Natural History of Post-Coronavirus Disease 19 Convalescence at the National Institutes of Health

Eligibility Criteria

• 1. Participants 18 and older
• 2. Ability to provide informed consent
• 3. Stated willingness to complete telephone interviews
• 1. PCR, NAA, or other EUA Approved test to confirm active COVID infection.
• 2. A positive home Antigen test is acceptable when documentation of a photograph of the test with a phone-based date and time stamp is provided.
• 3. A positive anti-Spike antibody test is accepted in unvaccinated individuals or those who had antibody testing prior to vaccination.
• 4. A positive anti-nucleocapsid antibody test
• 1. Participants 18 and older
• 2. Ability to provide informed consent
• 3. Stated willingness to complete telephone interviews
• 4. Reports having developed persistent symptoms as a consequence of an acute SARS/CoV2 infection
• 5. Provides documentation of a clinical diagnosis of an acute SARS/CoV2 infection from a medical practitioner OR meets the Clinical Criteria of the 2020 CDC Interim Case Definition for Probable SARS/CoV2 infection.
• 6. Has either negative or absent COVID-19 PCR, NAA, or other EUA Approved testing for the documented SARS/COV2 infection.
• 7. Provides documentation of a negative COVID-19 antibody test prior to vaccination.
• 1. Participants 18 and older
• 2. Ability to provide informed consent
• 3. Stated willingness to complete telephone interviews
• 4. Reports having developed persistent symptoms as a consequence of a COVID 19 vaccination
• 5. Provides documentation of COVID-19 vaccination
• 6. Provides documentation of a COVID-19 vaccine related medical condition from a medical practitioner
• 1. Participants 18 and older
• 2. Ability to provide informed consent
• 3. Stated willingness to complete telephone interviews
• 4. Reports having more than one SARS-CoV-2 infection
• 5. Provides documentation of at least one positive COVID-19 Test. Approved test can include the following:
• 5. PCR, NAA, or other EUA Approved test to confirm active COVID infection.
• 6. A positive home Antigen test is acceptable when documentation of a photograph of the test with a phone-based date and time stamp is provided.
• 7. A positive anti-Spike antibody test is accepted in unvaccinated individuals or those who had antibody testing prior to vaccination.
• 8. A positive anti-nucleocapsid antibody test
• * Clinical or radiographic evidence of pneumonia, OR
• * Acute respiratory distress syndrome (ARDS).
• 1. Adult participants aged 18 years and older
• 2. Self-reported completion of at least the 7th grade of school.
• 3. Fluency in English.
• 4. Willing and able to complete all study procedures
• 5. Participant has a primary care provider at the time of enrollment.
• 6. Able to provide informed consent
• 7. Participants must be at least six weeks out since the onset of COVID-19 symptoms with no fever for at least one week.
• 8. Participants must be within five years since starting to recover from acute COVID- 19 symptoms. The date of the start of recovery can be determined by:
• * The date that fever broke for the first time
• * The date the participant recalls starting to improve
• * If a participant is unable to report a reliable date, a date of six weeks from the onset of COVID-19 symptoms may be imputed.
• 9. 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.
• 1. 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.
• 2. 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.
• 3. 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.
• 4. 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
• 5. 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.
• 1. 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.
• 2. A self-reported illness narrative of recovery to prior health after a SARS/CoV2 infection.
• 3. 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.
• 4. 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
• 1. 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.
• 2. Either a self-reported illness narrative of near recovery to prior health or a 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.
• 3. 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.
• 4. Meets WHO Clinical Progression Scale\[61\] 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
• 5. Functional Criteria: Mild to moderate symptom severity as determined using SF-36v2: score of between 71 and 84 on the physical function subscale, or between 51 and 84 on role physical subscale, or between 76 and 84 on social function subscale.
• 1. Met inclusion and exclusion criteria for Mild to Moderate Illness COVID-19 with severe post-acute COVID-19 symptoms after completing Phase B.
• 2. No alternative explanation for PASC symptoms identified by adjudication committee during Phase B.
• 3. Fluency in English
• 1. Met inclusion and exclusion criteria for Mild to Moderate Illness COVID-19 without post-acute COVID-19 symptoms after completing Phase B.
• 2. Fluency in English
• 1. Not willing to provide personal identifying information to investigative team
• 2. Cognitive impairment that is severe enough to limit consent capacity
• 1. Current or past psychotic disorder including depression with psychosis, bipolar disorder with psychotic symptoms and schizophrenia
• 2. Major depression disorder, generalized anxiety disorder, post-traumatic stress disorder, panic disorder, or obsessive-compulsive disorder unless managed for more than six months with a stable treatment regimen
• 3. Current or past substance use disorder within last five years. Marijuana use within the past five years will not be an exclusion.
• 4. Positive urine toxicology screening for anything other than marijuana
• 5. Current suicidal ideation
• 6. History of head injury leading to moderate or severe traumatic brain injury. Persons having a history of mild TBI (mTBI) will not be excluded.
• 7. Women who are pregnant, breastfeeding, or are within one-year post-partum.
• 8. 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.
• 9. 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.
• 10. Current or previous long-term immune suppressive therapy. Recent or current steroid use for the treatment of COVID-19, PASC, recent allergic reactions, and topical steroid use is allowed.
• 11. Any premorbid medical condition that would potentially cause fatigue and exercise intolerance that would exclude from participation in Phase C. This includes many chronic medical diseases, such
• 12. 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.
• 13. Not willing to allow for research data and samples to be shared broadly with other researchers.
• 14. Employees at NIH that are under the direct supervision of the study investigators (family members of NIH employees are permitted to participate).
• 15. Symptom severity that makes it impossible for the volunteer to travel to NIH.
• 1. Current or past psychotic disorder including depression with psychosis, bipolar disorder with psychotic symptoms and schizophrenia
• 2. Current DSM-5-defined major depression disorder, generalized anxiety disorder, post-traumatic stress disorder, panic disorder, or obsessive-compulsive disorder unless managed for more than six months with a stable treatment regimen
• 3. Current or past substance use disorder within last five years as diagnosed on the Structured Clinical Interview for DSM-5 (SCID-5). Mar...