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Letter to the Editor

Development of COVID-19 Infection in Transplant Recipients After SARS-CoV-2 Vaccination

Ali, Nicole M. MD1; Alnazari, Nasser MD1; Mehta, Sapna A. MD1; Boyarsky, Brian MD2; Avery, Robin K. MD2; Segev, Dorry L. MD, PhD2; Montgomery, Robert A. MD, DPhil1; Stewart, Zoe A. MD, PhD1

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doi: 10.1097/TP.0000000000003836
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Immunocompromised patients were excluded from the trials of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. Boyarsky et al1,2 recently reported that only 17% of transplant recipients who received a single dose of SARS-CoV-2 vaccine developed detectable antispike antibody (compared with 100% of the nonimmunocompromised subjects in the pivotal trials) and after 2 doses, response increased to 54% in transplant recipients. However, the clinical impact of this low antibody response remains unclear, especially in light of second doses.

We performed a retrospective chart review of 14 solid organ transplant (SOT) recipients (10 kidney, 2 liver, 1 lung, and 1 heart) with a median age of 62 (27–78) y who were diagnosed with COVID-19, a median of 23.5 (3–57) d after completion of SARS-CoV-2 vaccination. Demographics of these patients are summarized in Table 1. Eight patients completed the BNT162b2 (Pfizer-BioNTech) series, 5 completed the mRNA-1273 (Moderna) series, and 1 patient received the JNJ-78436735 (Janssen/Johnson & Johnson) SARS-CoV-2 vaccine. Six (42.8%) patients presented with cough, 5 (35.7%) with fever, 4 (28.6%) with fatigue, 3 (21.4%) with dyspnea, 2 (14.3%) with diarrhea, and 2 (14.3%) with body aches. Diagnosis was confirmed by SARS-CoV-2 via nasopharyngeal swab polymerase chain reaction for all patients. Maintenance immunosuppression regimen included prednisone for all patients, calcineurin inhibitor in 13 (92.9%) patients, antimetabolite agent in 13 (92.9%) patients, belatacept in 1 (7.1%) patient, and mammalian target of rapamycin inhibitor in 1 (7.1%) patient. Seven (50%) patients were hospitalized, 5 with severe COVID-19 (mechanical ventilation, supplemental oxygen, oxygen saturation <94% on ambient air, or respiratory rate ≥24 breaths per minute). All patients with severe disease received dexamethasone and remdsevir, while 2 patients also received interleukin-6 inhibitor and 2 received convalescent plasma. Seven (50%) patients were treated with monoclonal antibody infusion outside of the hospital; however, 2 of these patients required admission for progressive illness. Two patients remain hospitalized at this time, 1 died, and 11 haverecovered at home. Approval for this study was obtained from both the NYU Grossman School of Medicine and Johns Hopkins Institutional Review Board.

TABLE 1. - Patient demographics and clinical points (patients 1–7 and patients 8–14)
Patient 1 2 3 4 5 6 7
 Age 44 68 58 72 27 69 71
 Time from txp (mo) 16 16 19 2.5 11 18 59
 Organ Kidney Kidney Kidney Kidney Kidney Kidney Lung
 Immunosuppression regimen TAC, MMF, Pred TAC, MMF, Pred TAC, MMF, Pred TAC, MMF, Pred TAC, MPA, Pred TAC, MMF, Pred TAC, MMF, Pred
 Vaccine to sx onset (d) 6 4 17 19 40 20 1
 Vaccine to infection diagnosis (d) 11 4 19 20 43 25 3
 Vaccine manufacturer Pfizer/BioNTech Moderna Janssen/Johnson & Johnson Pfizer/BioNTech Pfizer/BioNTech Pfizer/BioNTech Pfizer/BioNTech
 Initial symptoms Cough, fever, hypoxia Cough, fatigue Diarrhea Cough, fever, diarrhea Cough Dyspnea, fever Dyspnea, fever
 Result Positive positive Positive Positive Positive Positive Positive
 COVID-19 severity Severe Mild Mild Mild-mod Mild Severe Severe
 COVID-19-directed treatment Remd, Dex None MAB, Remd MAB MAB Remd, Dex MAB, Remd, Dex, L-6 inh
 Hospitalized Yes Yes Yes No No Yes Yes
 Outcome Alive Alive Inpatient Alive Alive Alive Alive
Patient 8 9 10 11 12 13 14
 Age 78 71 65 56 59 54 52
 Time from txp (mo) 126 24 12 67 47 48 53
 Organ Heart Kidney Liver Liver Kidney Kidney Kidney
 Immunosuppression regimen CSA, mTOR, Pred TAC, MMF, Pred TAC, MPA, Pred TAC, MMF, Pred TAC, MMF, Pred Bela, MMF, Pred TAC, MMF, Pred
 Vaccine to sx onset (d) 55 15 22 27 31 44 37
 Vaccine to infection diagnosis (d) 57 18 22 27 36 45 40
 Vaccine manufacturer Pfizer/BioNTech Moderna Moderna Moderna Moderna Pfizer/BioNTech Pfizer/BioNTech
 Initial symptoms Chills Fever, diarrhea, vomiting Cough, headache Fatigue Headache, body aches, fatigue Fatigue Cough, body aches
 NP PCR result Positive Positive Positive Positive Positive Positive Positive
 COVID-19 severity Severe Severe Mild-mod Mild Mild Mild Mild-mod
 COVID-19-directed treatment Remd, Dex, CCP, IL-6 inh MAB, Remd, Dex, CCP MAB None None None MAB
 Hospitalized Yes Yes No No No No No
 Outcome Died Inpatient Alive Alive Alive Alive Alive
Bela, belatacept; CCP, COVID convalescent plasma; CSA, cyclosporine; IL-6 inh, interleukin-6 inhibitor; MAB, monoclonal antibody; MMF, mycophenolate mofetil MPA, mycophenolic acid; mTOR, mammalian target of rapamycin inhibitors; NP PCR, nasopharyngeal polymerase chain reaction; Remd, remdesivir; TAC, tacrolimus.

Zervou et al3 reported that 83% of 56 SOT recipients who recovered from COVID-19 infection were positive for SARS-CoV-2 immunoglobulin G (IgG). Similarly, Benotmane et al4 reported a cohort of 36 kidney transplant patients, all of whom had detectable IgG by 15 d post–COVID-19 infection, and Boyarsky et al5 reported durable IgG formation in 18 SOT recipients. These studies suggested that the anti–SARS-CoV-2 humoral response is not significantly impaired in the immunocompromised population and provided some optimism that a similar response would occur after the mRNA vaccines. However, the uniform IgG antispike antibody response observed in the pivotal SARS-CoV-2 mRNA-12736 trial by d 15 and the BNT162b7 trial by d 21 differs dramatically from what has been seen in transplants patients.1 Additionally, the mean IgG antispike level is significantly higher in nonimmunosuppressed controls compared with kidney transplant recipients.8 This suggests that immunosuppressed patients need to be made aware that they may not be protected from infection postvaccine.1,2 With this report of 14 patients who developed COVID-19 infection after completion of vaccination, we believe that there is sufficient evidence to issue warnings that immunoincompetent populations should continue to practice strict COVID-19 precautions postvaccination. It is also possible that vaccine responses may be delayed in immunosuppressed patients and further clarity will likely be forthcoming as vaccinated transplant patients are followed longitudinally. Transplant centers should reinforce that guidance given to the general population may not be applicable to the transplant population. A centralized transplant registry of fully vaccinated SOT patients who develop COVID-19 infections is vital. Ongoing clinical trials will help determine if current COVID-19 vaccination protocols will reduce the incidence, severity, and mortality of COVID-19 in transplant recipients and whether additional doses of mRNA vaccines or crossover to vaccines with other mechanisms of action will be necessary to protect this population. Further studies are critically needed to optimize COVID-19 vaccination protocols in transplant recipients.


1. 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;325:1784–1786.
2. Boyarsky BJ, Werbel WA, Avery RK, et al. Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients. JAMA. 2021;325:2204–2206.
3. Zervou F, Ali N, Neumann H, et al. COVID-19 antibody tesponses in solid organ transplant recipients. 2020;7(suppl 1):S332.
4. Benotmane I, Gautier-Vargas G, Wendling MJ, et al. In-depth virological assessment of kidney transplant recipients with COVID-19. Am J Transplant. 2020;20:3162–3172.
5. Boyarsky BJ, Ou MT, Werbel WA, et al. Early development and durability of SARS-CoV-2 antibodies among solid organ transplant recipients: a pilot study. Transplantation. 2021;105:e52–e53.
6. Jackson LA, Anderson EJ, Rouphael NG, et al.; mRNA-1273 Study Group. An mRNA vaccine against SARS-CoV-2 - preliminary report. N Engl J Med. 2020;383:1920–1931.
7. Walsh EE, Frenck RW Jr, Falsey AR, et al. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N Engl J Med. 2020;383:2439–2450.
8. Grupper A, Rabinowich L, Schwartz D, et al. Reduced humoral response to mRNA SARS-Cov-2 BNT 162b2 vaccine in kidney transplant recipients without prior exposure to the virus. Am J Transpl. 2021. doi: 10.1111/ajt.16615
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