ABSTRACT
Purpose: Adverse events of a novel mRNA vaccine are not well described in Kidney Transplant Recipients(KTR), especially the risk of immune activation or recurrent glomerulonephritis(GN), which has been described in native GN after COVID-19 vaccines. Method(s): In this single-center prospective study, 147 KTR were enrolled after informed consent and administered 2 doses of Pfizer/BioNTech vaccine 21 days apart. Follow-up was 3 weeks after Dose2. Result(s): Mean age of KTR was 51 years;55.1% male;65.3% Chinese, 19% Malay, 11.6% Indian;69.5% Living donor, 29.9% Deceased donor, 0.7% Pancreas-kidney transplants;71.5% had biopsy-proven or presumptive chronic GN(CGN), 12.9% diabetic nephropathy, 15.6% other causes. 11(7.5%) KTR had delayed Dose2 administered at median 29 days(range 24-93) after Dose1. 7(4.8%)were delayed due to renal events: rise in creatinine(n=3), or proteinuria(n=2), or both creatinine and proteinuria with allograft biopsy showing acute T-cell and antibody-mediated rejection(n=1), new BK viraemia(n=1). Other reasons were possible anaphylaxis(n=1), intercurrent infection(n=2), and inability to attend due to quarantine(n=1). 27 KTR had new microhaematuria(MH) after Dose1;9 persisted after Dose2. Additional 18 had new MH after Dose2. Of 45 KTR with new MH, 7 had underlying IgAN, 5 had other biopsy-proven-CGN and 22 had presumed CGN, suggesting 34/45 with possible immune activation. 12 KTR had new onset proteinuria (rise in urine protein:creatinine ratio (UPCR) <=30 to >30mg/mmol);5/7 who developed a rise after Dose1 remained elevated;additional 5 had a rise after Dose2. 7 KTR had rise in proteinuria from UPCR <=100 to >100mg/mmol. Conclusion(s): Subclinical changes in allograft monitoring parameters are frequent after COVID-19 mRNA vaccines with up to 40.1% of KTRs showing rises in creatinine, proteinuria or new MH. Although overt recurrent GN and acute rejection are infrequent, high vigilance and monitoring for these occurrences should be undertaken in KTRs receiving mRNA vaccines.
ABSTRACT
Purpose: Kidney transplant recipients (KTRs) are at higher risk for severe COVID- 19 caused by the severe acute respiratory syndrome coronavirus-2 (SARS646 All Infections (Excluding Kidney & Viral Hepatitis) I CoV-2). Sotrovimab decreases the risk of disease progression in the general population, but efficacy and safety in KTRs is unknown. Herein, we describe our experience in treating COVID-19 infected KTRs with sotrovimab. Method(s): We performed a retrospective, single-center cohort study of KTRs diagnosed with COVID-19 by polymerase chain reaction from 07/15/21-11/30/21. KTRs with COVID-19 were admitted to the hospital to expedite evaluation and treatment. KTRs with COVID-19 were eligible for sotrovimab if they 1) were not requiring oxygen at admission, 2) were unvaccinated or if SARS-CoV-2 spike antibody (SAb) after vaccination was <100 U/mL, and 3) duration of symptoms/day of illness (DOI) was <=7 days. COVID-19 disease requiring oxygen therapy was treated with remdesevir + dexamethasone. Immunomodulator therapy (baricitinib or tocilizimab) was given for rapidly progressive disease requiring high-flow oxygen or ICU care. Baseline characteristics, treatments, and outcomes including oxygen supplementation, ICU admission, and mortality were manually ed and evaluated. Result(s): In all, 36 KTRs were diagnosed with COVID-19 - mean age 59 years, 72% male, 67% Chinese, 64% diabetic and 17% obese;72% were deceased donor and 28% were living donor KTRs presenting a mean 11 years from transplant. The majority (69%) were vaccinated with >=2 doses of mRNA-based SARS-CoV-2 vaccines, 22% received 3 doses, and 15% were unvaccinated. Among KTRs who received >=2 doses, SAb was reactive in 36% and >100 U/mL in 16%. In all, 14 (39%) required oxygen, 11 (31%) required ICU admission, 5 (14%) were mechanically ventilated, and 4 (11%) died (Table). Sotrovimab was given to 27 eligible KTRs at median DOI 2 (range 0-6). Of these, 8 (30%) required oxygen, 5 (19%) required ICU admission, 2 (7%) were mechanically ventilated, and 1 died (4%). KTRs receiving sotrovimab at DOI <=3 vs >3 were less likely to require oxygen (p=0.01) or ICU admission (p=0.02). Sotrovimab was well tolerated with one associated adverse event (self-limiting diarrhea). Conclusion(s): KTRs remain at high risk for severe COVID-19. Sotrovimab administered early in the disease course is associated with a lower rate of severe COVID-19. Outcomes of KTRs with COVID-19 overall and among those receiving sotrovimab by day of illness (Figure Presented).