Different reversibility of skeletal muscle mass and strength in elderly Japanese women after the first wave of COVID‐19

Restrictions on outdoor movements due to the coronavirus disease (COVID‐19) pandemic have led to a decreased physical activity; this can lead to sarcopenia and frailty in older adults. Our recent study has demonstrated a significant decrease in the trunk muscle mass immediately after the pandemic's first wave (April–May 2020) among Japanese community‐dwelling older women. In the present study, we further examined whether muscle mass recovery or deterioration occurs after 1 year of the pandemic's first wave by comparing physical measurements among the following assessment periods: before the first wave, immediately after the first wave, and at 1‐year follow‐up thereafter.


Introduction
The coronavirus disease  pandemic, caused by severe acute respiratory syndrome coronavirus 2, has resulted in restrictions on outdoor movements and a decrease in physical activities; these can lead to sarcopenia and frailty in older adults. [1][2][3][4] Our recent study has demonstrated a significant decrease in the trunk muscle mass, one of the risk factors for postural instability and falls, immediately after the pandemic's first wave (April-May 2020) among Japanese community-dwelling older women. 5 The area and density of the trunk muscle on computed tomography (CT) may be useful indicators of physical activity and are further correlated with the maximal inspiratory and expiratory pressures in patients with or at a risk of chronic obstructive pulmonary disease (COPD). 6 Moreover, in patients with COVID-19, a low density of the paraspinal muscle (one of the trunk muscles measured by CT) is reportedly associated with the occurrence of respiratory failure. 7 In the present study, we conducted a 1-year follow-up physical measurement and sociality assessment between January and March 2021. We aimed to compare the muscle mass, strength, and sociality between the pandemic's first wave and 1 year later and examine whether they recovered or deteriorated in community-dwelling older adults. Our findings may help in the understanding of the mechanisms of COVID-19-related sarcopenia among community-dwelling older adults and in the development of short-term or long-term prevention strategies for the same.

Participants
We included 77 community-dwelling older women aged ≥65 years who participated in a frailty checkup programme every 6 months. Five community-dwelling older men participated in the present study and their results were examined separately. These participants underwent physical measurements and completed surveys between July 2019 and February 2020 (before the first wave), July 2020 and September 2020 (after the first wave), and January 2021 and March 2021 (after a 1-year follow-up) in Iitsuka City, Fukuoka, Japan. We excluded participants with missing physical measurement and survey data for any of these three assessment periods. We also confirmed that none of the participants were diagnosed with COVID-19 throughout the study period. This study protocol was reviewed and approved by The University of Tokyo Institutional Review Committee (#19-320) and was conducted in accordance with the Declaration of Helsinki guidelines. All participants provided written informed consent.

Physical measurement
The total, trunk, and appendicular muscle masses were measured by bioelectrical impedance using a body composition analyser (Inner Scan Dual RD-800, TANITA, Tokyo, Japan). The handgrip strength was measured using a digital grip strength dynamometer (Takei Scientific Instruments Co., Ltd., Niigata, Japan). Physical function was measured with a one-leg stand-up from chair for 3 s. Furthermore, a decline of oral diadochokinesis is a feature of deterioration of oral motor skills, which leads to dietary deficiencies, malnutrition, and subsequent sarcopenia. 8 The ability to repeat the monosyllables /Ta/ and /Ka/ as quickly as possible for 5 s was measured with an appropriate device (Kenkou-Kun Handy, Takei Scientific Instruments Co., Ltd.). 9 The participants were diagnosed with sarcopenia or pre-sarcopenia on the basis of the Asian Working Group for Sarcopenia (AWGS2019) criteria. 10 The criterion for pre-sarcopenia diagnosis was a low appendicular skeletal muscle mass index (ASMI; men: <7.0 kg/m 2 , women: <5.7 kg/m 2 ) or a low grip strength (men: <28 kg, women: <18 kg). The criteria for sarcopenia diagnosis included a low ASMI and a low grip strength.

Medical history
Medical histories of hypertension, diabetes, stroke, hyperlipidaemia, osteoporosis, fall/fracture, heart failure, and respiratory disease were obtained through interview by investigators with medical knowledge during the three assessment periods (before and after the first wave and after a 1-year follow-up). Due to COVID-19 pandemic, the collection of information and data about respiratory diseases and related symptoms such as pneumonia, COPD, chronic bronchitis, and sleep apnoea syndrome was focused.
Before the first wave of COVID-19, prevalence of major chronic diseases including hypertension, hyperlipidaemia, and osteoporosis was 40.3%, 15.6%, and 15.6%, respectively. Among pulmonary diseases, such as pneumonia, COPD, chronic bronchitis, and sleep apnoea syndrome, we found only two participants with chronic bronchitis before the first wave; however, their symptoms improved or did not change throughout the study period.

Questionnaires
The frequency of 'going out', self-reported vitality, physical behaviours, and nutritional practices were assessed through questionnaires comprising 'yes/no' questions at three assessment periods: before the first wave of the pandemic, after the first wave of the pandemic, and at the 1-year follow-up. Physical behaviours were assessed by three self-reported questionnaires, one each for assessing the exercise habits (once a day for >30 min, more than twice per week for more than a year), walking/activities of daily living (>1 h/day), and gait speeds faster than normal for individuals of the same age and sex. These three questionnaires were adopted from 'Standard Health Checkup and Counseling Guidance Program' developed by the Japanese Health Bureau, Ministry of Health, Labor and Welfare (Japanese, 2018). Furthermore, in our recent reports, we confirmed physical factors assessed by these questionnaires significantly associated with sarcopenia 11 and frailty. 12 Nutritional practices were assessed by two self-reported questionnaires, which assessed the participants' awareness of a healthy diet and intake of balanced foods (more than twice vegetables and meat/fish dishes daily).
We assessed sociality based on the participants' social network, social participation, and social support. Social network was assessed using the Lubben Social Network Scale [short version; total score: 30 points (0-5 points for each item)]. 13 Social participation was surveyed by analysing the participation in seven groups (senior, health/sport, learning, hobbies, community activities, volunteer groups, and working groups with income). Social support was assessed by four questionnaires: (1) two questionnaires assessed whether the participants provided counselling support or help with housework/shopping and (2) two other questionnaires assessed whether the participants themselves received counselling to perform housework/shopping.

Statistical analysis
The data were confirmed to be normally distributed by the Shapiro-Wilk test. Statistically, we examined the impact of the COVID-19 pandemic by assessing the muscular measurements before the first wave of the pandemic, after the first wave of the pandemic, and at the 1-year follow-up using analysis of variance (ANOVA) with Bonferroni's post hoc and Friedman's tests. Changes in the individual physical parameters were assessed using the χ 2 test for categorical variables and ANOVA with the Bonferroni test and the Kruskal-Wallis test for continuous variables. Data were analysed using IBM SPSS Statistics Version 26 (IBM Japan, Tokyo, Japan) software. Statistical significance was set at P < 0.05.

Participants
We included 77 older women who underwent complete physical measurements and answered questionnaires before, after, and at the 1-year follow-up after the first wave of COVID-19. The average age was 78.0 ± 5.7 years before the first wave. Regarding the frequency of going out, participants who answered that they had the same or a higher frequency of going out as compared with the previous year dramatically decreased immediately after the first wave; however, significant recovery was seen at the 1-year follow-up (before the first wave: 85.7%, after the first wave: 36.4%, and at the 1year follow-up: 44.2%; P < 0.001; Data S1). Similarly, the self-reported vitality also decreased after the first wave and subsequently recovered at the 1-year follow-up (before the first wave: 89.6%, after the first wave: 71.4%, and at the 1year follow-up: 84.4%; P < 0.001; Data S1). These data suggest the effects of the first wave of COVID-19 on the physical and mental well-being of the participants.
The prevalence of active physical behaviours decreased significantly across the assessment periods (before the first wave: 58.4%, immediately after the first wave: 45.5%, and at the 1-year follow-up: 44.2%; P = 0.016; Data S1). Conversely, the number of participants who engaged in good nutritional practices did not differ significantly among the three assessment periods (before the first wave: 84.4%, immediately after the first wave: 80.5%, and at the 1-year follow-up: 79.2%; P = 0.420; Data S1).

Reversibility of muscular measures and sociality after the first wave of COVID-19
The total muscle mass decreased significantly immediately after the first wave and recovered at the 1-year follow-up ( Table 1). The trunk muscle mass index decreased dramatically immediately after the first wave. However, any clinical outcomes including COVID-19-related symptoms such as pneumonia were not due to the loss of trunk muscle (Data S2). At the 1-year follow-up, significant recovery of trunk muscle was observed. Conversely, the ASMI and grip strength continued to decrease for 1 year after the first wave. Regarding physical functions, we assessed the ability of the participants to perform a one-leg stand-up from chair for 3 s; however, no changes were observed among the three assessment periods ( Table 1).
We also examined the changes in the prevalence of pre-sarcopenia and sarcopenia in the three assessment periods; the prevalence of both conditions tended to increase by the 1-year follow-up. A significant recovery in the trunk muscle was also observed in men 1 year after the first wave (Data S3).
Regarding the oral function, no changes in the oral motor skills (i.e., the ability to pronounce /Ta/ and /Ka/ repeatedly for 5 s) were noted across the three assessment periods.
When sociality was compared before, immediately after, and at 1 year after the first wave, social network and social support had recovered significantly by the 1-year follow-up; however, social participation had further decreased by this time point. Table 2, 68.8% of the participants had recovered their trunk muscle mass; however, 54.5% of these had a reduced ASMI at the 1-year follow-up. Changes in each muscle parameter and sociality were further compared among the participants by dividing them into the enhanced/maintained, reduced, and recovered groups. In particular, changes in the trunk muscle index in the recovery group were significantly different from those in the reduced group, suggesting that their recoveries at 1 year after the first wave almost reached the pre-pandemic levels ( Table 2).

As shown in
Intriguingly, women who had recovered social participation showed a positive change in the calf circumference at 1 year after the first wave; however, women who had reduced social participation showed a negative change in the calf circumference at this time point (Data S4). These results imply that social participation might be beneficial to the recovery of the appendicular muscle mass and, thus, might be one of the strategies for the long-term management of COVID-19-related sarcopenia among community-dwelling older adults.

Discussion
In the present study, we found differences in the reversibility of skeletal muscle mass and strength in elderly Japanese women at 1 year after the first wave of COVID-19. An acute decline and rapid recovery in the trunk muscle mass and a continuous decline in the ASMI and grip strength were observed across the three assessment periods.
The differences in the reversibility among the trunk and appendicular muscles may be attributed to the differences in their susceptibilities to muscle loss and reversibility. The existence of multiplicity (local and systemic changes, fibre-type diversity and shift, and satellite cell diversity) may be responsible for these differences in the susceptibilities. 14-16 Muscle atrophy was suggested to occur preferentially in certain fibre types, according to the muscle type. 17 For instance, in rat, soleus muscle type-1 fibres undergo marked atrophy after denervation, whereas type-1 fibres in the fast extensor digitorum longus (EDL) muscle are maintained during the first 2 weeks after denervation. A similar difference is observed in type-2A fibres, which undergo dramatic atrophy in the soleus muscle, but only slight atrophy in the EDL muscle. Additionally, muscle atrophy is also accompanied by shifts in the fibre type. For example, muscle disuse involving denervation or limb immobilization causes a slow-to-fast shift in the fibre type and the MyHC isoform profile. 18,19 A similar slow-to-fast shift is also observed after hindlimb suspension in rats. 20 In humans, it was demonstrated that spinal cord injury leads to type-1 fibre disappearance. 21 Further studies are needed to identify the Note: Values are presented as mean ± standard deviation. Significant difference (P < 0.05). Total muscle mass: a, P = 0.004. Trunk muscle mass index: a, P < 0.001; b, P = 0002. Appendicular skeletal muscle mass index: a, P < 0.001; b, P < 0001. Grip strength: c, P = 0.003. Comparison of the following parametric continuous values among the three assessment periods using one-way analysis of variance with Bonferroni's post hoc test: total muscle mass, trunk muscle mass index, grip strength, and social network. Comparison of the following non-parametric values among the three assessment periods using Friedman's test: appendicular skeletal muscle mass index, calf circumference, pre-sarcopenia and sarcopenia prevalence, oral motor skills for 'Ta' and 'Ka', social support, and social participation. Long-term deterioration of muscle mass and strength by COVID-19 potential targets responsible for the differential responses of different muscle types to the COVID-19 pandemic-associated restrictions on physical activities. Due to such restrictions, the exposure of individuals to sunlight has also decreased dramatically. In older adults, it has been suggested that reduced outdoor activity has resulted in a decline in the skin's ability to synthesize vitamin D. 22 Thus, adverse impacts of vitamin D deficiency may plausibly explain the loss of muscle mass observed in this study after the first wave. In support of our notion, Yang et al. recently reported that physical inactivity and low serum vitamin D levels can synergistically promote sarcopenia in the elderly. 23 Under inactive conditions, vitamin D deficiency accelerates losses in the muscle mass, muscle cross-sectional area, and grip strength and conversely increases the expression of FOXO3a and its target genes (Atrogin-1 and MuRF1). In one study, the serum 25-hydroxyvitamin D3 levels and physical activity showed interactive effects on the physical performance (timed up-and-go test) and muscle strength (grip strength) in older adults. 23 In the present study, we examined changes in the physical and social parameters in men as well; however, the sample size was small (Data S2). The average age of men was 75.8 ± 3.4 years before the first wave. The trunk muscle mass index recovered significantly (P = 0.022); these observations were similar to those in women. However, unlike in women, the self-reported vitality and physical activities in men did not change during the assessment periods (P = 0.368 and P = 0.386, respectively).
Regarding sex difference in this investigation, on examination of the prevalence of frailty checkup programme based on sex before COVID-19 in the same area between October 2018 and March 2019, among 172 participants, 93.6% was women, which is the same as that in our assessment period. Thus, difference based on sex in the present study might be caused by regional characteristics, not by COVID-19. Similarly, a high number of women participants in this frailty checkup programme were seen in other regions (76.3% of participants were women in 47 local governments, n = 8369). Impacts of differences based on sex in the reversibility of skeletal muscle mass and strength, should be further investigated with sufficient sample sizes in both men and women by multiregional trial.
A strength of the present study was that the physical parameters were measured before the pandemic's first wave, after the pandemic's first wave, and at the 1-year follow-up thereafter in Japan. Conversely, the study's limitations included its small sample size and that the number of medications and over-the-counter drug prescriptions was not recorded.
Collectively, the main finding of our study was the difference in the reversibility between the skeletal muscle mass and strength at 1 year after the first wave of the COVID-19 pandemic. The total muscle mass and the trunk muscle mass recovered, whereas the ASMI and muscle strength continued to decrease, during the year after the first wave. These differential features of skeletal muscle reversibility might contribute to strategies for sarcopenia prevention after COVID-19.