The Natural History of Hospitalized COVID-19 Patients

BACKGROUND:

As of the end of February 2020, the ASST of Monza, with its two hospital wards of Monza and
Desio, has treated 1433 COVID+ patients, of which 507 have currently been discharged (35.4%)
and 206 (14%) transferred to other Low-intensity care facilities.

The importance of observational studies is now known in many fields of medicine and the "real
life" data produced have become an integral part of the authorization dossiers by the
competent authorities to govern the introduction of new drugs: in particular, in a disease
such as that from COVID-19 in which the absence of specific anti-viral therapies prevents an
"ad hoc" cure, it becomes fundamental to identify and validate systems of stratification of
the risk of fatal events, in order to optimize health intervention measures.

METHODS AND STUDY DESIGN:

The study protocol provides the collection of clinical, diagnostic and therapeutic and
laboratory data consistent with the objectives of the study (CORE DATA SET) to which other
specific protocols and relative data will connect (DATABASE "leaf"). The data collection will
be performed on eCRF (RedCap platform) and the database will have the "stem and leaf"
structure, compatible with WHO indications regarding pandemic data collection.

CORE DATA SET:

The protocol presents two important aspects of innovation in its formulation and design:

1. The "stem and leaf" structure will allow to collect all the core data of the study
("stem") capable of describing the primary objective, that is the natural history of the
disease, thus providing an important contribution to knowledge, currently very scarce ,
the evolution of the disease;

2. the extreme heterogeneity of the pathology itself, the methods of spreading the
contagion and the problematic treatment of some particular patient populations, however
impose the description and the potential validation, not only in the context of subgroup
analyzes, but in studies dedicated, of the data collected The "stem and leaf" design
could therefore answer both questions.

BIOLOGICAL SAMPLE COLLECTION:

The biological research areas that the protocol proposes to pursue are listed below:

1. Study of genetic determinants of COVID-19 infection with the aim of identifying the
bases of the different susceptibility in relation to age, sex and presence of
co-morbidity;

2. Study of the repertoire of B and T lymphocyte receptors and identification of the
virus-specific sequences of the T receptor for the antigen with the aim of identifying
the component of the viral genome relevant to the immune response with possible relapses
for the development of a vaccine;

3. Study of the activation of the inflammosome responsible for the abnormal and severe
inflammatory response characteristic of patients with COVID-19 infection and serious
lung complications with the aim of identifying possible specific targets of intervention
against one or more inflammatory cytokines;

4. Study of the serological response during the acute phase of the disease and
convalescence with the aim of defining the possible state of protection from the disease
itself;

5. Study of the proteome with the aim of defining biomarkers capable of evaluate the risk
of progression.

STATISTICAL ANALYSIS:

For each specific protocol, the study design and statistical data analysis plan will be
formulated according to the specific objectives. In general, in addition to the descriptive
methods, statistical regression models and methods for the definition of prognostic scores
will be used, with relative cross-validation, which will allow to evaluate both binary and
survival outcomes (in a broad sense, of events considered in time).