Case Report - (2021) Volume 13, Issue 4
Department of Cardiology, Angiology and Intensive Care, Philipps University Marburg, Marburg, Germany
Received Date: March 23, 2021; Accepted Date: April 15, 2021; Published Date: April 20, 2021
Citation: Chatzis G (2021) Complications of a Heart Transplanted Patient with COVID-19 Infection. Arch Med Vol.13 No.4:16.
Our knowledge of coronavirus disease-2019 (COVID-19) and its cardiovascular implications is growing every day. The pandemic has raised the question of whether to continue offering heart transplantations due to concerns regarding the risk for exposure to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during hospitalization and challenges in curbing the infection with high levels of immunosuppression. We present the case of a 47-year-old woman who presented with COVID-19 on immunosuppression therapy due to recent heart transplantation four months before admission. The patient’s condition worsened, and despite monitoring and treatment updates, she died on day 19 of admission. Although most immunocompromised persons effectively clear a SARS-CoV-2 infection, this case highlights the potential for ongoing and accelerated viral evolution associated with an immunocompromised state. Patients can manifest acute rejection in the months following transplantation surgery, which can ultimately lead to death.
Keywords
COVID 19; Heart transplant; Cardiology; Internal medicine
Introduction
Health care professionals worldwide are confronted with unprecedented challenges due to the emergence of the novel coronavirus disease-2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus’s high infectivity, ability to transmit during the asymptomatic phase and relatively low virulence has resulted in rapid transmission beyond geographic regions, leading to a pandemic. Cardiovascular Disease (CVD) and cardiovascular risk factors enhance vulnerability to COVID-19. Further, COVID-19 can worsen underlying CVD and even precipitate de novo cardiac complications [1]. One area of cardiovascular medicine vulnerable during the pandemic is that of Heart Transplantation (HT). The donors, recipients, and those awaiting HT are at increased risk of infection. The eminent risk for the recipients is more evident given their immunocompromised state. We present the case of a 47-year-old woman who presented with COVID-19 on immunosuppression therapy due to recent heart transplantation four months before admission.
Case Report
A 47-year-old Saudi female patient was referred from a peripheral hospital to our center with a COVID-19 respiratory infection. Her history was significant for long-term diabetes, diabetic nephropathy, and hypertension. Due to cardiomyopathy and excessive heart failure with an Ejection Fraction (EF) of 15%, she underwent HT at a specialized center in Riyadh four months before her admission with COVID-19. She was on full immunosuppression medication with mycophenolate 1000 mg twice daily, prednisolone 5 mg twice daily, and sirolimus 2 mg daily.
On admission, she reported dry cough concerns but did not have a fever, chest pain, or shortness of breath. She had no diarrhoea, vomiting, or abdominal pain on clinical examination. The patient was conscious, alert, and oriented, with oxygen saturation at 96% on room air (RA). Her chest x-ray showed peripheral bilateral infiltrates (Figure 1).
Figure 1: Admission chest x-ray.
Echocardiography on admission showed left ventricular dysfunction with hypokinesia of the anterior wall and estimated EF of 40% to 45%, dilated left atrium due to the recent transplant, and moderate tricuspid regurgitation. The electrocardiography directly following her HT showed an EF of 55% with no hypokinesia.
We initiated broad-spectrum antibiotics (ceftriaxone 1 g; doxycycline 100 mg every 12 hours) for prophylaxis of hospitalacquired pneumonia and antiviral agents against COVID-19. The transplant team modified her immunosuppressive medications to stop mycophenolate, continue sirolimus and changed prednisolone to dexamethasone 6 mg intravenous (IV) daily.
On day three, the patient required oxygen because her saturation was 88% to 90% on RA. She was connected to a nasal cannula of 4 L/min flow, and her oxygen saturation increased to 96%. A second chest x-ray showed increased bilateral infiltrations, but the patient was still afebrile with no shortness of breath and was not in respiratory distress. Her antibiotic treatment was upgraded to IV piperacillin/tazobactam. Her transplant center in Riyadh was contacted, and they advised initiating tocilizumab 4 mg/kg, but this medication was not available to our hospital at that time. A second echocardiography study showed only mild improvement of her EF.
Given her severe leukopenia, the patient was also evaluated by a haematologist who suggested her condition was due to immunosuppressive medications augmented with the viral infection, so filgrastim 300 μg daily (subcutaneous) was administered for three days, and her laboratory values were assessed (Table 1).
| Analytes | Admission Day to Hospital | Admission Day to ICU | Death Day | Reference Range |
|---|---|---|---|---|
| WBC Count (×1000/µL) | 1.86 | 3.02 | 31.6 | 3.6-11.4 |
| Hb (g/dl) | 7.7 | 7.8 | 7.7 | 11.8-17.2 |
| Platelets Count (×1000/µL) | 206 | 212 | 380 | 150-400 |
| Neutrophils (%) | 83.2 | 84.9 | 84 | 42-77 |
| Lymphocytes (%) | 9.8 | 8.2 | 7.5 | 20-44 |
| Ferritin (ng/ml) | 697.9 | >1650 | >1650 | 10-291 |
| D-Dimer (mg/L) | 22.6 | 23.3 | 5.36 | 0.0-0.5 |
| CRP (mg/dl) | 2.4 | 0.0-0.6 | ||
| BUN (mmol/L) | 17 | 31.7 | 15.6 | 2.5-6.4 |
| Creatinine (µmol/L) | 187 | 533 | 250 | 49-115 |
| Sodium (mmol/L) | 130 | 133 | 134 | 136-145 |
| Potassium (mmol/L) | 5.5 | 4.5 | 6.79 | 3.5-5.1 |
| Chloride (mmol/L) | 95 | 97 | 99 | 98-107 |
| Calcium (mmol/L) | 1.9 | 1.79 | 1.89 | 2.1-2.5 |
| Phosphorous (mmol/L) | 2.4 | 2.1 | 0.8-1.5 | |
| Total Protein (g/L) | 50.3 | 59.7 | 64-82 | |
| Albumin (g/L) | 17 | 28 | 43-50 | |
| ALP (U/L) | 113 | 323 | 46-116 | |
| ALT (U/L) | 18 | 47 | 14-63 | |
| AST (U/L) | 35 | 103 | 15-37 | |
| GGT (U/L) | 151 | 936 | 5-85 | |
| Total Bilirubin (µmol/L) | 6.3 | 19.5 | 3-17 | |
| Conjugated Bilirubin (µmol/L) | 2.16 | 11.19 | 0.8-3 |
Abbreviations: ICU: Intensive Care Unit; WBC: White Blood Cell; CRP: C-Reactive Protein; BUN: Blood Urea Nitrogen; ALP: Alkaline Phosphatase; ALT: Alanine Transaminase; AST: Aspartate Transaminase; GGT: Gamma-Glutamyl Transferase
Table 1: Laboratory tests.
On day five, she developed shortness of breath, and her oxygen saturation dropped to 85% on RA and 97% with the use of 7 L/ min flow via a simple face mask. After two hours, she developed a fever and increased dyspnoea. She also developed gastrointestinal symptoms (vomiting and diarrhoea).
The following day (day six), her oxygen requirement increased to 15 L/min flow in a Non-Rebreather Face Mask (NRFM) to keep her oxygen saturation 98%. Piperacillin/tazobactam was stopped, and meropenem with metronidazole was started. The Intensive Care Unit (ICU) team was consulted. On day seven, the patient was moved to the ICU. She did not require intubation or inotropic support, but she was placed on maximum oxygen supply at 15 L/min flow on NRFM and placed in the prone position; her oxygen saturation was 94% to 96%. She had developed acute kidney injury when she moved to the ICU, and her renal function deteriorated, so continuous renal replacement therapy was initiated. Acute rejection of the transplant was suspected, and the team monitoring her was informed. Her medications were adjusted according to the transplant team’s instructions, and that facility accepted the official transfer to their center. However, the medical evacuation team protocol required two negative COVID-19 tests within 48 hours, and the patient was still COVID- 19-positive.
On day 13, her oxygen saturation dropped to 60%, she became unconscious, and she was intubated. On day 17, she developed right pneumothorax, for that positive end-expiratory pressure was reduced from 8 cm to 4 cm water and tidal volume from 450 to 350 mL. The cardiothoracic surgeon inserted a chest tube (Figure 2). Pneumocystis carinii pneumonia was suspected, and adequate treatment was initiated. However, on day 19, the patient entered cardiac arrest. The care team started cardiopulmonary resuscitation per the advanced cardiac life support protocol, but the patient died.
Figure 2: Admission chest x-ray.
Discussion
The cardiovascular community faced unprecedented challenges in the COVID-19 pandemic. For HT clinicians, the global pandemic has unique implications for patients, including those on the waiting list and transplant recipients [2]. These populations are at increased risk of both acquiring COVID-19 infection and progression to severe disease given their multiple healthcare contacts, underlying health conditions, and immunosuppression; targeted prevention and treatment strategies are needed.
Experience with previous coronavirus epidemics such as severe acute respiratory syndrome and Middle East respiratory syndrome demonstrated that transplant patients have similar presentations to the general population. The first COVID-19 cases reported in two HT recipients were in China in March 2020. Both patients survived, one with a mild form of the illness allowing for treatment and recovery at home, the other with progressive respiratory failure requiring inpatient admission, intravenous immunoglobulin, and methylprednisolone [3].
Experience from other centres suggests that patients with longer post-transplant recovery time and those who did not require intubation during their COVID-19 infection have a better survival ratio [4]. This is unsurprising given the one-year survival rate after HT is approximately 90% [5]. Unfortunately, the patient, in this case, had undergone her HT procedure only four months before presenting with COVID-19 [6]. Kumar et al. provided new guidelines for managing these patients, especially for patients after transplantation procedures [7]. The new guidelines note the benefits of using interleukin-2 inhibitors such as tocilizumab (Table 2).
| Transplant Area | Recommendations [7] |
|---|---|
| Donor | COVID-19-focused travel and social history |
| Exclusion of donors at risk of other disease transmission (HIV, HPB, HCV) | |
| Exclusion of marginal donors having mild LVH and/or LV dysfunction | |
| Donor contract tracing | |
| Availability and rapid turn-around of PCR assay for donor | |
| At least two tests to increase sensitivity and specificity | |
| COVID-19-free interval of 14 days | |
| Chest CT for exclusion of pneumonia | |
| Separate consent for potential COVID-19 donors | |
| Recipient | COVID-19-free environment |
| Staying away of nurses who attend COVID-19 patients from patients awaiting HT | |
| Exclusion of hospital-acquired infection by PCR | |
| Telephonic and/or mail communication regarding expected delay and organizational changes | |
| Lower threshold for LVAD as a bridge to transplant | |
| Reduction of overall transplant program activity | |
| Post-transplant | Negative pressure ventilation room with airborne isolation |
| Staying away of nurses who attend COVID-19 patients from post-transplant patient | |
| Reduction of staff contact and outside visitors | |
| Stress on patient/family hygiene and social distancing | |
| Prompt testing and diagnosis of patients with symptoms related to rejection | |
| Delaying elective testing, echocardiography, RHC and EMB | |
| Adherence to local laboratory or home service for the tests | |
| Transplant patients infected with COVID-19 | Reduction of dose of calcineurin inhibitor |
| Reduction or withhold of mycophenolate mofetil/azathioprine dose | |
| Ruling out other bacterial or fungal infection | |
| Monitoring for viremia | |
| Monitoring for drug-drug interactions | |
| Continuation of statins unless contraindicated | |
| IL-6 inhibitors for cytokine storm? | |
| Monitoring for allograft dysfunction |
Abbreviations: COVID-19: Coronavirus Disease-2019; CT: Computed Tomography; EMB: Endomyocardial Biopsy; HBV: Hepatitis B Virus; HCV: Hepatitis C Virus; HIV: Human Immunodeficiency Virus; HT: Heart Transplant; IL: Interleukin; LVAD: Left Ventricular Assist Device; LV: Left Ventricular; LVH: Left Ventricular Hypertrophy; PCR: Polymerase Chain Reaction; RHC: Right Heart Catheterization
Table 2: Recommendations regarding heart transplant during the COVID-19 pandemic.
Conclusion
An acute cellular rejection triggered by a COVID-19 infection could not be ruled out for this patient. Recent transplantation, insulin resistance, female recipient of a female donor, coronary heart disease, and acute renal injury are factors to be considered. Additional early diagnostics that help prevent acute rejection are usually prohibited due to the high risk of COVID-19 transmission. While considering potential therapies, it is critical to recognize drug-drug interactions and the risk of rejection. Also, the frailty of the patient, her previous condition, and the relatively close transplant date should be considered as factors in her death.
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