Five years after the start of the COVID-19 pandemic, it has been estimated that a mean of
10-20% of COVID-19 patients will develop Long COVID, which represents at least 65 million
people worldwide. In Luxembourg, based on the current status of the COVID-19 pandemic and
the prevalence of Long COVID in other countries, we estimate that approximately 25,000
individuals may have been affected by Long COVID.

People with Long COVID (PWLC) present complaints such as tachycardia, extreme fatigue,
dyspnea, and inability to perform daily physical tasks. More than 200 symptoms have been
associated with Long COVID, and multiple organs are affected. Our previous work showed
that 59% of COVID-19-infected people from the PrediCOVID cohort study reported 1 or more
persisting symptom(s) after one year. The number of persisting symptoms increased with
the initial disease severity, and the quality of life of those participants was notably
impacted by sleep disorders (54%) and compromised respiratory function (12.9%).
Nonetheless, individuals with an initially asymptomatic or mild form of COVID-19
infection could also be affected.

Long COVID care, as for other chronic diseases, should align with the concept of
minimally disruptive medicine, aiming for a reduced burden on patients' lives while
maximizing health outcomes. PWLC frequently have several healthcare professionals in
charge of different aspects of their care, with many appointments and travels to manage.
They are also regularly asked to complete long standardized questionnaires or scales to
evaluate their symptoms, which generates an avoidable burden on their lives if care is
not coordinated. The development of innovative methods to integrate multiple Patient
Report Outcomes in a portable, versatile way, to reduce travels for medical care, and
overall for remote health's monitoring is therefore of the highest importance.

Few existing apps that could meet the needs of PWLC already exist, such as "Visible" or
"Living With". However, these apps are only available in the US and in the UK,
respectively. Furthermore, the "Living with" app is available only by invitation. This
limits their availability for PWLC in Europe. Some other apps designed for other chronic
conditions, like myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) Pacing app,
are also used by some PWLC to manage their daily energy levels. However, these apps do
not fully meet the specific needs of PWLC, and are only available in specific countries,
in English, and some of them only on the iOS operating system, which restricts their
potential use.

Voice is a promising candidate increasingly used in mobile health (mHealth) interactions
in chronic diseases. Voice is an easy and cheap medium to collect and can be easily
integrated into a device like a smartphone, now widely used by people of different ages
and education levels. It can be used for vocal biomarker assessment as new clinical
endpoints for relevant symptoms. Vocal biomarker candidates have already been identified
by the Deep Digital Phenotyping (DDP) research team, based on data from the PrediCOVID
cohort study, with performances above 80% to detect fatigue, loss of taste and smell, and
symptomatic status in COVID-19-infected people. However, further progress is required
before these vocal biomarkers can be used in clinical practice. New vocal biomarkers of
global health status or of other symptoms need to be developed to allow a more
personalized monitoring of PWLC.

The LIH developed the Long COVID Companion app based on the results of UpcomingVoice
co-design study and in collaboration with the ApresJ20 Long COVID patient association in
France. The app is the result of a participative process involving patients and
healthcare professionals in charge of PWLC patients. App users can monitor their health
and symptoms on a daily basis or at the frequency they want. App also offers the
possibility to complete a daily life and a medical diary, a voice journaling, and to
generate PDF reports with graphical visualization of symptom evolution. A new module
dedicated to research with standardized voice recordings has been integrated in the app
for the users who will take part in the present study The app was released in April 2024
and has more than 1700 users as of the end of March 2025.

It is of highest importance to assess the evolution of health of PWLC for a better
understanding of the disease. Results will allow the development of personalized
monitoring strategies by identifying vocal biomarkers of Long COVID symptoms and of the
global health of PWLC.

As fatigue is the most frequent and impairing symptom of PWLC it is crucial to better
understand the drivers of fatigue and to develop monitoring strategies.

The objectives of this study are :

Primary objective: To develop vocal biomarker candidates for the main Long COVID symptoms
(fatigue, brain fog, respiratory problems, sleep issues, stress, anxiety,..) in a
population of people with Long COVID.

Secondary objectives:

- to assess the intra-individual longitudinal evolution of voice characteristics of
people with LC

- to assess app usability and acceptability in the long-term.