Immune Responses after a Third Dose of mRNA Vaccine Differ in Virus-Naive versus SARS-CoV-2- Recovered Dialysis Patients.

BACKGROUND AND OBJECTIVES: After two doses of mRNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), patients on dialysis show a defective humoral response, but a third dose could increase anti-SARS-CoV-2 spike IgG titers. Responses could be different in virus-naive and SARS-CoV-2-recovered patients on dialysis. However, characterization of memory B cell response after three doses is lacking. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We evaluated the dynamics of antireceptor binding domain IgG titers and antireceptor binding domain memory B cells until 6 months after two and three doses (administered within 6 months after the second dose) of mRNA vaccine in SARS-CoV-2-recovered and virus-naive dialysis populations. Results were analyzed by ordinary one-way ANOVA, the Kruskal-Wallis test, or the Wilcoxon matched-pairs test as appropriate. RESULTS: In total, 108 individuals (59 patients on dialysis and 49 controls) were included. In virus-naive patients on dialysis, antireceptor binding domain IgG response was quantitatively lower after two doses compared with healthy controls, but IgG titers increased by three-fold after three doses (P=0.008). In SARS-CoV-2-recovered patients on dialysis, antireceptor binding domain IgG titers after two doses were significantly higher compared with virus-naive patients on dialysis but did not significantly increase after a third dose. Regarding memory B cell response, we detected receptor binding domain-specific memory B cells at similar proportions in virus-naive patients on dialysis and vaccinated controls after two doses. Moreover, a strong receptor binding domain-specific memory B cell expansion was observed after the third dose in virus-naive patients on dialysis (5.5-fold; P<0.001). However, in SARS-CoV-2-recovered patients on dialysis, antireceptor binding domain memory B cells remained unchanged after the third dose. CONCLUSIONS: The third dose of mRNA vaccine given within 6 months after the second dose boosts serologic and memory response in virus-naive patients but not in SARS-CoV-2-recovered patients on dialysis. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: COVID-19: SARS-CoV-2 Specific Memory B and T-CD4+ Cells (MEMO-COV2), NCT04402892.

Vaccination and COVID-19 Dynamics in Dialysis Patients.

BACKGROUND AND OBJECTIVES: Dialysis patients have a high mortality risk after coronavirus disease 2019 (COVID-19) and an altered immunologic response to vaccines, but vaccine clinical effectiveness remains unknown in this population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using Bayesian multivariable spatiotemporal models, we estimated the association between vaccine exposure and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) severe infections (with hospital admission) in dialysis patients from simultaneous incidence in the general population. For dialysis patients, cases were reported within the French end-stage kidney disease REIN registry from March 11, 2020, to April 29, 2021, and vaccine exposure (first dose) was reported in weekly national surveys since January 2021. Cases in the general population were obtained from the national exhaustive inpatient surveillance system (SI-VIC database), and vaccination coverage (first dose) was obtained from the national surveillance system (VAC-SI database). RESULTS: During the first wave, incidence in dialysis patients was approximately proportional to the general population. However, we showed a lower relative incidence for dialysis patients during the second wave (compared with that observed in nondialysis patients), suggesting an effect of prevention measures. Moreover, from the beginning of the vaccination rollout, incidence in dialysis patients was lower compared with predictions based on the first and second waves. Adding vaccination coverages in dialysis and nondialysis patients as predictors allowed the reported cases to be fit correctly (3685 predicted cases, 95% confidence interval, 3552 to 3816, versus 3620 reported). Incidence rate ratios were 0.37 (95% confidence interval, 0.18 to 0.71) for vaccine exposure in dialysis patients and 0.50 (95% confidence interval, 0.40 to 0.61) per 10% higher in vaccination coverage in the same-age general population, meaning that vaccine exposure in dialysis patients and the general population was independently associated with lower hospitalization rate of dialysis patients. CONCLUSIONS: Our findings suggest that vaccination may yield a protective effect against severe forms of COVID-19 in dialysis patients, despite altered immunologic vaccine responses.

Long-term impact of COVID-19 among maintenance haemodialysis patients.

BACKGROUND: Maintenance haemodialysis (MHD) patients have a high risk of initial mortality from coronavirus disease 2019 (COVID-19). However, long-term consequences of this disease in the MHD population are poorly described. We report the clinical presentation, outcome and long-term follow-up of MHD patients affected by COVID-19 in a multicentric cohort from the Paris, France area. METHODS: We conducted a retrospective analysis of clinical presentation and long-term follow-up of MHD patients affected by COVID-19 in 19 MHD centres in the Paris, France area. RESULTS: In this cohort of 248 patients with an initial mortality rate of 18%, age, comorbidities, dyspnoea and previous immunosuppressive treatment were associated with death at <30 days. Among the 203 surviving patients following the acute phase, long-term follow-up (median 180 days) was available for 189 (93%) patients. Major adverse events occurred in 30 (16%) patients during follow-up, including 12 deaths (6%) after a median of 78 days from onset of symptoms. Overall, cardiovascular events, infections and gastrointestinal bleeding were the main major adverse events. Post-COVID-19 cachexia was observed in 25/189 (13%) patients. Lower initial albuminaemia was significantly associated with this cachexia. No reinfection with severe acute respiratory syndrome coronavirus 2 was observed. CONCLUSIONS: This work demonstrates the long-term consequences of COVID-19 in MHD patients, highlighting both initial and long-term severity of the disease, including severe cachexia.

COVID-19 in dialysis: clinical impact, immune response, prevention, and treatment.

The COVID-19 pandemic has profound adverse effects on the population on dialysis. Patients requiring dialysis are at an increased risk of SARS-CoV-2 infection and mortality, and many have experienced psychological distress as well as delayed or suboptimal care. COVID-19 survivors have prolonged viral shedding, but generally develop a robust and long-lasting humoral immune response that correlates with initial disease severity. However, protection against reinfection is incomplete. A growing body of evidence reveals delayed and blunted immune responses to SARS-CoV-2 vaccination. Administration of a third dose within 1 to 2 months of prime-boost vaccination significantly increases antibody levels, in particular in patients with poor initial responses. Patients on dialysis have inferior immune responses to adenoviral vector vaccines than to mRNA vaccines. The immunogenicity of the mRNA-1273 vaccine is markedly better than that of the BNT162b2 vaccine, most likely by virtue of its higher mRNA content. Despite suboptimal immune responses in patients on dialysis, preliminary data suggest that vaccination partially protects against infection and severe disease requiring hospitalization. However, progressive waning of immunity and emergence of SARS-CoV-2 variants with a high potential of immune escape call for a booster dose in all patients on dialysis 4 to 6 months after prime-boost vaccination. Patients with persistent poor vaccine responses may be candidates for primary prophylaxis strategies. In the absence of specific data in patients on dialysis, therapeutic strategies in the event of established COVID-19 must be extrapolated from evidence obtained in the population not on dialysis. Neutralizing monoclonal antibodies may be an attractive option after a high-risk exposure or during the early course of infection.

[COVID-19 vaccination in dialysis and kidney transplant patients]. / Vaccination anti-COVID-19 chez les patients dialysés et transplantés rénaux.

Patients with end stage renal disease, including dialysis and kidney transplantation, have a high risk of severe COVID-19. In these populations, post-COVID-19 humoral response is prolonged until 6 months post-infection. However, post-vaccination humoral responses are frequently weak even when positive, notably in kidney transplant patients treated with belatacept. Actually, after 2 injectionos of mRNA vaccines, humoral response rates are 80-95% in dialysis patients, 30-50% in transplant patients, and about 5% in transplant patients treated with belatacept. These results have led to propose a 3rd injection of mRNA vaccine in dialysis and transplant patients in France. Numerous questions, regarding cellular responses, durability of response and clinical efficacy of vaccines remain in these high risk populations.

Case Report: Adult Post-COVID-19 Multisystem Inflammatory Syndrome and Thrombotic Microangiopathy.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide. A clinical series of Kawasaki-like multisystem inflammatory syndrome (MIS), occurring after SARS-CoV-2 infection, have been described in children (MIS-C) and adults (MIS-A), but the pathophysiology remains unknown. CASE PRESENTATION: We describe a case of post-COVID-19 MIS-A in a 46-year-old man with biopsy-proven renal thrombotic microangiopathy (TMA). Specific complement inhibition with eculizumab was initiated promptly and led to a dramatic improvement of renal function. CONCLUSION: Our case suggests that that TMA could play a central role in the pathophysiology of post-COVID-19 MIS-A, making complement blockers an interesting therapeutic option.

De Novo Focal and Segmental Glomerulosclerosis After COVID-19 in a Patient With a Transplanted Kidney From a Donor With a High-risk APOL1 Variant.

BACKGROUND: There is compelling evidence that renal complications in a native kidney are a major concern in patients infected with severe acute respiratory syndrome coronavirus 2, the causal agent of coronavirus disease 2019 (COVID-19). The spectrum of renal lesions observed on renal grafts in this context remains to be determined. METHODS: We report the case of a renal transplant recipient with non-severe COVID-19, who subsequently developed nephrotic syndrome associated with acute renal injury. RESULTS: Renal biopsy demonstrated focal and segmental glomerulosclerosis lesions classified as not otherwise specified histological variant. Genotyping for 2 risk alleles of the apolipoprotein L1 gene demonstrated that the donor was homozygous for the G2/G2 genotype. CONCLUSIONS: In renal transplant patients receiving kidneys from donors with high-risk apolipoprotein L1 variants, COVID-19 may promote acute glomerular injury in the form of focal and segmental glomerulosclerosis.

Kinetics of Anti-SARS-CoV-2 IgG Antibodies in Hemodialysis Patients Six Months after Infection.

BACKGROUND: The humoral response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the hemodialysis population, including its dynamics over time, remains poorly understood. METHODS: To analyze initial and long-term humoral responses against SARS-CoV-2 in a hemodialysis population, we retrospectively evaluated findings from SARS-CoV-2 IgG serologic assays targeting the nucleocapsid antigen or spike antigen up to 6 months of follow-up in patients on hemodialysis in the Paris, France, region who had recovered from coronavirus disease 2019 (COVID-19). RESULTS: Our analysis included 83 patients (median age 65 years); 59 (71%) were male and 28 (34%) had presented with severe COVID-19. We observed positive initial SARS-CoV-2 IgG antinucleocapsid serology in 74 patients (89%) at a median of 67 days postdiagnosis. By multivariable analysis, immunocompromised status was the only factor significantly associated with lack of an IgG antinucleocapsid antibody response. Follow-up data were available at 6 months postdiagnosis for 60 of 74 patients (81%) with positive initial antinucleocapsid serology, and 15 (25%) of them had negative antinucleocapsid serology at month 6. In total, 14 of 15 sera were tested for antispike antibodies, 3 of 14 (21%) of which were also negative. Overall, 97% of antinucleocapsid-antibody-positive specimens were also antispike-antibody positive. Female sex, age >70 years, and nonsevere clinical presentation were independently associated with faster IgG antinucleocapsid titer decay in multivariable analysis. After adjustment for sex and age >70 years, nonsevere clinical presentation was the only factor associated with faster decay of IgG antispike antibodies. CONCLUSIONS: This study characterizes evolution of the SARS-CoV-2 antibody response in patients on hemodialysis and identifies factors that are associated with lack of seroconversion and with IgG titer decay.