key: cord-1045464-wqivgx5z
authors: Marion, Olivier; Del Bello, Arnaud; Abravanel, Florence; Couat, Chloé; Faguer, Stanislas; Esposito, Laure; Hebral, Anne Laure; Izopet, Jacques; Kamar, Nassim
title: Safety and Immunogenicity of Anti–SARS-CoV-2 Messenger RNA Vaccines in Recipients of Solid Organ Transplants
date: 2021-05-25
journal: Ann Intern Med
DOI: 10.7326/m21-1341
sha: d1ef2705dc32ea4ce610fdecd894bc8044e781f5
doc_id: 1045464
cord_uid: wqivgx5z

nan

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-Pyr en ees 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 Jard e), anonymous retrospective studies do not require institutional review board approval. 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 followup after the second dose are presented in the Table. The 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. 

UW COVID-19 SOT Study Team. COVID-19 in solid organ transplant: a multi-center cohort study. Clin Infect Dis. 2020

COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses

Immunogenicity of a single dose of SARS-CoV-2 messenger RNA vaccine in solid organ transplant recipients

Reduced humoral response to mRNA SARS-Cov-2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus

Immunogenicity of SARS-CoV-2 BNT162b2 vaccine in solid organ transplant recipients