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Letters to the Editor

Real-world Impact of 2-dose SARS-CoV-2 Vaccination in Kidney Transplant Recipients

McEvoy, Caitríona M. MB BCh, PhD1; Lee, Anna BHSc2; Misra, Paraish S. MD2; Lebovic, Gerald PhD3; Wald, Ron MDCM, MPH2; Yuen, Darren A. MD, PhD1

Author Information
doi: 10.1097/TP.0000000000004081

The humoral response to 2 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine among transplant recipients is inferior to immunocompetent individuals.1 Data on the “real-world” impact of vaccination in kidney transplant recipients (KTRs) are lacking. We performed a cohort study investigating the impact of vaccination on coronavirus disease 2019 (COVID-19) infection and outcomes in our kidney transplant program. COVID-19 vaccination and infection status between March 11, 2020, and July 19, 2021, were recorded for all KTRs in our program, along with demographics and clinical covariates associated with COVID-19 severity.2 This initiative was reviewed by institutional authorities at Unity Health Toronto and deemed to require neither approval from the Research Ethics Board nor written informed consent from participants.

Weekly community infection rates for each public health unit of Ontario were used to define a patient-specific community infection risk. The primary outcome was COVID-19 infection in our study population. Severe COVID-19 infection (complicated by hospitalization and death) was analyzed as a secondary outcome. A time-varying Cox proportional-hazards model examined the association between vaccine status and the risk of COVID-19 infection, adjusting for age, sex, time posttransplant, kidney function, COVID-19–predisposing comorbidities, and the weekly infection rate in each patient’s community. Detailed methods are described in Supplementary Appendix S1 (SDC, https://links.lww.com/TP/C367).

We evaluated 1793 KTRs. One thousand five hundred forty (85.9%) KTRs had received 1 vaccine dose, and 1402 (78.2%) had received 2 doses by study end. The median age was 60.4 y (interquartile range, 51.0–69.2), and the median time from transplantation was 8.1 y (interquartile range, 3.9–13.6; Table S1, SDC, https://links.lww.com/TP/C367).

There were 114 COVID-19 infections, of which 61% were severe (Table S2, SDC, https://links.lww.com/TP/C367). Community infection rates (hazard ratio [HR], 1.08 per 10 in 100 000 increase in weekly infection rate; 95% confidence interval [CI], 1.04-1.12) and transplant duration <3 mo (HR, 4.29; 95% CI, 1.5-12.23) were associated with infection risk (Table 1). Similar associations were observed for severe COVID-19 infections (Table 1). As compared with unvaccinated patients, double vaccination was associated with a nonsignificant reduction in COVID-19 infection (HR, 0.52; 95% CI, 0.14-1.95) and severe infection (HR, 0.59; 95% CI, 0.12-2.89). A sensitivity analysis examined the effect of administration of any vaccine dose on any COVID-19 infection (HR, 0.78; 95% CI, 0.38-1.61; P = 0.5) and severe infection (HR, 1.22; 95% CI, 0.53-2.8; P = 0.64) and found no change in the overall result.

TABLE 1. - Associations between vaccine status and the risk of contracting COVID-19 or developing severe COVID-19 infection
Variable HR Lower CI Upper CI P
Association between vaccine status and the risk of contracting COVID-19
 Vaccine dose 1 0.87 0.41 1.87 0.73
 Vaccine dose 2 0.60 0.15 2.31 0.45
 Age 0.99 0.98 1.01 0.36
 Transplant duration >3 mo 1.24 0.51 2.30 0.64
 Transplant duration 0–3 mo 4.29 1.50 12.23 0.007
 Female sex 1.19 0.81 1.73 0.36
 Latest eGFR 0.99 0.98 1.00 0.11
 CDC score 1.03 0.89 1.19 0.73
 COVID-19 community infection burden 1.08 1.04 1.12 <0.001
Association between vaccine status and the risk of developing severe COVID-19 infection
 Dose 1 1.48 0.62 3.52 0.38
 Dose 2 0.40 0.08 1.97 0.26
 Age 1.01 0.99 1.03 0.25
 Transplant duration >3 mo 1.30 0.42 4.01 0.65
 Transplant duration 0–3 mo 6.19 1.87 20.49 0.003
 Female sex 1.09 0.67 1.77 0.74
 Latest eGFR 0.99 0.98 1.00 0.12
 CDC score 1.06 0.88 1.27 0.56
 COVID-19 community infection burden 1.10 1.05 1.15 <0.001
The model adjusts for age (per 1 y increase), sex, transplant duration, latest eGFR, and geographical COVID-19 burden. The following were treated as time-varying variables: vaccine (none, 1, and 2 doses), transplant duration (0–3, 3–12, and >12 mo), and COVID-19 community infection burden per 100 000 population (HR reflects an increase in 10/100 000 population).
CDC, Centers for Disease Control and Prevention; CI, confidence interval; COVID-19, coronavirus disease 2019; eGFR, estimated glomerular filtration rate; HR, hazard ratio.

Our study describes the impact of vaccines on COVID-19 infection when taking into account important time-varying nonvaccine variables such as community infection rates and transplant vintage, both of which were significant determinants of infection risk. Although our analysis of vaccination effectiveness may be limited by cohort size, importantly, a reduction in HR was observed with each vaccine dose, highlighting the benefit of vaccination in this cohort. These results form the basis for the guidance we provide our patients, which includes (1) the likely benefits of 2-dose vaccination regimens and (2) the importance of continued adherence to public health guidelines about masking and physical distancing to reduce infection risk. We were unable to directly address the role of mixed-dose vaccines, as only a very small minority received 2 different vaccines (Table S3, SDC, https://links.lww.com/TP/C367). Importantly, although the antibody levels that confer resistance to infection are unknown, recent work demonstrates that a third vaccine dose yields greater immunogenicity in transplanted individuals.3-6 We note that our study predates the emergence of the Omicron variant, which is rapidly gaining dominance worldwide. Future studies must examine whether multidose vaccination strategies enhance real-world vaccine effectiveness among transplant patients in the Omicron era.

REFERENCES

1. Boyarsky BJ, Werbel WA, Avery RK, et al. Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients. JAMA. 2021;325:2204–2206.
2. Centers for Disease Control and Prevention. People with certain medical conditions. 2019. Available at https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html. 2021. Accessed June 1, 2021.
3. Werbel WA, Boyarsky BJ, Ou MT, et al. Safety and immunogenicity of a third dose of SARS-CoV-2 vaccine in solid organ transplant recipients: a case series. Ann Intern Med. 2021;174:1330–1332.
4. Kamar N, Abravanel F, Marion O, et al. Three doses of an mRNA Covid-19 vaccine in solid-organ transplant recipients. N Engl J Med. 2021;385:661–662.
5. Del Bello A, Abravanel F, Marion O, et al. Efficiency of a boost with a third dose of anti-SARS-CoV-2 messenger RNA-based vaccines in solid organ transplant recipients. Am J Transplant. 2022;22:322–323.
6. Hall VG, Ferreira VH, Ku T, et al. Randomized trial of a third dose of mRNA-1273 vaccine in transplant recipients. N Engl J Med. 2021;385:1244–1246.

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