Effect of Lymphocyte Phenotypic Alterations on the Humoral Response to Vaccination Against SARS-COV-2 in Dialysis Patients.

Background: The response to vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) varies depending on comorbidities. This study evaluated the clinical and immunological factors affecting the humoral response of patients with end-stage renal disease (ESRD) to the BNT162b2 vaccine. Methods: Humoral immunity was evaluated in 54 ESRD patients using serum levels of anti-receptor-binding domain (RBD) and neutralizing antibodies (NAbs), measured by a chemiluminescent immunoassay 30 (T1), 60 (T2), and 120 (T3) days after the second vaccine dose. The results were correlated to baseline patient T- and B-lymphocyte subpopulations determined by flow cytometry. Results: The proportion of seroconverted patients based on the NAb titer decreased from 83.3% at T1 to 53.7% at T3. Age was negatively correlated to the NAb titer at T1 and T2. Patients receiving hemodiafiltration had higher NAb titers at T3. Diabetes was associated with a lower response rate at T3. Univariate analysis revealed a positive correlation between the naïve CD4 T-lymphocyte population and RBD titer at T1 and the NAb titer at T3, with no association observed with naïve CD8 T lymphocytes. NAb titers at T3 were significantly correlated with late-differentiated CD4 T lymphocytes and terminally differentiated effector memory cells re-expressing CD45RA (TEMRA) CD8 T lymphocytes. RBD levels were positively correlated with naïve and memory B-lymphocyte counts at T3. Conclusions: Age, diabetes, and hemodialysis prescription had significant impacts on the response to vaccination. T- and B-lymphocyte phenotypes are major determinants of the humoral response potency to SARS-CoV-2 vaccination with BNT162b2 in patients with ESRD.

Prospective Analysis of B Lymphocyte Subtypes, before and after Initiation of Dialysis, in Patients with End-Stage Renal Disease.

End-stage renal disease (ESRD) is followed by alterations in adaptive immunity. The aim of this study was to evaluate B lymphocyte subtypes in ESRD patients before and after hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). PATIENTS AND METHODS: CD5, CD27, BAFF, IgM and annexin were evaluated by flow cytometry on CD19+ cells in ESRD patients (n = 40), at time of initiating HD or CAPD (T0) and 6 months later (T6). RESULTS: A significant reduction in ESRD-T0 compared to controls was noticed for CD19+, 70.8 (46.5) vs. 171 (249), p < 0.0001, CD19+CD5-, 68.6 (43) vs. 168.9 (106), p < 0.0001, CD19+CD27-, 31.2 (22.1) vs. 59.7 (88.4), p < 0.0001, CD19+CD27+, 42.1 (63.6) vs. 84.3 (78.1), p = 0.002, CD19+BAFF+, 59.7 (37.8) vs. 127.9 (123.7), p < 0.0001 and CD19+IgM+ cells, 48.9 (42.8) vs. 112.5 (81.7) (K/µL), p < 0.0001. The ratio of early/late apoptotic B lymphocytes was reduced (16.8 (10.9) vs. 110 (25.4), p = 0.03). CD19+CD5+ cells were the only cell type with an increased proportion in ESRD-T0 patients (2.7 (3.7) vs. 0.6 (1.1), p < 0.0001). After 6 months on CAPD or HD, CD19+CD27-(%) and early apoptotic lymphocytes were reduced further. The HD patients also showed a significant increase in late apoptotic lymphocytes, from 1.2 (5.7) to 4.2 (7.2) K/mL, p = 0.02. CONCLUSIONS: B cells and most of their subtypes were significantly reduced in ESRD-T0 patients compared to controls, the only exception being CD19+CD5+ cells. Apoptotic changes were prominent in ESRD-T0 patients and were exacerbated by HD.

Relapse of Monoclonal Gammopathy of Renal Significance after mRNA COVID-19 Vaccination: A Case Report.

This case report represents the first suspected case of light chain deposition disease relapse associated with mRNA COVID-19 vaccination. The 75-year-old female patient of Greek ethnicity was admitted to the clinic for the investigation of worsening renal function detected on routine lab examinations, two weeks after she received the second dose of the Moderna COVID-19 vaccine (mRNA-1273). Rapidly progressive glomerulonephritis and anemia were the most notable findings. She had a history of LCDD, which had remained stable for four years. Serum protein immunofixation showed monoclonal kappa zones, and a bone marrow biopsy revealed 5% plasma cell infiltration. These, along with other investigations, established the diagnosis of LCDD recurrence. The patient was started on chemotherapy, which improved her immunological profile, but not her renal function. The patient has remained on hemodialysis since. The association between mRNA vaccinations and LCDD relapse may be grounds for investigations into the pathophysiology of MGRS, given the patient's previous long-term remission. This case report is not intended to directly inform changes in clinical practice. We must stress the importance of following all standardized vaccination protocols, especially in immunocompromised patients.

Two Cases of Autoimmune Thyroid Disorders after COVID Vaccination in Dialysis Patients.

SARS-CoV-2 infection and vaccination have been associated with autoimmune thyroid dysfunctions. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) and molecular mimicry have been referred to as potential causes. Such a case has not been reported in immunocompromised end-stage renal disease (ESRD) patients. Herein we present two dialysis patients with no previous history of thyroid disease who developed immune mediated thyroid disorders after BNT162b mRNA vaccine against SARS-CoV-2. The first patient is a 29-year-old man on hemodialysis diagnosed with Grave's disease four months post-vaccination and the second one is a 67-year-old female on peritoneal dialysis who developed Hashimoto's thyroiditis two months post-vaccination. Grave's disease is uncommon in dialysis patients, whereas Hashimoto's thyroiditis has a higher incidence in this population. Time proximity in both cases suggests potential causality. To our knowledge, this is the first report of de novo immune-mediated thyroid disorders in dialysis patients following vaccination against SARS-CoV-2.

COVID-19 Infection and Response to Vaccination in Chronic Kidney Disease and Renal Transplantation: A Brief Presentation.

Chronic kidney disease (CKD) is associated with phenotypic and functional changes in the immune system, followed by detrimental clinical consequences, such as severe infections and defective response to vaccination. Two years of the pandemic, due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have undoubtedly changed the world; however, all efforts to confront infection and provide new generation vaccines tremendously improved our understanding of the mechanisms of the immune response against infections and after vaccination. Humoral and cellular responses to vaccines, including mRNA vaccines, are apparently affected in CKD patients, as elimination of recent thymic emigrant and naïve lymphocytes and regulatory T-cells, together with contraction of T-cell repertoire and homeostatic proliferation rate, which characterized CKD patients are responsible for impaired immune activation. Successful renal transplantation will restore some of these changes, although several epigenetic changes are irreversible and even accelerated by the induction of immunosuppression. Response to vaccination is definitely impaired among both CKD and RT patients. In the present review, we analyzed the differences in immune response after vaccination between these patients and healthy individuals and depicted specific parameters, such as alterations in the immune system, predisposing to this deficient response.

A patient with dialysis-dependent acute kidney injury due to hantavirus complicated with SARS-CoV-2 infection.

In this case, we report a 64-year-old man presenting with anorexia, nausea and vomiting, mild abdominal pain, and oligoanuria for a few hours. His previous medical history included diabetes, hypertension, and chronic kidney disease (CKD) stage 3. Upon arrival, laboratory results revealed stage III acute kidney injury (AKI) with hyperkalemia requiring dialysis treatment. During hospitalization, both pre-renal and post-renal causes of AKI were excluded, and a careful diagnostic evaluation, including kidney biopsy and serology testing, revealed acute interstitial nephritis and positive IgM for hantavirus. The patient was started on steroid treatment, which led to complete recovery of kidney function over 3 months. Moreover, during his hospitalization, the patient was also diagnosed with SARS-CoV-2 infection, possibly due to intra-hospital transmission and was hospitalized at the COVID-19 Department for 14 days, eventually with no further complications. Hantavirus nephropathy should be at the differential diagnosis of AKI, even in the absence of typical symptoms. Steroid treatment may be helpful in reversal of kidney injury.

ANCA-Associated Vasculitis May Result as a Complication to Both SARS-CoV-2 Infection and Vaccination.

In the last two years, our world experienced one of the most devastating and fast-exploding pandemic, due to the wide spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The scientific community managed to develop effective vaccines, the main weapons to shield the immune system and protect people. Nevertheless, both SARS-CoV-2 infection and the vaccination against it have been associated with the stimulation of inflammatory cells such as T and B lymphocytes that results in a cytokine storm, endothelial inflammation and vascular injury, which can lead to different types of vasculitis. We present the first case of de novo MPO-ANCA-associated vasculitis, which developed shortly after SARS-CoV-2 vaccination, adequately responded to treatment, and subsequently relapsed after COVID-19 infection. With this case, we indicate an etiological connection between viral infection and disease development, as well as the possibility of a common immune mechanism between SARS-CoV-2 infection and vaccination, that can stimulate vascular events and lead to vasculitis. There have been several case reports of de novo vasculitis, affecting large, medium, or small vessels, following either infection or vaccination against COVID-19, during the pandemic outbreak. We summarize previous reports and also analyze proposed pathogenic mechanisms between SARS-CoV-2 and vasculitis.

De novo Minimal Change Disease in an Adolescent after Pfizer-BioNTech COVID-19 Vaccination: A Case Report.

This is the first report in an adolescent of minimal change disease (MCD) after the first injection of the BNT162b2 COVID-19 vaccine (Pfizer-BioNTech) with complete remission following steroid treatment. An 18-year-old white male with no prior medical history complained of gastrointestinal symptoms 11 days after his vaccination. Ascites and lower extremity edema were observed a few days later. He was admitted to a hospital as laboratory testing revealed proteinuria of 10.5 g/24 h, normal creatinine levels, and serum albumin of 1.8 g/dL, confirming the presence of nephrotic syndrome. Immunology and serology tests were unremarkable. A diagnostic kidney biopsy showed no significant glomerular or tubular abnormalities in light microscopy with negative immunofluorescence. Treatment with methylprednisolone 48 mg daily was initiated. A week after discharge, proteinuria declined to 1.2 g/24 h, and edema had disappeared, and 6 weeks later, complete remission was evident. As COVID-19 vaccination has been associated with the development of de novo and relapsing MCD, and this case provides additional support for this possible correlation.