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

• ClinicalTrials.gov Identifier: NCT04403880
• Recruitment Status: Completed
• First Posted: May 27, 2020
• Last Update Posted: May 27, 2022
• Sponsor: HIV Vaccine Trials Network
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); HIV Prevention Trials Network
• Information provided by (Responsible Party): HIV Vaccine Trials Network

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
SARS-CoV-2; COVID-19	Other: Sample collection

Detailed Description:

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.

Study Design

• Study Type: Observational
• Actual Enrollment: 759 participants
• Observational Model: Cohort
• Time Perspective: Other
• Official Title: Characterizing SARS-CoV-2-specific Immunity in Convalescent Individuals
• Actual Study Start Date: May 13, 2020
• Actual Primary Completion Date: April 21, 2022
• Actual Study Completion Date: April 21, 2022

Groups and Cohorts

Group/Cohort	Intervention/treatment
Group 1; 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; Optional nasal specimen(s); Blood collection
Group 2; 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; Optional nasal specimen(s); Blood collection
Group 3; 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; Optional nasal specimen(s); Blood collection

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Probability Sample

Study Population

Persons reporting a positive test for SARS-CoV-2 and resolution of COVID-19 within 1-8 weeks of enrollment OR, if asymptomatic infection, reporting positive SARS-CoV-2 test within 2-10 weeks of enrollment.

Criteria

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.

Contacts and Locations

Locations

United States, Alabama

Alabama Vaccine CRS

Birmingham, Alabama, United States, 35294

United States, California

UCLA CARE Center CRS

Los Angeles, California, United States, 90035

Bridge HIV CRS

San Francisco, California, United States, 94143

United States, District of Columbia

George Washington University CRS

Washington, District of Columbia, United States, 20037-1894

United States, Georgia

The Ponce de Leon Center CRS

Atlanta, Georgia, United States, 30308-2012

The Hope Clinic of the Emory Vaccine Center CRS

Decatur, Georgia, United States, 30030

United States, Illinois

Adolescent & Young Adult Research at The CORE Center (AYAR at CORE)

Chicago, Illinois, United States, 60612

United States, Louisiana

New Orleans Adolescent Trials Unit CRS

New Orleans, Louisiana, United States, 70112

United States, Maryland

Johns Hopkins University CRS

Baltimore, Maryland, United States, 21205

United States, Massachusetts

Brigham and Women's Hospital Vaccine CRS (BWH VCRS)

Boston, Massachusetts, United States, 02115-6110

Fenway Health Clinical Research Site CRS

Boston, Massachusetts, United States, 02215-4302

United States, New Jersey

New Jersey Medical School Clinical Research Center CRS

Newark, New Jersey, United States, 07103

United States, New York

Bronx Prevention Research Center CRS

Bronx, New York, United States, 10451

Harlem Prevention Center CRS

New York, New York, United States, 10027

Columbia P&S CRS

New York, New York, United States, 10032-3732

New York Blood Center CRS

New York, New York, United States, 10065

University of Rochester Vaccines to Prevent HIV Infection CRS

Rochester, New York, United States, 14642

United States, North Carolina

Chapel Hill CRS

Chapel Hill, North Carolina, United States, 27599

United States, Pennsylvania

Penn Prevention CRS

Philadelphia, Pennsylvania, United States, 19104

United States, Tennessee

Vanderbilt Vaccine CRS

Nashville, Tennessee, United States, 37232-2582

United States, Washington

Seattle Vaccine and Prevention CRS

Seattle, Washington, United States, 98109-1024

Malawi

Malawi CRS

Lilongwe, Malawi

Peru

CITBM - UNIDEC, Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales CRS

Bellavista, Callao, Peru, 15081

San Miguel CRS

San Miguel, Lima, Peru, 32-15088

Asociacion Civil Selva Amazonica (ACSA) CRS

Iquitos, Maynas, Peru, 1

Via Libra CRS

Lima, Peru, 15001

Barranco CRS

Lima, Peru, 15063

South Africa

Josha Research CRS

Bloemfontein, South Africa

Emavundleni CRS

Cape Town, South Africa

Groote Schuur HIV CRS

Cape Town, South Africa

Khayelitsha CRS / (CIDRI UCT)

Cape Town, South Africa

Masiphumelele Clinical Research Site (MASI) CRS

Cape Town, South Africa

Chatsworth CRS

Chatsworth, South Africa

Botha's Hill CRS

Durban, South Africa

CAPRISA eThekwini CRS

Durban, South Africa

Vulindlela CRS

Durban, South Africa

Isipingo CRS

Isipingo, South Africa

Kliptown Soweto CRS

Johannesburg, South Africa

Soweto HVTN CRS

Johannesburg, South Africa

Aurum Institute Klerksdorp CRS

Klerksdorp, South Africa

Qhakaza Mbokodo Research Clinic CRS

Ladysmith, South Africa

Nelson Mandela Academic Research Unit CRS

Mthatha, South Africa

Synexus Stanza Clinical Research Centre CRS

Pretoria, South Africa

Rustenburg CRS

Rustenburg, South Africa

Setshaba Research Centre CRS

Soshanguve, South Africa

Tembisa Clinic 4 CRS

Tembisa, South Africa

The Aurum Institute Tembisa Clinical Research Centre CRS

Tembisa, South Africa

Tongaat CRS

Tongaat, South Africa

Verulam CRS

Verulam, South Africa

Zambia

Matero Reference Clinic CRS

Lusaka, Zambia

Zimbabwe

St Mary's CRS

Chitungwiza, Zimbabwe

Zengeza CRS

Chitungwiza, Zimbabwe

Seke South CRS

Harare, Zimbabwe

Sponsors and Collaborators

HIV Vaccine Trials Network

National Institute of Allergy and Infectious Diseases (NIAID)

HIV Prevention Trials Network

Investigators

• Study Chair: Larry Corey; HIV Vaccine Trials Network, Fred Hutch
• Study Chair: Shelly Karuna; HIV Vaccine Trials Network, Fred Hutch

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Karuna S, Li SS, Grant S, Walsh SR, Frank I, Casapia M, Trahey M, Hyrien O, Fisher L, Miner MD, Randhawa AK, Polakowski L, Kublin JG, Corey L, Montefiori D; HVTN 405/HPTN 1901 Study Team. Neutralizing antibody responses over time in demographically and clinically diverse individuals recovered from SARS-CoV-2 infection in the United States and Peru: A cohort study. PLoS Med. 2021 Dec 6;18(12):e1003868. doi: 10.1371/journal.pmed.1003868. eCollection 2021 Dec.

• Responsible Party: HIV Vaccine Trials Network
• ClinicalTrials.gov Identifier: NCT04403880
• Other Study ID Numbers: HVTN 405/HPTN 1901; 5UM1AI068614-14 ( U.S. NIH Grant/Contract )
• First Posted: May 27, 2020
• Last Update Posted: May 27, 2022
• Last Verified: May 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

COVID-19; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases