Musculoskeletal Consequences of COVID-19

Abstract

Coronavirus disease 2019 (COVID-19) is an emerging pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the majority of patients who become infected with SARS-CoV-2 are asymptomatic or have mild symptoms, some patients develop severe symptoms that can permanently detract from their quality of life. SARS-CoV-2 is closely related to SARS-CoV-1, which causes severe acute respiratory syndrome (SARS). Both viruses infect the respiratory system, and there are direct and indirect effects of this infection on multiple organ systems, including the musculoskeletal system. Epidemiological data from the SARS pandemic of 2002 to 2004 identified myalgias, muscle dysfunction, osteoporosis, and osteonecrosis as common sequelae in patients with moderate and severe forms of this disease. Early studies have indicated that there is also considerable musculoskeletal dysfunction in some patients with COVID-19, although long-term follow-up studies have not yet been conducted. The purpose of this article was to summarize the known musculoskeletal pathologies in patients with SARS or COVID-19 and to combine this with computational modeling and biochemical signaling studies to predict musculoskeletal cellular targets and long-term consequences of the SARS-CoV-2 infection.

Figures

Fig. 1

Figs. 1-A and 1-B Gene expression of ACE2 and TMPRSS2 in single-cell RNA sequencing data sets (Fig. 1-A) and bulk RNA sequencing data sets (Fig. 1-B). Fig. 1-A The percentage of cells expressing ACE2 and TMPRSS2 and the normalized mean gene expression per cell type in the human airway, skeletal muscle, cartilage, meniscus, and synovial tissue. The percentage of expressed cells can indicate the relative presence of ACE2 and TMPRSS2-expressing cells across various tissues, although it might not capture the exact proportion of positive cells because of biases introduced by sample preparation protocols and scRNAseq technology. NK = natural killer cells. Fig. 1-B Gene expression of ACE2 and TMPRSS2 normalized as transcripts per kilobase million (TPM) reads from raw counts of composite cortical and trabecular bone, and osteoblast-enriched tissue fractions. Each point on the violin plot represents gene expression from a single sample, and the contour of the plot indicates the probability density of the data at different values.

Fig. 2

Overview of indirect and potential direct effects of SARS-CoV-2 infection on musculoskeletal tissues. The primary SARS-CoV-2 respiratory infection induces systemic inflammation that can impact the musculoskeletal system. Several types of musculoskeletal cells express the ACE2 and TMPRSS2 genes, which allow for direct viral infection. However, it is unknown whether the virus can directly infect musculoskeletal tissues.