A Retrospective Observational Non-Interventional Study (NIS) to Assess Patient Characteristics and Healthcare Resource Use (HRU) Among COVID-19 Patients With or Without Nirmatrelvir/Ritonavir (PAXLOVID™) Treatment in the Kingdom of Bahrain.
Conditions: COVID-19
Sponsor: Pfizer

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NON-INTERVENTIONAL (NI) STUDY PROTOCOL
Study Information
Title
A Retrospective Observational Non-Interventional 
Study (NIS) to assess Patient Characteristics and 
Healthcare Resource Use (HRU) among COVID-19 
Patients with or without Nirmatrelvir/Ritonavir
(PAXLOVID™) treatment in the Kingdom of Bahrain.
Protocol number
C4671050
Protocol version identifier
1.0
Date
16 November 2023
Active substance
PF-07321332; ATC code J05AE30
Medicinal product
nirmatrelvir; ritonavir (PAXLOVID™)
Research objectives
Primary objective:
1. To describe the baseline demographic and 
clinical characteristics, including pre-existing 
comorbidities, of adult COVID-19 patients 
treated with and those not treated with 
nirmatrelvir, ritonavir.
Secondary objectives:
1. To evaluate the number and proportion of 
COVID-19 patients who meet the most up-to-
date WHO recommendations for the use of 
therapeutics in the treatment of COVID-19 (ie, 
version 14, published 10Nov2023) in 
comparison to Kingdom of Bahrain national
recommendations.
2. To assess adult COVID-19 patients’ HRU and 
outcomes within the 28-day period

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1. TABLE OF CONTENTS
1. TABLE OF CONTENTS.......................................................................................................3
2. LIST OF ABBREVIATIONS................................................................................................5
3. RESPONSIBLE PARTIES....................................................................................................8
4. ABSTRACT...........................................................................................................................9
5. AMENDMENTS AND UPDATES.......................................................................................9
6. MILESTONES.....................................................................................................................10
7. RATIONALE AND BACKGROUND................................................................................10
8. RESEARCH QUESTION AND OBJECTIVES .................................................................12
9. RESEARCH METHODS ....................................................................................................12
9.1. Study Design ...........................................................................................................12
9.2. Setting......................................................................................................................13
9.2.1. Inclusion Criteria ........................................................................................13
9.2.2. Exclusion Criteria.......................................................................................13
9.3 Variables...................................................................................................................13
9.4. Data Sources............................................................................................................14
9.4.1. EHR Database.............................................................................................15
9.5. Study Size................................................................................................................20
9.6. Data Management ...................................................................................................20
9.6.1. Case Report Forms .....................................................................................21
9.6.2. Record Retention ........................................................................................21
9.7. Data Analysis ..........................................................................................................22
9.8. Quality Control........................................................................................................23
9.9. Limitations of the Research Methods......................................................................23
9.10. Other Aspects ........................................................................................................23
10. PROTECTION OF HUMAN PARTICIPANTS ...............................................................24
10.1. Patient Information................................................................................................24
10.2. Participant Consent ...............................................................................................24
10.3. Institutional Review Board (IRB)/Ethics Committee (EC)...................................24
10.4. Ethical Conduct of the Study ................................................................................24
0

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11. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS ......................................................................................................................25
12. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS........26
13. REFERENCES ..................................................................................................................27
14. LIST OF TABLES.............................................................................................................30
15. LIST OF FIGURES ...........................................................................................................30
ANNEX 1. LIST OF STANDALONE DOCUMENTS ..........................................................30
ANNEX 2. ADDITIONAL INFORMATION.........................................................................31
ANNEX 3. IMMUNOCOMPROMISED ICD-10 CODE LIST..............................................38

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2. LIST OF ABBREVIATIONS
Abbreviation
Definition
AE
Adverse Event
AEM
Adverse Event Monitoring
ATC
Anatomical Therapeutic Classification
BMI
Body Mass Index
CDC
Centers for Disease Control
COPD
Chronic Obstructive Pulmonary Disease
CRA
Clinical Research Associate
CT
Computed Tomography
DDI
Drug-drug interaction
DPIA
Data Protection Impact Assessment
eGFR
Estimated Glomerular Filtration Rate
EC
Ethics Committee
EHR
Electronic Health Record
ER
Emergency Room
EUA
Emergency Use Authorization
FDA
Food and Drug Administration

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Abbreviation
Definition
GDPR
Global Data Privacy Rule
GPP
Good Pharmacoepidemiology Practices
HRU
Healthcare Resource Utilization
ICD-10
International Classification of Diseases-10th Edition
ICU
Intensive Care Unit
IPTW
Inverse Probability of Treatment Weighting
IMV
Invasive Mechanical Ventilation
IQR
Interquartile Range
I-SEHA
Kingdom of Bahrain National Health Information
System
ISPE
International Society of Pharmacoepidemiology
LOA
List of Abbreviations
LOS
Length of Stay
NIH
National Institutes of Health
NIS
Non-Interventional Study
PCR
Polymerase Chain Reaction (COVID-19 test)
POS
Place of Service

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Abbreviation
Definition
PSM
Propensity Score Matching
RCSI
Royal College of Surgeons in Ireland
RQ
Research Question
SD
Standard Deviation
STROBE
Strengthening the Reporting of Observational
Studies in Epidemiology
US
United States
VOC
Variant of Concern
WHO
World Health Organization 
YRR
Your Reporting Responsibilities
09

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6. MILESTONES
Milestone and/or Deliverable Description
(Provider must use Pfizer CT24 designated
templates for Study Deliverables)
Planned Timeline/Dates
Draft study protocol
19 February 2023
Final study protocol
30 November 2023
Start of data collection
15 January 2024
End of data collection
15 February 2024
Start of data analysis
15 March 2024
End of data analysis
31 April 2024
Final Study Report
15 June 2024
7. RATIONALE AND BACKGROUND
In December 2019, COVID-19 was identified as a new, potentially fatal, respiratory infection
caused by the novel coronavirus, SARS-CoV-2. The WHO declared COVID-19 a Public
Health Emergency of International Concern1 on 30 January 2020 and further characterized
the disease outbreak as a pandemic on 11 March 2020.2 As of 01 January 2022, more than 
289,000,000 cases have been confirmed worldwide, and at least 5,440,154 deaths have 
occurred.3 Despite widespread use of COVID-19 vaccine since 2020 in Bahrain, COVID-19
caused 702830 cases, 26194 hospitalizations and 1546 deaths during the period 2020-2023 in 
Kingdom of Bahrain.
The clinical presentation of COVID-19 varies widely, ranging from an asymptomatic 
infection to critical illness characterized by respiratory failure, septic shock and other 
multiple organ dysfunction or failure.4 Although the majority of cases are asymptomatic or 
mild,5 patients who are hospitalized with COVID-19 may have significant morbidity and 
mortality.6,7 Between February 2020 and September 2021, the United States CDC estimated 
that of a total of 146.6 million infections, 85% of patients were symptomatic and only 
5% required hospitalization for treatment.8
According to the NIH guidelines, management of non-hospitalized patients with acute 
COVID-19 should include supportive care, advise on when to contact a health care provider 
and seek an in-person evaluation, and COVID-19 specific therapy for patients who have a 
high risk of disease progression. 9 More specifically, non-hospitalized patients with
mild-to-moderate COVID-19 who are at high risk of clinical progression may receive (listed 
in order of preference) nirmatrelvir (PF-07321332)/ritonavir (Paxlovid™), sotrovimab, 
remdesivir, or molnupiravir.10

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Kingdom of Bahrain:
Kingdom of Bahrain is one of the leading countries in COVID-19 outpatient treatment care. 
A unique outpatient clinic has been established in May 2021 to provide outpatient care for 
patients with positive Coronavirus. Treatment including monoclonal antibodies such as 
Bamlamivimab, Regen-Cov, Sotorovimab and Paxlovid™are offered for all high-risk and 
close contact patients, such treatments are in line with the guidelines of the FDA. 
The clinic has a dedicated call center providing different services to ease the patient 
treatment process and provides follow-up care. The overall aim of the clinic is to target mild 
to moderate high risk COVID-19 patients and provide outpatient treatment as early as 
possible to reduce disease progression, including hospitalization and death.
On 01 January 2022, the National Health Regulatory Authority (NHRA) approved the 
emergency use of Paxlovid™for mild-moderate cases who are at high risk – identified as per 
WHO definition of high-risk group – of developing severe COVID-19. Since approval, 
Paxlovid™has been established as the first line therapy along with Sotrovimab in the 
Kingdom of Bahrain. 
In the EPIC-HR trial, Paxlovid™reduced the risk of hospitalization or death by 
88% compared to placebo in non-hospitalized adults with laboratory-confirmed SARS-CoV-
2 infection and a risk factor for progression to severe disease, when treatment was initiated
within 5 days of symptom onset.10,11 Other efficacies reported for COVID-19 therapies, 
include sotrovimab (ie, 85% relative reduction reported),10,12 and remdesivir (ie, 87% relative 
reduction reported)10,13 and molnupiravir (ie, 30% relative reduction reported).10,14
Furthermore, in vitro analyses, suggested that Paxlovid™is active against the 
B.1.1.529 (Omicron) variant of concern (VOC).15
COVID-19 has put significant pressure on the healthcare system worldwide and caused an 
enormous economic burden to society. While patient characteristics, healthcare resource 
utilization (HRU) and healthcare costs of patients hospitalized with COVID-19 have 
previously been described in US studies, 16-26 such data are limited among non-US
countries.27,28 Furthermore, while the majority of current research focuses on hospitalized 
COVID-19 patients, little is known about COVID-19 patients identified in an outpatient 
setting.
The availability of antiviral treatments in the outpatient setting, such as Paxlovid™, have
potential to complement vaccination strategies during the COVID-19 pandemic and further 
reduce the burden on healthcare system capacity in the short- and long-term. There is a need 
to identify patients in the real-world setting globally, who are diagnosed with COVID-19 and 
may be at an increased risk of healthcare resource utilization, as prior literature suggests 
these patients are most likely to benefit from outpatient therapies. With the authorization 
(ie, EUA) of Paxlovid™, there is also a growing need to complement clinical trial findings 
and address data gaps by generating real-world evidence that may help inform healthcare 
decision-making globally during this early EUA utilization phase. 

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This study aims to describe the characteristics, outcomes and treatment patterns of 
COVID-19 patients, who are receiving Paxlovid™in Bahrain according to the local drug 
label.
8. RESEARCH QUESTION AND OBJECTIVES
The aim of this study is to describe the baseline demographic and clinical characteristics, and 
HRU of adult (≥18 years) COVID-19 patients who have been prescribed nirmatrelvir, 
ritonavir treatment in the outpatient setting.
Primary objective:
1. To describe the baseline demographic and clinical characteristics, including 
pre-existing comorbidities, of adult COVID-19 patients treated with and those not 
treated with nirmatrelvir, ritonavir.
Secondary objectives:
1. To evaluate the number and proportion of COVID-19 patients who meet the most up-
to-date WHO recommendations for the use of therapeutics in the treatment of 
COVID-19 (ie, version 14, published 10Nov2023) in comparison to Kingdom of 
Bahrain national recommendations.
2. To assess adult COVID-19 patients’ HRU and outcomes within the 28-day period 
Exploratory objective:
1. To assess HRU and outcomes at day 5, 7 and 21 as exploratory analyses
9. RESEARCH METHODS 
9.1. Study Design 
This will be a retrospective observational cohort study of patients diagnosed with COVID-19
in the Kingdom of Bahrain. Treated patients are defined as those have been prescribed
nirmatrelvir, ritonavir and managed in the outpatient setting (eg, receiving medical treatment 
without being admitted to a hospital for COVID-19) while control group is those not treated 
with nirmatrelvir, ritonavir. Data will be from the I-Seha electronic medical records and 
descriptive analyses will be conducted for these two cohorts and will compare healthcare 
resource use in patients treated with nirmatrelvir, ritonavir and those not treated with 
nirmatrelvir, ritonavir.

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Table 1.
Cohort Definitions
Name
Criteria
Identification Period
Index Date
Follow Up 
Period
Treated 
patients
Patients diagnosed
with COVID-19 and 
treated with 
Paxlovid™
After Paxlovid™
availability during the 
same dominant variant 
(ie, Omicron or Delta 
etc.) era timeframe as 
Cohort 
Paxlovid™
prescription written 
date or dispense date*
If neither of the above 
are available, the 
COVID-19 diagnosis 
date may be used as the 
index date
28 -days 
follow up
Control 
group
Patients diagnosed
with COVID-19 and 
not treated with
Paxlovid™
After Paxlovid™ 
availability during the 
same dominant variant 
(ie, Omicron or Delta 
etc.) era timeframe as 
Cohort
Date of COVID-19 
diagnosis
28 -days 
follow up
*If both dates are available in the data source, the most recent date should be used as the index date for Cohort.
9.2. Setting
9.2.1. Inclusion Criteria
!
Patients must meet all of the following inclusion criteria to be eligible for inclusion in 
the study: Age 18 years and older
!
Patients with a diagnosis of COVID-19 whose information can be extracted from the 
I-Seha database
9.2.2. Exclusion Criteria
There are no exclusion criteria for this study.
9.3 Variables
The following variables are used to obtain comprehensive descriptive results. 
1. Demographics
2. Date of symptoms 
3. Viral variant analysis where available (type of viral variant ie, omicron, delta etc.)
4. PCR date along with CT Value 

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5. Co-morbidities and
6. BMI if ≥30
7. Symptoms at presentation 
8. COVID 19 vaccine status (NB 92% of population has been vaccinated -with at least 
one dose of COVID 19 vaccine- in Bahrain)
9. Hospital admission
10. Follow up looking at compliance and reason of non-compliance 
11. Day 5,7, 21 and 28 symptoms for COVID-19 patients who receive and HRU limited 
to admission (ICU, ward, need for oxygen therapy) or death 
12. Date of symptoms resolution if applicable 
Table 2Table 2 below depicts the patient demographics that will be accessed during the 
baseline and follow-up periods. The baseline period is defined as one year before the index 
date. Comorbidities (full list in Table 6) and maintenance medication usage for chronic 
conditions (eg, statins, antihypertensives, etc.) will be described during the baseline period 
and follow-up periods and are listed in Table 3. 
Risk factors for severe COVID-19, intensive care unit (ICU) usage, invasive mechanical 
ventilation (IMV) usage, supplemental oxygen use, non-invasive ventilation, and high-flow 
nasal cannula usage are depicted in Table 5 and will be extracted from the I-Seha national
electronic health record database.
Where applicable, emerging treatment patterns may be assessed as the time from symptom 
onset to COVID-19 diagnosis, time from symptom onset to treatment initiation, and the time 
from COVID-19 diagnosis to treatment initiation as illustrated in Table 5.
10Nov23 WHO recommendations30 for Paxlovid treatments to define: 1. COVID-19 patients 
who meet the WHO criteria for “strongly recommended” 2. COVID-19 patients who meet 
the WHO criteria for “conditionally recommended”, and 3. COVID patients who are not 
falling into categories 1 or 2 will be used.
9.4. Data Sources
There is a database of all patients who were eligible for Paxlovid™therapy and details of 
those that accepted Paxlovid™therapy and those that did not. Between 16 February 2022 and 
30 November 2022, there were 8263 patients that met all study inclusion and exclusion 
criteria eligible for Paxlovid™therapy of whom at least 3000 patients were treated with 
Paxlovid™therapy and 1000 were not. All records from the participant cohort of 8263 will be 
reviewed.

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Data on these patients that were treated with Paxlovid™therapy and those that did not will 
be extracted from the I-Seha Electronic Health Record (EHR). I-Seha EHR will be used to 
collect the variables listed below including: medical, biochemical and pharmacy data, 
HER data, and patient registry data. The I-Seha EHR data contains unstructured data that will 
be anonymized. I-Seha uses a large, geographically diverse administrative claims dataset 
which comprises patients served by a number of different health systems, providers and 
benefit structures. Complete information regarding all healthcare utilization submitted for 
payment is included in database.
9.4.1. EHR Database
There is a database of all patients who were eligible for Paxlovid™therapy and details of 
those that accepted Paxlovid™therapy and those that did not. Data on these patients that 
were treated with Paxlovid™therapy and those that did not will be extracted from the I-Seha 
EHR. A retrospective review will be undertaken of patients symptom database to discern 
patient-reported symptoms (eg, time from onset, duration, severity, frequency) will be 
described in this study. Following Paxlovid™treatment initiation, patients were followed up 
by a telephone call, regarding their symptom onset and severity; review of this standard of 
care data will be used to complement emerging treatment patterns and clinical characteristics 
throughout this study. For those that did not take Paxlovid™treatment, data will be extracted 
by the CRAs from the EHR on patient reevaluation in a healthcare facility, admission to 
hospital or death.
Table 2.
Patient Demographic and Clinical Characteristic Variables at Index
Variable
Operational definition
Age
Age will be defined as of the index date and will be used to assign
patients to age groups: 18-29, 30-49, 50-64, 65-74, ≥75 years and
unknown/missing age.
Gender
Defined as of the index date as the distribution of female, male and
unknown/missing sex patients.
Region
Kingdom of Bahrain
Nationality
Nationality of the patient will be mentioned
Enrollment Date Place
of Service (POS)
Distribution of patients by the type of outpatient encounter during the
enrollment date (eg, office visit, emergency room (ER), outpatient
hospital, other, etc.).
Enrollment Date
Date (defined as MM/YYYY) of the enrollment date specified for each
Cohort.

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Variable
Operational definition
Specialty of Provider at
enrollment Date
Distribution of the provider specialties present during the enrollment
date. Patients with no provider specialty recorded will be included in an 
“Unknown/missing specialty” category. 
Patient-reported
COVID-19 symptoms
List of COVID-19 symptoms to be added by study team (US, CDC
definition).
1- Stuffy or runny nose
2- Sore throat
3- Shortness of breath
4- Cough
5- Low energy/tiredness/fatigue
6- Muscle ache/body aches
7- Headache
8- Chills or shivering
9- Feeling hot/feverish
10- Nausea or vomiting
11- Diarrhea
12- Loss of sense of smell
13- Loss of sense of taste
COVID-19 Symptom
Onset Date
Date of symptom onset during the post-Paxlovid™availability timeframe. 
Time to COVID-19
Symptom Resolution
The number of continuous days with the same COVID-19 symptom. 
When available, the number of consecutive days will be reported as 
counts and percentages. The date of symptom resolution (last date 
recorded) will be reported when available.
Date of COVID-19
Vaccination
Date of each COVID-19 vaccination received. Note: patient-specific 
vaccination history may require more than 6-months pre-index time
period.
Date of Paxlovid™
prescription written
and/or fill history (eg,
prescription claim)
Date of Paxlovid™prescription written or fill history. Note: if both dates 
are available within the database, use the most recent date provided.

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Table 3.
Clinical Characteristic Variables
Variable
Operational definition
Comorbidities
A full list of comorbidities is detailed below and according to eCRF:
Distribution of patients diagnosed with each comorbid condition during
the baseline and follow-up periods. Comorbid conditions will include,
but are not limited to, asthma, emphysema, chronic obstructive
pulmonary disease (COPD), hypertension, diabetes, obesity,
cerebrovascular disease, neurological disease, chronic kidney disease,
chronic liver disease, malignancy, etc.
Risk Factors for Severe
COVID-19
Distribution of patients with each of the following risk factors during the
baseline and follow-up periods:
!
Age ≥50 years
!
Obesity (BMI ≥30
!
Chronic kidney disease (eGFR ≥30 ml/min)
!
Diabetes Mellitus
!
Primary and Secondary Immunosuppressive disease or 
immunosuppressive treatment 
!
Cardiovascular disease (including congenital heart disease) 
or hypertension 
!
Chronic lung diseases (for example, chronic obstructive 
pulmonary disease, asthma [moderate-to-severe], interstitial 
lung disease, cystic fibrosis, and pulmonary hypertension)
!
Sickle cell disease 
!
Neurodevelopmental disorders (for example, cerebral 
palsy) or other conditions that confer medical complexity 
(for example, genetic or metabolic syndromes and severe 
congenital anomalies)
!
Having a medical-related technological dependence (for 
example, tracheostomy, gastrostomy, or positive pressure 
ventilation [not related to COVID-19]) 
Death
Distribution of patients who died on or after the enrollment date in the
follow up period.

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Variable
Operational definition
Inpatient Death
Distribution of patients who died during a hospitalization in the follow-
up period.
Table 4.
HRU Data
Variable
Operational definition
Hospital Length of Stay
The total length of stay (LOS) recorded for all hospitalizations during the
baseline period and follow-up period in days (excluding within 24 hours of
Paxlovid™initiation).
ICU/Non-ICU LOS
The total number of days in the intensive care unit (ICU) and the number of days
that were not spent in the ICU (non-ICU) recorded for all hospitalizations during
the baseline period and follow-up period in days (excluding within 24 hours of
Paxlovid™initiation).
IMV/No IMV LOS
The total number of days with and without invasive mechanical ventilation
(IMV) recorded for all hospitalizations during the baseline period and follow-up
period in days (excluding within 24 hours of Paxlovid™initiation).
Hospitalizations (Count
and Percentage)
The count and percentage of patients with all-cause and COVID-related
hospitalizations (excluding within 24 hours of Paxlovid™initiation) during the
baseline and follow-up period.
Number of
Hospitalizations per
Patient
The number of hospitalizations per patient in the baseline and follow-up periods
for all-cause and COVID-related hospitalizations (excluding within 24 hours of
Paxlovid™initiation) will be described.
Number of
Hospitalizations per
Patient among Patients
with Readmissions
The number of all-cause and COVID-related hospitalizations (excluding within
24 hours of Paxlovid™initiation) per patient in the baseline and follow-up
periods will be described among patients with readmissions during the same
period. The cause for readmission will be reported when available.
Time to First Outpatient
Encounter
Time from COVID-19 diagnosis to the earliest outpatient encounter to occur
after diagnosis during the baseline period.

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Table 5.
COVID-19 Disease Outcome Variables
Variable
Operational definition
ICU Admission
Patients with ICU admission during COVID-related hospitalizations in the
baseline and follow-up periods (excluding within 24 hours of Paxlovid™
initiation).
IMV Usage
Distribution of patients with IMV (ie, intubation and mechanical ventilation)
usage, including extracorporeal membrane oxygenation (ECMO), during
COVID-related hospitalizations in the baseline and follow-up periods (excluding
within 24 hours of Paxlovid™initiation).
Supplemental Oxygen
Usage
Distribution of patients with supplemental oxygen usage during COVID-related
hospitalizations in the baseline and follow-up periods (excluding within 24 hours
of Paxlovid™initiation).
Non-invasive Ventilation
Usage
Distribution of patients with non-invasive ventilation usage during
COVID-related hospitalizations in the baseline and follow-up periods (excluding
within 24 hours of Paxlovid™initiation).
High-flow Nasal Cannula
Usage
Distribution of patients with high-flow nasal cannula usage during COVID-
related hospitalizations in the baseline and follow-up periods (excluding within
24 hours of Paxlovid™initiation).
Hospital Discharge Status
Distribution of patient discharge status for COVID-related hospitalizations
during the baseline and follow-up periods (excluding within 24 hours of
Paxlovid™initiation). Discharge status should include transfer to skilled nursing
facility, transfer to another healthcare facility, home, expired (dead), transfer to
other long-term care facility, transfer to hospice based on the values recorded in
the database.
Time from COVID-19
Test to Paxlovid™
Treatment
Time from the earliest COVID-19 test in the baseline period to the earliest date
of Paxlovid™prescription written date AND dispense date.
COVID-19 Lab Tests with
Positive Result
The count and percentage of patients with a COVID-19 lab test with a positive
result during the baseline and follow-up periods will be reported.
COVID-19 Lab Test with
Variant Type
When available, the count and percentage of patients with each COVID-19
variant of concern (VOC) during the baseline period will be reported.
Monoclonal Antibody
Usage
Patients with monoclonal antibody usage during the baseline and follow-up
periods. Monoclonal antibody usage will include tocilizumab and
bamlanivimab/etesevimab.
Antiviral Usage
Patients with antiviral therapy usage during the baseline and follow-up periods.
Antiviral therapy usage will include remdesivir, nirmatrelvir/ritonavir
(PaxlovidTM) and molnupravir.
Steroid therapy
Patients with steroid therapy during admission

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Variable
Operational definition
Treatment drugs being
receiving at the Index date
Use Positive test as the INDEX Date and record use of any medicine listed in the
potential DDI/Contraindications section of the EUA/Label
9.5. Study Size
This is a retrospective observational study using a sample afforded by the I-Seha Electronic 
health record. While this study will be descriptive in nature, feasibility queries show that, 
between 16 February 2022 and 30 November 2022, there were 8263 patients that met all 
study inclusion and exclusion criteria eligible for Paxlovid™therapy of whom at least 
3000 patients were treated with Paxlovid™therapy and 1000 were not. All records from the 
participant cohort of 8263 will be reviewed.
9.6. Data Management 
EHR data will be obtained via a retrospective review of participant charts and used to discern 
participant-reported symptom onset, symptom duration, and relevant laboratory findings for 
diagnostic criteria or other related information described in Table 2 and Table 3. 
The unstructured data that is extracted will be put into the eCRF, will then be anonymized by 
the clinical research assistants and presented in the format requested by the statistician at the 
time of analysis.
The study will abide to European GDPR legislation for maintaining confidentiality of data.
A Data Protection Impact Assessment (DPIA) will be performed to help identify and 
minimize the data protection risks of the study.
The EHR database is unstructured data. Individual medical records will be extracted and 
anonymized and populated into an eCRF. All data will be kept securely. Details of outcome 
measures and adverse events will be documented in hospital healthcare records. Individual 
research participant data is stored in an encrypted electronic database. The study 
investigators will adhere to hospital protocols pertaining to healthcare record use and storage 
to protect the research participant's identity, a unique identification code will be assigned by 
the Investigator, or authorized designee, to each study participant. These will be used in lieu 
of the participant's name, and the unique individual study code for each participant will be 
used for adverse events reporting and/or other study related data to be reported. This coded 
form of identification, instead of the participant's name, will appear on all 
documents/databases and will be cross-referenced by the participants date of birth 
(month/year). This server has managed access and password protection. The information that 
this server contains is backed up every 24 hours. 

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Personal information will be treated as confidential, but may need to be reviewed by 
authorized representatives of the Sponsor (such as monitors and auditors), the Contract 
Research Organization, the ethics committee and the regulatory authorities. The investigators 
and authorized designees will ensure that the confidentiality of the participants data is 
preserved. 
9.6.1. Case Report Forms 
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study.
A CRF is required and will be completed for each included participant. The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to 
third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer. The party performing medical record 
review, Royal College of Surgeons in Ireland, Medical University of Bahrain, RCSI Bahrain, 
shall ensure that the CRFs are securely stored at the study site in encrypted electronic form and 
will be password protected to prevent access by unauthorized third parties.
RCSI Bahrain has ultimate responsibility for the collection and reporting of all clinical, 
safety, and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic/original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring, and available when required. The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs are true. Any corrections to entries made in the CRFs or source 
documents must be dated, initialed, and explained (if necessary) and should not obscure the 
original entry.
The source documents are the hospital or the physician's chart. In these cases, data collected 
on the CRFs must match those charts. 
9.6.2. Record Retention
To enable evaluations and/or inspections/audits from regulatory authorities or Pfizer, the 
third party responsible for performing medical record review, RCSI Bahrain agrees to keep all 
study-related records, including the identity of all participating patients (sufficient 
information to link records, eg, eCRFs and hospital records), copies of all eCRFs, safety 
reporting forms, source documents, detailed records of treatment disposition, and adequate 
documentation of relevant correspondence (eg, letters, meeting minutes, and telephone call 
reports). The records should be retained by RCSI Bahrain according to local regulations or as 
specified in the Statement of work, whichever is longer. RCSI Bahrain must ensure that the 
records continue to be stored securely for so long as they are retained.
If RCSI Bahrain becomes unable for any reason to continue to retain study records for the 
required period, Pfizer should be prospectively notified. The study records must be 
transferred to a designee acceptable to Pfizer.

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Study records must be kept for a minimum of 15 years after completion or discontinuation of 
the study, unless RCSI Bahrain and Pfizer have expressly agreed to a different period of 
retention via a separate written agreement. Record must be retained for longer than 15 years 
or as required by applicable local regulations. 
RCSI Bahrain must obtain Pfizer's written permission before disposing of any records, even if 
retention requirements have been met.
9.7. Data Analysis
Detailed methodology for summary and statistical analyses of data collected in this study will 
be documented in a statistical analysis plan (SAP), which will be dated, filed, and maintained 
by the sponsor. The SAP may modify the plans outlined in the protocol; any major 
modifications of primary endpoint definitions or their analyses would be reflected in a 
protocol amendment.
A separate statistical analysis plan will provide analysis and programming details along with 
detailed table shells. A sample of the table of results expected from the primary aim of this
descriptive study is listed in Table 8.
All descriptive statistics will be presented as n, % for the categorical variables, or mean ±SD, 
median (interquartile range) for the numerical (continuous variables), as appropriate. 
Study sample will be stratified by age group: 18-29, 30-49, 50-64, 65-74, ≥75. Numerical 
outcomes included the number of COVID-19 vaccines received, date of last vaccination, 
days from last COVID-19 vaccination to date of Paxlovid™treatment (eg, Prescription and 
dispensing date), days from COVID-19 diagnosis to date of Paxlovid™treatment (eg, 
dispensing date), days from COVID-19 symptom onset to date of Paxlovid™treatment 
(eg, dispensing date).
Categorical outcomes included comorbid conditions and COVID-19 therapy. Possible
comorbid conditions include obesity (BMI ≥ 30), chronic kidney disease, diabetes mellitus, 
primary and Secondary Immunosuppressive disease or immunosuppressive treatment, 
cardiovascular disease (including congenital heart disease) or hypertension, active 
immunosuppressive disease (such as lymphoma, leukemia, etc.), active Immunosuppressive
treatment (Chemo, Steroids, etc.) (Immunocompromised, defined in ANNEX 2. 
IMMUNOCOMPROMISED ICD-10 CODE LIST).
WHO guidelines on COVID-19 therapeutics include the following groups
!
High risk: people who are immunosuppressed; estimated hospitalization rate of 6%.
!
Moderate risk: >65 years of age, conditions like obesity, diabetes and/or chronic 
conditions including chronic obstructive pulmonary disease, kidney or liver disease, 
cancer, with disabilities, and with comorbidities of chronic disease; estimated 
hospitalization rate of 3%.

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!
Low risk: those who are not in the high or moderate risk categories; low risk of 
hospitalization (0.5%) – most people are low risk.
Data will be evaluated looking at frequency and percentage of COVID-19 patients who will 
fall in those criteria to understand strongly recommended or conditionally recommended use 
of PaxlovidTM in comparison to the country of issue recommendations.
9.8. Quality Control
Quality control for each project is performed by a specific audit team member assigned to the 
study. Quality control practices include, but are not limited, to: 
!
Having qualified individuals who did not have a role in the study review data analyses 
and any final study report documentation for accuracy 
!
Ensuring proper documentation of data sources and key analytical steps
!
Auditing all software programs and results both with respect to computer output and final 
tables
!
Performing internal consistency checks of data presentations
!
Aligning dissemination materials with external requirements.
Regarding statistical programming, each program undergoes interim tests to ensure the 
program is working as expected. A study member will apply one or more testing methods as 
appropriate. 
9.9. Limitations of the Research Methods
This is a retrospective observational study and therefore can only demonstrate association 
and not causality. The results of this study may not be generalizable to the entire population. 
9.10. Other Aspects
Not applicable.

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10. PROTECTION OF HUMAN PARTICIPANTS
10.1. Patient Information 
The EHR database is unstructured data. Individual medical records will be extracted, 
anonymized and entered into the eCRF. 
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant personal data.  
Such measures will include omitting participant names or other directly identifiable data in 
any reports, publications, or other disclosures, except where required by applicable laws. 
Participant personal data will be stored at the study site in encrypted electronic form and will 
be password protected to ensure that only authorized study staff have access. RCSI Bahrain
will implement appropriate technical and organizational measures to ensure that the personal 
data can be recovered in the event of disaster. In the event of a potential personal data breach, 
RCSI Bahrain shall be responsible for determining whether a personal data breach has in fact 
occurred and, if so, providing breach notifications as required by law.
To protect the rights and freedoms of natural persons with regard to the processing of 
personal data, when study data are compiled for transfer to Pfizer and other authorized 
parties, any participant names will be removed and will be replaced by a single, specific, 
numerical code, based on a numbering system defined by Pfizer. All other identifiable data 
transferred to Pfizer or other authorized parties will be identified by this single, participant-
specific code. The investigator site will maintain a confidential list of patients who 
participated in the study, linking each participant’s numerical code to his or her actual 
identity. In case of data transfer, Pfizer will maintain high standards of confidentiality and 
protection of patients’ personal data consistent with the clinical study agreement and 
applicable privacy laws.
10.2. Participant Consent
As this study does not involve data subject to privacy laws according to applicable legal 
requirements, obtaining informed consent from patients by Pfizer is not required. 
10.3. Institutional Review Board (IRB)/Ethics Committee (EC)
There must be prospective approval of the study protocol, protocol amendments, and other 
relevant documents (eg, informed consent forms if applicable) from the relevant IRBs/ECs.
All correspondence with the IRB/EC must be retained.  Copies of IRB/EC approvals must be 
forwarded to Pfizer.
10.4. Ethical Conduct of the Study
The study will be conducted in accordance with legal and regulatory requirements, as well as 
with scientific purpose, value and rigor and follow generally accepted research practices 
described in Guidelines for Good Pharmacoepidemiology Practices (GPP) issued by the 
International Society for Pharmacoepidemiology (ISPE), Declaration of Helsinki and its
amendments, and any applicable national guidelines. This study will follow the 

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Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting 
guideline.29
11. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS 
This study protocol requires human review of participant-level unstructured data; 
unstructured data refer to verbatim medical data, including text-based descriptions and visual 
depictions of medical information, such as medical records, images of physician notes, 
neurological scans, x-rays, or narrative fields in a database. The reviewer is obligated to
report adverse events (AEs) with explicit attribution to any Pfizer drug that appear in the 
reviewed information (defined per the participant population and study period specified in 
the protocol). Explicit attribution is not inferred by a temporal relationship between drug 
administration and an AE but must be based on a definite statement of causality by a 
healthcare provider linking drug administration to the AE.
The requirements for reporting safety events on the non-interventional study (NIS) adverse 
event monitoring (AEM) Report Form to Pfizer Safety are as follows:
!
All serious and non-serious AEs with explicit attribution to any Pfizer drug that appear 
in the reviewed information must be recorded on the data collection tool (eg, chart 
abstraction form) and reported, within 24 hours of awareness, to Pfizer Safety using the 
NIS AEM Report Form.
!
Scenarios involving drug exposure, including exposure during pregnancy, exposure 
during breast feeding, medication error, overdose, misuse, extravasation, lack of efficacy,
and occupational exposure associated with the use of a Pfizer product must be reported, 
within 24 hours of awareness, to Pfizer Safety using the NIS AEM Report Form.
!
For exposure during pregnancy in studies of pregnant women, data on the exposure to 
Paxlovid™during pregnancy, are not reportable unless associated with serious or non-
serious adverse events. 
!
For these AEs with an explicit attribution or scenarios involving exposure to a Pfizer 
product, the safety information identified in the unstructured data reviewed is captured in 
the Event Narrative section of the report form, and constitutes all clinical information 
known regarding these AEs. No follow-up on related AEs will be conducted.
All the demographic fields on the NIS AEM Report Form may not necessarily be completed, 
as the form designates, since not all elements will be available due to privacy concerns with 
the use of secondary data sources. While not all demographic fields will be completed, at the 
very least, at least one patient identifier (eg, gender, age as captured in the narrative field of 
the form) will be reported on the NIS AEM Report Form, thus allowing the report to be 
considered a valid one in accordance with pharmacovigilance legislation. All identifiers will 
be limited to generalities, such as the statement “A 35-year-old female...” or “An elderly 
male...” Other identifiers will have been removed. Additionally, the onset/start dates and stop 

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dates for “Illness,” “Study Drug,” and “Drug Name” may be documented in month/year 
(mmm/yyyy) format rather than identifying the actual date of occurrence within the month 
/year of occurrence in the day/month/year (DD/MMM/YYYY) format.
All research staff members must complete the following Pfizer training requirements: 
!
“Your Reporting Responsibilities (YRR) with Supplemental Topics.”
These trainings must be completed by research staff members prior to the start of data 
collection. All trainings include a “Confirmation of Training Statement” (for signature by the 
trainee) as a record of completion of the training, which must be kept in a retrievable format.
Copies of all signed training statements must be provided to Pfizer. 
12. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS
A final study report detailing the final study protocol and the analysis results will be provided 
when the study is complete. In the event of any prohibition or restriction imposed 
(eg, clinical hold) by an applicable competent authority in any area of the world, or if RCSI 
Bahrain is aware of any new information which might influence the evaluation of the benefits 
and risks of a Pfizer product, Pfizer should be informed immediately. 
0

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13. REFERENCES
1.
World Health Organization. 2019-nCoV outbreak is an emergency of international 
concern. 31 Jan 2020. Available from: https://www.euro.who.int/en/healthtopics/health-
emergencies/coronavirus-covid19/news/news/2020/01/2019-ncovoutbreak-is-an-
emergency-of-international-concern. Accessed on January 1, 2022.
2.
World Health Organization. WHO Situation Report 51 Coronavirus disease 2019 
(COVID-19). 11 March 2020. Available from: 
https://www.who.int/docs/defaultsource/coronaviruse/situation-reports/20200311-
sitrep-51-covid-19.pdf?sfvrsn=1ba62e57_10. Accessed on January 1, 2022.
3.
John Hopkins University.  COVID-19 Dashboard by the Center for Systems Science 
and Engineering (CSSE) at Johns Hopkins University (JHU). Available from: 
https://coronavirus.jhu.edu/map.html. Accessed on January 1, 2022.
4.
World Health Organization. 2019-nCoV outbreak is an emergency of international 
concern. 31 Jan 2020. Available from: https://www.euro.who.int/en/healthtopics/health-
emergencies/coronavirus-covid-19/news/news/2020/01/2019-ncovoutbreak-is-an-
emergency-of-international-concern. Accessed on January 1, 2022. 
5.
Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus 
Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72314 Cases 
From the Chinese Center for Disease Control and Prevention. JAMA. 
2020;323(13):1239-42.
6.
Docherty AB, Harrison EM, Green CA, et al. Features of 20 133 UK patients in hospital 
with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective 
observational cohort study. BMJ. 2020;369:m1985.
7.
Richardson S, Hirsch JS, Narasimhan M, et al. Presenting Characteristics, 
Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in 
the New York City Area. JAMA. 2020;323(20):2052-59.
8.
CDC. Estimated Disease Burden of COVID-19. Centers for Disease Control and 
Prevention. Data & Surveillance Web site. https://www.cdc.gov/coronavirus/2019-
ncov/cases-updates/burden.html. Published 2020. Updated October 2, 2021. Accessed 
January 1, 2022.
9.
NIH. Outpatient Management of Acute COVID-19. National Institutes of Health. 
COVID-19 Treatment Guidelines Web site. 
https://www.covid19treatmentguidelines.nih.gov/outpatient-management/. Published 
2021. Updated December 16, 2021. Accessed January 1, 2022.

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10.
NIH. The COVID-19 Treatment Guideline Panel’s Statement on Therapies for High-
Risk, Nonhospitalized Patients with Mild to Moderate COVID-10 Web site. 
https://www.covid19treatmentguidelines.nih.gov/therapies/statement-on-therapies-for-
high-risk-nonhospitalized-patients. Published 2021. Updated December 30, 2021. 
Accessed January 1, 2022.
11.
FDA. Fact Sheet for Healthcare Providers: Emergency Use Authorization for Paxlovid. 
https://www.fda.gov/media/155050/download. Published December 2021. Accessed 
January 1, 2022.
12.
Gupta A, Gonzalez-Rojas Y, Juarez E, et al. Early treatment for COVID-19 with SARS-
CoV-2 neutralizing antibody sotrovimab. N Engl J Med. 2021;385(21):1941-1950. 
13.
Gottlieb RL, Vaca CE, Paredes R, et al. Early remdesivir to prevent progression to 
severe COVID-19 in outpatients. N Engl J Med. 2021. 
14.
Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for oral 
treatment of COVID-19 in nonhospitalized patients. N Engl J Med. 2021.
15.
Rai DK, Yurgelonis I, McMonagle P, et al. Nirmatrelvir, an orally active Mpro 
inhibitor, is a potent inhibitor of SARS-CoV-2 Variants of Concern. bioRxiv. Preprint 
posted online January 2022. Accessed March 17, 2022. doi: 
10.1101/2022.01.17.476644.
16.
Petrilli CM, Jones SA, Yang J, et al. Factors associated with hospital admission and 
critical illness among 5279 people with coronavirus disease 2019 in New York City: 
prospective cohort study. BMJ. 2020;369:m1966. 
17.
Stokes EK, Zambrano LD, Anderson KN, et al. Coronavirus Disease 2019 Case 
Surveillance - United States, January 22-May 30, 2020. MMWR Morb Mortal Wkly Rep. 
2020;69(24):759-765. 
18.
Ko JY, Danielson ML, Town M, et al. Risk Factors for COVID-19-associated 
hospitalization: COVID-19-Associated Hospitalization Surveillance Network and
Behavioral Risk Factor Surveillance System. Clin Infect Dis. 2020. 
19.
Lavery AM, Preston LE, Ko JY, et al. Characteristics of Hospitalized COVID-19 
Patients Discharged and Experiencing Same-Hospital Readmission - United States, 
March-August 2020. MMWR Morb Mortal Wkly Rep. 2020;69(45):1695-1699. 
20.
Cunningham JW, Vaduganathan M, Claggett BL, et al. Clinical Outcomes in Young US 
Adults Hospitalized With COVID-19. JAMA Intern Med. 2020. 
21.
Rosenthal N, Cao Z, Gundrum J, Sianis J, Safo S. Risk Factors Associated With In-
Hospital Mortality in a US National Sample of Patients With COVID-19. JAMA Netw 
Open. 2020;3(12):e2029058.

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22.
Ioannou GN, Locke E, Green P, et al. Risk Factors for Hospitalization, Mechanical 
Ventilation, or Death Among 10131 US Veterans With SARS-CoV-2 Infection. JAMA 
Netw Open. 2020;3(9):e2022310. 
23.
Nguyen NT, Chinn J, Nahmias J, et al. Outcomes and Mortality Among Adults 
Hospitalized With COVID-19 at US Medical Centers. JAMA Netw Open. 
2021;4(3):e210417. 
24.
Di Fusco M, Shea KM, Lin J, et al. Health outcomes and economic burden of 
hospitalized COVID-19 patients in the United States. J Med Econ. 2021;24(1):308-317. 
25.
Best JH, Kong AM, Kaplan-Lewis E, et al. Treatment Patterns in US Patients 
Hospitalized With COVID-19 and Pulmonary Involvement. J Med Virol. 2021.
26.
Lin KJ, Schneeweiss S, Tesfaye H, et al. Pharmacotherapy for Hospitalized Patients 
with COVID-19: Treatment Patterns by Disease Severity. Drugs. 2020;80(18):1961-
1972.
27.
Oksuz E, Malhan S, Gonen MS, et al. COVID-19 heahtcare cost and length of hospital 
stay in Turkey: retrospective analysis form the first peak of the pandemic. Health 
Economics Review. 2021;11:39.
28.
Leeyaphan J, Leeyaphan C, Suttha P, et al. Healthcare Resource Utilization and 
Heatlhcare Costs of COVID-19 Paitnets in A Tertiary Care Public Hospital: A 
Retrospective Cohort Study in Thailand. J Med Assoc. 2021;104:1953-8.
29.
von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of 
Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting 
observational studies. Int J Surg. 2014;12(12):1495-1499.
30.
A living WHO guideline on drugs for covid-19. BMJ 2020;370:m3379.

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14. LIST OF TABLES 
Table 1.
Cohort Definitions
Table 2.
Patient Demographic and Clinical Characteristic Variables at Index
Table 3.
Clinical Characteristic Variables
Table 4.
HRU
Table 5.
COVID-19 Disease Outcome Variables
Table 6.
Additional Variables
Table 7.
Potentially Significant Drug Interactions
Table 8.
[SAMPLE] Results Table
Table 9.
ICD-10 Code List for Immunocompromised Patients
15. LIST OF FIGURES
None.
ANNEX 1. LIST OF STANDALONE DOCUMENTS
None.

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ANNEX 2. ADDITIONAL INFORMATION
Table 6.
Additional Variables
Category
Variables of Interest
Comorbidities
!
Cancer (active or history of cancer)
!
Chronic kidney disease (CKD) at any stage
!
Chronic liver disease (cirrhosis, non-alcoholic fatty liver disease, alcoholic liver 
disease, autoimmune hepatitis)
!
Chronic lung diseases
!
Chronic lung diseases: Interstitial lung disease, pulmonary fibrosis
!
Chronic lung diseases: COPD, emphysema and chronic bronchitis
!
Chronic lung diseases: Asthma (moderate to severe)
!
Chronic lung diseases: Cystic fibrosis
!
Chronic lung diseases: Pulmonary embolism
!
Chronic lung diseases: Pulmonary hypertension
!
Chronic lung diseases: Bronchopulmonary dysplasia
!
Chronic lung diseases: Bronchiectasis
!
Dementia or other neurological conditions
!
Diabetes (type 1 or type 2)
!
Down syndrome
!
Heart conditions (heart failure, coronary artery disease, or cardiomyopathies)
!
HIV infection
!
Hypertension
!
"Immunocompromised state (primary caused by genetic defects; 
secondary/acquired from prolonged use of corticosteroids or other
!
immune weakening medicines)"
!
Immunocompromised state: HIV/AIDS

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Category
Variables of Interest
!
Immunocompromised state: Solid malignancy
!
Immunocompromised state: Bone marrow transplant
!
Immunocompromised state: Organ transplant
!
Immunocompromised state: Rheumatologic/inflammatory
!
Immunocompromised state: Primary immunodeficiency
!
Immunocompromised state: Other immune conditions
!
Immunocompromised state: CKD or ESRD
!
Immunocompromised state: Hematologic malignancy
!
Immunocompromised state: IS drug only
!
Immunocompromised state: Anti-metabolites
!
Immunocompromised state: >1 IC condition
!
Mental health conditions (mood disorders, including depression, and schizophrenia 
spectrum disorders)
!
Overweight and obesity
!
Pregnancy and recent pregnancy (for at least 42 days following end of pregnancy)
!
Sickle cell disease (SCD) or thalassemia
!
Smoking, current or former
!
Solid organ or blood stem cell transplant (includes bone marrow transplants)
!
Stroke or cerebrovascular disease
!
Peripheral vascular disease
!
Transient Ischemic Attack
!
Substance use disorders (alcohol, opioid, or cocaine use disorder)
!
Tuberculosis

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Table 7.
Potentially Significant Drug Interactions
Drug Class
Product name
Antianginal
RANOLAZINE
Antiarrhythmics
BEPRIDIL
LIDOCAINE (SYSTEMIC)
Anticancer agents
ABEMACICLIB
CERITINIB
DASATINIB
ENCORAFENIB
IBRUTINIB
IVOSIDENIB
NERATINIB
NILOTINIB
VENETOCLAX
VINBLASTINE
VINCRISTINE
Anticoagulants 
WARFARIN
RIVAROXABAN
Antidepressants
BUPROPION
TRAZODONE
Antifungals
KETOCONAZOLE
VORICONAZOLE
ISAVUCONAZONIUM SULFATE
ITRACONAZOLE
Anti-HIV protease inhibitors
AMPRENAVIR
ATAZANAVIR
DARUNAVIR
FOSAMPRENAVIR
INDINAVIR
NELFINAVIR

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Drug Class
Product name
SAQUINAVIR
TIPRANAVIR 
Anti-HIV
DIDANOSINE
DELAVIRDINE
EFAVIRENZ
MARAVIROC
NEVIRAPINE
RALTEGRAVIR
ZIDOVUDINE
Anti-infective
CLARITHROMYCIN
ERYTHROMYCIN
Antimycobacterial
BEDAQUILINE
RIFABUTIN
Antipsychotics
QUETIAPINE
Calcium channel blockers
AMLODIPINE
DILTIAZEM
FELODIPINE
NICARDIPINE
NIFEDIPINE
Cardiac glycosides
DIGOXIN
Endothelin receptor 
antagonists
BOSENTAN
Hepatitis C direct acting 
antivirals
ELBASVIR/GRAZOPREVIR
GLECAPREVIR/PIBRENTASVIR
SOFOSBUVIR/VELPATASVIR/VOXILAPREVIR
OMBITASVIR/PARITAPREVIR/RITONAVIR AND DASABUVIR
HMG-CoA reductase 
inhibitors
ATORVASTATIN
ROSUVASTATIN
Hormonal contraceptive
ETHINYL ESTRADIOL

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Drug Class
Product name
Immunosuppressants
CYCLOSPORINE
TACROLIMUS
SIROLIMUS
Long-acting betaadrenoceptor 
agonist
SALMETEROL
Narcotic analgesics
FENTANYL
METHADONE
Sedative/hypnotics 
MIDAZOLAM (ADMINISTERED PARENTERALLY)
Systemic corticosteroids
BETAMETHASONE
BUDESONIDE
CICLESONIDE
DEXAMETHASONE
FLUTICASONE
METHYLPREDNISOLONE
MOMETASONE
PREDNISONE
TRIAMCINOLONE

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Table 8.
[SAMPLE] Results Table
Treated COVID-19 patients
(N = n)
Control Group
Untreated COVID-19 patients
(N = n)
Baseline Variables
1.0 Demographics
1.1 Age
-
1.2 Gender
-
2.0 Clinical Characteristics
-
2.1 Comorbidities (ICD-10)
-
2.2 Vaccination Status (incl.
date)
-
       2.3 Baseline Medication Usage
-
        2.4 COVID-19 Symptom (incl. date)
-
        2.5 COVID Diagnosis Date (index)
-
Outcome Variables
-
3.0 HRU
-
3.1 Hospitalizations
-
        3.2 Outpatient Visits
-
3.3 Emergency Room Visits
-
3.4 Procedures
-
3.5 Laboratory Tests (incl.
COVID-Related)
-
4.0 Medical Costs (incl. COVID-Related)
-
        4.1 Outpatient Costs
-
        4.2 Inpatient Costs
-
        4.3 Emergency Room Costs
-
        4.4 Ancillary Costs
-
5.0 Pharmacy Costs (incl. COVID-
Related)
-

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Treated COVID-19 patients
(N = n)
Control Group
Untreated COVID-19 patients
(N = n)
6.0 Medication Usage (incl. written date
of prescription and fill history)
-
        6.1 Antibiotic
-
        6.2 Antiviral (incl. PaxlovidTM,
              COVID-19 monoclonal
antibodies)
-
        6.3 Antithrombotic
-
        6.5 Anti-inflammatory (incl.
steroids)
-

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ANNEX 3. IMMUNOCOMPROMISED ICD-10 CODE LIST
Participants will be identified as immunocompromised (IC) if they had ≥1 hospitalization or 
≥2 outpatient visits on separate dates with an ICD-10-CM code on a healthcare claim 
indicating an IC condition or if they had usage of specific immunosuppressive medications 
during the 12-month baseline period.
The list of ICD-10-CM codes used to identify IC cases by diagnosis and list of 
immunosuppressive medications are shown below in Table 9
Table 9.
ICD-10 Code List for Immunocompromised Patients
IC Condition
ICD-10 Code
HIV/AIDS*
B20-B24
Solid malignancy
Organ/system malignant tumors
C00-C07; C11-C19; C22-C80; Z85
Neuroendocrine tumors
C7A; C7B; D3A
Neoplasms of uncertain behavior
D00-D49
Bone marrow transplant
Z94.81
Organ transplant
Complications of transplanted organ
T86
Organ transplant status
Z94 except Z94.81; Z98.85
Rheumatologic or other inflammatory condition
Sarcoidosis
D86
Amyloidosis Not Otherwise Specified (NOS)
E85
Familial Mediterranean fever
E85.0; M04
Amyloidosis Not Elsewhere Classified (NEC)
E85.1; E85.3; E85.8
Multiple sclerosis
G35
Other Central Nervous System (CNS) demyelination
G36; G37.1; G37.3; G37.8; G37.9
Acute infective polyneuritis
G61.0; G61.9
Acute myocarditis
I40
Polyarteritis nodosa and other
M30
Allergic alveolitis/pneumonitis NOS
T78.40; J67.9
Other alveolar pneumonopathy
J84.01; J84.02; J84.09
Enteritis and colitis
K50-K52

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IC Condition
ICD-10 Code
Lupus erythematosus
L93.0; L93.2; M32
Diffuse connective tissue disease
L94; M35.8; M35.9
Arthropathy with infection
M12.9; M01.X0; M02.10
Crystal arthropathies
M11
Rheumatoid arthritis/inflammatory polyarthropathy
M05-M14
Inflammatory spondylopathies
M46
Polymyalgia rheumatica
M31.5; M35.3
Chronic inflammatory demyelinating polyneuropathy
G61.81
Immune thrombocytopenic purpura
D69.3
Primary Immunodeficiency
X-linked agammaglobulinemia
D80.8
Common variable immunodeficiency
D83.1; D83.2; D83.8; D83.9
Immunoglobulin A (IgA) deficiency
D80.2
Immunoglobulin G (IgG) sub-class deficiency
D80.3
Severe combined immunodeficiency
D81.1
Di George syndrome
D82.1
Wiskott-Aldrich
D82.0
Ataxia telangiectasia
G11.3
Interferon-gamma/Interleukin 12 axis deficiencies
D84.89
Persistent complement, properdin or Factor B deficiency
D84.1
Received eculizumab for >14 days in the baseline period
Chronic granulomatous disease
D71
Chediak-Higashi
E70.330
Leukocyte adhesion deficiency
D72: Genetic anomalies of leukocytes
Myeloperoxidase deficiency
D72.89: Other specific disorders of White Blood Cells
(WBCs)
Other immune conditions
Disorders of immune mechanism
D89
Neutropenia
D70
Functional disorders of neutrophils
D71

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IC Condition
ICD-10 Code
Genetic anomalies of leukocytes
D72.0
Decreased leukocyte count
D72.81
Leukocyte disease NEC
D72.89
Leukocyte disease NOS
D72.9
Myelofibrosis
D75.81
Blood diseases NEC
D47.4; D75.89; D75.9; D89.2
Blood diseases NOS
D75.9; D75.89
Immunologic findings NEC
R76; R83.4-R87.4; R89.4
Nonspecific immune findings NEC and NOS
R76; R83.4-R87.4; R89.4
Sickle cell disease
D57
Asplenia
Q89.01
Psoriatic arthritis
L40.52
Kidney condition
Chronic kidney disease
A18.11; A52.75; B52.0; C64.x; C68.9; D30.0x; D41.0x-
D41.2x; D59.3; E08.2x; E09.2x; E10.2x; E10.65;
E11.2x; E11.65; E13.2x; E74.8; I12.xx; I13.0; I13.1x;
I13.2; K76.7; M10.3x; M32.14; M32.15; N01.x-N08.x;
N13.1; N13.1x-N13.39; N14.x; N15.0; N15.8; N15.9;
N16; N17.x; N18.1-N18.5; N18.8; N18.9; N19; N25.xx;
N26.1; N26.9; O10.4xx; O12.xx; O26.83x; O90.89;
Q61.02; Q61.1x-Q61.8; Q26.0-Q26.39; R94.4
End stage renal disease
N18.6 AND on dialysis (any type): Z99.2; Z49; Z9115;
Z4931; OR Z4901
On hemodialysis
Any participant with the ESRD codes above and
≥1 hemodialysis procedure session during the baseline
period identified by at ≥1 of the following codes: Z49.31;
Z49.32; I953; A4680; A4690; A4706-A4709; A4730;
A4740; A4750; A4755; A4802; A4870; A4890; A4918;
E1520; E1530; E1540; E1550; E1560; E1575; E1580;
E1590; E1600; E1610; E1615; E1620; E1625; E1636;
G0365; G0392; G0393; G8081; G8082; G8085; S9335;
90935; 90937; 90940; 93990; 36800; 36810; 36815
On peritoneal dialysis
Any participant with the ESRD codes above and
≥1 peritoneal dialysis procedure session during the
baseline period identified by ≥1 of the following codes:
Z49.02; 90945; 90947
Hematologic malignancy**

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IC Condition
ICD-10 Code
Lymphatic and hematopoietic tissue malignancy
C81-C83; C88-C96
CNS: central nervous system; ICD-10: International Classification of Diseases, 10th Revision; IgG: 
Immunoglobulin G, IgA: Immunoglobulin A, NOS: not otherwise specified; NEC: necrotizing enterocolitis; 
WBCs: White blood cells.
*Excluded asymptomatic HIV code of ICD-10: Z21.
**Required to have usage of an immunosuppressive medication (chemotherapeutic agent, immunomodulator, or 
systemic corticosteroids) for >14 days anytime during the baseline period.

D o c u m e nt A p pr o v al R e c or d
D o c u m e nt N a m e:
D o c u m e nt Titl e:
Si g n e d B y:
D at e( G M T)
Si g ni n g C a p a cit y
 
P P D