key: cord-0815820-0vb74m6t
authors: Spinner, Joseph A; Julien, Christopher L; Olayinka, Lily; Dreyer, William J; Bocchini, Claire E; Munoz, Flor M; Devaraj, Sridevi
title: SARS-CoV-2 Anti-Spike Antibodies After Vaccination in Pediatric Heart Transplantation: A First Report
date: 2021-11-14
journal: J Heart Lung Transplant
DOI: 10.1016/j.healun.2021.11.001
sha: ef26644087a9505fb266c8e7b66cc238db8965c6
doc_id: 815820
cord_uid: 0vb74m6t

There is a paucity of data regarding the antibody response to SARS-CoV-2 vaccination in children after solid organ transplant. We retrospectively reviewed the SARS-CoV-2 Anti-Spike IgG antibodies measured following SARS-CoV-2 vaccination at our pediatric heart transplant (HTx) center. Among patients (median age 17.1 years) in whom antibody testing was performed (median 118 days post-vaccine completion), a SARS-CoV-2 Anti-Spike IgG antibody was detected in 28/40 (70%) post-HTx recipients (median antibody level 10.9 AU/mL). Neutropenia, diabetes mellitus, and previous use of rituximab were associated with absence of a detectable antibody. All 7 post-HTx patients with a known pre-vaccination SARS-CoV-2 viral infection had a detectable SARS-CoV-2 Anti-Spike IgG. All 12 vaccinated pre-HTx patients had a detectable antibody (median antibody level 11.6 AU/mL) including 5 patients that maintained detectable antibodies post-HTx. There were no cases of myocarditis among the total of 17 pre-HTx and 81 post-HTx patients that underwent SARS-CoV-2 vaccination.

There is a paucity of data regarding the antibody response to SARS-CoV-2 vaccination in children after solid organ transplant. We retrospectively reviewed the SARS-CoV-2 Anti-Spike IgG antibodies measured following SARS-CoV-2 vaccination at our pediatric heart transplant (HTx) center. Among patients (median age 17.1 years) in whom antibody testing was performed (median 118 days post-vaccine completion), a SARS-CoV-2 Anti-Spike IgG antibody was detected in 28/40 (70%) post-HTx recipients (median antibody level 10.9 AU/mL). Neutropenia, diabetes mellitus, and previous use of rituximab were associated with absence of a detectable antibody. All 7 post-HTx patients with a known pre-vaccination SARS-CoV-2 viral infection had a detectable SARS-CoV-2 Anti-Spike IgG. All 12 vaccinated pre-HTx patients had a detectable antibody (median antibody level 11.6 AU/mL) including 5 patients that maintained detectable antibodies post-HTx. There were no cases of myocarditis among the total of 17 pre-HTx and 81 post-HTx patients that underwent SARS-CoV-2 vaccination.

On August 12, 2021, the United States Food and Drug Administration modified the Emergency Use Authorizations (EUAs) for SARS-CoV-2 messenger RNA (mRNA) vaccines to allow for administration of a third dose for certain immune-compromised people. 1 Thereafter, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) made a recommendation for use of an additional dose of the Pfizer-BioNTech antibodies. There are now data that a third mRNA vaccine dose in adult SOT recipients significantly improves the immunogenicity of the mRNA vaccine in this population. 6, 7 In light of the recent recommendations from the ACIP 2 and AST/ISHLT, 2,3 the paucity of data in pediatric SOT, and increasing spread of the SARS-CoV-2 Delta variant, it is imperative to study the antibody response to SARS-CoV-2 vaccination among pediatric SOT recipients.

At our pediatric hospital, we undertook a proactive strategy to vaccinate pediatric HTx recipients (and patients wait-listed for HTx) eligible to receive a SARS-CoV-2 vaccine. This is a retrospective, single-institutional experience aiming to describe the clinical characteristics and antibody responses of those vaccinated and in whom antibody testing was performed. Postvaccination SARS-CoV-2 Anti-Spike IgG antibody testing was performed at outpatient clinic appointments or surveillance cardiac biopsy. This protocol was approved by the Baylor College of Medicine Institutional Review Board. SARS-CoV-2 Anti-Spike IgG antibodies were quantitated using the FDA-EUA approved Vitros 5600 immunoassay. 8 (Figure 1 ). Among those with a detectable antibody, the median antibody level was 10.9 (IQR 5.5 -15.2) AU/mL. The previous use of rituximab within 6 months of vaccine dose 1, an absolute neutrophil count < 1500/mm 3 , and diabetes mellitus were associated with absence of a detectable antibody response (Table 1 ). There were no detectable antibodies in the 2 patients that received a J&J vaccine. All 7 patients with known pre-vaccination SARS-CoV-2 viral infection (diagnosed by RT-PCR) had a detectable SARS-CoV-2 Anti-Spike IgG. The use of mycophenolate and use of sirolimus were not associated with vaccine response (Table 1) . In light of the recently modified EUA, data from studies in immunosuppressed adults, lack of known protective antibody thresholds, and increasing spread of the SARS-CoV-2 Delta variant, our data support consideration of an additional dose of SARS-CoV-2 mRNA vaccine among recipients of pediatric heart transplantation to achieve an initial antibody response. Our data also support the AST/ISHLT recommendation 3 to complete the vaccination series prior to transplantation in those pediatric patients on the wait-list if possible. All pre-HTx patients in whom antibody testing was performed had detectable SARS CoV-2 Anti-Spike antibodies, and the 5 patients who underwent HTx after vaccination maintained detectable antibodies at a time of peak immunosuppression. While safety, clinical efficacy, and immunological response studies (including assessment of cell-mediated immunity) are ongoing among adult SOT recipients, it is also imperative that these studies be carefully planned and performed in children as well, as pediatric clinicians begin to consider and administer a third SARS-CoV-2 mRNA vaccine dose to pediatric solid organ transplant recipients.

Disclosure Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript. F. Munoz is a local PI for the pediatric Pfizer SARS-CoV-2 vaccination trials. She is also a member of Data Safety Monitoring Boards for Moderna and Pfizer. C. Bocchini is a local sub-I for the pediatric Pfizer SARS-CoV-2 vaccination trials. 

COVID-19) Update: FDA Authorizes Additional Vaccine Dose for Certain Immunocompromised Individuals

Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Authorized in the United States

AST Statement about Vaccine Efficacy in Organ Transplant Recipients

BNT162b2 vaccination in heart transplant recipients: Clinical experience and antibody response

Antibody Response to 2-Dose SARS-CoV-2 mRNA Vaccine Series in Solid Organ Transplant Recipients

Randomized Trial of a Third Dose of mRNA-1273 Vaccine in Transplant Recipients

Safety and Immunogenicity of a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series

Clinical Validation and Performance Evaluation of the Automated Vitros Total Anti-SARS-CoV-2 Antibodies Assay for Screening of Serostatus in COVID-19