1 Introduction
Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spread rapidly and became a severe global public problem[1]. Currently, the pandemic of COVID-19 is relatively under control but still caused high morbidity and mortality to the whole society. As of May 3, 2023, COVID-19 had been reported 765, 222, 932 cases globally and had accounted for 6921614 deaths[2]. The clinical manifestations of COVID-19 patients are various, ranging from mild and asymptomatic cases to severe cases, including cough, fever, myalgias and headache[3]. Moreover, various comorbidities, which included interstitial pneumonia, cytopenia, myocarditis, arthralgia, and sarcopenia, frequently occur in COVID-19 patients[4-11]. While, sarcopenia, the manifestation of skeletal muscles caused by COVID-19, is attracting extensive attention.
Sarcopenia is a generalized and progressive skeletal muscle disease with loss of muscle mass acceleratively, which causes a series of other negative consequences, such as frailty, diminished quality of life and mortality[12-14]. Sarcopenia is largely attributable to aging, which typically occurs in older-aged people[15]. The European Working Group on Sarcopenia in Older People 2 (EWGSOP 2) showed that the prevalence of sarcopenia in men is 1.3% and in women is 0.4%[16]. Furthermore, it has been discovered that the systemic disease that may invoke inflammatory processes can lead to sarcopenia, such as organ failure, malignancy or COVID-19[17].
Recently, the relationship between sarcopenia and COVID-19 has generated an abundance of discussions. Sarcopenia was reported to be in connection with the increasing severity and morality of COVID-19[18]. A few studies suggested that patients infected with COVID-19 had a higher incidence of sarcopenia, which varies among patients infected with different types of COVID-19[19, 20]. Patients in ICU who had COVID-19 were inclined to be diagnosed with sarcopenia, compared to other patients hospitalized for COVID-19[20, 21]. Moreover, the risk of sarcopenia was higher among the patients after severe or moderate COVID-19 infection with prolonged length of hospital stay and invasive mechanical ventilation[22]. However, some studies indicated that sarcopenia was unrelated to mortality of COVID-19[23, 24]. The conclusion about the relationship between sarcopenia and COVID-19 is inconsistent and the causal effect of sarcopenia on COVID-19 remains ambiguous.
Moreover, the majority of the above conclusions between sarcopenia and COVID-19 were from observational studies. Owing to the inherent defects of traditional designs, these observational studies cannot completely exclude the possibility of confounding factors, which may lead to biased associations and conclusions[25]. In addition, the randomized controlled trial (RCT) is immoral and impractical to perform due to the severe negative consequences of COVID-19 and the requirement of abundant human resources and time-consuming follow-up[26]. Estimating whether there is a link of cause and effect between sarcopenia and COVID-19 is urgently necessary. If the link of causation between sarcopenia and COVID-19 can be clarified, maybe more novel measures can be conducted to prevent the development of sarcopenia in COVID-19 patients; meanwhile, the patients with sarcopenia infected with COVID-19 can also get more beneficial care and treatment.
Under this circumstance, Mendelian randomization (MR) is an advanced study to assess the causal connection between sarcopenia and COVID-19. MR analysis uses genetic variants as instrumental variables (IVs) of exposures to evaluate the causality of exposure factors and outcomes[27]. Compared to observational studies, MR analysis can efficiently eliminate confounding factors and identify influencing factors of a certain outcome[28]; for the reason that genetic variations are assigned at random at conception, the confounding factors may not affect the connection between genetic variants and outcomes [27]. Furthermore, compared to RCT, the majority of the open-access data utilized in MR analysis comes from extensive genome-wide association studies (GWAS)[28], which avoids medical ethical issues and has no use for extensive human resources but expands its scope and power in statistics.
In the current study, we utilized a bidirectional two-sample MR study to evaluate the causal relationships of sarcopenia and COVID-19, which may benefit the formulation of strategies to promote the care and treatment of patients with sarcopenia during the COVID-19 pandemic.