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

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.

• INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet the following criteria:

• Aged 3 years and older.
• 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.
• Must meet the definition of affected participant or control participant:

• 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.
• 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.
• Ability to provide informed consent.
• Willing to have blood samples stored for future research.
• Able to proficiently speak, read, and write English.

Exclusion criteria

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

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