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The physiological/biomechanical characteristics related to muscle and tendon architecture and their possible relationship with the loss of muscle strength and fatigue in patients who were infected with COVID-19 are totally unknown. The aim of this study is to evaluate inflammatory markers, the isometric maximum voluntary force of the knee extensor torque, muscle fatigue, neuromuscular adaptations, muscle architecture, tendinous properties of quadriceps components, oxygen extraction, and body composition in participants after diagnosis with Covid-19 who had moderate and severe levels of involvement compared to a healthy control group.
The groups will be composed of participants who had COVID-19, except for the control group, which will be composed of healthy participants who did not have COVID-19. Participants will be divided into: (1) control group, (2) COVID-19 positive participants who had moderate symptoms, (3) COVID-19 positive participants who had severe symptoms. Participants will be recruited from 21 days after the onset of symptoms, the period recommended by the scientific community that the patient no longer transmits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). After recruitment, 4 evaluations will be carried out over 1 year.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control group | Healthy individuals will be evaluated only once throughout the study. Inflammatory markers, the isometric maximum voluntary force of knee extensor torque, muscle fatigue, neuromuscular adaptations, muscle architecture, quadriceps tendon properties, peripheral oxygen extraction, and body composition will be evaluated. | ||
| COVID-19 positive participants who had moderate symptoms group | These participants will be evaluated 4 times throughout the study. Baseline 1: This will be performed between 21 to 30 days after the onset of symptoms of COVID-19 infection. Assessment 2: This will be performed between 31 to 90 days after the onset of symptoms of COVID-19 infection. Assessment 3: This will be carried out between 91 and 180 days after the onset of symptoms of COVID-19 infection. Assessment 4: This will be performed between 181 to 360 days after the onset of symptoms of COVID-19 infection. Inflammatory markers, the isometric maximum voluntary force of knee extensor torque, muscle fatigue, neuromuscular adaptations, muscle architecture, quadriceps tendon properties, peripheral oxygen extraction, and body composition will be evaluated in each assessment. | ||
| COVID-19 positive participants who had severe symptoms group | These participants will be evaluated 4 times throughout the study. Baseline 1: This will be performed between 21 to 30 days after the onset of symptoms of COVID-19 infection. Assessment 2: This will be performed between 31 to 90 days after the onset of symptoms of COVID-19 infection. Assessment 3: This will be carried out between 91 and 180 days after the onset of symptoms of COVID-19 infection. Assessment 4: This will be performed between 181 to 360 days after the onset of symptoms of COVID-19 infection. Inflammatory markers, the isometric maximum voluntary force of knee extensor torque, muscle fatigue, neuromuscular adaptations, muscle architecture, quadriceps tendon properties, peripheral oxygen extraction, and body composition will be evaluated in each assessment. |
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| Measure | Description | Time Frame |
|---|---|---|
| Blood biomarkers | Blood biomarkers including metalloproteinase 9, interleukin-6, interleukin-8 and interleukin-10, interleukin 1 beta, tumor necrosis factor alpha type, nitric oxide, as well as creatine kinase will be collected in blood samples by venipuncture in the vein brachial, in heparinized tubes with separating gel using the vacutainer system with ethylenediaminetetraacetic acid (EDTA). The samples will be stored and later analyzed using appropriate techniques. | Change from baseline 1 (days 21-30) to assessments 2 (days 31-90), 3 (days 91-180), and 4 (days 181 to 360) for groups composed of COVID-19 positive participants. The Control group will be assessed only at baseline. |
| Sit to stand test | To carry out the test will be used a stopwatch and a chair with the back against a wall, seat height 43 cm from the floor and without armrest. The test consists of measuring how many times the participant can get up and sit down from a chair (counting as a movement) in a period of 30 seconds. | Change from baseline 1 (days 21-30) to assessments 2 (days 31-90), 3 (days 91-180), and 4 (days 181 to 360) for groups composed of COVID-19 positive participants. The Control group will be assessed only at baseline. |
| Electrodiagnostic stimulus test | The quadriceps femoris, gastrocnemius, soleus and tibialis anterior muscles will be evaluated. At the muscle motor point, the values of rheobase, chronaxia and accommodation will be investigated. | Change from baseline 1 (days 21-30) to assessments 2 (days 31-90), 3 (days 91-180), and 4 (days 181 to 360) for groups composed of COVID-19 positive participants. The Control group will be assessed only at baseline. |
| Body composition | Body composition will be estimated using dual x-ray absorptiometry. Fat mass and fat-free mass will be expressed in absolute values. | Change from baseline 1 (days 21-30) to assessments 2 (days 31-90), 3 (days 91-180), and 4 (days 181 to 360) for groups composed of COVID-19 positive participants. The Control group will be assessed only at baseline. |
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Inclusion Criteria:
Control group:
- The control group will include healthy participants, aged 18 and 80 years, who had not tested positive for COVID-19.
COVID-19 positive participants who had moderate symptoms group:
COVID-19 positive participants who had severe symptoms group:
Exclusion Criteria:
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Female and male participants aged between 18 and 80 years who had tested positive for COVID-19 will be included in this study. In addition, the control group will include healthy participants who had not tested positive for COVID-19.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Rita CM Durigan, PhD | Contact | +55 61 3107-8450 | marqueti@gmail.com | |
| João LQ Durigan, PhD | Contact | +55 61 3107-8450 | joaodurigan@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| João LQ Durigan, PhD | University of Brasilia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Brasilia | Recruiting | Brasília | Federal District | 72220-900 | Brazil |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42369154 | Derived | Salomao R, Pasquarelli-do-Nascimento G, Ananias M, Assis V, Ferreira LGJ, da Silva Almeida I, Silva L, Tostes K, Sorroche BP, Arantes LMRB, Magalhaes KG, Garcia LT, Rocha Costa R, Quagliotti Durigan JL, Marqueti RC. Longitudinal trajectories of hematological indices and serum metalloproteinases-2 and 9 over 1 year after moderate and severe COVID-19. Front Med (Lausanne). 2026 Jun 12;13:1824883. doi: 10.3389/fmed.2026.1824883. eCollection 2026. | |
| 42300213 |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D005221 | Fatigue |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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Blood samples to assess cytokines and matrix metalloproteinases (MMPs) involved in COVID-19 pathology.
| Muscle force | Muscle force will be assessed by muscle force changes, based on the torque generated during maximum voluntary contraction. | Change from baseline 1 (days 21-30) to assessments 2 (days 31-90), 3 (days 91-180), and 4 (days 181 to 360) for groups composed of COVID-19 positive participants. The Control group will be assessed only at baseline. |
| Peripheral oxygen extraction | The assessment of peripheral oxygen extraction will be performed both in rest and during voluntary contraction. The evaluation will be carried out by means of near-infrared spectroscopy (NIRS or near infrared spectroscopy). | Change from baseline 1 (days 21-30) to assessments 2 (days 31-90), 3 (days 91-180), and 4 (days 181 to 360) for groups composed of COVID-19 positive participants. The Control group will be assessed only at baseline. |
| Surface electromyographic activity | Electromyographic activity of each superficial component of the quadriceps muscle both in rest and during voluntary contraction. | Change from baseline 1 (days 21-30) to assessments 2 (days 31-90), 3 (days 91-180), and 4 (days 181 to 360) for groups composed of COVID-19 positive participants. The Control group will be assessed only at baseline. |
| Muscle architecture | Muscle architecture analyzes will be performed using ultrasound at rest and during voluntary contraction. The muscle volume of the knee extensors, muscle thickness, pennation angle, fascicle length and muscle echogenicity will be evaluated. | Change from baseline 1 (days 21-30) to assessments 2 (days 31-90), 3 (days 91-180), and 4 (days 181 to 360) for groups composed of COVID-19 positive participants. The Control group will be assessed only at baseline. |
| Properties of the patellar tendon | The morphological, material and mechanical properties will be evaluated based from the elongation of the patellar tendon during maximum voluntary contraction. | Change from baseline 1 (days 21-30) to assessments 2 (days 31-90), 3 (days 91-180), and 4 (days 181 to 360) for groups composed of COVID-19 positive participants. The Control group will be assessed only at baseline. |
| Muscle fatigue | Quadriceps muscle fatigue will be assessed in each leg after consecutive maximal isometric voluntary contractions of the quadriceps muscle. | Change from baseline 1 (days 21-30) to assessments 2 (days 31-90), 3 (days 91-180), and 4 (days 181 to 360) for groups composed of COVID-19 positive participants. The Control group will be assessed only at baseline. |
| Assessment of perceived exertion during the fatigue protocol | Assessment of perceived exertion will be analyzed before, during, and after the performance of maximum voluntary isometric contractions performed to analyze muscle fatigue using the BORG scale of perceived exertion. | Change from baseline 1 (days 21-30) to assessments 2 (days 31-90), 3 (days 91-180), and 4 (days 181 to 360) for groups composed of COVID-19 positive participants. The Control group will be assessed only at baseline. |
| Fatigue severity analysis | Fatigue severity analysis will be assessed using the fatigue severity scale. | Change from baseline 1 (days 21-30) to assessments 2 (days 31-90), 3 (days 91-180), and 4 (days 181 to 360) for groups composed of COVID-19 positive participants. The Control group will be assessed only at baseline. |
| Derived |
| da Silva Almeida I, de Jesus Ferreira LG, Vaz MA, Costa RR, Babault N, de Cassia Marqueti R, Durigan JLQ. Muscle fatigue in patients with severe long COVID: A 2-year follow-up study. PM R. 2026 Jun 16. doi: 10.1002/pmrj.70165. Online ahead of print. |
| 40991619 | Derived | Almeida IDS, Ferreira LGJ, Vaz MA, Cipriano Junior G, de Resende MA, Vieira DCL, Costa RR, Babault N, Marqueti RC, Durigan JLQ. Fatigue and neuromuscular function in long COVID: A one-year follow-up study. PLoS One. 2025 Sep 24;20(9):e0332242. doi: 10.1371/journal.pone.0332242. eCollection 2025. |
| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |