key: cord-0811074-oj9lqd6t authors: Renaud-Picard, Benjamin; Gallais, Floriane; Ohana, Mickael; Zeyons, Floriane; Kretz, Benjamin; Andre, Jocelyn; Sattler, Laurent; Hirschi, Sandrine; Kessler, Romain title: Bilateral acute cardioembolic limb ischemia after Covid-19 pneumonia in a lung transplant recipient: a case report date: 2020-06-30 journal: Transplant Proc DOI: 10.1016/j.transproceed.2020.06.024 sha: d7be7e3d1108e7fb99d8b2f828536455d8c8209d doc_id: 811074 cord_uid: oj9lqd6t ABSTRACT Very few cases of lung transplant patients affected by Covid-19 have been reported to date. A 31-year-old patient with bilateral lung transplantation for cystic fibrosis in 2012 was admitted for severe acute lower limb pain. He had a confirmed exposure to Covid-19, and a 3-week history of upper respiratory tract infection. Whole body computed tomography (CT) angiography revealed an occlusion of the two common femoral arteries. CT angiography detected an intracardiac thrombus in the left ventricle. Chest CT angiography showed ground-glass opacities consistent with a Covid-19. A bilateral femoral surgical embolectomy using Fogarty probe was successfully performed. Specific RT-PCR for SARS-CoV-2 performed on an extracted thrombus was negative but IgM antibodies specific to Covid-19 were detected. Cardiac MRI demonstrated a sub-endocardial and almost transmural late gadolinium enhancement in the mid and distal inferolateral and inferior wall segments, consistent with a non-recent myocardial infarction and an apical centimetric thrombus adjacent to the lesion. Thrombophilia laboratory tests found the presence of a positive lupus anticoagulant.Treatment with low-molecular weight heparin and aspirin was prescribed. On day 13, patient was discharged from hospital. This case underlines the need to be vigilant with respect to the thrombotic complications of Covid-19 and raises the issue of thrombosis prevention in Covid-19 patients. A bilateral femoral surgical embolectomy using Fogarty probe was successfully performed. Specific RT-PCR for SARS-CoV-2 performed on an extracted thrombus was negative but IgM antibodies specific to Covid-19 were detected. Cardiac MRI demonstrated a sub-endocardial and almost transmural late gadolinium enhancement in the mid and distal inferolateral and inferior wall segments, consistent with a non-recent myocardial infarction and an apical centimetric thrombus adjacent to the lesion. Thrombophilia laboratory tests found the presence of a positive lupus anticoagulant. Treatment with low-molecular weight heparin and aspirin was prescribed. On day 13, patient was discharged from hospital. This case underlines the need to be vigilant with respect to the thrombotic complications of Covid-19 and raises the issue of thrombosis prevention in Covid-19 patients. In late December 2019, the epidemic of a novel coronavirus (Covid-19) broke out in Wuhan, China, and then spread rapidly around the world. Though the clinical impact of the disease has been well described for immunocompetent patients, its consequences on populations treated with immunosuppressive drugs are still poorly understood, especially concerning solid organ transplant (SOT) recipients. Very few cases of lung transplant patients affected by Covid-19 have been reported to date 1 . We describe here the case of a young lung transplant patient suffering from Covid-19 pneumonia, which was followed by acute limb ischemia. We hypothesize that this complication was secondary to a lupus anticoagulant-induced intra-cardiac thrombus. A 31-year-old patient who had undergone double-lung transplantation (LTx) for cystic fibrosis in 2012, with known Covid-19 exposure, was admitted to the emergency department for severe acute pain of the lower limbs. One month before this episode, the patient had a 3-week history of fever, fatigue, anorexia, weight loss, dyspnea, nausea, ageusia, and nasal obstruction, for which he had received athome treatment with oseltamivir and cefuroxime. His main comorbidities were a superior vena cava syndrome secondary to a thrombosis of a totally implantable venous access device prior to LTx and a chronic lung allograft dysfunction (CLAD) with a Grade 2 bronchiolitis obliterans syndrome associated with mildly positive Class II donor specific antibodies. Regarding the high risk of rejection, the patient's immunosuppressive (IS) treatment combined cyclosporin (150 mg twice a day), everolimus (0.75 mg twice a day), mycophenolate mofetil (1500 mg twice a day), prednisone (10 mg per a day) associated with azithromycin (250 mg 3 times/week). In the emergency department, the patient reported painful and cold legs, loss of motricity and sensitivity that was predominant on the right side. Right and left dorsalis pedis artery pulses were abolished. Chest CT angiography showed bilateral consolidation areas and ground-glass opacities with basal and peripheral predominance, which was consistent with Covid-19 infection ( Laboratory tests revealed increased platelet levels (536 G/L) and white cell counts (15.2 G/L), as well as mild anemia (9.5 g/dL) and normal lymphocyte count (2.05 G/l). The troponin level was 0.038 ng/ml (normal range <0.01). D-Dimer testing was not performed. Measurements of arterial blood gases showed normal pH, pO2 of 192 mmHg and pCO2 of 24 mmHg at an O2 flow rate of 2 liters/min. The patient's creatinine level was 112 µmol/L (normal range 59-104), with normal liver function tests. The Creactive protein level was normal as well, as were prothrombin and activated partial thromboplastin times, but the fibrinogen level was 6.72 g/L (normal range 2 to 4). An emergency bilateral femoral surgical embolectomy using Fogarty probe was successfully performed, which enabled extraction of white inflammatory-like thrombi from both sides. These were sent for specific RT-PCR for SARS-CoV-2, which turned out to be negative. The same day, low-molecular-weight heparin was prescribed. On Day 2, the patient had fully recovered from acute limb ischemia and was transferred to the respirology department for further care and treatment. A second nasopharyngeal swab testing was negative, but specific serology for SARS-CoV-2 confirmed Covid-19 with strongly positive IgM and mildly positive IgG levels, using rapid test Biosynex COVID-19 BSS (Strasbourg, France). This test showed good diagnostic performance during current evaluation. On day 6, an echocardiography was carried out to investigate the origin of the intracardiac thrombus. It Aspirin was added to low-molecular-weight heparin, which was then replaced by oral vitamin Kantagonist treatment. The immunosuppressive regimen was not modified considering that infectious symptom onset occurred over one month earlier, and the risk of rejection was considered important. We did not observe any other clotting abnormality after the thrombectomy. On day 13, the patient was discharged from hospital after a second echocardiography considered as stable (figure 3). The main Covid-19-related thrombotic manifestations described until now include pulmonary embolism, acute coronary syndrome, and stroke 2 . Several potential risk factors for thrombosis have been What is remarkable in this case is that these arterial vascular complications occurred more than one month after respiratory infectious symptoms' onset and in a young patient without any known arterial peripheral comorbidity 5 . However, regarding his comorbidities and the elevated platelet count, we can consider that this patient could be at risk for thrombosis. This case underlines the need to be vigilant with respect to various thrombotic complications of Covid-19 and raises the issue of thrombosis prevention in SARS-CoV-2 patients. Furthermore, the specific impact of immunosuppressive treatment on Covid-19 severity is still not well defined. SOT recipient's specific care during Covid-19 epidemic was only the object of a few case reports, especially concerning immunosuppressive treatment management [6] [7] [8] . When treating opportunistic viral infection in a transplant patient, it is common to reduce or even suspend the immunosuppressive treatment to enable patients to reacquire anti-infection immunity and reduce symptoms' severity 9 . Similar recommendations were proposed for Covid-19-infected transplant patients. In our case, immunosuppressive treatment was not modified regarding the early respiratory symptoms' onset, absence of persistent infectious symptoms and high rejection risk. It is impossible to know if this could have played a role in the occurrence of this delayed Covid-19-related vascular complication despite initial recovery. This confirms the need to acquire new data concerning immunosuppressive treatment management in SOT patients. Cohort studies and, hopefully, prospective trials should help providing answers concerning these new issues. Pulmonary CT showing patchy areas of consolidation and ground glass opacities, one month after Covid-19 respiratory symptoms onset. I also acknowledge that if accepted, I am responsible for all manuscript page charges, which will be billed to me by Elsevier, the publisher of Transplantation Proceedings, at the rate of US$99.95 per submitted manuscript page, understanding that each Table and Figure will count as one manuscript page each along with the text. I understand that page charges are based on the typed, submitted page, not on the printed page, and no complimentary pages are automatically provided by Transplantation Proceedings. Authors will be contacted by the Editorial Office with a tracking number and will be informed of the final number of pages for which they are responsible. Further, I understand that use of color reproduction of graphics will result in an additional charge. The Abstract and Title page are complimentary by Transplantation Proceedings. Additionally, I agree that this manuscript has not been submitted or published in any other journal, including Transplantation Proceedings, and no parts of the manuscript are duplicated. I understand that if the manuscript is accepted for publication, copyright of the manuscript is transferred to Elsevier. Benjamin RENAUD-PICARD Romain KESSLER Signature of Person to be invoiced: COVID-19 in a lung transplant recipient COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-up Coagulopathy of COVID-19 and antiphospholipid antibodies High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study Venous thrombosis and arteriosclerosis obliterans of lower extremities in a very severe patient with 2019 novel coronavirus disease: a case report Case report of COVID-19 in a kidney transplant recipient: Does immunosuppression alter the clinical presentation? Novel Coronavirus-19 (COVID-19) in the immunocompromised transplant recipient: #Flatteningthecurve Clinical Course of COVID-19 in a Liver Transplant Recipient on Hemodialysis and Response to Tocilizumab Therapy: A Case Report Outcomes from pandemic influenza A H1N1 infection in recipients of solid-organ transplants: a multicentre cohort study The authors would like to thank all the persons who contributed to the realization of this study. We do not have any funding to disclosure for this study.Approval: Authorization was obtained from the patient to write this case report. Benjamin Renaud-Picard: benjaminrenaud@free.fr The authors would like to thank all the persons who contributed to the realization of this study. We do not have any funding to disclosure for this study.Approval: Authorization was obtained from the patient to write this case report. None of the authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose.