A Study of Immune Responses to the Virus That Causes COVID-19

Study Overview
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Brief Summary
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The purpose of this study is to learn more about the acute response to infection with and recovery from the virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Some people know this virus by the name coronavirus. It can cause the disease called COVID-19. The information gained from the study can be used to help develop better tests for SARS-CoV-2 infection and COVID-19 disease and may help in developing future vaccines, other prevention strategies, and treatments.

Detailed Description
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This is a prospective study of acute immune responses to SARSCoV-2 infection. The study will include 3 groups, as described in the table below. Groups are defined based on clinical status at enrollment, but for the purposes of data analysis, participants who experience disease progression can contribute data to other cohorts. Participants will complete six visits over 28 days followed by a health contact at Month 2 (one month after the last scheduled visit). Additional follow up visit(s) may be added over time in response to evolving information regarding SARS-CoV-2 infection and COVID-19. Study visits may include review of medical history; interviews/questionnaires; pregnancy tests (for participants assigned female sex at birth); blood draws; nasal swab, nasal wash, and saliva sample collection; and optional stool sample collection.

Official Title
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A Prospective Study of Acute Immune Responses to SARSCoV-2 Infection

Conditions
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SARS-CoV-2, COVID-19

Intervention / Treatment
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* Other: Sample collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older. Test result indicating presence of SARS-CoV-2 virus. Sites must have results from assays that are approved as FDA-emergency use authorized or as standard-of-care by other applicable regional governing bodies. For timing of testing, please see group specific criteria below. Ability and willingness to provide informed consent. Willingness to have clinical research staff come to place of residence or hospital if needed. Willingness to be followed for the planned duration of the study. Assessment of understanding: volunteer demonstrates understanding of this study. Agreement to allow access to medical records. Asymptomatic participants: No current symptoms. No symptoms consistent with COVID-19 within 2 weeks prior to positive test according to the clinical judgement of the investigating clinician. Symptoms include, but are not limited to, fever, headache, sore throat, cough, dyspnea, rhinorrhea, diarrhea, myalgias, chills, and anosmia. Please refer to https://www.cdc.gov/coronavirus/2019-ncov/symptomstesting/symptoms.html for the current list of symptoms consistent with COVID-19. Positive SARS-CoV-2 RNA test or antigen test within six days prior to enrollment (target time) up to 10 days prior to enrollment (upper allowable window). Symptomatic (non-hospitalized) participants: Onset of mild symptoms consistent with COVID-19 within 6 days prior to enrollment (target time) up to 14 days prior to enrollment (upper allowable window). Symptoms of COVID-19 to be determined by the clinical judgement of the investigating clinician including-- but not limited to-- fever, headache, sore throat, cough, dyspnea, rhinorrhea, diarrhea myalgias, chills, and anosmia. Please refer to https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html for the current list of symptoms consistent with COVID-19. Positive SARS-CoV-2 RNA test or antigen test within six days prior to enrollment (target time) up to 10 days prior to enrollment (upper allowable window). Symptomatic (hospitalized) participants Participant hospitalized for COVID-19 within 3 days prior to enrollment (note: there is no timeframe for either symptom onset or timing of SARS-CoV-2 PCR or antigen testing for hospitalized participants) Exclusion Criteria: Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence or a volunteer's ability to give informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1<br>Persons that are positive for SARS-CoV-2 and are asymptomatic | Other: Sample collection<br>* blood, nasal swab, nasal wash, and saliva optional stool swab<br>|
| Group 2<br>Persons that are positive for SARS-CoV-2 with recent onset of mild symptoms (not hospitalized) | Other: Sample collection<br>* blood, nasal swab, nasal wash, and saliva optional stool swab<br>|
| Group 3<br>Persons that are positive for SARS-CoV-2 and are symptomatic hospitalized patients | Other: Sample collection<br>* blood, nasal swab, nasal wash, and saliva optional stool swab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate of SARS-CoV-2-specific B cells in peripheral blood samples | Characterized using fluorescently labeled recombinant proteins in combination with a flow cytometry phenotyping panel | Measured through day 14 | 
| Magnitude of SARS-CoV-2-specific B cells in peripheral blood samples | Characterized using fluorescently labeled recombinant proteins in combination with a flow cytometry phenotyping panel | Measured through day 14 | 
| Phenotypic characterization of SARS-CoV-2-specific B cells in peripheral blood samples | Characterized using fluorescently labeled recombinant proteins in combination with a flow cytometry phenotyping panel | Measured through day 14 | 
| Response rate of SARS-CoV-2-specific antibody binding in serum samples | Measured by binding antibody multiplex assay (BAMA) | Measured through day 28 | 
| Response rate of SARS-CoV-2-specific neutralizing antibodies in serum samples | Measured by neutralizing antibody assay (nAb) | Measured through day 28 | 
| Magnitude of SARS-CoV-2-specific antibody binding antibodies in serum samples | Measured by binding antibody multiplex assay (BAMA) | Measured through day 28 | 
| Magnitude of SARS-CoV-2-specific neutralizing antibodies in serum samples | Measured by neutralizing antibody assay (nAb) | Measured through day 28 | 
| Response rate of SARS-CoV-2-specific binding antibodies in nasal wash samples | Measured by binding antibody multiplex assay (BAMA) | Measured through day 28 | 
| Magnitude of SARS-CoV-2-specific binding antibodies in nasal wash samples | Measured by binding antibody multiplex assay (BAMA) | Measured through day 28 | 
| Frequency of leukocyte populations in peripheral blood | Measured by flow cytometry | Measured through day 14 | 
| Transcriptional profiles of peripheral blood leukocytes | Measured by gene expression analysis by RNA sequencing, real-time PCR, single-cell proteogenomic profiling | Measured through day 14 | 
| Concentration of serum cytokines and other soluble factors | Measured by multiplexed protein detection assays and/or enzyme-linked immunosorbent assays (ELISA) | Measured through day 28 | 
| Response rate of SARS-CoV-2-specific CD4+ and CD8+ T cells | Measured by flow cytometry | Measured through day 28 | 
| Magnitude of SARS-CoV-2-specific CD4+ and CD8+ T cells | Measured by flow cytometry | Measured through day 28 | 
| Functional profiling, including intracellular cytokine staining, of SARS-CoV-2-specific CD4+ and CD8+ T cells | Measured by flow cytometry | Measured through day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantitation of viral RNA in nasal swabs | Measured by extraction of nucleic acid for analysis of microorganism RNA or DNA by qPCR and/or amplicon- or metagenomics-sequencing methods and subsequent gene and taxa-level bioinformatics analyses | Measured through day 28 |