To main content To main navigation
Research building

Methods

Study population and study area

The study is carried out amongst residents of the Northern Provinces of the Netherlands (Groningen, Friesland, Overijssel and Drenthe) comprising around 1.7 million inhabitants. The study design is fully described in Tami et. al. (2022).  Laboratory confirmed SARS-CoV-2 infected individuals of all ages (index cases) that do not merit hospitalisation, and their household (HH) members, were invited to join the study and enrolled after signing a written informed consent. Consenting parents/guardians of infected children (>16years) signed the informed consent form. The complete HH, i.e. all persons (contacts) living in the same home, was to join the study at enrolment. If this requirement was not fulfilled, the HH was excluded from the study.

Inclusion criteria of index participant

The index participant was the first laboratory-confirmed SARS-CoV-2 infected individual of any age identified in a HH and invited to join the study together with the complete HH.  The requirements for inclusion were:

  • Onset of symptoms <5 days before inclusion
  • Positive diagnostic RT-PCR for SARS-CoV-2 performed within 48h of inclusion
  • Index person should supply all required samples in the protocol for the duration of the study
  • All HH members should join the study
  • Signing of informed consent form.

Study design

An ongoing prospective longitudinal observational study of SARS-CoV-2 infected individuals that did not require hospitalisation and their HH members was initiated on March 2020, at the start of the pandemic in the Netherlands. Enrolled individuals comprised the identified laboratory COVID-19 index positive patients plus all their HH members.  Patients were followed daily at home approximately during 3 weeks post-infection to characterize their acute clinical phenotype (fig 1 and 2), and were followed at 3, 6, 12, 18 and 24 months to determine their long-term clinical and serological evolution. During the follow-up, clinical data and different types of samples were collected, as shown below (Fig 2)
COVID HOME inclusion criteria
Fig 1: Acute and long-term follow-up of participants enrolled in the COVID HOME study
COVID HOME Sampling Flowchart
Fig 2: Sampling flowchart in the acute phase

Case report forms

The following CRF/eCRFs were applied to infected individuals (Fig 3):

  • A self-completing clinical questionnaire (CRF-02) was given to patients at enrolment to record socio-demographic data, comorbidities, treatment and daily clinical history (symptoms and signs) during at least 21 days, and further if symptoms were still present. Participants still negative by RT-PCR but presenting symptoms were encouraged to fill this form as well.
  • An individual HH questionnaire (CRF-03) was applied at enrolment to record socioeconomic characteristics, preventive measures, behaviour and intradomiciliary isolation measures taken.
  • A phone interview (CRF-04) was carried out at 21 days, and at 3 and 6 months to assess smell and taste alterations in detail in consenting individuals.
  • To evaluate the development of PVFS as part of the assessment of Long COVID, participants older than 16 years were asked to answer on Day 14 and then at 3-, 6-, 12- and 18-months post-infection to:
    • The fatigue screening questionnaire (eCRF-05) to establish presence or absence of fatigue/tiredness, length of time of fatigue/tiredness, and any loss of activity
    • Additional fatigue questionnaire (eCRF-06) to identify presence and severity of symptoms associated with development of PVFS
    • Health-related Quality of Life (RAND-36) questionnaire (eCRF-07) and to
    • the Hospital Depression and Anxiety Scale (HADS) questionnaire (eCRF-08)
  • At 3-, 6-, 12- and 18-months post-infection, both adults and children receive eCRF-10 to assess Long COVID related symptoms, new comorbidities and re-infection.

CRF-02 and CRF-03 were given to participants to fill in paper while the rest were eCRFs and were answered online using the REDCapTM (Research Electronic Data Capture) secure web-based software platform [45]. Automatic electronic reminders were set up. In case of failure to complete the eCRFs, participants were called to check if email addresses were correct or if any other issues had arisen.
COVID HOME Case Report Forms
Fig 3: Case report forms applied to SARS-CoV-2 infected individuals, except CRF-03 which is applied to all participants and CRF-10a which is answered by non-infected individuals.