Immunotherapy for Neurological Post-Acute Sequelae of SARS-CoV-2

Exclusion Criteria

• •Previously diagnosed with mild-moderate COVID-19 (WHO Clinical Progression Scale between 2-5. Patients with severe acute COVID-19 requiring hospitalization or ICU care are excluded. Enrollment could take place 12 weeks after the diagnosis of acute COVID-19.
• •Prior COVID-19 diagnosis confirmed by patient reported infection followed by confirmatory nucleocapsid antibody testing or a positive SARS-CoV-2 PCR test result from the time of infection.
• •Exhibiting persistent neurologic symptoms evidenced by a self-reported illness narrative of the development of persistent PASC symptoms after recovering from a SARS-CoV-2 infection. These include symptoms such as fatigue, cognitive difficulties, orthostatic intolerance, and any ongoing issues with gait instability, vision, speech, swallowing, sensation or strength.
• •Non-negligible PASC symptom severity, as determined using PCFS (minimal score of 2).
• •Ability of subject to understand and the willingness to sign a written informed consent document.
• •Prior completion of a clinical brain MRI after the diagnosis of COVID-19, or willingness to complete a brain MRI.
• •Meets current Clinical Center HES' policy for discontinuing isolation and quarantine for COVID-19.
• •An individual who meets any of the following criteria will be excluded from participation in this study:
• •\- For participants who have not completed a brain MRI since onset of symptoms: inability to complete brain MRI with gadolinium including contraindicated metal in the body, prior allergic reaction to gadolinium, eGFR \<45 mmol/L, pregnancy or lactation, or claustrophobia that is unable to be adequately treated with a low dose oral
• •benzodiazepine.
• •Contraindication to a research lumbar puncture, including use of anticoagulant medication, platelets \< 50,000/uL, PT or PTT \>1.5 x ULN for the NIH Clinical Center, or otherwise inability to complete the procedure.
• •A condition that would significantly confound interpretation of the clinical and research tests as determined by the study investigators. This could include: traumatic brain injury, substance use disorder, active malignancy, systemic immunologic disorders, current or previous long-term immune suppressive therapy.
• •Received a SARS-CoV-2 vaccine dose within less than 4 weeks of enrollment or is planning for any additional vaccines during the course of the study.
• •Prior experimental treatment for PASC with immunoglobulins.
• •Current medications include oral steroids or other immunosuppressive medications.
• •Active participation in a clinical protocol which includes any intervention that may affect the results of the current study.
• •Contraindication of intravenous immunoglobulins, including:
• •* Renal insufficiency (eGFR\<45mmol/L)
• •* IgA deficiency
• •* History of ischemic heart disease
• •* Peripheral vascular disease
• •* Cerebrovascular disease
• •* Previously diagnosed hypercoagulability syndrome including antiphospholipid antibody syndrome, Protein C/S deficiency, Factor V Leiden, Antithrombin deficiency, MTHFR homozygosity
• •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3.0 times the upper limit of normal.precluding the use of acetaminophen.
• •Previously documented anaphylaxis or severe systemic reaction to immunoglobulins, acetaminophen, or diphenhydramine.
• •A severe psychiatric condition, which based on the assessment of the study investigators, will impact the ability to complete the 12-week study course.