The primary objective of this study is to establish differences in susceptibility to SARS CoV-2 infection among health care workers (HCW) highly exposed to patients with COVID-19 diagnosis. To ascertain this issue, we evaluated:

• Changes in receptor polymorphism (ACE2 and CD26 receptor study.
• SARS-CoV-2 CD4/CD8 T cell response (CTL)
• Different KIR phenotypes

Only 24% of health care workers (HCW) had developed inmunological response to SARS CoV-2 infection in one centre attending thousands of COVID-19 patients, and with shorteness of personal protective equipments. Our hypothesis is that this relatively low number of infected HCW could be secondary to:

1. Differences in susceptibility to infection mediated by changes in viral receptors. Thus, it is important to characterize and genotyping the main receptor for SARS-CoV-2, ACE2, and other related receptor, such as CD26.
2. Increased cellular immune response, offering cross-immunity against SARS CoV-2 infection by previous exposure to other coronavirus or respiratory pathogens. A specific CD4/CD8 T cell response to viral peptides could respond this question
3. Specific KIR phenotypes (Killer Immunoglobulin-like Receptors): Natural killer cells (NK) response to alterations of class I HLA molecules presented in infected cells. An increase in class I HLA expression could lead to an increase in NK activation by increasing its ability to produce IFN-gamma.

Inclusion criteria

• HCW older than 18 years
• Highly exposed to COVID-19 according to the definition
• Negative (cases) or positive (controls) serology against SARS-CoV-2 infection Exclusion criteria
• Presence of any disease / treatment which could alter the susceptibility (corticoid therapy, chemotherapy, monoclonal antibodies)
• Pregnancy

High exposure definition: direct and continued care of COVID-19 diagnosed patients for 2 weeks or more, without aerosol- generating procedures, with inappropriate personal protective equipment (PPE), or unprotected exposure to patients with COVID-19 during aerosol-generating procedures.

The definition of appropriate PPE was based on previous recommendations. The absence of any part of the PPE constituted an unprotected exposure. We defined the following as aerosol-generating procedures: airway suction, application of a high-flow O2 instrument, bronchoscopy, endotracheal intubation, tracheostomy, nebulizer treatment, sputum induction, positive pressure ventilation, manual ventilation and cardiopulmonary resuscitation.

• Cases: HCW highly exposed to COVID-19 diagnosed patients (see definition) who remained free of symptoms of disease and had a negative serology against SARS-CoV-2 (both IgG and IgM)
• Controls: HCW highly exposed to COVID-19 diagnosed patients who had suffered the infection and/or had presence of antibodies in the serological test, paired by sex and age (5 year interval)

Data about receptors could be shared with other investigators about the susceptiblity to SARS CoV-2 However, KIR phenotypes should be shared after ethical comitee approval