Background Very recent evidences support the hypothesis that the novel coronavirus 2019
(2019-nCoV) uses the SARS-1 coronavirus receptor ACE2 for gains entry into target cells.
Angiotensin receptor-blocker (ARB) drugs, one of the most commonly used antihypertensive
drug, typically increase ACE2 expression, often very markedly. With SARS-CoV-2 infection
increased ACE2 expression very definitely would not be beneficial, and could be adverse.
However, augmented ACE2 expression with ARB has been demonstrated in the kidneys and heart
but has not been tested in the lungs. So, the hypothesis that using of ARB or ACE inhibitors
(ACE-I) drugs during the COVID-19 may possibly be harmful is urgently to be verified in
epidemiological studies.

Aim To retrospectively test whether 2019-nCoV patients treated with ARB or ACE-I, in
comparison with patients who not, are at higher risk of having severe COVID-19 (coronavirus
infection disease 2019), including death.

Population Hospitalized patients with confirmed COVID-19 infection (any type).

Outcome The project will retrospectively collect data on the most severe manifestation of
COVID-19 occurred in 2019-nCoV infected patients during hospitalization. Severity will be
classified as: hospital discharge with healing, asymptomatic, mild complications but not
pneumonia, not severe pneumonia, severe pneumonia, acute respiratory distress syndrome (ARDS)
and death. Classification of pneumonia will follow WHO (World Health Organization) criteria.
Data on severity will be obtained from medical record at one-point time (at the moment of
inclusion in the study).

Exposure Treatment for ARB or ACE-I. When available, type of drugs will be recorded.

Study design Patients will be divided in two groups, a) controls: individuals who did not
develop severe COVID-19 respiratory disease (including individuals who recovered from the
infection) and b) cases: individuals who developed severe COVID-19 disease (including fatal
events). Association between use of ACE-I or ARB and severity of COVID-19 will be assessed by
using of multivariable logistic regression analysis. Data on potential confounders will be
obtained by medical records: age, sex, time intervals from hospital admission to worse
manifestation of COVID-19 and to eventual death or recovering, smoking, body mass index,
history of myocardial infarction, diabetes, hypertension, cancer, respiratory disease, other
morbidities, creatinine, insulin, glomerular filtration rate together with use of
Tocilizumab, anti-aldosterone agents, diuretics, Kaletra, cortisone, Remdesivir,
Hydroxychloroquine, Sacubitril or Valsartan.