ABSTRACT
Background: Kidney transplant recipients (KTR) are at higher risk for breakthrough COVID-19 infections and progression to severe disease. Herein, we compare the outcomes of KTR infected with the Delta and Omicron variants. Method(s): We performed a retrospective, single-centre study of all SARS-CoV-2-infected KTR confirmed by PCR from 17/09/21 to 30/04/22. At diagnosis, anti-metabolite doses were halved with further reductions of immunosuppression with increasing disease severity. Treatment for KTR not requiring supplemental oxygen (SuppO2) on admission was guided by SARS-CoV-2 spike antibody (SpAb), Roche Cobas SARSCoV-2-S assay. Sotrovimab 500mg IV was given if SpAb<100 U/mL. With community emergence of Omicron subvariant BA.2, sotrovimab was replaced by tixagevimab/ cilgavimab (EVUSHELDTM) 600mg IM in KTR with SpAb<250 U/mL or remdesivir if SpAb>250 U/mL. KTR with SuppO2 were treated with dexamethasone +/-remdesivir and immunomodulator therapy (baricitinib or tocilizumab). Characteristics and outcomes between KTR with Delta and Omicron were compared. Result(s): Clinical characteristics and outcomes are summarized in Table 1. Baseline demographics were similar between groups. Vaccination rates increased over time in concert with government vaccine programs and communications by our team. KTR with Omicron had higher vaccination rates, higher likelihood of SpAb>250 U/mL, and were less likely to have AKI, SuppO2, ICU stay, and mortality (p<0.05 for all). Of 16 KTR with Omicron with SuppO2, 5 were unvaccinated and only 1/16 had SpAb>250 u/mL. Conclusion(s): Severe disease was less frequent in KTR with Omicron likely due to improved vaccination rates, higher SpAb, and virus characteristics. However, KTR remain at risk for severe disease especially if unvaccinated or if SpAb is low.
ABSTRACT
Purpose: Administration of mRNA-based SARS-CoV-2 vaccines confers protection from SARS-CoV-2 infection and reduces its severity in the general population. It has been suggested that mounting a coordinated adaptive immune response characterized by production of neutralizing antibodies and SARS-CoV-2 spike proteinspecific T-cells correlates with protection from infection. Studies in organ transplant recipients have demonstrated suboptimal responses after 2 doses of SARS-CoV-2 vaccination;however, the impact of different immunosuppressive regimens (IS) on T-cell responses is not well described. This study prospectively evaluated the impact of IS on T-cell responses in a kidney transplant (KTx) population and compared these to 26 healthy controls. Method(s): In this single-centre, prospective study, 92 KTx on follow-up at our centre were enrolled after informed consent. T-cell responses were evaluated before and after each of 2 doses of BNT162b2 SARS-CoV-2 vaccine administered 21 days apart: before each dose, 10-14 days after Dose1 and 21-24 days after Dose2. The study population included 69.6% Live-Donor and 30.4% Deceased-Donor KTx. Longitudinal assessment of the quantity of spike-specific T-cells was performed by stimulating whole blood with peptides covering the SARS-CoV-2 spike protein, followed by cytokine (IFN-gamma, IL-2) measurement (JCI, Tan et al, 2021). KTx were stratified by maintenance IS into 4 groups and T-cell responses compared between groups. Result(s): As shown (Figures 1A, 1B), in comparison to healthy controls, KTx displayed poor spike-specific T-cell responses as measured by IFN-gamma and IL-2 release. Percent responders were significantly lower for KTx vs. healthy controls: 6.5% vs. 92.3% after Dose1 (P<0.00001) and 27.2% vs. 100% after Dose2 respectively. There was a significant impact of different IS regimens (Figure 1C);percent responders after Dose2 were 19%, 43%, 40% and 71% for KTx receiving CNI-MPA-Pred, CNI-Aza-Pred, mTORi and Other regimens respectively (P=0.013). Conclusion(s): Our results highlight the critical role of IS on T-cell responses to SARS-CoV-2 vaccination. In the context of the COVID-19 pandemic, monitoring T-cell and antibody responses over time after vaccination, modulating IS and modifying vaccination strategies are clearly needed to protect this vulnerable population.
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).
ABSTRACT
AIM: The COVID-19 pandemic poses unprecedented operational challenges to nephrology divisions in every country as they cope with COVID-19-related kidney disease in addition to regular patient care. Although general approaches have been proposed, there is a lack of practical guidance for nephrology division response in a hospital facing a surge of cases. Here, we describe the specific measures that our division has taken in the hope that our experience in Singapore may be helpful to others. METHODS: Descriptive narrative. RESULTS: A compilation of operational responses to the COVID-19 pandemic taken by a nephrology division at a Singapore university hospital. CONCLUSION: Nephrology operational readiness for COVID-19 requires a clinical mindset shift from usual standard of care to a crisis exigency model that targets best outcomes for available resources. Rapid multi-disciplinary efforts that evolve flexibly with the local dynamics of the outbreak are required.