In the COVID-19 pandemic presently affecting the whole world, solid-organ transplant recipients under immunosuppressive therapy are at higher risk than the general population. COVID-19 infection primarily affects the lungs, and so the risk is further increased in lung transplant recipients. The course of COVID-19 in lung transplant recipients is unclear. Here, we present the intensive care follow-up and treatment process of a bilateral lung transplant recipient who developed acute respiratory failure due to COVID-19, for whom the final outcome was favorable. Antiviral treatment was initiated for the 53-year-old male patient with COVID-19 pneumonia, and in the following hyperinflammatory phase, high-dose pulse steroid therapy was administered. The patient was followed up with high-flow nasal oxygen, and then he was supported by intermittent noninvasive mechanical ventilation as hypoxia became more severe. With these noninvasive ventilation strategies and good intensive care procedures, the patient was successfully discharged.
Key words : Acute respiratory failure, Coronavirus disease 2019, Pneumonia, Severe acute respiratory syndrome coronavirus 2
COVID-19 first emerged in Wuhan, China, in December 2019 and spread rapidly to other countries in a worldwide pandemic.1 Patients who undergo solid-organ transplant are usually treated with immunosuppressive therapy and therefore face a high risk of infection. The lungs are the primary affected organ in COVID-19 infection, and so the risk is greater in patients after lung transplant than for other patients. As well as COVID-19 infection, coinfections due to the immunosuppressive state can cause an increase in morbidity and mortality.2 There are inadequate data on the course of COVID-19 in lung transplant recipients. Here, we present the intensive care unit (ICU) management and treatment modalities of the COVID-19 infection that occurred in a lung transplant recipient.
A 53-year-old male patient, diagnosed with known hypertension and diabetes mellitus, had received a bilateral lung transplant in response to chronic obstructive pulmonary disease 2 years previously. He was admitted to the hospital with complaints of fever and newly developed dyspnea. Nasopharyngeal swabs were obtained from the patient and tested with reverse transcriptase polymerase chain reaction (PCR), and the results were positive for SARS-CoV-2. The patient was hospitalized on the same day and transferred to the ICU to treat existing dyspnea, tachypnea, and low oxygen saturation despite oxygen therapy. Thoracic computed tomography was consistent with widespread bilateral multisegmented and multilobar involvement and was typical for COVID-19 pneumonia (Figure 1).
At the time of ICU admission, his arterial blood gas results were 40 mm Hg Pao2, pH 7.36, and 42 mm Hg Paco2. His lymphocyte count was 0.21 ×109 cells/L (10.2%) with levels of 0.1 g/L C-reactive protein, 485 U/L lactate dehydrogenase, 1.4 mg/L D-dimer, 0.8 mg/dL creatine, 28 U/L alanine aminotransferase, 21 U/L aspartate aminotransferase, 0.47 μg/L procalcitonin, 146 μg/L ferritin, and 19 pg/mL interleukin 6. High-flow nasal oxygen (HFNO) treatment was initiated, and oxygen saturation was between 78 and 80 mm Hg. The fraction of inspired oxygen (Fio2) was set to 80% and the flow rate to 50 L/min. Favipiravir (2 × 1600 mg/day loading dose, 2 × 600 mg maintenance), methylprednisolone 1 mg/kg), acetylsalicylic acid (1 × 100 mg), enoxaparin (1 mg/kg/12 h), and vitamin C (4 × 1.5 g) were added to the treatment.
Because of the patient’s immunosuppressive state, all cultures were sent during ICU hospitalization to be screened for opportunistic infections with cytomegalovirus, Aspergillus, and Pneumocystis jirovecii. Piperacillin-tazobactam was initiated empirically with the recommendation of the infectious diseases consultant. The patient received tacrolimus, mycophenolate mofetil, and 5 mg prednisolone to maintain immunosuppressive therapy after lung transplant, and he had a tacrolimus drug level of 3.41 μg/L (reference range, 5-20 μg/L). Drug levels were checked at regular intervals, and doses were adjusted. He had received trimethoprim/sulfamethoxazole 2 days a week for P. jirovecii prophylaxis. The patient developed fever symptoms and increased procalcitonin levels despite the follow-up treatment, so the piperacillin-tazobactam treatment was stopped on day 4, and meropenem, teicoplanin, and inhaled colistin were initiated. A prophylactic dose of voriconazole was administered for Aspergillus. Favipiravir treatment was completed in 10 days.
On day 10 after ICU admission, chest radiography showed increased infiltration, the patient developed hypoxemia, and his respiratory symptoms worsened. The Fio2 was increased to 100% and flow rate to 60 L/min in the HFNO treatment. Intermittent noninvasive mechanical ventilation was initiated. Because of COVID pneumonia progression, which was in the hyperinflammatory phase, pulse steroid therapy was planned for the patient, whose acute phase reactants and D-dimer increased. Procalcitonin was within normal limits (0.07 μg/L). Methylprednisolone was administered as a pulse (10 mg/kg) for 3 days. Methylprednisolone, 1 mg/kg, was given as maintenance in the follow-up period. To treat the elevated D-dimer (15 mg/L), enoxaparin was continued at 1 mg/kg dose twice a day at 12-hour intervals, and antithromboembolic compression stockings were worn for mechanical prophylaxis. During follow-up for this patient, no thromboembolic complications occurred and D-dimer level regressed and decreased below 1 mg/L.
During follow-up, the HFNO rate and Fio2 decreased gradually, and the patient’s symptoms regressed and saturations increased. On day 14 of his ICU admission, the HFNO treatment was switched to a reservoir mask (10 L/min O2). The patient was transferred to the inpatient clinic with greater than 94 mm Hg oxygen saturation as measured by pulse oximetry while given 4 L/min HFNO on day 18 of hospitalization. The COVID-19 immunoglobulin G and M antibody level was 9.67 (normal range, 0-0.99). No additional complaint was observed during the inpatient clinical follow-up, and the patient was discharged with complete recovery (Figure 2).
Solid-organ transplant recipients are at higher risk for infections because of the immunosuppressive treatments they receive. Infections that primarily affect the lung, such as COVID-19, require rigorous management of the disease in lung transplant recipients. In our patient, COVID-19-positive tests occurred while under tacrolimus treatment. The tacrolimus level was carefully monitored during his hospitalization, and the therapeutic range of 5 to
20 μg/L was maintained. We believe that 2 details contributed to the healing process: (1) initiation of antiviral therapy in the early period as soon as polymerase chain reaction tests showed positive results for COVID-19 and (2) administration of pulse steroid therapy during the hyperinflammatory phase. Pulse steroid therapy via anti-inflammatory effects prevents fibrosis in COVID-19 pneumonia.3 In a study conducted on COVID-19 patients, it was reported that the use of 1 to 2 mg/kg/day methylprednisolone for 5 to 7 days had positive effects on the course of COVID-19, such as a decrease in oxygen need and faster improvement in radiological findings.4
In the case series from Aversa and colleagues,5 in which lung transplant recipients developed COVID-19, a total of 32 patients were reported. Eleven patients (34%) died within 14 days, and high levels of white blood cells, C-reactive protein, and D-dimer, as well as low lymphocyte count, were associated with greater severity of the disease and higher mortality. High-dose steroid was used in 44% of the patients, and tocilizumab was used in 19%. Aversa and colleagues reported that high-dose steroid was used only for 3 or 5 days in patients with elevated C-reactive protein, ferritin, D-dimer, or lactate dehydrogenase with worsening respiratory symptoms, and the dose was increased up to 15 mg/kg in patients who required intubation.5 In our patient, 10 mg/kg methylprednisolone was administered for 3 days during the hyperinflammatory phase. Anticytokine therapies such as tocilizumab and anakinra were not needed in our patient because there was a favorable clinical response to steroid treatment.
In a multicenter study by Messika and colleagues, there were 35 lung transplant recipients who developed COVID-19, and 31 patients (88.6%) were hospitalized.6 Of these 31 hospitalized patients, 13 (41.9%) required ICU admission and 4 developed acute thromboembolic complications during follow-up.6 Although severe elevations in D-dimer levels developed in our patient, the use of antithromboembolic compression stockings and administration of enoxaparin prevented possible thromboembolic complications. In their multicenter study, Messika and colleagues reported that 7 of 13 patients (53.9%) followed up in the ICU received invasive mechanical ventilation.6 Our patient was followed up with HFNO after ICU admission. On follow-up day 10, our patient’s clinical symptoms had worsened, and desaturation occurred. Both the amount and rate of HFNO were increased for our patient, who was near the threshold for invasive mechanical ventilation, and he was successfully supported with intermittent noninvasive mechanical ventilation. The successful management of the acute symptoms with HFNO and noninvasive mechanical ventilation prevented the need for invasive mechanical ventilation.
Lung transplant patients are at great risk during the COVID-19 pandemic. High morbidity and mortality rates are possible if COVID-19 infection develops in these patients. The prognosis for our patient was good with early interventions. We believe that hospitalization of the symptomatic patient on the same day of the diagnosis of COVID-19, prompt ICU admission when needed, and the rigorous ICU management via noninvasive ventilation strategies contributed to the successful outcome.
Volume : 20
Issue : 8
Pages : 786 - 788
DOI : 10.6002/ect.2021.0223
From the 1Department of Intensive Care Unit and the 2Department of Thoracic Surgery and Lung Transplantation, Ankara City Hospital, Ankara, Turkey
Acknowledgements: The authors have not received any funding or grants in support of the presented research or for the preparation of this work and have no declarations of potential conflicts of interest.
Corresponding author: Hayriye Cankar Dal, Ankara City Hospital, Department of Intensive Care Unit, Üniversiteler Mahallesi Bilkent Cad. No. 1, Çankaya/Ankara, Turkey
Phone: +90 534 368 3748
Figure 1. Computed Tomography Images Obtained During Admission to Intensive Care Unit Show Multisegmented, Multilobar, and Bilateral Diffuse Involvement
Figure 2. Chest Radiographs