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      COVID-19 in Solid Organ Transplant Recipients: A Systematic Review and Meta-Analysis of Current Literature

      review-article
      Author(s): a , 1 , b , * , b , a , c , d , b , a , c , e , a , a , c , a , a , c , a , c , *
      Publication date (Electronic):
      Journal: Transplantation Reviews (Orlando, Fla.)
      Publisher: Published by Elsevier Inc.
      Keywords: Solid organ transplant, COVID-19, SARS-CoV-2, Immunosuppression, Systematic review, Meta-analysis, AKI, Acute kidney injury, CI, Confidence interval, CNI, Calcineurin inhibitor, COVID-19, Coronavirus disease 2019, CRP, C-Reactive Protein, FEM, Fixed Effect Model, HSCT, Hematopoietic Stem Cell Transplant, ICU, Intensive Care Unit, IL-6, Interleukin Six, MERS, Middle East Respiratory Syndrome, NP, Nasopharyngeal, PRESS, Peer Review for Electronic Search Strategies, PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses, REM, Random Effect Model, RT-PCR, Reverse Transcriptase-Polymerase Chain Reaction, SARS, Severe Acute Respiratory Syndrome Coronavirus 1, SARS- CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2, SOT, Solid organ transplant

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          Abstract

          Severe acute respiratory virus syndrome 2 (SARS-CoV-2) has led to a worldwide pandemic. Early studies in solid organ transplant (SOT) recipients suggested a wide variety of presentations, however, there remains a paucity of robust data in this population. We conducted a systematic review and meta-analysis of SOT recipients with SARS-CoV-2 infection from January 1 st t October 9 th, 2020. Pooled incidence of symptoms, treatments and outcomes were assessed. Two hundred and fifteen studies were included for systematic review and 60 for meta-analysis. We identified 2,772 unique SOT recipients including 1,500 kidney, 505 liver, 141 heart and 97 lung. Most common presenting symptoms were fever and cough in 70.2% and 63.8% respectively. Majority (81%) required hospital admission. Immunosuppressive medications, especially antimetabolites, were decreased in 76.2%. Hydroxychloroquine and interleukin six antagonists were administered in59.5% and 14.9% respectively, while only few patients received remdesivir and convalescent plasma. Intensive care unit admission was 29% from amongst hospitalized patients. Only few studies reported secondary infections. Overall mortality was 18.6%. Our analysis shows a high incidence of hospital admission in SOT recipients with SARS-CoV-2 infection. As management of SARS-CoV-2 continues to evolve, long-term outcomes among SOT recipients should be assessed in future studies.

          HIGHLIGHTS

          • •

            High rate of hospital and ICU admission amongst SOT recipients with COVID-19

          • •

            Fever maybe absent in up to 30% of SOT recipients with COVID-19

          • •

            Majority of centers held anti-metabolites in SOT patients with COVID-19

          • •

            Overall mortality in SOT recipients with COVID-19 was 20%

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          Most cited references142

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Chaolin Huang, Yeming Wang, Xingwang Li … (2020)
          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.

            Alessandro Liberati, Douglas G. Altman, Jennifer Tetzlaff … (2009)
            Systematic reviews and meta-analyses are essential to summarize evidence relating to efficacy and safety of health care interventions accurately and reliably. The clarity and transparency of these reports, however, is not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (QUality Of Reporting Of Meta-analysis) Statement--a reporting guideline published in 1999--there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realizing these issues, an international group that included experienced authors and methodologists developed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA Statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this Explanation and Elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA Statement, this document, and the associated Web site (http://www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.
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              PRESS Peer Review of Electronic Search Strategies: 2015 Guideline Statement.

              Jessie L. McGowan, Margaret Sampson, Douglas M Salzwedel … (2016)
              To develop an evidence-based guideline for Peer Review of Electronic Search Strategies (PRESS) for systematic reviews (SRs), health technology assessments, and other evidence syntheses.
              Article 0 comments Cited 1076 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Transplant Rev (Orlando)
                Journal ID (iso-abbrev): Transplant Rev (Orlando)
                Title: Transplantation Reviews (Orlando, Fla.)
                Publisher: Published by Elsevier Inc.
                ISSN (Print): 0955-470X
                ISSN (Electronic): 1557-9816
                Publication date PMC-release: 14 November 2020
                Publication date (Electronic): 14 November 2020
                Electronic Location Identifier: 100588
                Affiliations
                [a ]Department of Medicine, Division of Infectious Disease, University of Miami Miller School of Medicine Miami, FL, USA
                [b ]Department of Medicine, Division of Internal Medicine, University of Miami Miller School of Medicine Miami, FL, USA
                [c ]Miami Transplant Institute, Jackson Health System, Miami, FL, USA
                [d ]Department of Health Informatics, Calder Memorial Library, University of Miami Miller School of Medicine Miami, FL, USA
                [e ]Department of Medicine, Division of Nephrology, University of Miami Miller School of Medicine Miami, FL, USA
                Author notes
                [* ]Corresponding author at: Division of Infectious Diseases, Miami Transplant Institute and University of Miami Miller School of Medicine. 1801 N.W. 9 th Ave., Suite 733, Miami, FL 33136.
                [1]

                co-first author.

                Article
                Publisher Item ID: S0955-470X(20)30061-6 Publisher ID: 100588
                DOI: 10.1016/j.trre.2020.100588
                PMC ID: 7666542
                PubMed ID: 33246166
                SO-VID: 38bf6299-9248-456d-a889-55a161d9ef56
                Copyright © © 2020 Published by Elsevier Inc.
                License:

                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.

                History
                Categories
                Subject: Review Article

                Keywords: solid organ transplant,covid-19,sars-cov-2,immunosuppression,systematic review,meta-analysis,aki, acute kidney injury,ci, confidence interval,cni, calcineurin inhibitor,covid-19, coronavirus disease 2019,crp, c-reactive protein,fem, fixed effect model,hsct, hematopoietic stem cell transplant,icu, intensive care unit,il-6, interleukin six,mers, middle east respiratory syndrome,np, nasopharyngeal,press, peer review for electronic search strategies,prisma, preferred reporting items for systematic reviews and meta-analyses,rem, random effect model,rt-pcr, reverse transcriptase-polymerase chain reaction,sars, severe acute respiratory syndrome coronavirus 1,sars- cov-2, severe acute respiratory syndrome coronavirus 2,sot, solid organ transplant
                Data availability:
                Keywords: solid organ transplant, covid-19, sars-cov-2, immunosuppression, systematic review, meta-analysis, aki, acute kidney injury, ci, confidence interval, cni, calcineurin inhibitor, covid-19, coronavirus disease 2019, crp, c-reactive protein, fem, fixed effect model, hsct, hematopoietic stem cell transplant, icu, intensive care unit, il-6, interleukin six, mers, middle east respiratory syndrome, np, nasopharyngeal, press, peer review for electronic search strategies, prisma, preferred reporting items for systematic reviews and meta-analyses, rem, random effect model, rt-pcr, reverse transcriptase-polymerase chain reaction, sars, severe acute respiratory syndrome coronavirus 1, sars- cov-2, severe acute respiratory syndrome coronavirus 2, sot, solid organ transplant

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