The spread of an infectious disease caused by a new coronavirus towards the end of 2019 (COVID-19) has become a global pandemic, threatening the health systems of all countries, with heavy health, social and economic consequences. The pandemic has hit South Tyrol very hard with a very high incidence of COVID-19: >2700 cumulative cases and ~300 deaths as of early August 2020 were registered. The recent survey by the national institute of statistics, ISTAT, has ranked South Tyrol the third among all Italian regions, with 3.3% of all inhabitants showing antibodies to SARS-Cov-2. The unpreparedness of the health care systems both in identifying cases early and in containment of infected persons along with contact tracing, the difficulty in distinguishing symptoms of COVID-19 from those of other respiratory infections including influenza, and the high prevalence of cases with light symptoms has led to a spread of the disease. In addition, asymptomatic patients may exist whose true number and role in the pandemic are largely unknown.

Knowing the real prevalence of the disease is fundamental to get insights into the epidemiology and spread of the infection and to provide a basis for political and health system decisions to develop and guide processes that help to combat the expansion of the infection while avoiding unnecessary restrictions. Furthermore, knowing the prevalence is essential to determine the utility of testing strategies, especially now when commercial serological tests are becoming available to the population.

It is also of primary importance to answer several unsolved questions such as the number of secondary transmissions, the extent of within-family transmissions, the efficacy of isolation precautions and specific epidemiological interventions, the duration of immunity of positive cases, and the identification of genetic, endogenous, and environmental factors that determine COVID-19 course and severity.

Within the immunological aspect, which is at the very core of COVID-19 disease, the role of innate immunity is becoming central to the debate: while serological tests reflect only a small part of the immune system reaction to SARS-Cov-2, there is lack of data on the innate immune system activity, which is suspected to cover a larger part of the response. In our proposed research plan, we aim at addressing this knowledge gap.

To address these aims, the Eurac Research Institute for Biomedicine in Bolzano/Bozen has established a multistep collaborative proposal to address the important questions associated with the COVID-19 pandemics. This collaboration involves three partners: the Eurac Research Institute for Biomedicine, specifically, the Cooperative Health Research In South Tyrol (CHRIS) study, directed by Prof. P. Pramstaller and Dr. C. Pattaro at Eurac Research, which will be the main resource exploited in this project; the South Tyrolean Health Authority (SABES), specifically the Val Gardena COVID-19 study directed by Prof. Dr. M. Mian (Hematology Department, Central Hospital of Bolzano), and the Medical University Innsbruck (MUI), specifically the study on COVID-19 in- and out-patients directed by Prof. G. Weiss (Department of Internal Medicine, MUI). The collaboration will allow to obtain an overall representation of COVID-19 in all environments and population groups through the analysis and integration of data from three different but complementary contexts: [1] the general population of a seemingly low prevalence area, the Val Venosta/Vinschgau; [2] the general population of a high prevalence area, the Val Gardena/Gröden; [3] a patient cohort collected at the Medical University Innsbruck.