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Letter to the Editor

Breakthrough COVID-19 Infections After mRNA Vaccination in Solid Organ Transplant Recipients in Miami, Florida

Anjan, Shweta MD1,2; Natori, Yoichiro MD1,2; Fernandez Betances, Anmary A. MD1; Agritelley, Matthew S. BA1; Mattiazzi, Adela MD2; Arosemena, Leopoldo MD2; Andrews, David M. MD3; Simkins, Jacques MD1,2; Guerra, Giselle MD2; Abbo, Lilian M. MD1,2

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doi: 10.1097/TP.0000000000003902
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Administration of coronavirus disease 2019 (COVID-19) vaccines is critical to ending the pandemic. The available mRNA vaccines are 94%–95% effective in preventing COVID-19 in the general population. Vaccine-induced antibody responses are reported to be lower in solid organ transplant recipients (SOTRs) compared with the general population; 17% after the first dose and 54% after the second dose, with poor response, are generally associated with the use of antimetabolite agents.1 In the United States, approximately 101 million persons are fully vaccinated with vaccine breakthrough infections reported in 10 262 (breakthrough rate 0.01%)2 as of April 30, 2021. Data on postvaccine infections in SOTRs are limited.

We reported the largest series of vaccine breakthrough COVID-19 infections in SOTRs in the United States (the study approved by the University of Miami Institutional Review Board). Twenty-six patients were diagnosed with COVID-19 infection by nasopharyngeal polymerase chain reaction, after receiving 1 (n = 3, 12%) or both (n = 23, 89%) doses of BNT162b2 (Pfizer-BioNTech) vaccine. They had no prior COVID-19 infection. The mean age at the time of vaccination was 58 y (32–81); 54% were males and 72% were of Hispanic ethnicity. Eleven patients (42.3%) reported exposure to unvaccinated family members with COVID-19. The median time from transplant to the vaccine (first dose) was 31 mo (range, 0.7–272), with 4 (15.3%) within 6 mo of transplant, and from vaccine to diagnosis was 34 d (range, 4–96). Antibody testing targeting the spike protein was performed via the VITROS test to measure immunoglobulin G and total antibodies (Table 1). All patients were symptomatic. Thirteen patients (50%) required hospital admission and were treated with remdesivir (92.3%, n = 12), high-dose steroids (84.6%, n = 11), and therapeutic plasma exchange (23%, n = 3; only for refractory cases in cytokine storm). Twelve patients (46%) were managed outpatient with early administration of monoclonal antibodies (MABs; casirivimab/imdevimab); all recovered with no progression of the disease. Two (16.6%) were admitted within 28 d of receiving MABs for non–COVID-19 issues. At a median follow-up of 28.5 d (range, 2–75), 5 (19.2%) had severe COVID-19 and 2 (7.6%) patients died. None of them developed rejection or graft loss.

TABLE 1. - Patient characteristics and outcomes
Patient Age/sex Type of organ transplant Maintenance IS at the time of vaccine Symptoms Chest X-ray Time from vaccine to COVID-19 diagnosis (d) Antibody testinga (total; IgG) Hospitalized for COVID-19/level of care Treatment Change in ISb Severity of COVID-19 Outcome
1 74/F Liver and kidney TAC, MMF, Pred Fatigue, nausea, vomiting, dyspnea Bilateral interstitial opacities 6 Nonreactive Yes/ICU Remdesivir, TPE, solumedrol IV MMF withheld Severe Death
2 61/F Kidney TAC, MMF, Pred Dyspnea, nasal congestion, diarrhea Bilateral interstitial opacities 26 Yes/ward Remdesivir, Dexa MMF withheld Moderate Alive
3c 41/M Kidney Everolimus, MMF, Bela, Pred Fever, cough, dyspnea Left-sided opacities 18 Nonreactive Yes/ICU Remdesivir, TPE, solumedrol IV MMF, Bela withheld Severe Alive
4 56/F Kidney TAC, MMF Fever, cough, myalgia Normal 7 Nonreactive No None MMF withheld Mild Alive
5 49/M Kidney TAC, MMF Cough, myalgia, headache Normal 9 Nonreactive No Casirivimab/imdevimab MMF withheld Mild Alive
6 46/M Kidney TAC, MMF Fatigue, diarrhea, hematuria Bilateral interstitial opacities 33 Nonreactive No Casirivimab/imdevimab MMF dose decreased by 50% Mild Alive
7 81/F Kidney TAC, MMF Fever Left sided consolidation 50 Total: 15.5; IgG: nonreactive Yes/ward Remdesivir MMF withheld Moderate Alive
8 46/M Kidney TAC, MMF, Pred Fever, chills, fatigue, nausea, diarrhea Bilateral opacities 6 Nonreactive Yes/ICU Remdesivir, Dexa, TPE MMF withheld Severe Inpatient
9 47/F Kidney-pancreas TAC, MMF, Pred Fever, fatigue, headache, cough Normal 37 Nonreactive No Casirivimab/imdevimab MMF withheld Mild Alive
10 63/F Kidney TAC, MMF Cough, dysuria, flank pain Normal 15 Nonreactive No Casirivimab/imdevimab MMF withheld Mild Alive
11 58/M Kidney TAC, MMF, Pred Cough, nasal congestion, fatigue Normal 41 Nonreactive No Casirivimab/imdevimab MMF withheld Mild Alive
12c 47/F Liver TAC, MMF, Pred Cough, fatigue Normal 11 Nonreactive No Casirivimab/imdevimab MMF withheld Mild Alive
13 65/M Liver Sirolimus, MMF Cough, dyspnea, diarrhea, nasal congestion, fatigue Bilateral opacities 73 Total: 36.10; IgG: nonreactive Yes/ward Remdesivir, Dexa MMF dose decreased by 50% Moderate Alive
14 62/F Kidney-pancreas TAC, MMF Fever, fatigue, dyspnea Right sided opacities 50 Nonreactive Yes/ward Remdesivir, Dexa MMF withheld Moderate Alive
15c 56/M Kidney TAC, MMF, Pred Cough, fatigue, arthralgia, fever, dyspnea Bilateral opacities 4 Total: 18.8; IgG: 2.68 Yes/ICU Remdesivir, Dexa MMF withheld Severe Death
16 70/F Lung TAC, Pred, MMF Nausea, diarrhea, chest pain Right-sided opacities 23 Nonreactive Yes/ward Remdesivir, Dexa MMF withheld Moderate Alive
17 62/M Kidney TAC, MMF Dyspnea Bilateral opacities 85 Total: 4.94; IgG: 3.85 Yes/ward Remdesivir, Dexa MMF withheld Moderate Alive
18 73/M Kidney Pred, MMF, Bela Fever, cough, dyspnea Bilateral interstitial opacities 96 Nonreactive No Casirivimab/imdevimab MMF withheld Mild Alive
19 73/M Heart Cyclosporine, MMF, Pred Cough Normal 74 Total: 51.6; IgG: 2.54 Yes/ICU None MMF withheld Moderate Alive
20 71/M Kidney Pred, Bela Fatigue, cough, dyspnea, dysgeusia Diffuse interstitial and alveolar opacities 68 Nonreactive Yes/ICU Remdesivir, Dexa Bela withheld Severe Inpatient
21 52/F Kidney MMF, TAC Cough, sore throat Normal 31 Total: 29.70; IgG: 9.82 Outpatient Casirivimab/imdevimab None Mild Alive
22 80/M Heart MMF, TAC Fever, chills, headache Normal 61 Total: 71.9; IgG: 1.37 Outpatient Casirivimab/imdevimab None Mild Alive
23 47/F Kidney TAC, MMF, Pred Fever, cough, myalgia Normal 34 Nonreactive Outpatient Casirivimab/imdevimab MMF withheld Mild Alive
24 37/M Kidney-pancreas TAC, MMF Azathioprine Cough, nausea, vomiting Normal 19 Total: 49.2; IgG: 16.2 Outpatient Casirivimab/imdevimab Azathioprine withheld Mild Alive
25 32/M Kidney TAC, MMF, Pred Fever, chills, fatigue, dyspnea Left-sided infiltrate 37 Nonreactive Outpatient Casirivimab/imdevimab None Mild Alive
26 53/F Kidney TAC, MMF, Pred Cough, dyspnea, diarrhea Bilateral opacities 91 Nonreactive Yes/ward Remdesivir, Dexa MMF withheld Moderate Inpatient
a Test developed by Ortho Clinical Diagnostics measured total and IgG antibodies, expressed in signal/cutoff ratio (lower limit of positivity: 1.0).
b Withheld until resolution of symptoms in each patient.
c Received only the first dose of the vaccine.
Bela, belatacept; COVID-19, coronavirus disease 2019; Dexa, dexamethasone; ICU, intensive care unit; IgG, immunoglobulin G; IS, immunosuppression; IV, intravenous; MMF, mycophenolate mofetil; Pred, prednisone; TAC, tacrolimus; TPE, therapeutic plasma exchange.

As of April 30, 2021, 2957 SOTRs have been vaccinated at our center, with 26 cases of vaccine breakthrough infection (breakthrough rate 0.87%), which is higher than that reported in the general population. Our findings confirmed that severe COVID-19 and mortality can occur from vaccine breakthrough infections in SOTRs.3,4 Data show transplant patients developed cellular and humoral responses despite immunosuppression, suggesting that vaccinated SOTRs may benefit from the vaccine even in the absence of antibody response.5

In conclusion, SOTRs remain at risk of severe COVID-19 even after the vaccination. Vaccinating SOTRs and ring vaccination of close contacts may provide better protection to immunocompromised patients. Transplant centers should continue to reinforce social distancing, mask use, and handwashing in fully vaccinated SOTR, even though mask mandates are relaxed nationally. Multicenter studies assessing cellular and humoral immunogenicity data, role of booster doses, use of MABs as prophylaxis in adjunct to vaccines, and genomic sequencing to identify variants causing vaccine breakthrough infections are needed.

REFERENCES

1. 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.
2. CDC COVID-19 Vaccine Breakthrough Case Investigations Team. COVID-19 vaccine breakthrough infections reported to CDC—United States, January 1–April 30, 2021. MMWR Morb Mortal Wkly Rep. 2021;70:792–793.
3. Tau N, Yahav D, Schneider S, et al. Severe consequences of COVID-19 infection among vaccinated kidney transplant recipients. Am J Transplant. 2021;21:2910–2912.
4. Ali NM, Alnazari N, Mehta SA, et al. Development of COVID-19 infection in transplant recipients after SARS-CoV-2 vaccination. Transplantation. 2021;105:e104–e106.
5. Thieme CJ, Anft M, Paniskaki K, et al. The magnitude and functionality of SARS-CoV-2 reactive cellular and humoral immunity in transplant population is similar to the general population despite immunosuppression. Transplantation. [Epub ahead of print. March 18, 2021]. doi:10.1097/TP.0000000000003755
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