Effectiveness of SARS-CoV-2 vaccination in fully vaccinated solid organ transplant recipients

Abstract

To the Editor: The COVID-19 pandemic has disproportionately impacted immunosuppressed patients, including solid organ transplant recipients (SOTR). COVID-19-associated mortality among SOTR was estimated at 20.5% in the early phase of the pandemic.1Kates OS, Haydel BM, Florman SS, et al. COVID-19 in solid organ transplant: a multi-center cohort study. Clin Infect Dis. 2020;2020 August 7:ciaa1097..Google Scholar SARS-CoV-2 vaccination may help reduce the morbidity and mortality of COVID-19 among SOTR. Under the emergency use authorization, the US Food Drug Administration approved two SARS-CoV-2 messenger RNA vaccines (BNT162b2 [Pfizer], mRNA-1273 [Moderna]), and an adenovirus vector-based vaccine (Ad26.COV2.S [Johnson and Johnson]). The efficacy of the mRNA vaccines and Ad26.COV2.S is >95% and 66% in the general population, respectively, but little is known about efficacy in SOTR due to their exclusion from clinical trials.2Polack FP Thomas SJ Kitchin N et al.Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.N Engl J Med. 2020; 383: 2603-2615Crossref PubMed Scopus (9742) Google Scholar, 3Baden LR El Sahly HM Essink B et al.Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.N Engl J Med. 2021; 384: 403-416Crossref PubMed Scopus (6728) Google Scholar, 4Sadoff J Gray G Vandebosch AN et al.Safety and efficacy of single-dose Ad26.COV2.S vaccine against Covid-19.N Engl J Med. 2021; 384: 2187-2201Crossref PubMed Scopus (1631) Google Scholar A retrospective, observational study of SOTR who received SARS-CoV-2 vaccine was conducted at Yale New Haven Hospital by chart review. This study was approved by the Yale University Institutional Review Board (HIC#2000027876). A total of 2197 adult SOTR are engaged in care. As of May 18, 2021, 557 SOTR (388 kidney, 105 liver, 50 heart, 14 combined organ transplants) (Table S1) without documented SARS-CoV-2 infection received ≥1 dose of a SARS-CoV-2 vaccine (Figure 1). Three-hundred and twenty-four (58%) and 206 (37%) SOTR received ≥1 dose of BNT162b2 and mRNA-1273, respectively. Twenty-seven (5%) SOTR received Ad26.COV2.S. Four hundred and eighty-two SOTR (86%) completed vaccination, and 459 (82%) were fully vaccinated (i.e., ≥14 days postcompletion of vaccine series). Of those who received ≥1 dose, 9 (1.6%) tested positive using SARS-CoV-2 nucleic acid amplification testing (NAAT) postvaccination. Six of 98 (6.12%) partially vaccinated SOTR developed SARS-CoV-2 infection. Breakthrough infection, defined as positive SARS-CoV-2 NAAT ≥14 days postvaccine series completion, occurred in 3 of 459 (0.65%) fully vaccinated SOTR (Table S2). Clinical characteristics of the SOTR who developed SARS-CoV-2 infection postvaccination are summarized in Table 1. All three had mild COVID-19, received bamlanivimab/etesevimab, and survived. Only one (patient 8) had an available cycle threshold, which was reported 15.5 and was hospitalized for a reason unrelated to COVID-19.TABLE 1Clinical characteristics of solid organ transplant recipients who developed SARS-CoV-2 infection after vaccinationOrganAge (years)RaceEthnicitySexInduction ISMaintenance ISCo-morbiditiesBMI (kg/m2)SARS-CoV–2 VaccineDose receivedLast dose of SARS-COV–2 Vaccine to first positive SARS-CoV–2 NAAT (days)Time from TXP to first SARS-CoV–2 positive NAAT (years)Severity of COVID–19aSeverity of COVID-19 was based on the National Institute of Health definition (https://www.covid19treatmentguidelines.nih.gov/overview/clinical-spectrum/). Mild disease: Individuals with symptoms but no respiratory symptoms nor abnormal chest imaging. Moderate disease: Individuals with evidence of lower respiratory disease by clinical assessment or imaging and who have oxygen saturation ≥94% on room air at sea level. Severe disease: Individuals who have oxygen saturation <94% on room air at sea level, respiratory rate of 30 breaths/min or lung infiltrates >50%.HospitalizedTreatment received for COVID-19Follow-up days after SARS-CoV2 positive NAAT (days)bAs of May 18, 2021.Status at last follow-up daybAs of May 18, 2021.Infections after partial vaccination1Kidney44WhiteLatinxFemaleAlemtuzumabTAC,MMF, PrednisoneHTNObesity47.26mRNA–12731163.7ModerateNoBamlavinimab103Alive2Kidney/Pancreas49WhiteLatinxMaleATGTAC, MMF, PrednisoneDMHTN25.24BNT162b2156.8SevereYesRemdesivirDexamethasone18Alive3Heart58BlackNon-LatinxMaleBasiliximabTAC,MMFHTNObesity30.61BNT162b21364.0SevereYesBamlavinimab/etesevimab19Alive4Kidney61WhiteNon-LatinxMaleAlemtuzumabBelatacept, MMF, PrednisoneHTNObesity32.75BNT162b2146.4MildNoBamlavinimab26Alive5Kidney64WhiteNon-LatinxMaleAlemtuzumabTAC, MMF, PrednisoneDM20.61BNT162b21164.6SevereYesBamlavinimab/etesevimab Dexamethasone39Alive6Kidney71WhiteLatinxMaleUnknownTAC, MMF, PrednisoneHTN20.85mRNA–12732714.5SevereYesRemdesivirDexamethasone41AliveBreakthrough infections ≥14 days after last dose of vaccine series7Kidney65WhiteNon-LatinxFemaleAlemtuzumabBelatacept, MMF, PrednisoneHTN27.95mRNA–12732182.2MildNoBamlavinimab/etesevimab30Alive8Liver66WhiteNon-LatinxFemaleNoneTAC, PrednisoneDMHTN22.65BNT162b22351.9MildYesBamlavinimab/etesevimab32Alive9Kidney80AsianNon-LatinxFemaleAlemtuzumabBelataceptDMHTN28.75BNT162b22636.3MildNoBamlavinimab/etesevimab30AliveAbbreviations: ATG, antithymocyte globulin; BMI, body mass index; DM, diabetes mellitus; HTN, hypertension; IS, immunosuppression; MMF, mycophenolate mofetil; NAAT, nucleic acid amplification test; TAC, tacrolimus; TXP, transplant.a Severity of COVID-19 was based on the National Institute of Health definition (https://www.covid19treatmentguidelines.nih.gov/overview/clinical-spectrum/). Mild disease: Individuals with symptoms but no respiratory symptoms nor abnormal chest imaging. Moderate disease: Individuals with evidence of lower respiratory disease by clinical assessment or imaging and who have oxygen saturation ≥94% on room air at sea level. Severe disease: Individuals who have oxygen saturation <94% on room air at sea level, respiratory rate of 30 breaths/min or lung infiltrates >50%.b As of May 18, 2021. Open table in a new tab Abbreviations: ATG, antithymocyte globulin; BMI, body mass index; DM, diabetes mellitus; HTN, hypertension; IS, immunosuppression; MMF, mycophenolate mofetil; NAAT, nucleic acid amplification test; TAC, tacrolimus; TXP, transplant. A recently published study demonstrated poor immunogenicity of mRNA SARS-CoV-2 vaccine among SOTR, measured by antispike antibody responses after completion of vaccination.5Grupper 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. https://doi.org/10.1111/ajt.16615.Google Scholar Though discouraging, such a finding was not unexpected given known reduced antibody responses to other vaccines posttransplant. Determining what antibody levels are protective against SARS-CoV-2, the role of the cellular immune responses and the utility of additional boosters in potentiating immune responses require further investigation. Despite concerns of poor humoral response, breakthrough SARS-CoV-2 infection was infrequent in our cohort. However, this rate is relatively higher compared to the general population reported by the CDC (i.e., 0.001%).6CDC. COVID-19 breakthrough case investigations and reporting. https://www.CDC.gov/vaccines/covid-19/health-departments/breakthrough-cases.html. Published 2021. Accessed May 18, 2021.Google Scholar Future prospective studies are needed to define the long-term effectiveness and immunogenicity of SARS-CoV-2 vaccines in SOTR and to determine the impact of variants on outcomes of vaccinated SOTR. As we wait for more studies, SOTR and their household members are strongly encouraged to be vaccinated and practice safety measures that include mask-wearing and social distancing. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation. Additional supporting information may be found online in the Supporting Information section. Download .docx (.02 MB) Help with docx files Table S1-S2

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