key: cord-1034372-205vk9tw authors: Guillen, Elena; Pineiro, Gaston J.; Revuelta, Ignacio; Rodriguez, Diana; Bodro, Marta; Moreno, Asunción; Campistol, Josep M.; Diekmann, Fritz; Ventura‐Aguiar, Pedro title: Case report of COVID‐19 in a kidney transplant recipient: Does immunosuppression alter the clinical presentation? date: 2020-04-09 journal: Am J Transplant DOI: 10.1111/ajt.15874 sha: 725eb73f9b5d80b7e8ad732fb8e74965ca58899e doc_id: 1034372 cord_uid: 205vk9tw COVID‐19 is novel infectious disease with an evolving understanding of its epidemiology and clinical manifestations. Immunocompromised patients often present atypical presentations of viral diseases. Herein we report a case of a COVID‐19 infection in a solid organ transplant recipient, in which the first clinical symptoms were of gastrointestinal viral disease and fever, which further progressed to respiratory symptoms in 48 hours. In these high risk populations, protocols for screening for SARS‐Cov2 may be needed to be re‐evaluated. Coronavirus Disease 2019 (COVID-19) is a novel viral disease with over 93 000 confirmed cases worldwide,1 in which knowledge regarding disease epidemiology and clinical presentation has been evolving in the past 4 months since the initial identification. In the general population, the reported case fatality rate is about 1%-6%.2 Solid organ transplant (SOT) recipients are under chronic immunosuppression, and respiratory infections may present atypically, often with two or more infectious processes presenting simultaneously. 3 There have been currently only a couple of reports of COVID-19 among SOT recipients. Hence, in such a high risk population, a strong clinical suspicion is crucial. Herein we present the case of a COVID-19 infection in a kidney transplant recipient. of gastrointestinal viral disease and fever, which further progressed to respiratory symptoms in 48 hours. In these high risk populations, protocols for screening for SARS-Cov2 may be needed to be re-evaluated. 1 .6 mg/dL, eGFR 50 mL/min). He was discharged with a presumptive diagnosis of non-severe viral gastroenteritis, and oral hydration and on demand acetaminophen were prescribed. Five days later patient returned to the ER with persistent fever, but at this time, with productive cough. He no longer presented gastrointestinal symptoms. Physical examination revealed a body temperature of 37.4°C, blood pressure of 180/100 mm Hg, pulse of 66 beats per minute, respiratory rate of 16 breaths per minute, and blood oxygen saturation of 98% on room air. He presented with signs of mucous dehydration and crackles in the right lower lung, as well as signs of conjunctivitis of his left eye. He presented no murmurs, rubs or gallops on heart exam. His abdomen was soft and nontender, and neurologic examination was unremarkable. WBC count on peripheral blood was 10.15 × 10 9 /L (total lymphocyte count 1.8 × 10 9 U/L), with a platelet count of 126 × 10 9 /L, a CRP of 13.2 mg/dL, and a procalcitonin of 0-18 ng/mL (normal range <0.50 ng/mL). Persistent mild kidney function impairment (Cr 1.6 mg/dL) and hyponatremia of 129 mEq/L were also observed. Liver transaminases and coagulation were within normal reference values. There was a medium lobe consolidation on posteroanterior chest radiograph ( Figure 1A) . Therefore, the diagnosis of community-acquired pneumonia was assumed, and he was empirically started on ceftriaxone 1 g QD and azithromycin 500 mg QD. A nasopharyngeal swab specimen was performed, and a rapid nucleic acid amplification test for influenza A and B and respiratory syncytial virus were reported back as negative. Thereafter, although the patient didn't have any travel history nor reported known contacts with contagious or infected people, nasopharyngeal and oropharyngeal swab specimens were collected for testing COVID-19, following an update of local authorities' screening protocol of pneumonia of undetermined aetiology. Both swabs for SARS-CoV-2 by real-time reverse-transcriptasepolymerase-chain-reaction (rRT-PCR) assay were reported positive (hereafter assumed as reference day -D0). Local protocol for COVID-19 was activated, with patient hospitalization under isolation, and treatment with oral Lopinavir/ Ritonavir 400/100 BID was initiated at D+1 (Figure 2 ). Due to the interaction of Ritonavir with calcineurin inhibitors, tacrolimus was withdrawn, as was everolimus due to its reported risk for mTOR-inhibitor induced neumonitis.4 Empirical broad spectrum antibiotic was also initiated (ceftaroline and meropenem) and maintained, despite negative microbiological cultures for viral, bacterial, or fungal infections, including aspergillosis, pneumocystis, and mycobacteria's. Oral hydroxychloroquine treatment was prescribed (400 mg BID for 24 hours, afterwards 200 mg BID; oral). After 10 days since the initial symptoms and 72 hours after supportive and anti-viral treatment, the patient presented a worsening in respiratory symptoms, with hypoxia in spite of the use of highflux nasal oxygen delivery, and a progression to diffuse bilateral infiltrates on chest X-ray ( Figure 1B In the general population, the reported case fatality rate is low, about 1%-6%. However, most of the fatal cases have occurred in patients with advanced age or underlying medical comorbidities. Therefore, high risk populations need more careful attention.13 In solid organ transplantation only two cases have been reported from the experience in China.14 Both were heart transplant recipients, with ages similar to our patient's. One of the reported cases is similar to the one herein, with an atypical presentation (fever, diarrhea, fatigue) without respiratory symptoms. Both these cases and now the one reported here highlight the need towards high suspicious and low threshold towards screening these patients for SARS-Cov2. We would like to emphasize the challenging differential diagnosis of this case. Due to high accumulated immunosuppressive load, initial gastrointestinal symptoms and electrolyte disorders (hyponatremia) F I G U R E 2 Graphic representation of symptoms presentation, diagnostic workup, treatment, and progression of creatinine levels associated with a unilobar pneumonia in a transplanted patient, we first approached the case as a community-acquired pneumonia due to encapsulated bacteria. Thus, pneumococcal urinary antigen, as well as sputum and blood cultures were requested. Furthermore, the fact that our patient did not have any epidemiologic risk factor for COVID-19 infection, made the diagnostic suspicion even more difficult. In conclusion, this is a case report of COVID-19 in a solid organ transplant recipient, and it reminds us that immunocompromised patients may present with atypical clinical manifestations. Thus, when faced with a transplanted patient with an unspecified viral clinical presentation, and without any microbiological isolation, we call upon all the medical personnel to be aware and take COVID-19 into account as a potential diagnosis, especially in epidemic areas. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Fritz Diekmann https://orcid.org/0000-0001-6199-3016 Pedro Ventura-Aguiar https://orcid.org/0000-0003-3381-7503 World Health Organization Understanding of COVID-19 based on current evidence Respiratory disease in the immunosuppressed patient Safety of mTOR inhibitors in adult solid organ transplantation Enfermedad por el coronavirus (COVID-19) -Situación actual Novel coronavirus infection and gastrointestinal tract Clinical features of patients infected with 2019 novel coronavirus in Wuhan Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study Protecting health-care workers from subclinical coronavirus infection Clinical characteristics of coronavirus disease 2019 in China The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. The epidemiological characteristics of an outbreak of 2019 novel coronavirus disease (COVID-19) -China Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention First cases of COVID-19 in heart transplantation from China