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

Cross-Sectional Evaluation of Persistence of SARS-CoV-2 Remnants After Recovery From Acute Infection

This study is trying to see if people who have recovered from COVID-19 still have leftover pieces of the virus in their bodies, especially those with ongoing neurological symptoms.

Quick facts

• Study type: Observational
• Enrollment: 12 (estimated)
• Ages: 18 Years to 110 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT06577467 on ClinicalTrials.gov

What this trial studies

This observational study aims to investigate whether individuals who have recovered from COVID-19, particularly those experiencing long-term neurological symptoms, retain inactive remnants of the SARS-CoV-2 virus in their bodies. Participants aged 18 and older will undergo 2 to 4 visits over four months, during which tissue samples will be collected for analysis. The study will focus on identifying the presence and biochemical characteristics of these viral remnants across various organ sites. By understanding the persistence of these remnants, researchers hope to shed light on their potential role in post-acute sequelae of COVID-19 (PASC).

Who should consider this trial

Good fit: Ideal candidates include individuals aged 18 and older who have recovered from COVID-19, with or without neurological symptoms.

Not a fit: Patients who are currently experiencing acute COVID-19 symptoms or have not recovered from the infection will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide insights into the mechanisms behind long COVID and inform future treatment strategies.

How similar studies have performed: While studies have explored the long-term effects of COVID-19, this specific investigation into viral remnants is novel and has not been extensively tested.

Eligibility criteria

* 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.

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Avindra Nath, M.D. — National Institute of Neurological Disorders and Stroke (NINDS)
• Study coordinator: Angelique A Gavin

Conditions PASC Post Acute Sequelae of COVID-19; PASC; COVID-19