Evaluating the Immune Response to COVID19 Vaccination in Immunodeficient Patients

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to understand the immune response to coronavirus disease-19 (COVID-19) vaccination in patients on B-cell depleting therapies (BCDT) over time, which in the future may help to inform clinical decision making in this patient population.

Detailed Description
-----------------
This will be a prospective, observational cohort study consisting of individuals with autoimmune diseases who are undergoing treatment with anti-CD20 medications at the time they receive a vaccine against COVID-19. Control groups will include healthy individuals, individuals with autoimmune diseases on other immunomodulators, and individuals with autoimmune diseases not on immunotherapy. Participants will undergo serial blood draws and saliva collections at prespecified time points surrounding vaccination. A subset of agreeable participants will undergo skin biopsy within days of the first vaccination, with the option to repeat skin biopsy after the second vaccination. Additional blood, saliva and skin biopsy specimens may be obtained after booster vaccinations or after known COVID19 infections . Specimens collected will be used for studies aimed at (1) understanding the pathobiology of neurologic/inflammatory/immune diseases and the immunologic response to COVID-19 vaccination, (2) identifying how and why treatments used for neurologic/immune diseases may impact the effectiveness of vaccination, and (3) identifying dermatologic manifestations of the immunologic response to the COVID-19 mRNA vaccine. The investigators are investigating both the production of antibodies against the virus over time and deeply interrogating the T-cell response to vaccination using methods that measure T-cell reactivity to the COVID-19 virus, including single cell RNA sequencing.

Official Title
-----------------
Evaluating the Immune Response to COVID19 Vaccination in Immunodeficient Patients

Conditions
-----------------
Multiple Sclerosis, Autoimmune Blistering Disease, B-Cell Deficiency

Intervention / Treatment
-----------------
* Biological: COVID19 vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Subjects with neurologic/immunologic condition: at least 18 years of age Known diagnosis of autoimmune neurologic disease (e.g. multiple sclerosis (MS), neuromyelitis optica, myelin oligodendrocyte glycoprotein (MOG) -associated disorder) or autoimmune blistering disease (AIBD). EITHER: Treated with an anti-CD20 (rituximab, ocrelizumab) medications for >6 months at the time of vaccination (B-cell depletion therapy, BCDT) On no immunomodulatory therapy for their autoimmune condition for >6 months at the time of vaccination Treated with a non-BCDT immunotherapy No relapse of neurologic/immunologic disease for >6 months prior to the time of enrollment Subject is eligible and willing to receive COVID-19 vaccination in accordance with local and national guidelines, or subject intends to receive booster COVID-19 vaccination in accordance with recommendations from their primary medical team. No active skin condition (e.g. open sores) preventing blood draw Healthy Controls: at least 18 years of age No evidence of neurological/immunologic disease/illness/condition Subject is eligible and willing to receive COVID-19 vaccination in accordance with local and national guidelines, or subject intends to receive booster COVID-19 vaccination in accordance with recommendations from their primary medical team. No active skin condition (e.g. open sores) preventing blood draw/skin biopsy Exclusion Criteria: Use of high dose steroids for treatment of neurologic/immunologic disease within 1 month of COVID-19 vaccination Anti-CD20 B-cell depleting therapy infused within 2 weeks of first study visit Inability to comply with the requirements of the protocol, in the opinion of the primary investigator

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy control<br>Healthy controls Participants will receive COVID19 vaccination according to standard of care (any FDA approved vaccine). They will donate serial biospecimens before and after vaccination according to the study design. | Biological: COVID19 vaccine<br>* All participants receive one or more FDA-authorized COVID19 vaccinations according to standard of care and current medical recommendations. The intervention is not specifically administered as part of the study.<br>|
| Disease control<br>Disease controls (individuals with a qualifying autoimmune condition, but not treated with any immunomodulator). Participants will receive COVID19 vaccination according to standard of care (any FDA approved vaccine). They will donate serial biospecimens before and after vaccination according to the study design. | Biological: COVID19 vaccine<br>* All participants receive one or more FDA-authorized COVID19 vaccinations according to standard of care and current medical recommendations. The intervention is not specifically administered as part of the study.<br>|
| B-cell depleted<br>Individuals with autoimmune disease (multiple sclerosis or autoimmune blistering disease) who are treated with B-cell depleting anti-CD20 monoclonal antibodies. Participants will receive COVID19 vaccination according to standard of care (any FDA approved vaccine). They will donate serial biospecimens before and after vaccination according to the study design. | Biological: COVID19 vaccine<br>* All participants receive one or more FDA-authorized COVID19 vaccinations according to standard of care and current medical recommendations. The intervention is not specifically administered as part of the study.<br>|
| Other immunomodulator<br>Individuals with autoimmune disease (multiple sclerosis or autoimmune blistering disease) who are treated with a non-CD20 monoclonal antibody immunomodulator to treat their disease. Participants will receive COVID19 vaccination according to standard of care (any FDA approved vaccine). They will donate serial biospecimens before and after vaccination according to the study design. | Biological: COVID19 vaccine<br>* All participants receive one or more FDA-authorized COVID19 vaccinations according to standard of care and current medical recommendations. The intervention is not specifically administered as part of the study.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in coronavirus disease 19 (COVID19) antibody titers over time | COVID 19 spike and neutralizing antibody titers will be monitored serially | Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines | 
| Change in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) specific T-cell activation over time | Flow cytometry characterizing immunophenotype of SARS-CoV2 specific T cells | Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skin biopsy analysis | Histologic and immunologic characterization of skin biopsy specimens, comparing vaccinated to unvaccinated arm, at one or more timepoints post-vaccination | 7 days post vaccine 1; 7 days post vaccine 2; 4 days post booster (all timepoints optional) | 
| Measurement of COVID19 antibodies in saliva | Descriptive assessment of whether COVID antibodies can be detected in saliva at any time point | Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines | 
| Immune analysis | Deep immunologic assessment (flow cytometry, single cell RNA sequencing) of blood specimens; descriptive analysis at each timepoint with comparisons over time will be performed. | Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines | 
| Changes in patient reported outcomes: COVID history | Subjective reports of vaccination-associated symptoms and COVID risk factors (COVID-19 survey) | Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines | 
| Change in patient reported outcomes: patient reported disability steps | Subjects will complete Patient Derived Disability Step score | Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines | 
| Change in patient reported outcomes: overall symptoms | SymptoMS screening questionnaire | Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines |