4 Discussion
In this study, we conducted a bidirectional two-sample MR study to
explore the causal association between sarcopenia (ASM, LH, RH, WP) and
COVID-19. After Bonferroni correction, except for WP, there were no
significant associations observed between ASM, LH or RH and COVID-19.
Nevertheless, the causal effect of WP on COVID-19 disappeared after
adjusting for BMI.
According to the IVW results, slow WP was significantly associated with
an increased risk of COVID-19 infection. Consistent with our study, a
prospective study indicated that the illness of patients with COVID-19
infection tended to get aggravated more frequently among patients with
fatigue and slow WP[37]. The role of WP in the
development of COVID-19 may attribute to the decline in immune function
caused by low physical activity and longtime of bed rest during the
COVID-19 pandemic[38]. Research indicated that
SARS-CoV-2 can survive in host cells by evading the host immune
mechanism to cause COVID-19 infection[39]. If the
immune function of patients with sarcopenia was declined, not only the
symptoms of patients may be aggravated, but also the risk of COVID-19
infection may get increased. Studies found that WP can be influenced by
age and BMI[40, 41]. Considering that
the GWAS data stratified by age were
not available, and BMI can reflect physical conditions including age
directly or indirectly, we re-analyzed the causal effect of WP on COVID
after adjusting for BMI.
As the results showed, after adjusting by BMI, there was no significant
relationship between WP and COVID-19, suggesting that BMI is involved in
the effect of WP on COVID-19. As we all know, WP and COVID-19 were both
associated with BMI [42, 43], and the causal
association between them may be due to the mediating role of BMI. An MR
study pointed out that genetically predicted higher BMI is significantly
linked with an elevated probability of COVID-19 infection and
hospitalization[44]. Another prospective
community-based cohort study found a linear increase in the risk of
hospitalization and death caused by severe COVID-19 at a BMI above 23
kg/m2[45]. Furthermore, some studies found that
patients with BMI outside the normal range are more susceptible to
COVID-19[46, 47]. Moreover, it was also revealed
that too high or low BMI usually led to slow WP in patients with
COVID-19[42]. It may attribute to the association
of adipose tissue with complement system hyperactivation, chronic
inflammation and the presence of other
complications[48], which damage skeletal muscle.
Therefore, we speculate that the effect of WP on COVID-19 may be caused
by the role of BMI.
In this study, we failed to figure out the causal effect of ASM, LH or
RH on COVID-19. However, a previous observational study indicated that
increased hand grip strength was related to shorter severe COVID-19
inpatient stays[49]. In another retrospective
observational study, higher hand grip strength was associated with lower
COVID-19 severity, which acted as the protective factor for severe
COVID-19[50]. Additionally, due to the reduction
of muscle mass of the patients with low ASM, the adipose tissue
gradually replaced the muscle fibers[13]. The
replacement consumes the adipose tissue, which was suggested to be a
probable risk factor for COVID-19 infection[43],
and it may be helpful to decrease the prevalence of COVID-19. Due to the
studies above almost observational studies, the conclusions cannot
completely exclude the possibility of confounding factors, which led to
the inconsistency.
Furthermore, the reverse MR study showed that there was no connection
between COVID-19 and sarcopenia, which differs from the results of
others. In a cross-sectional study, it has been proposed that patients
with COVID-19 had lower mean hand
grip strength values[51]. It may attribute to the
strong injurious stimulation of acute severe inflammation caused by
COVID-19 infection[38]. Among the various harmful
effects of inflammation, the increased concentration of c-reactive
protein (CRP), TNF-alpha and IL-6 have been the strongest connection
with the reduction of skeletal muscle fibers[52];
and the high level of inflammatory factors may impact the acute changes
of the amount, structure and function of skeletal
muscles[53], which causes sarcopenia. The results
in this study differed from previous studies possibly because these
studies were cross-sectional studies, which only found the short-term,
reversible and non-pathogenic effects resulting from fatigue caused by
COVID-19, rather than the direct causal relationship.