ImmuneRACE - Immune Response Action to COVID-19 Events

Completed

• Conditions: Covid19

• Registration Number: NCT04494893
• Lead Sponsor: Adaptive Biotechnologies

Brief Summary

ImmuneRACE is a study, which is designed to better understand the immune response to COVID-19. This is critically important because the immune system may be able to tell us important information about how our own bodies detect and respond to the disease that current tests cannot. De-identified data collected from this study may accelerate the development of better diagnostics for COVID-19 and improve outcomes for many.

Detailed Description

PURPOSE Aim 1. Compare disease-specific TCR signatures in patients vs. controls Aim 2. Identify antigens that elicit a T-cell response Aim 3. Risk Stratification based on immune signature Aim 4. Early detection

Secondary Aim:

Aim 5. Identify and/or confirm antigenic binding (BCR PairSEQ/neutralizing antibodies)

STUDY POPULATION Approximately 1000 individuals, between the ages of 18 - 89 Cohort 1. EXPOSED to someone with a confirmed diagnosis of COVID-19 Cohort 2. ACTIVE COVID-19

Individuals with a confirmed diagnosis of COVID-19:

Clinical diagnosis made by a medical professional, or Positive laboratory test Cohort 3. RECOVERED from COVID-19

Individuals with a previously confirmed diagnosed and cleared from active infection by either:

Testing negative on two consecutive swab tests, or Cleared by a healthcare professional, or Resolution of symptoms

METHODS Decentralized study (visits occur at participant's houses) Utilizing remote phlebotomy to collect (1) whole blood, (2) serum, (3) nose or throat swab Collection of relevant metadata by electronic questionnaire

Option for longitudinal collection of up to 4 additional blood draws and questionnaires

Study Timeline

• Study Start: 2020-04-24
• Study First Submitted: 2020-07-29
• Study First Submitted QC: 2020-07-29
• Study First Posted: 2020-07-31
• Primary Completion: 2021-03-23
• Study Completion: 2021-04-23
• Status Verified: 2022-02
• Last Update Submitted: 2022-02-14
• Last Update Posted: 2022-02-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 808

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Comparison of disease-specific TCR signatures in patients and controls	Baseline	We will run immunoSEQ on approximately 1000 patient samples with disease status unblinded. After sequencing these samples, we will quantitatively describe the compartment of the T-cell repertoire specific for the disease of interest. We will then use these data to construct a classifier that accurately distinguishes patients from controls.
Identify the immunodominant antigens that elicit a T-cell response to COVID-19	Baseline	We developed technology to query the antigen specificity of the T-cell repertoire to hundreds of peptide epitopes in a single blood sample5. This technology not only allows us to parse out immunodominant epitopes of a given infection from irrelevant epitopes, but also allows us to determine the TCR sequences of the T cells responding to these immunodominant epitopes. We will use this technology to determine which peptide epitopes derived from the SARS-CoV-2 genome commonly elicit an immunodominant T-cell response in different samples. The TCR sequence data generated from these studies will be used to boost the diagnostic classifier obtained in Aim 1. In addition, the identification of immunodominant epitopes can be disseminated to fuel studies in vaccine design and antigen specific T-cell responses relating to clinical outcome in other labs.
Risk Stratification based on an individual's immune signature	Baseline	There is a critical need for a reliable risk stratification test to enable treatment prioritization given the potentially massive number of symptomatic patients. Despite an emerging understanding of the diagnosis of COVID-19, how it spreads, and the death rate, there is no currently available way to predict who needs hospitalization beyond age associated risk and limited epidemiologically linked comorbidities.
Determine whether an immune signature can be detected in individuals exposed to SARS-CoV-2 earlier than currently available tests	Baseline	Another critical need to contain the spread of SARS-CoV-2 is to determine the false negative rate of the RNA test in asymptomatic people and offer an alternative diagnostic that is more sensitive in this cohort. For example, it is possible that early stage disease is not picked up by RNA tests because the virus may be isolated to regions such as the lower respiratory cavity that are not assessed by standard testing methods. We aim to determine whether the immune response can be used to detect the virus from a simple blood test thereby providing a more sensitive test in asymptomatic people even if the virus itself is not directly detectable in the upper respiratory region.

Secondary Outcome Measures

Name	Time	Method
Explore whether additional research assays could potential identify and/or confirm antigenic binding	Baseline	As a secondary aim, Adaptive will perform explorational research with additional sequencing-based research assays to profile the adaptive immune system, such as, but not limited to TCR pairSEQ26 and B-cell receptor (BCR) pairSEQ3. These assays use a combinatorial method for pairing TCR alpha and beta chain sequences and BCR heavy and light chain sequences. The output is a large set of full length paired BCR or TCR sequences, which allows reconstruction of a functional antibody or TCR. We regularly utilize the results of our pairSEQ assays to identify and/or confirm antigenic binding. For the case of BCR pairSEQ, the resulting antibody sequences could potentially have therapeutic value for imparting passive immunity.

Trial Locations

Locations (1)

Adaptive Biotechnologies; 🇺🇸 Seattle, Washington, United States