Host Response Mediators in Coronavirus (COVID-19) Infection

Purpose: To determine whether angiotensin II receptor blockers (ARBs) decrease severity or
mortality in hospitalized COVID-19 infected adults.

Main Hypothesis: Modulation of ACE2 by ARBs decreases the need for hospitalization, severity
(need for ventilation, vasopressors, extracorporeal membrane oxygenation or renal replacement
therapy) or mortality of hospitalized COVID-19 infected adults.

Secondary Hypotheses:

- Plasma angiotensin I and II and other biomarker levels are associated with effectiveness
of ARBs in hospitalized COVID-19 adults

- Modulation of ACE2 by angiotensin type I receptor blockers is associated with decreased
rate of hospitalization for COVID-19

- In patients already on ARBs when they are hospitalized continuing ARBs is associated
with decreased World Health Organization (WHO) COVID-19 ordinal outcome scale

Justification: The COVID-19 epidemic continues to grow exponentially affecting over 71,429
individuals with 1775 deaths (February 17, 2020), mostly in China but also in other
countries. The population mortality rate is 2% (lower than SARS (10%) and MERS (36%) but is
10% in hospitalized and 24% in ICU-admitted COVID-19 patients in China. Recent data from
China (not yet public domain) suggest ICU mortality is higher (J. Marshall personal
communication). Interventions to date include quarantine, isolation and usual clinical care.
There are no proven antiviral or host modulating interventions for COVID-19. Notably,
critically ill COVID-19 patients have similar mortality rates as sepsis and acute respiratory
distress syndrome. Cohort studies have shown that patients already on angiotensin-converting
enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have lower sepsis
mortality. Angiotensin II worsens lung injury in influenza models because ACE2 is
downregulated in H1N1, H5N1, H7N9, and SARS viral infections leading to increased angiotensin
II. Angiotensin II levels are increased in human influenza and are associated with influenza
viral load, disease progression and mortality. Preliminary data shows ARBs limits lung injury
in murine influenza H7N9, as well as viral titre and RNA. ARBs could limit viral titre and
organ injury in COVID-19.

Research Design:

Prospective clinical chart review: we will collect clinical data on the participant
throughout their hospital stay. Includes collection of baseline characteristics such as age,
sex, heart rate, respiratory rate, temperature, blood pressure, SaO2, respiratory
(PaO2/FiO2), renal (creatinine) and hepatic (bilirubin) function, use of oxygen,
vasopressors, ventilation and RRT. They will be followed daily throughout their hospital
stay, until death or discharge. Using left over clinical blood collected upon admission to
hospital, plasma angiotensin I and II and other biomarker levels will be measured in our
research laboratories.