Long COVID related inflammatory processes. What is its impact on bone, joints and musculoskeletal microvascular haemodynamics?

Abstract

Background: Long COVID (LC) refers to persistent symptoms following acute COVID-19 recovery, including fatigue, musculoskeletal (MSK) pain, and reduced quality of life. It has been hypothesised that chronic low-grade inflammation in LC could affect bone metabolism, joint health, and skeletal muscle microcirculation, but there is no or limited evidence relating to this. Aim: This study aims to determine the influence of LC on MSK function, encompassing bone health, body composition, joint integrity, and microvascular haemodynamics. Additionally, it aims to examine the role of inflammatory markers as potential etiological factors, assess health-related quality of life, and consider the contribution of inflammatory mechanisms to physiological changes. Methods: This study combined a systematic literature review with a longitudinal observational cohort study. In the cohort study, 45 adults with LC and 40 well- recovered (WR) post-COVID-19 controls were followed over 12 months. Baseline and follow-up assessments included evaluations of Health-Related Quality of Life (HRQoL) and pain rating questionnaires; blood analysis of inflammatory and bone turnover markers; dual-energy X-ray absorptiometry (DXA) for measuring bone mineral density (BMD) and body composition; ultrasound imaging of hand and knee joints; and near-infrared spectroscopy (NIRS) to evaluate microvascular haemodynamics of the lateral thigh and proximal tibial bone. Results: LC participants reported significantly lower HRQoL (p=0.001) compared to the WR group, with no change detected over 12 months at baseline. Additionally, LC showed higher Vitamin D levels at baseline compared to the WR group (p=0.0021). After 12 months, both groups experienced significant increases in Vitamin D levels (WR: p=0.0001; LC: p=0.0023). The LC group had more fat in the gynoid, android, and legs at each assessment point compared to WR controls. LC was also associated with more hand joint pain at baseline (p=0.003) than at follow-up, relative to the control group. This was confirmed by a borderline improvement in hand synovial hypertrophy observed via MSK ultrasound over time. No notable differences were found between groups regarding BMD, circulating bone turnover markers (BTM) ratio, microvascular haemodynamics, or systemic inflammatory cytokines in the LC group compared to controls, nor over time. Conclusion: Existing evidence suggests COVID-19 negatively affects bone health, shown by increased bone markers and decreased BMD, with no studies linking LC to bone and joint health. This cohort study on LC adults and controls found no clear signs of rapid bone loss or microvascular issues, but changes in HRQoL, adiposity, and joint symptoms indicated the need for ongoing monitoring. This research paves the way for future studies on MSK markers, muscle function, and advanced imaging to understand LC's long-term effects, along with research to improve musculoskeletal health and well-being.