Case Report SARS-CoV-2 and Norovirus Co-Infection after Lung Transplantation Carolin Steinack 1,2,* , René Hage 1,2 , Christian Benden 2,3 and Macé M. Schuurmans 1,2 1 Division of Pulmonology, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland; [email protected] (R.H.); [email protected] (M.M.S.) 2 Faculty of Medicine, University of Zurich, Raemistrasse 71, 8006 Zurich, Switzerland; [email protected] 3 Swisstransplant, Effingerstrasse 1, Postfach, 3011 Bern, Switzerland * Correspondence: [email protected] Received: 5 May 2020; Accepted: 27 May 2020; Published: 29 May 2020 Abstract: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spreading as a pandemic in 2020. Few reports on infections in thoracic transplantation have been published so far. We present a case of COVID-19 in a 55-year old female lung transplant recipient infected 5 months posttransplant, who additionally was co-infected with a Norovirus. Respiratory and gastrointestinal symptoms were observed without need of therapeutic escalation except for antibiotic therapy. We observed a moderate disease evolution likely due to triple immunosuppression. Keywords: Lung Transplantation; COVID-19; SARS-CoV-2; Coronavirus; norovirus 1. Introduction In late 2019, a novel coronavirus, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged from Wuhan, China [1]. This virus leads to the coronavirus disease 2019 (COVID-19), currently causing a pandemic with worldwide severe economic and healthcare consequences [2]. Among the most dominant clinical characteristics are fever, cough and fatigue, whereas gastrointestinal symptoms are rather uncommon. Critical disease conditions may be caused by severe and sustained systemic inflammatory responses (hyperinflammation or “cytokine storm”) and a cytopathic effect, leading to acute respiratory distress syndrome (ARDS), septic shock, metabolic acidosis that is hard to correct, coagulation dysfunction and multiple organ failure. The exact viral host factors that influence the pathogenesis are still being investigated. The SARS-CoV-2 infection binds to human host cell receptors, using human angiotensin-converting enzyme 2 (hACE2), although there are more factors influencing susceptibility to infection and disease progression. Elderly people (>65 years of age) with underlying diseases such as hypertension, chronic obstructive pulmonary disease (COPD), diabetes and cardiovascular disease seem more susceptible to an infection and prone to serious outcomes of this viral disease [3]. Since the spread of SARS-CoV-2 around the world, there have only been a few case reports describing COVID-19 in patients after solid organ transplantation (SOT). We present a case of COVID-19 in a lung transplant (LTX) recipient presenting with fever and gastrointestinal symptoms in our emergency department. Transplantology 2020, 1, 16–23; doi:10.3390/transplantology1010002 www.mdpi.com/journal/transplantology Transplantology 2020, 1 17 2. Case Report Transplantology 2020, 1, FOR PEER REVIEW 2 A 55-year-old female with advanced chronic obstructive pulmonary disease (COPD) underwent a successfulwas started bilateral on a standard LTX 5 immunosuppressive months earlier. Induction regime therapy (cyclosporine—C2 (basiliximab) target was used,level 1200–1500 and the patient µg/L wasafter started48 h), 1.0 on g a standardbid mycophenolate immunosuppressive mofetil, and regime i.v. methylprednisolone (cyclosporine—C2 targetaccording level to 1200–1500 our standardµg/L afterprotocol. 48 h), In 1.0 March g bid 2020 mycophenolate she presente mofetil,d with vomiting, and i.v. methylprednisolone diarrhea and a 38.9 °C according fever in toour our emergency standard protocol.department. In MarchIn the 2020recent she months presented and withweeks, vomiting, she had diarrhea an uneventful and a 38.9 post-transplant◦C fever in our course emergency except department.for a switch from In the cyclosporine recent months to andtacrolimus weeks, because she had anof strongly uneventful variable post-transplant trough levels. course A exceptrecent forsurveillance a switch frombronchoscopy cyclosporine showed to tacrolimus no evidence because of acute of strongly cellular variable rejection trough and alevels. stable Aallograft recent surveillancefunction with bronchoscopy an FEV1 of showed 104% predicted no evidence based of acute on standard cellular rejection triple immunosuppressive and a stable allograft functiontherapy with(tacrolimus, an FEV1 mycophenolate of 104% predicted and basedprednisolone). on standard At th triplee time immunosuppressive of presentation, she therapy had a new (tacrolimus, onset of mycophenolatemild respiratory and symptoms prednisolone). consisting At the of timea dry of cough presentation, and rhinorrhea. she had a Due new onsetto the offever, mild respiratory respiratory symptoms and consisting ongoing of SARS-CoV-2 a dry cough pandemic, and rhinorrhea. diagnostic Due sampling to the fever, included respiratory blood, feces, symptoms and urine and ongoingand a nasal SARS-CoV-2 swab for pandemic, SARS-CoV-2. diagnostic The sampling nasophar includedyngeal blood,swab feces,for SARS-CoV-2 and urine and was a nasal positive, swab forprompting SARS-CoV-2. hospitalization The nasopharyngeal on a special swab isolation for SARS-CoV-2 ward. Feces was were positive, positive prompting for norovirus hospitalization after having on abeen special negative isolation 2 months ward. earlier. Feces were The positivestool specimen for norovirus tested after negative having for been SARS-CoV-2. negative2 The months serological earlier. Theantibody stool test specimen for SARS-CoV-2 tested negative IgG und for SARS-CoV-2.IgM was negative The 14 serological days after antibody the positive test fornasopharyngeal SARS-CoV-2 IgGswab und test. IgM The wasmain negative results at 14 presentation days after theincluded positive CRP nasopharyngeal 77 mg/L, leukocytosis swab test. (9.9 g/L), The mainneutrophilia results at(8.96 presentation g/L) and a includedmarked declining CRP 77 mg lymphocytopenia/L, leukocytosis (0.52 (9.9 gg/L,/L), previously neutrophilia 1.3 (8.96 g/L). g The/L) andarterial a marked blood declininggas analysis lymphocytopenia was within normal (0.52 limits, g/L, previously thus no oxygen 1.3 g/L). supplementation The arterial blood was gas given analysis initially. was withinInitial normalserum interleukin limits, thus no(IL-)6 oxygen was supplementationslightly elevated was 4.5 givenpg/mL initially. (Ref < Initial3.1) and serum decreased interleukin subsequently. (IL-)6 was slightlySoluble elevatedIL-2-receptor 4.5 pg (sIL-2R)/mL (Ref was< 3.1) 394 andpg/mL decreased (Ref < 477) subsequently. at presentation, Soluble increased IL-2-receptor up to (sIL-2R)2778 on wasday 3946 and pg decreased/mL (Ref < to477) normal at presentation, levels (327) on increased day 15. upIgG to was 2778 in on the day lower 6 and normal decreased range towith normal 7.1 g/L levels (7– (327)16). Five on daydays 15. after IgG admission, was in the CRP lower dropped normal to range5.7 mg/L with (Ref 7.1 < g 5/L mg/L). (7–16). Bronchoalveolar Five days after lavage admission, was CRPnot performed dropped todue 5.7 to mgthe/ Lfavorable (Ref < 5 clinical mg/L). evolutio Bronchoalveolarn and the lack lavage of respiratory was not performed deterioration. due toChest the favorablecomputed clinicaltomography evolution (CT) andimaging the lack revealed, of respiratory at initial deterioration.presentation, three Chest small computed new solid tomography nodular (CT)consolidations imaging revealed, without predominant at initial presentation, ground-gla threess opacities small new or solidpleural nodular effusions consolidations (Figure 1a−c). without These predominant ground-glass opacities or pleural effusions (Figure1a c). These findings had not been findings had not been observed 3 months earlier in a routine CT −examination. The consolidations observeddiminished 3 monthsover time earlier and in some a routine of them CT examination.disappeared completely The consolidations in a follow diminished up chest over CT time6 weeks and somelater (Figure of them 1d–f). disappeared completely in a follow up chest CT 6 weeks later (Figure1d–f). (a) Figure 1. Cont. Transplantology 2020, 1 18 Transplantology 2020, 1, FOR PEER REVIEW 3 (b) (c) (d) Figure 1. Cont. Transplantology 2020, 1 19 Transplantology 2020, 1, FOR PEER REVIEW 4 (e) (f) Figure 1. (a–c) new pulmonary consolidations in the chest computed tomography (CT) on March 18th Figure 1. (a)−(c) new pulmonary consolidations in the chest computed tomography (CT) on March that were not visible in a chest CT 3 months before. (d–f): All of the consolidations resolved partially or 18th that were not visible in a chest CT 3 months before. (d)−(f): All of the consolidations resolved completely in the follow-up chest CT 6 weeks later. partially or completely in the follow-up chest CT 6 weeks later. The patient was treated empirically with intravenous piperacillin/tazobactam 4.5 g every 8 h for 10 days.The Wepatient administered was treated neither empirically lopinavir with/ritonavir intraven norous hydroxychloroquine, piperacillin/tazobactam the 4.5 drug g every regimen 8 h for COVID-1910 days. We used administered predominantly neither in lopinavir/ritonavir China and Italy at thatnor hydroxychloroquine, time and also the drug the regimen drug regimen for severe for casesCOVID-19 at our used hospital predominantly then.