The Musculoskeletal Involvement After Mild to Moderate COVID-19 Infection

Abstract

COVID-19, a disease caused by the novel coronavirus SARS-CoV-2, has been drastically affecting the daily lives of millions of people. COVID-19 is described as a multiorgan disease that affects not only the respiratory tract of infected individuals, but it has considerable effects on the musculoskeletal system, causing excessive fatigue, myalgia, arthralgia, muscle weakness and skeletal muscle damage. These symptoms can persist for months, decreasing the quality of life of numerous individuals. Curiously, most studies in the scientific literature focus on patients who were hospitalized due to SARS-CoV-2 infection and little is known about the mechanism of action of COVID-19 on skeletal muscles, especially of individuals who had the mild to moderate forms of the disease (non-hospitalized patients). In this review, we focus on the current knowledge about the musculoskeletal system in COVID-19, highlighting the lack of researches investigating the mild to moderate cases of infection and pointing out why it is essential to care for these patients. Also, we will comment about the need of more experimental data to assess the musculoskeletal manifestations on COVID-19-positive individuals.

Keywords: COVID-19; SARS-CoV-2; long COVID; mild to moderate COVID-19; muscle symptoms; musculoskeletal system; non-hospitalized individuals.

FIGURE 1

Structure of SARS-CoV-2. Schematic representation of SARS-CoV-2 virus structure highlighting its four major structural proteins: the spike glycoprotein (S), the envelope protein (E), the nucleocapsid protein (N) and the membrane glycoprotein (M). The RNA viral is also showed.

FIGURE 2

Mechanisms of action of SARS-CoV-2 on the skeletal muscle tissue. (A) Direct mechanism via SARS-CoV-2 binding to receptors on the skeletal muscle cell surface and entry of the virus into the cell. Several types of musculoskeletal cells express ACE2 and/or TMPRSS2, which allows this type of direct mechanism of action of the virus. (B) Indirect mechanism considering the adverse effects of the elevated inflammatory process (“cytokine storm”) caused by SARS-CoV-2 infection on the musculoskeletal tissue. The deregulated release of cytokines and chemokines (IL-6, IL-1β, IL-8, IFN-γ, IP-10, TNF-α) by the immune system results in exacerbated inflammation that can lead to multi-organ injuries. Both mechanisms (A,B) can affect the musculoskeletal system, causing manifestations such as fatigue and myalgia in symptomatic COVID-19 individuals. ACE2: angiotensin-converting enzyme 2; IFN-γ: interferon-gamma; IL-1β: interleukin-1β; IL-6: interleukin-6; IL-8: interleukin-8; IP-10: interferon-gamma inducible protein 10; TMPRSS2: transmembrane protease serine 2; TNF-α: tumor necrosis factor alpha.

FIGURE 3

Common muscle symptoms of COVID-19. Fatigue, arthralgia (joint pain), myalgia (muscle pain) and muscle weakness have been reported as initial and common symptoms by SARS-CoV-2-positive individuals. These extenuating symptoms can affect the daily lives of numerous individuals, reducing their quality of life.

FIGURE 4

The four main types of studies comprising COVID-19 and the skeletal muscle. (i) case reports and original articles of hospitalized individuals (severe COVID-19; functional and morphologic techniques); (ii) Review and observational articles citing only the musculoskeletal symptoms (mild and severe COVID-19; no experimental data); (iii) Follow-up studies of patients with persistent muscle symptoms (mild and severe COVID-19; no experimental data); and (iv) Neurological studies that includes musculoskeletal symptoms (mild to moderate and severe COVID-19; functional assays). ICU = intensive care unit. Figure produced using Servier Medical Art (smart.servier.com).