Observational Study of COVID-19 Treatment Efficacy

Background:

Several studies have indicated a potential role for Hydroxychloroquine in the treatment of
COVID-19 as caused by the SARS-CoV-2 virus. Hydroxychloroquine has demonstrated potent
inhibition of SARS-CoV-2 in vitro. Hydroxychloroquine and azithromycin together have
significantly reduced SARS-CoV-2 viral carriage over 6 days compared to a placebo and
COVID-19 patients who received a 5 day regimen of 400mg/day of Hydroxychloroquine had
significantly shortened times to clinical recovery characterized by improved pneumonia
compared with patients who did not receive Hydroxychloroquine.

Within OSF Healthcare approximately 50% of SARS-CoV-2 infected patients are currently
receiving some form of Hydroxychloroquine during the course of their hospitalization. The
utilization of this treatment has been approved by the FDA based upon the limited data
available.

Significance:

The optimal treatment regimen for COVID-19 patients has yet to be defined. Several small
studies have indicated a potential role for the utilization of Hydroxychloroquine in the
treatment of SARS-CoV-2 infected patients. However, very little evidence exists around the
optimal treatment regimen and efficacy with regard to tangible outcomes. This observational
retrospective/prospective chart review study aims to help provide epidemiological data that
may help to provide guidance to clinicians for both future patients, as well as provide
clinicians guidance for study design of more definitive controlled studies. Given the rapid
spread of this disease, the high mortality rate associated with it and the impact of the
disease upon society this study is anticipated to have the potential to contribute
significantly to the treatment of SARS-CoV-2 infected patients.

Study Design and Methodology:

The study will be a retrospective/prospective observational study of cohorts of hospitalized
patients across the OSF Healthcare System who have tested positive for SARS-CoV-2 and exhibit
signs or symptoms of respiratory distress during the course of their hospitalization. The
outcomes of patients who both receive and do not receive Hydroxychloroquine will be compared,
with particular attention to the timing of administration in relationship to the onset of
respiratory distress. Respiratory distress will be defined as a low SpO2, an elevated
respiratory rate or an increased oxygen demand. Hydroxychloroquine administration will be
defined as a documented administration of the medication on the patient's medication
administration record (MAR). Administration of Hydroxychloroquine prior to the onset of
respiratory distress, administration of Hydroxychloroquine on the day of respiratory distress
and administration of Hydroxychloroquine following the onset of respiratory distress will all
be assessed and compared across three outcome metrics; progression to an ICU location of
care, progression to ventilator support and mortality.

- Patients at all OSF HealthCare locations across the Ministry that meet
Inclusion/Exclusion criteria will be cohorted by:

- Hydroxychloroquine administered - yes (including the date started)

- Hydroxychloroquine - no

- For the Hydroxychloroquine administered - yes cohort, further subdivide into 3 cohorts:

- Hydroxychloroquine date started was before the date recorded for signs of
respiratory distress

- Hydroxychloroquine date started was the same as the date recorded for signs of
respiratory distress

- Hydroxychloroquine date started was after the date recorded for signs of
respiratory distress

- At this point the investigators would have 4 cohorts:

- Hydroxychloroquine - No

- Hydroxychloroquine date started was before the date recorded for signs of
respiratory distress

- Hydroxychloroquine date started was the same as the date recorded for signs of
respiratory distress

- Hydroxychloroquine date started was after the date recorded for signs of
respiratory distress

- These 4 cohorts would be compared to determine any difference in the following metrics:

- Mortality

- ICU Admissions

- Ventilator use

- Additional study of additional treatment regimens using a similar design may be repeated
for the following treatments

- Hydroxychloroquine + Azithromycin

- Remdesivir (This is a compassionate use medication with very limited use in OSF.
Observational study of this would be significantly limited and therefore unlikely
to be undertaken)

- Non-steroidal anti-inflammatories (some indication that these lead to poorer
outcomes)

Study Procedures:

OSF Data Analytics will pull reports of confirmed positive COVID-19 subjects. The data will
be kept securely on password-protected computers and analyzed by applicable research
personnel listed on this study.

Data Use and Management:

1. Results of this study will be presented within OSF Healthcare at national meetings
and/or published in academic journals. The investigators will not disclose any subject
PHI or identifying personal information in any presentation or publication about the
study.

2. The study investigators will be responsible for data safety monitoring. This is an
observational study which only involves data collection from the hospital/institutional
sources (e.g., hospital notes, office visit notes,). This study does not dictate any
specific surgical treatments or medications. All procedures performed on the patients
are standard of care and the study does not involve any additional hospital visits for
subject or the parents/guardians. Data that will be collected from patient records will
be securely stored on password-protected computers accessible only by applicable
research personnel.

Data Analysis:

Data analysis will be performed by the PI and applicable research personnel.

Oversight and Ethics:

This study will be conducted in compliance with the Peoria IRB research policies and
procedures and all applicable laws and regulations. The staff members will perform the study
in accordance with the protocol, and will report unexpected problems in accordance with the
Peoria IRB policies and procedures and applicable laws and regulations. Collection,
recording, and reporting of data will be accurate and will ensure the privacy, health, and
welfare of research subjects during and after the study.

Privacy and Confidentiality:

Study staff will maintain the highest degree of confidentiality permitted for clinical and
research information obtained from the participants. Medical and records will be maintained
in the strictest confidence. However, as a part of the quality assurance and legal
responsibilities of an investigation, the clinical site must permit monitoring
representatives of various governing facilities to examine clinical records for the purpose
of quality assurance reviews, audits, and evaluations of the registry safety and progress.
Unless required by the laws that permit copying of records, only the coded identity
associated with documents or with other participant data may be copied (and all personally
identifying information must be obscured). Authorized representatives as noted above are
bound to maintain the strict confidentiality of medical and research information that is
linked to individuals. The clinical site will normally be notified before auditing visits
occur.

Risks:

The main risk in this study is the potential breach of privacy and loss of confidentiality.
There is minimal risk of likelihood of harm. All reasonable safeguards to secure the
confidentiality of information will be taken by the investigators and their research
personnel.