ABSTRACT
Purpose: Lung transplant recipients (LTRs) are less likely than other solid organ transplant recipients (SOTRs) to develop an antibody response to SARS-CoV-2 vaccination. Mycophenolate has been associated with impaired humoral response to SARS-CoV-2 vaccination, leaving these patients vulnerable to infection. Perivaccination antimetabolite hold has been an effective strategy for some patients with rheumatic and musculoskeletal diseases. In this study, we describe the safety and efficacy of a peri-vaccination antimetabolite hold in LTRs on SARS-CoV-2 anti-spike protein development following a third vaccine dose. Method(s): We studied LTRs on mycophenolate or azathioprine based antimetabolite therapy (AMT) >1-year post-LT with no history of acute cellular or humoral rejection who received SARS-CoV-2 vaccine Dose 3 (D3) May-October 2021. Patients were instructed to hold AMT 1 week before and 2 weeks after D3. Antibody titers were measured pre- and post-D3 (Roche Elecsys or DiaSorin Liaison anti-S EIA). Safety was evaluated using donor specific antibody (DSA) trend and lung biopsy results. Result(s): Of 40 participants, 30 held AMT and 10 did not hold AMT. Median (IQR) time since transplant was 3.9 years (1.9-7.3). Median (IQR) time between vaccine dose 2 and D3 was 163 days (143- 180). Among participants seronegative pre-D3, seroconversion post-D3 occurred in 52% (12/23) who held AMT vs. 57% (4/7) who did not hold AMT (p>0.9). Among patients with pre- and post-D3 DSA levels (N=19), increasing or de novo positive DSA was seen in 8.3% (1/12) of patients who held AMT vs. 0% of patients who did not hold AMT. For patients who underwent lung biopsy post-D3 (N=8), abnormal biopsy was seen in 0% (0/1) of patients holding AMT vs. 28.6% (2/7) not holding AMT. Conclusion(s): A three-week AMT hold by LTRs was not associated with increased rejection but also showed no significant difference in seroconversion compared to LTRs who did not hold AMT, suggesting this hold protocol is safe but not effective. Further investigation of alternative strategies is needed to protect LTRs from COVID-19 infection who do not mount effective immunoprotection following SARS COV-2 vaccination. (Table Presented).
ABSTRACT
Background: An attenuated humoral response to SARS-CoV-2 vaccination has been observed in some patients with rheumatic and musculoskeletal diseases (RMD) (1). We sought to identify clinical factors associated with poor humoral response following primary (two-dose mRNA or single adenoviral vector dose) SARS-COV-2 vaccination in patients with RMD on immunosuppression. Objectives: To identify clinical predictors of an attenuated antibody response to primary SARS-CoV-2 vaccination in RMD patients on immunosuppression. Methods: We included patients ≥18 years old with RMD on immunosuppres-sion who received either two-dose mRNA or single dose Janssen/Johnson and Johnson (J&J) vaccination. Demographics, diagnoses, and therapeutic regimens were collected via participant report;those with prior COVID-19 infection were excluded. One month after vaccination, participants underwent SARS-CoV-2 antibody testing on the semi-quantitative Roche Elecsys anti-SARS-CoV-2 S enzyme immunoassay, which measures antibody to the SARS-CoV-2 S-recep-tor binding domain (RBD) protein (ceiling >250U/mL later expanded to >2500U/mL). Associations were evaluated using Fisher's exact and Wilcoxon rank sum tests. Logistic regression analyses were performed to evaluate for clinical factors associated with antibody response. We adapted survival methods to address right-truncation of titers;this methodology was used to calculate medians. Participants provided informed consent electronically and the study was approved by the local Institutional Review Board. Results: We studied 1138 RMD participants on immunosuppression;most were female (93%) and white (91%) (Table 1). One-hundred and ffteen (10%) had anti-RBD response in the negative range at a median (IQR) of 29 days (28-34) following completion of vaccine series. A greater proportion of participants with negative response were non-white, received J&J vaccine, reported use of myco-phenolate, rituximab, or glucocorticoids. Antibody response differed by immuno-suppressive regimen, with those receiving rituximab having poorest response (Figure 1). Use of mycophenolate (aOR 9.92, p=0.001), rituximab (aOR 56.99, p=0.001), glucocorticoids (aOR 2.99, p=0.001) or receipt of J&J (aOR 3.13, p=0.039) were associated with negative antibody response. Conclusion: Use of mycophenolate, glucocorticoids, rituximab and receipt of J&J vaccine were the strongest predictors of an attenuated antibody response to primary SARS-CoV-2 vaccination;these data support use of an additional primary dose in RMD patients.