Epidemiology of Immune-Mediated Glomerulopathies before and after SARS-CoV-2 Vaccination: A Tertiary Referral Hospital Experience.

BACKGROUND: Vaccination is a known trigger for the appearance of immune-mediated glomerulopathies (IMG). The appearance of IMG after SARS-CoV-2 vaccination with suspected causality has been described. Our aim is to analyze the incidence of IMG flares before and after SARS-CoV-2 vaccination in our center. METHODS: All persons with native kidney biopsy (KB) from January 2019 to March 2022 in our center were included in the study. We compared the incidence of IMG before and after the start of vaccination. We also collected information about whether the patients had received a SARS-CoV-2 vaccine or have suffered from COVID in the six weeks before the IMG. We also evaluated the analytical characteristics of the outbreaks. RESULTS: A total of 386 KB were studied. Of them, 86/218 (39.4%) were IMG performed pre- and 85/168 (50.6%) post-SV (029). The incidence of idiopathic nephrotic syndrome (INS), studied separately, was also significantly increased post-vaccination (n = 18 (10.7%)) compared to pre-vaccination (n = 11 (5%)) (p = 0.036). There were no differences in the incidence of vasculitis or IgA nephropathy. Up to 17 (20%) flares occurred 6 weeks before SARS-CoV-2 vaccination and only 2 (2.4%) within the first 6 weeks after SARS-CoV-2 infection. Within those 17 flares, the most common diagnosis was IgAN (n = 5 (29.4%)); a total of 14 (82.4%) received an mRNA vaccine and 9 (52.9%) took place after the 1st vaccine dose. There were 13 cases of minimal change disease (MCD) with debut/recurrence pre-SV and 20 MCD with debut/recurrence post-SV (p = 0.002). CONCLUSIONS: The incidence of IMG, INS and MCD flares in our center increased significantly after SARS-CoV-2 vaccination. Importantly, 20% of IMG flares took place within the first 6 weeks after receiving a vaccine dose, with the first dose being the riskiest one and IgAN the most frequent diagnosis.

Safety and immediate humoral response of COVID-19 vaccines in chronic kidney disease patients: the SENCOVAC study.

BACKGROUND: Chronic kidney disease (CKD) patients are at high-risk for severe coronavirus disease 2019 (COVID-19). The multicentric, observational and prospective SENCOVAC study aims to describe the humoral response and safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in CKD patients. Safety and immediate humoral response results are reported here. METHODS: Four cohorts of patients were included: kidney transplant (KT) recipients, and haemodialysis (HD), peritoneal dialysis (PD) and non-dialysis CKD patients from 50 Spanish centres. Adverse events after vaccine doses were recorded. At baseline and on Day 28 after the last vaccine dose, anti-Spike antibodies were measured and compared between cohorts. Factors associated with development of anti-Spike antibodies were analysed. RESULTS: A total of 1746 participants were recruited: 1116 HD, 171 PD, 176 non-dialysis CKD patients and 283 KT recipients. Most patients (98%) received mRNA vaccines. At least one vaccine reaction developed after the first dose in 763 (53.5%) and after the second dose in 741 (54.5%) of patients. Anti-Spike antibodies were measured in the first 301 patients. At 28 days, 95% of patients had developed antibodies: 79% of KT, 98% of HD, 99% of PD and 100% of non-dialysis CKD patients (P < 0.001). In a multivariate adjusted analysis, absence of an antibody response was independently associated with KT (odds ratio 20.56, P = 0.001) and with BNT162b2 vaccine (odds ratio 6.03, P = 0.023). CONCLUSION: The rate of anti-Spike antibody development after vaccination in KT patients was low but in other CKD patients it approached 100%, suggesting that KT patients require persistent isolation measures and booster doses of a COVID-19 vaccine. Potential differences between COVID-19 vaccines should be explored in prospective controlled studies.

Induction immunosuppression and outcome in kidney transplant recipients with early COVID-19 after transplantation.

Coronavirus disease 2019 (COVID-19) in kidney transplant recipients has a high risk of complications and mortality, especially in older recipients diagnosed during the early period after transplantation. Management of immunosuppression has been challenging during the pandemic. We investigated the impact of induction immunosuppression, either basiliximab or thymoglobulin, on the clinical evolution of kidney transplant recipients developing COVID-19 during the early period after transplantation. We included kidney transplant recipients with ˂6 months with a functioning graft diagnosed with COVID-19 from the initial pandemic outbreak (March 2020) until 31 July 2021 from different Spanish centres participating in a nationwide registry. A total of 127 patients from 17 Spanish centres developed COVID-19 during the first 6 months after transplantation; 73 (57.5%) received basiliximab and 54 (42.5%) thymoglobulin. Demographics were not different between groups but patients receiving thymoglobulin were more sensitized [calculated panel reactive antibodies (cPRAs) 32.7 ± 40.8% versus 5.6 ± 18.5%] and were more frequently retransplants (30% versus 4%). Recipients ˃65 years of age treated with thymoglobulin showed the highest rate of acute respiratory distress syndrome [64.7% versus 37.1% for older recipients receiving thymoglobulin and basiliximab (P < .05), respectively, and 23.7% and 18.9% for young recipients receiving basiliximab and thymoglobulin (P > .05)], respectively, and the poorest survival [mortality rate 64.7% and 42.9% for older recipients treated with thymoglobulin and basiliximab, respectively (P < .05) and 8.1% and 10.5% for young recipients treated with thymoglobulin and basiliximab (P > .05), respectively]. Older recipients treated with thymoglobulin showed the poorest survival in the Cox regression model adjusted for comorbidities. Thus thymoglobulin should be used with caution in older recipients during the present pandemic era.

Treatment with sotrovimab for SARS-CoV-2 infection in a cohort of high-risk kidney transplant recipients.

Background: Sotrovimab is a neutralizing monoclonal antibody (mAb) that seems to remain active against recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. The evidence on its use in kidney transplant (KT) recipients, however, is limited. Methods: We performed a multicenter, retrospective cohort study of 82 KT patients with SARS-CoV-2 infection {coronavirus disease 2019 [COVID-19]} treated with sotrovimab. Results: Median age was 63 years. Diabetes was present in 43.9% of patients, and obesity in 32.9% of patients; 48.8% of patients had an estimated glomerular filtration rate under 30 mL/minute/1.73 m2. Additional anti-COVID-19 therapies were administered to 56 patients, especially intravenous steroids (65.9%). Sotrovimab was administered early (<5 days from the onset of the symptoms) in 46 patients (56%). Early-treated patients showed less likely progression to severe COVID-19 than those treated later, represented as a lower need for ventilator support (2.2% vs 36.1%; P < .001) or intensive care admission (2.2% vs 25%; P = .002) and COVID-19-related mortality (2.2% vs 16.7%; P = .020). In the multivariable analysis, controlling for baseline risk factors to severe COVID-19 in KT recipients, early use of sotrovimab remained as a protective factor for a composite outcome, including need for ventilator support, intensive care, and COVID-19-related mortality. No anaphylactic reactions, acute rejection episodes, impaired kidney function events, or non-kidney side effects related to sotrovimab were observed. Conclusions: Sotrovimab had an excellent safety profile, even in high-comorbidity patients and advanced chronic kidney disease stages. Earlier administration could prevent progression to severe disease, while clinical outcomes were poor in patients treated later. Larger controlled studies enrolling KT recipients are warranted to elucidate the true efficacy of monoclonal antibody therapies.

Anti-Spike antibodies 3 months after SARS-CoV-2 mRNA vaccine booster dose in patients on hemodialysis: the prospective SENCOVAC study.

Background: Patients on hemodialysis are at high-risk for complications derived from coronavirus disease 2019 (COVID-19). The present analysis evaluated the impact of a booster vaccine dose and breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on humoral immunity 3 months after the booster dose. Methods: This is a multicentric and prospective study assessing immunoglobulin G anti-Spike antibodies 6 and 9 months after initial SARS-CoV-2 vaccination in patients on hemodialysis that had also received a booster dose before the 6-month assessment (early booster) or between the 6- and 9-month assessments (late booster). The impact of breakthrough infections, type of vaccine, time from the booster and clinical variables were assessed. Results: A total of 711 patients [67% male, median age (range) 67 (20-89) years] were included. Of these, 545 (77%) received an early booster and the rest a late booster. At 6 months, 64 (9%) patients had negative anti-Spike antibody titers (3% of early booster and 29% of late booster patients, P = .001). At 9 months, 91% of patients with 6-month negative response had seroconverted and there were no differences in residual prevalence of negative humoral response between early and late booster patients (0.9% vs 0.6%, P = .693). During follow-up, 35 patients (5%) developed breakthrough SARS-CoV-2 infection. Antibody titers at 9 months were independently associated with mRNA-1273 booster (P = .001), lower time from booster (P = .043) and past breakthrough SARS-CoV-2 infection (P < .001). Conclusions: In hemodialysis patients, higher titers of anti-Spike antibodies at 9 months were associated with mRNA-1273 booster, lower time from booster and past breakthrough SARS-CoV-2 infection.

Treatment with sotrovimab for SARS-CoV-2 infection in a cohort of high-risk kidney transplant recipients

Background Sotrovimab is a neutralizing monoclonal antibody (MAB) which seems to remain active against recent SARS-CoV-2 variants. However, the evidence on its use in kidney transplant (KT) recipients is limited. Methods We performed a multicenter retrospective cohort study of 82 KT patients with SARS-CoV-2 infection (COVID-19) treated with sotrovimab. Results Median age was 63 years. Diabetes was present in 43.9%, obesity in 32.9% and 48.8% of patients had an estimated Glomerular Filtration Rate <30 mL/min/1.73m2. Additional anti-COVID-19 therapies were administered in 56 patients, especially intravenous steroids (65.9%). Sotrovimab was administered early (<5 days from the onset of the symptoms) in 46 patients (56%). Early-treated patients showed less likely progression to severe COVID-19 than those treated later, represented as a lower need for ventilator support (2.2% vs. 36.1%, P<0.001) or intensive care admission (2.2% vs. 25%;P = 0.002) and COVID-19-related mortality (2.2% vs. 16.7%;P = 0.020). In the multivariable analysis, controlling for baseline risk factors to severe COVID-19 in KT recipients, early use of sotrovimab remained as a protective factor for a composite outcome including need for ventilator support, intensive care and/or COVID-19-related mortality. No anaphylactic reactions, acute rejection episodes, impaired renal function events or non-renal side effects related to sotrovimab were observed. Conclusions Sotrovimab had an excellent safety profile even in high-comorbidity patients and advanced chronic kidney disease stages. Earlier administration could prevent progression to severe disease while clinical outcomes were poor in patients treated later. Larger controlled studies enrolling KT recipients are warranted to elucidate the true efficacy of MAB therapies. Graphical Graphical

Anti-Spike antibodies three months after SARS-CoV-2 mRNA vaccine booster dose in patients on hemodialysis: the prospective SENCOVAC study

Introduction Patients on hemodialysis are at high-risk for complications derived from coronavirus disease-19 (COVID-19). The present analysis evaluated the impact of a booster vaccine dose and breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on humoral immunity three months after the booster dose. Methods This is a multicentric and prospective study assessing IgG anti-Spike antibodies 6 and 9 months after initial SARS-CoV-2 vaccination in patients on hemodialysis that had also received a booster dose before the 6-month assessment (early booster) or between the 6- and 9-month assessments (late booster). The impact of breakthrough infections, type of vaccine, time from the booster and clinical variables were assessed. Results A total of 711 patients (67% male, 67 [20-89] years) were included. Of which, 545 (77%) received an early booster and the rest a late booster. At 6 months, 64 (9%) patients had negative anti-Spike antibody titers (3% of early booster and 29% of late booster patients, p = 0.001). At 9 months, 91% of patients with 6-month negative response had seroconverted and there were no differences in residual prevalence of negative humoral response between early and late booster patients (0.9% vs 0.6%, p = 0.693). During follow-up, 35 patients (5%) developed breakthrough SARS-CoV-2 infection. Antibody titers at 9 months were independently associated to mRNA-1273 booster (p = 0.001), lower time from booster (p = 0.043) and past breakthrough SARS-CoV-2 infection (p<0.001). Conclusions In hemodialysis patients, higher titers of anti-Spike antibodies at 9 months were associated to mRNA-1273 booster, lower time from booster and past breakthrough SARS-CoV-2 infection. Graphical Graphical

Evolving spectrum but persistent high mortality of COVID-19 among patients on kidney replacement therapy in the vaccine era: the Spanish COVID-19 KRT Registry.

Background: Kidney replacement therapy (KRT) conferred a high risk for coronavirus disease 2019 (COVID-19) related mortality early in the pandemic. We evaluate the presentation, treatment and outcomes of COVID-19 in patients on KRT over time during the pandemic. Methods: This registry-based study involved 6080 dialysis and kidney transplant (KT) patients with COVID-19, representing roughly 10% of total Spanish KRT patients. Epidemiology, comorbidity, infection, vaccine status and treatment data were recorded, and predictors of hospital admission, intensive care unit (ICU) admission and mortality were evaluated. Results: Vaccine introduction decreased the number of COVID-19 cases from 1747 to 280 per wave. Of 3856 (64%) COVID-19 KRT patients admitted to the hospital, 1481/3856 (38%) were admitted during the first of six waves. Independent predictors for admission included KT and the first wave. During follow-up, 1207 patients (21%) died, 500/1207 (41%) during the first wave. Among vaccinated patients, mortality was 19%, mostly affecting KT recipients. Overall, independent predictors for mortality were older age, disease severity (lymphopaenia, pneumonia) and ICU rejection. Among patient factors, older age, male sex, diabetes, KT and no angiotensin receptor blockers (ARB) were independent predictors of death. In KT recipients, individual immunosuppressants were independent predictors of death. Over time, patient characteristics evolved and in later pandemic waves, COVID-19 was mainly diagnosed in vaccinated KT recipients; in the few unvaccinated dialysis patients, ICU admissions increased and mortality decreased (28% for the first wave and 16-22% thereafter). Conclusions: The clinical presentation and outcomes of COVID-19 during the first wave no longer represent COVID-19 in KRT patients, as the pandemic has become centred around vaccinated KT recipients. Vaccines lowered the incidence of diagnosed COVID-19 and mortality. However, mortality remains high despite increased access to ICU care.

Evolving spectrum but persistent high mortality of COVID-19 among patients on kidney replacement therapy in the vaccine era: the Spanish COVID-19 KRT Registry

Background Kidney replacement therapy (KRT) conferred a high risk for COVID-19-related mortality early in the pandemic. We evaluated the presentation, treatment, and outcomes of COVID-19 in patients on KRT over time during the pandemic. Methods This registry-based study involved 6080 dialysis and kidney transplant (KT) patients with COVID-19, representing roughly 10% of total Spanish KRT patients. Epidemiology, comorbidity, infection, vaccine status and treatment data were recorded and predictors of hospital admission, intensive care unit (ICU) admission and mortality evaluated. Results Vaccine introduction decreased COVID-19 cases from 1747 to 280 per wave. Of 3856 (64%) COVID-19 KRT patients admitted to hospital, 1481/3856 (38%) were admitted during the first of six waves. Independent predictors for admission included KT and first wave. During follow-up, 1207 patients (21%) died, 500/1207 (41%) during the first wave. Among vaccinated patients, mortality was 19%, mostly affecting KT recipients. Overall, independent predictors for mortality were older age, disease severity (lymphopenia, pneumonia) and ICU rejection. Among patient factors, older age, male sex, diabetes, KT, and no angiotensin receptor blockers were independent predictors of death. In KT recipients, individual immunosuppressants were independent predictors of death. Over time, patient characteristics evolved and in later pandemic waves, COVID-19 was mainly diagnosed in vaccinated KT recipients and in the few unvaccinated dialysis patients, ICU admissions increased, and mortality decreased (28% for the first wave and 16-22% thereafter). Conclusions The clinical presentation and outcomes of COVID-19 during the first wave no longer represent COVID-19 in KRT patients, as the pandemic has become centred around vaccinated KT recipients. Vaccines lowered the incidence of diagnosed COVID-19 and mortality. However, mortality remains high despite increased access to ICU care. Graphical Graphical

Induction immunosuppression and outcome in kidney transplant recipients with early COVID-19 after transplantation

COVID-19 in kidney transplants has a high risk of complications and mortality, especially in older recipients diagnosed during the early period after transplantation. Management of immunosuppression has been challenging during the pandemic. We investigated the impact of induction immunosuppression, either basiliximab or thymoglobulin, on the clinical evolution of kidney transplants developing COVID-19 during the early period after transplantation. Kidney transplant recipients with less than 6 months with a functioning graft diagnosed of COVID-19 from the initial pandemic outbreak (March 2020) until July 31st, 2021 from different Spanish centers participating in a nationwide registry. A total of 127 patients from 17 Spanish centers developed COVID-19 during the first 6 months after transplantation, 73 (57.5%) received basiliximab and 54 (42.5%) thymoglobulin. Demographics were not different between groups but patients receiving thymoglobulin were more sensitized (cPRA of 32.7±40.8% vs. 5.6±18.5%) and were more frequently re-transplants (30% vs. 4%). Recipients older than 65 years treated with thymoglobulin showed the highest rate of acute respiratory distress syndrome (64.7% vs. 37.1% for older recipients receiving thymoglobulin and basiliximab [p<0.05], and 23.7% and 18.9% for young recipients receiving basiliximab and thymoglobulin [p>0.05]) and the poorest survival (mortality rate of 64.7% and 42.9% for older recipients treated with thymoglobulin and basiliximab, respectively [p<0.05], and 8.1% and 10.5% for young recipients treated with thymoglobulin and basiliximab [p>0.05]). Older recipients treated with thymoglobulin showed the poorest survival in the Cox's regression model adjusted for comorbidities. Thus, thymoglobulin should be used with caution in older recipients during the present pandemic era.

Breakthrough Infections Following mRNA SARS-CoV-2 Vaccination in Kidney Transplant Recipients.

BACKGROUND: The clinical effectiveness of coronavirus disease 2019 (COVID-19) vaccination in kidney transplant (KT) recipients is lower than in the general population. METHODS: From April to October 2021, 481 KT recipients with COVID-19, included in the Spanish Society of Nephrology COVID-19 Registry, were analyzed. Data regarding vaccination status and vaccine type were collected, and outcomes of unvaccinated or partially vaccinated patients (n = 130) were compared with fully vaccinated patients (n = 351). RESULTS: Clinical picture was similar and survival analysis showed no differences between groups: 21.7% of fully vaccinated patients and 20.8% of unvaccinated or partially vaccinated died (P = 0.776). In multivariable analysis, age and pneumonia were independent risk factors for death, whereas vaccination status was not related to mortality. These results remained similar when we excluded patients with partial vaccination, as well as when we analyzed exclusively hospitalized patients. Patients vaccinated with mRNA-1273 (n = 213) showed a significantly lower mortality than those who received the BNT162b2 vaccine (n = 121) (hazard ratio: 0.52; 95% confidence interval, 0.31-0.85; P = 0.010). CONCLUSIONS: COVID-19 severity in KT patients has remained high and has not improved despite receiving 2 doses of the mRNA vaccine. The mRNA-1273 vaccine shows higher clinical effectiveness than BNT162b2 in KT recipients with breakthrough infections. Confirmation of these data will require further research taking into account the new variants and the administration of successive vaccine doses.

COVID-19 infection and renal injury: where is the place for acute interstitial nephritis disease?

Novel coronavirus disease infection (coronavirus disease 2019, COVID-19) was declared a global pandemic in March 2020 and since then has become a major public health problem. The prevalence of COVID-19 infection and acute kidney injury (AKI) is variable depending on several factors such as race/ethnicity and severity of illness. The pathophysiology of renal involvement in COVID-19 infection is not entirely clear, but it could be in part explained by the viral tropism in the kidney parenchyma. AKI in COVID-19 infection can be either by direct invasion of the virus or as a consequence of immunologic response. Diverse studies have focused on the effect of COVID-19 on glomerulonephritis (GN) patients or the 'novo' GN; however, the effect of COVID-19 in acute tubulointerstitial nephritis (ATIN) has been scarcely studied. In this article, we present five cases with different spectrums of COVID-19 infection and ATIN that may suggest that recent diagnosis of ATIN is accompanied by a worse clinical prognosis in comparison with long-term diagnosed ATIN.

A comprehensive assessment of long-term SARS-CoV-2-specific adaptive immune memory in convalescent COVID-19 Solid Organ Transplant recipients.

Long-term adaptive immune memory has been reported among immunocompetent individuals up to eight months following SARS-CoV-2 infection. However, limited data is available in convalescent patients with a solid organ transplant. To investigate this, we performed a thorough evaluation of adaptive immune memory at different compartments (serological, memory B cells and cytokine [IFN-γ, IL-2, IFN-γ/IL12 and IL-21] producing T cells) specific to SARS-CoV-2 by ELISA and FluoroSpot-based assays in 102 convalescent patients (53 with a solid organ transplants (38 kidney, 5 liver, 5 lung and 5 heart transplant) and 49 immunocompetent controls) with different clinical COVID-19 severity (severe, mild and asymptomatic) beyond six months after infection. While similar detectable memory responses at different immune compartments were detected between those with a solid organ transplant and immunocompetent individuals, these responses were predominantly driven by distinct COVID-19 clinical severities (97.6%, 80.5% and 42.1%, all significantly different, were seropositive; 84% vs 75% vs 35.7%, all significantly different, showed IgG-producing memory B cells and 82.5%, 86.9% and 31.6%, displayed IFN-γ producing T cells; in severe, mild and asymptomatic convalescent patients, respectively). Notably, patients with a solid organ transplant with longer time after transplantation did more likely show detectable long-lasting immune memory, regardless of COVID-19 severity. Thus, our study shows that patients with a solid organ transplant are capable of maintaining long-lasting peripheral immune memory after COVID-19 infection; mainly determined by the degree of infection severity.