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

Study Description:

It has been demonstrated that remnants of the SARS-CoV-2 virus remain after the resolution of the acute infective period. It is not known if these viral remnants interact with host tissues in the development and maintenance of the Post-Acute Sequelae of COVID-19 (PASC)/Long COVID. Better understanding of how to recover and characterize SARS-CoV-2 viral remnants from humans is a valuable first step in understanding the health impact that they may have on humans. This study will focus on the recovery and characterization of SARS-CoV-2 remnants from multiple organ sites of individual volunteers with persistent neurological complications from SARS-CoV-2 (Neuro-PASC) and volunteers those who have recovered from a SARS-CoV-2 infection (RV).

Objectives:

• Primary Objective:

--To determine where remnants of SARS-CoV-2 virus can be recovered in persons with neuro-PASC and RVs.

• Secondary Objectives:

• To characterize the biochemical nature of SARS-CoV-2 recovered viral remnants (e.g. proteins, nucleic acids).
• To determine if there are quantitative differences in recovered SARS-CoV-2 proteins between neuro-PASC and RV participants.
• To determine if there are quantitative differences in recovered SARS-CoV-2 nucleic acids between neuro-PASC and RV participants.

Endpoints:

This is an exploratory cross-sectional protocol to determine whether the presence or absence of viral remnants can be detected in a range of human tissues. Hence, tissue-specific detection of viral remnants is the primary end point. Secondary endpoints will characterize and quantify the recovered remnants to allow group comparisons between neuro-PASC and RV participants.

• 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.