Inclusion Criteria:

Infected Cohort:

Patients will be eligible for inclusion according to the following criteria:

1. Ages newborn-25 years

2. Infected individuals will have suspected, probable, or confirmed SARS-CoV-2
infection as defined by WHO criteria within 24 months of enrollment or have been
born to a mother meeting these criteria during pregnancy (congenitally exposed)

3. Children/young adults with or without history of MIS-C are eligible

4. Children/young adults with or without history of SARS-CoV-2 vaccination are eligible

5. Children/young adults with evidence of past SARS-CoV-2 infection based on serum
antibody profile are eligible (with or without history of acute symptoms)

6. Children/young adults with recurrent SARS-CoV-2 infections and those with
post-vaccination (breakthrough) infections are eligible to participate

7. Participants are eligible without exclusion related to sex, race/ethnicity,
geography, nationality, severity of disease, or underlying health conditions

Children/Young Adults with Suspected SARS-Cov-2 Infection

Children/young adults who meet these clinical criteria:

At least one of these clinical criteria:

- Acute onset of fever and cough OR

- Acute onset of ANY THREE OR MORE of the following signs or symptoms: fever, cough,
general weakness /fatigue, headache, myalgia, sore throat, coryza, dyspnea,
anorexia/nausea/vomiting, diarrhea, altered mental status.

AND at least one of these epidemiological criteria:

1. Residing or working in an area with a high risk of transmission of virus: closed
residential, school or camp settings anytime within the 14 days before symptom
onset; OR

2. Residing or travel to an area with community transmission anytime within the 14 days
before symptom onset; OR

3. Any known household contact or any member of the household working in any health
care setting, including within health facilities or within the community; anytime
within the 14 days before symptom onset.

4. A patient with history of severe acute respiratory illness (SARI):

- SARI: acute respiratory infection with history of fever or measured fever of ≥
38 C°; and cough; with onset within the last 10 days; and requires
hospitalization

5. An asymptomatic person not meeting epidemiologic criteria with a positive SARS-CoV-2
Antigen-RDT.

Children/Young Adults with Probable SARS-Cov-2 Infection

1. A patient who meets clinical criteria above AND is a contact of a probable or
confirmed case or linked to a COVID-19 cluster; OR

2. A suspect case with chest imaging showing findings suggestive of COVID-19 disease;
OR

3. A person with recent onset of anosmia (loss of smell) or ageusia (loss of taste) in
the absence of any other identified cause

Children/Young Adults with Confirmed SARS-Cov-2 Infection

1. A person with a positive Nucleic Acid Amplification Test (NAAT); OR

2. A person with a positive SARS-CoV-2Antigen-RDT AND meeting either the probable case
definition or suspect criteria A OR B; OR

3. An asymptomatic person with a positive SARS-CoV-2 Antigen-RDT who is a contact of a
probable or confirmed case

Children/Young Adults with Asymptomatic SARS-CoV-2 Infection

1. A person without history of acute COVID-19 symptoms who has one or more of the
epidemiological exposures for suspected infection and who also meets criteria b or c
for suspected or probable infection, or who meets any of the criteria for confirmed
infection

2. A person without history of acute COVID-19 symptoms who has positive nucleocapsid
antibody test result in medical history or Tier 1 testing with or without NAAT or
RDT testing or known contact to a probable or confirmed case.

Non-Infected Cohort

A person who meets the following criteria will qualify for enrollment as a non-infected
control subject:

1. Does not meet WHO criteria for a suspected, probable, or confirmed case of
SARS-CoV-2 infection AND

2. Does not have serological evidence of past asymptomatic SARS-CoV-2 infection in
medical history or Tier 1 testing, AND

3. Lives in the same communities or recruited from the same sources as those in the
SARS-CoV-2 infected cohort, AND

4. Either not hospitalized for any reason in prior 3 months, or hospitalized (with or
without ICU stay) within the prior 3 months

5. Uninfected individuals may participate independent of their vaccination status

6. Uninfected individuals who develop SARS-CoV-2 infection during the study period will
be reassigned to the SARS-Cov-2 infected group and will be considered to have been
enrolled prior to SARS-CoV-2 infection.

Children (≤3 years of age) born in and out of the context of maternal SARS-CoV-2
infection during pregnancy.

1. Children ≤3 years of age born to a childbearing parent with history of suspected,
probable, or confirmed SARS-COV-2 infection during pregnancy (according the same
criteria listed for the infected child cohort) will be enrolled in the study from
existing research cohorts at the maternal fetal medicine sites in the RECOVER.
network.

2. Children ≤3 years of age born to a childbearing parent without history of SARS-COV-2
infection during pregnancy (according to the same criteria listed for the
non-infected child cohort) will also be enrolled from the same existing research
cohorts at maternal fetal medicine sites in the RECOVER network.

Children with MIS-C

Children/young adults with SARS-CoV-2 infection who have history of MIS-C meeting the CDC
definition:

1. An individual aged <21 years presenting with fever*, laboratory evidence of
inflammation**, and evidence of clinically severe illness requiring hospitalization,
with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic,
gastrointestinal, dermatologic or neurological); AND

2. No alternative plausible diagnoses; AND

3. Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen
test; or exposure to a suspected or confirmed COVID-19 case within the 4 weeks prior
to the onset of symptoms.

- Fever >38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours
**Including, but not limited to, one or more of the following: an elevated
C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen,
procalcitonin, d-dimer, ferritin, lactic acid dehydrogenase (LDH), or
interleukin 6 (IL-6), elevated neutrophils, reduced lymphocytes and low albumin
Young adults with past history of MIS-C with current ages 22-25 years are
eligible to participate.

Children/Young Adults with Post-Vaccine Myocarditis

1. Age 3-25 years

2. Recipient of mRNA COVID-19 vaccination within last 4 weeks

3. Children or young adults with or without history of SARS-CoV-2 infection are
eligible

4. Children or young adults with or without history of MIS-C are eligible (if any prior
MIS-C-related cardiac abnormalities are known to have resolved pre-vaccination)

5. No other known auto-immune or other immune dysregulation disease

6. Participants are eligible without exclusion related to sex, race/ethnicity,
geography, nationality, severity of disease, or underlying health conditions

7. Clinical evidence of probable or confirmed myocarditis based on the following
criteria:

Children and young adults ages 3-25 years with presence of ≥1 new or worsening of the
following clinical symptoms:

- chest pain, pressure, or discomfort

- dyspnea, shortness of breath, or pain with breathing

- palpitations

- syncope

OR, children aged 3-12 years might instead have ≥2 of the following symptoms:

- irritability

- vomiting

- poor feeding

- tachypnea

- lethargy AND

≥1 new finding of:

- troponin level above upper limit of normal (any type of troponin)

- abnormal electrocardiogram (ECG or EKG) or rhythm monitoring findings consistent
with myocarditis

- abnormal cardiac function or wall motion abnormalities on echocardiogram

- cardiac MRI findings consistent with myocarditis

- histopathologic confirmation of myocarditis (Definite myocarditis)¶ AND

- No other identifiable cause of the symptoms and finding

Entry criteria are adapted from the CDC definition based on the assumptions that COVID-19
vaccines will be available in the future to children <5 years of age.

Primary Caregiver Entry Criteria

1. A primary caregiver is defined as an individual, such as a family member (biological
or nonbiological) or legal guardian, who is responsible for the care of the enrolled
child and resides in the same household as the child. When possible, the primary
caregiver identified at study entry will remain in the same role throughout the
study.

2. The primary caregiver is the caregiver who spends the most time with the child or
young adult, has substantial responsibility for taking care of him/her on a daily
basis, and is most knowledgeable about him/her.

3. If two or more persons share equally in the caregiver responsibilities for the child
or young adult, the person selected by the family to fill out study forms both about
themselves and the child will be considered the primary caregiver.

4. If a biological family member primary caregiver has not reached the legal age of
majority in their jurisdiction, the parent/legal guardian for the minor primary
caregiver will provide consent for participation, with assent provided by the minor
caregiver.

5. A nonbiological primary caregiver or legal guardian serving as primary caregiver
must be above the legal age of majority in their jurisdiction.

6. The primary caregiver cannot be a babysitter or other childcare provider who
receives money to care for the child.

Biological Parent Entry Criteria

- If the primary caregiver is a biological parent of the child or young adult who is
participating in the study, the other biological parent may be enrolled to provide a
home sample of saliva for DNA analysis.

Exclusion Criteria

An individual who meets any of the following criteria will be excluded from participation
in this study:

1. Any child, young adult, caregiver, or other biological parent who in the opinion of
the site investigator may be at increased risk of adverse events during
participation in the study, or who may not be able to complete study procedures due
to co-morbid disease or disability.

2. Any young adult age above the age of majority who lacks capacity to provide consent

3. Nonviable neonates and neonates of uncertain viability as determined by the treating
physician

4. Any child, young, adult, or caregiver with co-morbid illness with expected survival
<2 years

5. Any child who is being given up for adoption or is a ward of the state

6. Any caregiver or other biological parent who is incarcerated, or who lacks capacity
to provide consent

7. Currently enrolled in the study Understanding the Long-term Impact of COVID-19 in
Adults