EXPERIENCE IN THE USE OF NEUTRALIZING MONOCLONAL ANTIBODIES IN KIDNEY TRANSPLANT RECIPIENTS WITH COVID-19.

Therapy with neutralizing monoclonal antibodies (mAbs) is particularly relevant during COVID-19 outbreaks in patients at high risk of severe disease, including kidney transplant recipients (KTRs). Objective(s): to evaluate the efficacy and safety of neutralizing mAbs in KTRs with mild to moderate COVID-19. Materials and methods. The retrospective study included 99 KTRs who received inpatient treatment for COVID-19 between September 1 and December 31, 2021. Patients were 52.0 +/- 11.5 years old (M, 47.5%). Bamlanivimab/etesevimab combination drug at a dose of 700/1400 mg was used as mAbs. To evaluate the efficacy of mAbs therapy, two groups of patients were identified. Group 1 consisted of 33 KTRs who received mAbs as one of the therapy components, while group 2 consisted of 66 patients who received no mAbs. Discharge from the hospital or death was considered as the endpoint of follow-up. Results. In group 1, after the use of mAb, progression of pulmonary process was observed less frequently than in the control group with CT1-2 transformation to CT3-4 (9.1% vs. 30.3%, respectively, p < 0.01). Group 1 KTRs differed significantly from group 2 - lower need for ICU and ventilator care (6.1% vs. 27.3% and 3% vs. 19.8%, respectively). The groups were comparable by sex, age, body mass index, Charlson Comorbidity Index (CCI) and time after kidney transplant (KTx) at the onset of the disease and by aseline blood biochemistry parameter values at the time of hospitalization. Only C-reactive protein (CRP) and fibrinogen values were higher in the non-mAbs patients who were hospitalized later in the course of the disease (7.7 +/- 3.2 days versus 4.6 +/- 1.6 days in group 1, p < 0.001). The frequency of prescription of other therapies did not differ between the compared groups. Use of mAbs significantly reduced mortality from 19.7% in KTRs in group 2 to 3% in group 1 without adverse effect on graft function. Conclusion. The use of mAbs therapy in the early stages of COVID-19 in KTRs is safe, it prevents severe COVID-19, and reduces the incidence of adverse outcomes.Copyright © 2023 Russian Transplant Society. All rights reserved.

The role of interleukin-21 in COVID-19 vaccine-induced B cell-mediated immune responses in patients with kidney disease and kidney transplant recipients.

T-cell-mediated help to B cells is required for the development of humoral responses, in which the cytokine interleukin (IL)-21 is key. Here, we studied the mRNA-1273 vaccine-induced SARS-CoV-2-specific memory T-cell IL-21 response, memory B cell response, and immunoglobulin (Ig)G antibody levels in peripheral blood at 28 days after the second vaccination by ELISpot and the fluorescent bead-based multiplex immunoassay, respectively. We included 40 patients with chronic kidney disease (CKD), 34 patients on dialysis, 63 kidney transplant recipients (KTR), and 47 controls. We found that KTR, but not patients with CKD and those receiving dialysis, showed a significantly lower number of SARS-CoV-2-specific IL-21 producing T cells than controls (P < .001). KTR and patients with CKD showed lower numbers of SARS-CoV-2-specific IgG-producing memory B cells when compared with controls (P < .001 and P = .01, respectively). The T-cell IL-21 response was positively associated with the SARS-CoV-2-specific B cell response and the SARS-CoV-2 spike S1-specific IgG antibody levels (both Pearson r = 0.5; P < .001). In addition, SARS-CoV-2-specific B cell responses were shown to be IL-21 dependent. Taken together, we show that IL-21 signaling is important in eliciting robust B cell-mediated immune responses in patients with kidney disease and KTR.

Humoral vaccine response and breakthrough infections in kidney transplant recipients during the COVID-19 pandemic: a nationwide cohort study.

Background: Kidney transplant recipients (KTRs) experienced reduced SARS-CoV-2 vaccine response and were at increased risk of severe COVID-19. It is unknown if level of vaccine induced anti-receptor binding domain IgG (anti-RBD IgG) correlates with protection from and survival following COVID-19. We aimed to evaluate the effect of vaccine response on risk of breakthrough infections (BTI) and COVID-19 death in KTRs. Methods: We performed a nationwide study, examining the competing risk of SARS-CoV-2 infection, COVID-19 related/unrelated death, and vaccine efficacy as assessed by level of anti-RBD IgG response 4-10 weeks after each vaccination. The study included all KTR in Norway alive and with a functioning graft on February 20th, 2020, and events after November 11th, 2022 were right-censored. A pre-pandemic reference-cohort from January 1st 2019 to January 1st 2020 was included to evaluate excess mortality. The study was conducted at Oslo University Hospital, Rikshospitalet, Norway. Findings: The study included 3607 KTRs (59 [48-70] years) with a functioning graft at February 20th, 2020, who received (median [IQR]) 4 [3-4] vaccines (range 2-6, 99% mRNA). Anti-RBD IgG was measured in 12 701 serum samples provided by 3213 KTRs. Vaccine response was assessed 41 [31-57] days after vaccination. A total of 1090 KTRs were infected with SARS-CoV-2, 1005 (92%) were BTI, and vaccine response did not protect against BTI. The hazard ratio for COVID-19 related death 40 days post-infection was 1.71 (95% CI: 1.14, 2.56) comparing vaccine response levels (≥5 vs. ≥5000 BAU/mL). No excess non-COVID-19 mortality was registered in KTRs surviving SARS-CoV-2 infection compared to a 2019 pre-pandemic reference. Interpretation: Our findings suggested that SARS-CoV-2 mRNA vaccine response did not predict protection against infection, but prevention of fatal disease progression in KTRs and greater vaccine response further reduced the risk of COVID-19 death. No excess non-COVID-19 mortality was seen during the pandemic. Funding: CEPI and internal funds.

Experience in the use of neutralizing monoclonal antibo dies in kidney transp lant recipients withC OVID -19

Therapy with neutralizing monoclonal antibodies (mAbs) is particularly relevant during COVID-19 outbreaks in patients at high risk of severe disease, including kidney transplant recipients (KTRs). Objective: to evaluate the efficacy and safety of neutralizing mAbs in KTRs with mild to moderate COVID-19. Materials and methods. The retrospective study included 99 KTRs who received inpatient treatment for COVID-19 between September 1 and December 31, 2021. Patients were 52.0 +/- 11.5 years old (M, 47.5%). Bamlanivimab/etesevimab combination drug at a dose of 700/1400 mg was used as mAbs. To evaluate the efficacy of mAbs therapy, two groups of patients were identified. Group 1 consisted of 33 KTRs who received mAbs as one of the therapy components, while group 2 consisted of 66 patients who received no mAbs. Discharge from the hospital or death was considered as the endpoint of follow-up. Results. In group 1, after the use of mAb, progression of pulmonary process was observed less frequently than in the control group with CT1-2 transformation to CT3-4 (9.1% vs. 30.3%, respectively, p < 0.01). Group 1 KTRs differed significantly from group 2 - lower need for ICU and ventilator care (6.1% vs. 27.3% and 3% vs. 19.8%, respectively). The groups were comparable by sex, age, body mass index, Charlson Comorbidity Index (CCI) and time after kidney transplant (KTx) at the onset of the disease and by.aseline blood biochemistry parameter values at the time of hospitalization. Only C-reactive protein (CRP) and fibrinogen values were higher in the non-mAbs patients who were hospitalized later in the course of the disease (7.7 +/- 3.2 days versus 4.6 +/- 1.6 days in group 1, p < 0.001). The frequency of prescription of other therapies did not differ between the compared groups. Use of mAbs significantly reduced mortality from 19.7% in KTRs in group 2 to 3% in group 1 without adverse effect on graft function. Conclusion. The use of mAbs therapy in the early stages of COVID-19 in KTRs is safe, it prevents severe COVID-19, and reduces the incidence of adverse outcomes.

Declined Humoral Immunity of Kidney Transplant Recipients to SARS-CoV-2 Vaccines.

Background: Kidney transplant recipients (KTRs) commonly suffer from impaired immunity. KTRs' compromised immune response to COVID-19 vaccines indicates urgent revision of immunisation policies. Methods: A cross-sectional study was conducted in Madinah, Saudi Arabia of 84 KTRs who had received at least one dose of a COVID-19 vaccine. ELISA was used to evaluate anti-spike SARS-CoV-2 IgG and IgM antibody levels in blood samples obtained one month and seven months after vaccination. Univariate and multivariate analyses were performed to identify associations between seropositive status and factors such as the number of vaccine doses, transplant age, and immunosuppressive therapies. Results: The mean age of KTRs was 44.3 ± 14.7 years. The IgG antibody seropositivity rate (n=66, 78.5%) was significantly higher than the seronegativity rate (n=18, 21.4%) in the whole cohort (p<0.001). In KTRs seroconverting after one month (n=66), anti-SARS-CoV-2 IgG levels declined significantly between one month (median [IQR]:3 [3-3]) and seven months (2.4 [1.7-2.6]) after vaccination (p<0.01). In KTRs with hypertension, IgG levels significantly decreased between one and seven months after vaccination (p<0.01). IgG levels also decreased significantly in KTRs with a transplant of >10 years (p=0.02). Maintenance immunosuppressive regimens (triple immunosuppressive therapy and steroid-based and antimetabolite-based regimens) led to a significant decrease in IgG levels between the first and second sample (p<0.01). KTRs receiving three vaccine doses showed higher antibody levels than those receiving a single dose or two doses, but the levels decreased significantly between one (median [IQR]: 3 [3-3]) and seven months (2.4 [1.9-2.6]) after vaccination (p<0.01). Conclusion: KTRs' humoral response after SARS-CoV-2 vaccination is dramatically inhibited and wanes. Antibody levels show a significant decline over time in KTRs with hypertension; receiving triple immunosuppressive therapy or steroid-based or antimetabolite-based regimens; receiving mixed mRNA and viral vector vaccines; and with a transplant of >10 years.

A Peculiar Case of Idiopathic Herpes-Zoster-Like Stevens-Johnson Syndrome (SJS).

Epidermal necrolysis is a severe dermatological condition usually associated with adverse drug reactions involving the mucosa. Stevens-Johnson syndrome (SJS) is clinically diagnosed when an epidermal detachment of less than 10% of body surface area (BSA) is involved. In contrast, toxic epidermal necrolysis (TEN) is characterized when there is an epidermal detachment of more than 30% BSA. Epidermal necrolysis can be described as ulcerated, painful, and erythematous lesions typically appearing on the skin. Typical clinical presentations of SJS include epidermal detachment of less than 10% of BSA and mucosal involvement with prodromal flu-like symptoms. Atypical presentations of focal epidermal necrolysis include the presence of lesions in a dermatomal pattern, associated itching, and idiopathic cause. We report a rare case of suspected herpes-zoster virus (HZV)-like SJS with negative HZV serum PCR and negative varicella-zoster virus (VZV) biopsy immunostaining. This rare case of SJS was resolved with the administration of IV acyclovir and Benadryl.

Comparable cellular and humoral immunity upon homologous and heterologous COVID-19 vaccination regimens in kidney transplant recipients.

Background: Kidney transplant recipients (KTRs) are at high risk for a severe course of coronavirus disease 2019 (COVID-19); thus, effective vaccination is critical. However, the achievement of protective immunogenicity is hampered by immunosuppressive therapies. We assessed cellular and humoral immunity and breakthrough infection rates in KTRs vaccinated with homologous and heterologous COVID-19 vaccination regimens. Method: We performed a comparative in-depth analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T-cell responses using multiplex Fluorospot assays and SARS-CoV-2-specific neutralizing antibodies (NAbs) between three-times homologously (n = 18) and heterologously (n = 8) vaccinated KTRs. Results: We detected SARS-CoV-2-reactive T cells in 100% of KTRs upon third vaccination, with comparable frequencies, T-cell expression profiles, and relative interferon γ and interleukin 2 production per single cell between homologously and heterologously vaccinated KTRs. SARS-CoV-2-specific NAb positivity rates were significantly higher in heterologously (87.5%) compared to homologously vaccinated (50.0%) KTRs (P < 0.0001), whereas the magnitudes of NAb titers were comparable between both subcohorts after third vaccination. SARS-CoV-2 breakthrough infections occurred in equal numbers in homologously (38.9%) and heterologously (37.5%) vaccinated KTRs with mild-to-moderate courses of COVID-19. Conclusion: Our data support a more comprehensive assessment of not only humoral but also cellular SARS-CoV-2-specific immunity in KTRs to provide an in-depth understanding about the COVID-19 vaccine-induced immune response in a transplant setting.

Effectiveness, Immunogenicity and Harms of Additional SARS-CoV-2 Vaccine Doses in Kidney Transplant Recipients: A Systematic Review.

BACKGROUND: Kidney transplant recipients (KTRs) who have a highly impaired immune response are in need of intensified and safe vaccination strategies to achieve seroconversion and prevent severe disease. METHODS: We searched the Web of Science Core Collection, the Cochrane COVID-19 Study Register and the WHO COVID-19 global literature on coronavirus disease from January 2020 to 22 July 2022 for prospective studies that assessed immunogenicity and efficacy after three or more SARS-CoV-2 vaccine doses. RESULTS: In 37 studies on 3429 patients, de novo seroconversion after three and four vaccine doses ranged from 32 to 60% and 25 to 37%. Variant-specific neutralization was 59 to 70% for Delta and 12 to 52% for Omicron. Severe disease after infection was rarely reported but all concerned KTRs lacked immune responses after vaccination. Studies investigating the clinical course of COVID-19 found remarkably higher rates of severe disease than in the general population. Serious adverse events and acute graft rejections were very rare. Substantial heterogeneity between the studies limited their comparability and summary. CONCLUSION: Additional SARS-CoV-2 vaccine doses are potent and safe in general terms as well as regarding transplant-specific outcomes whilst the Omicron wave remains a significant threat to KTRs without adequate immune responses.

Association of Different Risk Scores and 30-Day Mortality in Kidney Transplant Recipients with COVID-19.

Background and Objectives: Clinical risk scores were poorly examined in kidney transplant recipients (KTR) with COVID-19. Materials and Methods: This observational study compared the association and discrimination of clinical risk scores (MEWS, qCSI, VACO, PSI/PORT, CCI, MuLBSTA, ISTH-DIC, COVID-GRAM and 4C) with 30-day mortality in 65 hospitalized KTRs with COVID-19. Cox regression was used to derive hazard ratios (HR) and 95% confidence intervals (95% CI), and discrimination was assessed by Harrell's C. Results: A significant association with 30-day mortality was demonstrated for MEWS (HR 1.65 95% CI 1.21-2.25, p = 0.002); qCSI (HR 1.32 95% CI 1.15-1.52, p < 0.001); PSI/PORT (HR 1.04 95% CI 1.02-1.07, p = 0.001); CCI (HR 1.79 95% CI 1.13-2.83, p = 0.013); MuLBSTA (HR 1.31 95% CI 1.05-1.64, p = 0.017); COVID-GRAM (HR 1.03 95% CI 1.01-1.06, p = 0.004); and 4C (HR 1.79 95% CI 1.40-2.31, p < 0.001). After multivariable adjustment, significant association persisted for qCSI (HR 1.33 95% CI 1.11-1.59, p = 0.002); PSI/PORT (HR 1.04 95% CI 1.01-1.07, p = 0.012); MuLBSTA (HR 1.36 95% CI 1.01-1.85, p = 0.046); and 4C Mortality Score (HR 1.93 95% CI 1.45-2.57, p < 0.001) risk scores. The best discrimination was observed with the 4C score (Harrell's C = 0.914). Conclusions: Risk scores such as qCSI, PSI/PORT and 4C showed the best association with 30-day mortality amongst KTRs with COVID-19.

Factors associated with vaccine-induced T cell immune responses against SARS-CoV-2 in kidney transplant recipients.

Vaccination against SARS-CoV-2 is an important prophylactic measure in kidney transplant recipients (KTRs), however, the immune response is often impaired. Here, we examined the T cell immune response against SARS-CoV-2 in 148 KTRs after three or four vaccine doses including 35 KTRs with subsequent SARS-CoV-2 infection. The frequency of spike-specific T cells was lower in KTRs compared to immunocompetent controls and correlated with the level of spike-specific antibodies. Positive predictors for detection of vaccine-induced T cells were detection of spike-specific antibodies, heterologous immunization with mRNA and a vector vaccine and longer time past transplant. In vaccinated KTRs with subsequent SARS-CoV-2 infection, the T-cell response was greatly enhanced and was significantly higher than in vaccinated KTRs without SARS-CoV-2 infection. Overall, the data show a correlation between impaired humoral and T-cell immunity to SARS-CoV-2 vaccination and provide evidence for greater robustness of hybrid immunity in KTRs.

Prediction of humoral and cellular immune response to COVID-19 mRNA vaccination by TTV load in kidney transplant recipients and hemodialysis patients.

BACKGROUND: Immunosuppressed individuals such as kidney transplant recipients (KTR) and hemodialysis patients (DP) show impaired immune responses to COVID-19 vaccination. Plasma Torque Teno Virus (TTV) DNA load is used as surrogate for the individual degree of immunosuppression. We now assessed the association of TTV load at time of COVID-19 vaccination with humoral and cellular immune response rates to vaccination in KTR, DP, and healthy medical personnel (MP). METHODS: A total of 100 KTR, 115 DP and 54 MP were included. All were SARS-CoV-2 seronegative at the time of vaccination with either BNT162b2 or mRNA-1273. Plasma TTV loads were assessed at the time of first vaccination. After two-dose vaccination, seroconversion (de novo detection of SARS-CoV-2 S1-IgA and/or IgG) was determined. In addition, cellular responses as assessed by interferon γ release and neutralizing antibodies were assessed in a subset of participants. ROC analyses were performed to define TTV load cut-offs predicting specific immune responses to vaccination. RESULTS: Plasma TTV loads at the time of first vaccination were negatively associated with seroconversion after two-dose vaccination in KTR (OR 0.87, 95% CI 0.76-0.99). TTV loads were significantly lower in KTR who developed humoral and cellular immune responses to vaccination compared to non-responders (p = 0.0411 and 0.0030, respectively). Of patients with TTV loads above 106 copies/ml, none developed cellular immune responses against SARS-CoV-2, and only 2 of 17 (12%) seroconverted in response to vaccination. CONCLUSION: Plasma TTV loads at the time of first vaccination in immunosuppressed individuals may be useful to predict individual vaccine-specific immune responses.

Immunity against Delta and Omicron variants elicited by homologous inactivated vaccine booster in kidney transplant recipients.

Background: A third mRNA vaccine booster is recommended to improve immunity against SARS-CoV-2 in kidney transplant recipients (KTRs). However, the immunity against SARS-CoV-2 Ancestral strain and Delta and Omicron variants elicited by the third dose of inactivated booster vaccine in KTRs remains unknown. Methods: The blood parameters related to blood cells count, hepatic function, kidney function, heart injury and immunity were explored clinically from laboratory examinations. SARS-CoV-2 specific antibody IgG titer was detected using an enzyme-linked immunosorbent assay. Cellular immunity was analyzed using interferon-γ enzyme-linked immunospot assay. Results: The results showed that there were no severe adverse effects and apparent changes of clinical laboratory biomarkers in KTRs and healthy volunteers (HVs) after homologous inactivated vaccine booster. A third dose of inactivated vaccine booster significantly increased anti-Ancestral-spike-trimer-IgG and anti-Ancestral-receptor binding domain (RBD)-IgG titers in KTRs and HVs compared with the second vaccination. However, the anti-Delta-RBD-IgG and anti-Omicron-RBD-IgG titers were significantly lower than anti-Ancestral-RBD-IgG titer in KTRs and HVs after the third dose. Notably, only 25.6% (10/39) and 10.3% (4/39) of KTRs had seropositivity for anti-Delta-RBD-IgG and anti-Omicron-RBD-IgG after booster, which were significantly lower than HVs (anti-Delta-RBD-IgG: 100%, anti-Omicron-RBD-IgG: 77.8%). Ancestral strain nucleocapsid protein and spike specific T cell frequency after booster was not significantly increased in KTRs compared with the second dose, significantly lower than that in HVs. Moreover, 33.3% (12/36), 14.3% (3/21) and 14.3% (3/21) of KTRs were positive for the Ancestral strain and Delta and Omicron spike-specific T cells, which were significantly lower than HVs (Ancestral: 80.8%, Delta: 53.8%, and Omicron: 57.7%). Conclusions: A third dose of inactivated booster vaccine may significantly increase humoral immunity against the Ancestral strain in KTRs, while humoral and cellular immunity against the Delta and Omicron variants were still poor in KTRs.

Performance of Derived Laboratory Biomarkers with Regard to 30-Day Mortality in Kidney Transplant Recipients with COVID-19.

There are limited data on the performance of laboratory-derived biomarkers in kidney transplant recipients (KTR) with COVID-19. This observational study enrolled 65 KTR with COVID-19 who were treated at the University Hospital of Split up to March 2022. Laboratory-derived biomarkers (neutrophile-to-lymphocyte (NLR) ratio, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, De Ritis ratio, C-reactive protein (CRP)-to-albumin ratio, lactate dehydrogenase (LDH)-to-hemoglobin ratio, CRP-to-lymphocyte ratio, red cell distribution width-to-albumin ratio, platelet-to-albumin ratio, D-Dimer-to-albumin ratio, D-Dimer-to-NLR ratio, LDH-to-albumin ratio, and LDH-to-white blood cell (WBC) ratio) were calculated, and their performance with regard to 30-day mortality was determined. Mortality events occurred in 12 patients (18.5%), which was significantly associated with increased De Ritis (HR 3.83, 95% CI 1.57-9.35, p = 0.003), CRP-to-albumin (HR 1.36, 95% CI 1.13-1.64, p = 0.001), LDH-to-hemoglobin (HR 1.44, 95% CI 1.07-1.92, p = 0.015), CRP-to-lymphocyte (HR 1.03, 95% CI 1.01-1.07, p = 0.003), D-dimer-to-albumin (HR 4.94, 95% CI 1.38-7.24, p = 0.038), LDH-to-albumin (HR 1.20, 95% CI 1.05-1.36, p = 0.008), and LDH-to-WBC (HR 1.03 95% CI 1.01-1.05, p = 0.024) ratios. Out of these, the best area-under-the-curve (AUC) values were achieved with De Ritis (AUC 0.691), CRP-to-albumin (AUC 0.764), LDH-to-hemoglobin (AUC 0.877), CRP-to-lymphocyte (AUC 0.739), and LDH-to-albumin (AUC 0.827) ratios, while the best discrimination displayed LDH-to-hemoglobin ratio (Harrell's C 0.808 and Somers' D 0.616). The overall calibration was satisfactory for all models. Derived laboratory biomarkers such as the de Ritis, CRP-to-albumin, LDH-to-hemoglobin, CRP-to-lymphocyte, and LDH-to-albumin ratios show significant association and discrimination with all-cause mortality in KTR with COVID-19, suggesting its potential risk stratification role.

COVID-19 Breakthrough Infections in Vaccinated Kidney Transplant Recipients.

Coronavirus disease 2019 (COVID-19) is associated with increased morbidity and mortality among kidney transplant recipients (KTRs). The administration of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is the only reliable strategy to prevent COVID-19 and alleviate the severity of COVID-19 in this particular population. The aim of this article was to evaluate the clinical protection by vaccines (breakthrough infections, deaths, and hospitalizations) in KTRs. There were 135 KTRs with COVID-19 breakthrough infections for whom patient-level data were available in PubMed and Web of Science. There was a male predominance (61.4%), 97 were given the standard vaccination regimen, and 38 received three or four doses of the vaccine. The median age was 59.0 (IQR: 49.0-69.0) years. A total of 67 patients were hospitalized, and 10 patients died. In 72.6% of cases, triple-maintenance immunosuppression was employed. The deceased patients were older than the survivors (p < 0.05); an age over 60 years was a risk factor for death (p < 0.05). The KTRs with booster vaccines had a longer time interval from the last vaccine to COVID-19 infection and lower hospitalization rates than the individuals who received the standard vaccination regimen (33.3% vs. 54.8%, p < 0.05). The hospitalized patients were older than the outpatients (p < 0.05). Among 16,820 fully vaccinated or boosted KTRs from 14 centers, there were 633 breakthrough infections (3.58%) and 73 associated deaths (0.41%). The center-level breakthrough infection rates varied from 0.21% to 9.29%. These findings highlight the need for booster doses for KTRs. However, more research is needed to define the long-term effectiveness and immunogenicity of booster doses and to identify methods to boost the protective response to vaccination in these immunocompromised patients.

Humoral Immune Response to a Timely Booster mRNA Vaccination in Non-Responders to a Standard Vaccination Schedule against COVID-19 in Kidney Transplant Recipients.

Kidney transplant recipients who are at increased risk for COVID-19 infection and associated morbidity and mortality have been shown to be prone to an impaired humoral immune response to a standard vaccination schedule against COVID-19 with two doses of SARS-CoV-2 mRNA vaccines. In this study, response rate of 94 kidney transplant recipients without detectable seroconversion after two doses of a mRNA vaccine who were offered a timely third mRNA vaccine after completion of the standard vaccination schedule was retrospectively analyzed. After a median of 28 days, antibody titers against the S1 spike protein showed a non-response rate of 53%. No significant risk factors for non-response could be identified. The responders showed a high variation in antibody titers (median 73.9 BAU/mL, IQR 221.5). In conclusion, a third booster mRNA vaccine in non-responding kidney transplant recipients leads to a detectable humoral immune response in approximately half of the patients. In the seroconversion group, antibody titers were highly variable, indicating that even non-responders to the standard vaccination schedule might develop a significant humoral immune response after a timely booster vaccine.

Outcome of COVID-19 in Kidney Transplant Patients from Eastern India: A Single Center Study.

Introduction: COVID-19 in kidney transplant recipients (KTR) had been associated with high incidence of acute kidney injury and higher mortality. Management of these patients is still evolving. Methods: A retrospective observational study was done that included all KTR aged ≥18 years and ≤65 years who had COVID-19 diagnosis via RTPCR test between 1 June 2020 and 30 May 2021. Severity of COVID-19 was determined as per the guidelines given by Government of India. Acute kidney injury was defined according to KDIGO guideline. Data was collected and analyzed using SPSS version 16.0 (Chicago, SPSS Inc.). Results: Out of 34 patients, 29 were men. Median age of patients was 39.9 years and median time since transplantation was 34 months. Presenting symptoms were fever (100%), cough (79.4%), gastrointestinal symptoms (23.5%), and dysgeusia/anosmia (23.5%). COVID-19 was severe in 17.6%, moderately severe in 32.4%, and mild in 50% of patients. Time since transplantation, duration of symptoms, hospital stay and inflammatory markers like CRP, LDH, ferritin and d-dimer were significantly associated with disease severity (P < 0.05). Steroids were increased in 55%, antiproliferative agents stopped in 97%, and calcineurin inhibitors stopped in 26% of patients. 70.6% of the patients were managed in home isolation. Acute kidney injury occurred in 58.8% cases. 75% of the AKI patients recovered by 28 days after discharge. Conclusion: Our study showed that outcome of COVID-19 in kidney transplant patients was reasonably good.

Antibody Response to ChAdOx1 nCoV-19 (AZD1222) Vaccine in Kidney Transplant Recipients.

Kidney transplant recipients (KTRs) are at a much higher risk of complications and death following COVID-19 and are poor vaccine responders. The data are limited on the immune response to Covishield® in KTRs. We prospectively recruited a cohort of 67 KTRs aged >18 between April 2021 and December 2021. Each participant was given two intramuscular doses of Covishield®, each of 0.5 mL, at an interval of 12 weeks. A blood specimen of 5.0 mL was collected from each participant at two points within a few days before administering the first dose of the vaccine and at any time between 4-12 weeks after administering the second dose. The sera were tested for anti-RBD antibody (ARAb) titre and neutralising antibody (NAb). An ACE2 competition assay was used as a proxy for virus neutralization. According to the prior COVID-19 infection, participants were grouped as (i) group A: prior symptomatic COVID-19 infection, (ii) group B: prior asymptomatic COVID-19 infection as evidenced by detectable ARAb in the prevaccination specimen, (iii) Group C: no prior infection with COVID-19, (iv) group D: Unclassified, i.e., participants had no symptoms suggestive of COVID-19, but their prevaccination specimen was not available for ARAb testing before vaccination. Fifty of sixty-seven participants (74.6%) provided paired specimens (group A 14, group B 27, and group C 9) and 17 participants (25.4%) provided only postvaccination specimens (group D). In the overall cohort (n = 67), 91% and 77.6% of participants developed ARAb and NAb, respectively. Their ARAb titre and NAb proportion were 2927 (520-7124) U/mL and 87.9 (24.4-93.2) %, respectively. Their median ARAb titre increased 65.6 folds, from 38.2 U/mL to 3137 U/mL. Similarly, the proportion of participants with NAb increased from 56% to 86%, and the NAb proportion raised 2.7 folds, from 23% to 91%. A comparison of vaccine response between the study groups showed that all those with or without prior COVID-19 infection showed a significant rise in ARAb titre (p < 0.05) and NAb proportion (p < 0.05) after the two doses of vaccine administration. The median value of folds rise in anti-RBD and NAb between groups A and B were comparable. Hence, ARAb is present in more than 3/4th of KTRs before the ChAdOx1 vaccine in India. The titer of ARAb and the proportion of NAb significantly increased after the two doses of the ChAdOx1 vaccine in KTRs.