Humoral vaccine response and breakthrough infections in kidney transplant recipients during the COVID-19 pandemic: a nationwide cohort study

Markus Hovd; Anders Åsberg; Ludvig A Munthe; Kristian Heldal; Anna V Reisæter; John T Vaage; Fridtjof Lund-Johansen; Karsten Midtvedt

doi:10.1016/j.eclinm.2023.102035

Humoral vaccine response and breakthrough infections in kidney transplant recipients during the COVID-19 pandemic: a nationwide cohort study

EClinicalMedicine. 2023 Jun:60:102035. doi: 10.1016/j.eclinm.2023.102035. Epub 2023 Jun 6.

Authors

Markus Hovd^{1

2

3}, Anders Åsberg^{1

2

3}, Ludvig A Munthe^{4

5}, Kristian Heldal^{1

6}, Anna V Reisæter^{1

3}, John T Vaage^{4

7}, Fridtjof Lund-Johansen^{7

8}, Karsten Midtvedt¹

Affiliations

¹ Department of Transplantation Medicine, Oslo University Hospital, Norway.
² Department of Pharmacy, University of Oslo, Norway.
³ The Norwegian Renal Registry, Department of Transplantation Medicine, Oslo University Hospital, Norway.
⁴ Institute of Clinical Medicine, University of Oslo, Norway.
⁵ KG Jebsen Centre for B Cell Malignancies, Institute of Clinical Medicine, University of Oslo, Norway.
⁶ Institute of Health and Society, University of Oslo, Norway.
⁷ Department of Immunology, Oslo University Hospital, Norway.
⁸ ImmunoLingo Convergence Center, Institute of Clinical Medicine, University of Oslo, Norway.

Abstract

Background: Kidney transplant recipients (KTRs) experienced reduced SARS-CoV-2 vaccine response and were at increased risk of severe COVID-19. It is unknown if level of vaccine induced anti-receptor binding domain IgG (anti-RBD IgG) correlates with protection from and survival following COVID-19. We aimed to evaluate the effect of vaccine response on risk of breakthrough infections (BTI) and COVID-19 death in KTRs.

Methods: We performed a nationwide study, examining the competing risk of SARS-CoV-2 infection, COVID-19 related/unrelated death, and vaccine efficacy as assessed by level of anti-RBD IgG response 4-10 weeks after each vaccination. The study included all KTR in Norway alive and with a functioning graft on February 20th, 2020, and events after November 11th, 2022 were right-censored. A pre-pandemic reference-cohort from January 1st 2019 to January 1st 2020 was included to evaluate excess mortality. The study was conducted at Oslo University Hospital, Rikshospitalet, Norway.

Findings: The study included 3607 KTRs (59 [48-70] years) with a functioning graft at February 20th, 2020, who received (median [IQR]) 4 [3-4] vaccines (range 2-6, 99% mRNA). Anti-RBD IgG was measured in 12 701 serum samples provided by 3213 KTRs. Vaccine response was assessed 41 [31-57] days after vaccination. A total of 1090 KTRs were infected with SARS-CoV-2, 1005 (92%) were BTI, and vaccine response did not protect against BTI. The hazard ratio for COVID-19 related death 40 days post-infection was 1.71 (95% CI: 1.14, 2.56) comparing vaccine response levels (≥5 vs. ≥5000 BAU/mL). No excess non-COVID-19 mortality was registered in KTRs surviving SARS-CoV-2 infection compared to a 2019 pre-pandemic reference.

Interpretation: Our findings suggested that SARS-CoV-2 mRNA vaccine response did not predict protection against infection, but prevention of fatal disease progression in KTRs and greater vaccine response further reduced the risk of COVID-19 death. No excess non-COVID-19 mortality was seen during the pandemic.

Funding: CEPI and internal funds.

Keywords: Anti-RBG IgG; COVID-19; Immunosuppression; Infectious disease; Kidney transplant recipients; Nephrology; Pandemic; Transplantation; Vaccination; Vaccine response.