The Natural History of Severe Viral Infections and Characterization of Immune Defects in Patients Without Known Immunocompromise

Inclusion criteria

• (Participants) Participants must meet all the following inclusion criteria in order to participate in this study:
• 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.
• Ongoing care by a referring physician.
• 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.
• Males and females will be accepted.
• 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.
• 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.
• 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:
• 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.
• Women who are pregnant.
• Any condition or major comorbidity that the study investigators believe will compromise the patient's ability to comply with the requirements of the study.