COVID­19 in patients requiring renal replacement therapy: an overview of current data and future challenges.

Patients with chronic kidney disease, especially those on renal replacement therapy, demonstrate increased incidence and mortality from COVID­ 19, as compared with the general population. One of the main reasons for this phenomenon is a dysfunction of the immune system associated with its accelerated aging, weakened immune functions, impaired regulation of proinflammatory reactions, chronic inflammation, and immunosuppressive therapy. Most of these patients have a high rate of comorbidities, which may also have a negative impact on the severity of COVID­ 19 and prognosis. Introduction of COVID 19 vaccines has significantly changed the course of the fight against the pandemic. Due to the very severe disease, in many countries the patients receiving renal replacement therapy were prioritized for vaccination right after health care professionals. Differences in the response to vaccination were noted, which required an individualized approach and modification of the vaccination program in this patient group. Difficulties in assessing these issues are due to the differences in the research methodology used in the available studies and their observational nature. Moreover, response to vaccination varied over time depending on the geographic region and variant of the virus causing the infection. The epidemiology was significantly influenced by the improved prevention methods and treatment of infections as well as the growing percentage of vaccinated and convalescent people. We present the most important differences in the epidemiology of COVID­ 19, the course of the disease, prognosis, and prevention, as well as the challenges associated with improving the prognosis in patients receiving renal replacement therapy.

COVID-19 vaccination reduces mortality in patients on maintenance hemodialysis

Patients with chronic kidney disease on maintenance hemodialysis (HD) have a very high risk of death in the course of COVID-19. The aim of the study was to assess the effectiveness of COVID-19 vaccination to reduce the incidence of COVID-19 and the fatality rate in HD patients. A retrospective registry-based cohort study was performed in all HD adult patients in the Pomeranian Voivodeship. Vaccinations were carried out from January to April 2021 with mRNA vaccines, either BNT162b2 or mRNA-1273 with two-dose schedule. In the first analysis (2nd pandemic wave), 1,160 unvaccinated patients were included (59.7% males, 25.7% diabetic). In the second analysis (4th pandemic wave), 1,131 (59.4% male, 30.7% diabetic) individuals were included, 1,042 (92.13%) were fully vaccinated. Three hundred and fifteen HD patients (27.2%) were COVID-19 positive during the 2nd wave, and 6.9% (78/1,131) during the 4th wave. Within the fully vaccinated patients of the 4th wave, 60 were COVID-19 positive, 5.8 vs. 20.2% of unvaccinated COVID-19 positive patients in 2nd wave, respectively. COVID-19 incidence rate ratio (IRR) was 0.21 (4th wave-vaccinated vs. 2nd wave-unvaccinated) indicating a 79% reduction. The IRR between vaccinated and unvaccinated patients of the 4th wave was 0.28 in favor of vaccinated patients with 72% reduction. In the 2nd wave, 93 patients died as a result of COVID-19 (fatality rate: 29.5%). The fatality rate of fully vaccinated patients during the 4th wave was 6.7% (p = 0.004), while the fatality rate in the 4th wave within unvaccinated patients accounted for 11.1%. Significant clinical effectiveness of COVID-19 vaccination was demonstrated in a multicenter study in HD patients.

Local and Systemic Immunity Are Impaired in End-Stage-Renal-Disease Patients Treated With Hemodialysis, Peritoneal Dialysis and Kidney Transplant Recipients Immunized With BNT162b2 Pfizer-BioNTech SARS-CoV-2 Vaccine.

Vaccination against COVID-19 in patients with end-stage renal disease (ESRD) on replacement therapy and kidney transplant recipients (KTRs) is particularly important due to the high mortality rate. Here, we tested the local and systemic immunity to the novel Pfizer BioNTech (BNT162b2) messenger RNA (mRNA) in ESRD, KTR patients, and healthy individuals (150 subjects). The ESRD group was divided into: hemodialysis (HD) and peritoneal dialysis (PD). We investigated the local and systemic immunity based on anti-N (nucleoprotein) and anti-S (spike1/2) Immunoglobulin A (IgA) and Immunoglobulin G (IgG) antibodies, respectively. Additionally, we performed an Interferon gamma (IFN-γ) release test Interferon-gamma release assay (IGRA) to monitor the cellular component of vaccine response. The control group had the highest level of anti-S IgG antibodies (153/2,080 binding antibody units (BAU)/ml) among all analyzed patients after the 1st and 2nd dose, respectively. The HD group (48/926 BAU/ml) had a diminished antibody level compared to PD (93/1,607 BAU/ml). Moreover, the seroconversion rate after the 1st dose was lower in HD than PD (56% vs. 86%). KTRs had extremely low seroconversion (33%). IgA-mediated immunity was the most effective in the control group, while other patients had diminished IgA production. We observed a lower percentage of vaccine responders based on the IFN-γ level in all research participants (100% vs. 85% in control, 100% vs. 80% in PD, 97% vs. 64% in HD). 63% of seropositive KTRs had a positive IGRA, while 28% of seronegative patients produced IFN-γ. Collectively, PD patients had the strongest response among ESRD patients. Two doses of the Pfizer vaccine are ineffective, especially in HD and KTRs. A closer investigation of ESRD and KTRs is required to set the COVID-19 vaccine clinical guidance. Clinical Trial Registration Number: www.ClinicalTrials.gov, identifier: NCT04 905 862.

Heterologous high dose SARS-CoV-2 mRNA vaccine booster may improve immune response in seronegative kidney transplant recipients.

Introduction: Three-dose mRNA vaccination against COVID-19 is unable to elicit a sufficient immune response in immunocompromised subjects. Methods: The aim of the study was to conduct a retrospective evaluation of the efficacy of a heterologous mRNA booster with mRNA-1273 in constantly seronegative kidney transplant recipients (KTRs) after three doses of the BNT162b2 mRNA vaccine. Twelve seronegative KTRs received a mRNA-1273 booster 5 months after the third dose of BNT162b2. Results: A total of 5 out of 12 patients (41.7%) seroconverted, with a mean titer of 353 BAU/ml. Conclusions: The administration of a heterologous mRNA vaccine as a booster may be an effective alternative for achieving post-vaccination immunity in seronegative KTRs.

Safety and Tolerability of mRNA COVID-19 Vaccines in Kidney Transplant Recipients.

BACKGROUND: COVID-19 mRNA vaccines have demonstrated excellent short-term safety in phase 3 trials. However, no kidney transplant recipients (KTR) were included. The aim of the study was to assess the safety and tolerability of COVID-19 mRNA vaccines in KTR. MATERIALS AND METHODS: A longitudinal controlled study was conducted in 300 KTR and 143 control patients (CRL) without chronic kidney disease who had received 2-dose vaccinations with the mRNA vaccine. Solicited local and systemic reactogenicity and unsolicited adverse events were assessed with a standardized questionnaire. The toxicity grading scales were derived from the FDA guidelines. RESULTS: KTR (62.7% men) with a median (interquartile range) age of 53 (41-63) and transplant vintage of 7.25 (3-13) years did not differ with respect to age and sex distribution from CRL. One hundred percent CRL and 83.3% KTR were vaccinated with BNT162b2 (BionTech/Pfizer); 16.7% KTR received mRNA-1273 (Moderna) vaccine. Any local reactions were present in 84.7% (first dose) and 65.3% (second dose) KTR vs 67.1% and 60.1% CRL within 7 days after the vaccination. Any systemic reactions were reported by 26.7% (first dose) and 20.9% (second dose) KTR vs 24.7 and 35.7% CRL. The most common systemic reactions in KTR were fatigue, headache and myalgia. No serious adverse events were observed. Many systemic reactions were observed less frequently in KTR than CRL. Younger KTR (<54 years) reported any local and any systemic reactions significantly more frequently than older patients. CONCLUSION: mRNA COVID-19 vaccines are safe and well-tolerated by KTR. The results may resolve patients' doubts and reduce their vaccine hesitancy.

Waning Humoral Response after COVID-19 mRNA Vaccination in Maintenance Dialysis Patients and Recovery after a Complementary Third Dose.

The aim of this study was to analyze the waning of anti-spike (S) antibodies after mRNA vaccination against COVID-19 in maintenance dialysis patients, and to assess the safety and effectiveness of the complementary third dose. This was a prospective, longitudinal study in which we analyzed the kinetics of antibodies up to six months after a two-dose vaccination (first protocol) in infection-naïve dialysis patients (IN-Ds), previously infected dialysis patients (PI-Ds) and subjects without chronic kidney disease (the controls), as well as their humoral response to the third dose of the same mRNA vaccine (second protocol). The respective reduction in antibody titer after 3 and 6 months by 82.9% and 93.03% in IN-Ds (n = 109), 73.4% and 93.36% in PI-Ds (n = 32) and 75.5% and 88.8% in the controls (n = 20) was demonstrated. Consequently, a protective antibody titer above 141 BAU/mL was found in only 47.7% and 23.8% of IN-Ds after 3 and 6 months, respectively. After the third vaccine dose, a significant increase in antibody titer was observed in all groups, with increases by a factor of ×51.6 in IN-Ds, ×30.1 in the controls and ×8.4 in PI-Ds. The median antibody titer after the third dose differed significantly between groups, and was the highest in PI-Ds: PI-Ds, 9090 (3300-15,000) BAU/mL; the controls, 6945 (2130-11,800); IN-Ds, 3715 (1470-7325) (p < 0.001). In conclusion, we observed similar degrees of antibody waning in all patients. After 3 months, over half of the infection-naïve dialysis patients had a very low antibody titer, and almost twenty percent of them had no antibodies at all. The humoral response to the third dose was very good, raising their titer of antibodies to a higher level than those in the general population who have received the primary two-dose scheme. The results support the administration of a complementary third dose of the mRNA vaccine for dialysis patients as soon as possible.

Changes in Kidney Graft Function in COVID-19 Convalescents.

BACKGROUND: Kidney transplant recipients (KTRs) are at an increased risk of infection with severe acute respiratory syndrome coronavirus 2, with mortality from 13% to over 30%. However, data concerning the influence of COVID-19 on long-term graft function in convalescents is lacking. The aim of this study was to evaluate the influence of COVID-19 on graft function at 6 months after recovery. METHODS: A longitudinal controlled study was conducted in a group of 1058 KTRs. Of 180 patients with COVID-19 in the past, 77 KTRs (45 male) with a mean age 50.57 ± 13.37 years, Charlson Comorbidity Index of 3 (median; interquartile range [IQR], 3-5), Fragility Score of 3 (median; IQR, 3-3), and minimum 6 months after acute COVID-19 were included. The most common symptoms were weakness (75.33%), fever (74.03%), cough (51.95%), and loss of appetite (48.05%). Thirty-three patients were hospitalized; none required invasive ventilation therapy, but 16 required oxygen support. The treatment of COVID-19 included antibiotics (38.96%), thromboprophylaxis (25.97%), and nonsteroidal anti-inflammatory drugs, or paracetamol (25.97%). RESULTS: The median (IQR) values of serum creatinine 3 months before the onset and 6 months after COVID-19 were 1.25 (0.98-1.86) and 1.26 (1.03-1.78) mg/dL (nonsignificant difference); in strata analysis, there were also no differences with regards to patients with higher and lower comorbidity (3 < Charlson Comorbidity Index < 3) and fragility (3 < Fragility Score < 3). Furthermore, creatinine concentration in KTRs and controls did not differ. CONCLUSIONS: In the group of KTRs with a mild course of COVID-19, no negative impact of the infection on graft function was observed 6 months after transplantation.

Angiotensin Converting Enzyme Inhibitors May Increase While Active Vitamin D May Decrease the Risk of Severe Pneumonia in SARS-CoV-2 Infected Patients with Chronic Kidney Disease on Maintenance Hemodialysis.

The group most at risk of death due to COVID-19 are patients on maintenance hemodialysis (HD). The study aims to describe the clinical course of the early phase of SARS-CoV-2 infection and find predictors of the development of COVID-19 severe pneumonia in this population. This is a case series of HD nonvaccinated patients with COVID-19 stratified into mild pneumonia and severe pneumonia group according to the chest computed tomography (CT) pneumonia total severity score (TSS) on admission. Epidemiological, demographic, clinical, and laboratory data were obtained from hospital records. 85 HD patients with a mean age of 69.74 (13.19) years and dialysis vintage of 38 (14-84) months were included. On admission, 29.14% of patients had no symptoms, 70.59% reported fatigue followed by fever-44.71%, shortness of breath-40.0%, and cough-30.59%. 20% of the patients had finger oxygen saturation less than 90%. In 28.81% of patients, pulmonary parenchyma was involved in at least 25%. The factors associated with severe pneumonia include fever, low oxygen saturation and arterial partial pressure of oxygen, increased C-reactive protein and ferritin serum levels, low blood count of lymphocytes as well as chronic treatment with angiotensin converting enzyme inhibitors; while the chronic active vitamin D treatment was associated with mild pneumonia. In conclusion, even though nearly one-third of the patients were completely asymptomatic, while the remaining usually reported only single symptoms, a large percentage of them had extensive inflammatory changes at diagnosis with SARS-CoV-2 infection. We identified potential predictors of severe pneumonia, which might help individualize pharmacological treatment and improve clinical outcomes.

Predictors of Mortality in Hemodialyzed Patients after SARS-CoV-2 Infection.

INTRODUCTION: The determinants of COVID-19 mortality are well-characterized in the general population. Less numerous and inconsistent data are among the maintenance hemodialysis (HD) patients, who are the population most at risk of an unfavorable prognosis. METHODS: In this retrospective cohort study we included all adult HD patients from the Pomeranian Voivodeship, Poland, with laboratory-confirmed SARS-CoV-2 infection hospitalized between 6 October 2020 and 28 February 2021, both those who survived, and also those who died. Demographic, clinical, treatment, and laboratory data on admission, were extracted from the electronic medical records of the dedicated hospital and patients' dialysis unit, and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with 3-month all-cause mortality. RESULTS: The 133 patients (53.38% males) aged 73.0 (67-79) years, with a median duration of hemodialysis of 42.0 (17-86) months, were included in this study. At diagnosis, the majority were considered to have a mild course (34 of 133 patients were asymptomatic, another 63 subjects presented mild symptoms), while 36 (27.07%) patients had low blood oxygen saturation and required oxygen supplementation. Three-month mortality was 39.08% including an in-hospital case fatality rate of 33.08%. Multivariable logistic regression showed that the frailty clinical index of 4 or greater (OR 8.36, 95%CI 1.81-38.6; p < 0.01), D-Dimer of 1500 ng/mL or greater (6.00, 1.94-18.53; p < 0.01), and CRP of >118 mg/L at admission (3.77 1.09-13.01; p = 0.04) were found to be predictive of mortality. CONCLUSION: Very high 3-month all-cause mortality in hospitalized HD patients was determined mainly by frailty. High CRP and D-dimer levels upon admission further confer mortality risk.

Analysis of Experiences in Preventing COVID-19 in Hemodialysis Centers of the North of Poland before the Era of Vaccination.

BACKGROUND: The appearance of very contagious SARS-CoV-2 variants and waning vaccine immunity may indicate the need to return to using universal methods of preventing the spread of COVID-19. METHODS: We performed a multicenter retrospective cohort survey study to describe the methods used in dialysis units to prevent and control the spread of SARS-CoV-2 and also the association between these methods and the incidence of COVID-19 among hemodialyzed (HD) patients before the era of vaccination. The study population included all maintenance HD patients (n = 1569) in 14 dialysis units in the Pomeranian Voivodeship. RESULTS: The group of 352 patients (199 men, 153 female) were confirmed for COVID-19. The absolute cumulative incidence in the studied period was 22.4%. It varied widely by dialysis units, ranging from 9.4% to 36.9%. Universal preventive methods were applied by all units. Different additional methods were implemented in some stations with varying frequency (36-86%). In order to quantify the scale of the applied additional preventive methods, we calculated a summary prevention index (PI), i.e., one point for one additional method. Lower incidence was found in centers applying dialysis in isolation of patients hospitalized due to diseases requiring hospitalization (17.42% ± 6.89 vs. 26.54 ± 6.34; p = 0.028) and higher incidence in medium-size dialysis centers (ANOVA F: p = 0.017). Significant inverse correlation between PI and incidence was demonstrated as well (r = -0.759; p = 0.002). CONCLUSIONS: The higher the number of implemented preventive measures, the lower the risk of COVID-19 infection in HD patients. Among applied procedures the isolation of hospitalized patients is of significant importance. The measures proved to be effective in prevention before the vaccination era should be continued, as the threat of SARS-CoV-2 still exists.

Boosting Humoral Immunity from mRNA COVID-19 Vaccines in Kidney Transplant Recipients.

Introduction: The immune response to the primary (two-dose) series of mRNA COVID-19 vaccines in kidney transplant recipients (KTRs) is very weak. We conducted a longitudinal observational study to compare the humoral response to a third, additional primary dose of mRNA vaccines between infection-naïve (IN-KTRs) and previously infected KTRs (PI-KTRs). Methods: We measured the levels of anti-spike (anti-s) IgG antibodies before and 14-21 days after the third dose and, in the secondary analysis, we compared the antibody response to BNT162b2 versus mRNA-1273. The reactogenicity assessment included solicited local and systemic reactions. Results: A total of 112 KTRs were enrolled, including 83 IN-KTR and 29 PI-KTR, among whom seroconversion in anti-s antibodies after the primary two-dose vaccination was achieved in 45.78% and 100% of cases, respectively. After three months, a waning antibodies titer by 67.4% (IN-KTR) and 7.5% (PI-KTR) was observed. After the third dose of the mRNA vaccine, 71.08% (59/83) of IN-KTR and 96.5% (28/29) of PI-KTR samples were seroconverted with a median anti-s titer of 468.0 (195.0-1620.0) BAU/mL and 1629.0 (1205-1815) BAU/mL, respectively. Of those IN-KTR in whom the primary vaccination failed, 46.67% (21/45) of patients achieved seroconversion after the third dose. No serious adverse events after the third dose were reported. In strata analyses, after the third dose, 66% (40/60) of patients vaccinated with BNT162b2 and 82.6% (19/23) of patients vaccinated with mRNA-1273 seroconverted with a median anti-s titer of 384.5 (144-837) BAU/mL and 1620 (671-2040) BAU/mL, respectively. Conclusions: The use of a third dose of mRNA vaccine may be of benefit for KTR, especially for those in whom the primary vaccination failed. Vaccines with a higher dose of mRNA and a longer interval between doses of the primary vaccination, such as mRNA-1273, seem to be the preparations of choice in immunocompromised individuals.

Post-COVID-19 Sydrome and Decrease in Health-Related Quality of Life in Kidney Transplant Recipients after SARS-COV-2 Infection-A Cohort Longitudinal Study from the North of Poland.

INTRODUCTION: Patients after SARS-CoV-2 infection frequently face "Post-COVID-19 Syndrome", defined by symptoms that develop during or after COVID-19, continue for more than 12 weeks, and are not explained by an alternative diagnosis. We aimed to evaluate the presence of post-COVID-19 syndrome and its predictors in kidney transplant recipients (KTR) 6 months after the disease. MATERIALS AND METHODS: A total of 67 KTR (38 m) with a mean age of 53.6 ± 14 years, 7.3 ± 6.4 years post-transplant were included in the cohort longitudinal study. Thirty-nine (58.2%) of them were hospitalized, but not one required invasive ventilation therapy. They were interviewed 6 months after being infected, with a series of standardized questionnaires: a self-reported symptoms questionnaire, the modified British Medical Research Council (mMRC) dyspnea scale, EQ-5D-5L questionnaire, and EQ-VAS scale. RESULTS: Post-COVID-19 syndrome was diagnosed in 70.1% of KTR and 26.9% of them reported at least three persistent symptoms. The most common symptoms were fatigue (43.3%), hair loss (31.3%), memory impairment (11.9%), muscle aches, and headaches (11.9%). Dyspnea with an mMRC scale grade of at least 1 was reported by 34.3% patients vs. 14.9% before infection; 47.8% stated that they still feel worse than before the disease. Mean EQ-VAS scores were 64.83 vs. 73.34 before infection. The persistent symptoms are more frequent in older patients and those with greater comorbidity. CONCLUSIONS: Persistent symptoms of post-COVID-19 syndrome are present in the majority of KTR, which highlights the need for long-term follow-up as well as diagnostic and rehabilitation programs.

Predictors of Humoral Response to mRNA COVID19 Vaccines in Kidney Transplant Recipients: A Longitudinal Study-The COViNEPH Project.

BACKGROUND: The efficacy of SARS-CoV-2 vaccination among kidney transplant recipients (KTR) is low. The main goal of this study was to analyze factors that may influence the humoral response to vaccination. METHODS: We analyzed the titer magnitude of IgG antibodies directed against spike (S)-SARS-CoV-2 antigen after the second dose of the mRNA vaccine in 142 infection naïve KTR (83 men, i.e., 58.4%) with a median age (IQR) of 54 (41-63), and 36 respective controls without chronic kidney disease. mRNA-1273 or BNT162b2 were applied in 26% and 74% of KTR, respectively. RESULTS: S-specific immune response (seroconversion) was seen in 73 (51.41%) of KTR, and in all controls 36 (100%). Independent predictors of no response were elder age, shorter transplantation vintage, and a more than two-drug immunosuppressive protocol. In subgroup analyses, the seroconversion rate was highest among KTR without MMF/MPS treatment (70%), treated with no more than two immunosuppressants (69.2%), treated without corticosteroid (66.7%), younger patients aged <54 years (63.2%), and those vaccinated with the mRNA-1273 vaccine (62.16%). The independent predictors of higher S-antibody titer among responders were younger age, treatment with no more than two immunosuppressants, and the mRNA-1273 vaccination. CONCLUSIONS: Our study confirmed a low rate of seroconversion after vaccination with the mRNA vaccine in KTR. The major modifiable determinants of humoral response were the composition of the immunosuppressive protocol, as well as the type of vaccine. The latter could be taken into consideration when initial vaccination as well as booster vaccination is considered in KTR.

Persistent Post-COVID-19 Syndrome in Hemodialyzed Patients-A Longitudinal Cohort Study from the North of Poland.

BACKGROUND: After recovery from COVID-19, patients frequently face so-called "Post-COVID-19 Syndrome" defined by clusters of persistent symptoms lasting for >12 weeks which may arise from any system in the body. The long-term health consequences of COVID-19 in maintenance hemodialyzed (HD) patients remain to be investigated. METHODS: In this longitudinal cohort study we described the health consequences in HD patients requiring hospitalization due to COVID-19. They were interviewed three and six months (M3 and M6) after discharge with a series of standardized questionnaires. RESULTS: Of 144 HD patients discharged from the 7th Naval Hospital in Gdansk, 79 participants were enrolled, 39 m (49.4%) and 40 f (50.6%) with a median age of 70.0 (64.0-76.5) and an HD vintage of 40 months (17.5-88). After discharge, 93.7% and 81% reported at least one persistent symptom at M3 and M6, respectively. The most common symptoms were fatigue or muscle weakness (60.76% and 47.04%) and palpitations (40.51% and 30.14%). Dyspnea with an mMRC scale grade of at least 1 was reported by 21.5% before infection, and by 43.03% and 34.25% at M3 and M6, respectively. A decrease in the quality of life was reported in all domains of the EQ-5D-5L questionnaire but mainly in the pain/discomfort and anxiety dimensions. Mean EQ-VAS scores were 69.05, 61.58 and 64.38, respectively. CONCLUSION: Our study showed that HD patients may still experience persistent symptoms six months after recovery from COVID-19, which can further reduce their already poor health-related quality of life. This study highlights the need for long-term follow-up on these patients for diagnostic and rehabilitation programs.

Extremely high mortality rates among hemodialysis patients with COVID-19 before the era of SARS-CoV-2 vaccination: results from a large database from the North of Poland.

INTRODUCTION: Preliminary reports suggested high incidence and mortality rates of SARS­ CoV 2 infection in patients receiving kidney replacement therapy. OBJECTIVES: We aimed to describe the incidence and outcomes of COVID­ 19 in hemodialysis patients. PATIENTS AND METHODS: We conducted a retrospective multicenter cohort study on the incidence and mortality of COVID­ 19 in hemodialysis patients as compared with the general adult population in the period from the beginning of the pandemic until the commencement of the SARS­ CoV 2 vaccination program. The study population included all patients who were receiving hemodialysis in any of the 14 dialysis units of Pomerania Province, Poland on December 31, 2019 and all individuals who were starting long­ term hemodialysis between January 1, 2020 and January 31, 2021, amounting to a total of 1567 patients. Data on the general population were obtained from reports of the health authorities. RESULTS: The absolute cumulative incidence of SARS­ CoV 2 infection in hemodialysis patients was 22.4%, and after standardization for age it was 3.98-fold higher compared with the general population (P <0.001). The epidemic trajectory of both groups ran in parallel, but the increase and decline in the number of new cases occurred earlier in hemodialysis patients. The fatality rate of COVID­ 19 among hemodialysis patients was 30.4%. It was the highest among the oldest patients, reaching 43.81% in individuals aged 75 years or older (P = 0.003). Age­ standardized fatality and mortality rates in hemodialysis patients were 5.5- and 10.9-fold higher than in controls, respectively (both P <0.001). CONCLUSIONS: The results of this study show the extremely high mortality rate of COVID­ 19 in hemodialysis patients during the first and second waves of the epidemic in Pomerania Province, before the vaccination era.

Humoral response to SARS-CoV-2 vaccination promises to improve the catastrophic prognosis of hemodialysis patients as a result of COVID-19: the COViNEPH Project.

Introduction: There is an urgent need to check the efficacy of SARS-CoV-2 vaccination among hemodialysis patients who are known to have large abnormalities of acquired immunity and a catastrophic risk of death from COVID-19. Objectives: In this cross-sectional study, we aimed to assess the humoral response following vaccination with the BNT162b2 (BioNTech / Pfizer Comirnaty) vaccine. Patients and methods: We analyzed the titer magnitude of the IgG antibodies directed against SARS-CoV-2 spike antigen 14 to 21 days after the second dose of the BNT162b2 vaccine in a group of hemodialysis patients who have not been confirmed with SARS-CoV-2 infection yet, compared with HD patients with a history of COVID-19. A total of 126 hemodialysis patients were stratified based on evidence of a previous infection with SARS-CoV-2 confirmed by the detection of viral RNA or nucleocapsid-specific IgG antibodies. Results: S-antigen immune response with a median (interquartile range) antibody titer of 366 (193­691) AU/ml was seen in 87 of 91 infection-naïve hemodialysis patients (95.6%), and in 68 (74.7%), a strong humoral response was observed with an anti-S antibodies titer greater than 200 AU/ml. Older patients were less likely to develop a response to S-antibodies (P <⁠0.001). The median (interquartile range) S-antigen antibody titer in 35 previously infected hemodialysis patients was over 12-fold higher than in infection-naïve hemodialysis patients: 4620 (1240­7820) AU/ml (P <⁠0.001). There were no significant differences in S-antibody titer between symptomatic and asymptomatic previously infected hemodialysis patients. Conclusions: Our study demonstrated that the majority of hemodialysis patients achieved a high immunization rate after vaccination with BNT162b2. Whether this translates into protecting this population from COVID-19 requires further research.

Safety and Tolerability of the BNT162b2 mRNA COVID-19 Vaccine in Dialyzed Patients. COViNEPH Project.

Background and Objectives: The Pfizer-BioNTech (BNT162b2) COVID-19 mRNA vaccine has demonstrated excellent efficacy and safety in phase 3 trials. However, no dialyzed patients were included, and therefore safety data for this patient group is lacking. The aim of the study was to assess the safety and tolerances of vaccinations with BNT162b2 performed in chronically dialyzed patients. Materials and Methods: We performed a prospective cohort study including a group of 190 dialyzed patients (65% male) at median age 68.0 (55-74) years. 169 (89.0%) patients were treated with hemodialysis and 21 (11.0%) with peritoneal dialysis. The control group consisted of 160 people (61% male) without chronic kidney disease at median age 63 (range 53-77) years. Both groups were vaccinated with BNT162b2 with a 21-day interval between the first and the second dose. Solicited local and systemic reactogenicity, unsolicited adverse events and antipyretic and pain medication use were assessed with a standardized questionnaire. The toxicity grading scales were derived from the FDA Center for Biologics Evaluation and Research guidelines. Results: 59.8% (dose 1), 61.4% (dose 2) and 15.9% (dose 1), 29.4% (dose 2) dialyzed patients reported at least one local and one systemic reaction respectively within seven days after the vaccination. Many local and systemic solicited reactions were observed less frequently in dialyzed patients than in the age and sex matched control group and much less frequently than reported in the pivotal study. They were mostly mild to moderate, short-lived, and more frequently reported in younger individuals and women. No related unsolicited adverse events were observed. Conclusions: We have shown here that BNT162b2, an mRNA vaccine from Pfizer-BioNTech against SARS-COV-2 is safe and well-tolerated by dialyzed patients. The results can be useful for the nephrological community to resolve patients' doubts and reduce their vaccine hesitancy.