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

NCT04403880 | Completed Results

• 2 other identifiers: HVTN 405/HPTN 19015UM1AI068614-14
• Study Type: observational
• Target: 760
• Locations: 5 countries
• Sites: 52

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.

Conditions

SARS-CoV-2; COVID-19

Outcome Measures

Primary Outcomes (62)

• SARS-CoV-2-specific Antibody Binding Response Rate (BAMA IgG1) by Region and Enrollment Group Among America Cohort

  BAMA assays was performed for samples from participants at Visit 1 (Month 0, baseline) and available samples at follow-up visits (Month 2, 4). Serum SARS-CoV-2-specific IgA, IgG1, IgG3 responses (dilution 1:50) to SARS-CoV-2 antigens were measured on a Bio-Plex instrument (Bio-Rad). The Bioplex software provides 2 readouts: a background-subtracted mean fluorescence intensity (MFI), where background refers to a plate level control (i.e., a blank well run on each plate), and a concentration based on a standard curve. Positive responses at each visit will be called if the MFI minus blank values are ≥ isotype, antigen, and dilution-specific cutoff (will be provided by the lab). MFIs minus blank (or net MFI) are used to summarize the magnitude at a given time-point. The table summarized SARS-CoV-2-specific Antibody Binding Response Rate by binding antibody multiplex assay (BAMA IgG1) at Visit 1, 2, 3, overall and by region and enrollment group

  Measured at Months 0, 2, 4

• SARS-CoV-2-specific Antibody Binding Response Magnitude (BAMA IgG1) by Region and Enrollment Group Among America Cohort

  BAMA assays was performed for samples from participants at Visit 1 (Month 0, baseline) and available samples at follow-up visits (Month 2, 4). Serum SARS-CoV-2-specific IgA, IgG1, IgG3 responses (dilution 1:50) to SARS-CoV-2 antigens were measured on a Bio-Plex instrument (Bio-Rad). The Bioplex software provides 2 readouts: a background-subtracted mean fluorescence intensity (MFI), where background refers to a plate level control (i.e., a blank well run on each plate), and a concentration based on a standard curve. Positive responses at each visit will be called if the MFI minus blank values are ≥ isotype, antigen, and dilution-specific cutoff (will be provided by the lab). MFIs minus blank (or net MFI) are used to summarize the magnitude at a given time-point. The table summarized SARS-CoV-2-specific Antibody Binding Response Magnitude by binding antibody multiplex assay (BAMA IgG1) at Visit 1, 2, 3, overall and by region and enrollment group

  Measured at Months 0, 2, 4

• SARS-CoV-2-specific Antibody Binding Response Rate (BAMA IgG3) by Region and Enrollment Group Among America Cohort

  BAMA assays was performed for samples from participants at Visit 1 (Month 0, baseline) and available samples at follow-up visits (Month 2, 4). Serum SARS-CoV-2-specific IgA, IgG1, IgG3 responses (dilution 1:50) to SARS-CoV-2 antigens were measured on a Bio-Plex instrument (Bio-Rad). The Bioplex software provides 2 readouts: a background-subtracted mean fluorescence intensity (MFI), where background refers to a plate level control (i.e., a blank well run on each plate), and a concentration based on a standard curve. Positive responses at each visit will be called if the MFI minus blank values are ≥ isotype, antigen, and dilution-specific cutoff (will be provided by the lab). MFIs minus blank (or net MFI) are used to summarize the magnitude at a given time-point. The table summarizedSARS-CoV-2-specific Antibody Binding Response Rate by binding antibody multiplex assay (BAMA IgG3) at Visit 1, 2, overall and by region and enrollment group among America Cohort

  Measured at Months 0, 2

• SARS-CoV-2-specific Antibody Binding Response Magnitude (BAMA IgG3) by Region and Enrollment Group Among America Cohort

  BAMA assays was performed for samples from participants at Visit 1 (Month 0, baseline) and available samples at follow-up visits (Month 2, 4). Serum SARS-CoV-2-specific IgA, IgG1, IgG3 responses (dilution 1:50) to SARS-CoV-2 antigens were measured on a Bio-Plex instrument (Bio-Rad). The Bioplex software provides 2 readouts: a background-subtracted mean fluorescence intensity (MFI), where background refers to a plate level control (i.e., a blank well run on each plate), and a concentration based on a standard curve. Positive responses at each visit will be called if the MFI minus blank values are ≥ isotype, antigen, and dilution-specific cutoff (will be provided by the lab). MFIs minus blank (or net MFI) are used to summarize the magnitude at a given time-point. The table summarizedSARS-CoV-2-specific Antibody Binding Response Magnitude by binding antibody multiplex assay (BAMA IgG3) at Visit 1, 2, overall and by region and enrollment group among America Cohort

  Measured at Months 0, 2

• SARS-CoV-2-specific Antibody Binding Response Rate (BAMA IgA) by Region and Enrollment Group Among America Cohort

  BAMA assays was performed for samples from participants at Visit 1 (Month 0, baseline) and available samples at follow-up visits (Month 2, 4). Serum SARS-CoV-2-specific IgA, IgG1, IgG3 responses (dilution 1:50) to SARS-CoV-2 antigens were measured on a Bio-Plex instrument (Bio-Rad). The Bioplex software provides 2 readouts: a background-subtracted mean fluorescence intensity (MFI), where background refers to a plate level control (i.e., a blank well run on each plate), and a concentration based on a standard curve. Positive responses at each visit will be called if the MFI minus blank values are ≥ isotype, antigen, and dilution-specific cutoff (will be provided by the lab). MFIs minus blank (or net MFI) are used to summarize the magnitude at a given time-point. The table summarized SARS-CoV-2-specific Antibody Binding Response Rate by binding antibody multiplex assay (BAMA IgA) at Visit 1, 2, overall and by region and enrollment group among America Cohort

  Measured at Months 0, 2

• SARS-CoV-2-specific Antibody Binding Response Magnitude (BAMA IgA) by Region and Enrollment Group Among America Cohort

  BAMA assays was performed for samples from participants at Visit 1 (Month 0, baseline) and available samples at follow-up visits (Month 2). Serum SARS-CoV-2-specific IgA, IgG1, IgG3 responses (dilution 1:50) to SARS-CoV-2 antigens were measured on a Bio-Plex instrument (Bio-Rad). The Bioplex software provides 2 readouts: a background-subtracted mean fluorescence intensity (MFI), where background refers to a plate level control (i.e., a blank well run on each plate), and a concentration based on a standard curve. Positive responses at each visit will be called if the MFI minus blank values are ≥ isotype, antigen, and dilution-specific cutoff (will be provided by the lab). MFIs minus blank (or net MFI) are used to summarize the magnitude at a given time-point. The table summarized SARS-CoV-2-specific Antibody Binding Response Magnitude by binding antibody multiplex assay (BAMA IgA) at Visit 1, 2, overall and by region and enrollment group among America Cohort

  Measured at Months 0, 2

• SARS-CoV-2-specific Antibody Binding Response Rate (Nab) by Region and Enrollment Group Among America Cohort

  Neutralizing antibodies against SARS coronaviruses are measured in 293T/ACE2 cells for all HIV negative samples. MPI (maximum percent inhibition) is also measured. Positivity calls are an ID50/ID80 (50% and 80% inhibitory dose) value either \>20 (the lower limit of detection (LLOD) of the assay) or MPI is between 10%-50%. The neutralizing antibody ID50/ID80 of all HIV positive samples are measured by a different assay, VSV pseudovirus neutralization assay. Positivity calls are based on whether or not any neutralization is observed through entire titration (starting dilution 1:20) with MPI between 10%-50%. For the positive calls but the neutralization does not reach 50% or 80%, ID50/ID80 titer is first estimated by Prism. The table summarized SARS-CoV-2-specific Antibody Binding Response Rate by neutralizing antibody assay (NAb) at Visit 1, 2, 3, 4, overall and by region and enrollment group among America Cohort (USA and Peru only)

  Measured at Months 0, 2, 4, 12

• SARS-CoV-2-specific Antibody Binding Response Magnitude (Nab) by Region and Enrollment Group Among America Cohort

  Neutralizing antibodies against SARS coronaviruses are measured in 293T/ACE2 cells for all HIV negative samples. MPI (maximum percent inhibition) is also measured. Positivity calls are an ID50/ID80 (50% and 80% inhibitory dose) value either \>20 (the lower limit of detection (LLOD) of the assay) or MPI is between 10%-50%. The neutralizing antibody ID50/ID80 of all HIV positive samples are measured by a different assay, VSV pseudovirus neutralization assay. Positivity calls are based on whether or not any neutralization is observed through entire titration (starting dilution 1:20) with MPI between 10%-50%. For the positive calls but the neutralization does not reach 50% or 80%, ID50/ID80 titer is first estimated by Prism. The table summarized SARS-CoV-2-specific Antibody Binding Response Magnitude by neutralizing antibody assay (NAb) at Visit 1, 2,3,4, overall and by region and enrollment group among America Cohort (USA and Peru only)

  Measured at Months 0, 2, 4, 12

• SARS-CoV-2-specific Antibody Binding Response Rate (Nab) by Region and Enrollment Group Among Africa Cohort

  Neutralizing antibodies against SARS coronaviruses are measured in 293T/ACE2 cells for all HIV negative samples. MPI (maximum percent inhibition) is also measured. Positivity calls are an ID50/ID80 (50% and 80% inhibitory dose) value either \>20 (the lower limit of detection (LLOD) of the assay) or MPI is between 10%-50%. The neutralizing antibody ID50/ID80 of all HIV positive samples are measured by a different assay, VSV pseudovirus neutralization assay. Positivity calls are based on whether or not any neutralization is observed through entire titration (starting dilution 1:20) with MPI between 10%-50%. For the positive calls but the neutralization does not reach 50% or 80%, ID50/ID80 titer is first estimated by Prism. The table summarized SARS-CoV-2-specific Antibody Binding Response Rate by neutralizing antibody assay (NAb) at Visit 1, 2, 3, 4, overall and by region and enrollment group among Africa Cohort

  Measured at Months 0, 2, 4, 12

• SARS-CoV-2-specific Antibody Binding Response Magnitude (Nab) by Region and Enrollment Group Among Africa Cohort

  Neutralizing antibodies against SARS coronaviruses are measured in 293T/ACE2 cells for all HIV negative samples. MPI (maximum percent inhibition) is also measured. Positivity calls are an ID50/ID80 (50% and 80% inhibitory dose) value either \>20 (the lower limit of detection (LLOD) of the assay) or MPI is between 10%-50%. The neutralizing antibody ID50/ID80 of all HIV positive samples are measured by a different assay, VSV pseudovirus neutralization assay. Positivity calls are based on whether or not any neutralization is observed through entire titration (starting dilution 1:20) with MPI between 10%-50%. For the positive calls but the neutralization does not reach 50% or 80%, ID50/ID80 titer is first estimated by Prism. The table summarized SARS-CoV-2-specific Antibody Binding Response Magnitude by neutralizing antibody assay (NAb) at Visit 1, 2, 3, 4, overall and by region and enrollment group among Africa Cohort

  Measured at Months 0, 2, 4, 12

• SARS-CoV-2-specific Antibody Binding Response Rate (ADCC) by Region and Enrollment Group Among America Cohort

  Antibody-dependent NK cell degranulation will be measured using ADCC assay at a dilution 1:500. Two readouts will be the background-subtracted % CD107A+ NK cells for the infected cells and the background-subtracted % CD107A+ NK cells for the transfected cells. The positive responses will be called if the values of background-subtracted % CD107A+ ≥ 4.07 and ≥5.27 for the infected and transfected cells, respectively. The cutoffs are determined by mean+2SD, respectively, from the SARS-CoV-2 negative controls. Percent CD107a+ NK Cells was the response magnitudes. The table summarized SARS-CoV-2-specific Antibody Binding Response Rate by antibody-dependent cellular cytotoxicity assay (ADCC) at Visit 1, overall and by region and enrollment group among America Cohort (USA and Peru only)

  Measured at Months 0

• SARS-CoV-2-specific Antibody Binding Response Magnitude (ADCC) by Region and Enrollment Group Among America Cohort

  Antibody-dependent NK cell degranulation will be measured using ADCC assay at a dilution 1:500. Two readouts will be the background-subtracted % CD107A+ NK cells for the infected cells and the background-subtracted % CD107A+ NK cells for the transfected cells. The positive responses will be called if the values of background-subtracted % CD107A+ ≥ 4.07 and ≥5.27 for the infected and transfected cells, respectively. The cutoffs are determined by mean+2SD, respectively, from the SARS-CoV-2 negative controls. Percent CD107a+ NK Cells was the response magnitudes. The table summarized SARS-CoV-2-specific Antibody Binding Response Magnitude by antibody-dependent cellular cytotoxicity assay (ADCC) Visit 1, overall and by region and enrollment group among America Cohort

  Measured at Months 0

• SARS-CoV-2-specific CD4+ and CD8+ T Cell Response Rate (ICS) by Region and Enrollment Group Among America Cohort

  Flow cytometry was used to examine SARS-CoV-2 specific CD4+ and CD8+ T-cell responses using an intracellular cytokine staining (ICS). Positive calls will be made using Fisher's exact positivity test for all the markers. The magnitudes are % T cells expressing IFN-g/IL-2. The table summarized SARS-CoV-2-specific CD4+ and CD8+ T Cell Response Rate by flow cytometry at Visit 1 , overall and by region and enrollment group among America Cohort (USA and Peru only)

  Measured at Months 0

• SARS-CoV-2-specific CD4+ and CD8+ T Cell Response Magnitude (ICS) by Region and Enrollment Group Among America Cohort

  Flow cytometry was used to examine SARS-CoV-2 specific CD4+ and CD8+ T-cell responses using an intracellular cytokine staining (ICS). Positive calls will be made using Fisher's exact positivity test for all the markers. The magnitudes are % T cells expressing IFN-g/IL-2. The table summarized SARS-CoV-2-specific CD4+ and CD8+ T Cell Response Magnitude by flow cytometry at Visit 1, overall and by region and enrollment group among America Cohort positive responders (USA and Peru)

  Measured at Months 0

• SARS-CoV-2-specific Memory B Cell Response Magnitude (B Cell) by Region and Enrollment Group Among America Cohort

  SARS-CoV-2-specific B cell responses and B cell phenotypic data was identified and characterized using fluorescently-labelled recombinant Env proteins (S6P and RBD) in combination with a flow cytometry antibody panel on all available samples from the enrollment visit (V1). There is no positivity call for B cell phenotypic data. The magnitude is B cell subset frequency. The table summarized SARS-CoV-2-specific Memory B Cell Response Magnitude by flow cytometry at Visit 1, overall and by region and enrollment group among America Cohort (USA and Peru only)

  Measured at Months 0.

• SARS-CoV-2-specific Antibody Binding Response Rate (IgG1) by Region and COVID-19 Severity Among America Cohort

  BAMA assays was performed for samples from participants at Visit 1 (Month 0, baseline) and available samples at follow-up visits (Month 2, 4). Serum SARS-CoV-2-specific IgA, IgG1, IgG3 responses (dilution 1:50) to SARS-CoV-2 antigens were measured on a Bio-Plex instrument (Bio-Rad). The Bioplex software provides 2 readouts: a background-subtracted mean fluorescence intensity (MFI), where background refers to a plate level control (i.e., a blank well run on each plate), and a concentration based on a standard curve. Positive responses at each visit will be called if the MFI minus blank values are ≥ isotype, antigen, and dilution-specific cutoff (will be provided by the lab). MFIs minus blank (or net MFI) are used to summarize the magnitude at a given time-point. The table summarized SARS-CoV-2-specific Antibody Binding Response Rate by binding antibody multiplex assay (BAMA IgG1) at Visit 1, 2, 3 , overall and by region and COVID-19 severity among America Cohort (USA and Peru)

  Measured at Months 0, 2, 4

• SARS-CoV-2-specific Antibody Binding Response Magnitude (IgG1) by Region and COVID-19 Severity Among America Cohort

  BAMA assays was performed for samples from participants at Visit 1 (Month 0, baseline) and available samples at follow-up visits (Month 2, 4). Serum SARS-CoV-2-specific IgA, IgG1, IgG3 responses (dilution 1:50) to SARS-CoV-2 antigens were measured on a Bio-Plex instrument (Bio-Rad). The Bioplex software provides 2 readouts: a background-subtracted mean fluorescence intensity (MFI), where background refers to a plate level control (i.e., a blank well run on each plate), and a concentration based on a standard curve. Positive responses at each visit will be called if the MFI minus blank values are ≥ isotype, antigen, and dilution-specific cutoff (will be provided by the lab). MFIs minus blank (or net MFI) are used to summarize the magnitude at a given time-point. The table summarized SARS-CoV-2-specific Antibody Binding Response Magnitude by binding antibody multiplex assay (BAMA IgG1) at Visit 1, 2, 3, overall and by region and COVID-19 severity among America Cohort (USA and Peru)

  Measured at Months 0, 2, 4

• SARS-CoV-2-specific Antibody Binding Response Rate (IgG3) by Region and COVID-19 Severity Among America Cohort

  BAMA assays was performed for samples from participants at Visit 1 (Month 0, baseline) and available samples at follow-up visits (Month 2, 4). Serum SARS-CoV-2-specific IgA, IgG1, IgG3 responses (dilution 1:50) to SARS-CoV-2 antigens were measured on a Bio-Plex instrument (Bio-Rad). The Bioplex software provides 2 readouts: a background-subtracted mean fluorescence intensity (MFI), where background refers to a plate level control (i.e., a blank well run on each plate), and a concentration based on a standard curve. Positive responses at each visit will be called if the MFI minus blank values are ≥ isotype, antigen, and dilution-specific cutoff (will be provided by the lab). MFIs minus blank (or net MFI) are used to summarize the magnitude at a given time-point. The table summarized SARS-CoV-2-specific Antibody Binding Response Rate by binding antibody multiplex assay (BAMA IgG3) at Visit 1, 2, overall and by region and COVID-19 severity among America Cohort (USA and Peru)

  Measured at Months 0, 2

• SARS-CoV-2-specific Antibody Binding Response Magnitude (IgG3) by Region and COVID-19 Severity Among America Cohort

  BAMA assays was performed for samples from participants at Visit 1 (Month 0, baseline) and available samples at follow-up visits (Month 2, 4). Serum SARS-CoV-2-specific IgA, IgG1, IgG3 responses (dilution 1:50) to SARS-CoV-2 antigens were measured on a Bio-Plex instrument (Bio-Rad). The Bioplex software provides 2 readouts: a background-subtracted mean fluorescence intensity (MFI), where background refers to a plate level control (i.e., a blank well run on each plate), and a concentration based on a standard curve. Positive responses at each visit will be called if the MFI minus blank values are ≥ isotype, antigen, and dilution-specific cutoff (will be provided by the lab). MFIs minus blank (or net MFI) are used to summarize the magnitude at a given time-point.SARS-CoV-2-specific Antibody Binding Response Magnitude by binding antibody multiplex assay (BAMA IgG3) at Visit 1, 2, overall and by region and COVID-19 severity among America Cohort (USA and Peru)

  Measured at Months 0, 2

• SARS-CoV-2-specific Antibody Binding Response Rate (IgA) by Region and COVID-19 Severity Among America Cohort

  BAMA assays was performed for samples from participants at Visit 1 (Month 0, baseline) and available samples at follow-up visits (Month 2, 4). Serum SARS-CoV-2-specific IgA, IgG1, IgG3 responses (dilution 1:50) to SARS-CoV-2 antigens were measured on a Bio-Plex instrument (Bio-Rad). The Bioplex software provides 2 readouts: a background-subtracted mean fluorescence intensity (MFI), where background refers to a plate level control (i.e., a blank well run on each plate), and a concentration based on a standard curve. Positive responses at each visit will be called if the MFI minus blank values are ≥ isotype, antigen, and dilution-specific cutoff (will be provided by the lab). MFIs minus blank (or net MFI) are used to summarize the magnitude at a given time-point. The table summarized SARS-CoV-2-specific Antibody Binding Response Rate by binding antibody multiplex assay (BAMA IgA) at Visit 1, 2, overall and by region and COVID-19 severity among America Cohort (USA and Peru)

  Measured at Months 0, 2

• SARS-CoV-2-specific Antibody Binding Response Magnitude (IgA) by Region and COVID-19 Severity Among America Cohort

  BAMA assays was performed for samples from participants at Visit 1 (Month 0, baseline) and available samples at follow-up visits (Month 2, 4). Serum SARS-CoV-2-specific IgA, IgG1, IgG3 responses (dilution 1:50) to SARS-CoV-2 antigens were measured on a Bio-Plex instrument (Bio-Rad). The Bioplex software provides 2 readouts: a background-subtracted mean fluorescence intensity (MFI), where background refers to a plate level control (i.e., a blank well run on each plate), and a concentration based on a standard curve. Positive responses at each visit will be called if the MFI minus blank values are ≥ isotype, antigen, and dilution-specific cutoff (will be provided by the lab). MFIs minus blank (or net MFI) are used to summarize the magnitude at a given time-point. The table summarized SARS-CoV-2-specific Antibody Binding Response Magnitude by binding antibody multiplex assay (BAMA IgA) at Visit 1, 2, overall and by region and COVID-19 severity among America Cohort (USA and Peru)

  Measured at Months 0, 2

• SARS-CoV-2-specific Antibody Binding Response Rate (Nab) by Region and COVID-19 Severity Among America Cohort

  Neutralizing antibodies against SARS coronaviruses are measured in 293T/ACE2 cells for all HIV negative samples. MPI (maximum percent inhibition) is also measured. Positivity calls are an ID50/ID80 (50% and 80% inhibitory dose) value either \>20 (the lower limit of detection (LLOD) of the assay) or MPI is between 10%-50%. The neutralizing antibody ID50/ID80 of all HIV positive samples are measured by a different assay, VSV pseudovirus neutralization assay. Positivity calls are based on whether or not any neutralization is observed through entire titration (starting dilution 1:20) with MPI between 10%-50%. For the positive calls but the neutralization does not reach 50% or 80%, ID50/ID80 titer is first estimated by Prism. The table summarized SARS-CoV-2-specific Antibody Binding Response Rate by neutralizing antibody assay (NAb) at Visit 1, 2, 3, 4, overall and by region and COVID-19 severity

  Measured at Months 0, 2, 4, 12

• SARS-CoV-2-specific Antibody Binding Response Magnitude (Nab) by Region and COVID-19 Severity Among America Cohort

  Neutralizing antibodies against SARS coronaviruses are measured in 293T/ACE2 cells for all HIV negative samples. MPI (maximum percent inhibition) is also measured. Positivity calls are an ID50/ID80 (50% and 80% inhibitory dose) value either \>20 (the lower limit of detection (LLOD) of the assay) or MPI is between 10%-50%. The neutralizing antibody ID50/ID80 of all HIV positive samples are measured by a different assay, VSV pseudovirus neutralization assay. Positivity calls are based on whether or not any neutralization is observed through entire titration (starting dilution 1:20) with MPI between 10%-50%. For the positive calls but the neutralization does not reach 50% or 80%, ID50/ID80 titer is first estimated by Prism. The table summarized SARS-CoV-2-specific Antibody Binding Response Magnitude by neutralizing antibody assay (NAb) at Visit 1, 2,3,4, overall and by region and COVID-19 severity among America Cohort

  Measured at Months 0, 2, 4, 12

• SARS-CoV-2-specific Antibody Binding Response Rate (Nab) by Region and COVID-19 Severity Among Africa Cohort

  Neutralizing antibodies against SARS coronaviruses are measured in 293T/ACE2 cells for all HIV negative samples. MPI (maximum percent inhibition) is also measured. Positivity calls are an ID50/ID80 (50% and 80% inhibitory dose) value either \>20 (the lower limit of detection (LLOD) of the assay) or MPI is between 10%-50%. The neutralizing antibody ID50/ID80 of all HIV positive samples are measured by a different assay, VSV pseudovirus neutralization assay. Positivity calls are based on whether or not any neutralization is observed through entire titration (starting dilution 1:20) with MPI between 10%-50%. For the positive calls but the neutralization does not reach 50% or 80%, ID50/ID80 titer is first estimated by Prism. The table summarized SARS-CoV-2-specific Antibody Binding Response Rate by neutralizing antibody assay (NAb) at Visit 1, 2, 3, 4, overall and by region and COVID-19 severity

  Measured at Months 0, 2, 4, 12

• SARS-CoV-2-specific Antibody Binding Response Magnitude (Nab) by Region and COVID-19 Severity Among Africa Cohort

  Neutralizing antibodies against SARS coronaviruses are measured in 293T/ACE2 cells for all HIV negative samples. MPI (maximum percent inhibition) is also measured. Positivity calls are an ID50/ID80 (50% and 80% inhibitory dose) value either \>20 (the lower limit of detection (LLOD) of the assay) or MPI is between 10%-50%. The neutralizing antibody ID50/ID80 of all HIV positive samples are measured by a different assay, VSV pseudovirus neutralization assay. Positivity calls are based on whether or not any neutralization is observed through entire titration (starting dilution 1:20) with MPI between 10%-50%. For the positive calls but the neutralization does not reach 50% or 80%, ID50/ID80 titer is first estimated by Prism. The table summarized SARS-CoV-2-specific Antibody Binding Response Magnitude by neutralizing antibody assay (NAb) at Visit 1, 2, 3, 4, overall and by region and COVID-19 severity among Africa Cohort

  Measured at Months 0, 2, 4, 12

• SARS-CoV-2-specific Antibody Binding Response Rate (ADCC) by Region and COVID-19 Severity Among America Cohort

  Antibody-dependent NK cell degranulation will be measured using ADCC assay at a dilution 1:500. Two readouts will be the background-subtracted % CD107A+ NK cells for the infected cells and the background-subtracted % CD107A+ NK cells for the transfected cells. The positive responses will be called if the values of background-subtracted % CD107A+ ≥ 4.07 and ≥5.27 for the infected and transfected cells, respectively. The cutoffs are determined by mean+2SD, respectively, from the SARS-CoV-2 negative controls. Percent CD107a+ NK Cells was the response magnitudes. The table summarized SARS-CoV-2-specific Antibody Binding Response Rate by antibody-dependent cellular cytotoxicity assay (ADCC) at Visit 1, overall and by region and COVID-19 severity among America Cohort (USA and Peru)

  Measured at Months 0

• SARS-CoV-2-specific Antibody Binding Response Magnitude (ADCC) by Region and COVID-19 Severity Among America Cohort

  Antibody-dependent NK cell degranulation will be measured using ADCC assay at a dilution 1:500. Two readouts will be the background-subtracted % CD107A+ NK cells for the infected cells and the background-subtracted % CD107A+ NK cells for the transfected cells. The positive responses will be called if the values of background-subtracted % CD107A+ ≥ 4.07 and ≥5.27 for the infected and transfected cells, respectively. The cutoffs are determined by mean+2SD, respectively, from the SARS-CoV-2 negative controls. Percent CD107a+ NK Cells was the response magnitudes. The table summarized SARS-CoV-2-specific Antibody Binding Response Magnitude by antibody-dependent cellular cytotoxicity assay (ADCC) Visit 1, overall and by region and COVID-19 severity among America Cohort (USA and Peru)

  Measured at Months 0

• SARS-CoV-2-specific CD4+ and CD8+ T Cell Response Rate (ICS) by Region and COVID-19 Severity Among America Cohort

  Flow cytometry was used to examine SARS-CoV-2 specific CD4+ and CD8+ T-cell responses using an intracellular cytokine staining (ICS). Positive calls will be made using Fisher's exact positivity test for all the markers. The magnitudes are % T cells expressing IFN-g/IL-2. The table summarized SARS-CoV-2-specific CD4+ and CD8+ T Cell Response Rate by flow cytometry at Visit 1, overall and by region and COVID-19 severity among America Cohort (USA and Peru)

  Measured at Months 0

• SARS-CoV-2-specific CD4+ and CD8+ T Cell Response Magnitude (ICS) by Region and COVID-19 Severity Among America Cohort

  Flow cytometry was used to examine SARS-CoV-2 specific CD4+ and CD8+ T-cell responses using an intracellular cytokine staining (ICS). Positive calls will be made using Fisher's exact positivity test for all the markers. The magnitudes are % T cells expressing IFN-g/IL-2. The table summarized SARS-CoV-2-specific CD4+ and CD8+ T Cell Response Magnitude by flow cytometry at Visit 1, overall and by region and COVID-19 severity among America Cohort

  Measured at Months 0

• SARS-CoV-2-specific Memory B Cell Response Magnitude (B Cell) by Region and COVID-19 Severity Among America Cohort

  SARS-CoV-2-specific B cell responses and B cell phenotypic data was identified and characterized using fluorescently-labelled recombinant Env proteins (S6P and RBD) in combination with a flow cytometry antibody panel on all available samples from the enrollment visit (V1). The sample will be included in the analysis only if the number of IgD- B cells is equal or greater than 1000 for that sample. The table summarized SARS-CoV-2-specific Memory B Cell Response Magnitude by flow cytometry at Visit 1, overall and by region and COVID-19 severity among America Cohort (USA and Peru)

  Measured at Months 0

• SARS-CoV-2-specific Antibody Binding Response Rate (IgG1) by Region and Days Since SARS-CoV-2 Diagnosis Group Among America Cohort

  BAMA assays was performed for samples from participants at Visit 1 (Month 0, baseline) and available samples at follow-up visits (Month 2, 4). Serum SARS-CoV-2-specific IgA, IgG1, IgG3 responses (dilution 1:50) to SARS-CoV-2 antigens were measured on a Bio-Plex instrument (Bio-Rad). The Bioplex software provides 2 readouts: a background-subtracted mean fluorescence intensity (MFI), where background refers to a plate level control (i.e., a blank well run on each plate), and a concentration based on a standard curve. Positive responses at each visit will be called if the MFI minus blank values are ≥ isotype, antigen, and dilution-specific cutoff (will be provided by the lab). MFIs minus blank (or net MFI) are used to summarize the magnitude at a given time-point. The table summarized SARS-CoV-2-specific Antibody Binding Response Rate by binding antibody multiplex assay (BAMA IgG1) at Visit 1, 2, 3, overall and by region and days since SARS-CoV-2 diagnosis group among America Cohort

  Measured at Months 0, 2, 4

• SARS-CoV-2-specific Antibody Binding Response Magnitude (IgG1) by Region and Days Since SARS-CoV-2 Diagnosis Group Among America Cohort

  BAMA assays was performed for samples from participants at Visit 1 (Month 0, baseline) and available samples at follow-up visits (Month 2, 4). Serum SARS-CoV-2-specific IgA, IgG1, IgG3 responses (dilution 1:50) to SARS-CoV-2 antigens were measured on a Bio-Plex instrument (Bio-Rad). The Bioplex software provides 2 readouts: a background-subtracted mean fluorescence intensity (MFI), where background refers to a plate level control (i.e., a blank well run on each plate), and a concentration based on a standard curve. Positive responses at each visit will be called if the MFI minus blank values are ≥ isotype, antigen, and dilution-specific cutoff (will be provided by the lab). MFIs minus blank (or net MFI) are used to summarize the magnitude at a given time-point. The table summarized SARS-CoV-2-specific Antibody Binding Response Magnitude by BAMA IgG1 at Visit 1, 2, 3, overall and by region and days since SARS-CoV-2 diagnosis group among America Cohort

  Measured at Months 0, 2, 4

• SARS-CoV-2-specific Antibody Binding Response Rate (IgG3) by Region and Days Since SARS-CoV-2 Diagnosis Group Among America Cohort

  BAMA assays was performed for samples from participants at Visit 1 (Month 0, baseline) and available samples at follow-up visits (Month 2, 4). Serum SARS-CoV-2-specific IgA, IgG1, IgG3 responses (dilution 1:50) to SARS-CoV-2 antigens were measured on a Bio-Plex instrument (Bio-Rad). The Bioplex software provides 2 readouts: a background-subtracted mean fluorescence intensity (MFI), where background refers to a plate level control (i.e., a blank well run on each plate), and a concentration based on a standard curve. Positive responses at each visit will be called if the MFI minus blank values are ≥ isotype, antigen, and dilution-specific cutoff (will be provided by the lab). MFIs minus blank (or net MFI) are used to summarize the magnitude at a given time-point. The table summarized SARS-CoV-2-specific Antibody Binding Response Rate by binding antibody multiplex assay (BAMA IgG3) at Visit 1, 2, overall and by region and days since SARS-CoV-2 diagnosis group among America Cohort

  Measured at Months 0, 2

• SARS-CoV-2-specific Antibody Binding Response Magnitude (IgG3) by Region and Days Since SARS-CoV-2 Diagnosis Group Among America Cohort

  BAMA assays was performed for samples from participants at Visit 1 (Month 0, baseline) and available samples at follow-up visits (Month 2, 4). Serum SARS-CoV-2-specific IgA, IgG1, IgG3 responses (dilution 1:50) to SARS-CoV-2 antigens were measured on a Bio-Plex instrument (Bio-Rad). The Bioplex software provides 2 readouts: a background-subtracted mean fluorescence intensity (MFI), where background refers to a plate level control (i.e., a blank well run on each plate), and a concentration based on a standard curve. Positive responses at each visit will be called if the MFI minus blank values are ≥ isotype, antigen, and dilution-specific cutoff (will be provided by the lab). MFIs minus blank (or net MFI) are used to summarize the magnitude at a given time-point. The table summarized SARS-CoV-2-specific Antibody Binding Response Magnitude by binding antibody multiplex assay (BAMA IgG3) at Visit 1, 2, overall and by region and days since SARS-CoV-2 diagnosis group among America Cohort

  Measured at Months 0, 2

• SARS-CoV-2-specific Antibody Binding Response Rate (IgA) by Region and Days Since SARS-CoV-2 Diagnosis Group Among America Cohort

  BAMA assays was performed for samples from participants at Visit 1 (Month 0, baseline) and available samples at follow-up visits (Month 2, 4). Serum SARS-CoV-2-specific IgA, IgG1, IgG3 responses (dilution 1:50) to SARS-CoV-2 antigens were measured on a Bio-Plex instrument (Bio-Rad). The Bioplex software provides 2 readouts: a background-subtracted mean fluorescence intensity (MFI), where background refers to a plate level control (i.e., a blank well run on each plate), and a concentration based on a standard curve. Positive responses at each visit will be called if the MFI minus blank values are ≥ isotype, antigen, and dilution-specific cutoff (will be provided by the lab). MFIs minus blank (or net MFI) are used to summarize the magnitude at a given time-point. The table summarized SARS-CoV-2-specific Antibody Binding Response Rate by binding antibody multiplex assay (BAMA IgA) at Visit 1, 2, overall and by region and days since SARS-CoV-2 diagnosis group among America Cohort

  Measured at Months 0, 2

• SARS-CoV-2-specific Antibody Binding Response Magnitude (IgA) by Region and Days Since SARS-CoV-2 Diagnosis Group Among America Cohort

  BAMA assays was performed for samples from participants at Visit 1 (Month 0, baseline) and available samples at follow-up visits (Month 2, 4). Serum SARS-CoV-2-specific IgA, IgG1, IgG3 responses (dilution 1:50) to SARS-CoV-2 antigens were measured on a Bio-Plex instrument (Bio-Rad). The Bioplex software provides 2 readouts: a background-subtracted mean fluorescence intensity (MFI), where background refers to a plate level control (i.e., a blank well run on each plate), and a concentration based on a standard curve. Positive responses at each visit will be called if the MFI minus blank values are ≥ isotype, antigen, and dilution-specific cutoff (will be provided by the lab). MFIs minus blank (or net MFI) are used to summarize the magnitude at a given time-point. The table summarized SARS-CoV-2-specific Antibody Binding Response Magnitude by binding antibody multiplex assay (BAMA IgA) at Visit 1, 2, overall and by region and days since SARS-CoV-2 diagnosis group among America Cohort

  Measured at Months 0, 2

• SARS-CoV-2-specific Antibody Binding Response Rate (Nab) by Region and Days Since SARS-CoV-2 Diagnosis Group Among America Cohort

  Neutralizing antibodies against SARS coronaviruses are measured in 293T/ACE2 cells for all HIV negative samples. MPI (maximum percent inhibition) is also measured. Positivity calls are an ID50/ID80 (50% and 80% inhibitory dose) value either \>20 (the lower limit of detection (LLOD) of the assay) or MPI is between 10%-50%. The neutralizing antibody ID50/ID80 of all HIV positive samples are measured by a different assay, VSV pseudovirus neutralization assay. Positivity calls are based on whether or not any neutralization is observed through entire titration (starting dilution 1:20) with MPI between 10%-50%. For the positive calls but the neutralization does not reach 50% or 80%, ID50/ID80 titer is first estimated by Prism. The table summarized SARS-CoV-2-specific Antibody Binding Response Rate by neutralizing antibody assay (NAb) at Visit 1, 2, 3, 4, overall and by region and days since SARS-CoV-2 diagnosis group among America Cohort

  Measured at Months 0, 2, 4, 12

• SARS-CoV-2-specific Antibody Binding Response Magnitude (Nab) by Region and Days Since SARS-CoV-2 Diagnosis Group Among America Cohort

  Neutralizing antibodies against SARS coronaviruses are measured in 293T/ACE2 cells for all HIV negative samples. MPI (maximum percent inhibition) is also measured. Positivity calls are an ID50/ID80 (50% and 80% inhibitory dose) value either \>20 (the lower limit of detection (LLOD) of the assay) or MPI is between 10%-50%. The neutralizing antibody ID50/ID80 of all HIV positive samples are measured by a different assay, VSV pseudovirus neutralization assay. Positivity calls are based on whether or not any neutralization is observed through entire titration (starting dilution 1:20) with MPI between 10%-50%. For the positive calls but the neutralization does not reach 50% or 80%, ID50/ID80 titer is first estimated by Prism. The table summarized SARS-CoV-2-specific Antibody Binding Response Magnitude by neutralizing antibody assay (NAb) at Visit 1, 2,3, 4, overall and by region and days since SARS-CoV-2 diagnosis group among America Cohort

  Measured at Months 0, 2, 4, 12

• SARS-CoV-2-specific Antibody Binding Response Rate (Nab) by Region and Days Since SARS-CoV-2 Diagnosis Group Among Africa Cohort

  Neutralizing antibodies against SARS coronaviruses are measured in 293T/ACE2 cells for all HIV negative samples. MPI (maximum percent inhibition) is also measured. Positivity calls are an ID50/ID80 (50% and 80% inhibitory dose) value either \>20 (the lower limit of detection (LLOD) of the assay) or MPI is between 10%-50%. The neutralizing antibody ID50/ID80 of all HIV positive samples are measured by a different assay, VSV pseudovirus neutralization assay. Positivity calls are based on whether or not any neutralization is observed through entire titration (starting dilution 1:20) with MPI between 10%-50%. For the positive calls but the neutralization does not reach 50% or 80%, ID50/ID80 titer is first estimated by Prism. The table summarized SARS-CoV-2-specific Antibody Binding Response Rate by neutralizing antibody assay (NAb) at Visit 1, 2, 3, 4, overall and by region and days since SARS-CoV-2 diagnosis group among Africa Cohort

  Measured at Months 0, 2, 4, 12

• SARS-CoV-2-specific Antibody Binding Response Magnitude (Nab) by Region and Days Since SARS-CoV-2 Diagnosis Group Among Africa Cohort

  Neutralizing antibodies against SARS coronaviruses are measured in 293T/ACE2 cells for all HIV negative samples. MPI (maximum percent inhibition) is also measured. Positivity calls are an ID50/ID80 (50% and 80% inhibitory dose) value either \>20 (the lower limit of detection (LLOD) of the assay) or MPI is between 10%-50%. The neutralizing antibody ID50/ID80 of all HIV positive samples are measured by a different assay, VSV pseudovirus neutralization assay. Positivity calls are based on whether or not any neutralization is observed through entire titration (starting dilution 1:20) with MPI between 10%-50%. For the positive calls but the neutralization does not reach 50% or 80%, ID50/ID80 titer is first estimated by Prism. The table summarized SARS-CoV-2-specific Antibody Binding Response Magnitude by neutralizing antibody assay (NAb) at Visit 1, 2, 3, 4, overall and by region and days since SARS-CoV-2 diagnosis group among Africa Cohort

  Measured at Months 0, 2, 4, 12

• SARS-CoV-2-specific Antibody Binding Response Rate (ADCC) by Region and Days Since SARS-CoV-2 Diagnosis Group Among America Cohort

  Antibody-dependent NK cell degranulation will be measured using ADCC assay at a dilution 1:500. Two readouts will be the background-subtracted % CD107A+ NK cells for the infected cells and the background-subtracted % CD107A+ NK cells for the transfected cells. The positive responses will be called if the values of background-subtracted % CD107A+ ≥ 4.07 and ≥5.27 for the infected and transfected cells, respectively. The cutoffs are determined by mean+2SD, respectively, from the SARS-CoV-2 negative controls. Percent CD107a+ NK Cells was the response magnitudes. The table summarized SARS-CoV-2-specific Antibody Binding Response Rate by antibody-dependent cellular cytotoxicity assay (ADCC) at Visit 1, overall and by region and days since SARS-CoV-2 diagnosis group among America Cohort (USA and Peru)

  Measured at Months 0

• SARS-CoV-2-specific Antibody Binding Response Magnitude (ADCC) by Region and Days Since SARS-CoV-2 Diagnosis Group Among America Cohort

  Antibody-dependent NK cell degranulation will be measured using ADCC assay at a dilution 1:500. Two readouts will be the background-subtracted % CD107A+ NK cells for the infected cells and the background-subtracted % CD107A+ NK cells for the transfected cells. The positive responses will be called if the values of background-subtracted % CD107A+ ≥ 4.07 and ≥5.27 for the infected and transfected cells, respectively. The cutoffs are determined by mean+2SD, respectively, from the SARS-CoV-2 negative controls. Percent CD107a+ NK Cells was the response magnitudes. The table summarized SARS-CoV-2-specific Antibody Binding Response Magnitude by antibody-dependent cellular cytotoxicity assay (ADCC) Visit 1, overall and by region and days since SARS-CoV-2 diagnosis group among America Cohort

  Measured at Months 0

• SARS-CoV-2-specific CD4+ and CD8+ T Cell Response Rate (ICS) by Region and Days Since SARS-CoV-2 Diagnosis Group Among America Cohort

  Flow cytometry was used to examine SARS-CoV-2 specific CD4+ and CD8+ T-cell responses using an intracellular cytokine staining (ICS). Positive calls will be made using Fisher's exact positivity test for all the markers. The magnitudes are % T cells expressing IFN-g/IL-2. The table summarized SARS-CoV-2-specific CD4+ and CD8+ T Cell Response Rate by flow cytometry at Visit 1, overall and by region and days since SARS-CoV-2 diagnosis group among America Cohort

  Measured at Months 0

• SARS-CoV-2-specific CD4+ and CD8+ T Cell Response Magnitude (ICS) by Region and Days Since SARS-CoV-2 Diagnosis Group Among America Cohort

  Flow cytometry was used to examine SARS-CoV-2 specific CD4+ and CD8+ T-cell responses using an intracellular cytokine staining (ICS). Positive calls will be made using Fisher's exact positivity test for all the markers. The magnitudes are % T cells expressing IFN-g/IL-2. The table summarized SARS-CoV-2-specific CD4+ and CD8+ T Cell Response Magnitude by flow cytometry at Visit 1, overall and by region and days since SARS-CoV-2 diagnosis group among America Cohort

  Measured at Months 0

• SARS-CoV-2-specific Memory B Cell Response Magnitude (B Cell) by Region and Days Since SARS-CoV-2 Diagnosis Group Among America Cohort

  SARS-CoV-2-specific B cell responses and B cell phenotypic data was identified and characterized using fluorescently-labelled recombinant Env proteins (S6P and RBD) in combination with a flow cytometry antibody panel on all available samples from the enrollment visit (V1). The sample will be included in the analysis only if the number of IgD- B cells is equal or greater than 1000 for that sample. The table summarized SARS-CoV-2-specific Memory B Cell Response Magnitude (B Cell) by Region and Days Since SARS-CoV-2 Diagnosis Group among America Cohort

  Measured at Months 0

• SARS-CoV-2-specific Antibody Binding Response Rate (IgG1) by Region and Comorbidity Group Among America Cohort

  BAMA assays was performed for samples from participants at Visit 1 (Month 0, baseline) and available samples at follow-up visits (Month 2, 4). Serum SARS-CoV-2-specific IgA, IgG1, IgG3 responses (dilution 1:50) to SARS-CoV-2 antigens were measured on a Bio-Plex instrument (Bio-Rad). The Bioplex software provides 2 readouts: a background-subtracted mean fluorescence intensity (MFI), where background refers to a plate level control (i.e., a blank well run on each plate), and a concentration based on a standard curve. Positive responses at each visit will be called if the MFI minus blank values are ≥ isotype, antigen, and dilution-specific cutoff (will be provided by the lab). MFIs minus blank (or net MFI) are used to summarize the magnitude at a given time-point. The table summarized SARS-CoV-2-specific Antibody Binding Response Rate by binding antibody multiplex assay (BAMA IgG1) at Visit 1, 2, 3 , overall and by region and comorbidity group among America Cohort

  Measured at Months 0, 2, 4

• SARS-CoV-2-specific Antibody Binding Response Magnitude (IgG1) by Region and Comorbidity Group Among America Cohort

  BAMA assays was performed for samples from participants at Visit 1 (Month 0, baseline) and available samples at follow-up visits (Month 2, 4). Serum SARS-CoV-2-specific IgA, IgG1, IgG3 responses (dilution 1:50) to SARS-CoV-2 antigens were measured on a Bio-Plex instrument (Bio-Rad). The Bioplex software provides 2 readouts: a background-subtracted mean fluorescence intensity (MFI), where background refers to a plate level control (i.e., a blank well run on each plate), and a concentration based on a standard curve. Positive responses at each visit will be called if the MFI minus blank values are ≥ isotype, antigen, and dilution-specific cutoff (will be provided by the lab). MFIs minus blank (or net MFI) are used to summarize the magnitude at a given time-point. The table summarized SARS-CoV-2-specific Antibody Binding Response Magnitude by binding antibody multiplex assay (BAMA IgG1) at Visit 1, 2, 3, overall and by region and comorbidity group among America Cohort

  Measured at Months 0, 2, 4

• SARS-CoV-2-specific Antibody Binding Response Rate (IgG3) by Region and Comorbidity Group Among America Cohort

  BAMA assays was performed for samples from participants at Visit 1 (Month 0, baseline) and available samples at follow-up visits (Month 2, 4). Serum SARS-CoV-2-specific IgA, IgG1, IgG3 responses (dilution 1:50) to SARS-CoV-2 antigens were measured on a Bio-Plex instrument (Bio-Rad). The Bioplex software provides 2 readouts: a background-subtracted mean fluorescence intensity (MFI), where background refers to a plate level control (i.e., a blank well run on each plate), and a concentration based on a standard curve. Positive responses at each visit will be called if the MFI minus blank values are ≥ isotype, antigen, and dilution-specific cutoff (will be provided by the lab). MFIs minus blank (or net MFI) are used to summarize the magnitude at a given time-point. The table summarized SARS-CoV-2-specific Antibody Binding Response Rate by binding antibody multiplex assay (BAMA IgG3) at Visit 1, 2, overall and by region and comorbidity group among America Cohort

  Measured at Months 0, 2

• SARS-CoV-2-specific Antibody Binding Response Magnitude (IgG3) by Region and Comorbidity Group Among America Cohort

  BAMA assays was performed for samples from participants at Visit 1 (Month 0, baseline) and available samples at follow-up visits (Month 2, 4). Serum SARS-CoV-2-specific IgA, IgG1, IgG3 responses (dilution 1:50) to SARS-CoV-2 antigens were measured on a Bio-Plex instrument (Bio-Rad). The Bioplex software provides 2 readouts: a background-subtracted mean fluorescence intensity (MFI), where background refers to a plate level control (i.e., a blank well run on each plate), and a concentration based on a standard curve. Positive responses at each visit will be called if the MFI minus blank values are ≥ isotype, antigen, and dilution-specific cutoff (will be provided by the lab). MFIs minus blank (or net MFI) are used to summarize the magnitude at a given time-point. The table summarized SARS-CoV-2-specific Antibody Binding Response Magnitude by binding antibody multiplex assay (BAMA IgG3) at Visit 1, 2, overall and by region and comorbidity group among America Cohort

  Measured at Months 0, 2

• SARS-CoV-2-specific Antibody Binding Response Rate (IgA) by Region and Comorbidity Group Among America Cohort

  BAMA assays was performed for samples from participants at Visit 1 (Month 0, baseline) and available samples at follow-up visits (Month 2, 4). Serum SARS-CoV-2-specific IgA, IgG1, IgG3 responses (dilution 1:50) to SARS-CoV-2 antigens were measured on a Bio-Plex instrument (Bio-Rad). The Bioplex software provides 2 readouts: a background-subtracted mean fluorescence intensity (MFI), where background refers to a plate level control (i.e., a blank well run on each plate), and a concentration based on a standard curve. Positive responses at each visit will be called if the MFI minus blank values are ≥ isotype, antigen, and dilution-specific cutoff (will be provided by the lab). MFIs minus blank (or net MFI) are used to summarize the magnitude at a given time-point. The table summarized SARS-CoV-2-specific Antibody Binding Response Rate by binding antibody multiplex assay (BAMA IgA) at Visit 1, 2, overall and by region and comorbidity group among America Cohort

  Measured at Months 0, 2

• SARS-CoV-2-specific Antibody Binding Response Magnitude (IgA) by Region and Comorbidity Group Among America Cohort

  BAMA assays was performed for samples from participants at Visit 1 (Month 0, baseline) and available samples at follow-up visits (Month 2, 4). Serum SARS-CoV-2-specific IgA, IgG1, IgG3 responses (dilution 1:50) to SARS-CoV-2 antigens were measured on a Bio-Plex instrument (Bio-Rad). The Bioplex software provides 2 readouts: a background-subtracted mean fluorescence intensity (MFI), where background refers to a plate level control (i.e., a blank well run on each plate), and a concentration based on a standard curve. Positive responses at each visit will be called if the MFI minus blank values are ≥ isotype, antigen, and dilution-specific cutoff (will be provided by the lab). MFIs minus blank (or net MFI) are used to summarize the magnitude at a given time-point. The table summarized SARS-CoV-2-specific Antibody Binding Response Magnitude by binding antibody multiplex assay (BAMA IgA) at Visit 1, 2, overall and by region and comorbidity group among America Cohort

  Measured at Months 0, 2

• SARS-CoV-2-specific Antibody Binding Response Rate (Nab) by Region and Comorbidity Group Among America Cohort

  Neutralizing antibodies against SARS coronaviruses are measured in 293T/ACE2 cells for all HIV negative samples. MPI (maximum percent inhibition) is also measured. Positivity calls are an ID50/ID80 (50% and 80% inhibitory dose) value either \>20 (the lower limit of detection (LLOD) of the assay) or MPI is between 10%-50%. The neutralizing antibody ID50/ID80 of all HIV positive samples are measured by a different assay, VSV pseudovirus neutralization assay. Positivity calls are based on whether or not any neutralization is observed through entire titration (starting dilution 1:20) with MPI between 10%-50%. For the positive calls but the neutralization does not reach 50% or 80%, ID50/ID80 titer is first estimated by Prism. The table summarized SARS-CoV-2-specific Antibody Binding Response Rate by neutralizing antibody assay (NAb) at Visit 1, 2, 3, 4, overall and by region and comorbidity group among America Cohort

  Measured at Months 0, 2, 4, 12

• SARS-CoV-2-specific Antibody Binding Response Magnitude (Nab) by Region and Comorbidity Group Among America Cohort

  Neutralizing antibodies against SARS coronaviruses are measured in 293T/ACE2 cells for all HIV negative samples. MPI (maximum percent inhibition) is also measured. Positivity calls are an ID50/ID80 (50% and 80% inhibitory dose) value either \>20 (the lower limit of detection (LLOD) of the assay) or MPI is between 10%-50%. The neutralizing antibody ID50/ID80 of all HIV positive samples are measured by a different assay, VSV pseudovirus neutralization assay. Positivity calls are based on whether or not any neutralization is observed through entire titration (starting dilution 1:20) with MPI between 10%-50%. For the positive calls but the neutralization does not reach 50% or 80%, ID50/ID80 titer is first estimated by Prism. The table summarized SARS-CoV-2-specific Antibody Binding Response Magnitude by neutralizing antibody assay (NAb) at Visit 1, 2,3,4, overall and by region and comorbidity group among America Cohort

  Measured at Months 0, 2, 4, 12

• SARS-CoV-2-specific Antibody Binding Response Rate (Nab) by Region and Comorbidity Group Among Africa Cohort

  Neutralizing antibodies against SARS coronaviruses are measured in 293T/ACE2 cells for all HIV negative samples. MPI (maximum percent inhibition) is also measured. Positivity calls are an ID50/ID80 (50% and 80% inhibitory dose) value either \>20 (the lower limit of detection (LLOD) of the assay) or MPI is between 10%-50%. The neutralizing antibody ID50/ID80 of all HIV positive samples are measured by a different assay, VSV pseudovirus neutralization assay. Positivity calls are based on whether or not any neutralization is observed through entire titration (starting dilution 1:20) with MPI between 10%-50%. For the positive calls but the neutralization does not reach 50% or 80%, ID50/ID80 titer is first estimated by Prism. The table summarized SARS-CoV-2-specific Antibody Binding Response Rate by neutralizing antibody assay (NAb) at Visit 1, 2, 3, 4, overall and by region and comorbidity group among Africa Cohort

  Measured at Months 0, 2, 4, 12

• SARS-CoV-2-specific Antibody Binding Response Magnitude (Nab) by Region and Comorbidity Group Among Africa Cohort

  Neutralizing antibodies against SARS coronaviruses are measured in 293T/ACE2 cells for all HIV negative samples. MPI (maximum percent inhibition) is also measured. Positivity calls are an ID50/ID80 (50% and 80% inhibitory dose) value either \>20 (the lower limit of detection (LLOD) of the assay) or MPI is between 10%-50%. The neutralizing antibody ID50/ID80 of all HIV positive samples are measured by a different assay, VSV pseudovirus neutralization assay. Positivity calls are based on whether or not any neutralization is observed through entire titration (starting dilution 1:20) with MPI between 10%-50%. For the positive calls but the neutralization does not reach 50% or 80%, ID50/ID80 titer is first estimated by Prism. The table summarized SARS-CoV-2-specific Antibody Binding Response Magnitude by neutralizing antibody assay (NAb) at Visit 1, 2, 3, 4, overall and by region and comorbidity group among Africa Cohort

  Measured at Months 0, 2, 4, 12

• SARS-CoV-2-specific Antibody Binding Response Rate (ADCC) by Region and Comorbidity Group Among America Cohort

  Antibody-dependent NK cell degranulation will be measured using ADCC assay at a dilution 1:500. Two readouts will be the background-subtracted % CD107A+ NK cells for the infected cells and the background-subtracted % CD107A+ NK cells for the transfected cells. The positive responses will be called if the values of background-subtracted % CD107A+ ≥ 4.07 and ≥5.27 for the infected and transfected cells, respectively. The cutoffs are determined by mean+2SD, respectively, from the SARS-CoV-2 negative controls. Percent CD107a+ NK Cells was the response magnitudes. The table summarized SARS-CoV-2-specific Antibody Binding Response Rate by antibody-dependent cellular cytotoxicity assay (ADCC) at Visit 1, overall and by region and comorbidity group among America Cohort

  Measured at Months 0

• SARS-CoV-2-specific Antibody Binding Response Magnitude (ADCC) by Region and Comorbidity Group Among America Cohort

  Antibody-dependent NK cell degranulation will be measured using ADCC assay at a dilution 1:500. Two readouts will be the background-subtracted % CD107A+ NK cells for the infected cells and the background-subtracted % CD107A+ NK cells for the transfected cells. The positive responses will be called if the values of background-subtracted % CD107A+ ≥ 4.07 and ≥5.27 for the infected and transfected cells, respectively. The cutoffs are determined by mean+2SD, respectively, from the SARS-CoV-2 negative controls. Percent CD107a+ NK Cells was the response magnitudes. The table summarized SARS-CoV-2-specific Antibody Binding Response Magnitude by antibody-dependent cellular cytotoxicity assay (ADCC) Visit 1, overall and by region and comorbidity group among America Cohort

  Measured at Months 0

• SARS-CoV-2-specific CD4+ and CD8+ T Cell Response Rate (ICS) by Region and Comorbidity Group Among America Cohort

  Flow cytometry was used to examine SARS-CoV-2 specific CD4+ and CD8+ T-cell responses using an intracellular cytokine staining (ICS). Positive calls will be made using Fisher's exact positivity test for all the markers. The magnitudes are % T cells expressing IFN-g/IL-2. The table summarized SARS-CoV-2-specific CD4+ and CD8+ T Cell Response Rate by flow cytometry at Visit 1, overall and by region and comorbidity group among America Cohort

  Measured at Months 0

• SARS-CoV-2-specific CD4+ and CD8+ T Cell Response Magnitude (ICS) by Region and Comorbidity Group Among America Cohort

  Flow cytometry was used to examine SARS-CoV-2 specific CD4+ and CD8+ T-cell responses using an intracellular cytokine staining (ICS). Positive calls will be made using Fisher's exact positivity test for all the markers. The magnitudes are % T cells expressing IFN-g/IL-2. The table summarized SARS-CoV-2-specific CD4+ and CD8+ T Cell Response Magnitude by flow cytometry at Visit 1, overall and by region and Comorbidity Group among America Cohort

  Measured at Months 0

• SARS-CoV-2-specific Memory B Cell Response Magnitude (B Cell) by Region and Comorbidity Group Among America Cohort

  SARS-CoV-2-specific B cell responses and B cell phenotypic data was identified and characterized using fluorescently-labelled recombinant Env proteins (S6P and RBD) in combination with a flow cytometry antibody panel on all available samples from the enrollment visit (V1). The sample will be included in the analysis only if the number of IgD- B cells is equal or greater than 1000 for that sample. The table summarized SARS-CoV-2-specific Memory B Cell Response Magnitude by flow cytometry at Visit 1, overall and by region and comorbidity group among America Cohort

  Measured at Months 0

• SARS-CoV-2-specific Infection Presentation, Including Clinical Course, Along With Demographics and Corresponding Medical History of Participants , Overall and by Region Among America Cohort

  SARS-CoV-2-specific Infection Presentation, Including Clinical Course, Along With Demographics and Corresponding Medical History of Participants , overall and by region

  Measured at Months 0

• SARS-CoV-2-specific Infection Presentation, Including Clinical Course, Along With Demographics and Corresponding Medical History of Participants , Overall and by Region Among Africa Cohort

  SARS-CoV-2-specific Infection Presentation, Including Clinical Course, Along With Demographics and Corresponding Medical History of Participants , overall and by region

  Measured at Months 0

Secondary Outcomes (2)

• SARS-CoV-2-specific Antibody Binding Response Magnitude (IgA Nasal Sample) by Region and Enrollment Group Among America Cohort

  Measured at Months 0, 2, 5

• Detection of Viral RNA in Nasopharyngeal or Nasal Swab Samples Via RT-PCR

  Measured at Months 0, Month 2, Month 4, Month 12

Study Arms (3)

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

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

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

Interventions

Sample collection OTHER

* Optional nasal specimen(s) * Blood collection

Group 1; Group 2; Group 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• HIV Vaccine Trials Network: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• HIV Prevention Trials Network: collaborator

Study Sites (53)

Alabama Vaccine CRS

Birmingham, Alabama, 35294, United States

Location

UCLA CARE Center CRS

Los Angeles, California, 90035, United States

Location

Bridge HIV CRS

San Francisco, California, 94143, United States

Location

George Washington University CRS

Washington D.C., District of Columbia, 20037-1894, United States

Location

The Ponce de Leon Center CRS

Atlanta, Georgia, 30308-2012, United States

Location

The Hope Clinic of the Emory Vaccine Center CRS

Decatur, Georgia, 30030, United States

Location

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

Chicago, Illinois, 60612, United States

Location

New Orleans Adolescent Trials Unit CRS

New Orleans, Louisiana, 70112, United States

Location

Johns Hopkins University CRS

Baltimore, Maryland, 21205, United States

Location

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

Boston, Massachusetts, 02115-6110, United States

Location

Fenway Health Clinical Research Site CRS

Boston, Massachusetts, 02215-4302, United States

Location

New Jersey Medical School Clinical Research Center CRS

Newark, New Jersey, 07103, United States

Location

Harlem Prevention Center CRS

New York, New York, 10027, United States

Location

Columbia P&S CRS

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

Location

New York Blood Center CRS

New York, New York, 10065, United States

Location

University of Rochester Vaccines to Prevent HIV Infection CRS

Rochester, New York, 14642, United States

Location

Bronx Prevention Research Center CRS

The Bronx, New York, 10451, United States

Location

Chapel Hill CRS

Chapel Hill, North Carolina, 27599, United States

Location

Penn Prevention CRS

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt Vaccine CRS

Nashville, Tennessee, 37232-2582, United States

Location

Seattle Vaccine and Prevention CRS

Seattle, Washington, 98109-1024, United States

Location

Malawi CRS

Lilongwe, Malawi

Location

San Miguel CRS

San Miguel, Lima region, 32-15088, Peru

Location

Asociacion Civil Selva Amazonica (ACSA) CRS

Iquitos, Maynas, 1, Peru

Location

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

Bellavista, Provincia Constitucional del Callao, 15081, Peru

Location

Via Libra CRS

Lima, 15001, Peru

Location

Barranco CRS

Lima, 15063, Peru

Location

Josha Research CRS

Bloemfontein, South Africa

Location

Emavundleni CRS

Cape Town, South Africa

Location

Groote Schuur HIV CRS

Cape Town, South Africa

Location

Khayelitsha CRS / (CIDRI UCT)

Cape Town, South Africa

Location

Masiphumelele Clinical Research Site (MASI) CRS

Cape Town, South Africa

Location

Chatsworth CRS

Chatsworth, South Africa

Location

Botha's Hill CRS

Durban, South Africa

Location

CAPRISA eThekwini CRS

Durban, South Africa

Location

Vulindlela CRS

Durban, South Africa

Location

Isipingo CRS

Isipingo, South Africa

Location

Kliptown Soweto CRS

Johannesburg, South Africa

Location

Soweto HVTN CRS

Johannesburg, South Africa

Location

Aurum Institute Klerksdorp CRS

Klerksdorp, South Africa

Location

Qhakaza Mbokodo Research Clinic CRS

Ladysmith, South Africa

Location

Nelson Mandela Academic Research Unit CRS

Mthatha, South Africa

Location

Synexus Stanza Clinical Research Centre CRS

Pretoria, South Africa

Location

Rustenburg CRS

Rustenburg, South Africa

Location

Setshaba Research Centre CRS

Soshanguve, South Africa

Location

Tembisa Clinic 4 CRS

Tembisa, South Africa

Location

The Aurum Institute Tembisa Clinical Research Centre CRS

Tembisa, South Africa

Location

Tongaat CRS

Tongaat, South Africa

Location

Verulam CRS

Verulam, South Africa

Location

Matero Reference Clinic CRS

Lusaka, Zambia

Location

St Mary's CRS

Chitungwiza, Zimbabwe

Location

Zengeza CRS

Chitungwiza, Zimbabwe

Location

Seke South CRS

Harare, Zimbabwe

Location

Related Publications (2)

• Karuna S, Gallardo-Cartagena JA, Theodore D, Hunidzarira P, Montenegro-Idrogo J, Hu J, Jones M, Kim V, De La Grecca R, Trahey M, Karg C, Takalani A, Polakowski L, Hutter J, Miner MD, Erdmann N, Goepfert P, Maboa R, Corey L, Gill K, Li SS; HVTN 405/HPTN 1901 Study Team. Post-COVID symptom profiles and duration in a global convalescent COVID-19 observational cohort: Correlations with demographics, medical history, acute COVID-19 severity and global region. J Glob Health. 2023 Jun 23;13:06020. doi: 10.7189/jogh.13.06020.

  PMID: 37352144 DERIVED

• 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.

  PMID: 34871308 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

Specimen Handling

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Results Point of Contact

• Title: Jessica Andriesen, PhD, Associate Director of HVTN SDMC Operations
• Organization: Fred Hutchinson Cancer Center

hvtn.covpn.sdmc@hvtn.org

206-667-5812

Study Officials

• Larry Corey

  HIV Vaccine Trials Network, Fred Hutch

  STUDY CHAIR

• Shelly Karuna

  HIV Vaccine Trials Network, Fred Hutch

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2020
• First Posted: May 27, 2020
• Study Start: May 13, 2020
• Primary Completion: April 21, 2022
• Study Completion: April 21, 2022
• Last Updated: January 12, 2026
• Results First Posted: January 12, 2026

Record last verified: 2025-12

Locations

US (21); ZI (3); MA (1); PE (5); ZA (22)