Abstract
The clinical manifestation of COVID-19 can vary from an asymptomatic course to ARDS requiring invasive mechanical ventilation and extracorporeal membrane oxygenation. A kidney transplanted patient infected with SARS CoV-2 infection showed a mild disease despite immune suppression. It is possible that Immunosuppression can “be protective” as the cytokine storm is an important factor in the disease story. Despite the good outcome reported in the present case report, is remains of vital importance the solid organ transplant patients use precautions in order to avoid the infection.
KEYWORDS: clinical research/practice, immunosuppressant – calcineurin inhibitor: tacrolimus, infection and infectious agents – viral, infectious disease
Abbreviations: ARDS, severe acute respiratory distress syndrome; COVID-19, coronavirus disease 19; ICU, intensive care unit; MERS-CoV, Middle East respiratory syndrome CoV; SARS-CoV-2, respiratory syndrome coronavirus 2
1. INTRODUCTION
A pandemic due to a novel coronavirus, named severe SARS-CoV-2, is ongoing. At the beginning of January, 2020, SARS-CoV-2 has been first identified as the cause of COVID-19 in China and it is now spreading worldwide.
The clinical manifestation of COVID-19 can vary from an asymptomatic course to ARDS requiring invasive mechanical ventilation and extracorporeal membrane oxygenation.1 Patients at higher risk to develop a severe disease usually suffer from hypertension, cardiovascular diseases, diabetes and malignancy. Roughly, 25% of hospitalized patients need ICU admission, and mortality in this group is around 5%.2 Patients with solid organ transplant might be at higher risk to develop a severe disease and to have an unfavorable outcome. However, data on these patients are lacking. We report here a case of a kidney-transplanted patient who received a diagnosis of infection due to SARS-CoV-2.
2. CASE REPORT
A 50-year-old man received a kidney transplant in 2016 (a previous kidney transplant was performed in 1993, but the organ was lost due to rejection in 2008) for IGA correlated nephropathy. He suffered from hypertension, treated with amlodipine, and diabetes. His immunosuppressive regimen consisted of tacrolimus and mycophenolate mofetil. On March 4, 2020 he started complaining fever and cough and he was admitted to the emergency room of another hospital Hospital on March 8, 2020. His parameters on admission were a body temperature of 37.3°C, blood pressure 120/80 mm Hg, heart rate 64 bpm. An arterial blood gas analysis showed pH 7.38, pO2 79 mm Hg, pCO2 31 mm Hg. Blood examination revealed a white blood cells count (WBC) of 3200 × 103/µL, Lymphocytes 600 × 103/µL, lactate dehydrogenase 277 mU/mL. IL6 plasma level on March 16, 2020 was 26.22 pg/mL (normal value 0-3.12). The patient was dismissed home the same day. Due to persistence of fever (around 37.5°C) and cough he was admitted to our hospital on March 13, 2020. Nasopharyngeal swab was positive for SARS CoV-2 RT-PCR. Chests x-ray showed minimal interstitial lesions. Laboratory data are reported in Table 1. Since no respiratory symptoms were reported and drug interactions between lopinavir/ritonavir (LPV/r) and patients’ daily medications were extensively detected, antivirals and hydroxychloroquine were not administrated. Immunosuppressive therapy was unchanged. Conversely, ceftriaxone was administrated as prophylactic antibiotic coverage. On March 17, 2020 he was discharged home breathing in ambient air and without fever.
TABLE 1.
Laboratory parameters
| March 8, 2020 | March 13, 2020 | March 17, 2020 | |
|---|---|---|---|
| White blood cell (×103/µL) | 3530 | 3200 | 2880 |
| Neutrophils (×103/µL) | 1850 | 2400 | 1590 |
| Lymphocytes (×103/µL) | 1210 | 600 | 890 |
| Monocytes (×103/µL) | 640 | 300 | 380 |
| Eosinophils (×103/µL) | 10 | 0 | 0 |
| Creatinine (mg/dL) | 1.7 | 1.65 | 1.37 |
| C-reactive protein (mg/dL) | 1.86 | ||
| LDH (mU/mL) | 167 | 277 | |
| ASL (mU/mL) | 22 | ||
| ALT (mU/mL) | 14 | 62 | |
| IL6 (pg/mL) | 26.22a |
Performed on March 16, 2020.
3. DISCUSSION
Given to the extent of the SARS-CoV-2 pandemic, solid organ transplant recipients are at risk to contract the disease. Nonetheless, disease course and prognosis in this group are unknown at the moment.
Although viral pneumonia in solid organ transplant patients may present with mild or atypical symptoms at onset, complications occur more frequently than in immunocompetent hosts.3
A previous study described the clinical characteristics of two kidney-transplant recipients affected by MERS-CoV infection and reported a variable outcome – death in one case and complete resolution in the other case.4 The first case was complicated by acute renal failure. Despite a T lymphocyte depletion due to antithymocyte globulin 6 weeks before MERS Cov infection, the second patient had a favorable outcome. As the novel corona virus belongs to the Betacoronavirus family, which also contains SARS-CoV and MERS-CoV, it is possible the infections due to these different viruses share some similarities.
At the time of writing, a published report described two heart transplant recipients in China who presented with variable severity of disease (one mild and another with more severe manifestations requiring a prolonged hospitalization). Both patients eventually survived.5
Lung viral infections can be associated with ARDS characterized by elevated levels of different cytokines, such as IL 2R, IL 6, and IL 10.6 The pathogenesis of SARS-CoV-2 infection is as well associated with an immune over-reaction, resulting in a cytokines dysregulated release in particular in those patients who develop this condition.7
Patients needing ICU care have higher plasma levels of many innate cytokines, IP-10, MCP-1, MIP-1A, and TNFα. These clinical features suggest that involvement of highly pro-inflammatory condition in the disease progression and severity is likely. In patients with a benign outcome, the symptoms are cleared by the fifth day from onset.2 The evolution of the disease in the patient described here was favorable, as he was discharged in good clinical conditions after 10 days from symptoms onset. In general 8 days is the main time window between onset of first symptoms and development of ARDS.2 The IL 6 plasma level at discharge was 26.22 pg/mL, a value below the median level observed in patients requiring high O2 flow.8 It can be hypothesized that solid organ transplant patients might be protected by immunosuppressive therapy that might dampen the cytokine storm, is an important factor in the disease story.
Despite the good outcome reported in the present case report, it is of vital importance for solid organ transplant patients to use precautions in order to avoid the infection.
Acknowledgments
DISCLOSURE
The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.
COVID19 IRCCS SAN MATTEO PAVIA TASK FORCE
ID Staff: Raffaele Bruno, Mario U. Mondelli, Enrico Brunetti, Angela Di Matteo, Elena Seminari, Laura Maiocchi, Valentina Zuccaro, Layla Pagnucco, Bianca Mariani, Serena Ludovisi, Raffaella Lissandrin, Aldo Parisi, Paolo Sacchi, Savino F. A. Patruno, Giuseppe Michelone, Roberto Gulminetti, Domenico Zanaboni, Stefano Novati, Renato Maserati, Paolo Orsolini, Marco Vecchia. ID Residents: Marco Sciarra, Erika Asperges, Marta Colaneri, Alessandro Di Filippo, Margherita Sambo, Simona Biscarini, Matteo Lupi, Roda Silvia, Teresa C. Pieri, Ilaria Gallazzi, Michele Sachs, Pietro Valsecchi. Emergency Care Unit: ECU Staff: Stefano Perlini, Claudia Alfano, Marco Bonzano, Federica Briganti, Giuseppe Crescenzi, Anna G. Falchi, Roberta Guarnone, Barbara Guglielmana, Elena Maggi, Ilaria Martino, Pietro Pettenazza, Serena Pioli di Marco, Federica Quaglia, Anna Sabena, Francesco Salinaro, Francesco Speciale, Ilaria Zunino. ECU Residents: Marzia De Lorenzo, Gianmarco Secco, Lorenzo Dimitry, Giovanni Cappa, Igor Maisak, Benedetta Chiodi, Massimiliano Sciarrini, Bruno Barcella, Flavia Resta, Luca Moroni, Giulia Vezzoni, Lorenzo Scattaglia, Elisa Boscolo, Caterina Zattera, Tassi M. Fidel, Capozza Vincenzo, Damiano Vignaroli, Marco Bazzini. Intensive Care Unit: Giorgio Iotti, Francesco Mojoli, Mirko Belliato, Luciano Perotti, Silvia Mongodi, Guido Tavazzi. Paediatric Unit: Gianluigi Marseglia, Amelia Licari, Ilaria Brambilla. Virology Staff: Barbarini Daniela, Bruno Antonella, Cambieri Patrizia, Campanini Giulia, Comolli Giuditta, Corbella Marta, Daturi Rossana, Furione Milena, Mariani Bianca, Maserati Roberta, Monzillo Enza, Paolucci Stefania, Parea Maurizio, Percivalle Elena, Piralla Antonio, Rovida Francesca, Sarasini Antonella, Zavattoni Maurizio. Virology Technical staff: Adzasehoun Guy, Bellotti Laura, Cabano Ermanna, Casali Giuliana, Dossena Luca, Frisco Gabriella, Garbagnoli Gabriella, Girello Alessia, Landini Viviana, Lucchelli Claudia, Maliardi Valentina, Pezzaia Simona, Premoli Marta. Virology Residents: Bonetti Alice, Caneva Giacomo, Cassaniti Irene, Corcione Alfonso, Raffella Di Martino, Annapia Di Napoli, Ferrari Alessandro, Ferrari Guglielmo, Fiorina Loretta, Giardina Federica, Mercato Alessandra, Novazzi Federica, Ratano Giacomo, Rossi Beatrice, Sciabica I. Maria, Tallarita Monica, Vecchio N. Edoardo. Research Laboratories, Division of Infectious Diseases and Immunology: Antonella Cerino, Stefania Varchetta, Barbara Oliviero, Stefania Mantovani, Dalila Mele. Pharmacy Unit: Monica Calvi, Michela Tizzonis. Hospital Management: Carlo Nicora, Antonio Triarico, Vincenzo Petronella, Carlo Marena, Alba Muzzi, Paolo Lago. Data Unit: Francesco Comandatore, Gherard Bissignandi, Stefano Gaiarsa, Marco Rettani, Claudio Bandi.
DATA AVAILABILITY STATEMENT
Data sharing is not applicable to this article as no new data were created or analyzed in this study.
REFERENCES
- 1.Lai CC, Shih TP, Ko WC, et al. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges. Int J Antimicrob Agents. 2020;55(3):105924. doi: 10.1016/j.ijantimicag.2020.105924. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Wang D, Hu BO, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061. doi: 10.1001/jama.2020.1585. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Manuel O, Estabrook M. RNA respiratory viral infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13511. doi: 10.1111/ctr.13511. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.AlGhamdi M, Mushtaq F, Awn N, et al. MERS CoV infection in two renal transplant recipients: case report. Am J Transplant. 2015;15(4):1101–1104. doi: 10.1111/ajt.13085. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Aslam S, Mehra MR. COVID-19: yet another coronavirus challenge in transplantation [published online ahead of print March 14, 2020]. J Lung Heart Tranplant. 2020. pii: S1053-2498(20)31468-6. 10.1016/j.healun.2020.03.007 [DOI] [PMC free article] [PubMed]
- 6.Guo L, Wei D, Zhang X, et al. Clinical features predicting mortality risk in patients with viral pneumonia: the MuLBSTA Score. Front Microbiol. 2019;10:2752. doi: 10.3389/fmicb.2019.02752. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Prompetchara E, Ketloy C, Palaga T. Immune responses in COVID-19 and potential vaccines: lessons learned from SARS and MERS epidemic [published online ahead of print 2020]. Asian Pac J Allergy Immunol. 10.12932/AP-200220-0772 [DOI] [PubMed]
- 8.Wang Z, Yang B, Li Q, et al. Clinical features of 69 cases with coronavirus disease 2019 in Wuhan, China [published online ahead of print 2020]. Clin Infect Dis. 10.1093/cid/ciaa272 [DOI] [PMC free article] [PubMed]
Associated Data
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Data Availability Statement
Data sharing is not applicable to this article as no new data were created or analyzed in this study.