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COVID-19 Vaccination and Outcomes in Individuals With and Without Immune Deficiencies and Dysregulations

Completed
Conditions
Immunodeficiencies
Immune Dysregulations
Registration Number
NCT04852276
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

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.

Detailed Description

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
308
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Change in S and Receptor Binding Domain (RBD) Immunoglobulin G (IgG) Antibody Titer From Baseline Depending on Vaccine Manufacturer and PlatformBaseline, post dose 1 (14-21 days), and post dose 2 (21-28 days), 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

Secondary Outcome Measures
NameTimeMethod
Incidence of Vaccine-associated Adverse Events (AE) Experienced by Immunodeficient Individuals Compared to Healthy VolunteersBaseline up to a maximum of 24 months

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.

Trial Locations

Locations (1)

National Institutes of Health Clinical Center

🇺🇸

Bethesda, Maryland, United States

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