Overview
Background
Mitochondrial disease is a rare disorder. It can cause poor growth, developmental delays, muscle weakness, and other symptoms. The disease is usually inherited. It can be present at birth or develop later in life. Infection is a major cause of disease and death in people with this disease. Researchers want to learn more about how infection and the declining health of people who have this disease may be related to the COVID-19 pandemic. To do this, researchers will study the DNA of people who become ill with suspected or confirmed coronavirus. Their DNA will be compared to the DNA of their family members.
ObjectiveTo learn more about how genes may play a role in how COVID-19 affects people with mitochondrial disease.
EligibilityPeople age 2 months and older with mitochondrial disease and a suspected or confirmed diagnosis of COVID-19.<TAB>
DesignParticipants will complete a questionnaire about their health history. Their medical records may be reviewed. They will give a blood sample.
If the participant becomes ill, they may have a videoconference with a doctor or nurse at the NIH to perform a physical exam. They may be contacted after their illness to give updates on their health. They may be asked to give extra blood samples or complete extra questionnaires.
Participants genetic data will be put into a database. The data will be labeled with a code and not their name. The data will be shared with other researchers.
Participation lasts about 1 year. This may be extended if the participant is very ill.
Description
Infection is a major cause of morbidity and mortality individuals with mitochondrial disease, frequently triggering metabolic decompensation, multiorgan dysfunction, and neurologic deterioration. In the context of the recent COVID19 pandemic, people with mitochondrial disease are at increased risk for severe disease and poor outcomes if infected. However, the mechanisms for this link between infection and clinical decline are incompletely understood. Given that people with mitochondrial disease are particularly susceptible to infection and may experience delayed recovery, we hypothesize that this is in part due to immune factors that influence host-pathogen interactions. The purpose of this protocol is to collect biological specimens to identify immune signatures that contribute to the phenotype of infection and outcomes in patients with mitochondrial disease who become ill during the COVID19 pandemic. In order to compare these cases with others of similar genetic backgrounds and environmental exposures, we will also collect specimens from family members. We will then examine how these signatures correlate with comprehensive quantifiable clinical measures throughout the course of disease, from presenting symptoms, through acute decompensation, stabilization and convalescence. While this protocol is developed during the COVID-19 pandemic with a focus on a specific infectious pathogen, we hope that this study will extend beyond the pandemic in an effort to more broadly understand acute infectious illness in patients with mitochondrial disease. Additionally, it will serve as a remote adjunct to the NIH MINI Study, a natural history study focused on the immunophenotype of mitochondrial disease that is conducted at the NIH Clinical Center.
Eligibility
- INCLUSION CRITERIA:
In order to be eligible to participate in this study, an individual must meet all of the following criteria:
Group 1
- Participants must be two months of age or older.
- Participants must have a diagnosis of mitochondrial disease based on a determination by a physician with expertise in genetics and/or neurology. Supportive evidence may include genetic testing, muscle biopsy, biochemical testing, neuroimaging or enzyme analysis consistent with mitochondrial disease.
- Participants must have suspected or confirmed COVID-19 as defined by
- New onset of any of the following symptoms after January 2020 without an alternative diagnosis: fever, cough, shortness of breath, fatigue, sore throat, rhinorrhea, musculoskeletal pain, vomiting, diarrhea, anosmia, neurologic decline;
AND report that testing for COVID-19/SARS-COV-2 is clinically indicated based on evaluation by a healthcare provider.
OR
2. Laboratory confirmed positive testing for COVID-19/SARS-Cov-2 performed at a local healthcare setting.
Note: It is well recognized at the time of this protocol that testing for COVID-19/SARS-Cov-2 is not consistently available or efficient throughout the United States, particularly in low healthcare resource settings. In order to avoid bias by limiting recruitment to only those individuals with access to these healthcare resources, inclusion criteria for participants with acute illness have intentionally been kept
broad. Participants in Group 1 who are initially suspected to have COVID-19 but are later found to have an alternative infectious illness will be used for comparison studies. Please also note that there is no minimum weight requirement for Group 1. However, there is a minimum weight requirement for phlebotomy procedures (See Sections 1.2 and 7.3.1). Group 1 participants who do not meet minimum weight requirements may enroll for records and questionnaires only.
Group 2
- Participants must be two months of age or older.
- Participants must weigh greater than 4 kilograms.
- Participants must be genetically related family member of a participant in Group 1 above.
EXCLUSION CRITERIA:
An individual who meets any of the following criteria will be excluded from participation in this study:
Group 1
- Participants who are less than two months of age.
- Participants who do not have mitochondrial disease.
- Study team may decline to enroll a participant for other reasons based on clinical judgement.
Group 2
- Participants who are less than two months of age.
- Participants who are not family members of Group 1.
- Study team may decline to enroll a participant for other reasons based on clinical judgement.