key: cord-0951417-uscivogq authors: Turkkan, Sinan; Beyoglu, Muhammet Ali; Sahin, Mehmet Furkan; Yazicioglu, Alkın; Tezer Tekce, Yasemin; Yekeler, Erdal title: COVID‐19 in lung transplant recipients: A single‐center experience date: 2021-08-16 journal: Transpl Infect Dis DOI: 10.1111/tid.13700 sha: c6cb753045fff6abf442193751fb63dae609d19b doc_id: 951417 cord_uid: uscivogq BACKGROUND: Coronavirus disease 2019 (COVID‐19) is a global health problem. However, the course of this disease in immunosuppressed patients remains unknown. This study aimed to describe the course of COVID‐19 infection and its effects on lung transplant recipients. METHODS: This was a single‐center, retrospective, observational study. The recipients with suspicious symptoms and/or a contact history with infected individuals were diagnosed with COVID‐19 by performing a reverse transcription‐polymerase chain reaction (RT‐PCR) test using samples obtained from the nasopharynx swabs or bronchial lavage. We classified the patients into mild, moderate, and high severity groups according to their clinical conditions. In patients with positive RT‐PCR results, cell cycle inhibitor drugs were withdrawn, while steroids were maintained at the same level as in patients without clinical deterioration. RESULTS: Of the seven recipients diagnosed with COVID‐19 infection, one experienced a re‐infection. Each recipient had at least one comorbidity. Smell disorder (12.5%), cough/dyspnea (37%), and fever/chills/shivering (37%) were the most frequent symptoms. The mean follow‐up time after infection was 108 days. No deaths were recorded due to COVID‐19; however, the pulmonary function test values of two recipients were decreased during subsequent follow‐ups. CONCLUSION: In our small group of transplant recipients with COVID‐19, there were two cases of pulmonary function deterioration and a case of re‐infection, and no recipient died. It is suggested that steroid therapy should be initiated in the early period in patients with pulmonary opacities. The coronavirus disease 2019 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide within a short time. 1 The course of COVID-19 in immunosuppressed patients remains unknown. Previous studies have reported that COVID-19 has high morbidity and mortality rates in solid organ transplant (SOT) recipients. 2 Available data on COVID-19 regarding lung transplant recipients are limited compared to liver and kidney transplant recipients. Therefore, we sought to describe the course and short-to long-term COVID-19 outcomes in lung transplant recipients. This was a single-center, retrospective, observational study to evaluate the effects of COVID-19 in lung transplant recipients. A positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test was required for diagnosis. The test was performed using nasopharyngeal swab or bronchial lavage samples obtained from recipients presenting with suspicious symptoms and/or a contact history with individuals infected with SARS-CoV-2. Inpatient treatment was recommended for all recipients with positive RT-PCR. Individuals presenting with symptoms of cough, fever, dyspnea, generalized muscle pain, and/or radiological findings were hospitalized while waiting for the RT-PCR results. Outpatients with mild symptoms or negative RT-PCR results were advised to visit the hospital in case of symptoms such as fever, cough, dyspnea, and diffuse pain. Coagulation parameters, including D-dimer, fibrinogen, troponin, interleukin-6 (IL-6), ferritin, as well as routine hemogram, biochemistry, C-reactive protein (CRP), and procalcitonin tests were performed. Posteroanterior (PA) chest radiography and thoracic computed tomography (CT) were also performed. Respiratory virus PCR panel and influenza rapid test were performed using oropharyngeal swabs obtained from each hospitalized patient. COVID-19-specific imaging findings (infiltration, consolidation, and ground-glass opacities) were examined using PA radiography and CT. We classified the patients into mild, moderate, and high severity groups according to their clinical conditions. Patients who were followed up as outpatients or those who did not need supplemental oxygen were classified in the mild severity group. Patients who were admitted in the ward requiring supplemental nasal oxygen at any time during their follow-up were included in the moderate severity group, whereas those requiring noninvasive ventilation, high-flow oxygen (HFO) treatment, or invasive mechanical ventilation were included in the high severity group. In patients with positive RT-PCR results, cell cycle inhibitor drugs were withdrawn. The target blood levels of calcineurin inhibitor (CNI) and mammalian target of rapamycin (mTOR) inhibitor did not change. Steroids were maintained at the same level as in patients without clinical deterioration. The target levels of CNI and mTOR did not change; however, MMF administration was stopped after detecting positive RT-PCR results. Seven (87.5%) cases were followed up as inpatients, and one (12.5%) was followed up as an outpatient. The patient with smell dysfunction treated as an outpatient improved within five days of treatment. Only one patient required long-term oxy- Data regarding COVID-19 infection in lung transplant recipients are gradually increasing. However, to date, most studies have focused on management and short-term results. 5 In this study, we aimed to investigate the effects of COVID-19 on demographic, clinical, and laboratory data of patients and its short-to long-term clinical outcomes in lung transplant recipients. From the beginning of the pandemic, several clinicians and researchers were curious to know the impact of COVID-19 on SOT recipients and the recipients with the greatest disease severity. We It is a well-known fact that infections in immunosuppressed patients may present with atypical symptoms and signs, which may lead to delays in diagnosis and treatment. 6 It is also known that COVID-19 intensifies by causing cytokine storms in the following days.. 7 Since we had sufficient numbers of negative pressure, isolation, intensive care, and ward room allocated to our clinic in the hospital, we preferred treating our patients by hospitalizing them regardless of their symptoms. Therefore, we detected new-onset fever, dyspnea, and chest radiography findings in two cases (25%), which were related to cytokine storms on the 7th to 8th days of hospitalization. There are also insufficient data on SARS-CoV-2 re-infection. Only approximately 30 cases were reported by the end of 2020, and we did not find a re-infection case of a lung transplant recipient in the English literature. The most important aspect of this issue is the distinction between re-infection and reactivation. 8 One of the cases was evaluated as a re-infection case, although sequence analysis was not performed. He received remdesivir as part of the study. His first attack led him to use long-term oxygen therapy, but as expected, 8, 9 he survived his second attack with mild symptoms. Studies are ongoing to access demographic and laboratory data of patients with progressive disease. 10 To date, some predictive markers have been suggested. 11 Although statistical analyses were not performed due to the small number of cases, there are some prominent findings. Our data, similar to the results of some other studies, 12 show that the elevation in D-dimer, CRP, and IL-6 observed at the time of application, the highest IL-6, ferritin, and procalcitonin levels were proportional to the severity of COVID-19. We observed that the low percentage of lymphocytes during patient follow-up was also proportional to the severity of the disease (the percentage of lymphocytes was lower in more severe disease), indicating that lymphocyte depletion is a part of the pathogenesis of COVID-19. 13 In addition, the lymphocyte percentages of the two patients who required intensive care follow-up were the lowest in the study, and IL-6 levels were the two highest values. Our practice in immunosuppressive drug management has been stopping antimetabolite drugs and going on the same target levels of CNI and mTOR inhibitor drugs. Several articles have pointed out the positive and negative aspects of everolimus and tacrolimus during the course of COVID-19. 14-17 Moreover, many parameters determine the development and progression of the disease, 18 but we believe that one of the important findings in our study was the presence of everolimus in the immunosuppressive drug regimens of three patients. This finding requires clinical and statistical verification in more patients. At the beginning of the pandemic, there was insufficient data on the effects of high-dose steroids on COVID-19 in SOT recipients. Increasing data on this issue has encouraged clinicians during treatment applications. 19 In cases with pulmonary involvement and findings of cytokine storm, high-dose steroid therapies (steroid augmentation/pulse application) were applied to four of our cases, three of whom were administered pulse steroids. Symptoms and inflammatory markers improved in all three patients after pulse steroids; thus, we did not need treatments such as tocilizumab and anakinra or other treatments. The average follow-up period of COVID-19 cases was 108 days (median: 101 days), which could provide insight into the effects of the disease on recipients in the medium to long term. Serious forced expiratory volume in one-second (FEV1) declines was observed in two patients after infection. One was in our follow-up for approximately 8 months after infection and was accepted as CLAD stage 4 because of the 60% decrease in FEV1 values compared to the basal best value. 20 However, the other patient was not followed up for a sufficient time for CLAD assessment; hence CLAD classification was not made for him; however, a 30% reduction compared to the best FEV1 value was found in PFT performed in the second month of COVID-19. These two cases may indicate the importance of COVID-19-induced morbidity in lung transplant recipients in the mid-long term. The main limitation of our study is that it was single-centered and covered few cases. Due to the long follow-up period after COVID-19, it may lighten the medium-to long-term effects of the disease. In conclusion, the course and long-term effects of COVID-19 on SOT recipients remain unclear. Our small group of transplant recipients with COVID-19 consisted of two cases with loss of pulmonary function and one case with a re-infection, suggesting that steroid therapy should be initiated in the early period in patients with pulmonary opacities. Although no patient died among our patients, moderate-to-severe COVID-19 with pulmonary signs may cause loss of graft function in lung transplant recipients. COVID-19 mortality in transplant recipients Observational study of hydroxychloroquine in hospitalized patients with covid-19 Clinical and microbiological effect of a combination of hydoxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow-up: a pilot observational study COVID-19 in lung transplant recipients: a case series from Milan Infection in organ transplantation COVID-19: consider cytokine storm syndromes and immunosuppression What we know about covid-19 reinfection so far A case of COVID-19 reinfection in the UK Clinical course and risk factors for mortality of adult inpatients with COVID19 in Wuhan, China: a retrospective cohort study COVID-19 in solid organ transplant recipients: initial report from the US epicenter COVID-19 in lung transplant recipients: a single center case series from New York City Immunosuppression drug-related and clinical manifestation of Coronavirus disease 2019: a therapeutical analysis Case report of COVID-19 in a kidney transplant recipient: does immunosuppression alter the clinical presentation? Successful recovery of COVID-19 pneumonia in a renal transplant recipient with long-term immunosuppression COVID-19: yet another coronavirus challenge in transplantation Complete recovery from COVID-19 of a kidney-pancreas transplant recipient: potential benefit from everolimus? Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State A retrospective controlled cohort study of the impact of glucocorticoid treatment in SARS-CoV-2 Infection mortality Chronic lung allograft dysfunction: definition, diagnostic criteria, and approaches to treatmen-tąA consensus report from the Pulmonary Council of the ISHLT COVID-19 In Lung transplant recipients: A single-center experience We acknowledge all the health-care professionals in our lung transplant clinic. The authors declare that they have no competing interests. The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. All the authors contributed equally to the review of the existing literature, drafting the article, and approval of the final document.