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.

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.

A hybrid data envelopment analysis-artificial neural network prediction model for COVID-19 severity in transplant recipients.

In an overwhelming demand scenario, such as the SARS-CoV-2 pandemic, pressure over health systems may outburst their predicted capacity to deal with such extreme situations. Therefore, in order to successfully face a health emergency, scientific evidence and validated models are needed to provide real-time information that could be applied by any health center, especially for high-risk populations, such as transplant recipients. We have developed a hybrid prediction model whose accuracy relative to several alternative configurations has been validated through a battery of clustering techniques. Using hospital admission data from a cohort of hospitalized transplant patients, our hybrid Data Envelopment Analysis (DEA)-Artificial Neural Network (ANN) model extrapolates the progression towards severe COVID-19 disease with an accuracy of 96.3%, outperforming any competing model, such as logistic regression (65.5%) and random forest (44.8%). In this regard, DEA-ANN allows us to categorize the evolution of patients through the values of the analyses performed at hospital admission. Our prediction model may help guiding COVID-19 management through the identification of key predictors that permit a sustainable management of resources in a patient-centered model. Supplementary Information: The online version contains supplementary material available at 10.1007/s10462-021-10008-0.

SARS-CoV-2 Infection in a Spanish Cohort of CKD-5D Patients: Prevalence, Clinical Presentation, Outcomes, and De-Isolation Results.

INTRODUCTION: COVID-19 is a highly contagious disease that has easily spread worldwide. Outpatient maintenance hemodialysis seems to entail an increased risk of contagion, and previous reports inform of increased mortality among this population. METHODS: We retrospectively analyzed clinical and laboratory parameters, outcomes, and management once discharged of CKD-5D patients infected with SARS-CoV-2 from our health area. RESULTS: Out of the 429 CKD-5D population, 36 were diagnosed with SARS-CoV-2 infection (8%): 34 on in-center hemodialysis and 2 on peritoneal dialysis. Five were asymptomatic. The most common symptom was fever (70%), followed by dyspnea and cough. History of cardiovascular disease and elevation of LDH and C-reactive protein during admission were associated with higher mortality. Thirteen patients died (36%), 8 patients were admitted to an ICU, and survival was low (38%) among the latter. The mean time to death was 12 days. Most discharged patients got negative rRT-PCR in nasopharyngeal swabs within 26 days of diagnosis. However, there is a portion of cured patients that continue to have positive results even more than 2 months after the initial presentation. CONCLUSIONS: Patients on dialysis have an increased mortality risk if infected with SARS-CoV-2. Preventive measures have proven useful. Thus, proper ones, such as universal screening of the population and isolation when required, need to be generalized. Better de-isolation criteria are necessary to ensure an appropriate use of public health resources.