key: cord-0951158-ki9hqdv8
authors: Hsu, Caroline M.; Weiner, Daniel E.; Aweh, Gideon N.; Manley, Harold J.; Ladik, Vladimir; Frament, Jill; Miskulin, Dana; Argyropoulos, Christos; Abreo, Kenneth; Chin, Andrew; Gladish, Reginald; Salman, Loay; Johnson, Doug; Lacson, Eduardo K.
title: Seroresponse to SARS-CoV-2 Vaccines Among Maintenance Dialysis Patients
date: 2021-11-07
journal: Am J Kidney Dis
DOI: 10.1053/j.ajkd.2021.10.002
sha: c3ee63b89e2fa648e493e3f7fe255f506c196af1
doc_id: 951158
cord_uid: ki9hqdv8

nan

As of October 2021, three vaccines against SARS-CoV-2 are available in the United States, all of which appear highly effective in the general population. Studies to date suggest high seroresponse to mRNA vaccines among maintenance dialysis patients, albeit lower than that in the general population. [1] [2] [3] [4] [5] [6] Data regarding adenoviral vector vaccines and predictors of vaccine non-response are limited by small sample sizes. 7 Accordingly, we retrospectively analyzed seroresponse to SARS-CoV-2 vaccines among maintenance dialysis patients, updating an earlier report. 8 Dialysis Clinic, Inc. (DCI) is a national not-for-profit provider caring for more than 15,000 patients at 260 outpatient dialysis clinics across 29 states. Beginning in January 2021, DCI physicians had the option of activating a SARS-CoV-2 vaccine protocol, in which anti-spike immunoglobulin G (SAb-IgG) antibodies were drawn monthly with routine labwork (details in the Supplement). Demographic and clinical data, vaccination dates, and SAb-IgG titer results were obtained from the DCI electronic health record. Patients with previously diagnosed COVID-19 or positive SAb-IgG titer before vaccination or within 10 days after first vaccine dose were excluded from this report.

In primary analyses, seroresponse was defined by at least one SAb-IgG titer ≥1 U/L at 14 to 74 days after completion of a vaccine series. Because SAb-IgG antibody titers were drawn alongside monthly labs, most patients have two assessments in this 60-day period. The association of demographic and clinical factors with vaccine seroresponse was analyzed using multivariable log Poisson regression with robust variances. Secondary analyses used alternate definitions of vaccine seroresponse: (1) having at least one SAb-IgG titer ≥2 U/L at 14 to 74 days after completion of a vaccine series, and (2) having a SAb-IgG titer ≥1 U/L on the first assessment at least 14 days after completion of a vaccine series. This study was reviewed and approved by the WCG IRB (Work Order 1-1456342-1) with exemption for informed consent. Statistical analyses were performed using SAS v9. 4 Ad26.COV2.S/Janssen recipients) across 130 dialysis facilities had SAb-IgG titers measured after receiving SARS-CoV-2 vaccination. Baseline characteristics were similar to those of the broader DCI vaccinated patient population. Between 14 and 74 days after completion of the vaccine series, 437 (29%), 946 (62%), and 145 (9%) had one, two, and more than two titers checked, respectively. Patients who received BNT162b2/Pfizer tended to be older (Table) .

Vaccine seroresponse occurred in 87% of BNT162b2/Pfizer recipients, 96% of mRNA-1273/Moderna recipients, and 37% of Ad26.COV2.S/Janssen recipients (Table S1). Patients without seroresponse were assumed to maintain the absence of seroresponse between the last titer assessment and the 74 th day after completion of a vaccine series. Among those without seroresponse, median [IQR] time from last titer and the 74 th day after completion of a vaccine series was 19.5 [12-29], 24.5 [12-34], and 16 [9-20] days for BNT162b2/Pfizer, mRNA-1273/Moderna, and Ad26.COV2.S/Janssen recipients, respectively ( Figure S2 ).

At titer ≥2 U/L, seroresponse was slightly lower for all vaccine types, most notably among Ad26.COV2.S/Janssen recipients. When limiting to the first SAb-IgG titer ≥14 days after vaccine series completion, seroresponse rate was significantly lower only among Ad26.COV2.S/Janssen recipients. (Table S1 ). Vaccine type, older age, non-Black and non-Native American race, immune-modulating medications, history of transplantation, and lower serum albumin were associated with lower likelihood of vaccine seroresponse (Figure) .

Among maintenance dialysis patients, mRNA vaccines against SARS-CoV-2 elicited seroresponse in the vast majority, consistent with prior reports. [1] [2] [3] [4] [5] [6] In contrast, seroresponse to the Ad26.COV2.S/Janssen vaccine was low, consistent with an earlier small study, 7 suggesting that maintenance dialysis patients should receive mRNA-based SARS-CoV-2 vaccines, particularly given their high morbidity and mortality from COVID-19. 9 The low seroresponse rate to the Ad26.COV2.S/Janssen vaccine is concerning because post-vaccination SAb-IgG antibody titers correlate with protection from COVID-19, possibly via direct neutralization of the spike protein. 10 Of note, as a single-dose regimen, response to Ad26.COV2.S/Janssen was assessed 3-4 weeks earlier relative to the initial vaccine dose than response to mRNA vaccines. However, longer term data elsewhere do not indicate increased response over time. 11 Thus, even allowing for possible later increase in seroresponse, the Ad26.COV2.S/Janssen vaccine appears less effective than mRNA vaccines among maintenance dialysis patients.

The difference between BNT162b2/Pfizer and mRNA-1273/Moderna may reflect differences in dosage (100 μg vs 30 μg of mRNA content, respectively), or, given the earlier availability of the BNT162b2/Pfizer vaccine, unaccounted-for confounding factors. Admittedly, the SAb-IgG antibody titer needed for protection from COVID-19 and the role of vaccineinduced cellular immunity remain uncertain, issues that are complicated by emerging variants. Other than vaccine type, predictors of vaccine non-response were largely factors related to potential immunocompromise. 2, 3 Our study limitations include potential selection bias and unaccounted-for confounders. We did not examine breakthrough infections, which are a growing concern. Lastly, while the assessment of SAb-IgG titer ≥14 days after completion of vaccine series corresponds with the current definition of "fully vaccinated," there remains a difference in timing relative to the initial dose between one-dose and two-dose regimens.

In conclusion, among maintenance dialysis patients, mRNA vaccines are associated with greater seroresponse and therefore should be preferred. Further study is needed on the durability of this seroresponse; its correlation with breakthrough infection, morbidity, and mortality; and the role of additional vaccine doses, particularly among recipients of the Ad26.COV2.S/Janssen vaccine. Figure S1 -S2, Item S1, Table S1

Article Information 

SARS-CoV-2 vaccine response defined as immunoglobulin-G spike antibodies (SAb-IgG) against the receptor-binding domain of the S1 subunit of SARS-CoV-2 spike antigen titer ≥1 U/L measured 14-74 days after completion of a vaccine series. Hepatitis B seroimmunity defined as hepatitis B surface antibody ≥10 mIU/mL. Immune-modulating medications include anti-inflammatory medications, anti-neoplastic agents, corticosteroids, and certain anti-infective medications. Comorbidities include diabetes mellitus, hypertension, congestive heart failure, chronic obstructive pulmonary disease, cerebrovascular disorders, peripheral vascular disease, thyroid disorder, and history of cancer. COPD Chronic Obstructive Pulmonary Disease. The association for number of comorbidities is expressed per additional comorbidity. Peritoneal dialysis modality is compared to hemodialysis modality (either in-center or home). Analysis was performed with multivariable log Poisson regression with robust variances. 

Humoral and Cellular Responses to mRNA-1273 and BNT162b2 SARS-CoV-2 Vaccines Administered to Hemodialysis Patients

Antibody response to mRNA SARS-CoV-2 vaccine among dialysis patients -a prospectivecohort study

High immunogenicity of a messenger RNA-based vaccine against SARS-CoV-2 in chronic dialysis patients

SARS-CoV-2 Antibody Response After a Third Dose of the BNT162b2 Vaccine in Patients Receiving Maintenance Hemodialysis or Peritoneal Dialysis

Antibody Response to mRNA-1273 SARS-CoV-2 Vaccine in Hemodialysis Patients with and without Prior COVID-19

Immunogenicity of BNT162b2 SARS-CoV-2 Vaccine in a Multicenter Cohort of Nursing Home Residents Receiving Maintenance Hemodialysis

Humoral Response to mRNA versus an Adenovirus Vector-Based SARS-COV2 (Ad26.COV2.S) Vaccine in Dialysis Patients

Immunogenicity of SARS-CoV-2 Vaccine in Dialysis

Epidemiology and Outcomes of COVID-19 in Home Dialysis Patients Compared with In-Center Dialysis Patients

Evidence for antibody as a protective correlate for COVID-19 vaccines

Durable Humoral and Cellular Immune Responses Following Ad26.COV2.S Vaccination for COVID-19. Infectious Diseases (except HIV/AIDS)