Humoral and Cellular Immune Responses After a 3-dose Course of mRNA-1273 COVID-19 Vaccine in Kidney Transplant Recipients: A Prospective Cohort Study.

In kidney transplant recipients, there is discordance between the development of cellular and humoral response after vaccination against SARS-CoV-2. We sought to determine the interplay between the 2 arms of adaptive immunity in a 3-dose course of mRNA-1273 100 µg vaccine. Methods: Humoral (IgG/IgM) and cellular (N- and S-ELISpot) responses were studied in 117 kidney and 12 kidney-pancreas transplant recipients at the following time points: before the first dose, 14 d after the second dose' and before and after the third dose, with a median of 203 and 232 d after the start of the vaccination cycle, respectively. Results: After the second dose, 26.7% of naive cases experienced seroconversion. Before the third dose and in the absence of COVID-19, this percentage increased to 61.9%. After the third dose, seroconversion occurred in 80.0% of patients. Naive patients who had at any time point a detectable positivity for S-ELISpot were 75.2% of the population, whereas patients who maintained S-ELISpot positivity throughout the study were 34.3%. S-ELISpot positivity at 42 d was associated with final seroconversion (odds ratio' 3.14; 95% confidence interval' 1.10-8.96; P = 0.032). Final IgG titer was significantly higher in patients with constant S-ELISpot positivity (P < 0.001). Conclusions: A substantial proportion of kidney transplant recipients developed late seroconversion after 2 doses. Cellular immunity was associated with the development of a stronger humoral response.

Acute Renal Failure in COVID-19: Aetiology and Renal Evolution. AKI-COVID Registry of the Spanish Society of Nephrology

BACKGROUND AND AIMS Acute kidney injury (AKI) has been described as a frequent complication in patients with COVID-19. The incidence of AKI is estimated to be around 5%–80% depending on the series;however, data characterizing the type of AKI and the evolution of renal function parameters in the medium-long term are still limited. METHOD Based on the initial AKI-COVID Registry, we developed an extended registry where we registered retrospectively new variables that included clinical and demographic characteristics, infection severity parameters and data related to AKI (ethology, KDIGO classification, need of renal replacement therapy, analytic values: baseline creatinine, maximum creatinine during admission, creatinine at discharge or death, creatinine at 1 month after hospitalization and urinary parameters). Recovery of kidney function was defined as difference in at discharge or posthospitalization creatinine < 0.3 mg/dL with respect basal creatinine. RESULTS Our analysis included 196 patients: 74% male, mean age 66 + 13 years;65% hypertensive, 33% diabetic and 22% chronic kidney disease. According to the KDIGO classification: 66% AKI KDIGO3, 17% KDIGO2 and 15% KDIGO1. Creatinine values ​​are summarized in Table 1. We found significant differences in the baseline/high creatinine differential;these differences were lost after hospitalization.Table 1. Analytical evolution of the patients included in the study. ANOVA test for independent samples The main types of AKI were prerenal (35%) and acute tubular necrosis secondary to sepsis (ATN) (53%). 89% of patients with ATN presented AKI KDIGO 3, compared with 57% in the prerenal group (P < .001). Patients with prerenal AKI had greater comorbidity. On the other hand, patients with ATN AKI developed more serious COVID-19 infection: higher percentage of severe pneumonia, admission to the intensive care unit and need for orotracheal intubation. The analytical parameters were more extreme in patients with ATN AKI, except for creatinine and urea upon admission, which were higher in the prerenal AKI group. A total of 89 patients died during the study;65% of ATN AKI patients versus 31% of prerenal-AKI patients (P < .001). The ATN was a mortality risk factor, whit a hazard ratio 2.74 [95% confidence interval (95% CI )1.29–5.7] (P = .008) compared with the prerenal AKI. CONCLUSION AKI in hospitalized patients with COVID19 presented with two different clinical patterns. Prerenal AKI more frequently affected older, more comorbid patients, and with a mild COVID19 infection. The NTA AKI affected younger patients, with criteria of severity of infection and multiplying mortality almost three times. In analytical control 1-month post-hospitalization, most of the patients recovered their kidney function. Although the implications of AKI associated with COVID-19 in the development of chronic kidney disease are still unclear, our data suggest that most patients will recover kidney function in a medium term.

Incidence of severe breakthrough SARS-CoV-2 infections in vaccinated kidney transplant and haemodialysis patients.

INTRODUCTION: Given the increased COVID-19 observed in kidney transplant recipients (KTRs) and haemodialysis patients, several studies have tried to establish the efficacy of mRNA vaccines in these populations by evaluating their humoral and cellular responses. However, there is currently no information on clinical protection (deaths and hospitalizations), a gap that this study aims to fill. METHODS: Observational prospective study involving 1,336 KTRs and haemodialysis patients from three dialysis units affiliated to Hospital Clínic of Barcelona, Spain, vaccinated with two doses of mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 mRNA vaccines. The outcomes measured were SARS-CoV-2 infection diagnosed by a positive RT-PCR fourteen days after the second vaccine dose, hospital admissions derived from infection, and a severe COVID-19 composite outcome, defined as either ICU admission, invasive and non-invasive mechanical ventilation, or death. RESULTS: Six per cent (18/302) of patients on haemodialysis were infected, of whom four required hospital admission (1.3%), only one (0.3%) had severe COVID-19, and none of them died. In contrast, 4.3% (44/1034) of KTRs were infected, and presented more hospital admissions (26 patients, 2.5%), severe COVID-19 (11 patients, 1.1%) or death (4 patients, 0.4%). KTRs had a significantly higher risk of hospital admission than HD patients, and this risk increased with age and male sex (HR 3.37 and 4.74, respectively). CONCLUSIONS: The study highlights the need for booster doses in KTRs. In contrast, the haemodialysis population appears to have an adequate clinical response to vaccination, at least up to four months from its administration.

Severe acute kidney injury in critically ill COVID-19 patients.

BACKGROUND: Acute kidney injury (AKI) is frequent in Coronavirus Infection Disease 2019 (COVID-19) patients. Factors associated with AKI in COVID-19 intensive care unit (ICU) patients and their outcomes have not been previously explored. METHODS: Prospective observational study of COVID-19 patients admitted to the ICUs of the Hospital Clínic of Barcelona (Spain), from March 25th to April 21st, 2020, who developed AKI stage 2 or higher (AKIN classification). The primary goal was to describe the characteristics of moderate-severe AKI of COVID-19 patients in an ICU context. As a secondary goal, we aimed to find independent predictors of AKI progression, Renal Replacement Therapy (RRT) requirement and mortality among these patients. RESULTS: During the study period, 52 out of 237 ICU patients, developed AKIN stage 2 or higher and were included in the study. A Sequential Organ Failure Assessment (SOFA) score at AKI diagnosis of 8 or higher was associated with RRT, OR 5.2, p 0.032. At the time of AKI diagnosis, patients had a worse liver profile and higher inflammation markers than at admission. Fifty per cent of the patients presented AKI progression from AKIN 2 to 3 and 28.85% required RRT. The use of corticosteroids in 69.2% of patients was associated with a reduced requirement of RRT, OR 0.13 (CI 95% 0.02-0.89), p 0.037. AKI was associated with high mortality (50%) and a longer hospital stay, median 35 vs 18 days (p 0.024). CONCLUSIONS: The prevalence of moderate/severe AKI in COVID-19 patients admitted to the ICU is high and has a strong correlation with mortality and length of hospital stay.