We aim at identifying potential biomarkers in plasma indicative of post-acute coronavirus SARS-CoV-2 Syndrome (Long COVID). Our case-control study will compare Long COVID patients to healthy patients from Sutter Health.

Two measures will be obtained from participants' plasma:

1. microbial signatures using Karius' agnostic metagenomic assay via microbial cell-free DNA (mcfDNA) sequencing (kariusdx.com)
2. cytokine signatures using 71-plex and 18-plex assays (evetechnologies.com).

The diagnostic utility of the potential biomarkers, including signatures derived from microbial cell-free DNA fragments found in plasma and plasma cytokines, will be evaluated independently and in various combinations to determine whether and to what extent we can accurately identify Long COVID patients. Moreover, we plan to leverage the Karius Test and the underlying Karius microbial cell-free DNA technology to determine whether there is evidence of more frequent reactivations of latent infections in patients with long COVID compared to matched healthy control. Plasma samples will also be stored for future comparative studies of additional immune profiles.

Inclusion Criteria:

• ≥ 18-year-old

• English speaking (per Sutter medical records information)

• Ability and willingness to provide signed Consent Form

• Ability to comply with the study protocol

• Ability to attend the study visit, complete questionnaires, have blood collected and tested And, either Long-COVID or Healthy control as described below

• Long-COVID patient Cohort (n=75)

  • Sutter patient who is a patient from Sutter Health Holistic/Integrative Medicine clinic

  • Documentation of a long-COVID diagnosis (U09.9) for patient's initial visit in clinic between 01/01/2021 and 06/30/2024.

  • Presence of active and ongoing long-COVID symptoms

  • Ongoing long-COVID symptoms consistently present over the previous 6 months or longer

  • Presence of the following long-COVID symptoms (a, b, and c plus either d or e) affecting you more than 50% of your life:

    1. Fatigue that does not go away with rest.
    2. Post-exertional malaise ((worsening of your symptoms following cognitive, emotional, physical efforts)
    3. Unrefreshing sleep (sleep is not restorative)
    4. Brain "fog" (e.g., difficulty with finding words or mental tasks)
    5. Postural Orthostatic Hypotension (e.g., lightheadedness, dizziness, and/or palpitations with sitting up or standing up positions).

• Healthy controls with no Long COVID syndrome (n=75)

  • Sutter Health patients
  • Matched by age to a long COVID subject (+/-10 years and preferably by sex).

Exclusion Criteria:

• Pregnant or nursing woman

• Alcohol or another drug abuse ongoing within one year

• Severe depression or acute suicidal ideation

• Bipolar disorder, schizophrenia, or other psychosis

• History of malignancy, except basal cell carcinoma

• History of significant autoimmune disorder:

  • Addison disease
  • Dermatomyositis
  • Graves' disease
  • Multiple sclerosis
  • Myasthenia gravis
  • Pernicious anemia
  • Rheumatoid arthritis
  • Sjögren syndrome
  • Systemic lupus erythematosus
  • Type I diabetes
  • Celiac disease

• Active pulmonary infection (active pneumonia)

• Chronic kidney disease

• Chronic liver disease

• Chronic lung disease

• Pulmonary fibrosis

• Interstitial pneumonitis

• Uncontrolled asthma

• Chronic obstructive pulmonary disease (COPD)

• Reactive arthritis

• Immunocompromised conditions or weaken immune system:

  • Cancer under treatment or treated within one year of enrollment
  • AIDS
  • Transplant patient

• Biologicals impacting the immune system

• Taking immunosuppressor

• Neurologic conditions:

  • Dementia or other neurological conditions
  • Acute Spinal Cord Injury
  • Alzheimer's Disease
  • Amyotrophic Lateral Sclerosis (ALS)
  • Ataxia
  • Cerebral Aneurysm diagnosed within one year of enrollment
  • Epilepsy and Seizures uncontrolled with medication

• Heart conditions:

  • Congestive heart failure
  • Myocardial infarction

This study will focus on participants with a diagnosis code for long-COVID (U09.9) in their Sutter EMR and healthy controls who are Sutter Health's patients.

It will enroll 75 patients diagnosed with long-COVID and 75 matched healthy controls respectively.

Healthy controls will be matched 1:1 to long-COVID patients for age (+/-10 years and preferably by sex).