Safety and Immunogenicity of Anti–SARS-CoV-2 Messenger RNA Vaccines in Recipients of Solid Organ Transplants
Authors: Olivier Marion, Arnaud Del Bello, Florence Abravanel, Chloé Couat, Stanislas Faguer, Laure Esposito, Anne Laure Hebral, Jacques Izopet, Nassim Kamar
Journal: Annals of Internal Medicine (2021)

Letters25 May 2021Safety and Immunogenicity of Anti–SARS-CoV-2 Messenger RNA Vaccines in Recipients of Solid Organ TransplantsFREEOlivier Marion, MD, Arnaud Del Bello, MD, Florence Abravanel, PharmD, PhD, Chloé Couat, MSc, Stanislas Faguer, MD, PhD, Laure Esposito, MD, Anne Laure Hebral, MD, Jacques Izopet, PharmD, PhD, Nassim Kamar, MD, PhDOlivier Marion, MDToulouse Rangueil University Hospital, Paul Sabatier University, and INSERM UMR 1291, Toulouse Institute for Infectious and Inflammatory Disease (Infinity), Toulouse, FranceSearch for more papers by this author, Arnaud Del Bello, MDToulouse Rangueil University Hospital and Paul Sabatier University, Toulouse, FranceSearch for more papers by this author, Florence Abravanel, PharmD, PhDToulouse Purpan University Hospital, Paul Sabatier University, and INSERM UMR 1291, Toulouse Institute for Infectious and Inflammatory Disease (Infinity), Toulouse, FranceSearch for more papers by this author, Chloé Couat, MScToulouse Rangueil University Hospital, Toulouse, FranceSearch for more papers by this author, Stanislas Faguer, MD, PhDToulouse Rangueil University Hospital and Paul Sabatier University, Toulouse, FranceSearch for more papers by this author, Laure Esposito, MDToulouse Rangueil University Hospital, Toulouse, FranceSearch for more papers by this author, Anne Laure Hebral, MDToulouse Rangueil University Hospital, Toulouse, FranceSearch for more papers by this author, Jacques Izopet, PharmD, PhDToulouse Purpan University Hospital, Paul Sabatier University, and INSERM UMR 1291, Toulouse Institute for Infectious and Inflammatory Disease (Infinity), Toulouse, FranceSearch for more papers by this author, Nassim Kamar, MD, PhDToulouse Rangueil University Hospital, Paul Sabatier University, and INSERM UMR 1291, Toulouse Institute for Infectious and Inflammatory Disease (Infinity), Toulouse, FranceSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M21-1341 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: Recipients of solid organ transplant (SOT) are a high-risk group for severe SARS-CoV-2 infection. The mortality rate of patients with SOT during the COVID-19 pandemic has been reported to be approximately 20% (1). The anti–SARS-CoV-2 vaccines represent a hope to protect this population against this life-threatening infection.Objective: To assess the humoral response to messenger RNA (mRNA)–based vaccination in recipients of SOT.Methods: All patients with heart, kidney, liver, or pancreas transplants from the Midi-Pyrénées region (southwest France) are followed in our department. When the vaccination campaign started (7 January 2021), these patients were invited via text message, e-mail, or transplant patients' associations to be vaccinated. Patients were asked to register via a dedicated telephone number or website. They were vaccinated consecutively according to their registration date. According to the recommendations of the Francophone Society of Transplantation, anti–SARS-CoV-2 spike protein antibodies were monitored before and after vaccination. We used the SARS-CoV-2 total antibodies enzyme-linked immunosorbent assay test (Beijing Wantai Biological Pharmacy Enterprise) (80% of patients) or another validated anti–SARS-CoV-2 spike protein assay. According to French law (loi Jardé), anonymous retrospective studies do not require institutional review board approval.Findings: By 16 April 2021, 950 patients of the 2666 from our cohort had received at least 1 dose of an mRNA vaccine (BNT162b2 vaccine [Pfizer-BioNTech], n = 942; mRNA-1273 vaccine [Moderna], n = 8) and had anti–SARS-CoV-2 antibodies monitored. Fifty patients had vaccination without monitoring of antibodies, 80 patients are planned to be vaccinated within the next month, and 257 patients declined the vaccine. We had no feedback from the remaining 1329 patients.A total of 895 of the 950 patients had an available serologic screening just before the first injection. The prevalence of anti–SARS-CoV-2 antibodies was 2.1% (95% CI, 1.3% to 3.3%; n = 19 of 895). Only 5 of the 19 patients who were seropositive previously had symptomatic COVID-19. A total of 576 patients benefited from a second injection at day 28. The prevalence of anti–SARS-CoV-2 antibodies before the second injection was 6.4% (CI, 4.6% to 8.8%; n = 37 of 576).In 367 patients who had a 4-week follow-up after the second dose, the prevalence of anti–SARS-CoV-2 antibodies increased from 1.4% (CI, 0.4% to 3.2%; n = 5 of 367) at baseline to 6.3% (CI, 4.0% to 9.3%; n = 23 of 367) at day 28 and 33.8% (CI, 29.0% to 38.9%; n = 124 of 367) 1 month after the second dose (Figure). Characteristics of patients who were vaccinated with and without a 4-week follow-up after the second dose are presented in the Table.Figure. Prevalence of anti–SARS-CoV-2 antibodies at 4 wk after the second vaccine dose in all transplant patients and by type of organ transplant.Percentages with exact binomial 95% CIs are presented. Download figure Download PowerPoint Table Characteristics of Recipients of SOT With and Without a 4-Week Follow-up After 2-Dose Messenger RNA–Based VaccinationThe tolerance of mRNA vaccines was excellent, with no serious adverse events reported, except in 1 patient with a liver transplant who developed paresthesia of the lower limb. Kidney function and liver enzymes remained stable in recipients of kidney and liver transplants before and 28 days after the first dose (data not shown). One recipient of a kidney transplant presented 3 weeks after the first injection with a 50% increase in serum creatinine level related to drug-induced dehydration. The patient recovered after rehydration and reduction of diuretics. Only 1 patient, who had vaccination without the requested biological monitoring and who is not included in this report, had an acute cellular rejection.Discussion: In immunocompetent patients, mRNA vaccines have shown strong antibody response, even after a single dose (2). In immunocompromised patients, such as recipients of SOT, a weak humoral response to mRNA vaccines was reported. Boyarsky and colleagues (3) reported the appearance of specific antibodies in 17% of transplant recipients 3 weeks after a single dose of an mRNA vaccine. Recently, in a small series of patients with SOT, including mainly those who had a kidney transplant, anti–SARS-CoV-2 antibodies were detected in 37.5% to 58.8% of patients at 4 weeks after the second dose (4, 5). Our study, which included many patients with SOT, confirms a weak immunogenicity of mRNA vaccines in those who had a transplant. Recipients of liver transplant showed a better humoral response than recipients of other organs. Considering the good tolerance of mRNA vaccines, an increased antigen dose or a third vaccine dose can be proposed to improve the vaccination response in this specific population. In France, the French National Authority for Health has recently recommended offering a third dose to immunosuppressed patients.Further studies are required to assess both cellular and humoral responses to vaccines and to determine their long-term protective capacity. Meanwhile, enhanced barrier measures should be maintained, and vaccination of household members and close contacts is recommended.References1. Kates OS, Haydel BM, Florman SS, et al; UW COVID-19 SOT Study Team. COVID-19 in solid organ transplant: a multi-center cohort study. Clin Infect Dis. 2020. [PMID: 32766815] doi:10.1093/cid/ciaa1097 CrossrefGoogle Scholar2. Sahin U, Muik A, Derhovanessian E, et al. COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature. 2020;586:594-599. [PMID: 32998157] doi:10.1038/s41586-020-2814-7 CrossrefMedlineGoogle Scholar3. Boyarsky BJ, Werbel WA, Avery RK, et al. Immunogenicity of a single dose of SARS-CoV-2 messenger RNA vaccine in solid organ transplant recipients. JAMA. 2021. [PMID: 33720292] doi:10.1001/jama.2021.4385 CrossrefGoogle Scholar4. Grupper A, Rabinowich L, Schwartz D, et al. Reduced humoral response to mRNA SARS-Cov-2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus. Am J Transplant. 2021. [PMID: 33866672] doi:10.1111/ajt.16615 CrossrefGoogle Scholar5. Marinaki S, Adamopoulos S, Degiannis D, et al. Immunogenicity of SARS-CoV-2 BNT162b2 vaccine in solid organ transplant recipients [Letter]. Am J Transplant. 2021. [PMID: 33864722] doi:10.1111/ajt.16607 CrossrefMedlineGoogle Scholar Comments 0 Comments Sign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Olivier Marion, MD; Arnaud Del Bello, MD; Florence Abravanel, PharmD, PhD; Chloé Couat, MSc; Stanislas Faguer, MD, PhD; Laure Esposito, MD; Anne Laure Hebral, MD; Jacques Izopet, PharmD, PhD; Nassim Kamar, MD, PhDAffiliations: Toulouse Rangueil University Hospital, Paul Sabatier University, and INSERM UMR 1291, Toulouse Institute for Infectious and Inflammatory Disease (Infinity), Toulouse, FranceToulouse Rangueil University Hospital and Paul Sabatier University, Toulouse, FranceToulouse Purpan University Hospital, Paul Sabatier University, and INSERM UMR 1291, Toulouse Institute for Infectious and Inflammatory Disease (Infinity), Toulouse, FranceToulouse Rangueil University Hospital, Toulouse, FranceDisclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M21-1341.Reproducible Research Statement: Study protocol: Available from Dr. Kamar (e-mail, kamar.n@chu-toulouse.fr). Statistical code and data set: Not available.Corresponding Author: Olivier Marion, MD, Toulouse Rangueil University Hospital, 1 Avenue du Professeur Jean Poulhès, Toulouse, France 31000; e-mail, marion.o@chu-toulouse.fr.This article was published at Annals.org on 25 May 2021. 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Keywords Antibodies COVID-19 Disclosure Liver transplantation Messenger RNA Proteins Renal transplantation Statistical data Transplantation Vaccines ePublished: 25 May 2021 Issue Published: September 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. 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