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

Immunocompromised patients were excluded from the trials of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. Boyarsky et al^1,2 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
Diagnostic test	NP PCR	NP PCR	NP PCR	NP PCR	NP PCR	NP PCR	NP PCR
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
Diagnostic test	NP PCR	NP PCR	NP PCR	NP PCR	NP PCR	NP PCR	NP PCR
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.