Viral infections in orthopedics: A systematic review and classification proposal

Table 2 Study characteristics of the included articles dealing with the Ross River Virus

Author (year)	Study design	Inoculated groups and number of subjects	Outcomes	Follow-up
Chen (2014)	In vitro and in vivo animal interventional study	For the in vitro experiment: 21-day-old male and female C57BL/6 WT mice were inoculated in the thorax with 104 PFU of RRV. Those mice received 500 μg of anti-IL-6 antibody injections on days 0 and 2, 4, 6, 8 post-infection. For the in vivo investigation: Serum samples from 14 Ross River virus patients (7M and 7F) were obtained, and serum from 13 healthy individuals (7M). Synovial fluid samples from 12 RRV-induced polyarthritis patients (6M) were retrieved and from 6 healthy individuals (3M).	The animal part of the study investigated whether RRV replicates in the bone (murine model) and viral titers were measured. μCT imaging was used to assess the impact of the infection on bone architecture and loss. The role of IL-6 on bone loss was evaluated. The human part of the study looked at OPG, RANKL, and TRAP5b levels in RRV-positive patients.	Not specified
Soden (2000)	Prospective observational study involving humans	Biopsy tissue from inflamed knees from 12 patients was retrieved.	Histological examination of the synovial membrane. RT-PCRto look for the presence of viral RNA	The follow-up was performed at 3-mo intervals until 6 m following symptom resolution

RANKL: Receptor activator of nuclear factor kappa beta (NF-kB ligand); TRAP5b: Tartrate-resistant acid phosphatase serum band 5 (TRAP5b); WT: Wild type; RT-PCR: Reverse transcription-polymerase chain reaction; μCT: Micro-computed tomography; RRV: Ross River virus; M: Male; F: Female; IL-6: interleukin 6.