[Skip to Content]
[Skip to Content Landing]
Figure.  Inpatient Course for 17 Patients With Heart Transplant Admitted to the Study Institution With Coronavirus Disease 2019 Infection
Inpatient Course for 17 Patients With Heart Transplant Admitted to the Study Institution With Coronavirus Disease 2019 Infection

The length of hospitalization is indicated by the length of each line. Timing of medication administration is indicated along each line.

Table 1.  Patient Characteristics, Symptoms, Treatment, and Outcomes
Patient Characteristics, Symptoms, Treatment, and Outcomes
Table 2.  Laboratory Data of 17 Patients of Heart Transplant Admitted at the Study Institution With Coronavirus Disease 2019 Infection
Laboratory Data of 17 Patients of Heart Transplant Admitted at the Study Institution With Coronavirus Disease 2019 Infection
1.
Dong  E, Du  H, Gardner  L.  An interactive web-based dashboard to track COVID-19 in real time.   Lancet Infect Dis. 2020;20(5):533-534. doi:10.1016/S1473-3099(20)30120-1PubMedGoogle ScholarCrossref
2.
Richardson  S, Hirsch  JS, Narasimhan  M,  et al; and the Northwell COVID-19 Research Consortium.  Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area.   JAMA. Published online April 17, 2020. doi:10.1001/jama.2020.6775PubMedGoogle Scholar
3.
Goyal  P, Choi  JJ, Pinheiro  LC,  et al.  Clinical characteristics of Covid-19 in New York City.   N Engl J Med. Published online April 22, 2020. doi:10.1056/NEJMc2010419PubMedGoogle Scholar
4.
Wu  Z, McGoogan  JM.  Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China.   JAMA. 2020;323:1239-1242. doi:10.1001/jama.2020.2648PubMedGoogle ScholarCrossref
5.
Chen  G, Wu  D, Guo  W,  et al.  Clinical and immunological features of severe and moderate coronavirus disease 2019.   J Clin Invest. 2020;130(5):2620-2629. doi:10.1172/JCI137244PubMedGoogle ScholarCrossref
6.
Zhou  F, Yu  T, Du  R,  et al.  Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China.   Lancet. 2020;395(10229):1054-1062. doi:10.1016/S0140-6736(20)30566-3PubMedGoogle ScholarCrossref
7.
Li  F, Cai  J, Dong  N.  First cases of COVID-19 in heart transplantation from China.   J Heart Lung Transplant. 2020;39(5):496-497. doi:10.1016/j.healun.2020.03.006PubMedGoogle ScholarCrossref
8.
Fernández-Ruiz  M, Andrés  A, Loinaz  C,  et al.  COVID-19 in solid organ transplant recipients.   Am J Transplant. Published online April 16, 2020. doi:10.1111/ajt.15929PubMedGoogle Scholar
9.
Zong-Li Ren  RH, Wang  Z-W, Zhang  M,  et al.  Epidemiological and clinical characteristics of heart transplant recipients during the 2019 coronavirus outbreak in Wuhan, China.   J Heart Lung Transplant. Published online March 25, 2020. doi:10.1016/j.healun.2020.03.008Google Scholar
10.
Shen  L, Niu  J, Wang  C,  et al.  High-throughput screening and identification of potent broad-spectrum inhibitors of coronaviruses.   J Virol. 2019;93(12):93. doi:10.1128/JVI.00023-19PubMedGoogle ScholarCrossref
11.
Tanaka  Y, Sato  Y, Sasaki  T.  Suppression of coronavirus replication by cyclophilin inhibitors.   Viruses. 2013;5(5):1250-1260. doi:10.3390/v5051250PubMedGoogle ScholarCrossref
12.
Carbajo-Lozoya  J, Müller  MA, Kallies  S, Thiel  V, Drosten  C, von Brunn  A.  Replication of human coronaviruses SARS-CoV, HCoV-NL63 and HCoV-229E is inhibited by the drug FK506.   Virus Res. 2012;165(1):112-117. doi:10.1016/j.virusres.2012.02.002PubMedGoogle ScholarCrossref
13.
Pfefferle  S, Schöpf  J, Kögl  M,  et al.  The SARS-coronavirus-host interactome.   PLoS Pathog. 2011;7(10):e1002331. doi:10.1371/journal.ppat.1002331PubMedGoogle Scholar
14.
Li  HS, Kuok  DIT, Cheung  MC,  et al.  Effect of interferon alpha and cyclosporine treatment separately and in combination on Middle East respiratory syndrome coronavirus (MERS-CoV) replication in a human in-vitro and ex-vivo culture model.   Antiviral Res. 2018;155:89-96. doi:10.1016/j.antiviral.2018.05.007PubMedGoogle ScholarCrossref
15.
Clerkin  KJ, Fried  JA, Raikhelkar  J,  et al.  Coronavirus disease 2019 (COVID-19) and cardiovascular disease.   Circulation. Published online March 21, 2020. doi:10.1161/CIRCULATIONAHA.120.046941PubMedGoogle Scholar
Views 9,807
Citations 0
Brief Report
May 13, 2020

Characteristics and Outcomes of Recipients of Heart Transplant With Coronavirus Disease 2019

Author Affiliations
  • 1Division of Cardiology, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, New York
  • 2Division of Cardiac Surgery, Department of Surgery, Columbia University Vagelos College of Physicians and Surgeons, New York, New York
JAMA Cardiol. Published online May 13, 2020. doi:10.1001/jamacardio.2020.2159
Key Points

Question  What are the characteristics and outcomes of patients with heart transplant who are infected with coronavirus disease 2019 (COVID-19)?

Findings  In this case series of 28 patients who had received heart transplant in a large academic center, the case fatality rate among patients infected with COVID-19 was 25%. Cardiovascular comorbidities were frequent in this population, and immunosuppressive therapy was reduced in most patients.

Meaning  Recipients of heart transplant are at high risk for severe complications from coronavirus disease 2019 infection; management of this population is complex and should take place in a transplant center.

Abstract

Importance  Recipients of heart transplant (HT) may be at increased risk of adverse outcomes attributable to infection with coronavirus disease 2019 (COVID-19) because of multiple comorbidities and clinically significant immunosuppression.

Objective  To describe the characteristics, treatment, and outcomes of recipients of HT with COVID-19.

Design, Setting, and Participants  This case series from a single large academic heart transplant program in New York, New York, incorporates data from between March 1, 2020, and April 24, 2020. All recipients of HT followed up by this center who were infected with COVID-19 were included.

Interventions  Heart transplant and a confirmed diagnosis of COVID-19.

Main Outcomes and Measures  The primary measure was vital status at end of study follow-up. Secondary measures included patient characteristics, laboratory analyses, changes to immunosuppression, and treatment administered for COVID-19.

Results  Twenty-eight patients with HT received a confirmed diagnosis of COVID-19. The median age was 64.0 (interquartile range [IQR], 53.5-70.5) years, 22 (79%) were men, and the median time from HT was 8.6 (IQR, 4.2-14.5) years. Comorbid conditions included hypertension in 20 patients (71%), diabetes in 17 patients (61%), and cardiac allograft vasculopathy in 16 patients (57%). Twenty-two participants (79%) were admitted for treatment, and 7 (25%) required mechanical ventilation. Most (13 of 17 [76%]) had evidence of myocardial injury (median high-sensitivity troponin T, 0.055 [IQR, 0.0205-0.1345] ng/mL) and elevated inflammatory biomarkers (median peak high-sensitivity C-reactive protein, 11.83 [IQR, 7.44-19.26] mg/dL; median peak interleukin 6, 105 [IQR, 38-296] pg/mL). Among patients managed at the study institution, mycophenolate mofetil was discontinued in 16 patients (70%), and 6 (26%) had a reduction in the dose of their calcineurin inhibitor. Treatment of COVID-19 included hydroxychloroquine (18 patients [78%]), high-dose corticosteroids (8 patients [47%]), and interleukin 6 receptor antagonists (6 patients [26%]). Overall, 7 patients (25%) died. Among 22 patients (79%) who were admitted, 11 (50%) were discharged home, 4 (18%) remain hospitalized at the end of the study, and 7 (32%) died during hospitalization.

Conclusions and Relevance  In this single-center case series, COVID-19 infection was associated with a case fatality rate of 25% in recipients of HT. Immunosuppression was reduced in most of this group of patients. Further study is required to evaluate the optimal approach to management of COVID-19 infection in the HT population.

Introduction

Coronavirus disease 2019 (COVID-19) is a pandemic affecting more than 3 million people worldwide and carrying a case fatality rate exceeding 7% as of early May 2020.1 New York, New York, has emerged as the most recent epicenter of the disease, with more than 150 000 confirmed cases and nearly 11 000 fatalities (as of April 26, 2020).1 Preexisting cardiovascular diseases, such as hypertension, coronary artery disease, and diabetes, have been associated with an increased risk for COVID-19.2-4 Disease severity appears to be driven not only by viral invasion and proliferation but also by an intense immune response marked by cytokine storm, myocardial injury, and death.5,6 Recipients of heart transplant (HT) may be at an increased risk for infection and adverse outcomes with COVID-19 infection because of a number of comorbidities that are common following heart transplant, including hypertension, diabetes, and cardiac allograft vasculopathy. Moreover, while all require maintenance immunosuppression that predisposes recipients to a greater infectious risk, immunosuppression has also been theorized to be protective from cytokine storm. Preliminary case reports7,8 have not indicated a disproportionate outcome of COVID-19 on the posttransplant population, and a survey9 from China did not find an increased risk of infection among recipients of HT. In this article, we present a large case series of recipients of HT with COVID-19 and describe their presentation, disease course, outcomes, and immunosuppression management. The aim of this case series is to describe the outcomes of recipients of HT who are chronically immunosuppressed and develop COVID-19 and raise important questions about the role of the immune system in the disease process.

Methods

We retrospectively reviewed all adult recipients of HT (>18 years of age) followed at a large academic center in New York, New York. Those who received a laboratory diagnosis of COVID-19 were included in the study. Laboratory data were collected for patients hospitalized in our health system. Treatment data were collected for those admitted to our hospital or managed by our program as outpatients. Outcomes and follow-up were recorded for all patients through April 24, 2020. All continuous data are presented as medians with interquartile ranges (IQRs). Analyses were performed using SAS version 9.4 (SAS Institute Inc). This study was approved by the Columbia University Irving Medical Center institutional review board. A waiver of consent was granted to protect the safety of the staff, since consent would have required direct exposure while patients were actively infected with COVID-19. All data were deidentified following collection.

Results

In this cohort of recipients of HT (N = 803), we identified 28 who had presented for acute care for COVID-19 disease over a 6-week period. The median age of patients with COVID-19 was 64.0 (IQR, 53.5-70.5) years, 22 (79%) were men, and the median time from transplant was 8.6 (IQR, 4.2-14.5) years (Table 1). Twenty patients (71%) had hypertension, 17 of 28 (61%) had diabetes mellitus, 7 of 28 (25%) were obese (body mass index [calculated as weight in kilograms divided by height in meters squared] >30), 10 of 28 (36%) had stage IV or greater chronic kidney disease (with 5 [18%] on hemodialysis), 16 of 28 (57%) had cardiac allograft vasculopathy, and 4 of 28 (14%) had preexisting allograft dysfunction. Disease presentation included fever (19 [83%]), dyspnea or cough (21 [91%]), and gastrointestinal symptoms (11 [48%]).

Twenty-two patients (79%) were admitted, and 6 (21%) were managed as outpatients. Among the inpatients, 7 required admission to the intensive care unit. Seventeen were admitted to the study hospital and thus had complete laboratory data for analysis. Laboratory results are summarized in Table 2. The median (IQR) white blood cell count was 4900 (3000-8900) per microliter (to convert to ×109/L, multiply by 0.001), with a median (IQR) absolute lymphocyte count of 600 (300-800) per microliter (to convert to ×109/L, multiply by 0.001). Evidence of myocardial injury was present in 13 patients (77%), and the median peak high-sensitivity troponin T level was 0.055 (0.0205-0.1345) nanograms per milliliter (to convert to micrograms per liter, multiply by 1.0). Inflammatory parameters were markedly elevated, in that high-sensitivity C-reactive protein was greater than normal in all patients, with a median (IQR) peak of 11.83 (7.44-19.26) milligrams per deciliter (to convert to milligrams per liter, multiply by 10); interleukin 6 was elevated in 15 patients (88%), with a median (IQR) peak of 105 (38-296) picograms per milliliter; and D-dimer was greater than 1 microgram per milliliter in 14 patients (82%). Seven patients had an echocardiogram during hospitalization. When compared with the most recent echocardiogram, left ventricular ejection fraction was unchanged in 5 patients, improved in 1 patient, and decreased in 1 patient. Notably, both patients with changes from baseline had preexisting allograft dysfunction.

Supplemental oxygen was required in 20 of the hospitalized patients (91%), 7 of these patients required intubation (5 at outside hospitals and 2 at our institution), and de novo dialysis was required in 3 patients. Baseline immunosuppressive medications included calcineurin inhibitors in 27 patients (96%), mycophenolate mofetil in 19 (68%), proliferation signal inhibitors in 5 (18%), and corticosteroids in 19 (68%). During infection with COVID-19, mycophenolate mofetil was discontinued in 16 of 23 patients (70%) and the calcineurin inhibitor dosage was reduced in 6 patients (26%). Twenty-three patients (87%) received treatments directed at COVID-19: high-dose corticosteroids (8 of 23 [47%]), hydroxychloroquine (18 of 23 [78%]), or an interleukin 6 receptor antagonist (6 of 23 [26%]) (Figure). None of the patients in our cohort experienced an episode of clinically overt rejection during this period.

Among all patients with HT diagnosed with COVID-19, 22 (79%) were hospitalized and 7 (25%) died (Table 1). Of the hospitalized patients, 11 (50%) were discharged, 4 (18%) remain hospitalized at the end of the study, and 7 (50%) died in the hospital. Six patients (21%) were treated as outpatients. The mortality rate of the patients admitted to the study center with COVID-19 was 11.2% (2 of 17 patients), while all 5 patients admitted to outside institutions died.

Discussion

In this case series of recipients with HT who had confirmed COVID-19 infection, we report a high case fatality rate of 25%, which was much higher than currently reported in other patient populations. Of note, we did not routinely test patients who were asymptomatic, and there were limitations on testing patients with mild symptoms at the earliest phases of the pandemic. Therefore, we may have underestimated the prevalence of COVID-19 infection in this transplant population. Furthermore, we were unable to address whether cardiovascular risk factors, immunosuppression, or HT status itself increased the risk of mortality among this population. The effect of immunosuppression on the course of this disease remains unclear. While in vitro evidence suggests that immunosuppressive medications may inhibit viral replication,10-14 long-term immunosuppression nonetheless increases susceptibility to infection, dampening the ability to mount an effective response. Most patients in this case series had their immunosuppression medications reduced following diagnosis, although the population size is too small to evaluate the effectiveness of this strategy. Whether immunosuppression can temper the immune dysregulation seen in cases of severe disease remains unknown. The high case fatality rate in this cohort does not suggest a protective benefit from immunosuppression; however, randomized studies to assess each individual immunosuppressive agent would be needed to provide a definitive answer.

Managing recipients of HT with COVID-19 has increased complexity because they have more intense immunosuppression than many other solid organ transplant recipients, combined with the potential for the virus to cause both primary and secondary myocardial injury.15 Although our cohort is small, we recommend that patients who have received HT are treated at a transplant center while infected with COVID-19. Furthermore, these patients will require ongoing monitoring in the recovery phase as an immunosuppression regimen is reintroduced and the consequences to the allograft itself become apparent. The high case fatality rate in this cohort calls for close monitoring of recipients of HT and a low threshold for hospitalization during acute infection with COVID-19.

Back to top
Article Information

Accepted for Publication: May 1, 2020.

Corresponding Author: Nir Uriel, MD, MSc, Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, Weill Cornell Medicine, 622 W 168th St, PH 4-129, New York, NY 10032 (nu2126@cumc.columbia.edu).

Published Online: May 13, 2020. doi:10.1001/jamacardio.2020.2159

Author Contributions: Drs Uriel and Clerkin had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Latif and Farr had an equal contribution to the manuscript.

Concept and design: Latif, Farr, Clerkin, Habal, Naka, Sayer, Uriel.

Acquisition, analysis, or interpretation of data: Latif, Farr, Clerkin, Habal, Takeda, Restaino, Uriel.

Drafting of the manuscript: Farr, Clerkin, Naka, Restaino, Sayer, Uriel.

Critical revision of the manuscript for important intellectual content: Latif, Farr, Clerkin, Habal, Takeda, Naka, Sayer, Uriel.

Statistical analysis: Clerkin, Uriel.

Administrative, technical, or material support: Clerkin.

Supervision: Latif, Sayer, Uriel.

Conflict of Interest Disclosures: Dr Naka reported personal fees from Abbott, CryoLife, and Zimmer-Biomet outside the submitted work. No other disclosures were reported.

Funding/Support: Dr Clerkin is supported by the National Heart, Lung, and Blood Institute (grant K23HL148528).

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

References
1.
Dong  E, Du  H, Gardner  L.  An interactive web-based dashboard to track COVID-19 in real time.   Lancet Infect Dis. 2020;20(5):533-534. doi:10.1016/S1473-3099(20)30120-1PubMedGoogle ScholarCrossref
2.
Richardson  S, Hirsch  JS, Narasimhan  M,  et al; and the Northwell COVID-19 Research Consortium.  Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area.   JAMA. Published online April 17, 2020. doi:10.1001/jama.2020.6775PubMedGoogle Scholar
3.
Goyal  P, Choi  JJ, Pinheiro  LC,  et al.  Clinical characteristics of Covid-19 in New York City.   N Engl J Med. Published online April 22, 2020. doi:10.1056/NEJMc2010419PubMedGoogle Scholar
4.
Wu  Z, McGoogan  JM.  Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China.   JAMA. 2020;323:1239-1242. doi:10.1001/jama.2020.2648PubMedGoogle ScholarCrossref
5.
Chen  G, Wu  D, Guo  W,  et al.  Clinical and immunological features of severe and moderate coronavirus disease 2019.   J Clin Invest. 2020;130(5):2620-2629. doi:10.1172/JCI137244PubMedGoogle ScholarCrossref
6.
Zhou  F, Yu  T, Du  R,  et al.  Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China.   Lancet. 2020;395(10229):1054-1062. doi:10.1016/S0140-6736(20)30566-3PubMedGoogle ScholarCrossref
7.
Li  F, Cai  J, Dong  N.  First cases of COVID-19 in heart transplantation from China.   J Heart Lung Transplant. 2020;39(5):496-497. doi:10.1016/j.healun.2020.03.006PubMedGoogle ScholarCrossref
8.
Fernández-Ruiz  M, Andrés  A, Loinaz  C,  et al.  COVID-19 in solid organ transplant recipients.   Am J Transplant. Published online April 16, 2020. doi:10.1111/ajt.15929PubMedGoogle Scholar
9.
Zong-Li Ren  RH, Wang  Z-W, Zhang  M,  et al.  Epidemiological and clinical characteristics of heart transplant recipients during the 2019 coronavirus outbreak in Wuhan, China.   J Heart Lung Transplant. Published online March 25, 2020. doi:10.1016/j.healun.2020.03.008Google Scholar
10.
Shen  L, Niu  J, Wang  C,  et al.  High-throughput screening and identification of potent broad-spectrum inhibitors of coronaviruses.   J Virol. 2019;93(12):93. doi:10.1128/JVI.00023-19PubMedGoogle ScholarCrossref
11.
Tanaka  Y, Sato  Y, Sasaki  T.  Suppression of coronavirus replication by cyclophilin inhibitors.   Viruses. 2013;5(5):1250-1260. doi:10.3390/v5051250PubMedGoogle ScholarCrossref
12.
Carbajo-Lozoya  J, Müller  MA, Kallies  S, Thiel  V, Drosten  C, von Brunn  A.  Replication of human coronaviruses SARS-CoV, HCoV-NL63 and HCoV-229E is inhibited by the drug FK506.   Virus Res. 2012;165(1):112-117. doi:10.1016/j.virusres.2012.02.002PubMedGoogle ScholarCrossref
13.
Pfefferle  S, Schöpf  J, Kögl  M,  et al.  The SARS-coronavirus-host interactome.   PLoS Pathog. 2011;7(10):e1002331. doi:10.1371/journal.ppat.1002331PubMedGoogle Scholar
14.
Li  HS, Kuok  DIT, Cheung  MC,  et al.  Effect of interferon alpha and cyclosporine treatment separately and in combination on Middle East respiratory syndrome coronavirus (MERS-CoV) replication in a human in-vitro and ex-vivo culture model.   Antiviral Res. 2018;155:89-96. doi:10.1016/j.antiviral.2018.05.007PubMedGoogle ScholarCrossref
15.
Clerkin  KJ, Fried  JA, Raikhelkar  J,  et al.  Coronavirus disease 2019 (COVID-19) and cardiovascular disease.   Circulation. Published online March 21, 2020. doi:10.1161/CIRCULATIONAHA.120.046941PubMedGoogle Scholar
×