Validation of Biomarkers for Long COVID in the LIINC Viral Immunopathogenesis and Persistence Repeat Donor Cohort (VIPER)

Validation of Biomarkers for Long COVID in the LIINC Viral Immunopathogenesis and Persistence Repeat Donor Cohort (VIPER)

The purpose of this study is to better understand the biological changes associated with Long COVID and to identify laboratory tests (biomarkers) that may help diagnose the condition and measure how it changes over time. Researchers will enroll people with Long COVID as well as people who have fully recovered after COVID-19 infection.

Participants will provide health information and biological samples, such as blood, saliva, stool, and, for some participants, tissue biopsies. These samples will be used to study the biological processes involved in Long COVID and to support the development of new diagnostic tests that may improve future research, clinical trials, and patient care.

The lack of a biomarker for Long COVID (LC) is the single biggest obstacle to the development of a cure for this disabling infection-associated chronic condition (IACC). Development of biomarkers to date has been sluggish and uncoordinated, in part due to the lack of resources invested in this effort and in part due to the lack of a central biospecimen collection, distribution, and analytic resource to support the work of laboratories who are developing compelling assays for this condition using novel technologies. Currently, the work of assay development is highly siloed - individual laboratories working with relatively small numbers of samples from participants from individual cohorts with a variable degree of clinical phenotyping are developing individual assays that have not been robustly validated or compared head-to-head with similar assays. The result has been a lack of progress in advancing Long COVID diagnostics, which in turn has limited the development of Long COVID treatments and ultimately a cure.

The UCSF Viral Immunology and Persistence Repeat Donor Cohort (VIPER) program aims to address these challenges by serving as a central, gold-standard resource to support the development of biomarkers for Long COVID. Developed within the UCSF Long-term Impact of Infection with Novel Coronavirus (LIINC) research program (UCSF IRB # 20-30479) - one of the most highly visible and productive Long COVID studies in the world - VIPER will enroll and deeply phenotype individuals with well-defined Long COVID as well as those who have fully recovered from SARS-CoV-2 infection. All participants will undergo a combination of non-invasive (blood, saliva, stool) and invasive (tissue biopsy) sampling using established procedures, with collection of ample amounts of biological specimens to support downstream biomarker development. VIPER specimens will be centrally housed and distributed to collaborating laboratories, who while blinded to the characteristics of the participants will generate measurements that are shared with a central data core for analysis. This will enable the determination of how each assay performs relative to both clinical and laboratory "gold standards" and how each assay performs relative to each other.

Following the identification and validation of these biomarkers, this program will also determine how these tests can be used to assess eligibility and outcomes in LC trials. Ultimately, the goal of VIPER is to promote the development of biomarker tests that can be utilized in the clinic setting to identify those who are likely to benefit from therapeutics targeting each of the mechanisms of Long COVID.

Inclusion Criteria:

• Willing and able to provide written informed consent, and
• Age >/= 18 years, and
• Either:

History of a SARS-CoV-2 infection resulting in Long COVID symptoms, confirmed by the investigator, or

Exposure to SARS-CoV-2 without establishment of Long COVID.

• Enrolled or willing to enroll and complete at least 1 visit in the UCSF Long-term Impact of Infection with Novel Coronavirus (LIINC).
• Enrolled or willing to be referred for a gut biopsy procedure under related IRB-approved protocols.

Exclusion Criteria:

• Self-reported or documented chronic anemia with hemoglobin < 9 g/dL. Anemia during a preceding acute illness will not be exclusionary.
• Serious medical or psychiatric illness that, in the opinion of the site investigator, would interfere with the ability to adhere to study requirements or to give informed consent.
• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.