Characterizing SARS-CoV-2-specific Immunity in Individuals Who Have Recovered From COVID-19

Study Overview
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Brief Summary
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The purpose of this study is to learn more about 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 will be used to help develop better tests for SARS-CoV-2 infection and COVID-19 disease and may help in developing future vaccines and treatments by allowing researchers to determine the difference between the body's immune response to natural SARS-CoV-2 infection and immunization with a SARS-CoV-2 vaccine.

Detailed Description
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This study aims to characterize the SARS-CoV-2-specific immunity in convalescent individuals. The observational cohort study will include 3 groups, as described in the table below. Participants will complete a minimum of one visit (1-8 weeks post resolution of COVID-19 OR 2-10 weeks post most recent positive SARS-CoV-2 test, if asymptomatic) and optional visits approximately 2 months, 4 months, and 1 year later. Participants diagnosed with SARS-CoV-2 infection at an optional follow-up visit may be contacted more frequently. 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 physical examinations, medical history, questionnaires, pregnancy tests (for participants assigned female at birth), blood draws, optional nasal samples, and optional HIV testing.

Official Title
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Characterizing SARS-CoV-2-specific Immunity in Convalescent Individuals

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 or older. Reports having had a positive test for SARS-CoV-2. Reports resolution of COVID-19 within 1-8 weeks of enrollment OR, if asymptomatic infection, reports positive SARS-CoV-2 test within 2-10 weeks of enrollment. Not excluded: individuals with symptoms consistent with residual sequelae of resolved COVID-19, in the clinical judgement of the investigator. Access to a participating HVTN or HPTN CRS and willingness to be followed for the planned duration of the study. Ability and willingness to provide informed consent. Assessment of understanding: volunteer demonstrates understanding of this study. Volunteers who were assigned female sex at birth: negative urine or serum beta human chorionic gonadotropin (β-HCG) pregnancy test within 4 days of enrollment visit (ie, prior to enrollment blood draw or nasal collections). Persons who are NOT of reproductive potential due to having undergone hysterectomy or bilateral oophorectomy (verified by medical records) or having reached menopause (no menses for ≥ 1 year ), are not required to undergo pregnancy testing. Exclusion Criteria: Reports current COVID-19. Pregnant. Receipt of SARS-CoV-2 specific antibodies (eg, convalescent plasma or sera, monoclonal antibodies, hyperimmune globulin). Not excluded: antibody therapy without SARS-CoV-2 specificity (eg, IL-6 pathway inhibitors for COVID-19). SARS-CoV-2 vaccine(s) received in a prior vaccine trial. 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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Accepts Healthy Volunteers

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 not hospitalized for COVID-19, without clinical spectrum or outcomes specified in group 3 1A: Persons with asymptomatic infection, ages 18 through 55, inclusive 1B: Persons with asymptomatic infection, age > 55 1C: Persons with symptomatic infection (ie, COVID-19) ages 18 through 55 1D: Persons with symptomatic infection (ie, COVID-19), age > 55 | Other: Sample collection<br>* Optional nasal specimen(s) Blood collection<br>|
| Group 2<br>Persons previously hospitalized for COVID-19, without clinical spectrum or outcomes specified in group 3 2A: Persons 18 through 55 years of age 2B: Persons > 55 years of age | Other: Sample collection<br>* Optional nasal specimen(s) Blood collection<br>|
| Group 3<br>Persons with specific clinical spectrums or outcomes, regardless of hospitalization history (eg, persons recovered after intubation, with prolonged viral shedding, with myocarditis/pericarditis, with rapid recovery from COVID-19, with a second positive SARS-CoV-2 RT-PCR test result after a negative result) | Other: Sample collection<br>* Optional nasal specimen(s) Blood collection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Humoral responses to peptide antigens derived from SARS-CoV-2 structural proteins and regions of the spike protein not present in vaccines | Measured by peptide microarray | Measured through participant's last visit at Month 0, 2, 4, or 12 | 
| SARS-CoV-2-specific antibody binding response rate | Measured by binding antibody multiplex assay (BAMA) | Measured through participant's last visit at Month 0, 2, 4, or 12 | 
| SARS-CoV-2-specific antibody binding response magnitude | Measured by binding antibody multiplex assay (BAMA) | Measured through participant's last visit at Month 0, 2, 4, or 12 | 
| SARS-CoV-2-specific antibody binding response epitope specificity | Measured by binding antibody multiplex assay (BAMA) | Measured through participant's last visit at Month 0, 2, 4, or 12 | 
| SARS-CoV-2-specific antibody neutralization response rate | Measured by neutralizing antibody assay (NAb) | Measured through participant's last visit at Month 0, 2, 4, or 12 | 
| SARS-CoV-2-specific antibody neutralization response magnitude | Measured by neutralizing antibody assay (NAb) | Measured through participant's last visit at Month 0, 2, 4, or 12 | 
| SARS-CoV-2-specific antibody neutralization response epitope specificity | Measured by neutralizing antibody assay (NAb) | Measured through participant's last visit at Month 0, 2, 4, or 12 | 
| SARS-CoV-2-specific Antibody-Dependent Cellular Cytotoxicity (ADCC) response rate | Measured by antibody-dependent cellular cytotoxicity assay (ADCC) | Measured through participant's last visit at Month 0, 2, 4, or 12 | 
| SARS-CoV-2-specific Antibody-Dependent Cellular Cytotoxicity (ADCC) response magnitude | Measured by antibody-dependent cellular cytotoxicity assay (ADCC) | Measured through participant's last visit at Month 0, 2, 4, or 12 | 
| SARS-CoV-2-specific Antibody-Dependent Cellular Cytotoxicity (ADCC) response epitope specificity | Measured by antibody-dependent cellular cytotoxicity assay (ADCC) | Measured through participant's last visit at Month 0, 2, 4, or 12 | 
| SARS-CoV-2-specific CD4+ and CD8+ T cell responses | Measured by flow cytometry | Measured through participant's last visit at Month 0, 2, 4, or 12 | 
| SARS-CoV-2-specific CD4+ and CD8+ T cell response rate | Measured by flow cytometry | Measured through participant's last visit at Month 0, 2, 4, or 12 | 
| SARS-CoV-2-specific CD4+ and CD8+ T cell response magnitude | Measured by flow cytometry | Measured through participant's last visit at Month 0, 2, 4, or 12 | 
| SARS-CoV-2-specific CD4+ and CD8+ T cell response functional profiling | Measured by flow cytometry | Measured through participant's last visit at Month 0, 2, 4, or 12 | 
| SARS-CoV-2-specific memory B cell characterization | Measured by phenotyping and monoclonal antibody isolation | Measured through participant's last visit at Month 0, 2, 4, or 12 | 
| SARS-CoV-2-specific infection presentation, including clinical course, along with demographics and corresponding medical history of participants | Tabulated overall and by group | Measured through participant's last visit at Month 0, 2, 4, or 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection of viral RNA in nasopharyngeal or nasal swab samples | Measured by real-time reverse transcription polymerase chain reaction (RT-PCR) assay | Measured through participant's last visit at Month 0, 2, 4, or 12 | 
| Response rate of SARS-CoV-2-specific binding antibodies in nasal samples | Measured by binding antibody multiplex assay (BAMA) | Measured through participant's last visit at Month 0, 2, 4, or 12 | 
| Response magnitude of SARS-CoV-2-specific binding antibodies in nasal samples | Measured by binding antibody multiplex assay (BAMA) | Measured through participant's last visit at Month 0, 2, 4, or 12 |