ABSTRACT
Background: Due to waning humoral immunity, a third COVID-19 vaccine dose is recommended but there is a lack of evidence regarding whether there is benefit to homologous versus heterologous mRNA vaccination. Method(s): This was a multi-centre parallel group randomized controlled trial in Toronto, Ontario from September 30, 2021 to May 13, 2022 which enrolled participants with stage 3B-5 chronic kidney disease with prior homologous mRNA two dose vaccination. Overall 273 participants were randomized 1:1 to either 30mug BNT162b2 (n=137) or 100 mug mRNA-1273 (n=136) third dose stratified by initial vaccine type. Neutralizing antibodies against the B.1.1.529 (Omicron) variant of concern as well as binding SARS-CoV-2 IgG antibodies to the spike protein, receptor binding domain, and nucleocapsid protein were measured. Result(s): Participants had a median age of 67 years, 94% were on dialysis, 3% had prior COVID-19, and 59% had received BNT162b2 for initial two dose vaccination. Prior to the third vaccine dose, detectable Omicron neutralizing antibodies were present in 2% with BNT162b2 and 54% with mRNA-1273 two dose vaccination. At 1 month post third dose, among those with baseline BNT162b2, Omicron-specific neutralizing antibodies were detectable in 84% with third dose BNT162b2 in comparison to 83% with third dose mRNA-1273 (p=0.70). In those with baseline mRNA-1273, 100% receiving third dose mRNA-1273 had Omicron-specific neutralizing antibodies in comparison to 96% with third dose BNT162b2 (p=0.75). During the study period, 9.3% of participants (n=25) contracted COVID-19 and two died from COVID-19 with no difference in infection based on vaccine type (p=0.26). Conclusion(s): In this randomized controlled trial of third dose COVID-19 vaccination, both homologous and heterologous vaccination elicited robust SARS-CoV-2 neutralizing antibody response. (Figure Presented).
ABSTRACT
Background: Kidney transplant recipients (KTR) have a diminished response to SARS-CoV-2 vaccination in comparison to immunocompetent individuals. Deeper understanding of the antibody response in KTRs following third-dose vaccination would enable identification of those who remain unprotected against Omicron and require additional treatment strategies. Method(s): We profiled antibody responses in KTRs pre-and at one and three months post-third-dose SARS-CoV2 mRNA-based vaccine. Anti-spike and anti-RBD IgG levels were determined by ELISA. Neutralization against wild-type, Beta, Delta and Omicron (BA.1) variants was determined using a SARS-CoV-2 spike pseudotyped lentivirus assay. Result(s): 44 KTRs were analysed at 1 and 3 months (n=26) post-third-dose. At one month, the proportion of participants with a robust antibody response had increased significantly from baseline, but Omicron-specific neutralizing antibodies were detected in just 45% of KTRs. Median anti-spike and anti-RBD antibody levels declined at 3 months, but the proportion of KTRs with a robust antibody response was unchanged. 38.5% KTRs maintained Omicron-specific neutralization at 3 months. No clinical variables were significantly associated with detectable Omicron neutralizing antibodies, but anti-RBD titres appeared to identify those with Omicron-specific neutralizing capacity. Conclusion(s): Over 50% of KTRs lack an Omicron-specific neutralization response 1 month following a third mRNA-vaccine dose. Among responders, binding and neutralizing antibody responses were well preserved at 3 months. Anti-RBD antibody titres may be a useful identifier of patients with detectable Omicron neutralizing antibody response.
ABSTRACT
Background: Recent research suggests that COVID-19 infection is associated with acute kidney injury (AKI). Together the inflammation caused by the virus in the kidneys and the episodes of AKIs are risk factors for progression of kidney diseases. We investigated the risk of progression to kidney failure among chronic kidney disease (CKD) patients from BC, Canada who were infected with COVID-19. Method(s): In this retrospective cohort study, we analyzed a cohort of 22,188 nondialysis CKD patients aged >=18 years, with no prior history of ESKD and COVID-19 infection before the cohort entry date between January 27, 2020 & December 15, 2021. The cohort was derived from Patient Records and Outcome Management Information System (PROMIS), a population based integrated registry database for CKD patients under the nephrologist care in BC. Incident COVID-19 cases were iteratively matched without replacement to non-COVID-19 controls (1:3 ratio) based on age, sex, region of residency, diabetes status, eGFR and urine ACR, CKD vintage and COVID-19 vaccination status as of COVID-19 diagnosis date. The primary outcome was a composite of initiation of maintenance dialysis defined by dialysis performed for >=4 weeks, a sustained decline in eGFR defined by >=40% decline from baseline that sustained over >=4 weeks or incident kidney transplantation. Estimated HR and 95% CI using Fine and Gray subdistribution hazard model to account for death as a competing risk. Result(s): The analytic data included 1,708 patients, 475 (28%) COVID-19 cases and 1,233 (72%) non-COVID-19 controls. Median age was 71 years, 53% was male. Median follow-up was 8.3 months, 70 (4.10%) patients progressed to kidney failure. Among the non-dialysis CKD patients, the risk of developing kidney failure in COVID-19 infected cases was 24% higher compared to matched, non-COVID-19 infected controls. The HR (95% CI) was 1.24 (0.75, 2.06) (p-value: 0.39). Conclusion(s): COVID-19 infection in non-dialysis CKD patients appeared to be associated with higher risk of progression to kidney failure. Although not statistically significant, the substantial increase in risk estimate warrants close monitoring of kidney function among CKD patients after COVID-19 infection.
ABSTRACT
Background: Hemodialysis (HD) patients have high mortality from COVID-19 and immunity following vaccination remains uncertain. This study evaluated SARS-CoV-2 antibody response in HD patients following BNT162b2 COVID-19 vaccination compared to health care workers (HCW) and convalescent serum. Methods: This single centre observational cohort study enrolled 142 HD patients and 35 HCW receiving the BNT162b2 vaccine. SARS-CoV-2 IgG antibodies to the spike protein (anti-spike), receptor binding domain (anti-RBD), and nucleocapsid protein (anti-NP) were measured in 66 HD patients receiving one vaccine dose, 76 HD patients receiving two vaccine doses, and 35 HCW receiving two vaccine doses. Results: In HD patients receiving a single BNT162b2 dose, seroconversion occurred in 53/66 (80%) for anti-spike and 35/66 (55%) for anti-RBD by 28 days post dose, but only 15/66 (23%) and 4/66 (6%), respectively attained a robust response defined as reaching the median level of anti-spike and anti-RBD in convalescent serum. In patients receiving two doses of BNT162b2 vaccine, seroconversion occurred in 69/72 (96%) for anti-spike and 63/72 (88%) for anti-RBD by 2 weeks following the second dose while 52/72 (72%) and 43/72 (60%) reached median convalescent serum levels of anti-spike and anti-RBD. In HCW, 35/35 (100%) exceeded median levels of anti-spike and anti-RBD in convalescent serum 2-4 weeks post second dose. Conclusions: This study found poor immunogenicity 28 days following a single dose of BNT162b2 vaccine in HD patients, supporting adherence to recommended vaccination schedules, and avoiding delay of the second dose in this population.