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.