Design:

The present study will be a laboratory study. The intervention group being persons suffering
from Long COVID, and the control group being a healthy aged match group. Both the
experimental and control groups will be randomised into either performing uninterrupted or
interrupted sitting first to reduce the risk of order and learning effects associated with
the trials. All individuals who are identified from general practitioner (GP) practices (e.g.
Park and St Francis Surgery, Chandlers Ford near Winchester or associated surgeries and
clinics) or long COVID clinics (e.g. Gloucestershire Health and Care NHS (National Health
Service) Foundation Trust, Post Covid Syndrome Service and Southampton and Isle of Wight Long
Covid Clinic, Solent NHS Trust, Southern Health NHS Trust and Isle of Wight NHS Trust), who
meet the inclusion criteria will be provided with equal opportunity to engage with the study
provided they are able to travel to either the University of Winchester or University of
Gloucestershire for assessment. Healthy participants who will form the control group will
also have equal opportunity to engage with the study providing they meet the inclusion
criteria and are able to travel to either the University of Winchester or University of
Gloucestershire for assessment.

The purpose and design of this study has been discussed with all members of the study team,
and at a Patient and Public Involvement (PPI) meeting, with people currently suffering from
Long COVID.

Recruitment:

Potential participants will initially be identified by the healthcare team at Park and St
Francis Surgery, the Gloucestershire Health and Care NHS Foundation Trust, Post Covid
Syndrome Service, Southampton and Isle of Wight Long Covid Clinic, Solent NHS Trust, Southern
Health NHS Trust and Isle of Wight NHS Trust or associated surgeries and clinics according to
study inclusion/exclusion criteria. The clinical team will gain documented verbal consent
from potential participants for their contact details to be provided to the research team at
the University of Winchester (Prof. James Faulkner, Dr Helen Ryan-Stewart and Mr Nick Hudson)
and University of Gloucestershire (Dr Simon Fryer, Dr Keeron Stone and Mr Callum Thomas) who
will then contact patients directly to discuss their potential participation.

As described above (Design), the research team will make every effort to provide all
participants a fair and equal opportunity to engage with the study provided they are able to
travel to the University sites for study participation.

Informed Consent:

Participants will be provided with a study information sheet which outlines their possible
involvement and will have opportunities to discuss the study with the research team prior to
deciding as to whether to participate or not. Each participant will have had sufficient time
(>24-hours) to read the information sheet and will be able to ask questions to the research
team both by phone prior to attending their first assessment visit and upon arrival to the
Exercise Physiology Laboratory at the University of Winchester or University of
Gloucestershire before providing voluntary written consent for participation in this study.
Participants will be reminded that they can withdraw from the study at any time and without
repercussion of any kind.

Procedures:

All participants will complete an adapted health history questionnaire and the EQ-5D-5L
quality of life questionnaire during familiarisation. Participants will be fitted with an
activity monitor for seven days following familiarisation to attain measures of physical
activity/sedentary behaviour during a typical week. Participants with long COVID will be
asked to complete a series of questionnaires which measure the type and severity of their
symptoms as well as their functional status (COVID-19 Yorkshire Rehabilitation tool, COVID-19
symptom score, Post COVID-19 Functional Status Scale). Central and peripheral blood pressure,
pulse wave velocity, cognitive function and cerebral perfusion will be measured in a supine
and seated position at baseline and following 120 minutes of interrupted or uninterrupted
sitting. Central and peripheral blood pressure, pulse wave velocity and cerebral perfusion
will be measured while seated during the sitting period. Following visiting the laboratory,
long COVID participants will complete the DePaul Symptom Questionnaire Post-Exertional
Malaise (DSQ-PEM) and receive a telephone call from the research team within 72 hours of
their visit. Should participants present symptoms of PEM, their participation in future
visits to the laboratory will be delayed. Should symptoms of PEM persist for 30 days they
will be withdrawn from the study and their GP will be contacted.

Confidentiality:

Participants will be assured of the confidentiality of the research process. All data will be
anonymised using alpha- numeric code which will be stored on a password protected network,
accessible by only the named researchers involved with the study. Hard copies of data will be
locked in a filing cabinet in the office of Prof. James Faulkner in Centre for Sport of the
University of Winchester's King Alfred campus and in Dr Simon Fryer's locked office at the
Oxstalls campus at the University of Gloucestershire. Physical copies of data will not be
removed from these offices. Due to collaboration, data will need to be shared between
institutions. Data will be uploaded to a secure, password protected folder on Microsoft
OneDrive. All data will be presented as group means and standard deviations. All data will be
kept for 7 years, with Prof. Faulkner and Dr Fryer responsible for its security during this
time and its appropriate disposal once this period has elapsed.

Risks/Burdens:

Potential risks to participants could be caused by over exertion during a physical activity
intervention within the experimental condition. To minimise this risk, the type and intensity
of physical activity chosen is low and comfortable to complete for participants with low
levels of mobility and who experience fatigue after minimal activity. Participants will have
up to 30 days between visits to further minimise any risks. In addition, participants will
undertake the Covid 19 Yorkshire Rehab Screen (C19-YRS). This will allow the researchers to
gain prior knowledge of participants level of fatigue, mobility, and cognitive function prior
to involvement in the study and participant selection.