key: cord-0272783-7gw561ue
authors: Brunelli, S. M.; Sibbel, S.; Karpinski, S.; Marlowe, G.; Walker, A. G.; Giullian, J.; Van Wyck, D.; Kelley, T.; Lazar, R.; Zywno, M. L.; Connaire, J. J.; Young, A.; Tentori, F.
title: Comparative Effectiveness of BNT162b2 versus Ad26.COV2.S for the Prevention of COVID-19 among Dialysis Patients
date: 2021-10-25
journal: nan
DOI: 10.1101/2021.10.21.21265339
sha: 91adbfbe279a11ec4928483b30e9fa18413d0315
doc_id: 272783
cord_uid: 7gw561ue

Background: mRNA-based SARS-CoV-2 vaccines have been shown to be highly effective among dialysis patients. Because individual vaccines may be differentially available or acceptable to patients, it is important to understand comparative effectiveness of other vaccines, such those based on adeno-virus technologies. Methods: This retrospective study compared the clinical effectiveness of Ad26.COV2.S (Janssen/Johnson and Johnson) to BNT162b2 among dialysis patients. Patients initiating BNT162b2 (Pfizer/BioNTech) were matched 1:1 to Ad26.COV2.S recipients based on age, race, US state of residence, calendar week of first vaccine receipt, and history of COVID-19. The primary outcome was the comparative rate of COVID-19 considered over 3 follow-up intervals: weeks 1-3, 4-6, and [≥] 7 post-vaccination. In a subset of consented Ad26.COV2.S patients, blood samples were collected [≥]28 days after vaccination and anti-SARS-Cov-2 immunoglobulin G antibodies were measured. Results: There were 2659 matched pairs of patients who received a first dose of each vaccine. During weeks 1-3, incidence rates were 1.13 vs 1.39 per 1000 patient-weeks (pt-wks) for BNT162b2 and Ad26.COV2.S recipients, respectively (incident rate difference [IRD]: 0.25; 95% CI: 0.90, 1.36). During weeks 4-6, incidence rates were 0.78 vs 0.39 per 1000 pt-wks for BNT162b2 and Ad26.COV2.S recipients, respectively (IRD: -0.39; 95% CI: -1.16, 0.38). After week 7, incidence rates were 1.29 vs 1.39 per 1000 pt-wks for BNT162b2 and Ad26.COV2.S recipients, respectively (IRD: 0.10; 95% CI: -0.35, 0.55). Results were similar when considering only patients without a history of COVID-19 and among matched pairs in which BNT162b2 recipients completed the 2-dose regimen. SARS-CoV-2 antibodies were detected in 59.4% (95% CI: 53.0%-65.5%) of Ad26.COV2.S patients. Conclusion: In a large real-world cohort of dialysis patients, no difference was detected in the clinical effectiveness of BNT162b2 and Ad26.COV2.S, despite an inconsistent antibody response to the latter. These data support the use of either agent in ongoing vaccination efforts in this population.

The population of patients receiving maintenance dialysis for end-stage kidney disease is enriched for risk factors for-and has borne a disproportionate burden of-infection with SARS-CoV-2 and severe COVID-19 manifestation. [1] [2] [3] [4] As such, efforts to vaccinate these patients and Overall vaccine uptake in the US dialysis population has been robust, with the majority of patients having received BNT162b2 or mRNA-1273, both of which have been demonstrated to be highly effective in preventing COVID-19. 6 As vaccination efforts proceed, a meaningful number of dialysis patients have indicated hesitancy to receive either of these vaccines because they are mRNA-based; however, such patients do express a willingness to receive the All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Therefore, we leveraged the natural experiment established by vaccine allocation programs to test the real-world comparative effectiveness of the adenovirus-based Ad26.COV2.S versus one of the mRNA-based vaccines (BNT162b2) in preventing clinical cases of COVID-19 among a large, representative cohort of US dialysis patients. Given that real world effectiveness is impacted by patient adherence (ie, to the 2 nd of two-dose regimen), we began by considering all matched BNT162b2 : AD26.COV2.S pairs, regardless of whether the latter followed through with a second dose. Recognizing that there is interest in effectiveness when regimens are followed as intended, we performed restricted analyses in which matched pairs were considered only if the BNT162b2 patient completed a 2-dose regimen ("completer pairs"). Furthermore, for each comparison, we performed separate analyses including and not including patients with a prior history of COVID-19.

This retrospective study was designed to compare 2 potential vaccination regimens: "use BNT162b2" versus "use Ad26.COV2.S." BNT162b2 was chosen as the comparator messenger RNA vaccine (as opposed to mRNA-1273) because it had better geo-temporal overlap with AD26.COV2.S in our population. The study included dialysis patients who were ≥18 years and All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. approximately one-third of patient vaccinations occurred in dialysis facilities. For those patients who did not receive a vaccine in-clinic, vaccine information was ascertained through verbal attestation and review of vaccine cards. To account for geo-temporal variability in the intensity of the epidemic, BNT162b2 patients were exactly matched to Ad26.COV2.S patients on US state of residence and calendar week of vaccine receipt. Furthermore, to promote balance on susceptibility factors, BNT162b2 and Ad26.COV2.S patients were also matched on age (± 5 years), race, and history of prior COVID-19. Covariate balance between matched patients was assessed using descriptive statistics (means, SDs, counts, and proportions) and quantified in terms of standardized differences; standardized differences exceeding ± 10% indicate substantial imbalance. 8 The primary outcome was a polymerase chain reaction (PCR)-confirmed clinical diagnosis of COVID-19. Clinical surveillance protocols at the dialysis organization have been described elsewhere. 9, 10 To summarize, at the time of each clinic visit, all patients undergo a standardized COVID-19 screening. Patients who screen positive for COVID-19 symptoms, or who indicate a recent contact with COVID-19-infected individuals, immediately receive PCR testing.

Additional surveillance procedures are in place to identify COVID-19 diagnoses made at other sites of care (e.g., emergency departments, hospitals) and to confirm and document PCR test results from these sites.

Patients were considered at-risk beginning on the day after index date, and remained at-risk until the earliest of documented COVID-19 diagnosis, death, loss to follow-up, or on study end (28 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. September 2021). The follow-up period was separated into 3 intervals based on a priori assumptions: weeks 1-3, 4-6, and ≥7, corresponding to the interval between doses, the period after the second dose and before development of immunity, and the period of presumed immunity for BNT162b2 recipients, respectively. Corresponding follow-up time intervals were used for Ad26.COV2.S. Comparative effectiveness was estimated using Poisson regression and expressed as incidence rate differences (IRD) and 95% CIs for each of the 3 follow-up periods.

As standard, IRDs for which 95% CIs exclude zero were considered statistically significant. In addition, because finite statistical power increases the likelihood of type 2 errors, we further consider a "worst case" scenario for Ad26.COV2.S based on the upper confidence bound, which is a conservative approach since statistical imprecision implicitly "counts against" Ad26.COV2.S under this approach. In the dialysis population, concerns about the effectiveness of Ad26.COV2.S are further compounded by recent evidence that antibody responses to Ad26.COV2.S are less robust and consistent than other SARS-CoV-2 vaccines. 7 In the present study, we observed that approximately 60% of dialysis patients vaccinated with Ad26.COV2.S had detectable SARS-CoV-2 antibodies. This is comparatively lower than in our previous report in patients who received mRNA vaccines (96-98%). 6 Obviously, the serologic results and clinical effectiveness for Ad26.COV2.S is discordant. The reason why the serologic data do not accurately reflect the clinical effectiveness of this vaccine remain unknown.

Given these uncertainties, it has been unclear how best to approach vaccination among dialysis patients who, either by circumstance (i.e., vaccine availability) cannot-or, by personal choice, will not-receive an mRNA-based vaccine. Moreover, the appropriate course of action for patients who have received Ad26.COV2.S remains to be determined. In this regard, our results should be seen as reassuring. In fact, using the upper 95% confidence bound (which yields a more conservative estimate due to statistical imprecision), our estimates suggest that the excess number of COVID-19 diagnoses following a "use Ad26.COV2.S" (versus "use BNT162b2") approach should not exceed 0.55 per week per 1000 patients treated from week 7 on (i.e., the time period in which both vaccines should be at maximal effectiveness). In addition, because the period of time between first vaccination and presumed immunity is consequential both for patients and logistics of care delivery, we also provide estimates for earlier time periods; these are likewise reassuring in that Ad26.COV2.S appeared equivalent or (for weeks 4-6) trended toward superior, albeit the latter was not statistically significant due to a low number of events.

Our primary analysis included all patients who began a vaccine regimen, regardless of whether individual BNT162b2 patients completed the 2-dose series; this deliberate choice was made to All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 25, 2021. ; https://doi.org/10.1101/2021.10.21.21265339 doi: medRxiv preprint BNT162b2 vs Ad26.COV2.S in dialysis-13 reflect the reality that some patients do not follow through with a second dose, with real-world consequences on effectiveness. Nevertheless, follow-through rates were very high, and Ad26.COV2.S remained noninferior, even in sensitivity analyses restricted to patients who received both BNT162b2 doses.

The strengths of this study include a large sample size, a representative patient population, and a robust statistical matching procedure to account for the geo-temporal nature of the COVID-19 pandemic and vaccine rollout in the United States. The study should be viewed in light of the following limitations. As with any observational study, there is the possibility of residual confounding and bias (e.g., misclassification of exposure status for patients reporting vaccinations outside of the clinic). Data limitations precluded the ability to study COVID-19related hospitalizations as we well as severity of illness and asymptomatic infections, or to study side effects of vaccines. Low case counts also precluded study of case fatality. Given the fluctuating nature of background COVID-19 rates in the US population over the course of follow-up, COVID-19 rates within an exposure group should not be compared across follow-up periods, but rather limited to within period comparisons across exposure groups. Finally, we could not compare the effectiveness of these vaccines against specific SARS-CoV-2 variants.

In summary, our results demonstrate equivalent effectiveness of Ad26.COV2.S to an mRNAbased vaccine (BNT162b2) in dialysis patients. These results support the continued use of Ad26.COV2.S as a SARS-CoV-2 vaccine option in this vulnerable population.

All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 

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No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity