key: cord-0971833-1mw03neu authors: Machado, David José de Barros; Ianhez, Luiz Estevam title: COVID‐19 pneumonia in kidney transplant recipients—Where we are? date: 2020-05-26 journal: Transpl Infect Dis DOI: 10.1111/tid.13306 sha: bc62edebce956c9703ce19db69b813eba15ae653 doc_id: 971833 cord_uid: 1mw03neu In late December 2019, China reported cases of respiratory illness in humans that involved a novel coronavirus SARS‐CoV‐2. On March 20, 2020, the first coronavirus disease 2019 (COVID‐19) in Brazil was diagnosed, and by now, we present the report on the first case of COVID among transplant recipients in our country. A liver and kidney transplant patient with SARS‐CoV‐2 pneumonia without respiratory failure was treated in a clinical multimodal strategy consisting of symptomatic support therapy, immunosuppression reduction, use of anti‐coronavirus drugs and heparin leading to a progressive improvement of patient symptoms till discharge. The authors also present a comprehensive review of published cases. In late December 2019, China reported cases of respiratory illness in humans appearing first in Wuhan that involved a novel coronavirus SARS-CoV-2. 1 The coronavirus disease 2019 (COVID-19) rapidly spread over countries due to the high viral contagiousness, the transmission during the asymptomatic phase, and the underestimation of the importance of the virus by the population and turned into a public health emergency of international concern in just 1 month 2 The largest case series to date of COVID-19 is the China Center for Disease Control and Prevention's report of 44 672 people with laboratory confirmed disease. The overall case-fatality rate (CFR) was 2.3% with poor clinical outcomes associated with older age and underlying health conditions-cardiovascular disease, diabetes, chronic respiratory disease, hypertension, and cancer. 3 The relative importance of different underlying health conditions is unclear, such as immunosuppression in solid organ transplantation. Brazil has a huge transplantation program and ranks second among all countries regarding the number of transplants performed. 4 On February 26, the virus entered Brazil and currently, after 2 months, we have 43 079 confirmed cases and 2741 deaths. 5 But so far, we do not have any COVID-19 described case among the solid organ transplantation patient's in Brazil. Herein, we report on the outcomes of a kidney after liver transplant recipient with COVID-19 pneumonia admitted to the Hospital Alemão Oswaldo Cruz (São Paulo-Brazil) and review the literature. COVID-19 pneumonia in kidney transplant recipients-Where we are? David José de Barros Machado 1,2 | Luiz Estevam Ianhez 1 laparoscopic appendicectomy on 16 March and was at home convalescent, when he met his son just returning from Ontario the day before and asymptomatic. In Canada, there were 103 confirmed cases of COVID-19 reported up to that day. 6 His wife presented flu-like symptoms on 19 March and was advised to stay in self-quarantine. Both were confirmed COVID-19 serum-positive afterward. He was under maintenance immunosuppression with tacrolimus, mycophenolate sodium and prednisone and also taking omeprazole, escitalopram, lamivudine (prevention of recurrence of HBV infection with anti-HBc positive grafts), glimepiride, and ramipril. Lung CT scanning at admission showed lesions in 40% of lungs' volume, characterized as bilateral ground-glass opacities and foci of condensation, typical radiological findings of COVID-19 pneumonia. Baseline ECG showed a 441 ms QTc interval, and therefore, specific treatment was started, even before arrival of nasopharyngeal swab secretion RT-PCR confirming SARS-CoV-2 infection (on day 2 after admission) with hydroxychloroquine 400 mg BID, nitazoxanide 500 mg BID, empirical antibiotic scheme with ceftriaxone 1 g BID and azithromycin 500 mg OD for 10 days, and unfractionated heparin 5000 IU TID. Tacrolimus was decreased to half dose for levels 3-5 ng/mL, mycophenolate sodium was stopped, and prednisone was increased to 10 mg. The patient did not need supplemental oxygen, and O 2 saturation stayed greater than 94% during his hospitalization. Acidosis, hyponatremia, and hyperkalemia were corrected in the next 4 days with bicarbonate solution, and the patient recovered consciousness. Tacrolimus through level on D + 4 was 4.2 ng/mL. Total lymphocytes count kept above 1.0 × 10 3 /mm 3. D-dimer reduced to 3834 ng/mL on the fourth day (D + 4) and was 1382 ng/mL on D + 21; C-reactive protein reduced to 3.96 mg/dL after 7 days and 0.76 mf/dL on D + 21. Serum creatinine returned to baseline levels (1.7 mg/dL). CT showing bilateral ground-glass opacities and sparse bilateral consolidation foci, predominating in peripheral regions; CT scan (B) after 4 d with reduced extension of ground-glass opacities and appearance of parenchymal consolidation and septal thickening; CT scan (C) after 8 d with reduced extension of groundglass opacities and septal thickening, more parenchymal consolidation and fibrous bands in both lungs and CT scan (D) at D + 21 in a resolution stage the consolidation were partially absorbed, and residual laminar atelectasis and small parenchymal bands persisted scan repeated every 4 days is shown in Figure 1 , with progressive changing patterns from ground-glass opacities to irregular alveolar consolidation and at D + 21 as outpatient in a resolution stage the consolidation were partially absorbed, and residual laminar atelectasis and small parenchymal bands persisted. SARS-CoV-2 at D + 12 returned negative and patient was discharged. Our case shows successful outcome of COVID-19 in a long-term liver-kidney transplant patient admitted in early phase of disease to the ward. Diagnosis was promptly made in addition to stratification for complication risk. We considered our patient as having a moderate disease as he has never presented hypoxemia, lung lesions compromised <50% of lungs volume, but he was an elderly patient, with Regarding treatment, we proceeded as always with potential severe respiratory diseases and promptly reduced total immunosuppression. As our patient presented with pulmonary infiltrates but without hypoxemia or toxemic (moderate impairment), we did not stop but reduced tacrolimus to reach through levels of 3-5 ng/ mL, withdrawn mycophenolate and doubled prednisone dose. CoV was diminished after tacrolimus treatment, but whether SARS-CoV-2 is also inhibited is unknown. 15 Table 2 . Hydroxychloroquine was given in 32 (80%), as shown in Table 2 . Hydroxychloroquine has immunomodulatory, antithrombotic, and antiviral effects. Its antiviral effect is attributed to the alkalinization of intracellular acidic organelles and to the inhibition of entry steps and viral proteins glycosylation. Recently, chloroquine was shown to inhibit the replication and spread of coronavirus Oxygen support device No oxygen support-n (%) 10 (25) Nasal catheter/Low support-n (%) Face mask/High-flux nasal delivery/High support-n (%) Non-invasive ventilation-n (%) Invasive ventilation-n (%) 3 (7.5) Abbreviations: CNI, calcineurin inhibitor; IVIg intravenous immunoglobulin; mTORi, mammalian target or rapamycin inhibitor. Inpatient-n (%) 23 (57. 5) in vitro and to prevent infection with hCoV in newborn mice showing promise as a potential therapy of this resistant virus. 16 In an open-label study of 36 patients with COVID-19, use of hydroxychloroquine was associated with a higher rate of undetectable SARS-CoV-2 RNA on nasopharyngeal specimens at day 6 compared with no specific treatment. 17 Our patient had d-dimer >10 000 ng/mL or >20-fold of upper limit of normal. Three patients used mechanical ventilation, and only five were admitted to intensive care units (ICU), as presented in Table 3 . However, eight patients had died at publications date. The reasons for not providing mechanical ventilation and ICU are not clear in publications, except in one already cited. 8 Importantly, renal function should be monitored because acute kidney injury is frequent (22.5%). Two patients (5%) required dialysis. Most cases reported have incomplete evolution and outcomes data due to short follow-up time. Only nine patients had been discharged. In conclusion in this liver and kidney transplant patient with SARS-CoV-2 pneumonia without respiratory failure, we applied a multimodal strategy consisting of symptomatic support therapy, total immunosuppression reduction, use of anti-coronavirus drugs, and heparin leading to a progressive improvement of the patient symptoms till discharge. Except for heparin, it has been the main used scheme. In the literature cases, management was individualized according to severity, but case-fatality rate cannot be extrapolated be- to mitigate organ/tissue injures by COVID-19 need to be identified in future researches. The authors of this manuscript have no conflicts of interest to disclose. DJBM and LEI contributed to the analysis of the data and the writing of the manuscript. David José de Barros Machado https://orcid. org/0000-0002-3874-7957 WHO. Novel Coronavirus (2019-nCoV): Situation Report -1 World Health Organization WHO. 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