ABSTRACT
Purpose: Solid organ transplant recipients (SOTR) develop weak antibody responses after SARS-CoV-2 vaccination. Published data on neutralizing activity of plasma, a better measure of protection, in SOTR following an additional dose of SARSCoV- 2 vaccine is limited. Method(s): Plasma was longitudinally collected from SOTR following initial COVID- 19 vaccination. Neutralizing activity against SARS-CoV-2 was assessed using the cPass Neutralization Antibody Detection Kit (GenScript, Biotech). ELISAs were performed against SARS-CoV-2 proteins (S1, N, RBD), CMV (glycoprotein B), Influenza A H1N1 (nucleoprotein), HSV-1, EBV glycoprotein (gp350), and tetanus toxoid for comparison. Result(s): Demographic and clinical characteristics are summarized in table 1. No participants had evidence of COVID-19 infection as IgG titers to SARS-CoV-2 N protein were low. Neutralizing activity against SARS-CoV-2 RBD was observed in 39.6% of individuals (N=21/53) ~93 days after initial vaccination. Participants with neutralizing activity were more likely to have received a liver transplant (47.6% vs 6.25%, p=0.001), and less likely to be on an anti-metabolite (52.4% vs. 87.5%, p=0.009) or triple immunosuppression (14.3% vs. 53.1%, p=0.008). After an additional vaccine dose, 78.1% (N=25/32) of participants developed neutralizing activity with significant increases in viral neutralization (figure 1, median 36.8% [95%CI 18.9-64.6] to 97.2% [95%CI 74.0-98.9], p<0.0001). Participants with low neutralizing activity demonstrated adequate antibody titers to other microbial antigens (figure 2). Conclusion(s): An additional dose of SARS-CoV-2 vaccine increased the number of SOTR with neutralizing activity and the magnitude of the seroresponse. SOTR with low neutralizing activity maintain humoral responses to other microbial antigens suggesting the diminished seroresponse might be related to inhibition of new B cell responses.
ABSTRACT
Purpose: Describe outcomes of patients (pt) with pre-tx COVID-19. Method(s): Multicenter study of SOT/HCT candidates who had a positive (pos) SARS-CoV-2 PCR pre-tx. Result(s): Pre-tx: Of 208 pt, median age was 56 (range 3-76). 87.8% were SOT candidates (40.5% kidney, 40.5% liver, 9.8% lung, 6.9% heart, 2.3% pancreas) and 13.9% were HCT candidates (54.2% allo, 45.8% auto). Pt underwent a median of 2 tests (range 1 - 14). In 41% of pt, > 1 neg PCR was required by the tx center before reactivation. Neg PCR was documented in 67.4% of pt at a median of 41 days (18-68) after pos PCR. Waitlist mortality was 11.0%;deaths were due to COVID-19 in 60% (12/20). Post-tx (all pt): 78 pt underwent tx at a median of 65.5 days (range 17-324) from COVID-19;71/78 have completed 4-weeks of follow-up. 24/78 (30.7%) pt were still PCR pos at time of tx (details below). 54/78 (69.2%) pt underwent routine PCR testing post-tx;62% were tested regularly for 8 weeks. Only 1 pt, who remained asymptomatic, developed recurrent pos PCR on surveillance testing 18 days post-tx. 1 pt had graft loss. There were no deaths at 4 weeks post-tx. Pt transplanted without a negative PCR: 24 pt with COVID-19 did not have neg PCR at time of tx: 9 (37.5%) kidney, 9 (37.5%) liver, 2 (8.3%) SLK, 1 (4.2%) lung, 1 heart (4.2%), 2 auto-HSCT (8.3%), 2 allo-HSCT (8.3%). Of 24 pt who were reactivated at a median of 21 days (range 8 - 38) from COVID-19 diagnosis, 7 underwent tx emergently (5 liver, 1 lung, 1 heart). 20/24 completed 4-weeks of follow-up;all were alive. PCR Cycle thresholds (Ct) increased over time, suggesting a reduction in SARS-CoV-2 viral loads with time elapsed since COVID-19 diagnosis. Conclusion(s): Short-term outcomes of transplantation in SOT/HCT candidates with prior COVID-19 were promising in this small cohort, even with a positive PCR going into transplant. Whether documentation of a negative PCR should be required for all tx candidates with a history of COVID-19 prior to transplantation should be investigated further, particularly among lung tx candidates. For certain tx candidates with COVID-19, relying time-based strategy instead of a test-based strategy may be safe.