0.0, 0.0) 3 (25.0, 100.0) 3 (20.0, 100.0) 0 (0.0, 0.0) Heart Disease 0.6027 0.5598 No 15 (75.0) 7 (87.5, 46.7) 8 (66.7, 53.3) 12 (80.0, 80.0) 3 (60.0, 20.0) Yes 5 (25.0) 1 (12.5, 20.0) 4 (33.3, 80.0) 3 (20.0, 60.0) 2 (40.0, 40.0) CKD 0.8367 0.2088 No 7 (35.0) 2 (25.0, 28.6) 5 (41.7, 71.4) 6 (40.0, 85.7) 1 (20.0, 14.3) Stage 3 and 4 10 (50.0) 5 (62.5, 50.0) 5 (41.7, 50.0) 8 (53.3, 80.0) 2 (40.0, 20.0) Stage 5 3 (15.0) 1 (12.5, 33.3) 2 (16.7, 66.7) 1 (6.67, 33.3) 2 (40.0, 66.7) Immunosuppressant Regimen, n (col %, row %) 0.6444 0.3025 Rituximab 13 (65.0) 7 (87.5, 46.7) 8 (66.7, 53.3) 12 (80.0, 80.0) 3 (60.0, 20.0) Prednisone 3 (15.0) 1 (12.5, 33.3) 2 (16.7, 66.7) 2 (13.3, 66.7) 1 (20.0, 33.3) Cyclophosphamide 1 (5.0) 0 (0.0, 0.0) 1 (8.3, 100.0) 0 (0.0, 0.0) 1 (20.0, 100.0) Azathioprine 1 (5.0) 0 (0.0, 0.0) 1 (8.3, 100.0) 1 (6.7, 100.0) 0 (0.0, 0.0) SARS-CoV-2 Vaccination, n (col %, row %) 0.6945 0.097 No 7 (87.5, 43.8) 9 (75.0, 56.3) 13 (86.7, 81.3) 3 (60.0, 18.8) Yes 4 (20.0) 1 (12.5, 25.0) 3 (25.0, 75.0) 2 (13.2, 50.0) 2 (40.0, 50.0) Bamlanivimab, n (col %, row %) 0.0044 0.1137 No 13 (65.0) 2 (25.0, 15.4) 11 (91.7, 84.6) 8 (53.3, 61.5) 5 (100.0, 38.5) Yes 7 (35.0) 6 (75.0, 85.7) 1 (8.33, 14.3) 7 (46.7, 100.0) 0 (0.0, 0.0) The median (IQR) time from SARS-CoV-2 symptom onset to hospitalization was 3 days (2–4. days). The median (IQR) duration of hospitalization was 8 days (6.5–13.8 days). The median (IQR) time from SARS-CoV-2 symptom onset to death was 14 days (11–49 days). Eleven patients (55%) required supplemental oxygen and five (25%) required mechanical ventilation. Eleven patients received dexamethasone, 10 received remdesivir and 3 patients received plasma therapy. Seven patients including six on rituximab therapy received treatment with the monoclonal antibody Bamlanivimab and hospitalization showed a statistically significant decrease in this group; hospitalization was required for one patient (14.3%) of those who received Bamlanivimab vs eleven (84.6%) of those who did not (P=0.0044). No patient who received Bamlanivimab died of SARS-CoV-2; 38.5% of those who did not receive Bamlanivimab died. Older age is one factor known to increase the risk of severe outcomes in SARS-CoV-2. 5 T-test showed a statistically significant difference (P=0.0138) between the age of those hospitalized (mean 68.3 years) and those who were not (mean 50.9 years). We found no differences attributable to BMI, but other comorbidities demonstrated non-statistically significant differences. The small absolute number of patient fatalities meant that observable differences between SARS-CoV-2 survivors and non-survivors were minimal for many factors. Managing AAV patients on rituximab therapy has been challenging due to risk of severe SARS-CoV-2 infection and impaired immune response to the SARS-CoV-2 vaccine. Our data demonstrates that Bamlanivimab decreases risk of severe outcomes offering hope in this vulnerable cohort. Early use of monoclonal antibody therapy should be advocated in AAV patients on immunosuppressive therapy.