COVID-19 Booster Vaccine in Autoimmune Disease Non-Responders

This is a randomized, multi-site, adaptive, open-label clinical trial comparing the immune response to different additional doses of COVID-19 vaccine in participants with autoimmune disease requiring IS medications. All study participants will have negative serologic or suboptimal responses (defined as a Roche Elecsys® Anti-SARS-CoV-2 S result ≤200 U/mL) or a low immune response (defined as a Roche Elecsys® Anti-SARS-CoV-2 S result \>200 U/ml and ≤2500 U/mL) to their previous doses of COVID-19 vaccine. The study will focus on 5 autoimmune diseases in adults: * Systemic Lupus Erythematosus (SLE) * Rheumatoid Arthritis (RA) * Multiple Sclerosis (MS) * Systemic Sclerosis (SSc), and * Pemphigus. This study will focus on 4 autoimmune diseases in pediatric participants: * Systemic Lupus Erythematosus (SLE) * Juvenile Idiopathic Arthritis (JIA) * Pediatric-Onset Multiple Sclerosis (POMS) * Juvenile Dermatomyositis (JDM)

General Adult Inclusion Criteria: 1\. Willing and able to sign informed consent 2. Documented full COVID-19 vaccination (CDC card or documentation in medical records) that was completed at least 4 weeks prior and no more than 52 weeks prior to the Stage 1 Screening visit, or if participating in Stage 2, no more than 48 weeks prior to the Stage 2 Screening visit. General Exclusion Criteria 2. History of severe allergic reaction to the initial COVID-19 vaccine regimen, to any component of any of the COVID-19 vaccines, or to polyethylene glycol (PEG). 3\. New diagnosis of malignancy that will require chemotherapy or immunotherapy, or ongoing treatment for a malignancy with chemotherapy or immunotherapy. 4\. Active disease (per the Investigator's decision) resulting in inability to hold the IS therapy in the MMF/MPA or MTX arms of the study. a. The potential impact of temporarily holding medication for participants with a recent mild disease flare within 4 weeks should be carefully considered. 5\. Active disease during the Screening period resulting in: 1. An increase/addition of any IS medications, or 2. A suggestion of MS relapse per the investigator. 6. Recent or current SARS-CoV-2 infection defined as: 1. Documented SARS-CoV-2 infection in the past 30 days (from the day the participant is diagnosed by positive test to Screening). 2. Positive result on a molecular COVID-19 test at Screening. 8. Inflammatory myocarditis/pericarditis within 6 weeks of any COVID-19 vaccine doses. 9\. Participants with active, ongoing chronic infections. Note: Participants are permitted to be on chronic prophylactic antimicrobial therapy. Adults with evidence of HIV, Hepatitis B indicated by surface antigen, and Hepatitis C indicated by anti-hepatitis C antibody positivity will be excluded. If an adult is negative for Hepatitis C viral load at Screening, he/she will be eligible to participate. 10\. Participants with common variable immunodeficiency disease, as well as any participants currently receiving immune globulin replacement therapy. Note: Pediatric participants on IVIG therapeutically may enter the study provided they have sufficiently quiet disease that they can withhold their IVIG from 8 weeks prior to the Screening visit through 4 weeks after vaccination. 11\. Participants who received licensed or investigational monoclonal antibodies or plasma products directed against SARS-CoV-2 within 30 days of Screening. 12\. Participants who have received any live vaccines within 2 months of the anticipated study vaccine dose or who will have need of a live vaccine at any time during the study. 13\. Currently pregnant or breastfeeding (For pediatric participants postmenarchal females must have a negative urine pregnancy test at Screening). 15\. Hemoglobin (Hgb) \