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Analysis of the Immune Response to COVID-19 Vaccination and Outcomes in Individuals With and Without Immune Deficiencies and Dysregulations

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04852276
Recruitment Status : Recruiting
First Posted : April 21, 2021
Last Update Posted : December 16, 2021
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Brief Summary:


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.


To learn about how people with immune deficiencies respond to COVID-19 vaccines.


People age 12 and older with an immune deficiency who plan to get a COVID-19 vaccine. Healthy volunteers are also needed.


Participants will be screened with a medical record review.

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.

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 a second (booster) vaccine, 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.

Participation will last from 1 month to 2 years after the participant s last vaccine.

Condition or disease
Immunodeficiencies Immune Dysregulations

Detailed Description:

The novel human severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease (COVID-19). This acute respiratory syndrome is associated with activation of the innate immune system and a hyper-inflammatory response which can lead to life-threatening symptoms. There are a number of primary immunodeficiencies (PIDs) that prevent complete activation of innate immune cells or other pro-inflammatory mediators, as well as secondary immune deficiencies that evoke the same dysfunctional immune response. Because the extent to which these individuals experience COVID-19 is unknown, vaccination against SARS-CoV-2 is critical.

In December 2020, the FDA announced Emergency Use Authorization for two mRNA-based SARS-CoV-2 vaccines. While evaluation of the immune response to these vaccines in healthy volunteers is ongoing, no large-scale characterization of the immune response in immunodeficient individuals has been undertaken. This prospective cohort study will assess and describe the baseline and post-vaccination immune response in individuals with select immune deficiencies compared to healthy volunteers who receive a COVID-19 vaccine, as well as any adverse events (AEs) experienced after either dose. 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 collected approximately 21 days after dose 1 and approximately 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 will again be drawn approximately 28 days after the booster dose. For individuals who are enrolled but have not yet had samples collected, a sample will be drawn prior to the booster. 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 about vaccine AEs using standardized questionnaires.

The goal of this protocol is to gain a comprehensive understanding of the variety of immune responses in immunodeficient individuals.

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Study Type : Observational
Estimated Enrollment : 600 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Analysis of the Immune Response to COVID-19 Vaccination and Outcomes in Individuals With and Without Immune Deficiencies and Dysregulations
Actual Study Start Date : April 20, 2021
Estimated Primary Completion Date : June 30, 2025
Estimated Study Completion Date : June 30, 2025

Resource links provided by the National Library of Medicine

Control particpants
Control participants will be healthy volunteers, and may include unaffected relatives of immunodeficient/dysregulated participants
Patients with immunodeficiencies and immune dysregulations
Affected patients with evidence of a primary or secondary immune deficiency or dysregulation

Primary Outcome Measures :
  1. Change in S and RBD immunoglobulin G (IgG) antibody titer from baseline depending on vaccine manufacturer and platform [ Time Frame: 14-21 days or 21-28 days, depending on vaccine manufacturer and platform ]
    To characterize the immune response to COVID-19 vaccination among immunodeficient and immune dysregulated individuals compared to healthy volunteers

Secondary Outcome Measures :
  1. Incidence of vaccine-associated AEadverse events experienced by immunodeficient individuals compared to healthy volunteers [ Time Frame: Throughout study ]
    To characterize the COVID-19 vaccine-associated adverse events among immunodeficient and immune dysregulated individuals compared to healthy volunteers

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   3 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
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:

  1. Aged 3 years and older.
  2. Must be eligible to receive (based on official FDA authorization or approval) and scheduled to receive or have already received a COVID-19 vaccine outside of this facility.
  3. Must meet the definition of affected participant or control participant:

    1. Affected participants must have evidence of a primary or secondary immune deficiency or dysregulation under another NIAID protocol or as documented by an outside physician.
    2. Control participants are healthy volunteers that do not have evidence of a primary or secondary immune deficiency or dysregulation and may include unaffected relatives of affected participants.
  4. Ability to provide informed consent.
  5. Willing to have blood samples stored for future research.
  6. Able to proficiently speak, read, and write English.


Individuals meeting any of the following criteria will be excluded from study participation:

  1. Receipt of any other vaccine within 14 days prior to screening.
  2. Planned non-COVID-19 vaccination within 28 days after COVID-19 vaccination(s).
  3. Any condition that, in the opinion of the investigator, contraindicates participation in this study (e.g. specific autoinflammatory diseases, interferonopathies).
  4. Self-reported history of HIV.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04852276

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Contact: Emily E Ricotta, Ph.D. (301) 761-7784

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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010   
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
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Principal Investigator: Emily E Ricotta, Ph.D. National Institute of Allergy and Infectious Diseases (NIAID)
Additional Information:
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID) Identifier: NCT04852276    
Other Study ID Numbers: 10000384
First Posted: April 21, 2021    Key Record Dates
Last Update Posted: December 16, 2021
Last Verified: November 3, 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
Adaptive immunity
clinical epidemiology
Natural History
Additional relevant MeSH terms:
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Immunologic Deficiency Syndromes
Immune System Diseases