Humoral Response to Third Dose of Sars-Cov-2 Vaccines in the CKD Spectrum: The Sencovac Study

BACKGROUND AND AIMS There is incomplete information on the impact of a third dose of the SARS-CoV-2 vaccine in advance chronic kidney disease (CKD). The aim of the present analysis was to evaluate the kinetics of humoral response in the CKD spectrum (KT, HD, PD and ND-CKD) 6 months after completing the initial vaccine schedule. Some patients of each group received a third dose before 6 months, providing a pragmatic insight into real-world responses to different vaccine schedules in patients with advanced CKD not on dialysis, on dialysis or in KT recipients. METHOD The SENCOVAC study describes the humoral response and safety of different SARS-CoV-2 vaccines in a real-world setting in 3687 CKD patients: 787 kidney transplant (KT), 319 peritoneal dialysis (PD), 2297 haemodialysis (HD) and 284 non-dialysis-CKD (ND-CKD) patients. Anti-Spike antibodies were assessed in an efficacy analysis at 28 days (n = 1755), 3 months (n = 1386), and 6 months (n = 1018, of whom 628 had received a third vaccine dose). Adverse events (AEs) were registered during follow-up, including SARS-CoV-2 infections in the safety analysis. RESULTS Among the patients included in the efficacy analysis, KT recipients presented lower anti-Spike antibody titers than other CKD cohorts at 28 days and 3 months (P < .001 for all). A total of 943 patients [249 (26%) KT, 108 (11%) PD, 511 (54%) HD and 75 (8%) ND-CKD] had negative baseline anti-Spike antibodies. Again, at 28 days or 3 months, KT recipients developed lower anti-Spike antibody titers than PD (P < .001), HD (P < .001) and ND-CKD (P< .001) patients. At 6 months, patients that had received a third vaccine dose had higher anti-Spike antibody titers than those without the third dose [1837 (507–9726) UI/mL versus 80 (19–409) ml/UI;P < .001] and this was evident in all CKD cohorts. Anti-Spike titers after the third dose were higher in patients boosted with mRNA-1273 than with BNT162b2 [1710 (322–9615) versus 472 (34–2094);P < .001). At 6 months, in patients that had received a third dose, a positive humoral response (anti-Spike antibodies > 36 UI/mL) was achieved in 584 (93%): 94 (80%) of 118 KT recipients, 20 (100%) of 20 patients on PD, 436 (96%) of 455 patients on HD and 34 (97%) of 35 patients with ND-CKD (Fig. 1). Among patients without humoral response 3 months after completing the initial vaccination schedule, 72 (69%) seroconverted after the third dose (62% KT, 76% HD, 100% ND-CKD, all PD patients had a positive humoral response at 3 months). Independent predictors of a positive humoral response at 6 months were not-KT (HR for KT 0.26, P = .011), third dose (HR 22.9, P < .001), initial mRNA-1273 (HT 1.78, P = .017) and humoral response at 3 months (HR 26.2, P < .001). Breakthrough SARS-CoV-2 infections occurred in 1.1% of patients, and mortality was 14.6%, none after the third dose. CONCLUSION In the CKD spectrum, anti-Spike antibody titers continued to decrease from 3 to 6 months after complete vaccination, and KT recipients presented higher rates of negative humoral response at 6 months. A third dose of mRNA vaccine increased anti-Spike antibody titers but was still insufficient to spur a humoral immune response in at least 38% of KT recipients and 24% of patients on HD that lacked anti-SARS-CoV-2 antibodies 3 months post-initial vaccination. New strategies are urgently needed to protect CKD patients that remain negative for anti-SARS-CoV-2 antibodies, given the high mortality of breakthrough SARS-CoV-2 infections.FIGURE 1: Presence of anti-Spike antibodies during follow-up in the different CKD cohorts. Data expressed as % of patients with presence of anti-Spike antibodies (i.e. titer > 36 IU/mL). GRAPHICAL Graphical

Management of Hemodialysis Patients with Suspected or Confirmed COVID-19 Infection: Perspective from the Spanish Nephrology.

Background: The recent SARS-CoV-2 coronavirus pandemic has signified a significant effect on the health of the population worldwide. Patients on chronic RRT have been affected by the virus, and they are at higher risk due to the frequent comorbid conditions. Here, we show the results of the COVID-19 Registry of the Spanish Society of Nephrology during the first 6 weeks of the outbreak. Methods: This study is an analysis of the data recorded on a registry of patients with ESKD on RRT who tested positive for COVID-19. The aim was to evaluate clinical conditions, therapeutic management, and consequences, including outcome. The registry began on March 18th, 2020. It includes epidemiologic data, cause of CKD, signs and symptoms of the infection, treatments, and outcomes. Patients were diagnosed with SARS-CoV-2 infection on the basis of the results of PCR of the virus obtained from nasopharyngeal/oropharyngeal swabs. The tests were performed on symptomatic patients and on those who mentioned contact with infected patients. Results: As of May 2, the registry included data on 1397 patients (in-center hemodialysis [IC-HD], 63%; kidney transplant [Tx], 34%; peritoneal dialysis [PD], 3%; and home hemodialysis, 0.3%). The mean age was 67±15 years, and two-thirds were men. Dialysis vintage was 46±41 months, and the time after transplantation was 59±54 months. Eighty-five percent of the patients required hospital admission, and 8% had to be transferred to intensive care units. Overall mortality was 25% (IC-HD, 27%; Tx, 23%; and PD, 15%), and significant proportions of deceased patients have advanced age, are on IC-HD, and presented pneumonia. Age and pneumonia were independently associated with the risk of death. Conclusions: SARS-CoV-2 infection affected a significant number of Spanish patients on RRT, mainly those on IC-HD. Hospitalization rates and mortality were high. The factors more closely related to mortality were age and pneumonia.

More difficult still: Treating severe rapidly progressive glomerulonephritis in the context of COVID-19 pneumonia☆ Más difícil todavía: tratar una glomerulonefritis rápidamente progresiva grave en el seno de una neumonía por COVID-19

We present the case of a male patient with severe SARS-CoV-2 pneumonia, with simultaneous onset of p-ANCA positive rapidly progressive glomerulonephritis. We discuss the different therapeutic possibilities, emphasising the appropriateness of their administration according to the time in the course of the infection.

More difficult still: Treating severe rapidly progressive glomerulonephritis in the context of COVID-19 pneumonia.

We present the case of a male patient with severe SARS-CoV-2 pneumonia, with simultaneous onset of p-ANCA positive rapidly progressive glomerulonephritis. We discuss the different therapeutic possibilities, emphasising the appropriateness of their administration according to the time in the course of the infection.

Acute kidney injury in 3182 patients admitted with COVID-19: a single-center, retrospective, case-control study.

BACKGROUND: Acute kidney injury (AKI) may develop in coronavirus disease 2019 (COVID-19) patients and may be associated with a worse outcome. The aim of this study is to describe AKI incidence during the first 45 days of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Spain, its reversibility and the association with mortality. METHODS: This was an observational retrospective case-control study based on patients hospitalized between 1 March and 15 April 2020 with SARS-CoV-2 infection and AKI. Confirmed AKI cases were compared with stable kidney function patients for baseline characteristics, analytical data, treatment and renal outcome. Patients with end-stage kidney disease were excluded. RESULTS: AKI incidence was 17.22% among 3182 admitted COVID-19 patients and acute kidney disease (AKD) incidence was 6.82%. The most frequent causes of AKI were prerenal (68.8%) and sepsis (21.9%). Odds ratio (OR) for AKI was increased in patients with pre-existent hypertension [OR 2.58, 95% confidence interval (CI) 1.71-3.89] and chronic kidney disease (CKD) (OR 2.14, 95% CI 1.33-3.42) and in those with respiratory distress (OR 2.37, 95% CI 1.52-3.70). Low arterial pressure at admission increased the risk for Stage 3 AKI (OR 1.65, 95% CI 1.09-2.50). Baseline kidney function was not recovered in 45.73% of overall AKI cases and in 52.75% of AKI patients with prior CKD. Mortality was 38.5% compared with 13.4% of the overall sample population. AKI increased mortality risk at any time of hospitalization (hazard ratio 1.45, 95% CI 1.09-1.93). CONCLUSIONS: AKI is frequent in COVID-19 patients and is associated with mortality, independently of acute respiratory distress syndrome. AKD was also frequent and merits adequate follow-up.

More difficult still: Treating severe rapidly progressive glomerulonephritis in the context of COVID-19 pneumonia. / Más difícil todavía: tratar una glomerulonefritis rápidamente progresiva grave en el seno de una neumonía por COVID-19.

We present the case of a male patient with severe SARS-CoV-2 pneumonia, with simultaneous onset of p-ANCA positive rapidly progressive glomerulonephritis. We discuss the different therapeutic possibilities, emphasising the appropriateness of their administration according to the time in the course of the infection.