BRII-196/BRII-198 for Inpatients With COVID-19 (An ACTIV-... | NCT05780424

Status Module

Name	Class
International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)	NETWORK
University of Copenhagen	OTHER
Medical Research Council	OTHER_GOV

Description Module

Detailed Description

This is a treatment trial of the ACTIV-3/TICO master protocol (NCT04501978) to evaluate the safety and efficacy of BRII-196/BRII-198 in hospitalized patients infected with COVID-19.

This is a randomized, blinded, controlled sub-study of BRII-196/BRII-198 plus current standard of care (SOC) against placebo plus current SOC. The placebo arm may be shared across other sub-studies of the ACTIV-3/TICO master protocol. When more than one drug is being tested at the same time, participants will be randomly allocated to treatments or placebo.

Randomization will be stratified by study site pharmacy and disease severity. There are 2 disease severity strata: Participants without organ failure (severity stratum 1) and participants with organ failure (severity stratum 2).

An independent Data and Safety Monitoring Board (DSMB) will regularly review interim analyses and summarize safety and efficacy outcomes. The pace of enrollment with be initially restricted, and there will be an early review of safety data by the DSMB. At the outset of the trial, only participants in disease severity stratum 1 will be enrolled. This will continue until approximately 300 participants are enrolled and followed for 5 days. The exact number will vary according to the speed of enrollment and the timing of DSMB meetings. Prior to expanding enrollment to also include patients in disease severity stratum 2, safety will be evaluated and a pre-specified futility assessment by the DSMB will be carried out using 2 ordinal outcomes assessed at Day 5.

If BRII-196/BRII-198 passes the futility assessment, enrollment of participants will be expanded, seamlessly and without any data unblinding, to include participants in disease severity stratum 2 as well as those in disease severity stratum 1. Future interim analyses will be based on the primary endpoint of sustained recovery and will use pre-specified guidelines to determine early evidence of benefit, harm, or futility for the investigational agent. Participants will be followed for 18 months following randomization.

This trial will be conducted in several hundred clinical sites. Participating sites are affiliated with networks funded by the United States National Institutes of Health (NIH) and the US Department of Veterans Affairs.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
BRII-196/BRII-198 plus SOC	Experimental	BRII-196 1000 mg solution; administered as IV infusion BRII-198 1000 mg solution; administered as IV infusion Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion	Biological: BRII-196 Biological: BRII-198 Biological: Remdesivir
Placebo plus SOC	Placebo Comparator	Placebo administered by IV infusion Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion	Biological: Placebo Biological: Remdesivir

Interventions

Name	Type	Description	Arm Group Labels	Other Names
BRII-196	Biological	BRII-196 is a fully human immunoglobulin G (IgG)-1 monoclonal antibody (mAb) derived from antibody P2C-1F11 that was isolated directly from human B cells of a convalescent COVID-19 patient.

Outcomes Module

Measure	Description	Time Frame
Number of Participants With an Ordinal Outcome on Day 5	Ordinal outcome with 7 mutually exclusive categories	Status on Day 5

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants Who Died From All Causes	All-cause mortality	Through Day 90
Number of Participants With a Safety Outcome Through Day 5	Death, SAE, clinical organ failure, serious infections, or Grade 3 or 4 event through Day 5

Eligibility Module

Name	Affiliation	Role
Jens Lundgren, Prof.	INSIGHT Copenhagen International Coordinating Centre, Rigshospitalet, University of Copenhagen	Principal Investigator
James Neaton, Prof.	INSIGHT Statistical and Data Management Center, University of Minnesota	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Banner University Medical Center Tucson (Site 206-004), 1625 N. Campbell Avenue		Tucson	Arizona	85719	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
34953520	Result	ACTIV-3/Therapeutics for Inpatients with COVID-19 (TICO) Study Group. Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial. Lancet Infect Dis. 2022 May;22(5):622-635. doi: 10.1016/S1473-3099(21)00751-9. Epub 2021 Dec 23.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	BRII-196/BRII-198 Plus SOC	BRII-196 1000 mg solution; administered as IV infusion BRII-198 1000 mg solution; administered as IV infusion Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion BRII-196: BRII-196 is a fully human immunoglobulin G (IgG)-1 monoclonal antibody (mAb) derived from antibody P2C-1F11 that was isolated directly from human B cells of a convalescent COVID-19 patient. BRII-198: BRII-198 is a fully human immunoglobulin G (IgG)-1 monoclonal antibody (mAb) derived from antibody P2B-1G5 that was isolated directly from human B cells of a convalescent COVID-19 patient. Remdesivir: Antiviral agent

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol: Trial H3 Protocol	Nov 20, 2020

Arm/Group Information

ID	Title	Description
BG000	BRII-196/BRII-198 Plus SOC	BRII-196 1000 mg solution; administered as IV infusion BRII-198 1000 mg solution; administered as IV infusion Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion BRII-196: BRII-196 is a fully human immunoglobulin G (IgG)-1 monoclonal antibody (mAb) derived from antibody P2C-1F11 that was isolated directly from human B cells of a convalescent COVID-19 patient. BRII-198: BRII-198 is a fully human immunoglobulin G (IgG)-1 monoclonal antibody (mAb) derived from antibody P2B-1G5 that was isolated directly from human B cells of a convalescent COVID-19 patient. Remdesivir: Antiviral agent
BG001	Placebo Plus SOC	Placebo administered by IV infusion Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion Placebo: Commercially available 0.9% sodium chloride solution Remdesivir: Antiviral agent
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00060.2± 14.4 BG00159.5± 14.8 BG00259.8± 14.5

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00078 BG00174 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00034 BG00132 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Asian	BG00012 BG0019 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With an Ordinal Outcome on Day 5

Ordinal outcome with 7 mutually exclusive categories

Posted

Count of Participants

Participants

Status on Day 5

ID	Title	Description
OG000	BRII-196/BRII-198 Plus SOC	BRII-196 1000 mg solution; administered as IV infusion BRII-198 1000 mg solution; administered as IV infusion Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion BRII-196: BRII-196 is a fully human immunoglobulin G (IgG)-1 monoclonal antibody (mAb) derived from antibody P2C-1F11 that was isolated directly from human B cells of a convalescent COVID-19 patient. BRII-198: BRII-198 is a fully human immunoglobulin G (IgG)-1 monoclonal antibody (mAb) derived from antibody P2B-1G5 that was isolated directly from human B cells of a convalescent COVID-19 patient. Remdesivir: Antiviral agent
OG001	Placebo Plus SOC	Placebo administered by IV infusion Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion Placebo: Commercially available 0.9% sodium chloride solution Remdesivir: Antiviral agent

Units	Counts
Participants	OG000173 OG001177

Title

Denominators

Categories

Title	Measurements
7 = Death	OG0001 OG0011
6 = Invasive ventilation, ECMO, mechanical circulatory support, new renal replacement therapy	OG000

Secondary

Number of Participants Who Died From All Causes

All-cause mortality

Posted

Count of Participants

Participants

Through Day 90

ID	Title	Description
OG000	BRII-196/BRII-198 Plus SOC	BRII-196 1000 mg solution; administered as IV infusion BRII-198 1000 mg solution; administered as IV infusion Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion BRII-196: BRII-196 is a fully human immunoglobulin G (IgG)-1 monoclonal antibody (mAb) derived from antibody P2C-1F11 that was isolated directly from human B cells of a convalescent COVID-19 patient. BRII-198: BRII-198 is a fully human immunoglobulin G (IgG)-1 monoclonal antibody (mAb) derived from antibody P2B-1G5 that was isolated directly from human B cells of a convalescent COVID-19 patient. Remdesivir: Antiviral agent
OG001	Placebo Plus SOC	Placebo administered by IV infusion Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion Placebo: Commercially available 0.9% sodium chloride solution Remdesivir: Antiviral agent

Units	Counts
Participants

Secondary

Number of Participants With a Safety Outcome Through Day 5

Death, SAE, clinical organ failure, serious infections, or Grade 3 or 4 event through Day 5

Posted

Count of Participants

Participants

Through Day 5

ID	Title	Description
OG000	BRII-196/BRII-198 Plus SOC	BRII-196 1000 mg solution; administered as IV infusion BRII-198 1000 mg solution; administered as IV infusion Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion BRII-196: BRII-196 is a fully human immunoglobulin G (IgG)-1 monoclonal antibody (mAb) derived from antibody P2C-1F11 that was isolated directly from human B cells of a convalescent COVID-19 patient. BRII-198: BRII-198 is a fully human immunoglobulin G (IgG)-1 monoclonal antibody (mAb) derived from antibody P2B-1G5 that was isolated directly from human B cells of a convalescent COVID-19 patient. Remdesivir: Antiviral agent
OG001	Placebo Plus SOC	Placebo administered by IV infusion Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion Placebo: Commercially available 0.9% sodium chloride solution Remdesivir: Antiviral agent

Units

Secondary

Number of Participants With a Safety Outcome Through Day 28

Death, SAE, clinical organ failure, serious infections, or Grade 3 or 4 event through Day 28

Posted

Count of Participants

Participants

Through Day 28

ID	Title	Description
OG000	BRII-196/BRII-198 Plus SOC	BRII-196 1000 mg solution; administered as IV infusion BRII-198 1000 mg solution; administered as IV infusion Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion BRII-196: BRII-196 is a fully human immunoglobulin G (IgG)-1 monoclonal antibody (mAb) derived from antibody P2C-1F11 that was isolated directly from human B cells of a convalescent COVID-19 patient. BRII-198: BRII-198 is a fully human immunoglobulin G (IgG)-1 monoclonal antibody (mAb) derived from antibody P2B-1G5 that was isolated directly from human B cells of a convalescent COVID-19 patient. Remdesivir: Antiviral agent
OG001	Placebo Plus SOC	Placebo administered by IV infusion Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion Placebo: Commercially available 0.9% sodium chloride solution Remdesivir: Antiviral agent

Units

Secondary

Number of Participants With a Safety Outcome Through Day 90

Death, SAE, clinical organ failure, serious infections through Day 90

Posted

Count of Participants

Participants

Through Day 90

ID	Title	Description
OG000	BRII-196/BRII-198 Plus SOC	BRII-196 1000 mg solution; administered as IV infusion BRII-198 1000 mg solution; administered as IV infusion Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion BRII-196: BRII-196 is a fully human immunoglobulin G (IgG)-1 monoclonal antibody (mAb) derived from antibody P2C-1F11 that was isolated directly from human B cells of a convalescent COVID-19 patient. BRII-198: BRII-198 is a fully human immunoglobulin G (IgG)-1 monoclonal antibody (mAb) derived from antibody P2B-1G5 that was isolated directly from human B cells of a convalescent COVID-19 patient. Remdesivir: Antiviral agent
OG001	Placebo Plus SOC	Placebo administered by IV infusion Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion Placebo: Commercially available 0.9% sodium chloride solution Remdesivir: Antiviral agent

Units	Counts

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	BRII-196/BRII-198 Plus SOC	BRII-196 1000 mg solution; administered as IV infusion BRII-198 1000 mg solution; administered as IV infusion Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion BRII-196: BRII-196 is a fully human immunoglobulin G (IgG)-1 monoclonal antibody (mAb) derived from antibody P2C-1F11 that was isolated directly from human B cells of a convalescent COVID-19 patient. BRII-198: BRII-198 is a fully human immunoglobulin G (IgG)-1 monoclonal antibody (mAb) derived from antibody P2B-1G5 that was isolated directly from human B cells of a convalescent COVID-19 patient. Remdesivir: Antiviral agent	15	176	13	176	45	176
EG001	Placebo Plus SOC	Placebo administered by IV infusion Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion Placebo: Commercially available 0.9% sodium chloride solution Remdesivir: Antiviral agent	13	177	11	177	40	177

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Atrial fibrillation	Cardiac disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Small intestinal obstruction	Gastrointestinal disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
COVID-19 pneumonia	Infections and infestations	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Infusion related reaction	Injury, poisoning and procedural complications	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Transaminases increased	Investigations	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Hepatic enzyme increased	Investigations	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Dehydration	Metabolism and nutrition disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Hyperglycemia	Metabolism and nutrition disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Glioblastoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Encephalopathy	Nervous system disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Presyncope	Nervous system disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Syncope	Nervous system disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Bronchospasm	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0011 events1 affected177 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0002 events2 affected176 at risk EG0011 events1 affected177 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0011 events1 affected177 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Organizing pneumonia	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Orthostatic hypotension	Vascular disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Extremity necrosis	Vascular disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Iron deficiency anaemia	Blood and lymphatic system disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Arrhythmia	Cardiac disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Atrial fibrillation	Cardiac disorders	Non-systematic Assessment	EG0002 events2 affected176 at risk EG0010 events0 affected177 at risk
Bradycardia	Cardiac disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Pericarditis	Cardiac disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Sinus tachycardia	Cardiac disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Supraventricular tachycardia	Cardiac disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Tachycardia	Cardiac disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Pneumopericardium	Cardiac disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Vertigo	Ear and labyrinth disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Abdominal pain	Gastrointestinal disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Constipation	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Diarrhea	Gastrointestinal disorders	Non-systematic Assessment	EG0004 events4 affected176 at risk EG0010 events0 affected177 at risk
Dysphagia	Gastrointestinal disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Gastrointestinal hemorrhage	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Melena	Gastrointestinal disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Nausea	Gastrointestinal disorders	Non-systematic Assessment	EG0002 events2 affected176 at risk EG0010 events0 affected177 at risk
Vomiting	Gastrointestinal disorders	Non-systematic Assessment	EG0002 events2 affected176 at risk EG0010 events0 affected177 at risk
Asthenia	General disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Fatigue	General disorders	Non-systematic Assessment	EG0002 events2 affected176 at risk EG0016 events6 affected177 at risk
Pyrexia	General disorders	Non-systematic Assessment	EG0002 events2 affected176 at risk EG0012 events2 affected177 at risk
Hepatitis	Hepatobiliary disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Bacteraemia	Infections and infestations	Non-systematic Assessment	EG0002 events2 affected176 at risk EG0010 events0 affected177 at risk
Clostridium difficile colitis	Infections and infestations	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Pneumonia	Infections and infestations	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0012 events1 affected177 at risk
Pneumonia staphylococcal	Infections and infestations	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Pneumonia viral	Infections and infestations	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Pyelonephritis	Infections and infestations	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Sepsis	Infections and infestations	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Septic shock	Infections and infestations	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Urinary tract infection	Infections and infestations	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0012 events2 affected177 at risk
Pneumonia bacterial	Infections and infestations	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0011 events1 affected177 at risk
Blood glucose increased	Investigations	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Oxygen consumption increased	Investigations	Non-systematic Assessment	EG0002 events2 affected176 at risk EG0010 events0 affected177 at risk
Dehydration	Metabolism and nutrition disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Diabetes mellitus	Metabolism and nutrition disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Fluid retention	Metabolism and nutrition disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Hyperglycemia	Metabolism and nutrition disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0012 events2 affected177 at risk
Hypoglycemia	Metabolism and nutrition disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Decreased appetite	Metabolism and nutrition disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0002 events1 affected176 at risk EG0010 events0 affected177 at risk
Myalgia	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0012 events1 affected177 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Cerebrovascular accident	Nervous system disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Dizziness	Nervous system disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Headache	Nervous system disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0011 events1 affected177 at risk
Hypoaesthesia	Nervous system disorders	Non-systematic Assessment	EG0002 events1 affected176 at risk EG0010 events0 affected177 at risk
Syncope	Nervous system disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Metabolic encephalopathy	Nervous system disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Anxiety	Psychiatric disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Delirium	Psychiatric disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0013 events3 affected177 at risk
Mental status changes	Psychiatric disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0013 events3 affected177 at risk
Anxiety disorder	Psychiatric disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Acute kidney injury	Renal and urinary disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0011 events1 affected177 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0003 events2 affected176 at risk EG0014 events4 affected177 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG00016 events14 affected176 at risk EG00115 events13 affected177 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0008 events8 affected176 at risk EG0018 events6 affected177 at risk
Lung infiltration	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0011 events1 affected177 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0003 events3 affected176 at risk EG0012 events2 affected177 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0011 events1 affected177 at risk
Tachypnoea	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected177 at risk
Hypotension	Vascular disorders	Non-systematic Assessment	EG0008 events7 affected176 at risk EG0013 events3 affected177 at risk
Orthostatic hypotension	Vascular disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Shock	Vascular disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Thrombosis	Vascular disorders	Non-systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected177 at risk
Ear and Labyrinth	Vascular disorders	Non-systematic Assessment	EG0002 events2 affected176 at risk EG0010 events0 affected177 at risk

ID	Term
D000086382	COVID-19
D003333	Coronaviridae Infections
D018352	Coronavirus Infections
D012327	RNA Virus Infections
D014777	Virus Diseases
D030341	Nidovirales Infections
D045169	Severe Acute Respiratory Syndrome

ID	Term
D011024	Pneumonia, Viral
D011014	Pneumonia
D012141	Respiratory Tract Infections
D007239	Infections
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
C000721042	amubarvimab
C000721043	romlusevimab
C000606551	remdesivir