COVID-19 infection in solid organ transplant recipients after SARS-CoV-2 vaccination

Abstract

To the Editor: The prevalence and mortality of COVID-19 are higher in solid organ transplant recipients (SOTs) compared to the general population.1Hasan I Rashid T Suliman S et al.Predictors of disease severity and outcome of hospitalized renal transplant recipients with COVID-19 infection: a systematic review of a globally representative sample.Rom J Intern Med. 2021; 59: 10-42PubMed Google Scholar, 2Pereira MR Mohan S Cohen DJ et al.COVID-19 in solid organ transplant recipients: Initial report from the US epicenter.Am J Transplant. 2020; 20: 1800-1808Abstract Full Text Full Text PDF PubMed Scopus (542) Google Scholar, 3Akalin E Azzi Y Bartash R et al.Covid-19 and kidney transplantation.N Engl J Med. 2020; 382: 2475-2477Crossref PubMed Scopus (548) Google Scholar Two SARS-CoV-2 messenger RNA (mRNA) vaccines have been approved by the FDA; both are 95% efficient in preventing COVID-19 in the general population. The efficacy of these vaccines in SOTs remains to be unknown as immunocompromised patients have been excluded from the vaccine studies. Initial reports indicate low immunogenicity in SOTs with only 11%–17% having detectable antispike antibody 20–28 days after one vaccine dose.4Boyarsky 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. https://doi.org/10.1001/jama.2021.4385Google Scholar,5Benotmane I, Gautier-Vargas G, Cognard N, et al. Weak anti-SARS-CoV-2 antibody response after the first injection of an mRNA COVID-19 vaccine in kidney transplant recipients. Kidney Int. 2021. https://doi.org/10.1016/j.kint.2021.03.014Google Scholar This finding concerned the transplant community but there is hope that the second vaccine dose will be more efficacious. After obtaining Mayo Institutional Review Board (IRB) approval, we reviewed the records of 7 SOTs (2 heart, 1 lung, 1 heart/kidney, 1 kidney/pancreas, and 2 kidney alone) who received either 1 (n = 2, 28%) or 2 (n = 5, 71%) doses of the BNT162b2 (Pfizer-BioNTech) or the mRNA-1273 (Moderna) SARS-CoV-2 mRNA vaccines and developed COVID-19 after a median of 28 (6–44) days of their last dose. Demographics of these patients are summarized in Table 1. Five of the 7 (71%) patients had blood type A, 1 had AB, and 1 had O blood type. All patients were symptomatic. Fever developed in 4 (57%), 4 (57%) had hypoxia/dyspnea, and 2 (28%) had diarrhea. Diagnosis was confirmed in all patients with polymerase chain reaction (PCR) of nasal swabs. Six of the patients had antibodies to COVID-19 tested at presentation. Of these, five patients had undetectable antispike antibodies and one patient, who had received his second mRNA-1273 vaccine dose 44 days prior, had low titer antispike antibody (1.4 U/ml, reference range <0.8 U/ml). None of the six tested had detectable nucleocapsid antibody. Five patients required hospitalization, four due to hypoxia and lung infiltrates that required supplemental oxygen but no intubation, while one patient was hospitalized with acute kidney injury from severe vomiting and diarrhea. All hospitalized patients received remdesivir, three received dexamethasone, four received convalescent plasma, and two received tocilizumab. Two patients had received monoclonal antibody treatment. Antimetabolites were discontinued in three of five hospitalized patients. All five patients were discharged, three on supplemental oxygen. Clinical presentation, management, and outcome of these seven patients are summarized in Table 2.TABLE 1Baseline characteristics of 7 SOT recipients who had COVID-19 infection after SARS-COV-2 mRNA vaccinationPatientOrganAgeGenderRaceBlood typeCause of organ failurePrevious organ TxInduction ISMaintenance ISRejection historyYears from Tx to COVID-19Vaccine nameNumber of dosesDays from last vaccine dose to COVID-19 diagnosis1Double Lung64MCACOPDNoATGBela/Pred/MMFYes7.37Pfizer/BioNTech2352Heart/Kidney68MCAICM/FSGSNoATGTac/MMF/PredNo3.21Pfizer/BioNTech2263Kidney60MAAADMNoAlemtuzumabTac/MMF/PredNo1.3Moderna2444Kidney42MAAOHIVANYesATGTac/MMF/PredNo0.58Pfizer/BioNTech165Kidney Pancreas43MCADMNoATGTac/MMF/PredYes11.35Moderna1286Heart69MCABICMNoBasiliximabTac/MMF/PredNo0.85Pfizer/BioNTech267Heart67MCANICMNoBasiliximabTac/MMF/PredNo0.58Moderna219Abbreviations: AA, African American; ATG, antithymocyte globulin; Bela, Belatacept; C, Caucasian; COPD, chronic obstructive pulmonary disease; DM, diabetes mellitus; HIVAN, HIV associated nephropathy; ICM, ischemic cardiomyopathy; IS, immunosuppression; M, male; MMF, mycophenolate mofetil; NICM, nonischemic cardiomyopathy; Pred, prednisone; Tac, Tacrolimus. Open table in a new tab TABLE 2Clinical presentation, serological findings, and outcome of 7 SOT recipients who had developed COVID-19 infection after SARS-COV-2 vaccinationPatientPresentationHospitalization, durationHypoxia (O2 Sat < 92% on RA)Lung infiltrateIntubationLymphopenia (absolute lymphocytes <900/mcL)AKI (Cr >0.3 mg/dl from baseline)Antispike antibody at COVID-19 diagnosisAntinucleocapside antibody at COVID-19 diagnosisIS managementCOVID-19 specific treatmentOutcome1Fever, rigors, SOBYes, 5 daysYesBilateral R>LNoYesNoNegativeNegativeMMF heldMAB1, Remd, Dexa, CP, TocilizumabDC on RA2Fever, chills, SOB, cough, N/VYes, 8 daysYesBilateral R>LNoYesNoNegativeNegativeMMF dose reducedRemd, Dexa, CPDC on 2 L O23CoughNoNoNoneNoYesNoPos (1.4 U/ml)NegativeNo changeNoneRecovered4N/V, diarrheaYes, 3 daysNoNoneNoYesYesNegativeNegativeMMF heldRemdDC on RA5Fever, cough, SOBYes, 11 daysYesBilateralNoYesYesNegativeNegativeMMF heldRemd, Dexa, CP, TocilizumabDC on 2 L O26Cough, runny noseNoNoN/ANoNoNoNDNDNo changeMAB 2Recovered7Cough, chills, weaknessYes, 5 daysYesBilateralNoYesYesNegativeNegativeNo ChangeRemd, CPDC on 2 L O2Abbreviations: CP, convalescent plasma; DC, discharged; Dexa, dexamethasone; L, left; MAB 1, bamlanivimab; MAB2, casirivimab/imdevimab; N/V, nausea and vomiting; ND, not done; R, right; RA, room air; Remd, remdesivir; SOB, shortness of breath. Open table in a new tab Abbreviations: AA, African American; ATG, antithymocyte globulin; Bela, Belatacept; C, Caucasian; COPD, chronic obstructive pulmonary disease; DM, diabetes mellitus; HIVAN, HIV associated nephropathy; ICM, ischemic cardiomyopathy; IS, immunosuppression; M, male; MMF, mycophenolate mofetil; NICM, nonischemic cardiomyopathy; Pred, prednisone; Tac, Tacrolimus. Abbreviations: CP, convalescent plasma; DC, discharged; Dexa, dexamethasone; L, left; MAB 1, bamlanivimab; MAB2, casirivimab/imdevimab; N/V, nausea and vomiting; ND, not done; R, right; RA, room air; Remd, remdesivir; SOB, shortness of breath. Of the 1624 SOT recipients transplanted in our center over the last 6 years who are Florida residents, 629 (39%) received two doses and 163 (10%) have received one dose of the BNT162b2 (Pfizer-BioNTech) or the mRNA-1273 (Moderna) SARS-CoV-2 mRNA vaccine. Five out of the seven patients in this report were Florida residents suggesting a post-vaccination infection rate of approximately 0.6% which is much higher than the rate of 0.05% reported in the general population,6Keehner J, Horton LE, Pfeffer MA, et al. SARS-CoV-2 infection after vaccination in health care workers in California. N Engl J Med. 2021. https://doi.org/10.1056/NEJMc2101927Google Scholar but this needs to be confirmed with more complete vaccination data. In conclusion, we report seven SOTs with undetectable or low titer antispike antibodies who developed COVID-19 infection after receiving one or two doses of the SARS-CoV-2 mRNA vaccine. The clinical presentation and course of these patients were comparable to those of SOTs who had COVID-19 infection and have not been vaccinated.2Pereira MR Mohan S Cohen DJ et al.COVID-19 in solid organ transplant recipients: Initial report from the US epicenter.Am J Transplant. 2020; 20: 1800-1808Abstract Full Text Full Text PDF PubMed Scopus (542) Google Scholar This finding suggests that SOTs are still at risk of acquiring COVID-19 infection even after vaccination and calls to continue measures to prevent COVID-19 infection including masking, social distancing, and regular hand hygiene in these patients even after receiving the required doses of the SARS-CoV-2 vaccine. Our findings also call for further research to study the efficacy of vaccination, to examine the post-vaccination infection rate, and to identify methods to boost the vaccine-related immune response in these immunocompromised patients. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

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