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

This is an interventional treatment trial for Systemic Inflammation focused on measuring Long Haul Covid, COVID-19, Long Covid Read More

• INCLUSION CRITERIA:

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

• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Male or female, aged at least 18 and older.
• Enrolled in the screening phase of Protocol 000089 'Post-Coronavirus Disease 19 Convalescence at the National Institutes of Health.'
• Previously diagnosed with mild-moderate COVID-19 (WHO Clinical Progression Scale between 2-5). Enrollment could take place between 12 weeks and 18 months after the diagnosis of acute COVID-19.
• Prior COVID-19 diagnosis confirmed by patient reported positive antigen test for SARS-CoV-2 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.

EXCLUSION CRITERIA:

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.
• Contraindication to autonomic testing, including refractory ventricular arrhythmias or symptomatic coronary artery disease.
• A condition prior to the diagnosis of COVID-19 infection 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 IV steroids or 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.
• Diabetes mellitus treated with medications or HbA1c >6.5.

• 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 steroids, immunoglobulins, acetaminophen, or diphenhydramine.
• Positive QuantiFERON-TB Gold test.
• A severe psychiatric condition prior to the diagnosis of COVID-19, which based on the assessment of the study investigators, will significantly increase the risk of psychiatric side effects from IV steroids.