Dysfunctional Breathing in Post COVID-19 Condition.

The overall aim with the proposed research project is to describe and investigate the underlying mechanisms of dysfunctional breathing and the experience of living with dysfunctional breathing in patients with post-COVID-19 conditions. In addition, validate and evaluate which methods measure dysfunctional breathing regarding content validity, conceptual validity, test-retest reliability, and sensitivity to change for patients with post-COVID-19 conditions. Furthermore, to develop and evaluate an individually adapted intervention with the aim of normalizing the breathing pattern. In the next step, to evaluate the effects of an individually adapted intervention on physical and psychological function and health-related quality of life (HRQoL) in patients with post-COVID-19 conditions, as well as to describe the patients' experiences of rehabilitation.

Methods and planned studies This project is a part of a larger multi-disciplinary and multi-professional study, ReCOV, that takes a holistic perspective on the consequences of the disease. ReCOV is a three-armed project including patients, next of kin and staff (23). Patients have been followed up at the out-patient clinic for patients with PCC at Karolinska University Hospital (K).

The longitudinal observational study is about physical and psychological recovery, objectively measured physical activity and also an interview study of the patients' overall experiences of rehabilitation after COVID-19 both in the acute and long-term perspective. In total approximately 950 patients have accepted to be apart of ReCOV and to this proposed project patients will be recruited from this cohort but also from primary care. This research project will be performed in collaboration with Karolinska Institutet, Karolinska university Hospital (K), Sahlgrenska University Hospital (SH). University of Gothenburg and primary care in Region Stockholm.

Study 1: Dysfunctional breathing in patients with post COVID-19 condition?

Aim: To investigate what signs, symptoms and assessment which can describe and explain dysfunctional breathing in patients with post COVID-19 condition.

Design: Cross-sectional design

Participants: Patients (approximately n=200) for this study will be recruited from the ReCov cohort. All patients will be \> 18 years old. Patients that state that they have persistent respiratory problems and abnormal clinical respiratory findings will be included. Patients will also be recruited from primary care if they have suspected dysfunctional breathing pattern (unable to breathe with a normal breathing pattern in standing). Exclusion Criteria: Not able to perform the measurements because of cognitive or physical impairments, ongoing intervention of breathing exercises.

Procedure and outcomes: All included patients will be evaluated for physical and psychological function, symptoms and HrQoL. The following measurements and questionnaires will be used:

Dependent variables (primary outcome):

Health-related Quality of Life (EQ-5D-5L), EQ VAS Breathing pattern by Respiratory Movement Measuring Instrument (RMMI)

Independent, confounding and possible moderating variables:

Inspiratory and expiratory muscle strength (MIP and MEP) (Micro-RPM) Chest mobility by thoracic expansion Six-minute walk to measure endurance (in meters) Spirometry Diaphragmatic ultrasound End tidal CO2 measured during exercise

Physical Activity level (Frändin/ Grimby) Nijmegen questionnaire (dysfunctional breathing) COPD Assessment Test (CAT), questionnaire of symptoms related to breathing and now commonly used for this group of patients Dyspnea (mMRC, Modified Medical Research Council, Dyspnea Scale and BORG CR10) Patient Health Questionnaire (PHQ-9) Generalized Anxiety Disorder 7-item scale (GAD-7) Breathing Pattern Assessment Tool (BPAT)

• Maximal Inspiratory Pressure (MIP) [Time frame: Assessment will be applied only once and takes about 5-10 minutes to be completed.]
• Maximal Expiratory Pressure ( MEP) [Time frame: Assessment will be applied only once and takes about 5-10 minutes to be completed.]
• Chest mobility [Time frame: Assessment will be applied only once and takes about 5 minutes to be completed.]
• Six-minute walk test (6MWT) [Time frame: Assessment will be applied only once and takes about 15 minutes to be completed.]
• Spirometry [Time frame: Assessment will be applied only once and takes about 30 minutes to be completed.]
• End tidal CO2 [Time frame: Assessment will be applied only once and takes about 15 minutes to be completed.]
• Physical Activity level (Frändin/ Grimby) [Time frame: Assessment will be applied only once and takes about 2 minutes to be completed.]
• Nijmegen questionnaire (dysfunctional breathing) [Time frame: Assessment will be applied only once and takes about 5-10 minutes to be completed.]
• COPD Assessment Test (CAT) [Time frame: Assessment will be applied only once and takes about 5-10 minutes to be completed.]
• Dyspnea [Time frame: Assessment will be applied only once and takes about 5 minutes to be completed.]
• Depression [Time frame: Assessment will be applied only once and takes about 5-10 minutes to be completed.]
• Anxiety [Time frame: Assessment will be applied only once and takes about 5-10 minutes to be completed.]