Understanding severe viral infections in patients without known immune issues

The Natural History of Severe Viral Infections and Characterization of Immune Defects

This study is trying to understand why some healthy people get severe viral infections and how different tests can help figure it out.

Quick facts

• Study type: Observational
• Enrollment: 600 (estimated)
• Ages: 2 Years to 100 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT01011712 on ClinicalTrials.gov

What this trial studies

This observational study aims to investigate patients who experience severe or unusual viral infections despite having no known immunocompromise. Researchers will evaluate various factors that may predispose these individuals to severe disease, focusing on infections caused by herpesviruses, adenoviruses, and other viruses. The study will also assess the effectiveness of different microbiologic tests in understanding these infections. By identifying genetic changes related to immune response, the study seeks to enhance our understanding of viral infections in otherwise healthy individuals.

Who should consider this trial

Good fit: Ideal candidates include children and adults with severe or unusual viral infections, such as herpesvirus encephalitis or CMV colitis.

Not a fit: Patients with well-controlled viral infections or those without severe manifestations may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved understanding and management of severe viral infections in immunocompetent patients.

How similar studies have performed: While there have been case reports on severe viral infections in immunocompetent hosts, this study's comprehensive approach is relatively novel.

Eligibility criteria

* INCLUSION CRITERIA:

(Participants)

Participants must meet all the following inclusion criteria in order to participate in this study:

1. Children or adults (regardless of age) with a definitively diagnosed severe or unusual viral infection, including but not limited to infections caused by herpesviruses (HSV-1, HSV-2, CMV, EBV, VZV, HHV-6, HHV-7, HHV-8), human papillomavirus (e.g., severe recalcitrant warts), adenovirus, calicivirus (e.g. norovirus), polyomavirus (such as JC virus and BK virus), or influenza virus. Viral infections that would be considered opportunistic-like , such as herpesvirus esophagitis, herpesvirus encephalitis, CMV colitis, or progressive multifocal leukoencephalopathy (caused by the JC polyoma virus) will be of particular interest in this protocol.

   OR

   Children or adults with a well-documented prior, severe, persistent, or treatment-refractory viral infection(s), who have clinically recovered from the viral infection.
2. Ongoing care by a referring physician.
3. Willingness to allow storage of blood and tissue samples for future analyses.

(Relatives)

Relatives (2 years or above) may be recruited and enrolled to improve interpretation of genetic results, to expand the phenotype of the suspected or confirmed inborn error of immunity in the proband with severe viral infection, and to understand the co-factors in affected and/or unaffected family members that may influence variable expressivity and penetrance of viral infections in inborn errors of immunity.

1. Males and females will be accepted.
2. Relatives may either be healthy or have features concerning for an inborn error of immunity including, but not limited to, autoimmunity, severe atopy, other forms of immune-dysregulation, or severe or unusual infections. While the enrolled proband must have a current or prior severe or unusual viral infection, family members who are suspected to have an inborn error of immunity do not need to have a history of severe or unusual viral infection in the presence of other features suspicious for inborn errors of immunity.
3. Adult relatives or the guardians of minor relatives must be willing and capable of providing informed consent after review of protocol procedures that are described in the consent form with an appropriate study team member.
4. Participating relatives agree to have blood stored for future studies of the immune system.

EXCLUSION CRITERIA:

Participants meeting any of the following exclusion criteria at baseline will be excluded from study participation:

1. Patients with previously diagnosed conditions associated with acquired or iatrogenic immunodeficiency and/or immunosuppresion (e.g., a history of HIV infection, a positive test for HIV, chemotherapy or high dose glucocorticoids). Patients on immunosuppression and/or immunomodulatory therapy for the treatment of conditions that may be attributable to an underlying inborn error of immunity may be included in the study at the discretion of the PI or their designee.
2. Women who are pregnant.
3. Any condition or major comorbidity that the study investigators believe will compromise the patient's ability to comply with the requirements of the study.

Where this trial is running

Bethesda, Maryland

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

Study contacts

• Principal investigator: Jessica R Durkee-Shock, M.D. — National Institute of Allergy and Infectious Diseases (NIAID)
• Study coordinator: Kayla D Morgan

Conditions EBV; HSV; VZV; HPV; CMV; Genetics; Virus; Defense