COVID-19 in heart transplant recipients

Introduction: After solid organ transplantation, patients require lifelong immunosuppressive medication, increasing susceptibility to COVID-19. We evaluated the clinical outcomes of heart transplant recipients in patients with COVID-19. Methods: We enrolled twenty-two COVID-19 cases of adult heart transplantation from February 2020 to September 2021. Results: The most common symptoms in patients were fever and myalgia. The death occurred in 3 (13.6 %). Conclusion: Although heart transplantation mortality may increase in the acute rejection phase concomitant with COVID-19, immunosuppressive dose reduction may not be necessary for all heart transplant patients with COVID-19.


Introduction
The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic has posed unprecedented health challenges. Patients receiving solid organ transplantation require lifelong immunosuppression, thus more susceptible to COVID-19. 1 There are few data on the prevalence and clinical features of COVID-19 in heart transplant patients. Heart transplant recipients have comorbidities such as diabetes mellitus (DM), hypertension (HTN), chronic kidney disease (CKD), obesity, coronary heart disease, coronary allograft vasculopathy (CAV), and chronic lung diseases, making them prone to severe diseases. 2 While managing immunosuppressive medication in individuals with severe COVID-19 is uncertain, 3 the relationship between COVID-19 and heart transplant rejection needs attention. Therefore, we evaluated the clinical outcomes of heart transplantation in patients with confirmed COVID-19.

Study design
We conducted observational research at Rajaie Heart Center (RHC), Iran. From February 2020 to September 2021, this research included all adult heart transplant patients with positive nasopharyngeal reverse transcriptase-polymerase chain reaction (RT-PCR) testing for SARS-CoV-2.
We gathered data from medical records on hospitalized patients and outpatients. Patients' clinical and laboratory data, immunosuppression, and early antiviral treatments were documented.
Patients were classified as having a mild infection (requiring just outpatient treatment), a moderate infection (requiring admission to the general inpatient ward), or a severe disease (mechanical ventilation, intensive care unit (ICU) admission, or death).

Statistical analysis
Continuous variables were expressed as mean ± standard deviation. Categorical data were provided as frequency and were compared using the Chi-square test. Significance was defined as a two-sided p-value of < 0.05. SPSS software version 24 was used for analysis.

Results
The detailed characteristics of the patients are shown in Table 1. Table 2 summarizes on-admission characteristics, risk factors, and laboratory data. Although SARS-CoV-2 PCR was negative in five individuals, a chest computed tomography (CT) scan suggested COVID-19.
Fever (16 (72.7%)) was the most common symptom in our patients. A summary of the patents' outcomes is  Table 3. Three patients (13.6%) died in this research (Table 3), one with severe gastrointestinal complications (patient 8) and suspicion of acute rejection. He died of sudden cardiac death one day after discharge. Another patient suspected of acute rejection and experiencing cough and dyspnea was treated with methylprednisolone. Three days after discharge, he was readmitted with COVID-19 to the ICU and ultimately expired (patient 7). The last patient, with early COVID-19 after the transplant, had a severe clinical course with sepsis and multiple end-organ failures, which led to death (patient 16) ( Table 1). Due to severe leukopenia, immunosuppressive discontinuation and mycophenolate mofetil dosage reduction was required in 2 (9%) and 7 (31.8%) patients, respectively ( Table 1).
The COVID-19 risk factors were not significantly different between survivors and non-survivors (Table 4).

Discussion
COVID-19 is more common in solid organ transplant recipients compared to the general population. This increased prevalence is probably due to increased susceptibility to infections due to their chronic use of immunosuppressants. 4 Our study's mortality rate (13.6%) was lower compared to previous studies (29.7%, 28.75%, and 22.7% in the studies by Bottio et al, Rivinius et al and Singhvi et al respectively). [4][5][6] This could be due to the higher prevalence of risk factors or older patients in the mentioned studies. Pereira et al evaluated 90 individuals undergoing solid organ transplantation with COVID-19, 9 of whom were heart transplant recipients. Overall, 76% of patients were hospitalized, and 18% died. The mortality rate was similar, but ICU admission was lower than ours, possibly because their study was conducted in the early days of COVID-19, in which the appropriate treatments were not widely known. 7 In the present study, only 2 patients (9%) required immunosuppressive discontinuation due to sepsis and severe leukopenia, while 7 patients (31.8%) required mycophenolate mofetil dosage reduction due to leukopenia. Even though we did not reduce the dosage in other patients, we witnessed a reduced death rate. As a result, maintaining antimetabolite dosage in individuals without leukopenia seems reasonable. Discontinuation of these medicines solely due to COVID-19, without adverse effects or complications, is not recommended.

Conclusion
As RHC is a large tertiary heart transplant center, we had a high rate of COVID-19 in our transplant patients. Our patients were younger than in other studies, and the other risk factors were less prevalent. This may explain why our patients had lower rates of mortality and ICU admission Abreviations: ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; BMI, body mass index; BNP, brain natriuretic peptide; CRP, c-reactive protein; FBS, fasting blood sugar; IU, international unit; LDH, lactate dehydrogenase; SD, standard deviation; WBC, white blood cell.
-All values are reported as mean ± SD unless otherwise stated. * Number (%). Abreviations: GCSF, granulocyte colony-stimulating factor; ICU, intensive care unit. The analyses were performed using the Chi-square test. P value < 0.05