*Viro-immunological, clinical and psychosocial correlates of disease severity and long-term outcomes of infection in SARSCoV-2 - a prospective cohort study*: *the VIS cohort study

Coronavirus disease 2019 (COVID-19) is caused by the coronavirus SARS-CoV-2
(hereafter named *COVID-19* virus) and is a rapidly spreading pandemic. Upon
infection, COVID-19 is accompanied with a significant morbidity and mortality,
in particular among those with comorbidities. The clinical picture in the
subgroup of patients that experience severe symptoms is characterized by an
exaggerated inflammatory response and ARDS (acute respiratory distress
syndrome). The host and viro-immunological factors that determine which
patients are at risk for the development of such severe disease are currently
unknown. It is unclear how SARS-CoV-2-specific immune responses are induced and
what role the innate and adaptive immune systems play in clearance of the virus
and disease severity. Furthermore it is unknown if and how lasting protective
immune response are induced and how the latter affect re-infection risk. In
addition, mid and long-term sequelae and their determinants are not yet known.

The majority of individuals clinically recover from COVID-19 but data are
lacking on the long-term effects of (re-)infection. It is unclear how
reinfections with SARS-CoV-2 are related to the durability of the SARS-CoV-2
specific immune response and what the impact of severe disease is on clinical
recovery, long term pulmonary function, quality of life and psycho-social
well-being.

The overall aim of the proposed project is to establish a longitudinal cohort
of adult patients who are infected with SARS-CoV-2, at different levels of
disease severity, ranging from mild illness to severe and life-threatening
disease requiring hospitalization and intensive care. These patients will be
followed in a study for one year after initial diagnosis of infection.
This cohort will be used (1) to identify socio-demographic, clinical,
virological and/ host factors predictive of disease progression, (2) to
Investigate the induction of lasting protective SARS-CoV-2-specific antibody
and SARS-CoV-2-specific T cell responses in relation to disease severity,
clinical recovery or re-infection over time and (3) to gather insight into the
clinical and socio-psychological sequelae of COVID-19. In addition, (4) to gain
insight in the immune response after vaccination (5) to investigate influenza
vaccine responses in the context of waning immunity after prolonged absence of
influenza circulation; (6) to establish a data- and biobank for future in-depth
pathophysiological, immunological, host-genetic and further clinical and
epidemiologic studies. The addition of a substudy on reinfections enables to
investigate (7) risk factors for SARS-CoV-2 reinfections in order to identify
populations at risk for reinfections (8) determinants of the longevity and
breadth of antibody- and T-cell mediated SARS-CoV-2 immunity and (9) the health
impact of SARS-CoV-2 reinfections or their sequelae in order to estimate the
impact on individual health and society.

The study is designed as a prospective observational cohort study. Patients are
enrolled in the AUMC and the GGD Amsterdam and will be followed during the
initial study for up to 2 year after diagnosis.
For the reinfections substudy, the time points of data and biological
collections are: S0 (October 2022), S3 (January 2023), S6 (April 2023), S9
(July 2023), and S18 (April 2024).
In total, participants will be followed for up to 4 years after diagnosis.

Several study visits will be required (while hospitalized, at GGD or at home).
Participants will be exposed to online questionnaires. In the first month,
detailed information on symptoms will be assessed by the investigator.
Thereafter, symptoms will be assessed monthly in a brief online questionnaire,
standardized validated questionnaires on quality of life will be included.The
risk of sampling (blood draw, feces collection, nasopharyngeal swabs, saliva
and brushes) is considered minimal. There is no direct benefit of participation
in the study for the patient. Regarding group relatedness, the sampling is
considered to be necessary since it is the only approach to accurately
investigate SARS-CoV-2 (re-) infection determinants and outcomes. This
knowledge will help understand risk of reinfection and risk of severe disease
progression for certain subgroups of patients (elderly, comorbidities,
immunodeficiencies etc), contributing to future guidelines and protocols aimed
at preventing spread and reducing severity of illness.