Long-term consequences of more severe COVID-19 infections (complicated respiratory tract infections), in patients managed in general practice and risk factors for a delayed recovery

Much is unknown about long-term prognosis of patients that are treated in
primary care with complicated COVID-19 respiratory tract infections.
Complicated COVID-19 respiratory tract infections in hospitalized patients can
cause long lasting lingering symptoms, both somatically and psychologically.
The long term impact of complicated COVID-19 respiratory tract infections
managed at home is still unknown. General practitioners, however, frequently
report patients with long-term symptoms. Knowledge on the prognosis of patients
with a complicated COVID-19 respiratory tract infection and identifying
patients at risk for long-term symptoms is important in order to improve
follow-up and adequate support of these patients. Ongoing fundamental research
focusses on the role of cellular markers on the prognosis of patients with
complicated COVID-19 respiratory tract infections. Amongst other markers,
neutrophil CD10 (neuCD10) has been found to be a relevant cellular marker.
Expression of neuCD10 is decreased in both hospitalized and non-hospitalized
patients with a complicated COVID-19 respiratory tract infection. NeuCD10 poses
the function to reduce the level of bradykinin, a key enzyme in the development
of pulmonary edema. Whether these reduced neuCD10 levels are still present
after disease resolution and whether neuCD10 levels correlate with long-term
symptoms has yet to be determined.

The primary objective of this study is to determine the difference in the
health-related quality of life (determined by SF-36) between patients with and
without an established SARS-CoV-2 infection in a 12 month follow-up period in
patients managed in general practice with more severe suspected COVID-19
infections (complicated respiratory tract infections), and to determine risk
factors that influence recovery.
Secundairy objectives are to assess in patients who were suspected of having
serious COVID-19 infections: differences in the different sections of the
SF-36 from index consultation to 12 months after the index consultation, the
severity and duration of physical complaints and risk factors that influence
recovery, the number of episodes of respiratory infections requiring antibiotic
prescription, exacerbations of chronic disorders, hospital referrals, mortality
within 12 months, number of contacts with GP, the extent of mental complaints
or mental disorders and impact on daily activities.
Additionally, the objective of the sub-study is to determine neuC10 expression
in subjects more than two years after a complicated at home COVID-19
respiratory tract infection to explore whether neuCD10 levels are still
decreased and whether neuCD10 levels are related to long-lasting complaints
after a more severe COVID-19 infection managed in primary care.

Observational study

Risks/disadvantages: Risks for the participants are negligible. The only
invasive procedures performed are one or two venipunctures, which are low risk
procedures. Moreover, the second venepuncture will only be performed in a
subset of the included subjects (those with positive SARS-CoV-2 serology).
Besides, it will take time (about 30-45 minutes) from participants to complete
the follow-up interviews every 3 months, for a period of 1 year. The additional
questionnaire of the substudy will take even less time (10-20 minutes). The
burden of completing these questionnaires is estimated to be low, as the time
interval is relatively long and the nature of the questions not burdensome.
Benefits: Participant can, if they whish, be informed on their SARS-CoV-2
status at the end of the study. There are no compensations for participants.
In summary: benefits are in balance with disadvantages of the study. Risks for
participants are negligible.