Evaluating remnants of SARS-CoV-2 in people recovering from COVID-19

* INCLUSION CRITERIA:

Recovered Volunteers (RV): Six healthy persons who have recovered from an acute SARS-CoV-2 infection.

Inclusion criteria:

* Participants 18 and older
* Ability to provide informed consent
* Completed participation in Phase B of Protocol 000089
* Met 000089 Inclusion criteria for Mild to Moderate COVID-19 without PASC symptoms:

  * Licensed Independent Practitioner documentation of a stable state of general well-health and physical function prior to contracting SARS-CoV-2. This may include medical records, correspondence letters, or information gathered from telephone calls with study personnel.
  * A self-reported illness narrative of recovery to prior health after a SARS/CoV2 infection.
  * Laboratory documentation of a positive COVID-19 PCR, NAA, or other EUA Approved test to confirm active COVID infection at the time of the SARS-CoV-2 infection. Participants with positive home tests during Phase A will be required to have a positive anti-SARS nucleocapsid antibody test.
  * Meets WHO Clinical Progression Scale of 2 - 6:

    2: Ambulatory; symptomatic, independent

    3: Ambulatory; symptomatic, assistance needed

    4: Hospitalized; no oxygen therapy

    5: Hospitalized; oxygen by mask or nasal prongs

    6: Hospitalized; oxygen by non-invasive ventilation or high flow oxygen
  * Functional Criteria: No substantial symptom severity as determined using SF-36v2: score of \>=85 physical function subscale, and \>=85 on role physical subscale, and \>=85 on social function subscale.
* Determined to be a Healthy Comparator by the 000089 Case Adjudication Committee
* Does not have an active SARS-CoV-2 infection. The protocol will conform with NIH CC standards for documenting a participant does not have active SARS-CoV-2 infection. This may include screening interviews and/or testing. Testing may be repeated with each admission. Participants may be rescreened 6 weeks after acute infection has resolved.

Neurologic Post-Acute Sequelae of COVID-19 Participants (Neuro-PASC):

Six persons with ongoing neurological complaints following an acute SARS-CoV-2 infection.

Inclusion criteria:

* Participants 18 and older
* Ability to provide informed consent
* Completed participation in Phase B of Protocol 000089
* Met 000089 Inclusion criteria for Mild to Moderate COVID-19 with PASC symptoms:

  * Licensed Independent Practitioner documentation of a stable state of general well-health and physical function prior to contracting SARS-CoV-2. This may include medical records, correspondence letters, or information gathered from telephone calls with study personnel.
  * 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, unrefreshing sleep, neuropathic pain, mood change, and post-exertional malaise.
  * Laboratory documentation of a positive COVID-19 PCR, NAA, or other EUA Approved test to confirm active COVID infection at the time of the SARS-CoV-2 infection. Participants with positive home tests during Phase A will be required to have a positive anti-SARS nucleocapsid antibody test .
  * Meets WHO Clinical Progression Scale of 2 - 6:

    2: Ambulatory; symptomatic, independent

    3: Ambulatory; symptomatic, assistance needed

    4: Hospitalized; no oxygen therapy

    5: Hospitalized; oxygen by mask or nasal prongs

    6: Hospitalized; oxygen by non-invasive ventilation or high flow oxygen
  * Functional Criteria: Substantial symptom severity as determined using SF-36v2: score of \<= 70 physical function subscale, or \<=50 on role physical subscale, or \<=75 on social function subscale.
* Determined to have Post-Acute Sequelae of COVID-19 by the 000089 Case Adjudication Committee
* Primary PASC complaint is neurologic including:

  * Neuropathic sensations
  * Cognitive complaints
  * Postural (Orthostatic) complaints
  * Motor complaints
* Does not have an active SARS-CoV-2 infection. The protocol will conform with NIH CC standards for documenting a participant does not have active SARS-CoV-2 infection. This may include screening interviews and/or testing. Testing may be repeated with each admission. Participants may be rescreened 6 weeks after acute infection has resolved.

EXCLUSION CRITERIA:

* Current suicidal ideation
* Women who are pregnant, breastfeeding, or are within one-year post-partum.
* Current or previous malignancy. A history of malignancy that has fully resolved with surgical resection only (e.g. no chemotherapy, radiation therapy, or immunotherapy) will be allowed.
* Current systemic immunologic disorders (e.g. Type 1 diabetes, rheumatoid arthritis). Local immunological disorder (e.g. atopic dermatitis, stable autoimmune thyroid disease) and allergic disorders will be allowed.
* Current or previous long-term immune suppressive therapy. Systemic steroid use, even short-term, must not have been used within the month prior to enrollment.
* Long term use of anticoagulant or antiplatelet medications.
* Active participation in a clinical protocol (e.g. anti-inflammatory drug intervention study) which includes an intervention that may affect the results of the current study.
* Not willing to allow for research data and samples to be shared broadly with other researchers.
* Employees of NIH.
* Symptom severity that makes it impossible for the volunteer to travel to NIH for an extended inpatient evaluation
* Use of medications with a high-risk for withdrawal-related complications (i.e. long-acting opiates or benzodiazepines).
* Unwillingness to co-enroll in protocol 17-I-0122: NIAID Centralized Sequencing Protocol.