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American Journal of Kidney Diseases

Seroresponse to SARS-CoV-2 Vaccines Among Maintenance Dialysis Patients

Published:November 07, 2021DOI:https://doi.org/10.1053/j.ajkd.2021.10.002
      To the Editor:
      As of October 2021, 3 SARS-CoV-2 vaccines are available in the United States, and all appear highly effective in the general population. Studies suggest high seroresponse to messenger RNA vaccines among maintenance dialysis patients, albeit lower than that in the general population.
      • Broseta J.J.
      • Rodríguez-Espinosa D.
      • Rodríguez N.
      • et al.
      Humoral and cellular responses to mRNA-1273 and BNT162b2 SARS-CoV-2 vaccines administered to hemodialysis patients.
      • Agur T.
      • Ben-Dor N.
      • Goldman S.
      • et al.
      Antibody response to mRNA SARS-CoV-2 vaccine among dialysis patients - a prospective cohort study.
      • Longlune N.
      • Nogier M.B.
      • Miedougé M.
      • et al.
      High immunogenicity of a messenger RNA-based vaccine against SARS-CoV-2 in chronic dialysis patients.
      • Bensouna I.
      • Caudwell V.
      • Kubab S.
      • et al.
      SARS-CoV-2 antibody response after a third dose of the BNT162b2 vaccine in patients receiving maintenance hemodialysis or peritoneal dialysis.
      • Chan L.
      • Fuca N.
      • Zeldis E.
      • Campbell K.N.
      • Shaikh A.
      Antibody response to mRNA-1273 SARS-CoV-2 Vaccine in hemodialysis patients with and without prior COVID-19.
      • Labriola L.
      • Scohy A.
      • Van Regemorter E.
      • et al.
      Immunogenicity of BNT162b2 SARS-CoV-2 vaccine in a multicenter cohort of nursing home residents receiving maintenance hemodialysis.
      Data regarding adenoviral vector vaccines and predictors of vaccine nonresponse are limited by small sample sizes.
      • Mulhern J.
      • Fadia A.
      • Patel R.
      • et al.
      Humoral response to mRNA versus an adenovirus vector-based SARS-COV2 (Ad26.COV2.S) vaccine in dialysis patients.
      Accordingly, we retrospectively analyzed seroresponse to SARS-CoV-2 vaccines among maintenance dialysis patients, updating an earlier report.
      • Lacson E.
      • Argyropoulos C.
      • Manley H.
      • et al.
      Immunogenicity of SARS-CoV-2 vaccine in dialysis.
      DCI is a national not-for-profit provider caring for more than 15,000 patients at 260 outpatient dialysis clinics across 29 states. As of January 2021, DCI physicians had the option of activating a SARS-CoV-2 vaccine protocol, in which anti–spike immunoglobulin G antibodies (SAb-IgG) were measured monthly with routine lab work (details in Item S1). We obtained demographic and clinical data, vaccination dates, and SAb-IgG titers from the DCI electronic health record. We excluded patients with previously diagnosed COVID-19 or positive SAb-IgG titer before or within 10 days after first vaccine dose.
      In primary analyses, seroresponse was defined by at least one ≥1 SAb-IgG titer ≥1 U/L at 14-74 days after completion of a vaccine series. Because samples for antibody titers were drawn alongside monthly labs, most patients have 2 assessments in this 60-day period. Associations of demographic and clinical factors with vaccine seroresponse were analyzed using multivariable log Poisson regression with robust variances. Secondary analyses used alternate definitions of vaccine seroresponse: (1) ≥1 SAb-IgG titer ≥2 U/L at 14-74 days after vaccine series completion, and (2) SAb-IgG titer ≥1 U/L on the first assessment at least 14 days after vaccine series completion. 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.
      Between January 1 and June 30, 2021, 1,528 patients (437 BNT162b2/Pfizer, 766 mRNA-1273/Moderna, and 325 Ad26.COV2.S/Janssen recipients) across 130 dialysis facilities had SAb-IgG titers measured after SARS-CoV-2 vaccination (Fig S1). Baseline characteristics were similar to those of the broader DCI vaccinated patient population. Between 14 and 74 days after vaccine series completion, 437 (29%), 946 (62%), and 145 (9%) had 1, 2, and more than 2 titers checked, respectively. BNT162b2/Pfizer recipients tended to be older (Table 1).
      Table 1Patient Characteristics by SARS-CoV-2 Vaccine Administered
      DemographicsAll Vaccinated DCI Patients
      Patients fully vaccinated with an emergency-use approved vaccine series of one type without additional doses as of June 30, 2021, excluding those with prior COVID-19.
      (N = 9,599)
      Study Patients
      Overall (N = 1,528)BNT162b2/Pfizer (n = 437 [29%])mRNA-1273/Moderna (n = 766 [50%])Ad26.COV2.S/Janssen (n = 325 [21%])P
      P value for comparisons across the 3 vaccine types among study patients.
      Age, y64.9 ± 13.564.2 ± 13.566.8 ± 12.964.0 ± 13.961.3 ± 12.6<0.001
      Female sex3,901 (40.6%)646 (42.3%)191 (43.7%)308 (40.2%)147 (45.2%)0.2
      Race<0.001
       White4,639 (48.3%)768 (50.3%)198 (45.3%)447 (58.4%)123 (37.8%)
       Black3,287 (34.2%)356 (23.3%)80 (18.3%)116 (15.1%)160 (49.2%)
       Native American262 (2.7%)126 (8.3%)61 (14.0%)60 (7.8%)5 (1.5%)
       Asian/Pacific Islander347 (3.6%)93 (6.1%)49 (11.2%)37 (4.8%)7 (2.2%)
       Other/unknown1,064 (11.1%)185 (12.1%)49 (11.2%)106 (13.8%)30 (9.2%)
      Hispanic ethnicity590 (6.2%)205 (13.4%)63 (14.4%)134 (17.5%)8 (2.5%)<0.001
      Dialysis vintage, mo48.9 ± 56.153.0 ± 58.150.9 ± 57.652.4 ± 57.057.4 ± 61.20.3
      Body mass index, kg/m228.8 ± 7.328.4 ± 7.128.4 ± 7.428.1 ± 6.429.2 ± 8.00.06
      Long-term care facility1,046 (10.9%)139 (9.1%)41 (9.4%)69 (9.0%)29 (8.9%)0.9
      Home dialysis1,335 (13.9%)224 (14.7%)59 (13.5%)130 (17.0%)35 (10.8%)0.02
       Peritoneal dialysis1,225 (12.8%)198 (13.0%)50 (11.4%)113 (14.8%)35 (10.8%)
       Home hemodialysis110 (1.2%)26 (1.7%)9 (2.1%)17 (2.2%)0 (0.0%)
      Adequate dialysis dose
      Hemodialysis single-pool Kt/V≥1.2 or peritoneal dialysis weekly Kt/V≥1.7.
      7,155 (74.5%)1,205 (78.9%)350 (80.1%)597 (77.9%)258 (79.4%)0.7
      Serum albumin, g/dL3.8 ± 0.43.9 ± 0.43.9 ± 0.43.9 ± 0.43.8 ± 0.40.05
      Other vaccines within 14 days881 (9.2%)129 (8.4%)40 (9.2%)62 (8.1%)27 (8.3%)0.8
       Pneumococcal186 (1.9%)32 (2.1%)5 (1.1%)21 (2.7%)6 (1.9%)0.2
       HBV717 (7.5%)101 (6.6%)35 (8.0%)44 (5.7%)22 (6.8%)0.3
       Influenza38 (0.4%)6 (0.4%)2 (0.5%)4 (0.5%)0 (0.0%)0.9
      HBV seroimmunity
      Hepatitis B virus (HBV) seroimmunity defined as antibody to HBV surface antigen≥10mIU/mL.
      6,231 (64.9%)1,099 (71.9%)317 (72.5%)557 (72.7%)225 (69.2%)0.3
      Potential immunosuppression1,738 (18.1%)276 (18.1%)94 (21.5%)126 (16.5%)56 (17.2%)0.08
       Immune-modulating medications
      Medications include anti-inflammatory medications, antineoplastic agents, corticosteroids, and certain anti-infective medications.
      1,260 (13.1%)197 (12.9%)69 (15.8%)91 (11.9%)37 (11.4%)0.1
       Prior transplant670 (7.0%)102 (6.7%)32 (7.3%)53 (6.9%)17 (5.2%)0.5
       Immunodeficiency disorder342 (3.6%)71 (4.7%)23 (5.3%)31 (4.1%)17 (5.2%)0.5
      Hospitalization within 14 days1,195 (12.5%)194 (12.7%)58 (13.3%)103 (13.5%)33 (10.2%)0.3
      Disability430 (4.5%)62 (4.1%)16 (3.7%)30 (3.9%)16 (4.9%)0.7
      Tobacco use1,530 (15.9%)205 (13.4%)48 (11.0%)101 (13.2%)56 (17.2%)0.04
      Alcohol abuse disorder1,023 (10.7%)143 (9.4%)38 (8.7%)71 (9.3%)34 (10.5%)0.7
      Drug abuse disorder441 (4.6%)51 (3.3%)14 (3.2%)27 (3.5%)10 (3.1%)0.9
      No. of comorbidities3.0 ± 1.82.9 ± 1.72.9 ± 1.62.9 ± 1.63.1 ± 1.80.1
       Diabetes mellitus5,765 (60.1%)909 (59.5%)269 (61.6%)437 (57.1%)203 (62.5%)0.2
       Hypertension8,023 (83.6%)1,310 (85.7%)371 (84.9%)657 (85.8%)282 (86.8%)0.8
       Congestive heart failure2,090 (21.8%)298 (19.5%)72 (16.5%)150 (19.6%)76 (23.4%)0.06
       COPD1,500 (15.6%)230 (15.1%)65 (14.9%)100 (13.1%)65 (20.0%)0.01
       Stroke/cerebrovascular disorder909 (9.5%)114 (7.5%)33 (7.6%)51 (6.7%)30 (9.2%)0.3
       Peripheral vascular disease1,297 (13.5%)178 (11.7%)43 (9.8%)78 (10.2%)57 (17.5%)0.001
       Thyroid disorder1,558 (16.2%)248 (16.2%)64 (14.7%)136 (17.8%)48 (14.8%)0.3
       History of cancer1,018 (10.6%)136 (8.9%)41 (9.4%)74 (9.7%)21 (6.5%)0.2
      Continuous variables given as mean ± standard deviation. Abbreviations: COPD, chronic obstructive pulmonary disease; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; DCI, Dialysis Clinic, Inc.
      a Patients fully vaccinated with an emergency-use approved vaccine series of one type without additional doses as of June 30, 2021, excluding those with prior COVID-19.
      b Hemodialysis single-pool Kt/V≥1.2 or peritoneal dialysis weekly Kt/V≥1.7.
      c Hepatitis B virus (HBV) seroimmunity defined as antibody to HBV surface antigen ≥10 mIU/mL.
      d Medications include anti-inflammatory medications, antineoplastic agents, corticosteroids, and certain anti-infective medications.
      e P value for comparisons across the 3 vaccine types among study patients.
      Vaccine seroresponse occurred in 87% of BNT162b2/Pfizer, 96% of mRNA-1273/Moderna, 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 74th day after vaccine series completion. Among those without seroresponse, the median duration of this period was 19.5 [IQR, 12-29], 24.5 [IQR, 12-34], and 16 [IQR, 9-20] days for BNT162b2/Pfizer, mRNA-1273/Moderna, and Ad26.COV2.S/Janssen recipients, respectively (Fig S2).
      At titer ≥2 U/L, seroresponse was slightly lower for all vaccine types, most notably Ad26.COV2.S/Janssen. 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 seroresponse (Fig 1).
      Figure thumbnail gr1
      Figure 1Multivariable regression of clinical characteristics associated with SARS-CoV-2 vaccine response. Response defined as SAb-IgG titer ≥1 U/L measured 14-74 days after vaccine series completion. The association for number of comorbidities is expressed per additional comorbidity. Peritoneal dialysis is compared to hemodialysis (either in-center or home). Analysis was performed with multivariable log Poisson regression with robust variances. See notes for abbreviations and definitions.
      Among maintenance dialysis patients, mRNA vaccines against SARS-CoV-2 elicited seroresponse in the vast majority, consistent with prior reports.
      • Broseta J.J.
      • Rodríguez-Espinosa D.
      • Rodríguez N.
      • et al.
      Humoral and cellular responses to mRNA-1273 and BNT162b2 SARS-CoV-2 vaccines administered to hemodialysis patients.
      • Agur T.
      • Ben-Dor N.
      • Goldman S.
      • et al.
      Antibody response to mRNA SARS-CoV-2 vaccine among dialysis patients - a prospective cohort study.
      • Longlune N.
      • Nogier M.B.
      • Miedougé M.
      • et al.
      High immunogenicity of a messenger RNA-based vaccine against SARS-CoV-2 in chronic dialysis patients.
      • Bensouna I.
      • Caudwell V.
      • Kubab S.
      • et al.
      SARS-CoV-2 antibody response after a third dose of the BNT162b2 vaccine in patients receiving maintenance hemodialysis or peritoneal dialysis.
      • Chan L.
      • Fuca N.
      • Zeldis E.
      • Campbell K.N.
      • Shaikh A.
      Antibody response to mRNA-1273 SARS-CoV-2 Vaccine in hemodialysis patients with and without prior COVID-19.
      • Labriola L.
      • Scohy A.
      • Van Regemorter E.
      • et al.
      Immunogenicity of BNT162b2 SARS-CoV-2 vaccine in a multicenter cohort of nursing home residents receiving maintenance hemodialysis.
      In contrast, seroresponse to Ad26.COV2.S/Janssen was low, consistent with an earlier small study,
      • Mulhern J.
      • Fadia A.
      • Patel R.
      • et al.
      Humoral response to mRNA versus an adenovirus vector-based SARS-COV2 (Ad26.COV2.S) vaccine in dialysis patients.
      suggesting that maintenance dialysis patients should receive mRNA-based SARS-CoV-2 vaccines, particularly given their high morbidity and mortality from COVID-19.
      • Hsu C.M.
      • Weiner D.E.
      • Aweh G.
      • Salenger P.
      • Johnson D.S.
      • Lacson E.
      Epidemiology and outcomes of COVID-19 in home dialysis patients compared with in-center dialysis patients.
      The low seroresponse rate to Ad26.COV2.S/Janssen is concerning because postvaccination SAb-IgG titers correlate with protection from COVID-19, possibly via direct neutralization of the spike protein.
      • Earle K.A.
      • Ambrosino D.M.
      • Fiore-Gartland A.
      • et al.
      Evidence for antibody as a protective correlate for COVID-19 vaccines.
      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.
      • Barouch D.H.
      • Stephenson K.E.
      • Sadoff J.
      • et al.
      Durable Humoral and Cellular Immune Responses 8 Months after Ad26.COV2.S Vaccination.
      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 vs 30 μg of mRNA content, respectively), or, given the earlier availability of BNT162b2/Pfizer, unaccounted-for confounding factors. Admittedly, the SAb-IgG titer needed for protection from COVID-19 and the role of vaccine-induced cellular immunity remain uncertain, issues that are complicated by emerging variants. Other than vaccine type, predictors of vaccine nonresponse were largely factors related to potential immunocompromise.
      • Agur T.
      • Ben-Dor N.
      • Goldman S.
      • et al.
      Antibody response to mRNA SARS-CoV-2 vaccine among dialysis patients - a prospective cohort study.
      ,
      • Longlune N.
      • Nogier M.B.
      • Miedougé M.
      • et al.
      High immunogenicity of a messenger RNA-based vaccine against SARS-CoV-2 in chronic dialysis patients.
      Our study limitations include potential selection bias and unaccounted-for confounders. We did not examine breakthrough infections, which are a growing concern. Also, although assessing SAb-IgG titer ≥14 days after completion of vaccine series meets the current definition of “fully vaccinated,” there remains a difference in timing relative to the initial dose between 1- and 2-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 Ad26.COV2.S/Janssen vaccine recipients.

      Article Information

      Authors’ Contributions

      Research area and study design: CMH, DEW, GNA, HJM, DM, EKL; data acquisition: GNA, VL, JF, CA, KA, AC, RG, LS; data analysis and interpretation: CMH, DEW, GNA, HJM, VL, JF, DM, EKL; statistical analysis: GNA; supervision or mentorship: DEW, DJ, EKL. Each author contributed important intellectual content during manuscript drafting or revision and agrees to be personally accountable for the individual’s own contributions and to ensure that questions pertaining to the accuracy or integrity of any portion of the work, even one in which the author was not directly involved, are appropriately investigated and resolved, including with documentation in the literature if appropriate.

      Support

      This report was supported by DCI. CMH receives support from ASN KidneyCure’s Ben J. Lipps Research Fellowship, which had no role in study design, data collection, reporting, or the decision to submit.

      Financial Disclosure

      GNA, HJM, VL, JF, DJ, and EKL are all employees of DCI, where DJ is Vice Chair of the Board. DEW, DM, CA, KA, AC, RG, and LS receive salary support to their institution from DCI. CMH declares that she has no relevant financial interests.

      Prior Presentation

      A preprint version of this Research Letter was posted August 22, 2021 at medRxiv with doi 10.1101/2021.08.19.2126229.

      Peer Review

      Received June 14, 2021 as a submission to the expedited consideration track with 3 external peer reviews. Direct editorial input from a Statistics/Methods Editor, an Associate Editor, and the Editor-in-Chief. Accepted in revised form October 25, 2021. Further information on expedited consideration (AJKD Express) is available in the Information for Authors & Journal Policies.

      Supplementary Material

      References

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