Systematic Reviews
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Orthop. Nov 18, 2022; 13(11): 1015-1028
Published online Nov 18, 2022. doi: 10.5312/wjo.v13.i11.1015
Viral infections in orthopedics: A systematic review and classification proposal
Konstantinos Sidiropoulos, Savvas Ilias Christofilos, Konstantinos Tsikopoulos, Dimitrios Kitridis, Lorenzo Drago, Gabriele Meroni, Carlo Luca Romanò, Venu Kavarthapu
Konstantinos Sidiropoulos, General Hospital of Serres, Serres 62100, Greece
Savvas Ilias Christofilos, Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, United Kingdom
Konstantinos Tsikopoulos, Department of Orthopaedics, 404 Army General Hospital, Larissa 41222, Greece
Dimitrios Kitridis, the First Department of Orthopaedics, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
Lorenzo Drago, Department of Biomedical Sciences for Health and Microbiome, University of Milan, Milan 20133, Italy
Gabriele Meroni, Department of Biomedical, Surgical, and Dental Sciences, One Health Unit, University of Milan, Milan 20133, Italy
Carlo Luca Romanò, Gruppo di Studio SIOT Infezioni-Clinica San Gaudenzio-Novara-Gruppo Policlinico di Monza, University of Milan, Milan 20100, Italy
Venu Kavarthapu, Trauma, and Orthopaedics, Kings College Hospital London, Denmark Hill, London SE59RS, United Kingdom
Author contributions: Drago L and Kavarthapu V were involved in the study's conceptualization; Tsikopoulos K and Sidiropoulos K conducted the literature research and extracted relevant information; Tsikopoulos K and Kitridis D assessed the quality of the included studies; Christofilos SI and Meroni G were involved in the generation of tables and writing the paper; Drago L, Kavarthapu V, and Romanò CL supervised the paper and revised the paper accordingly.
Conflict-of-interest statement: All authors report no relevant conflict of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Savvas Ilias Christofilos, MD, Doctor, Department of Genetics, Evolution, and Environment, University College London, London WC1E 6BT, United Kingdom. savvaschristofilos@gmail.com
Received: August 23, 2021
Peer-review started: August 26, 2021
First decision: November 17, 2021
Revised: December 1, 2021
Accepted: October 27, 2022
Article in press: October 27, 2022
Published online: November 18, 2022
Abstract
BACKGROUND

Although the impact of microbial infections on orthopedic clinical outcomes is well recognized, the influence of viral infections on the musculoskeletal system might have been underestimated.

AIM

To systematically review the available evidence on risk factors and musculoskeletal manifestations following viral infections and to propose a pertinent classification scheme.

METHODS

We searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), the Reference Citation Analysis (RCA), and Scopus for completed studies published before January 30, 2021, to evaluate risk factors and bone and joint manifestations of viral infection in animal models and patient registries. Quality assessment was performed using SYRCLE's risk of bias tool for animal studies, Moga score for case series, Wylde score for registry studies, and Newcastle-Ottawa Scale for case-control studies.

RESULTS

Six human and four animal studies were eligible for inclusion in the qualitative synthesis. Hepatitis C virus was implicated in several peri- and post-operative complications in patients without cirrhosis after major orthopedic surgery. Herpes virus may affect the integrity of lumbar discs, whereas Ross River and Chikungunya viruses provoke viral arthritis and bone loss.

CONCLUSION

Evidence of moderate strength suggested that viruses can cause moderate to severe arthritis and osteitis. Risk factors such as pre-existing rheumatologic disease contributed to higher disease severity and duration of symptoms. Therefore, based on our literature search, the proposed clinical and pathogenetic classification scheme is as follows: (1) Viral infections of bone or joint; (2) Active bone and joint inflammatory diseases secondary to viral infections in other organs or tissues; and (3) Viral infection as a risk factor for post-surgical bacterial infection.

Keywords: Viral infection, Musculoskeletal system, Bone and joint manifestations, Chikungunya, Zika, Hepatitis C virus, Herpesviridae, Ross River virus, Cross-reactivity, Classification

Core Tip: Viral infections can include multiple orthopedic manifestations, thus resulting in significant distress. In addition, the outcome of orthopedic surgeries may be influenced by certain chronic viral infections such as hepatitis C virus. There is evidence of autoimmune-mediated mechanisms, immunosuppression, and perhaps direct viral infection provoking this, although the precise mechanisms have yet to be fully understood. In this review, a classification scheme was proposed. However, further research is needed to unveil the relative contributions of the identified mechanisms and develop novel preventative and treatment strategies.