COVID-19 in heart transplant recipients

    Authors

    Abstract

    **Introduction**: Data on heart transplant (HTx) patients and infection with acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are very limited. There is significant heterogeneity in the clinical presentation. (1) Immunosuppression-related issues are of the main concern because of an increased risk for viral replication and superimposed infections. There is no evidence-based recommendation for the management of these patients. Some authors suggest modification in immunosuppression, i.e. discontinuation of mycophenolate mofetil (MMF) and calcineurin inhibitor (CNI) reduction in patients with more severe clinical presentation. (2) **Patients and Methods**: This is a case series of 5 HTx recipients from our center who tested positive for COVID-19 infection and were treated in different COVID-19 specialized units. **Results**: There were 4 male and one female patients, 62-75 years old. Four of them were symptomatic and hospitalized, while one remained self-quarantined at home. The clinical presentation was mild to moderate, with symptoms including mild fever, dyspnea, and myalgia. X-ray signs of pneumonia were present in 3 patients, but none needed ICU care nor mechanical ventilation. Both a reduction of CNI dose with lower target serum concentration and MMF was discontinued in all patients. One patient was treated with hydroxychloroquine, one with remdesivir and one with steroid therapy. Antibiotics prophylaxis was administered in 2 patients. None of the patients experienced overt graft rejection and all patients have successfully recovered (**Table 1**). ### TABLE 1: Main characteristics of the 5 heart transplant patients with COVID-19. | | **Patient 1** | **Patient 2** | **Patient 3** | **Patient 4** | **Patient 5** | | --- | --- | --- | --- | --- | --- | | **Age (years)** | 63 | 57 | 62 | 75 | 66 | | **Gender** | Female | Male | Male | Male | Male | | **Time from HTx (years)** | 3 | 3 | 3 | 10 | 5 | | **Imumunosuppressive therapy (mg/day)** | | | | | | | **Tacrolimus** | 1.5 | 2 | - | 1.5 | - | | **Cyclosporine** | - | - | 160 | - | 160 | | **Mycophenolate mofetil** | 1500 | - | 3000 | 2000 | 2000 | | **Everolimus** | - | 0.5 | - | - | - | | **COVID-19 onset** | | | | | | | **Presenting symptoms** | | | | | | | **Cough** | - | + | - | - | - | | **Shortness of breath** | + | + | + | - | + | | **Myalgia** | + | + | + | - | + | | **Anosmia** | + | + | - | - | - | | **Headache** | + | - | - | - | + | | **Sinusitis** | - | - | - | - | - | | **Gastrointestinal symptoms** | - | - | - | - | + | | **NPS test** | + | + | + | + | + | | **X-ray pneumonia signs** | - | + | + | - | + | | **Fever peak (°C)** | 37.9 | 38 | 37.6 | 36.6 | 37.8 | | **Hospitalization** | - | + | + | + | + | | **SpO2 at admission (%)** | / | 90 | 95 | 96 | 96 | | **Worst SpO2 during hospitalization** | / | 90 | 94 | 91 | 96 | | **Laboratory results at admission** | | | | | | | **WBC count (cells per 109/l)** | 4.0 | 5.5 | 5.3 | 2.8 | 7.5 | | **Hb (g/l)** | 121 | 139 | 139 | 105 | 149 | | **Platelets (cells per 109/l)** | 283 | 124 | 192 | 111 | 140 | | **Lymphoyte (cells per 109/l)** | 0.60 | 1.70 | 0.55 | 0.62 | / | | **CRP (mg/l)** | 0.9 | 57.4 | 6.8 | 0.4 | 20 | | **Creatinine (umol/l)** | 107 | 126 | 72 | 136 | 169 | | **Troponin I (ug/l)** | / | / | 4 | / | / | | **Treatment and outcomes** | | | | | | | **Hydroxychloroquine** | - | - | - | - | + | | **Remdesivir** | - | - | + | - | - | | **Corticosteroid therapy** | - | + | - | - | - | | **Discontinuation of mycophenolate mofetil** | + | + | + | + | + | | **Antibiotics prophylaxis** | - | + | - | - | + | | **ICU stay** | - | - | - | - | - | | **Mechanical ventilation** | - | - | - | - | - | | **Complications** | - | - | - | - | - | | **In-hospital length of stay (days)** | / | 5 | 9 | 21 | 11 | | **Outcome** | Alive | Alive | Alive | Alive | Alive | [†] NPS- nasop haryngeal swab test, SpO2 - oxygen saturation, CRP- C-reactive protein, ICU - intensive care unit **Conclusion**: Lacking any evidence-based recommendation for the treatment of HTx patients infected with SARS-CoV-2, we are challenged to modify maintenance immunosuppression carefully balancing between the risk of uncontrolled viral replication with a superimposed infection on one side, and the increased risk of graft rejection on the other side. Further studies are needed to determine the optimal management of COVID-19 infection in these patients.

    Keywords

    heart transplantation, COVID-19, immunosuppression therapy

    DOI

    https://doi.org/10.15836/ccar2021.25

    Literature

    1. Caraffa R, Bagozzi L, Fiocco A, Bifulco O, Nadali M, Ponzoni M, et al. Coronavirus disease 2019 (COVID-19) in the heart transplant population: a single-centre experience. Eur J Cardiothorac Surg. 2020 November 1;58(5):899–906. https://doi.org/10.1093/ejcts/ezaa323
    2. Latif F, Farr MA, Clerkin KJ, Habal MV, Takeda K, Naka Y, et al. Characteristics and Outcomes of Recipients of Heart Transplant With Coronavirus Disease 2019. JAMA Cardiol. 2020 May 13:e202159. https://doi.org/10.1001/jamacardio.2020.2159
    Cardiologia Croatica
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    COVID-19 in heart transplant recipients

    Extended Abstract
    Issue1-2
    Published
    Pages25-26
    PDF via DOIhttps://doi.org/10.15836/ccar2021.25
    heart transplantation
    COVID-19
    immunosuppression therapy

    Authors

    Petra Mjehović*ORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Maja ČikešORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Mia DubravčićORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Dora FabijanovićORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Nina JakušORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Hrvoje JurinORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Daniel LovrićORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Jana Ljubas MačekORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Marijan PašalićORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Ivo PlanincORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Jure SamardžićORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Boško SkorićORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Davor MiličićORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia

    *Correspondence email: petra.mjehovic@gmail.com

    Abstract

    **Introduction**: Data on heart transplant (HTx) patients and infection with acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are very limited. There is significant heterogeneity in the clinical presentation. (1) Immunosuppression-related issues are of the main concern because of an increased risk for viral replication and superimposed infections. There is no evidence-based recommendation for the management of these patients. Some authors suggest modification in immunosuppression, i.e. discontinuation of mycophenolate mofetil (MMF) and calcineurin inhibitor (CNI) reduction in patients with more severe clinical presentation. (2) **Patients and Methods**: This is a case series of 5 HTx recipients from our center who tested positive for COVID-19 infection and were treated in different COVID-19 specialized units. **Results**: There were 4 male and one female patients, 62-75 years old. Four of them were symptomatic and hospitalized, while one remained self-quarantined at home. The clinical presentation was mild to moderate, with symptoms including mild fever, dyspnea, and myalgia. X-ray signs of pneumonia were present in 3 patients, but none needed ICU care nor mechanical ventilation. Both a reduction of CNI dose with lower target serum concentration and MMF was discontinued in all patients. One patient was treated with hydroxychloroquine, one with remdesivir and one with steroid therapy. Antibiotics prophylaxis was administered in 2 patients. None of the patients experienced overt graft rejection and all patients have successfully recovered (**Table 1**). ### TABLE 1: Main characteristics of the 5 heart transplant patients with COVID-19. | | **Patient 1** | **Patient 2** | **Patient 3** | **Patient 4** | **Patient 5** | | --- | --- | --- | --- | --- | --- | | **Age (years)** | 63 | 57 | 62 | 75 | 66 | | **Gender** | Female | Male | Male | Male | Male | | **Time from HTx (years)** | 3 | 3 | 3 | 10 | 5 | | **Imumunosuppressive therapy (mg/day)** | | | | | | | **Tacrolimus** | 1.5 | 2 | - | 1.5 | - | | **Cyclosporine** | - | - | 160 | - | 160 | | **Mycophenolate mofetil** | 1500 | - | 3000 | 2000 | 2000 | | **Everolimus** | - | 0.5 | - | - | - | | **COVID-19 onset** | | | | | | | **Presenting symptoms** | | | | | | | **Cough** | - | + | - | - | - | | **Shortness of breath** | + | + | + | - | + | | **Myalgia** | + | + | + | - | + | | **Anosmia** | + | + | - | - | - | | **Headache** | + | - | - | - | + | | **Sinusitis** | - | - | - | - | - | | **Gastrointestinal symptoms** | - | - | - | - | + | | **NPS test** | + | + | + | + | + | | **X-ray pneumonia signs** | - | + | + | - | + | | **Fever peak (°C)** | 37.9 | 38 | 37.6 | 36.6 | 37.8 | | **Hospitalization** | - | + | + | + | + | | **SpO2 at admission (%)** | / | 90 | 95 | 96 | 96 | | **Worst SpO2 during hospitalization** | / | 90 | 94 | 91 | 96 | | **Laboratory results at admission** | | | | | | | **WBC count (cells per 109/l)** | 4.0 | 5.5 | 5.3 | 2.8 | 7.5 | | **Hb (g/l)** | 121 | 139 | 139 | 105 | 149 | | **Platelets (cells per 109/l)** | 283 | 124 | 192 | 111 | 140 | | **Lymphoyte (cells per 109/l)** | 0.60 | 1.70 | 0.55 | 0.62 | / | | **CRP (mg/l)** | 0.9 | 57.4 | 6.8 | 0.4 | 20 | | **Creatinine (umol/l)** | 107 | 126 | 72 | 136 | 169 | | **Troponin I (ug/l)** | / | / | 4 | / | / | | **Treatment and outcomes** | | | | | | | **Hydroxychloroquine** | - | - | - | - | + | | **Remdesivir** | - | - | + | - | - | | **Corticosteroid therapy** | - | + | - | - | - | | **Discontinuation of mycophenolate mofetil** | + | + | + | + | + | | **Antibiotics prophylaxis** | - | + | - | - | + | | **ICU stay** | - | - | - | - | - | | **Mechanical ventilation** | - | - | - | - | - | | **Complications** | - | - | - | - | - | | **In-hospital length of stay (days)** | / | 5 | 9 | 21 | 11 | | **Outcome** | Alive | Alive | Alive | Alive | Alive | [†] NPS- nasop haryngeal swab test, SpO2 - oxygen saturation, CRP- C-reactive protein, ICU - intensive care unit **Conclusion**: Lacking any evidence-based recommendation for the treatment of HTx patients infected with SARS-CoV-2, we are challenged to modify maintenance immunosuppression carefully balancing between the risk of uncontrolled viral replication with a superimposed infection on one side, and the increased risk of graft rejection on the other side. Further studies are needed to determine the optimal management of COVID-19 infection in these patients.

    Literature

    1. 1.
      Caraffa R, Bagozzi L, Fiocco A, Bifulco O, Nadali M, Ponzoni M, et al. Coronavirus disease 2019 (COVID-19) in the heart transplant population: a single-centre experience. Eur J Cardiothorac Surg. 2020 November 1;58(5):899–906.DOI
    2. 2.
      Latif F, Farr MA, Clerkin KJ, Habal MV, Takeda K, Naka Y, et al. Characteristics and Outcomes of Recipients of Heart Transplant With Coronavirus Disease 2019. JAMA Cardiol. 2020 May 13:e202159.DOI