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SPECIAL SECTION on COVID-19 and PM&R

Muscle Strength and Physical Performance in Patients Without Previous Disabilities Recovering From COVID-19 Pneumonia

Paneroni, Mara PT, MSc; Simonelli, Carla PT; Saleri, Manuela PT; Bertacchini, Laura PT; Venturelli, Massimo PhD; Troosters, Thierry PhD; Ambrosino, Nicolino MD; Vitacca, Michele MD

Author Information
American Journal of Physical Medicine & Rehabilitation: February 2021 - Volume 100 - Issue 2 - p 105-109
doi: 10.1097/PHM.0000000000001641

Abstract

COVID-19 disease is an infectious condition characterized by rapid human-to-human transmission. Studies describe a wide variety of clinical presentations ranging from absence of symptoms to light flu, pneumonia with acute respiratory failure, and severe acute respiratory distress syndrome requiring admission to the intensive care unit and possible death.1

Muscle soreness, fatigue, and weakness are reported symptoms in COVID-19, regardless of the severity of clinical presentation.2 Limited data are available on the prevalence and severity of de novo COVID-19–related skeletal muscle impairment and disability at hospital discharge. Critical illness myopathy associated with COVID-19 as a spectrum of myophatic changes induced by the virus has been reported in COVID-19 survivors3 as well as in post-mortem examinations, which documented immune-mediated focal myofiber necrosis or atrophy in patients with severe acute respiratory syndrome.4 Moreover, delayed neurologic sequelae such as peripheral neuropathy, Bickerstaff brainstem encephalitis, and Guillain-Barre syndrome have been described after both Middle East respiratory syndrome coronavirus5 and severe acute respiratory syndrome coronavirus 1 infection.6 In addition, in patients requiring an intensive care unit stay, the muscle impairment could be related to systemic inflammation, mechanical ventilation, sedation, and prolonged bed rest.7

The aim of this cross-sectional study was to describe skeletal muscle strength, exercise intolerance, and symptoms in a cohort of the patients recovering from COVID-19 pneumonia without preexisting locomotor disabilities. The secondary aim was to investigate associations between these functional outcome measures.

METHODS

At the Istituti Clinici Scientifici Maugeri IRCCS, Lumezzane, Italy, we conducted a cross-sectional analysis in consecutive patients recovering from COVID-19 pneumonia at the time of discharge from the postacute department. We included patients admitted from April 1 to 30, 2020. Inclusion criteria were as follows: normoxemia (pulse oximetry >94%) at rest, spontaneous breathing, a respiratory rate of less than 22 beats per minute, and absence of fever for at least 3 days. Exclusion criteria were as follows: refusal to participate, the presence of cognitive or locomotor impairment before the infection, and any preexisting condition such as orthopedic or neurological comorbidities limiting the ability to cope with activities of daily life, as defined by a Barthel index8 score equal to 100.

Ethics committee approval was obtained (EC2414, April 23, 2020), and written informed consent was obtained from all patients. This study conforms to all STrengthening the Reporting of OBservational studies in Epidemiology guidelines and reports the required information accordingly (see Supplemental Checklist, Supplemental Digital Content 1, https://links.lww.com/PHM/B167).

During the hospital admission, the patients received best practice respiratory care according to the evolving information and current research.9 One or more of the following drugs were added as specific therapy for COVID-19: cloroquine, antiviral medication, corticosteroids, and anticoagulants, and the patients also received the therapy prescribed for their underlying comorbidities. The patients received 20 mins of daily individual physiotherapy sessions promoting early mobilization, lung expansion, and airways clearance.10

The following measurements were performed at the time of discharge:

  • a) Muscle strength by means of maximal voluntary contraction (isometric contraction) of dominant biceps brachii and quadriceps. Reference values for healthy normal individuals were calculated using the equation of Andrews et al.11 (data from a White population aged 50–79 yrs). The following reference equations were used: for brachial biceps (N): = 229.4 − 84.8 × sex (0 = male, 1 = female) + 0.165 × weight − 1.503 × age; for quadriceps (N): = 358.5 − 87.6 × sex + 0.300 × weight − 3.140 × age. Subjects were labeled with “muscle weakness” for a muscle group if the muscle strength was inferior to 80% of the predicted normal value.
  • b) Exercise tolerance and exercise-induced oxygen desaturation were evaluated with the 1-min sit-to-stand (1-min STS) test12 using the reference values for healthy normals of Strassmann et al.13 The predicted normal values used referred to European, sex-, and age-stratified subjects up to the age of 79 yrs. Desaturation was defined as a reduction in pulse oximetry with more than 4% compared with rest.
  • c) Physical performance was assessed using the short physical performance battery with as the predicted normal values those suggested by Bergland et al.14; these refer to a Norwegian population 40 yrs or older and are stratified for age and sex.
  • d) Exercise-induced muscle contractile fatigue was evaluated as the difference in maximal voluntary contraction of the quadriceps before and after the 1-min STS.15
  • e) Perceived symptoms of dyspnea and fatigue assessed by the modified Borg scale16 were collected at rest and immediately after the 1-min STS as well as during patient’s activities of daily living such as walking in the hospital room and going to the toilet and eating.
  • f) The single-breath counting test17 measures how far an individual can count with a normal speaking voice after a maximal inhalation (from total lung capacity). The counting follows the rhythm to a metronome set at 2 Hz. A correlation with standard pulmonary function measures has been shown in adults.17

Data were analyzed using statistical software (STATA 13.1) and expressed as mean and standard deviation for continuous measures and percentage for categorical or binary data. T test was used to investigate differences between subgroups of patients and to investigate whether values deviated from predicted normal values. A Pearson correlation test was used to detect associations between quadriceps strength, 1-min STS and respiratory muscle performance, and other clinical and functional variables. A P value of less than 0.05 was considered for statistical significance.

RESULTS

Of the 114 patients admitted to the hospital, 41 met the inclusion criteria and were included in the study (Table 1). Seventy-three patients were excluded because of one or more of the following conditions: resting pulse oximetry of less than 94% (n = 35), preexisting neurological (n = 26), orthopedic comorbidities (n = 22), cognitive impairment (n = 21), reported previous motor disability (n = 20), fever (n = 10), continued use of noninvasive ventilation (n = 8), and tachypnea (n = 5).

TABLE 1 - Patients characteristics
Patients, n 41
Age, yr 67.1 (11.6)
 Range (min–max) 40–88
Males, n (%) 25 (61.0)
BMI, kg/m2 26.7 (4.9)
Patients with comorbidities, n (%) 17 (41.5)
 Cardiac comorbidities 15 (36.6)
 Pulmonary comorbidities 6 (14.6)
Spo 2/Fio 2 at discharge 454.9 (8.7)
Time from symptom onset, d 28.6 (8.2)
Acute care hospital LOS, d, 9.7 (5.5)
Postacute hospital LOS, d 10.6 (7.2)
Total hospital LOS, d 20.7 (7.5)
Patients treated with CPAP or NIV, n (%)
 In acute care hospital 9 (21.4)
 In postacute hospital 1 (2.3)
Patients treated with invasive mechanical ventilation, n (%) 2 (4.8)
Patients treated with oxygen therapy only, n (%)
 In acute care hospital 28 (68.3)
 In postacute hospital 36 (85.7)
Maximal Fio 2 used during hospitalization 0.49 (0.25)
Drugs, patients, n (%)
 Antiviral 20 (80.5)
 Steroids 7 (17.1)
 Antirheumatics 32 (78.0)
 Antibiotics 30 (73.2)
 Antithrombotics 18 (43.9)
Data are reported as mean (SD) unless otherwise indicated.
BMI, body mass index; CPAP, continuous positive airways pressure; Fio2, oxygen inspiratory fraction; LOS, length of stay; NIV, noninvasive ventilation; Spo2, pulse oxymetry.

Quadriceps and biceps weakness was observed in 86% and 73% of the patients, respectively. The mean maximal voluntary contraction of quadriceps was 18.9 (6.8) kg, whereas that of biceps was 15.0 (5.5) kg; the percentage of the predicted normal values for quadriceps and biceps were 54 (18)% and 69 (18)%, respectively. The number of rises during the 1-min STS was 22.1 (7.3), corresponding to 63 (19)% of the predicted normal value, and the short physical performance battery score was 7.9 (3.3), corresponding to 74 (30)% of the predicted normal value.

Figure 1 shows the percentage of predicted values of muscle strength and physical performance measures in the overall group and in the patients according to the presence or absence of comorbidities. At the end of the 1-min STS test, 24% of the patients showed exercise-induced desaturations and the quadriceps strength decreased by 1.4 (1.6) kg, corresponding to 7.4 (8.1)% of the baseline value. Table 2 shows dyspnea and leg fatigue perceived by the patients, as assessed by the Borg scale. Most patients (53%) still had a “good” physical autonomy as assessed by the short physical performance battery (scores = 9–12), whereas 25% showed high levels of disability (scores <5) and 22% had low-moderate disability (scores = 5–8).

FIGURE 1
FIGURE 1:
Comparison of muscle strength (panels A and B) and physical performance (panels C and D) expressed as percentage of the predicted values in the overall group and according to the presence or not of comorbidities. 1 min-STS, 1 minute sit-to-stand; SPPB, short physical performance battery.
TABLE 2 - Perceived dyspnea and leg fatigue
Dyspnea Leg Fatigue
At rest, Borg scale score 0 (0–1) 0 (0–1)
During ADL, Borg scale score 0.5 (0–2) 1 (0–2)
During ADL, % of the patients with a Borg scale score ≥ 3 17 20
At the end of 1-min STS, Borg scale score 3 (2–5) 1 (0–3)
At the end of 1-min STS, % of the patients with a Borg scale score ≥ 3 70 29
Data are described as median (interquartile range).
ADL, activities of daily living.

Weak but statistically significant correlations were observed between muscle strength and indices of physical performances (R = 0.31–0.69). Significant inverse relationships were observed between quadriceps strength and length of stay in the acute hospital (R = −0.35, P = 0.03), between biceps strength and age (R = −0.33, P = 0.0324) and between 1-min STS and symptoms (dyspnea [R = −0.40, P = 0.01] and fatigue [R = −0.35, P = 0.03] at rest and dyspnea [R = −0.49, P = 0.001] and fatigue [R = −0.35, P = 0.03] during activities of daily living).

The single-breath counting test was 35.4 (12.3) counts, which equals 72% of the data recorded in 40 healthy controls (personal data due to lack of predictive normal values), suggesting a reduction in vital capacity and/or expiratory flow.

After discharge 28 patients returned home, 4 patients were transferred to a dedicated pulmonary rehabilitation ward, 7 patients were prescribed 1 mo of telerehabilitation at home, and 1 patient was transferred to another acute hospital.

DISCUSSION

This is the first report showing impairment in comprehensively assessed physical performance in individuals in the early recovery from COVID-19 infection at discharge from hospital. Our results indicate that the patients who have recovered from respiratory distress requiring assisted ventilation or oxygen therapy and who were without any previous disability have reduced physical performance. Despite the relatively small sample size and the possible lack of external validity of these results, our findings may be useful to guide clinicians in taking care of patients surviving COVID-19 infection.

Although there was a weak significant inverse relationship between quadriceps strength and length of stay in the acute hospital, the reduction in physical performance observed in our patients cannot be ascribed to a prolonged intensive care unit stay and/or prolonged mechanical ventilation, as the vast majority of our patients had not experienced such conditions. Only 2 of the 41 patients had been intubated in the acute hospital for 5 and 9 days, and their length of stay was 13.5 (0.7) days.

Almost one of the four patients, normoxemic at rest, showed significant exercise-induced oxygen desaturations during the 1-min STS, and the patients reported low levels of perceived dyspnea or fatigue as assessed by the Borg scale. Indeed, the low intensity and short duration of this test might have underestimated the severity of exercise-induced desaturations as compared with standard exercise tests such as the 6-min walking test or cardiopulmonary exercise tests. The latter tests, however, would have been impossible to conduct in our clinical conditions. Similarly, the evaluation of symptoms during hospital activities is clearly influenced by the level of effort chosen by patients. We assessed perceived leg fatigue using the Borg scale. More specific tools such as the Chronic Respiratory Questionnaire, the Fatigue Impact Scale, or the Fatigue Severity Scale may be more appropriate, although no scale is specifically validated for COVID-19.18 Nevertheless, the reduction in post–1-min STS quadriceps strength indicates that leg fatigue was present in our patients.

Our patients received pharmacotherapy. No adverse effects were reported, but at the time of the writing of this manuscript, no pharmacotherapy has been proven to be safe and effective for treating patients with COVID-19 disease.19 Furthermore, we cannot exclude potential effects of any of these drugs on peripheral muscle strength or physical performance.

Limitations of the Study

First, for safety reasons, it was impossible to perform standard lung or respiratory muscle function tests including the assessment of lung diffusion capacity. Therefore, we used the single-breath counting test as a surrogate and found a reduction in single-breath counting values. This suggests, but does not proves, an impairment in lung function.20 Hence, we are unable to define to what extent the decline in physical performance can be ascribed to impairment in lung or respiratory muscle function. With 25% of the patients showing significant desaturations even during a short 1-min STS test, it is highly likely that lung function (diffusion) impairment may remain clinically relevant in many patients, even after discharge.

Second, a parallel COVID-free control group could not be studied because of the local lockdown. Between March and July 2020, our unit was dedicated full time to COVID-19 patients, while patients with others chronic diseases were strictly maintained at home. However, muscles of the upper and lower limbs of our COVID-19 patients seem weaker compared with patients with chronic cardiorespiratory conditions of similar age (data published previously by the present authors).21

Third, our study may lack external validity because of our restrictive inclusion criteria and the restriction that limited the study to patients without functional limitations before their COVID-19 infection. This, however, allowed us to focus on the direct effect of the virus on muscle and functional ability, reducing confounding effects.

Last, the lack of baseline measures at the time of admission to the postacute hospital is unfortunate. This would have allowed us to describe muscle strength and function closer to nadir as well as to assess the impact of the postacute care. Similarly, follow-up data after the period of inpatient rehabilitation might have contributed to an even more comprehensive description of the recovery of these patients.

CONCLUSIONS

We observed a high prevalence of muscle weakness and physical performance impairment in patients recovering from a moderate-to-severe COVID-19 pneumonia and hospitalized without any previous motor limitation. With the limitations imposed by the present clinical circumstances, these findings strongly suggest the need for follow-up evaluation of physical function and rehabilitation programs in a large fraction of these patients.

ACKNOWLEDGMENT

The authors thank all physiotherapists of the Istituti Clinici Scientifici Maugeri IRCCS, Respiratory Rehabilitation of the Istitute of Lumezzane (BS), who treated the patients enrolled in this study, as well as Rosemary Allpress for English revision and Laura Comini and Adriana Olivares for technical assistance and editing.

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Keywords:

Respiratory Failure; Pulmonary Rehabilitation; Intermediate Care; Outcome; Fatigue

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