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      First Cases of COVID-19 in Heart Transplantation From China

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          Abstract

          Emerging studies suggest that the novel coronavirus SARS-CoV-2 and the disease it causes, COVID-19, selectively afflicts the elderly, particularly those with chronic comorbidities. 1 , 2 Here, we report on two heart transplant recipients with COVID-19, one a severe presentation and another mild. The first was a 51-year-old man with a heart transplant on November 8th, 2003. His immunosuppression was tacrolimus 1 mg twice daily plus mycophenolate mofetil 0.5 g twice daily. The last known blood concentration of tacrolimus was 6.5 ng/ml, and cardiac allograft function was normal with a history of well controlled hypertension. On Jan 23rd 2020, he complained of intermittent fever, chills, fatigue, poor appetite and diarrhea. On examination, his temperature was 38.5°C, oxygen saturation was 99% on room air, respiratory rate of 20 breaths per minute without distress. Laboratory tests showed a white blood cell count of 4.87 × 109 /L (normal range, 4.0–10.0 × 109 /L), C Reactive Protein of 18.6 mg/L (normal range, 0-10 mg/L). Chest computed tomographic (CT) scan showed bilateral ground-glass opacities (Figure 1 ). He was initially treated with intravenous levofloxacin and ribavirin, but remained febrile. He was admitted to Wuhan Fifth Hospital on Jan 26th 2020 and a throat swab nucleic acid test was positive for 2019-nCoV. Moxifloxacin 0.4 g and ganciclovir 0.25 g were then given intravenously daily (and continued until Feb 5th 2020). Initially, his temperature rose to 39°C with a dry cough on Jan 27th,2020 and oxygen saturation decreased gradually requiring oxygen nasal supplementation. Body temperature dropped to normal on Jan 29th, however oxygen saturation deteriorated, (75% without supplemental oxygen after slight activity). CT scan revealed worsening of lung lesions (Figure 1) and oxygen was given through a face mask with improvement of oxygen saturation to 95%. Intravenous human gamma globulin 10 g / day plus methylprednisolone 80 mg/day for initiated for 5 consecutive days and other immunosuppressive drugs were held from Jan 30th to Feb 5th, 2020. After treatment, the patient's symptoms improved, and oxygen saturation maintained above 96% with nasal cannula oxygen. Intravenous medications were then stopped, and oral administration of moxifloxacin 0.4 g/day and arbidol (a non-nucleoside antiviral and immunomodulating drug given for influenza), at a dose of 0.2 g three times a day was administered for 5 days. Immunosuppressive and antihypertensive drugs were resumed on Feb 12th, 2020. The patient's temperature normalized for more than 20 days, without cough for 10 days and preserved oxygen saturation. Two consecutive RT-PCR throat swabs for 2019-nCoV on Feb 14th and 18th 2020, were negative. CT scan on Feb 24th showed significant resolution of lung lesions (Figure 1). The patient was discharged on Feb 27th 2020. Typical imaging demonstrated dynamic progress of the disease (Figure 1). However, resolution of lung lesions lagged behind symptoms relief. Figure 1 Dynamic chest CT manifestations of severe COVID-19 in a heart transplant recipient. Figure 1 A second heart transplant male recipient aged 43-years old presented to the outpatient clinic with fever for 2 days on Jan 25th 2020, exhibited mild lung lesions on CT scan, but a nucleic acid test for 2019-nCoV was positive. The patient was quarantined at home and then admitted to the hospital on Feb 6th, 2020 following which he was discharged on Feb 11th when two nucleic acid tests for 2019-nCoV tested negative. (Detailed information on this patient is in Table 1 ). Table 1 Clinical characteristics of the second patient Table 1 Date of transplant May 17th, 2017 Immunosuppression Tacrolimus 1.5 mg in the morning, 2 mg in the evening mycophenolate mofetil 0.5 g twice daily Blood concentration of tacrolimus 8.3 ng/ml Allograft function Left ventricular ejection fraction 64% Comorbidities Hyperlipidemia and impaired glucose tolerance Lab test on Jan 25th2020, WBC 8.2 × 109 /L, Lymphocyte 0.8 × 109 /L, CRP 13.4 mg/Lon Feb 7th2020: WBC 8.4 × 109 /L, Lymphocyte 1.5 × 109 /L, CRP 1.0 mg/L RT-PCR of 2019-nCoV (throat swab) Positive on Jan 28th, negative on Feb 8th and 10th Treatment Ceftriaxone sodium 2.0 g and ganciclovir 0.25 g intravenously (Jan 25th to 31st); Oral moxifloxacin 0.4 g/day and arbidol 0.2 g three times a day (Feb 1st to 10th) Symptoms evolution Fever for two days, up to 38.5 degrees CFatigue and poor appetite from Jan 28th to Feb 5th Rejection during or after COVID-19 None Other Complications None These cases may represent the first descriptions of COVID-19 in heart transplant recipients and suggest that presentations appear to be similar to those observed in non-transplant recipients. We have also followed 200 heart transplant patients in Hubei area by telephone and found a third confirmed patient who is currently under treatment in another hospital, but the case details are not available to us and therefore not included in our report. Whether organ transplant recipients are more susceptible to COVID-19 requires further large-scale epidemiological investigation, but the presentation pattern and resolution of the disease using the described supportive measures may serve to inform direction of care if such patients are encountered elsewhere. Conflicts of interest and Funding None.

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          Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study

          Summary Background An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia. Methods In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation. Findings Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3–11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients. Interpretation The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1–2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced. Funding None.
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            Author and article information

            Contributors
            Journal
            J Heart Lung Transplant
            J. Heart Lung Transplant
            The Journal of Heart and Lung Transplantation
            ished by Elsevier Inc. on behalf of International Society for Heart and Lung Transplantation.
            1053-2498
            1557-3117
            17 March 2020
            17 March 2020
            Affiliations
            [0001]Department of cardiovascular surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
            Author notes
            [* ]Correspondence to: Nianguo Dong, Department of cardiovascular surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. dongnianguo@ 123456hotmail.com
            [** ]Correspondence to: Jie Cai, Department of cardiovascular surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. cjdoctor@ 123456163.com
            Article
            S1053-2498(20)31467-4
            10.1016/j.healun.2020.03.006
            7156127
            32362394
            33646d96-d7d2-4177-90c7-f3227c9e4a27
            © Published by Elsevier Inc. on behalf of International Society for Heart and Lung Transplantation.

            Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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