Evaluating Modes of Influenza Transmission 2b Baseline SAR

Inclusion criteria

Recipients:

• Enrolled in the Recipient Registry (UMD IRB Protocol # 2303473, eligible age ≥18 and ≤49)
• Provides written informed consent, can comply with the planned study procedures, is available for an up to ~14-day home semi-quarantine period, and can attend scheduled exposure events and scheduled follow-up visits.
• Participants must be able to comprehend the study requirements, as evidenced by a score of 100% on the comprehension assessment (repeated tries permitted).
• No significant change (for the worse) in general health history or in concomitant medication use, as compared from their responses collected during screening (Recipient Protocol).
• Live in a private, single occupancy bedroom and agree to take precautions to avoid contracting a respiratory infection outside of the controlled exposure events through a home semi-quarantine prescribed by investigators.
• Agree not to meet with other participants (Recipients or Donors) outside of the programmed exposure events during their participation in the home semi-quarantine.

Exclusion criteria

Recipients:

• Female of childbearing potential who has a positive urine pregnancy test within 24 hours of enrollment in a Recipient Cohort or is breastfeeding or planning to become pregnant within 2 months after enrollment.
• Presence of infection with influenza, SARS-CoV-2, or other respiratory pathogens detected via a multiplex nucleic acid amplification test (e.g., TaqMan Array Card assay) at entry to the transmission trial.

a. Volunteers with influenza infection may be eligible to enroll as Donors.

• Within the past 72 hours, presence of influenza-like illness, as defined as fever of ≥100.2°F AND cough or sore throat, in the absence of an alternative cause.
• Receipt of any blood products within the past 2 months.
• Does not agree to provide permission for secondary research use of extra samples collected and stored specimens.
• Habitual smoker of tobacco, marijuana, or e-cigarettes per self-report. (Habitual smokers are those who smoke or vape more than four cigarettes, other tobacco products, e-cigarettes or marijuana in a week for more than three months or use an inhaled nicotine or marijuana product more than 3 days a week on average. Edible or patch forms of tobacco or marijuana products do not constitute an exclusion.)
• Self-reported or known history of alcohol or drug abuse in the past two years and/or illicit drug use within the last 30 days. (Prescribed stimulants for the treatment of ADHD and cannabinoids use do not constitute exclusionary criteria)
• Has an ongoing symptomatic condition for which the individual has had or has ongoing medical investigations but has not yet received a diagnosis or treatment plan. (symptomatic condition means for example ongoing chronic fatigue without a diagnosis for symptom.)
• Presence of self-reported or medically documented significant medical or psychiatric condition(s) Significant medical or psychiatric conditions include but are not limited to:

• Respiratory disease (e.g., chronic obstructive pulmonary disease [COPD], asthma, cystic fibrosis) requiring daily medications* currently or any treatment of respiratory disease exacerbations or hospitalizations for acute respiratory illnesses (e.g., asthma exacerbation) in the last 5 years. (* Asthma medications: inhaled, oral, or intravenous (IV) corticosteroids, leukotriene modifiers, long and short acting beta agonists, theophylline, ipratropium, biologics.)
• Significant cardiovascular disease (e.g., congestive heart failure, cardiomyopathy, ischemic heart disease) or history of myocarditis or pericarditis as an adult.
• Neurological or neurodevelopmental conditions (e.g., epilepsy, stroke, seizures, encephalopathy, focal neurologic deficits, Guillain-Barré syndrome, encephalomyelitis or transverse myelitis).
• Ongoing malignancy or recent diagnosis of malignancy, including leukemia; treated, non-melanoma skin cancers are permissible.
• An autoimmune disease.
• An immunodeficiency of any cause.
• A blood disorder (e.g., sickle cell disease)
• Endocrine disorders (e.g., diabetes)
• Liver, kidney, metabolic disorders
• BMI ≥40 kg/m2
• Persistent post-viral syndromes with ongoing cardiovascular, respiratory, or neurologic conditions.
• Any other condition or behavior that in the opinion of the PI would affect the ability to participate in the screening or future transmission studies.
• Presence of immunosuppression or any medications that may be associated with impaired immune responsiveness. Including, but not limited to, corticosteroids exceeding 10 mg/day of prednisone equivalent, immunoglobulin, interferon, immunomodulators, cytotoxic drugs, or systemic corticosteroids or other similar or toxic drugs during the preceding 2-month period. Low dose topical and intranasal steroid preparations used for a discrete period are permitted.
• Known allergy or intolerance to treatments for influenza and other respiratory infections (including but not limited to oseltamivir, baloxavir, acetaminophen/paracetamol).
• History of a previous severe allergic reaction to medicines of any kind with generalized urticaria, angioedema, or anaphylaxis.
• Participating in any other interventional clinical trial that has a scheduled intervention 30 days prior to the start or after the end of the home semi-quarantine.

Inclusion criteria

Donors:

• Provides written informed consent, able to comply with the planned study procedures, available for between 1 and 5 days of multiple hour daily transmission experiments in a controlled environment research facility for the transmission trial and can attend the scheduled follow-up visits.
• Comprehends the study requirements, as evidenced by a score of 100% on the comprehension assessment (repeated tries permitted).
• Males and non-pregnant, non-breastfeeding females1 aged ≥18 and ≤59 years of age, at time of initial consent. Pregnancy and breastfeeding status to be determined by self-report.
• Agrees to the collection of specimens for secondary research.
• Evidence of onset of respiratory infection within the past 48 hours at time of entry into the Donor's initial exposure event, including one or more of the following:

• Onset of influenza-like illness, as defined as fever (measured oral temperature of ≥100.2°F or self-reported fever in the absence of a measured temperature) AND cough or sore throat in the setting of local influenza activity.
• Onset of less specific symptoms with a positive molecular test for influenza virus infection.
• Laboratory-confirmed influenza infection (including rapid antigen test in the setting of known local influenza activity) with significant exposure to a laboratory confirmed influenza case (e.g., a roommate) within the last 4 days in the absence of symptoms.

Exclusion criteria

Donors:

• Female of childbearing potential who is breastfeeding or has positive urine pregnancy test upon enrollment.
• Presence of self-reported or medically documented significant medical or psychiatric condition(s) Significant medical or psychiatric conditions include but are not limited to:

• Respiratory disease (e.g., chronic obstructive pulmonary disease [COPD], asthma, cystic fibrosis) requiring daily medications currently or any treatment of respiratory disease exacerbations or hospitalizations for acute respiratory illnesses (e.g., asthma exacerbation) in the last 5 years. Asthma medications: inhaled, oral, or intravenous (IV) corticosteroids, leukotriene modifiers, long and short acting beta agonists, theophylline, ipratropium, biologics.
• Significant cardiovascular disease (e.g., congestive heart failure, cardiomyopathy, ischemic heart disease) or history of myocarditis or pericarditis as an adult.
• Neurological or neurodevelopmental conditions (e.g., epilepsy, stroke, seizures, encephalopathy, focal neurologic deficits, Guillain-Barré syndrome, encephalomyelitis or transverse myelitis).
• Ongoing malignancy or recent diagnosis of malignancy, including leukemia; treated, non-melanoma skin cancers are permissible.
• An autoimmune disease.
• An immunodeficiency of any cause.
• A blood disorder (e.g., sickle cell disease)
• Endocrine disorders (e.g., diabetes)
• Liver, kidney, metabolic disorders
• BMI ≥40 kg/m2
• Persistent post-viral syndromes with ongoing cardiovascular, respiratory, or neurologic conditions.
• Any other condition or behavior that in the opinion of the PI would affect the ability to participate in the transmission study over the next several days.
• Meets criteria for escalation of care at the time of enrollment visit (will be referred for care).
• Presence of immunosuppression or any medications that may be associated with impaired immune responsiveness Including, but not limited to, corticosteroids exceeding 10 mg/day of prednisone equivalent, immunoglobulin, interferon, immunomodulators, cytotoxic drugs, or systemic corticosteroids or other similar or toxic drugs during the preceding 2-month period. Low dose topical and intranasal steroid preparations used for a discrete period are permitted.
• Ongoing symptomatic condition for which individual has had or has ongoing medical investigations but has not yet received a diagnosis or treatment plan.

e.g., ongoing and debilitating fatigue without a diagnosis for the symptom.

• Self-reported or known history of alcohol or drug abuse within the past two years or illicit drug use within the last 30 days.
• Is a habitual smoker of tobacco, marijuana, or e-cigarettes per self-report. Habitual smokers are those who smoke or vape more than four cigarettes, other tobacco products, e-cigarettes or marijuana in a week for more than three months or use an inhaled nicotine or marijuana product more than 3 days a week on average. Edible or patch forms of tobacco or marijuana products do not constitute an exclusion.
• Known allergy or intolerance to treatments for influenza and other respiratory infections (including but not limited to acetaminophen/paracetamol).
• History of a previous severe allergic reaction to medicines of any kind with generalized urticaria, angioedema, or anaphylaxis.
• Presence of infection with SARS-CoV-2, as detected via a multiplex nucleic acid amplification test (e.g., Cepheid 4-Plex).
• Participating in any other interventional clinical research study that has a scheduled intervention 30 days prior to or after the transmission trial.
• Any condition, to include medical and psychiatric conditions, that in the opinion of the Investigator, might interfere with the safety of the participant or the study objectives.