An observational study in Immunodeficiencies and Immune Dysregulations, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 1 site in United States. Open to participants aged 3 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-10-01.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Observational
Background:
The immune system defends the body against disease and infection. Immune deficiencies are health conditions that decrease the strength of this response. Vaccines stimulate the immune system to create a defense against a specific type of germ. Researchers want to compare immune system responses to COVID-19 vaccines in people with and without immune deficiencies.
Objective:
To learn about how people with immune deficiencies respond to COVID-19 vaccines.
Eligibility:
People age 3 and older with an immune deficiency who plan to get a COVID-19 vaccine. Healthy volunteers are also needed.
Design:
Participants will be pre-screened for eligibility, including COVID-19 vaccination history and immune status.
Participants will give a blood sample before they get their first COVID-19 vaccine. Blood will be drawn from an arm vein using a needle. Blood can be drawn at the NIH, at a local doctor's office, or at a laboratory. It may also be drawn through a fingerstick at home. Participants will also complete 2 online surveys about their health and COVID-19 history. Additional surveys are optional.
Participants will give a second blood sample 2 to 4 weeks after they get the vaccine. They will complete 2 surveys about changes in their health and side effects from the vaccine.
If participants get another COVID-19 vaccine dose, they will repeat the blood draw and surveys 3 to 4 weeks later.
Participants may give 3 optional blood samples in the 24 months after their last vaccine. They may also give saliva samples every 2 weeks while they are in the study for 6 months following their last vaccine.
Participation will last from 1 month to 2 years after the participant's last vaccine.
Study Description:
This prospective cohort study will assess the pre- and post-vaccination immune responses in individuals with select immunodeficiencies and immune dysregulations compared to healthy volunteers who receive a coronavirus disease 2019 (COVID-19) vaccine, as well as any adverse events (AEs) experienced after vaccination. All required study visits for this protocol may be conducted remotely; in-person visits at the NIH are optional. Subjects who have not yet been vaccinated will undergo baseline blood sampling using finger stick microsampler kits and/or venous blood draw within 7 days prior to receiving the vaccine. Additional samples will be requested from participants approximately 14-21 days after dose 1 and 21-28 days after dose 2 (if applicable). Optional samples may be collected at 6, 12, and 24 months post-vaccination. If subsequent booster doses are received while a participant is still on study, blood samples will again be requested approximately 28 days after each booster dose, through the 5th COVID-19 vaccine dose received, and then participants may proceed with the optional 6-, 12-, and 24-month follow-up sample collection. Participants who are able to attend in-person visits at NIH will have optional on-site blood draws 1 and 3 days after doses 1 and 2 (as applicable). Research evaluations will include baseline severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) antibody titers to the spike (S), nucleocapsid (N), and receptor binding domain (RBD) proteins, to assess pre-vaccination SARS-CoV-2 exposure and evaluate responses to vaccination. Additional immune markers of interest may include presence of autoantibodies, transcriptomic profiling, T-cell receptor (TCR) repertoire, among others. Participants who only submit finger stick home microsampler kits at the timepoints listed above will be evaluated for SARS-CoV-2 antibody titers and autoantibodies only. All subjects will be asked at baseline about prior COVID-19 diagnosis, symptoms, and severity, and will be asked additional questions at follow-up timepoints (including after additional booster doses) about vaccine AEs using standardized questionnaires.
Primary Objective:
To characterize the immune response to COVID-19 vaccination among immunodeficient and immune dysregulated individuals compared to healthy volunteers.
Secondary Objectives:
To characterize the COVID-19 vaccine-associated AEs among immunodeficient and immune dysregulated individuals compared to healthy volunteers.
Exploratory Objectives:
Assess the relationship between prior SARS-CoV-2 infection and vaccine-induced immune response.
To characterize pre-vaccine COVID-19 disease prevalence and severity among immunodeficient and immune dysregulated individuals.
To assess induction, strength, and durability of T- and B-cell specific immune responses to SARS-CoV-2 (as measured by frequency and diversity of SARS-CoV-2 specific T and B cell clonotypes and titers of specific antibody responses), and their correlation to the underlying immune deficiency/dysregulation.
To characterize auto-antibodies present in immunodeficient and immune dysregulated individuals before and after COVID-19 vaccination.
To assess the incidence of post-vaccination breakthrough SARS-CoV-2 infection and to determine the SARS-CoV-2 virus genomic sequence in such cases.
Primary Endpoint:
Change in S and RBD immunoglobulin G (IgG) antibody titer from baseline to 14-21 days or 21-28 days (depending on vaccine manufacturer and platform) after vaccine dose 1, and 21-28 days after dose 2 and any subsequent doses (depending on vaccine manufacturer and platform).
Secondary Endpoints:
Incidence of vaccine-associated AEs experienced by immunodeficient individuals compared to healthy volunteers.
Exploratory Endpoints:
Characterization of post-vaccine immune response and AEs in patients with antibody evidence of prior SARS-CoV-2 infection
Pre- and post-vaccination incidence of COVID-19-associated symptoms experienced in individuals with immune deficiency/dysregulation who are positive for SARS-CoV-2 by serology or diagnostic polymerase chain reaction (PCR).
Characterize how various forms of immune deficiency or dysregulation impact generation, strength, and durability of T- and B-cell responses.
Incidence of autoantibodies pre- and post-COVID-19 vaccination comparing individuals with immune deficiency/dysregulation to healthy volunteers.
698 studies on the registry are indexed under Immunologic Deficiency Syndromes; 67 are open to participants now.
This study's enrollment of 308 is above the median of 150 across 179 observational studies indexed under Immunologic Deficiency Syndromes.
Browse Immunologic Deficiency Syndromes studies →National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,401 studies on the registry; 179 are open to participants now.
Of its 396 completed or terminated interventional studies of FDA-regulated products, 294 (74%) have results posted.
Counted across the registry records on this site, refreshed daily.
Immunodeficient individuals will be recruited from NIAID protocols that evaluate primary or secondary immune deficiencies. Potential subjects will be identified by discussion between the study teams and review of medical and research records if necessary. They may also be referred from community practitioners who see this population.Healthy adult volunteers will be recruited through the NIH Clinical Research Volunteer Program, the Office of Patient Recruitment, MMG Patient Recruitment, ResearchMatch, or BuildClinical. Volunteers will also be recruited from existing NIH protocols. Healthy relatives of immunodeficient participants can be recruited for participation as controls if they meet enrollment criteria.
In order to be eligible to participate in this study, an individual must meet the following criteria:
Must meet the definition of affected participant or control participant:
EXCLUSION CRITERIA:
Individuals meeting any of the following criteria will be excluded from study participation:
Control participants will be healthy volunteers, and may include unaffected relatives of immunodeficient/dysregulated participants
Affected patients with evidence of a primary or secondary immune deficiency or dysregulation
Change in S and Receptor Binding Domain (RBD) Immunoglobulin G (IgG) Antibody Titer From Baseline Depending on Vaccine Manufacturer and Platform
To characterize the immune response to coronavirus disease 2019 (COVID-19) vaccination among immunodeficient and immune dysregulated individuals compared to healthy volunteers
Time frame: Baseline, post dose 1 (14-21 days), and post dose 2 (21-28 days), depending on vaccine manufacturer and platform
Incidence of Vaccine-associated Adverse Events (AE) Experienced by Immunodeficient Individuals Compared to Healthy Volunteers
To characterize the COVID-19 vaccine-associated adverse events among immunodeficient and immune dysregulated individuals compared to healthy volunteers. Note on terminology: "No vaccine-associated side effects" means participants reported zero symptoms or reactions after vaccination. A "mild vaccine-associated side effect" means a participant reported any symptom/reaction and reported is as "mild" on the scale of "mild", "moderate", or "severe". A participant could have reported several mild symptom/reactions and several moderate or severe symptoms/reactions. Therefore, the number of mild, moderate, and severe vaccine-associated side effects will not sum to the total number of surveys completed.
Time frame: Baseline up to a maximum of 24 months
April 2021 through December 2022. Immune deficient individuals were recruited from NIAID protocols evaluating immune deficiencies, referred from physicians, or self-referred. Healthy adult volunteers were recruited through various avenues. Healthy relatives of immunodeficient participants were recruited for participation as controls if they met enrollment criteria.
| Milestone | Immune Deficient/Disordered | Healthy Control |
|---|---|---|
| Started | 235 | 73 |
| Completed | 192 | 58 |
| Not completed | 43 | 15 |
| Withdrew: Death | 2 | 0 |
| Withdrew: Lost to follow-up | 15 | 9 |
| Withdrew: Withdrawal by subject | 26 | 6 |
To characterize the immune response to coronavirus disease 2019 (COVID-19) vaccination among immunodeficient and immune dysregulated individuals compared to healthy volunteers
| ug/ml | Immune Deficient/Disordered | Healthy Control |
|---|---|---|
| Change in anti-S titer from Baseline to Post-dose 1 | 0.447333 ± 1.118685 | 2.10678 ± 4.048595 |
| Change in anti-S titer from Post-dose 1 to Post-dose 2 | 0.83819 ± 8.953689 | 2.8153 ± 5.749115 |
To characterize the COVID-19 vaccine-associated adverse events among immunodeficient and immune dysregulated individuals compared to healthy volunteers. Note on terminology: "No vaccine-associated side effects" means participants reported zero symptoms or reactions after vaccination. A "mild vaccine-associated side effect" means a participant reported any symptom/reaction and reported is as "mild" on the scale of "mild", "moderate", or "severe". A participant could have reported several mild symptom/reactions and several moderate or severe symptoms/reactions. Therefore, the number of mild, moderate, and severe vaccine-associated side effects will not sum to the total number of surveys completed.
| participants | Immune Deficient/Disordered | Healthy Control |
|---|---|---|
| Vaccine-associated side-effects after dose 1 : No vaccine-associated side effects | 31 | 6 |
| Vaccine-associated side-effects after dose 1 : Mild vaccine-associated side effects | 134 | 45 |
| Vaccine-associated side-effects after dose 1 : Moderate vaccine-associated side effects | 85 | 26 |
| Vaccine-associated side-effects after dose 1 : Severe vaccine-associated side effects | 19 | 9 |
| Vaccine-associated side-effects after dose 1 : Total Volunteers completing dose survey | 187 | 57 |
| Vaccine-associated side-effects after dose 2 : No vaccine-associated side effects | 28 | 8 |
| Vaccine-associated side-effects after dose 2 : Mild vaccine-associated side effects | 143 | 43 |
| Vaccine-associated side-effects after dose 2 : Moderate vaccine-associated side effects | 88 | 24 |
| Vaccine-associated side-effects after dose 2 : Severe vaccine-associated side effects | 16 | 6 |
| Vaccine-associated side-effects after dose 2 : Total Volunteers completing dose survey | 189 | 53 |
| Vaccine-associated side-effects after dose 3 : No vaccine-associated side effects | 16 | 7 |
| Vaccine-associated side-effects after dose 3 : Mild vaccine-associated side effects | 120 | 22 |
| Vaccine-associated side-effects after dose 3 : Moderate vaccine-associated side effects | 55 | 9 |
| Vaccine-associated side-effects after dose 3 : Severe vaccine-associated side effects | 19 | 1 |
| Vaccine-associated side-effects after dose 3 : Total Volunteers completing dose survey | 148 | 29 |
| Vaccine-associated side-effects after dose 4 : No vaccine-associated side effects | 7 | 0 |
| Vaccine-associated side-effects after dose 4 : Mild vaccine-associated side effects | 44 | 6 |
| Vaccine-associated side-effects after dose 4 : Moderate vaccine-associated side effects | 18 | 1 |
| Vaccine-associated side-effects after dose 4 : Severe vaccine-associated side effects | 3 | 0 |
| Vaccine-associated side-effects after dose 4 : Total Volunteers completing dose survey | 60 | 6 |
| Vaccine-associated side-effects after dose 5 : Mild vaccine-associated side effects | 4 | 0 |
| Vaccine-associated side-effects after dose 5 : Moderate vaccine-associated side effects | 1 | 0 |
| Vaccine-associated side-effects after dose 5 : Severe vaccine-associated side effects | 1 | 0 |
| Vaccine-associated side-effects after dose 5 : Total Volunteers completing dose survey | 4 | 0 |
Collected over 2 years 4 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Immune Deficient/Disordered | 2/235 (0.9%) | — | — |
| Healthy Control | 0/73 (0%) | — | — |
| Age, Categorical(Participants) | Immune Deficient/Disordered | Healthy Control | Total |
|---|---|---|---|
| <=18 years | 31 | 7 | 38 |
| Between 18 and 65 years | 172 | 55 | 227 |
| >=65 years | 32 | 11 | 43 |
| Age, Continuous(years) | Immune Deficient/Disordered | Healthy Control | Total |
|---|---|---|---|
| Mean | 43 ± 19 | 42 ± 19 | 43 ± 19 |
| Sex: Female, Male(Participants) | Immune Deficient/Disordered | Healthy Control | Total |
|---|---|---|---|
| Female | 145 | 45 | 190 |
| Male | 90 | 28 | 118 |
| Ethnicity (NIH/OMB)(Participants) | Immune Deficient/Disordered | Healthy Control | Total |
|---|---|---|---|
| Hispanic or Latino | 15 | 5 | 20 |
| Not Hispanic or Latino | 212 | 62 | 274 |
| Unknown or Not Reported | 8 | 6 | 14 |
| Race (NIH/OMB)(Participants) | Immune Deficient/Disordered | Healthy Control | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 10 | 5 | 15 |
| Native Hawaiian or Other Pacific Islander | 1 | 0 | 1 |
| Black or African American | 10 | 7 | 17 |
| White | 204 | 51 | 255 |
| More than one race | 4 | 5 | 9 |
| Unknown or Not Reported | 6 | 5 | 11 |
| Region of Enrollment(Participants) | Immune Deficient/Disordered | Healthy Control | Total |
|---|---|---|---|
| United States | 233 | 73 | 306 |
| Canada | 2 | 0 | 2 |
| Antibody deficiency(Participants) | Immune Deficient/Disordered | Healthy Control | Total |
|---|---|---|---|
| Count of participants | 54 | 0 | 54 |
| Primary immune regulatory disorder(Participants) | Immune Deficient/Disordered | Healthy Control | Total |
|---|---|---|---|
| Count of participants | 56 | 0 | 56 |
4 further baseline measures are reported on the registry.
Documents are hosted by the registry — open the source record to download them.
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Immunologic Deficiency Syndromes→
National Institute of Allergy and Infectious Diseases (NIAID)