SARS-CoV-2 Vaccine Effectiveness and Breakthrough Infections Among Patients Receiving Maintenance Dialysis.

RATIONALE & OBJECTIVE: SARS-CoV-2 vaccine effectiveness and immunogenicity threshold associated with protection against COVID-19 related hospitalization or death in the dialysis population is unknown. STUDY DESIGN: Retrospective, observational study. SETTING & PARTICIPANTS: Adult patients receiving maintenance dialysis through a national dialysis provider without COVID-19 history treated between February 1, 2021 and December 18, 2021 with follow up through January 17, 2022. PREDICTOR(S): SARS-CoV-2 vaccination status. OUTCOME(S): All SARS-CoV-2 infections, composite of hospitalization or death following COVID-19. ANALYTICAL APPROACH: Logistic regression was used to determine COVID-19 case rates and vaccine effectiveness. RESULTS: Of 16,213 patients receiving dialysis during the study period, 12,278 (76%) were fully vaccinated, 589 (4%) were partially vaccinated and 3,346 (21%) were unvaccinated by the end of follow-up. Of 1,225 COVID-19 cases identified, 550 (45%) occurred in unvaccinated patients, while 891 (73%) cases occurring during the Delta period. Between pre-Delta period and Delta periods vaccine effectiveness against a severe COVID-19 related event (hospitalization or death) was 84% and 70%, respectively. In the subset of 3,202 vaccinated patients with at least one anti-spike IgG assessment, lower anti-spike IgG levels were associated with higher case rates per 10,000 days and adjusted hazard ratios for both infection and COVID-related hospitalization or death. LIMITATIONS: Observational design, residual biases and confounding may exist. CONCLUSIONS: Among maintenance dialysis patients, SARS-CoV-2 vaccination was associated with a lower risk of COVID-19 diagnosis and associated hospitalization or death. Among vaccinated patients, low anti-spike IgG level is associated with worse COVID-19 related outcomes.

Immunogenicity of SARS-CoV-2 Vaccine in Dialysis.

BACKGROUND: Patients receiving maintenance dialysis represent a high-risk, immune-compromised population with 15%-25% COVID-19 mortality rate who were unrepresented in clinical trials of mRNA vaccines. METHODS: All patients receiving maintenance dialysis who received two doses of SARS-CoV-2 mRNA vaccines with antibody test results drawn ≥14 days after the second dose, as documented in the electronic health record through March 18, 2021, were included. Response was on the basis of levels of Ig-G against the receptor binding domain of the S1 subunit of SARS-CoV-2 spike-antigen (seropositive ≥2 U/L) using an FDA-approved semiquantitative chemiluminescent assay (ADVIA Centaur XP/XPT COV2G). RESULTS: Among 186 patients on dialysis from 30 clinics in eight states tested 23±8 days after receiving two vaccine doses, there were 165 (88.7%) responders with 70% at maximum titer. There was no significant difference between BNT162b2/Pfizer (148 out of 168, 88.1%) and mRNA-1273/Moderna (17 out of 18, 94.4%), P=0.42. All 38 patients with COVID-19 history were responders, with 97% at maximum titer. Among patients without COVID-19, 127 out of 148 (85.8%) were responders, comparable between BNT162b2/Pfizer (113 out of 133) and mRNA-1273/Moderna (14 out of 15) vaccines (85.0% versus 93.3%, P=0.38). CONCLUSIONS: Most patients receiving maintenance dialysis responded after two doses of BNT162b2/Pfizer or mRNA-1273/Moderna vaccine, suggesting the short-term development of antispike antibody is good, giving hope that most of these patients who are vulnerable, once immunized, will be protected from COVID-19. Longer-term evaluation is needed to determine antibody titer durability and if booster dose(s) are warranted. Further research to evaluate the approach to patients without a serologic response is needed, including benefits of additional dose(s) or administration of alternate options.

Seroresponse to SARS-CoV-2 Vaccines among Maintenance Dialysis Patients over 6 Months.

BACKGROUND AND OBJECTIVES: Although most patients receiving maintenance dialysis exhibit initial seroresponse to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, concerns exist regarding the durability of this antibody response. This study evaluated seroresponse over time. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study included patients on maintenance dialysis, from a midsize national dialysis provider, who received a complete SARS-CoV-2 vaccine series and had at least one antibody titer checked after full vaccination. IgG spike antibodies (anti-spike IgG) titers were assessed monthly with routine laboratory tests after vaccination; the semiquantitative assay reported a range between zero and ≥20 Index. Descriptive analyses compared trends over time by history of coronavirus disease 2019 (COVID-19) and vaccine type. Time-to-event analyses examined the outcome of loss of seroresponse (anti-spike IgG <1 Index or development of COVID-19). Cox regression adjusted for additional clinical characteristics. RESULTS: Among 1870 patients receiving maintenance dialysis, 1569 had no prior COVID-19. Patients without prior COVID-19 had declining titers over time. Among 443 recipients of BNT162b2 (Pfizer), median (interquartile range) anti-spike IgG titer declined from ≥20 (5.89 to ≥20) in month 1 after full vaccination to 1.96 (0.60-5.88) by month 6. Among 778 recipients of mRNA-1273 (Moderna), anti-spike IgG titer declined from ≥20 (interquartile range, ≥20 to ≥20) in month 1 to 7.99 (2.61 to ≥20) by month 6. The 348 recipients of Ad26.COV2.S (Janssen) had a lower titer response than recipients of an mRNA vaccine over all time periods. In time-to-event analyses, recipients of Ad26.COV2.S and mRNA-1273 had the shortest and longest time to loss of seroresponse, respectively. The maximum titer reached in the first 2 months after full vaccination was associated with durability of the anti-spike IgG seroresponse; patients with anti-spike IgG titer 1-19.99 had a shorter time to loss of seroresponse compared with patients with anti-spike IgG titer ≥20 (hazard ratio, 15.5; 95% confidence interval, 11.7 to 20.7). CONCLUSIONS: Among patients receiving maintenance dialysis, vaccine-induced seroresponse wanes over time across vaccine types. Early titers after full vaccination are associated with the durability of seroresponse.

Kidney Recovery and Death in Critically Ill Patients With COVID-19-Associated Acute Kidney Injury Treated With Dialysis: The STOP-COVID Cohort Study.

RATIONALE & OBJECTIVE: Acute kidney injury treated with kidney replacement therapy (AKI-KRT) occurs frequently in critically ill patients with coronavirus disease 2019 (COVID-19). We examined the clinical factors that determine kidney recovery in this population. STUDY DESIGN: Multicenter cohort study. SETTING & PARTICIPANTS: 4,221 adults not receiving KRT who were admitted to intensive care units at 68 US hospitals with COVID-19 from March 1 to June 22, 2020 (the "ICU cohort"). Among these, 876 developed AKI-KRT after admission to the ICU (the "AKI-KRT subcohort"). EXPOSURE: The ICU cohort was analyzed using AKI severity as the exposure. For the AKI-KRT subcohort, exposures included demographics, comorbidities, initial mode of KRT, and markers of illness severity at the time of KRT initiation. OUTCOME: The outcome for the ICU cohort was estimated glomerular filtration rate (eGFR) at hospital discharge. A 3-level outcome (death, kidney nonrecovery, and kidney recovery at discharge) was analyzed for the AKI-KRT subcohort. ANALYTICAL APPROACH: The ICU cohort was characterized using descriptive analyses. The AKI-KRT subcohort was characterized with both descriptive analyses and multinomial logistic regression to assess factors associated with kidney nonrecovery while accounting for death. RESULTS: Among a total of 4,221 patients in the ICU cohort, 2,361 (56%) developed AKI, including 876 (21%) who received KRT. More severe AKI was associated with higher mortality. Among survivors, more severe AKI was associated with an increased rate of kidney nonrecovery and lower kidney function at discharge. Among the 876 patients with AKI-KRT, 588 (67%) died, 95 (11%) had kidney nonrecovery, and 193 (22%) had kidney recovery by the time of discharge. The odds of kidney nonrecovery was greater for lower baseline eGFR, with ORs of 2.09 (95% CI, 1.09-4.04), 4.27 (95% CI, 1.99-9.17), and 8.69 (95% CI, 3.07-24.55) for baseline eGFR 31-60, 16-30, ≤15 mL/min/1.73 m2, respectively, compared with eGFR > 60 mL/min/1.73 m2. Oliguria at the time of KRT initiation was also associated with nonrecovery (ORs of 2.10 [95% CI, 1.14-3.88] and 4.02 [95% CI, 1.72-9.39] for patients with 50-499 and <50 mL/d of urine, respectively, compared to ≥500 mL/d of urine). LIMITATIONS: Later recovery events may not have been captured due to lack of postdischarge follow-up. CONCLUSIONS: Lower baseline eGFR and reduced urine output at the time of KRT initiation are each strongly and independently associated with kidney nonrecovery among critically ill patients with COVID-19.

COVID-19 Among US Dialysis Patients: Risk Factors and Outcomes From a National Dialysis Provider.

RATIONALE & OBJECTIVE: During the coronavirus disease 2019 (COVID-19) pandemic, patients receiving maintenance dialysis are a highly vulnerable population due to their comorbidities and circumstances that limit physical distancing during treatment. This study sought to characterize the risk factors for and outcomes following COVID-19 in this population. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Maintenance dialysis patients in clinics of a midsize national dialysis provider that had at least 1 patient who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from February to June 2020. PREDICTORS: Demographics, dialysis characteristics, residence in a congregated setting, comorbid conditions, measurements of frailty, and use of selected medications. OUTCOMES: COVID-19, defined as having a positive SARS-CoV-2 test result, and all-cause mortality among those with COVID-19. ANALYTICAL APPROACH: Logistic regression analyses conducted to identify clinical characteristics associated with COVID-19 and risk factors associated with mortality among patients following COVID-19. RESULTS: 438 of 7948 (5.5%) maintenance dialysis patients developed COVID-19. Male sex, Black race, in-center dialysis (vs home dialysis), treatment at an urban clinic, residence in a congregate setting, and greater comorbidity were associated with contracting COVID-19. Odds of COVID-19 were 17-fold higher for those residing in a congregated setting (odds ratio [OR], 17.10 [95% CI, 13.51-21.54]). Of the 438 maintenance dialysis patients with COVID-19, 109 (24.9%) died. Older age, heart disease, and markers of frailty were associated with mortality. LIMITATIONS: No distinction was detected between symptomatic and asymptomatic SARS-CoV-2 positivity, with asymptomatic screening limited by testing capacity during this initial COVID-19 surge period. CONCLUSIONS: COVID-19 is common among patients receiving maintenance dialysis, particularly those residing in congregate settings. Among maintenance dialysis patients with COVID-19, mortality is high, exceeding 20%.

COVID-19 in dialysis patients: outlasting and outsmarting a pandemic.

Coronavirus disease 2019 (COVID-19) has affected the care and outcomes of patients treated with dialysis worldwide. In this issue of Kidney International, 3 reports highlight the disproportionately severe impact of COVID-19 on patients on dialysis, noting its high prevalence, particularly among patients receiving in-center dialysis. This likely reflects patients' limited ability to physically distance as well as community exposures, including residence in areas with high rates of infection. Patients on dialysis are at extremely high risk should they develop COVID-19, with short-term mortality of 20% or higher. Accordingly, it is imperative that the kidney community intervenes to reduce the threat of COVID-19 in this vulnerable population by focusing on modifiable factors, including universal masking of patients and staff and enhanced screening, including testing for COVID-19 in the patients who are asymptomatic during times of high local prevalence.