Effects of Inspiratory Muscle Training After Covid-19 (ReCOV)

Introduction:

Covid-19 was declared a global pandemic in March 2020 by the World Health Organization
(WHO). So far (August 2021), there are over 1 100 000 confirmed cases and over 14 000
deaths in Sweden. Initially, it was suspected that Covid-19 would primarily affect the
airways, but several studies have now shown that it is a disease with multisystem
manifestations. The impact of the virus ranges from an asymptomatic infection to a severe
and life-threatening disease that can affect the cardiac, renal gastrointestinal,
nervous, endocrine, and musculoskeletal systems. Therefore, Covid-19 has the potential to
affect physical, cognitive, and psychological functions in multiple ways. It has been
clear that a significant proportion of patients with Covid-19 develop long-term symptoms.
Signs and symptoms may arise from any system in the body, often with significant overlap,
and may develop over time. The term post- acute Covid-19 syndrome (PACS) is now used to
describe the wide range of prolonged symptoms following the infection.

Fatigue, decreased physical and psychological function have been reported in the initial
recovery phase, but still little is known on the long-term consequences. Patients who
have been in hospital for Covid-19 for a long time may need specialized rehabilitation,
however, also non-hospitalized patients with mild symptoms may need specific
rehabilitation to be able to meet the complex symptoms and problems that may arise.
Previous studies on the recovery and rehabilitation after other coronavirus shows the
importance to develop tailored interventions so that these patients receive appropriate
rehabilitation with a multi-professional approach throughout the whole care chain. Some
studies suggest that the rehabilitation should be similar to pulmonary rehabilitation,
but since a lot of patients often have symptoms from different organ systems this is not
yet fully investigated and needs to be addressed from different perspectives. A study by
Liu et al (2020), showed that 6 weeks of physical exercise and respiratory muscle
training improved lung function and physical capacity compared to a control group in
elderly patients after Covid-19.

At the Karolinska University Hospital there is a specialized multidisciplinary and
multi-professional approach aiming to follow up patients who have been hospitalized.
However, from mid-2020 and onwards, referrals from primary care have significantly
increased. This includes patients who have never been hospitalized but with varying
symptoms from several organs that have lasted for more than 3 months.

This study is part of a bigger research project (ReCoV) and is integrated with the
clinical follow-up and linked research project of patients who have been hospitalized or
referred from primary care

Hypothesis: The overall hypothesis of the hole research project is that physical and
physiological function, work ability and HRQoL are important factors for recovery after
Covid-19 which can be improved by individual tailored rehabilitation.

The aim of this study is to evaluate the effects of inspiratory muscle training (IMT) on
physical and psychological function, work ability and HRQoL in patients with decreased
respiratory muscle strength after Covid-19.

Methods:

To evaluate the effects of IMT, a randomized controlled trial design will be used.

Participants:

Patients with PACS above 18 years old (N=90) with 80% or less of predicted value in
maximal inspiratory pressure (MIP) are eligible for participation in the study.

Procedure:

Baseline assessment before the intervention period will be performed at an outpatient
visit at Karolinska university hospital. After baseline assessment participants will be
randomized to either an intervention group or to an active control group using random
permuted blocks. The intervention will take place at the physiotherapy outpatient clinic
at the hospital or at a primary care facility and in the participants' homes. The
intervention group will perform IMT twice daily (two sets of 30 receptions) at home
during 8 weeks with a resistance of 20-50 % of MIP using an inspiratory muscle trainer
(Threshold or digital advice). Follow-up of execution and increase in intensity during
IMT will be conducted weekly by the physiotherapist. This will be combined with an 8-week
physical exercise program including aerobic, strength and mobility exercises which will
be performed at the care facility and at home at least two times a week. The active
control group will perform the same physical exercise program according to standard care.

Outcome assessment:

All measurements will be performed at baseline and after the intervention period (8
weeks).

Primary outcome is maximal inspiratory pressure (MIP) and secondary outcomes are: maximal
expiratory pressure (MEP), lung function, physical capacity (6-min walk test), Chair
stand test, physical activity, respiratory status and symptoms, health-related quality of
life, work ability, fatigue, self-reported outcome measure of physical function and voice
function.

Statistical analyses:

Data will be described with mean (standard deviation), median (inter-quartile range) and
proportion and analyzed with parametric and non-parametric methods depending on data
level. All voice recordings will be assessed by a group of speech and language
pathologists all experts on voice disorders. The longitudinal group variations will be
analyzed using Linear Mixed Models that in addition to studying change at the group level
also can model change on the individual level. In addition, the method can handle
dependency for repeated observations and provide correct estimates with missing data. To
detect differences of 10% in the MIP a calculation of 36 patients in each group plus 25%
drop-out in the power analyses, which lead to 45 participants in each group.

Clinical significance:

Covid-19 has the potential to affect physical, cognitive, and psychological functions in
multiple ways and lead to a negative impact on quality of life in the long-term
perspective. Therefore, development of a rehabilitation program with specific tailored
interventions will be necessary to improve physical and psychological function, as well
as health-related quality of life and work ability.

Covid-19 is a new disease and large knowledge gaps need to be filled. Previous studies
indicate that the patients are affected at several levels and a rehabilitation period is
necessary. It is of great importance that data is collected systematically and
standardized. If significant effects occur, the possibility to generalize the results to
other individuals with Covid-19, are promising. The physical interventions may thus
improve the ability to adjust to the implications of Covid-19, which can potentially have
significant health economic effects. For example, the interventions may prolong patients'
meaningful activities of daily living and their ability to return to their previous
workplaces (conduct their professions). This project will deepen the knowledge about the
effects of specialized rehabilitation

Ethical considerations:

The project has been approved by the Swedish Ethical Review Authority. The participants
will receive verbal and written information about the study and informed consent will be
obtained from all participants.