Physiotherapy for Persistent COVID-19 Disease Using Aerobic Exercise
Condition: COVID-19; Genetic Predisposition to Disease
MeSH terms: COVID-19; Post-Acute COVID-19 Syndrome; Genetic Predisposition to Disease
Study type: Interventional

Summary: 
      Aerobic exercise - Nordic walking in Persistent Covid (PC) vs. healthy controls.

      The main objective of this study is to analyse the genes associated with increased physical
      performance in patients with PC vs. healthy controls and to measure the level of lactic acid
      in blood, pre and post exercise session in patients affected by PC.

      Relevance: It is intended to be a tool for patients with CP who have not been hospitalised,
      nor have been offered outpatient rehabilitation treatment. They have not recovered their
      work, family, sporting or leisure functions. They have particular problems in returning to
      aerobic exercise.

      We think that they may need to be accompanied in the recovery of their physical condition
      under the supervision of health professionals. Most of the studies offered to them are
      exploratory, not intervention. Our proposal is a 12-week intervention.

      Our proposal, delves into the mechanisms that may underlie their fatigue and their problems
      in returning to aerobic exercise, in order to collaborate in approaching possible solutions.

      Secondary objectives: To study in each of the patients with persistent covid, included in the
      aerobic Nordic walking programme, their DNA in order to, based on two candidate genes,
      analyse the role of genetic polymorphisms associated with increased VO2 max training,
      compared to a healthy control group.

      To assess the blood lactic acid level pre and post exercise in a group of patients with
      persistent covid pre and post aerobic Nordic walking programme. Patients and Methods: 33
      patients with CP and 33 healthy controls will follow a Nordic walking programme for 12 weeks.
      QIAGEN Cube automatic extractor and lactic acid meter will be used.
    

Detailed description: 
      Design: Parallel non-randomized clinical trial. Study arms: Experimental group with Nordic
      walking programme (n=15) and healthy control group with the same programme (n=15).

      Patients will be recruited by means of a mass mailing to their addresses in the Covid
      Persistente Madrid group. Participants must meet the inclusion criteria and sign the informed
      consent form. Patients will be asked to submit a recent basic blood test and an
      electrocardiogram if available.

      Medical Rehabilitation Consultation for screening of patients It is assumed that the patient
      has already been diagnosed with longCOVID, so he/she should provide data from previous
      clinical history in relation to the process: time of evolution, characteristics of the
      syndrome, and treatments carried out.....

      It is essential that the patient provides a recent blood test. Objectives To ascertain the
      main symptomatology presented by the patient, with relevance of signs and symptoms that cause
      functional limitation.

      Determine the presence of comorbidities that may be a contraindication or precaution for the
      practice of the activity.

      The estimated effect size for the main outcome measures established in this project was 0.25.
      Considering a power of the statistical test of 0.95, an alpha error of 0.05 and a total of
      five measurements in two participant groups, a minimum number of 30 participants is required,
      according to the G*Power software (version 3.1.7). Taking into account a loss rate of 10%,
      the sample size will finally consist of 30 subjects (15 subjects for each intervention
      group). In order to prevent possible losses, 17 subjects will be included in each group.

      5.3. Spatial scope

      The assessment will take place:

      Consultations with the rehabilitation doctor will take place at the University Clinic of the
      Faculty of Health Sciences of the Rey Juan Carlos University, Madrid, Spain.

      Genetic analysis: Faculty of Health Sciences. Francisco de Vitoria University. Lactic acid
      measurement: Outdoors, pre- and post-Nordic walking session. Since the measurement must be
      immediate.

      The intervention will take place in the outdoor space of the Casa de Campo. Madrid, Spain.

      The Nordic walking sessions will last 90 minutes (warm-up, exercise and cool down), and will
      be carried out for 12 weeks, with a frequency of once a week.

      The instructor will start by designing routes without gradients during the first four
      sessions of intervention and will adapt the protocol for the following two months according
      to the evolution of the groups and adapted to the needs of the longCOVID patients.

      Patients will be asked to record post-exercise fatigue and their heart rate and oxygen
      saturation will be monitored during the sessions.

      DNA collection for the determination of polymorphisms will be performed on samples to
      optimize resources (samples will be anonymized and coded).

      Samples will be obtained by swabbing and scraping of the buccal mucosa by the participant.
      DNA will be isolated by QIAGEN Cube automatic extractor. The DNA will be stored at -20º until
      use.

      The genetic study will analyze single nucleotide polymorphisms (SNPs) related fundamentally
      to functions associated with:

        -  Polymorphisms of genes associated with muscle performance; ACE, ACTN3, AMPD1, CKM and
           MLCK

        -  Polymorphisms of genes for sensitivity and resistance to Covid-19 infection; ACE-2 The
           data will be entered into the SPSS statistical package (version 25) for analysis.

      First, the Kolmogorov-Smirnov test will be used to determine whether the study variables show
      a normal distribution (p>0.05). Those quantitative variables that do not show a normal
      distribution will be analysed with non-parametric tests and their data will be expressed as
      median and interquartile range, while quantitative variables that show a normal distribution
      will be analysed with parametric tests and their data expressed as mean and standard
      deviation.

      For variables with a normal distribution, a repeated measures analysis of variance (ANOVA)
      with Bonferroni a posteriori adjustment will be performed, establishing as an inter-subject
      factor the group parameter (experimental and control) and as an intra-subject factor each of
      the measurements.

      The contrast of variables that do not follow a normal distribution will be carried out using
      the Mann-Whitney U test, comparing the differences between the groups in each measurement.
      Intra-group differences will be analysed using the Friedman test for k related samples. In
      case this test detects intra-group differences at follow-up, the Wilcoxon signed-rank test
      for two related samples will be used.

      Between-group analysis of qualitative variables, expressed as proportions and percentages,
      will be performed using Pearson's chi-squared test. Intra-group differences of qualitative
      variables will be performed using McNemar's test for paired data.

      The statistical analysis will be carried out with a confidence level of 95%, so that values
      with a p-value of less than 0.05 will be considered significant.
    

Intervention name(s): Experimental; Control
Intervention type(s): Device; Genetic
Intervention description(s): Pre- and post-intervention measurement of quality of life, self-perceived fatigue and blood lactic acid concentration after each Nordic Walking session.; Genetic polymorphism study by Polymerase Chain Reaction (PCR) to determine genetic profile and allele frequencies of patients with persistent COVID and association by Total Genotype Score (TGS) with fatigue status.
Other intervention name(s): Lactic acid; EuroQool EQ5D; SF-36; MFIS; ACE polimorphism; ACTN3 polymorphism; AMPD1 polymorphism; CKM polymorphism; MLCK polymorphisms; ACE2 polymorphisms
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: longCOVID; Aerobic exercise; Muscle performance; Genetics