key: cord-252933-bu4oihem authors: Xu, Jieqing Jessica; Samaha, Daniel; Mondhe, Suhas; Massicotte‐Azarniouch, David; Knoll, Gregory; Ruzicka, Marcel title: Renal Infarct in a COVID‐19 Positive Kidney‐Pancreas Transplant Recipient date: 2020-06-01 journal: Am J Transplant DOI: 10.1111/ajt.16089 sha: doc_id: 252933 cord_uid: bu4oihem The novel coronavirus disease 2019 (COVID‐19) is associated with increased risk of thromboembolic events, but the extent and duration of this hypercoagulable state remains unknown. We describe the first case report of renal allograft infarction in a 46‐year‐old kidney‐pancreas transplant recipient with no prior history of thromboembolism, who presented 26 days after diagnosis of COVID‐19. At the time of renal infarct, he was COVID‐19 symptom free and repeat test for SARS‐CoV‐2 was negative. This case report suggests that a hypercoagulable state may persist even after resolution of COVID‐19. Further studies are required to determine thromboprophylaxis indications and duration in solid organ transplant recipients with COVID‐19. In December 2019, the novel coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in Wuhan, China. COVID-19 has now spread worldwide and caused significant morbidity and mortality with 3.8 million cases and upwards of 267,000 deaths at the time of writing (1). COVID-19 primarily affects the respiratory system, but is increasingly recognized to have multisystemic manifestations (2) (3) (4) . There is a high prevalence of arterial and venous thromboembolic events in patients with severe COVID-19 (5, 6) . At this time there are no guidelines delineating which patients should be anticoagulated, and for how long. Immunosuppressed patients, such as transplant recipients, may be more susceptible to COVID-19 infection and its subsequent complications. Here, we describe a kidney-pancreas transplant recipient who developed a clinically significant coagulopathy resulting in segmental infarction of his kidney allograft in the context of COVID-19 infection. A 46-year-old male presented to a screening center with dyspnea and cough. He had a history of simultaneous kidney-pancreas transplant 13 years ago for Type 1 diabetes mellitus complicated by diabetic nephropathy and neurogenic bladder. Maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil (MMF) and prednisone. He had history of hypertension and dyslipidemia, but no history of coagulopathy or conditions predisposing him to arterial or venous thromboembolism. His BMI was 26.6 kg/m 2 . He was tested for SARS-CoV-2 using a qualitative polymerase chain reaction test (Seegene Allplex 2019-nCoV Assay) and the diagnosis of COVID-19 was confirmed on April 2, 2020. He was admitted to our hospital two weeks later (April 15) for nausea, diarrhea, weakness, worsening cough and hypoxemia requiring supplemental oxygen. He was treated for COVID-19 with Accepted Article lopinavir/ritonavir, hydroxychloroquine, and azithromycin for 5 days as well as 7 days of cefuroxime. Tacrolimus was held due to lopinavir/ritonavir administration, but MMF and prednisone were continued at the same doses. Throughout his hospitalization, he received high dose thromboembolism prophylaxis with enoxaparin 40 mg subcutaneously every 12 hours, as per institutional protocol which was modified to reflect the higher rate of thromboembolic events observed in COVID-19 patients. During this admission, he had 3 electrocardiograms to monitor QTc, all of which demonstrated sinus rhythm. His creatinine was elevated from a baseline of 120 to 147 umol/L and remained elevated at time of discharge. Other laboratory values are summarized in Table 1 This article is protected by copyright. All rights reserved Therapeutic anticoagulation with enoxaparin 80 mg subcutaneously every 12 hours was initiated with a plan to switch to apixaban 5 mg p.o. twice daily at discharge for at least 3 months. Outpatient echocardiogram, Holter monitor, and age-appropriate malignancy screening were arranged prior to patient's discharge home. . COVID-19 is thought to affect the kidneys through several postulated mechanisms, including systemic illness, renal hypoperfusion, cytokine storm, and direct effects of SARS-CoV-2 itself on the nephron (7). There is mounting evidence that COVID-19 patients are predisposed to both venous (5, 8, 9) and arterial (10) thromboembolic events. The pathophysiology of COVID-19 induced hypercoagulability appears to be multifactorial. Firstly, the hyperinflammatory state caused by the SARS-CoV-2 virus activates coagulation pathways and creates a hypercoagulable state (11, 12) . This may precipitate disseminated intravascular coagulation. Endothelial dysfunction provoked by the cytokine storm as well as direct adhesion of the virus to endothelial cells via ACE2 receptor further exacerbates hypercoagulability and may be responsible for microvascular disease manifestations (11) . Another potential mechanism of SARS-CoV-2 induced coagulopathy, albeit less well characterized, is the association with the production of antiphospholipid antibodies (13) . COVID-19 patients frequently demonstrate high erythrocyte sedimentation rate, C-reactive protein, D-dimer and fibrinogen, along with thrombocytopenia (11, 12, 14) . Reports have demonstrated a potential role for D-dimer in both the prediction and prognostication of DVT in COVID-19 infection (13, 15) . Early case reports and case series have highlighted that kidney transplant recipients often present with similar initial symptoms to the general population (16) (17) (18) . Immunosuppressive medications This article is protected by copyright. All rights reserved potentially predispose them to more severe or atypical forms of the disease (19) . Consistent with this, they are more likely to deteriorate rapidly and have poorer outcomes (19, 20) . Reports also suggest that COVID-19 patients may benefit from thromboprophylaxis (9, 21) . The American Society of Hematology has stated that it is reasonable to consider thromboprophylaxis beyond hospitalization in certain populations (22) . Whether solid organ transplant recipients present an even higher risk of thromboembolism in the setting of COVID-19 remains unclear. Since we are the first to report this complication, further investigation is required before making recommendations for thromboembolic prophylaxis in all solid organ transplant recipients with COVID-19. In summary, we present the case of a kidney-pancreas transplant recipient with moderate to severe COVID-19 complicated by late kidney allograft segmental infarction. This is the first case of a thromboembolic event in a SARS-CoV-2 positive solid organ recipient. We hypothesize that COVID-19 related hypercoagulable state is responsible for this thromboembolic event. Furthermore, this event occurred after the resolution of symptoms. The extent of thromboembolic risk in transplant patients with COVID-19 requires further investigation, as does the potential role for prolonged thromboprophylaxis in patients with moderate to severe COVID-19 infection. This case report highlights an unexpected consequence of COVID-19 and adds to the recent reports suggesting an association with large-vessel arterial thrombosis. Table 1 . Laboratory investigations at the time of first and second admission. 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Successful recovery of CoVID-19 pneumonia in a renal transplant recipient with long-term immunosuppression Early description of coronavirus 2019 disease in kidney transplant recipients in New York CoVID-19 and kidney transplantation A single center observational study of the clinical characteristics and short-term outcome of 20 kidney transplant patients admitted for SARS-CoV2 pneumonia Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy CoVID-19 and VTE/anticoagulation: frequently asked questions The authors would like to thank the patient for allowing his case to be presented in this article. The authors of this manuscript have no sources of funding to declare. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation. Data sharing is not applicable to this article as no new data were created or analyzed in this study. This article is protected by copyright. All rights reserved This article is protected by copyright. All rights reserved