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Muscle Weakness in COVID-19 Patients (MIOCOVID)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04959773
Recruitment Status : Recruiting
First Posted : July 13, 2021
Last Update Posted : May 18, 2022
Sponsor:
Collaborator:
Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria
Information provided by (Responsible Party):
Simone Porcelli, University of Pavia

Brief Summary:

Although the Covid-19 infection mainly manifests itself with respiratory symptoms, as early as two months after the onset of the pandemic, the presence of other symptoms, including muscle ones, became clear. With the disappearance of the emergency and the advancement of knowledge, medium- and long-term effects have been reported at the level of different organs and systems. Many patients, after several months from infection, report intolerance to exercise and many suffer from pain and muscle weakness. No studies has been carried out on the muscular consequences of the infection and on their possible contribution to intolerance to exercise. Since skeletal muscle possesses the ACE2 receptor (Angiotensin converting enzyme 2) to which SARS-Cov-2 binds, it follows that the involvement of the skeletal muscle could be due not only to the secondary effects of the infection (e.g. reduced oxygen supply from persistent lung disease, perfusion defects from cardiovascular defects and vascular damage), but also to the direct action of virus (SARS-Cov-2 myositis).

The general purpose of the research is to quantify the spread of symptoms and signs of muscle weakness and pain among the patient population welcomed at the Cardiorespiratory Rehabilitation Department of the Alexandria Hospital which have been suffering from SARS-CoV-2, being discharged and healed for more than two months, and define the possible contribution of muscular modifications to exercise intolerance.


Condition or disease
SARS-CoV Infection Covid19 Muscle Weakness Exercise Intolerance

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Study Type : Observational
Estimated Enrollment : 30 participants
Observational Model: Case-Control
Time Perspective: Retrospective
Official Title: Potential Mechanisms of Long-term Muscle Weakness and Decreased Exercise Tolerance in Patients Infected by SARS-COV-2
Actual Study Start Date : November 15, 2020
Actual Primary Completion Date : May 15, 2022
Estimated Study Completion Date : December 30, 2022


Group/Cohort
COVID+ with exercise intolerance

Patients of both sexes who have contracted SARS-COV-2 infection (swab positive and positive serological test (IgG)) and who suffer from muscle weakness after more than two months from infection.

The presence of cardiovascular or internal pathologies or in any case of serious disease will be considered an exclusion criterion.

general conditions.

COVID+ without exercise intolerance

Patients of both sexes who have contracted SARS-COV-2 infection (swab positive and positive serological test (IgG)) and who recovered and came to their normal life.

The presence of cardiovascular or internal pathologies or in any case of serious disease will be considered an exclusion criterion.

Control healthy subjects (CTRL)
Subjects of both sexes who do not have contracted SARS-COV-2 infection (swab negative and negative serological test (IgG)). The presence of cardiovascular or internal pathologies or in any case of serious disease will be considered an exclusion criterion.



Primary Outcome Measures :
  1. Functional status [ Time Frame: at least 2 months after infection ]
    Post-COVID-19 Functional Status scale

  2. Perceived quality of life by EQ-5D-5L [ Time Frame: at least 2 months after infection ]
    The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.

  3. Exercise intolerance [ Time Frame: at least 2 months after infection ]
    Maximal oxygen consumption during incremental test

  4. Muscle weakness [ Time Frame: at least 2 months after infection ]
    Reduced muscle force during isometric contraction

  5. Pulmonary function [ Time Frame: at least 2 months after infection ]
    Spirometry and DLCO capacity


Secondary Outcome Measures :
  1. Muscle fatiguability [ Time Frame: at least 2 months after infection ]
    Central and peripheral indexes of fatigue after an isotonic exercise

  2. Histology and morphology of skeletal muscle [ Time Frame: at least 2 months after infection ]
    The muscle sections will be stained with: 1) Hoechst nuclear dye for evaluating the presence of nucleated center cells and 2) Hematoxylin and Eosin (H&E) for measuring the area of the cross section of the individual muscle fibers (CSA) and to reveal morphological alterations. The morphological analysis should first demonstrate the presence of atrophy of individual muscle fibers. From the morphological analysis it will also be possible to highlight the presence of inflammatory infiltrates, the presence of core nucleated cells and other signs of structural alteration.

  3. Single muscle fiber mechanics [ Time Frame: at least 2 months after infection ]

    Functional analyzes will be performed on single muscle fibers and on isolated myosin.

    The absolute isometric force (Po), the specific isometric force (Po / CSA) and the no-load shortening rate (Vo) of the individual muscle fibers will be determined with the slack test technique. The fibers, chemically deprived of the cell membrane through exposure to detergent (Triton X 100), will be stimulated by exposure to a solution containing Ca2 + and ATP ions. At the end of the functional experiment, the fibers will be collected and typed through the analysis of the isoform content of the myosin heavy chain (MHC).


  4. Ex-vivo muscle oxidative function [ Time Frame: at least 2 months after infection ]
    Through molecular analyzes it will be possible to investigate the mechanisms underlying the possible myopathic condition. The following molecular investigations will be performed with Real Time-PCR (RT-PCR) and Western Blot (WB) techniques: activation of the signaling pathways of synthesis and protein degradation (IGF-1 / Akt / mTOR; ubiquitin proteosome system, autophagy ); apoptosis; mitochondrial dynamics; redox state.



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Ages Eligible for Study:   35 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Sampling Method:   Non-Probability Sample
Study Population

Patients will be divided into three Groups :

  • COVID+ with exercise intolerance Patients of both sexes who have contracted SARS-COV-2 infection (swab positive and positive serological test (IgG)) and who suffer from muscle weakness after more than two months from infection.
  • COVID+ without exercise intolerance Patients of both sexes who have contracted SARS-COV-2 infection (swab positive and positive serological test (IgG)) and who recovered and came to their normal life.
  • CTRL Subjects of both sexes who do not have contracted SARS-COV-2 infection (swab negative and negative serological test (IgG)).
Criteria

Inclusion Criteria:

-

Exclusion Criteria:

  • presence of cardiovascular, neurological and metabolic disorders.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04959773


Contacts
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Contact: Simone Porcelli, MD, PhD +390382987538 simone.porcelli@unipv.it
Contact: Roberto Bottinelli, MD, PhD +390382987257 roberto.bottinelli@unipv.it

Locations
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Italy
Azienda Ospedaliera Recruiting
Alessandria, AL, Italy, 15121
Contact: Biagio Polla, MD         
Sponsors and Collaborators
University of Pavia
Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria
Investigators
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Principal Investigator: Biagio Polla, MD AO SS Alessandria
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Responsible Party: Simone Porcelli, MD, PhD, University of Pavia
ClinicalTrials.gov Identifier: NCT04959773    
Other Study ID Numbers: UPavia-MIOCOVID
First Posted: July 13, 2021    Key Record Dates
Last Update Posted: May 18, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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COVID-19
Severe Acute Respiratory Syndrome
Muscle Weakness
Paresis
Asthenia
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Pathologic Processes