Patients who meet all of the following inclusion criteria will be eligible to participate in the study: 1. Male or female patients 18 years of age or older. 2. Patients must be eligible to undergo kidney transplantation from a living donor as per institutional standards. 3. For Groups 1 and 2 only: Patients must be CMV immunoglobulin G (IgG) seronegative (-) and receiving kidney for transplantation from donors who are CMV IgG seropositive (+). 4. For Group 3 only: Patients must be CMV immunoglobulin G (IgG) seropositive (+) and receiving kidney for transplantation from donors who are either CMV IgG seronegative (-) or seropositive (+). 5. Patients who would comply with the requirements of this protocol (e.g., return for follow up visits), as judged by the investigator. Patients who meet any of the following criteria will be excluded from the study: 1. Patients planning to undergo multi-organ transplantation. 2. Patients participating in another interventional clinical study. 3. Previous vaccination with an investigational CMV vaccine. 4. Any confirmed or suspected immunodeficiency disorder (based on medical history and physical examination) that could interfere with the immune response or that presents a risk for the patient to receive a vaccine candidate in development. 5. Treatment with any chronic immunosuppressive medication or other immuno modifying drugs within 6 months prior to study entry. However, inhaled and topical steroids and low-dose oral corticosteroids (<10 milligrams a day of prednisone or equivalent) are allowed. 6. Prior history of CMV disease or CMV infection requiring anti-viral therapy 7. Patients with a rash, dermatological condition, or tattoo in the area of the injection site(s) that could interfere with administration site reaction rating. (Note: The injection site(s) can be the non-dominant arm [most preferred injection site], dominant arm, or either thigh [least preferred injection site], as judged by the investigator). 8. It is anticipated that the patient will be unavailable to complete the study follow-up.

• SARS-CoV-2 infection documented by polymerase chain reaction (PCR) or other nucleic acid test (NAT) within 3 days prior to randomization OR documented by NAT more than 3 days prior to randomization AND progressive disease suggestive of ongoing SARS-CoV-2 infection
• Symptomatic COVID-19 disease
• Duration of symptoms attributable to COVID-19 ≤ 12 days
• Requiring inpatient hospital medical care for clinical manifestations of COVID-19 (admission for public health or quarantine only is not included)
• Willingness to abstain from participation in other COVID-19 treatment trials until after study Day 7
• Provision of informed consent by participant or legally authorized representative
• Prior receipt of SARS-CoV-2 hIVIG or convalescent plasma from a person who recovered from COVID-19 at any time
• Prior receipt of standard IVIG (not hyperimmune to SARS-CoV-2) within 45 days
• Current or predicted imminent (within 24 hours) requirement for any of the following: 1. Invasive ventilation 2. Non-invasive ventilation 3. Extracorporeal membrane oxygenation 4. Mechanical circulatory support 5. Continuous vasopressor therapy
• History of allergy to IVIG or plasma products
• History of selective IgA deficiency with documented presence of anti-IgA antibodies
• Any medical conditions for which receipt of the required volume of intravenous fluid may be dangerous to the patient (includes New York Association Class III or IV stage heart failure)
• Any of the following thrombotic or procoagulant disorders: 1. Acute coronary syndromes, cerebrovascular syndromes and pulmonary or deep venous thrombosis within 28 days of randomization 2. History of prothrombin gene mutation 20210, homozygous Factor V Leiden mutations, antithrombin III deficiency, protein C deficiency, protein S deficiency or antiphospholipid syndrome
• Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject or that could prevent, limit, or confound the protocol-specified assessments

• Clinical risk based on age ≥ 55 years or an adult (age ≥ 18 years) with an immunosuppressed condition.
• Positive test for SARS-CoV-2 within ≤5 days (if >1 test, the first positive is within ≤5 days). Tests may include an institutional-based nucleic acid amplification test (NAAT), or any protocol-approved rapid test.
• Within ≤5 days from symptom onset, if symptomatic from current SARS-CoV-2 infection.
• Agrees to not participate in another clinical trial for the treatment or management of SARS-CoV-2 infection through Day 7, or until hospitalized or significant disease progression if prior to Day 7 (defined by ordinal category 4 or 5).
• Participant provides written informed consent prior to study procedures, and understands and agrees to adhere to planned study procedures through Day 28. Ongoing immunosuppressive condition or immunosuppressive treatment, includes: 1. Steroids equivalent to prednisone > 10 mg/day for at least the last 28 days 2. Rheumatologic or autoimmune disorder treated with a biologic or non-biologic immunosuppressive therapy 3. Antirejection medicine after solid organ or stem cell transplantation 4. Cancer treatment with systemic chemotherapy, biologic and/or cell-based therapy in the last 12 months 5. Primary or acquired severe B- or T-lymphocyte immune dysfunction 6. HIV infection 7. Splenectomy or functional asplenia
• Asymptomatic and had prior symptoms from the current infection that have now resolved (for >24 hours).
• Asymptomatic and has received a vaccination for COVID-19 (≥1 dose).
• Undergoing evaluation for possible admission to hospital for medical management (this does not include evaluation of possible hospitalization for public health purposes).
• Evidence of pneumonia and/or hypoxia due to COVID-19 (NOTE: chest imaging is not required, but if available it should not show new infiltrates suggestive of pneumonia; hypoxia is defined by new oxygen supplementation or increase above pre-illness level).
• Prior receipt of immunoglobulin product or passive immune therapy for SARS-CoV-2 in the past 90 days (i.e., convalescent plasma, SARS-CoV-2 monoclonal antibodies, or any IVIG).
• Any of the following thrombotic or procoagulant conditions or disorders: 1. acute coronary syndrome, cerebrovascular syndrome, pulmonary embolism, or deep venous thrombosis within 28 days of randomization. 2. prothrombin gene mutation 20210, homozygous Factor V Leiden mutations, antiphospholipid syndrome, or a deficiency in antithrombin III, protein C, or protein S.
• History of hypersensitivity to blood, plasma or IVIG excipients.
• Known IgA deficiency or anti-IgA antibodies.
• Medical conditions for which receipt of a 300 mL volume of IV fluid from study treatment may pose specific risk to the patient (e.g., decompensated congestive heart failure).
• In the opinion of the investigator, any condition for which participation would not be in the best interest of the participant or that could prevent or confound protocol assessments.

• Hospitalized with COVID-19 pneumonia confirmed per WHO criteria (including a positive PCR of any specimen; e.g., respiratory, blood, urine, stool, other bodily fluid) and evidenced by chest X-ray or CT scan
• Peripheral capillary oxygen saturation (SpO2) ≤93% (on room air or supplemental oxygen) or partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ≤300 millimetres of mercury (mmHg) or requiring supplemental oxygen to maintain SpO2 >93% or requirement for supplemental oxygen to maintain SpO2 at an acceptable level per local standard of care
• Pregnant or breastfeeding, or positive pregnancy test at screening
• Any serious medical condition or abnormality of clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
• In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments
• Participating in another clinical drug trial
• Treatment with investigational therapy (other than for COVID-19) within 5 half-lives or 30 days (whichever is longer) prior to initiation of study drug
• Use of Janus kinase (JAK) inhibitor within 30 days or 5 drug elimination half-lives (whichever is longer) prior to screening
• Have received high-dose systemic corticosteroids (≥1 mg/kg/day methylprednisolone or equivalent) within 72 hours prior to Day 1
• Known HIV infection with CD4 <200 cells/microlitre (uL) or <14% of all lymphocytes
• ALT or AST >10 times the upper limit of normal (ULN) detected at screening
• History of anaplastic large-cell lymphoma or mantle-cell lymphoma
• History of cancer within the previous 5 years unless it has been adequately treated and considered cured or remission-free in the investigator's judgment
• Clinical evidence of active or unstable cardiovascular disease (e.g., acute myocardial ischemia or decompensated heart failure), as determined by investigator assessment, ECG, laboratory assessment, or echocardiographic data
• History of moderate or severe allergic, anaphylactic, or anaphylactoid reactions or hypersensitivity to any component of study treatment

• Signed informed consent.
• Positive test for COVID-19 and progressive disease suggestive of ongoing COVID-19 infection.
• Symptoms of COVID-19 for ≤ 12 days.
• Require admission to hospital for acute medical care (not for purely public health or quarantine purposes).
• Patients who have received plasma from a person who recovered from COVID-19 or who have received neutralizing monoclonal antibodies at any time prior to hospitalization.
• Patients not willing to abstain from participation in other COVID-19 treatment trials until after Day 5 of the study. Co-enrollment in certain trials that compare recommended Standard of Care treatments may be allowed, based on the opinion of the study leadership team.
• Any condition which, in the opinion of the responsible investigator, participation would not be in the best interest of the participant or that could prevent, limit, or confound the protocol-specified assessments.
• Patients considered unable to participate in study procedures.
• Women of child-bearing potential who are not already pregnant at study entry and who are unwilling to acknowledge strong advice to abstain from sexual intercourse with men or practice appropriate contraception through 18 months of the study.
• Women of child-bearing potential who are unwilling to acknowledge the strong advice to abstain from sexual intercourse with men or practice appropriate contraception through 5 weeks of the study (PF-07304814 investigational agent).
• Pregnant women (AZD7442, MP0420 and PF-07304814 investigational agents).
• Nursing mothers (AZD7442, MP0420 and PF-07304814 investigational agents).
• Men who are unwilling to acknowledge the strong advice to abstain from sexual intercourse with women of child-bearing potential or to use barrier contraception through 18 months of the study.
• Men who are unwilling to acknowledge the strong advice to abstain from sexual intercourse with women of child-bearing potential or to use barrier contraception through 5 weeks of the study (PF-07304814 investigational agent).
• Presence at study enrollment of any of the following: 1. stroke 2. meningitis 3. encephalitis 4. myelitis 5. myocardial ischemia 6. myocarditis 7. pericarditis 8. symptomatic congestive heart failure 9. arterial or deep venous thrombosis or pulmonary embolism
• Current or imminent requirement for any of the following: 1. invasive mechanical ventilation 2. ECMO (extracorporeal membrane oxygenation) 3. Mechanical circulatory support 4. vasopressor therapy 5. commencement of renal replacement therapy at this admission (i.e. not patients on chronic renal replacement therapy).
• Participants with moderate to severe hepatic impairment (i.e. Child-Pugh class B or C) or acute liver failure (PF-07304814 investigational agent).
• Participants receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450 (CYP) 3A4 (PF-07304814 investigational agent).
• Patients will be excluded if taking drugs which have a narrow therapeutic window that are substrates of CYP3A4, including but not limited to: astemizole, cisapride, cyclosporine, dihydroergotamine, ergotamine, pimozide, quinidine, sirolimus, tacrolimus, and terfenadine (PF-07304814 investigational agent).
• Patients with a history of deep vein thrombosis or pulmonary thrombotic embolism (Prior to initial futility assessment of PF-07304814 investigational agent).

• ≥ 18 years of age
• Hospitalized for COVID-19
• Enrolled within 72 hours of hospital admittance or 72 hours of positive COVID test
• Expected to require hospitalization for > 72 hours
• Imminent death
• Requirement for chronic mechanical ventilation via tracheostomy prior to hospitalization
• Pregnancy
• Based on a recommendation from the ACTIV4 DSMB on December 19, 2020, enrollment of patients requiring ICU level of care into the therapeutic anti-coagulation arm was stopped due to meeting a futility threshold and a potential for harm for this sub-group could not be excluded. Enrollment continues for moderately ill hospitalized COVID-19 patients.

• Participant meets the standard criteria for liver transplant at the local center.
• Participants being listed for a simultaneous liver kidney (SLK) are eligible if participants meet the standard criteria for both organs.
• Participant is able to understand and provide informed consent.
• Participant meets with an independent advocate per the HIV Organ Policy Equity (HOPE) Act Safeguards and Research Criteria.
• Documented HIV infection (by any licensed assay or documented history of detectable HIV-1 RNA).*
• Participant is ≥ 18 years old.
• Opportunistic complications: prior history of certain opportunistic infections is not an exclusion if the participant has received appropriate therapy and has no evidence of active disease. Medical record documentation should be provided whenever possible.
• CD4+ T-cell count: ≥ 100/µL within 16 weeks prior to transplant if no history of AIDS-defining infection; or ≥ 200 μL if history of opportunistic infection is present.
• HIV-1 RNA is below 50 RNA/mL.* Viral blips between 50-400 copies will be allowed as long as there are not consecutive measurements > 200 copies/mL. *Organ recipients who are unable to tolerate anti-retroviral therapy (ART) due to organ. failure or recently started ART may be eligible despite a detectable viral load if safe and effective ART to be used by the recipient after transplantation is described.
• Participant must have or be willing to start seeing a primary medical care provider with expertise in HIV management.
• Participant is willing to comply with all medications related to participant's transplant and HIV management.
• For participants with a history of aspergillus colonization or disease, no current clinical evidence of active disease.
• Agreement to use contraception.
• Participant is not suffering from significant wasting (e.g. body mass index < 21) thought to be related to HIV disease.
• Participant has a history of progressive multifocal leukoencephalopathy (PML), or primary central nervous system (CNS) lymphoma.*
• Participant is pregnant or breastfeeding. (Note: Participants who become pregnant post-transplant will continue to be followed in the study and will be managed per local site practice. Women that become pregnant should not breastfeed.)
• Past or current medical problems or findings from medical history, physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.

• Age greater than or equal to 1 month and less than or equal to 12 months at the time of randomization; AND
• Positive congenital CMV by urine culture or polymerase chain reaction test(PCR), OR saliva culture or PCR followed by confirmatory urine PCR by 21 days of age, OR urine culture or PCR after 21 days of age followed by newborn dry blood spot PCR; AND
• Confirmed sensorineural hearing loss (SNHL) by auditory brainstem response (ABR) testing. For ABR assessments, hearing loss is defined as levels greater than 25 dB normal hearing levels (NHL) at 1, 2, or 4 kHz in one or both ears.
• Imminent demise; OR
• Known hypersensitivity reaction to valganciclovir, ganciclovir, or any components of the investigational product formulation; OR
• ALT (Alanine Aminotransferase) five times baseline U/L, hepatomegaly, or significant gastrointestinal disorders (e.g., eosinophilic esophagitis, ulcerative colitis); OR
• Absolute neutrophil count (ANC) less than 500 cells/mm^3, Hemoglobin less than 8 g/dL, or platelets less than 50,000/mm^3, splenomegaly, or significant hematologic disorders (e.g., hemophilia, leukemia, sickle cell anemia); OR
• Creatinine clearance less than 60 mL/min/1.73m^2 or significant renal disorders (e.g., nephrotic syndrome); OR
• Receiving other antiviral medications or immune globulin therapy; OR
• Receiving other investigational drugs; OR
• Breast feeding from a mother receiving antiviral or immunosuppressive medication; OR
• Known HIV positive mother (risk of immunosuppression); OR
• Subject is currently using list of prohibited medication specified by the package insert; OR
• Other known cause contributing to SNHL (e.g., meningitis, aminoglycoside ototoxicity); OR
• Bilateral profound SNHL or auditory neuropathy spectrum disorder; OR
• Existing conductive hearing loss or mixed permanent hearing loss is present; OR
• Evidence of intracranial calcification; OR
• Evidence of hydrocephalus; OR
• Microcephaly; OR
• Presence of petechiae; OR
• Intrauterine growth retardation; OR
• Chorioretinitis, optic atrophy or pale optic nerves; OR
• Parent or guardian unable to speak English or Spanish; OR
• Subject exposed to a language other than English or Spanish a majority of the time; OR
• Subject unable to complete hearing assessments or parent/guardian unable to complete communication questionnaires; OR
• < 32 weeks gestational age at birth; OR
• Weight at the time of birth < 1800 g.

Key
• Has SARS-CoV-2-positive antigen or molecular diagnostic test (by validated SARS-CoV-2 antigen, RT-PCR, or other molecular diagnostic assay, using an appropriate sample such as NP, nasal, oropharyngeal [OP], or saliva) ≤72 hours prior to randomization. A historical record of positive result from test conducted ≤72 hours prior to randomization is acceptable
• Meets 1 of the following 2 criteria: 1. Symptomatic Cohort (All Phases): Has symptoms consistent with COVID-19, as determined by the investigator, with onset ≤7 days before randomization or 2. Asymptomatic Cohort (Phase 2): Meets all of the following:
• Has had no symptoms consistent with COVID-19 (as determined by the investigator) occurring at any time <2 months prior to randomization
• Has had no positive SARS-CoV-2 test results from a sample collected >7 days prior to randomization
• Has had no known contact (of any duration) with an individual who has confirmed COVID-19 or confirmed positive SARS-COV-2 test result >14 days prior to randomization.
• Has experienced COVID-19 symptoms for <7 days
• Has symptoms consistent with COVID-19, as determined by investigator, with onset ≤7 days before randomization Key
• Has been admitted to a hospital prior to randomization, or is hospitalized (inpatient) at randomization, due to COVID-19
• Has participated, or is participating, in a clinical research study evaluating COVID-19 convalescent plasma, monoclonal antibodies (mAbs) against SARS-CoV-2, or intravenous immunoglobulin (IVIG) within 3 months or less than 5 half-lives of the investigational product (whichever is longer) prior to the screening visit
• Prior, current, or planned future use of any of the following treatments: COVID-19 convalescent plasma, mAbs against SARS-CoV-2, IVIG (any indication), systemic corticosteroids (any indication), or COVID-19 EUA approved treatments, where prior use is defined as the past 30 days or less than 5 half-lives of the investigational product (which is longer) from screening NOTE: Other Protocol defined Inclusion/Exclusion criteria apply

Key
• Aged < 18 years of age who meet one of the following weight criteria (where permitted according to local law and approved nationally and by relevant institutional review board (IRB) or independent ethics committee (IEC)).
• a) Cohort 1: ≥ 12 years to < 18 years of age and weight at screening ≥ 40 kg
• b) Cohorts 2-4: ≥ 28 days to < 18 years of age and weight at screening ≥ 3 kg and < 40 kg
• c) Cohort 5: ≥ 14 days to < 28 days of age, gestational age > 37 weeks and weight at screening ≥ 2.5 kg
• d) Cohort 6: 0 days to < 14 days of age, gestational age > 37 weeks and birth weight of ≥ 2.5 kg
• e) Cohort 7: 0 days to < 56 days of age, gestational age ≤ 37 weeks and birth weight of ≥ 1.5 kg
• f) Cohort 8: < 12 years of age and weight at screening ≥ 40 kg
• Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR)
• Hospitalized and requiring medical care for coronavirus disease 2019 (COVID-19) Key
• Concurrent treatment with other agents with actual or possible direct antiviral activity against SARS-CoV-2 < 24 hours prior to study drug dosing
• Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 X upper limit of normal (ULN)
• Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m^2 using Schwartz formula for individuals ≥ 1 year of age
• Creatinine above protocol specified thresholds for < 1 year of age
• Positive pregnancy test at Screening only for female of child bearing potential. Note: If female participants who become pregnant during the study or are discovered to be pregnant after receiving at least one dose may continue study drug, after discussion with the investigator
• On renal replacement therapies (intermittent hemodialysis (iHD), peritoneal dialysis (PD), continuous renal replacement therapy (CRRT)) Note: Other protocol defined Inclusion/Exclusion criteria may apply

1. Birth to <18 years of age; AND 2. Positive nucleic acid test for SARS-CoV-2 within the past 7 days; AND 3. Hospitalized, <72 hours post-admission; AND 4. One or more signs and/or symptoms of COVID-19 illness within the past 72 hours, as follows: 1. Cough; OR 2. Fever (oral temperature >100.4°F/38°C); OR 3. Chest pain; OR 4. Shortness of breath; OR 5. Myalgia; OR 6. Acute unexplained loss of smell or taste; OR 7. New/increased supplemental oxygen requirement; OR 8. Acute respiratory failure requiring non-invasive or invasive ventilation; OR 9. Encephalitis. An individual who meets any of the following criteria will be excluded from participation in this study: 1. Receiving therapeutic anticoagulation for treatment of a thromboembolic event diagnosed within the past 12 weeks; OR 2. Clinical-relevant bleeding (see criteria under Primary Outcome, below) within the past 72 hours; OR 3. Platelet count <50,000/µL within the past 24 hours; OR 4. Prothrombin time (PT) ≥2 seconds above the upper limit of age-appropriate local reference range within the past 24 hours; OR 5. Activated partial thromboplastin time (aPTT) ≥4 seconds above the upper limit of age-appropriate local reference range within the past 24 hours; OR 6. Fibrinogen level <75 mg/dL; OR 7. Severe renal impairment, as defined by estimated glomerular filtration rate (eGFR) <31 mL/min/ 1.73 m2, as calculated by the Schwartz formula; OR 8. Parent or legally authorized representative unwilling to provide informed consent for patient participation.

Individuals who meet all of the following criteria are eligible for enrollment as study participants: Both groups (e.g., High-Allergy and Mast Cell Disorder (HA/MCD) Group and Comparison Group): 1. Able to understand and provide informed consent 2. Male or non-pregnant female ≥12 years of age on the date of first study vaccination/placebo administration 3. Females of childbearing potential must have a negative pregnancy test prior to the first vaccination and placebo administration, if applicable. --If a participant becomes pregnant after receiving a placebo dose but prior to receiving study vaccination, she will be discontinued from the study 4. Females of reproductive potential° and sexually active must agree to use FDA approved methods of birth control for the duration of the study. These include hormonal contraceptives, intrauterine device, double barrier contraception (i.e., condom plus diaphragm), or male partner with documented vasectomy.
• Menopause is defined as at least 12 consecutive months without menses; if in question, a follicle stimulating hormone of ≥25 U/mL must be documented.
• Hysterectomy, bilateral oophorectomy, or bilateral tubal ligation must be documented, as applicable; if documented, women with these conditions are not required to use additional contraception. High-Allergy and Mast Cell Disorder (HA/MCD) Group: Individuals who meet at least one of the following criteria are eligible for enrollment in the HA/MCD group: 1. History of a severe allergic reaction to food(s), allergen immunotherapy, insect venom(s), or latex with use of epinephrine within the last 15 years 2. History of an Emergency Department visit with convincing evidence of a systemic allergic reaction (consistent with CoFAR Grade 3 or higher) to food(s), allergen immunotherapy, insect venom(s), or latex within the last 15 years 3. History of documented, immediate allergic reactions to 2 or more unrelated drugs within the last 15 years 4. A convincing clinical history, or a history that is accompanied by a positive skin test, of an immediate reaction to a drug, vaccine, or latex within the last 15 years 5. History of physician-diagnosed idiopathic anaphylaxis requiring epinephrine or an Emergency Department visit in the last 15 years 6. History of a physician-diagnosed mast cell disorder (e.g., mastocytosis, mast cell activation syndrome [MCAS], or hereditary alpha-tryptasemia). MCAS must meet consensus criteria as defined below:
• Criterion A: Typical clinical signs of severe, recurrent (episodic) systemic Mast Cell Activation are present (often in form of anaphylaxis) ---Definition of systemic: involving at least 2 organ systems
• Criterion B: Involvement of Mast Cell (MC) is documented by biochemical studies --- Preferred marker: increase in serum tryptase level from the individual's baseline to plus 20% + 2 ng/ml
• Criterion C: Response of symptoms to therapy with MC-stabilizing agents, drugs directed against MC mediator production or drugs blocking mediator release or effects of MC-derived mediators
• NOTE: All 3 Mast Cell Activation Syndrome (MCAS) criteria (A + B + C) must be fulfilled to call a condition MCAS. Comparison Group: Individuals who meet all of the following criteria are eligible for enrollment in the comparison group: 1. No history of allergic asthma or atopic dermatitis within the last 10 years 2. No history of chronic spontaneous urticaria, or angioedema 3. No history of allergic reactions to foods or insect venoms 4. No history of allergic reactions to drugs or vaccines 5. No history of anaphylaxis 6. No history of a mast cell disorder (e.g., mastocytosis, mast cell activation syndrome [MCAS], or hereditary alpha- tryptasemia) Individuals who meet any of these criteria are not eligible for enrollment as study participants: 1. Inability or unwillingness of a participant and/or parent/legal guardian to give written informed consent and/or assent, as applicable, or to comply with study protocol 2. Weight less than 36 kg (79 lbs) 3. Prior receipt of any doses of the Pfizer-BioNTech coronavirus disease 2019 (COVID-19) Vaccine, Moderna COVID-19 Vaccine, or any other COVID-19 vaccine 4. History of a severe reaction to any component of the Pfizer-BioNTech COVID-19 Vaccine or Moderna COVID-19 Vaccine 5. History of contact dermatitis with confirmed patch test reaction to Prevalence of polyethylene glycol (PEG) 6. History of reaction to Doxil® 7. Known exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and still within the quarantine window 8. Symptoms consistent with acute COVID-19 infection or known COVID-19 infection (positive Polymerase chain reaction [PCR] or antigen test) and still within the quarantine window 9. Have an acute illness, including body temperature greater than 100.4 degrees Fahrenheit, within 14 days of the first study vaccination/placebo administration or 3 days prior to each subsequent vaccination 10. History of autoimmune or other disorders requiring systemic immune modulators 11. History of acute urticaria within 28 days of randomization 12. Pregnant 13. Have received any vaccines within 14 days of the first study vaccination/placebo administration or plan to receive other vaccines during the study period 14. Had any allergen immunotherapy administration within 24 hours prior to vaccination/placebo administration or plan to receive within 24 hours after vaccination/placebo administration 15. Have received a biologic therapy within 6 months of randomization 16. Use of systemic steroids for any reason within 28 days of randomization 17. Use of Zileuton® within 14 days of randomization 18. Use of any monoclonal antibody agent for treatment or prevention of COVID-19 within 3 months of randomization 19. Coronary artery disease, peripheral or cerebral vascular disease, unstable angina, or cardiac arrhythmia, other than supraventricular tachycardia (SVT) 20. Medically unstable hypertension 21. Current use of beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, monoamine oxidase (MAO) inhibitors, tricyclic anti-depressants or other agents that could interfere with the treatment of anaphylaxis, in the opinion of the investigator 22. Unstable asthma within 3 months of randomization or symptomatic asthma on the day of vaccination, as assessed by the site investigator 23. Have past or current medical problems or findings from physical exam or laboratory testing not listed above, which in the opinion of the investigator, may pose additional risks from participation in the study or which may interfere with the ability to comply with study requirements --This includes individuals with underlying conditions or other medications that, in the opinion of the investigator, may increase risk in the event of an anaphylactic reaction or lead to complications following administration of epinephrine

• Biopsy proven (from primary lesion and/or lymph nodes) diagnosis of cancer of the nasopharynx
• Patients must have detectable pretreatment plasma EBV DNA, determined by the central lab prior to Step 2 registration
• Stage II-IVB disease (American Joint Committee on Cancer [AJCC], 7th edition [ed.]) with no evidence of distant metastasis, based upon the following minimum diagnostic workup:
• History/physical examination by a Medical Oncologist or Clinical Oncologist or Radiation Oncologist or Ear, Nose, Throat specialist (ENT), which must include an endoscopic evaluation, a complete list of current medications, and assessment of weight and weight loss in the past 6 months within 21 days prior to registration
• Evaluation of tumor extent with magnetic resonance imaging (MRI) of the nasopharynx and neck within 28 days prior to registration; if MRI is medically contraindicated, obtain computed tomography (CT) scan with =< 3 mm contiguous slices with contrast and bone windows (to evaluate base of skull involvement); Note: If a treatment planning CT scan is used, it must be with =< 3 mm contiguous slices with contrast and be read by a radiologist
• To rule out distant metastasis, patients must undergo the following imaging within 28 days prior to registration:
• A CT scan with contrast of the chest, abdomen, and/or pelvis or a total body positron emission tomography (PET)/CT scan (non-contrast PET/CT is acceptable)
• A bone scan only when there is suspicion of bone metastases (a PET/CT scan can substitute for the bone scan)
• Zubrod performance status 0-1 within 21 days prior to registration
• Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
• Platelets >= 100,000 cells/mm^3
• Hemoglobin >= 8.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 1.5 x institutional ULN
• Alkaline phosphatase =< 1.5 x institutional ULN
• Serum creatinine =< 1.5 mg/dl or calculated creatinine clearance (CC) >= 50 ml/min determined by 24-hour urine collection or estimated by Cockcroft-Gault formula
• Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential
• Women of childbearing potential and male participants who are sexually active must agree to use a medically effective means of birth control throughout protocol treatment
• Patient must provide study specific informed consent prior to study entry, including the mandatory pre-treatment plasma EBV DNA assay
• Prior invasive malignancy (except node negative, non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years) (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
• Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable; however, at least 6-weeks recovery is necessary if the last regimen included nitrosourea or mitomycin
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• Patients with hearing loss assessed to be primarily sensorineural in nature, requiring a hearing aid, or intervention (i.e. interfering in a clinically significant way with activities of daily living); a conductive hearing loss that is tumor-related is allowed
• >= Grade 2 peripheral sensory neuropathy (CTCAE, v. 4.0)
• Severe, active co-morbidity, defined as follows:
• Major medical or psychiatric illness, which in the investigator's opinion would interfere with the completion of therapy and follow up or with full understanding of the risks and potential complications of the therapy
• Unstable angina and/or uncontrolled congestive heart failure within the past 6 months
• Myocardial infarction within the last 6 months
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; note that patients switched from IV antibiotics and currently on oral antibiotics whose infection is assessed to be adequately treated or controlled are eligible
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to registration
• Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol
• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
• Prior allergic reaction to the study drug(s) involved in this protocol
• Patients with undetectable pre-treatment plasma EBV DNA

Inclusion Criteria Patients who have received any type of allogeneic transplant or who have a primary immunodeficiency disorder will be eligible if they have CMV, adenovirus, and/or EBV infection/disease with failure of treatment after 7 days of standard therapy OR if unable to tolerate standard therapy.
• Patients must meet one of the following criteria:
• Recipient of prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant using either bone marrow or peripheral blood stem cell or single or double cord blood within the previous 18 months, OR
• Have a diagnosed primary immunodeficiency disorder (as defined by clinical and laboratory evaluations) and not undergone HSCT.
• Treatment of the following persistent or relapsed infections despite standard therapy:
• CMV: Treatment of persistent or relapsed CMV disease or infection after standard therapy. For CMV infection, standard therapy is defined as antiviral therapy with ganciclovir, foscarnet or cidofovir for at least 14 days.
• Adenovirus: Treatment of persistent or relapsed adenovirus infection or disease despite standard therapy. Standard therapy is defined as antiviral therapy with cidofovir or brincidofovir.
• EBV: Treatment of persistent or relapsed EBV infection despite standard therapy. For EBV infection, standard therapy is defined as rituximab given at 375 mg/m2 in patients for 1-4 doses with a CD20+ tumor. Additional
• Patients with simultaneous infections with CMV, EBV and/or Adenovirus infections are eligible if one or more infection(s) is persistent or relapsed despite standard therapy as defined above. Patients with multiple infections with one or more reactivation and one or more controlled infection are eligible to enroll.
• Clinical status at enrollment that allows tapering of steroids to equal or less than 0.5 mg/kg/day prednisone (or equivalent) prior to infusion of the VST doses.
• Negative pregnancy test in female patients if applicable (childbearing potential who have received a reduced intensity conditioning regimen).
• Written informed consent and/or signed assent line from patient, parent or guardian. Exclusion Criteria
• Patients receiving ATG, Campath, Basiliximab or other immunosuppressive monoclonal antibodies targeting T-cells within 28 days of screening for enrollment.
• Patients who have received donor lymphocyte infusion (DLI) or other experimental cellular therapies within 28 days.
• Current therapy with ruxolitinib or other JAK inhibitors within the previous 3 days.
• Patients with other uncontrolled infections, defined as bacterial or fungal infections with clinical signs of worsening despite standard therapy. For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections, patients must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to enrollment.
• Progressing infection is defined as hemodynamic instability, worsening physical signs, or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
• Patients with active and uncontrolled relapse of malignancy (if applicable).

Sites:
• Serve a cohort of at least 100 HIV patients
• Have an Electronic Health Record (EHR)
• Agree to collaborate on implementing feasible adaptations of intervention strategies Patients:
• Patient of the site with a diagnosis of HIV
• Age 40-79 years
• ≥5% risk for CVD as calculated using the ASCVD Risk Estimator Plus
• Willing to participate
• No plans to leave the site in the next 12 months
• Proficient in either English or Spanish
• Own a cell phone with texting capabilities Clinicians:
• Physicians, Physicians Assistants, or Nurse Practitioners who provide direct HIV care to patients
• Work at a participating site
• Willing to implement the project's intervention strategies Patients:
• Currently participating in another CVD trial
• Have experienced a prior cardiac or vascular event such as myocardial infarction (MI) or cerebrovascular accident (CVA)
• Have had a CVD procedure such as installation of a stent or angioplasty
• Have peripheral vascular disease, intermittent claudication or peripheral arterial disease
• Are pregnant
• Lacks capacity to consent Clinicians: • Planning to leave the site within the next 12 months

1. Diagnosis of COVID-19 by positive RT-PCR requiring hospitalization within 72 hours 2. Age ≥18 years old 3. Able to provide informed consent, or (as allowed by IRB), immediate availability of designated legally authorized representative to provide consent by proxy 4. Anticipated hospitalization for >48 hours 1. Participation in any other clinical trial with antiviral activity against COVID-19 2. Breastfeeding women 3. Known hypersensitivity to atovaquone or formulation excipient 4. Active treatment with rifampin 5. HIV patients with AIDS requiring treatment for Pneumocystis jirovecii or Toxoplasma gondii 6. Not expected to survive for 72 hours. 7) >14 days from symptom onset

• Signed informed consent.
• Documentation of laboratory-confirmed SARS-CoV-2 infection, as determined by a molecular (nucleic acid) or antigen test from any respiratory tract specimen (e.g. oropharyngeal, nasopharyngeal (NP), or nasal swab, or saliva) collected ≤240 hours (10 days) prior to study entry. Laboratory-confirmed SARS-CoV-2 infection outside the US must be conducted at a DAIDS-approved laboratory.
• Able to begin study treatment no later than 7 days from self-reported onset of COVID-19 related symptom(s) or measured fever, where the first day of symptoms is considered symptom day 0 and defined by the self-reported date of first reported sign/symptom from the following list:
• subjective fever or feeling feverish
• cough
• shortness of breath or difficulty breathing at rest or with activity
• sore throat
• body pain or muscle pain/aches
• fatigue
• headache
• chills
• nasal obstruction or congestion
• nasal discharge
• loss of taste or smell
• nausea or vomiting
• diarrhea
• temperature > 38°C (100.4°F)
• One or more of the following signs/symptoms within 24 hours of participating in the study:
• subjective fever or feeling feverish
• cough
• shortness of breath or difficulty breathing at rest or with activity
• sore throat
• body pain or muscle pain/aches
• fatigue
• headache
• chills
• nasal obstruction or congestion
• nasal discharge
• loss of taste or smell
• nausea or vomiting
• diarrhea
• temperature > 38°C (100.4°F)
• Oxygen levels of ≥92% obtained at rest (adjusted as needed for altitude) by study staff within 24 hours of study entry. For a potential participant who regularly receives chronic supplementary oxygen for an underlying lung condition, their oxygen saturation should be measured while on their standard home oxygen supplementation level.
• Participant must agree not to participate in another clinical trial for the treatment of COVID-19 or SARS-CoV-2 during the study period until hospitalization or 28 days after the start of the study, whichever occurs first.
• Meet the protocol definition of being at "higher" risk of progression to hospitalization or death (BRII-196/BRII-198).
• In Phase III, meeting the protocol definition of being at "higher" risk of progression to hospitalization or death (SNG001, SAB-185, BMS 986414+BMS 986413)
• For participants of reproductive potential, negative serum or urine pregnancy test within 48 hours prior to study entry by any clinic or laboratory that has a CLIA certification or its equivalent, or by a point of care (POC)/CLIA-waived test. Note: Participants not of reproductive potential are eligible without requiring the use of a contraceptive method (BRII-196/BRII-198. AZD7442 [IV], AZD7442 [IM], SNG001, Camostat, SAB-185, BMS 986414+BMS 986413).
• Participants that engage in sexual activity that may lead to pregnancy in their partner must agree to either remain abstinent or use male contraceptives. They are strongly advised to inform their non-pregnant sexual partners of reproductive potential to use effective contraceptives for 24 weeks after investigational product is administered. Participants with pregnant partners should use condoms during vaginal intercourse through 24 weeks after investigational agent administration. Participants should refrain from sperm donation for 24 weeks after investigational agent administration (BRII-196/BRII-198, AZD7442 [IV], AZD7442 [IM], SAB-185).
• Participants that engage in sexual activity that may lead to pregnancy in their partner must agree to either remain abstinent or use male contraceptives for 30 days after investigational agent administration. They are also strongly advised to inform their non-pregnant sexual partners of reproductive potential to sue effective contraceptives for 30 days after investigational agent is administered to the participant. Participants with pregnant partners should use condoms during vaginal intercourse through 30 days after last dose of investigational agent administration. Participants should refrain from sperm donation for 30 days after investigational agent administration (SNG001).
• Participants that engage in sexual activity that may lead to pregnancy in their partner must agree to either remain abstinent or use male contraceptives. They are also strongly advised to inform their non-regnant sexual partners of reproductive potential to use effective contraceptives from study entry through 90 days after study treatment. Participants with pregnant partners should use condoms during vaginal intercourse from study entry through 90 days after the last dose of the study treatment. Participants should refrain from sperm donation from study entry through 90 days after the last dose of study treatment (Camostat).
• If participating in sexual activity that could lead to pregnancy, participants who are of reproductive potential must agree to use effective contraception for 24 weeks after investigational agent is administered. This would include oral contraceptives, implanted contraceptives, implanted contraceptives, intrauterine devices, and barrier methods.
• If participating in sexual activity that could lead to pregnancy, participants who are of reproductive potential must agree to use highly effective contraception for 24 weeks after investigational agent is administered (AZD7442 [IV], AZD7442 [IM], SAB-185).
• If participating in sexual activity that could lead to pregnancy, participants who are of reproductive potential must agree to use effective contraception for 30 days after investigational agent is administered (SNG001).
• If participating in sexual activity that could lead to pregnancy, participants who are of reproductive potential must agree to use effective contraception for 90 days after the last dose of treatment (Camostat).
• If participating in sexual activity that could lead to pregnancy, participants who are of reproductive potential must agree to use highly effective contraception for at least 48 weeks after the investigational agent is administered (BMS 986414+BMS 986413).
• History of or current hospitalization for COVID-19.
• For the current SARS-CoV-2 infection, any positive SARS-CoV-2 nucleic acid or antigen tests from any respiratory tract specimen collected > 240 hours prior to study entry.
• Current need for hospitalization or immediate medical attention.
• Use of any prohibited medication listed in the protocol and/or use of systemic or inhaled steroids for the purpose of COVID-19 treatment (new or increased dose from chronic baseline) within 30 days prior to study.
• Receipt of convalescent COVID-19 plasma or other antibody-based anti-SARS-CoV-2 treatment or prophylaxis at any time prior to study entry.
• Receipt of other investigational treatments for SARS-CoV-2 any time before participating in the study (not including drugs approved and taken for other conditions/diseases or COVID-19 vaccines).
• Known allergy/sensitivity or hypersensitivity to study drug or placebo.
• Any condition requiring surgery up to 7 days before participating in the study, or that is considered life threatening up to 30 days before participating in the study.
• Currently pregnant or breastfeeding (BRII-196/BRII-198, AZD7442 [IV], AZD7442 [IM], SNG001, Camostat, SAB-185, BMS 986414+BMS 986413).
• In phase II, meeting the protocol definition of being at "higher" risk of progression to hospitalization or death (AZD7442 [IV], AZD7442 [IM], SNG001, Camostat, SAB-185, BMS 986414+BMS 986413).
• Inflammatory skin conditions that compromise the safety of intramuscular (IM) injections, or other overlying skin conditions or tattoos that would preclude the assessment of injection site reactions, per the discretion of the investigator (AZD7442 [IM]).
• Inflammatory skin conditions that compromise the safety of subcutaneous (SC) injections, or other overlying skin conditions or tattoos that would preclude the assessment of infection site reactions, per the discretion of the investigator (BMS 986414+BMS 986413).
• History of coagulopathy which, in the opinion of the investigator, would preclude IM injection, or use of oral or injectable anticoagulants (protocol provides more information on prohibited medications) (AZD7442 [IM]).
• Use of or need for chronic supplemental oxygen (SNG001).
• Known severe liver disease prior to enrollment (defined as ALT or AST > 5 times upper limit of normal or end stage liver disease with Child-Pugh Class C or Child-Pugh-Turcotte score ≥ 10) (Camostat).
• Known severe kidney disease prior to enrollment (defined as estimated glomerular filtration rate (eGFR) <30 ml/min/1.73m² or on renal-replacement therapy such as peritoneal dialysis or hemodialysis (Camostat) Other investigational drug protocol-defined inclusion/exclusion criteria may apply.

• All "high energy" tibial plateau fractures treated operatively with plate and screw fixation.
• We define "high energy" tibial plateau fractures as patients who are either:
• Initially treated with an external fixation (with or without limited internal fixation) and treated definitively more than 3 days later after swelling has resolved.
• Any open type I, II, or IIIA fracture, regardless of timing of definitive treatment.
• Any tibial plateau fracture associated with ipsilateral leg compartment syndrome fasciotomy wounds.
• All "high energy" pilon (distal tibial plafond) fractures treated operatively with plate and screw fixation. We define "high energy" pilon fractures as patients who are either:
• Initially treated with an external fixation (with or without fibula fixation or limited internal fixation) and treated definitively more than 3 days later after swelling has resolved.
• Any open type I, II, or IIIA fracture, regardless of timing of definitive treatment.
• Any tibial pilon fracture associated with ipsilateral leg compartment syndrome fasciotomy wounds.
• Ages 18 to 80 years
• Patients may have co-existing non-tibial infection, with or without antibiotic treatment.
• Patients may have risk factors for infection including diabetes, immunosuppression from steroids or other medications, HIV, or other infections.
• Patients may have a head injury
• Patients may have a portion of the fixation (e.g. fibula fixation in pilon or percutaneous screws across a tibial plateau fracture) prior to definitive plate fixation, at the initial surgery before randomization.
• Patients may have other orthopedic and non-orthopaedic injuries.
• Patients may have pre-existing musculoskeletal injuries, be non ambulators, or have spinal cord injuries.
• Women and minorities are included
• The study injury: tibial plateau, pilon, is already infected at time of study enrollment.
• Patient speaks neither English nor Spanish.
• Patients who have already had definitive fixation prior to enrollment in the study.
• Severe problems with maintaining follow-up (e.g. patients who are homeless at the time of injury or those how are intellectually challenged without adequate family support).
• Patients with allergies, drug administration reactions, or other sensitivities to Vancomycin (such as a history of Redman's Syndrome).
• Pregnancy.
• The study injury is a type IIIB or IIIC open fracture.

• All participants 12 to <18 years old must have documented positive CMV serostatus (CMV IgG seropositive) for the recipient (R+) within 90 days prior to enrollment. Participants from birth to <12 years old must have documented positive CMV serostatus (CMV IgG seropositive) for the recipient (R+) within 90 days prior to enrollment and/or the donor (D+); the donor serostatus should be documented within 1 year prior to enrollment.
• Is the recipient of a first allogeneic HSCT (bone marrow, peripheral blood stem cell, or cord blood transplant).
• Has undetectable CMV DNA from a plasma or whole blood sample collected within 5 days prior to enrollment.
• Is within 28 days post-HSCT at the time of enrollment.
• Females are not pregnant, not breastfeeding,and is not a woman of childbearing potential (WOCBP); or is a WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 28 days after the last dose of study intervention.
• Participants from 2 to <18 years of age must not be on concomitant Cyclosporin A (CsA), and must be able to take LET tablets or the oral granules (either by mouth or via G tube/NG tube), provided the participant does not have a condition that may interfere with the absorption of oral medication (e.g. vomiting, diarrhea, or a malabsorptive condition) from the day of enrollment until the intensive PK sampling is completed in these participants.
• For participants 2 <12 years old their weight should be at least 10 kg; for participants from birth to <2 years old their weight should be at least 2.5 kg and less than or equal to 15 kg at the time of enrollment.
• Has received a previous allogeneic HSCT (Note: receipt of a previous autologous HSCT is acceptable).
• Has a history of CMV end-organ disease within 6 months prior to enrollment.
• Has evidence of CMV viremia at any time from either signing of the ICF or the HSCT procedure, whichever is earlier, until the time of enrollment.
• Has suspected or known hypersensitivity to active or inactive ingredients of LET formulations.
• Has severe hepatic insufficiency within 5 days prior to enrollment.
• Is a) on renal replacement therapy (eg, hemodialysis, peritoneal dialysis) OR b) has end-stage renal impairment.
• Has both moderate hepatic insufficiency and moderate-to-severe renal insufficiency.
• Has an uncontrolled infection on the day of enrollment.
• Requires mechanical ventilation or is hemodynamically unstable at the time of enrollment.
• Has a documented positive result for a human immunodeficiency virus antibody (HIVAb) test at any time prior to enrollment, or for hepatitis C virus antibody (HCV-Ab) with detectable HCV RNA, or hepatitis B surface antigen (HBsAg) within 90 days prior to enrollment.
• Has active solid tumor malignancies with the exception of localized basal cell or squamous cell skin cancer or the condition under treatment (e.g. lymphomas).
• Has a preexisting cardiac condition a) for which the patient is currently being treated or b) which required hospitalization within the last 6 months or c) that may be expected to recur during the course of the trial.
• Has received within 7 days prior to screening any of the following: ganciclovir; valganciclovir; foscarnet; acyclovir; valacyclovir; famciclovir.
• Has received within 30 days prior to screening of any of the following: cidofovir; CMV immunoglobulin; any investigational CMV antiviral agent/biologic therapy; Rifampin and other strong inducers (such as phenytoin, carbamazepine, St John's wort (Hypericum perforatum), rifabutin and phenobarbital) and moderate inducers such as nafcillin, thioridazine, modafinil and bosentan.
• Has received LET at any time prior to enrollment in this study.
• Is currently participating or has participated in a study with an unapproved investigational compound or device within 28 days, or 5X half-life of the investigational compound (excluding monoclonal antibodies), whichever is longer, of initial dosing in this study.
• Has previously participated in this study or any other study involving LET.
• Has previously participated or is currently participating in any study involving administration of a CMV vaccine or another CMV investigational agent, or is planning to participate in a study of a CMV vaccine or another CMV investigational agent during the course of this study.
• Is pregnant or expecting to conceive, is breastfeeding, or plans to breastfeed from the time of consent through 28 days after the last dose of study intervention.
• Is expecting to donate eggs starting from the time of consent through 28 days after the last dose of study intervention.
• Has clinically relevant drug or alcohol abuse within 12 months of screening that may interfere with participant treatment, assessment, or compliance with the protocol, as assessed by the investigator.

Key Inclusion Criteria (Parts A & B):
• A documented diagnosis of EoE by endoscopic biopsy
• Baseline endoscopic biopsies with a demonstration on central reading of intraepithelial eosinophilic infiltration
• History (by patient report) of an average of at least 2 episodes of dysphagia (with intake of solids) per week in the 4 weeks prior to screening Key Exclusion Criteria (Parts A & B):
• Body weight ≤40 kg
• Prior participation in a dupilumab clinical trial, or past or current treatment with dupilumab
• Initiation or change of a food-elimination diet regimen or re-introduction of a previously eliminated food group in the 6 weeks prior to screening.
• Other causes of esophageal eosinophilia or the following conditions: hypereosinophilic syndrome and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
• Active Helicobacter pylori infection
• History of achalasia, Crohn's disease, ulcerative colitis, celiac disease, and prior esophageal surgery
• Any esophageal stricture unable to be passed with a standard, diagnostic, 9 to10 mm upper endoscope or any critical esophageal stricture that requires dilation at screening
• History of bleeding disorders or esophageal varices
• Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study Key Exclusion Criteria (Part C):
• Participants who, during Part A or Part B, developed a serious adverse event (SAE) and/or adverse event (AE) deemed related to study drug, which in the opinion of the investigator could indicate that continued treatment with study drug may present an unreasonable risk for the participant
• Participants who became pregnant during Part A or Part B
• Participants who are prematurely discontinued from study drug due to an AE (patients who are prematurely discontinued from study drug due to lack of efficacy are eligible to enter Part C)
• Patients who did not undergo endoscopy with biopsies prior to receiving rescue treatment Note: Other inclusion/ exclusion criteria apply

• Patients who have had a high-risk Allogeneic Hematopoietic Transplant within 15 to 42 days of first dose in study
• Either no evidence of viral infection or viremia, or asymptomatic, viral infection with 3 or fewer viruses of interest at time of screening
• At least 1 identified, suitably matched Viralym-M cell line for infusion is available
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
• Contraceptive use by men and women consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Not pregnant or breastfeeding
• Has a history of AdV, BKV, CMV, HHV-6, and/or JCV end-organ disease within 6 months prior to treatment assignment
• Evidence of active Grade >2 graft versus host disease (GVHD)
• Presence of non-minor uncontrolled or progressive bacterial or fungal infections (ie, evidence of bacteremia, fungemia, disseminated)
• Ongoing therapy with high-dose systemic corticosteroids
• Pregnant or lactating or planning to become pregnant
• Weight <30 kg

• Men and non-pregnant women 18-80 years old who were previously hospitalized with confirmed COVID-19
• Were alive at the time of discharge from COVID-19 hospitalization
• Had measured hs-cTnT levels during hospitalization
• Prior cardiovascular disease (before COVID-19 infection), defined as self-reported history or electronic medical record diagnosis of cardiac arrest, myocardial infarction, coronary revascularization, heart failure, or stroke prior to COVID-19 hospitalization
• Urgent-coronary revascularization or type I myocardial infarction within the preceding 30 days
• Cardiac transplantation
• Body weight >250 lbs
• Moderate to severe chronic renal dysfunction defined by an eGFR ≤30 mL/min/1.73 m2
• Inability to safely undergo a CMR
• Unwilling or unable to provide informed consent

• COVID-19 PCR positive (within 7 days)
• COVID-19 PCR pending
• COVID-19 high clinical suspicion
• Patient without Prior Research Authorization (applicable to Mayo Clinic sites)
• Non COVID-19 related admissions
• Repeated Admission to ICUs/Hospital

Key
• Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) positive as determined by Polymerase Chain Reaction (PCR) or other commercially available or public health assay (eg, Nucleic Acid Amplification Test (NAAT) and antigen tests) in any respiratory specimen
• Hospitalized for COVID-19
• Weighing at least 40 kilograms (kg)
• Oxygen (O2) saturation ≤ 94% on room air or requiring O2 supplement or Radiographic evidence of pulmonary infiltrates for COVID-19
• Have either:
• a) Severely reduced kidney function (estimated Glomerular Filtration Rate (eGFR) < 30 mL/min/1.73 m^2), including people with end-stage kidney disease (ESKD) requiring chronic dialysis
• b) Ongoing acute kidney injury (AKI): defined as a 50% increase in serum creatinine (SCr) within a 48-hour period that is sustained (ie, requires confirmatory SCr) for ≥ 6 hours despite supportive care
• The interval between COVID-19 symptoms onset and randomization is no more than 10 days Key
• Received any investigational drug, RDV, or other antiviral treatment for COVID-19
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 times the upper limit of normal
• Invasive mechanical ventilation, noninvasive mechanical ventilation, ECMO, or RRT for acute kidney injury (AKI)
• Positive serum pregnancy test at screening for women of childbearing potential or currently breastfeeding
• Known hypersensitivity to the study drug, metabolites, or formulation sulfobutylether-beta-cyclodextrin (SBECD) Note: Other protocol defined Inclusion/Exclusion criteria may apply

• Enrolled in & completed the baseline evaluation in NCT01263600 OR completed necessary components of NCT01263600 baseline evaluation by the end of the baseline visit.
• 3 to <18 years at time of randomization (day 0).
• Documented chronic HBV infection as evidenced by detection of HBsAg in serum for ≥ 24 weeks prior to baseline OR positive HBsAg and negative anti-HBc IgM within 24 weeks of baseline visit.
• Presence of HBeAg in serum at the last screening visit within 6 weeks of baseline visit.
• Serum HBV DNA level >10^7 IU/mL on at least 2 occasions at least 12 weeks apart during the 52 weeks before baseline visit. The HBV DNA levels must be within 6 weeks of baseline visit.
• ALT ≤60 U/l in males or ≤40 U/l in females, measured on at least 2 occasions, at screening (within 6 weeks prior to baseline visit) & at least 12 weeks prior to the screening visit & within the 52 weeks prior to baseline visit.
• Compensated liver disease, with normal total bilirubin (except if Gilbert's syndrome), direct bilirubin ≤0.5 mg/dL, INR ≤1.5, and serum albumin ≥3.5 g/dL.
• Creatinine clearance 90 ml/min.
• Absence of hepatocellular carcinoma on liver ultrasound in the past 48 weeks. Exclusion criteria:
• Presence of infection with HCV-RNA or anti-HCV, anti-HDV, or HIV at screening.
• Presence of another cause of liver disease or HCC (serum alpha-fetoprotein >50ng /ml).
• Evidence of decompensated liver disease (Childs B-C).
• History or other evidence of a medical condition associated with chronic liver disease (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposures).
• Females who are pregnant or breastfeeding.
• Adolescent females unwilling or unable to use an acceptable method of contraception if sexually active during the treatment period.
• Children currently breastfeeding while their mother is taking lamivudine, or those who were exposed to lamivudine for ≥24 weeks via maternal lamivudine treatment during pregnancy and/or while breastfeeding.
• Previous liver or other organ transplantation including engrafted bone marrow transplant.
• Hematological abnormalities during the screening period that contraindicate full dosing with study drugs, e.g absolute neutrophil count < 1.5 x 10^9 cells/L or platelet count < 120 x 10^9 cells/L.
• Known allergy to study drugs; peginterferon alfa-2a or entecavir.
• Treatment with systemic acyclovir or famciclovir within the previous 6 months.
• Need for ongoing use of any antivirals with activity against HBV during the course of the study or history of receiving treatment for HBV.
• Any use of illegal drugs OR use of alcoholic beverages which in the opinion of a study physician is sufficient to prevent adequate compliance with study procedures or increase the risk of pancreatitis or hepatotoxicity.
• History of immunologically mediated disease (e.g. inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune haemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis).
• History or other evidence of bleeding from esophageal varices or consistent with decompensated liver disease.
• History or other evidence of chronic pulmonary disease associated with functional limitation.
• History of significant cardiovascular diseases.
• History of a severe seizure disorder or current anticonvulsant use.
• History or other evidence of severe retinopathy.
• History of thyroid disease poorly controlled on prescribed medications. Participants with elevated thyroid stimulating hormone concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease are excluded.
• Concomitant use or use during ≤ 6 months prior to the first dose of study drug of anti-neoplastic, immunosuppressive, nephrotoxic or hepatotoxic medication, methadone, theophylline or medications that may affect renal excretion or hepatic metabolism are not permitted.
• Concomitant use of complementary or alternative medications purported to have antiviral activity.
• A participant may not be co-enrolled in another clinical trial where an investigational drug is administered.
• Any other condition or situation that in the opinion of a study physician would make the participant unsuitable for enrollment or could interfere with the participant participating in and completing the study.

Prospective Seraph® 100 1. Subject must be 18 years of age 2. Per the FDA Approve EUA: Subject must have confirmed COVID-19 infection and be admitted to the ICU with confirmed or imminent respiratory failure and any one of the following conditions: 1. Early acute lung injury (ALI)/early acute respiratory distress syndrome (ARDS); or 2. Severe disease, defined as: 1. Dyspnea, 2. Respiratory frequency ≥ 30/min, 3. Blood oxygen saturation ≤ 93%, 4. Partial pressure of arterial oxygen to fraction of inspired oxygen ratio <300, and/or 5. Lung infiltrates > 50% within 24 to 48 hours; or 3. Life-threatening disease, defined as: 1. Respiratory failure, 2. Septic shock, and/or 3. Multiple organ dysfunction or failure. 2. Prospective study patients (or their Legally Authorized Representative (LAR)) provides informed consent. Patients or their legally authorized representative will be consented in their main language if they are not fluent in English. 3. Prospective study patient is willing to complete all study visits as required by the protocol 4. For Military Treatment Facility (MTF) enrollment only
•must be DEERS eligible for care at the MTF Retrospective Seraph® 100 1. Subject must be 18 years of age 2. Per the FDA Approve EUA: Subject must have confirmed COVID-19 infection and be admitted to the ICU with confirmed or imminent respiratory failure and any one of the following conditions: 1. Early acute lung injury (ALI)/early acute respiratory distress syndrome (ARDS); or 2. Severe disease, defined as: 1. Dyspnea, 2. Respiratory frequency ≥ 30/min, 3. Blood oxygen saturation ≤ 93%, 4. Partial pressure of arterial oxygen to fraction of inspired oxygen ratio <300, and/or 5. Lung infiltrates > 50% within 24 to 48 hours; or 3. Life-threatening disease, defined as: 1. Respiratory failure, 2. Septic shock, and/or 3. Multiple organ dysfunction or failure. 3. Treated with Seraph® 100 from 17 April 2020 (date of EUA approval) to the date of study approval at the study site. Historical Control 1. Subject must be 18 years of age 2. Per the FDA Approve EUA: Subject must have confirmed COVID-19 infection and be admitted to the ICU with confirmed or imminent respiratory failure and any one of the following conditions: 1. Early acute lung injury (ALI)/early acute respiratory distress syndrome (ARDS); or 2. Severe disease, defined as: 1. Dyspnea 2. Respiratory frequency ≥ 30/min, 3. Blood oxygen saturation ≤ 93%, 4. Partial pressure of arterial oxygen to fraction of inspired oxygen ratio <300, and/or 5. Lung infiltrates > 50% within 24 to 48 hours; or 3. Life-threatening disease, defined as: 1. Respiratory failure, 2. Septic shock, and/or 3. Multiple organ dysfunction or failure. 3. Hospitalized from 20 January 2020 to the date of study approval at the study site. Prospective 1. Unwilling to provide informed consent 2. Unable to provide informed consent and no LAR available to provide permission Retrospective No specific exclusion criteria. However, patients treated with Seraph® 100 prior to approval of the study at a site and who remains admitted to the hospital at the time the study is approved, will be given the opportunity to participate in the study by signing consent for their health data to be collected (and not biospecimens). Historical Controls: Patients who remain admitted to the hospital at the time that the study is approved at the study site will be excluded.

• Index community members will be: 1. 18 years or older; 2. spend majority of their time in the metropolitan area or county where recruited; 3. have access to a phone for 21-day follow-up call; and 4. primary communication in English or Spanish (based on site chart above) AND at least one of the following: (i) CJI in the previous five years (operationalized as any jail, prison, arrest, parole (completed), probation, drug court during this timeframe); (ii) lower-income Latinx (operationalized as at or below 250% of FPL). Social network referrals will be: 1. linked to the index as a "friend, family, coworker or someone you spend time with on a regular basis"; 2. visit within two weeks of index visit; 3. 18 years or older; 4. spend the majority of their time in the metropolitan area or county where recruited; 5. have access to a phone for 21-day follow-up call; and 6. primary communication in English or Spanish. 1. inability to provide informed consent; and 2. active COVID-19 symptoms per CDC. Participants with COVID-19 symptoms will be referred for free testing at existing partners for each of the study sites. 3. currently on parole

• • Age ≥ 18 years
• PCR-positive COVID-19 infection
• Hospitalized for two or more days
• Pre-existing indication for anticoagulation (e.g., pulmonary embolism or deep vein thrombosis; atrial fibrillation; mechanical cardiac valve)
• Contraindication to antithrombotic therapy (e.g., known bleeding within the last 30 days requiring emergency room presentation or hospitalization; major surgery within 14 days; ischemic stroke, intracranial bleed or neurosurgery within 3 months.
• Platelet count < 50,000/mcL
• Hemoglobin <8 gm/dL
• Renal insufficiency (eGFR < 30 mL/min/1.73 m2)
• Pregnancy
• Prison inmate
• Life expectancy less than 90 days
• Unwilling or unable to provide informed consent/unwilling or unable to complete the study protocol
• Dual antiplatelet therapy that cannot be discontinued
• Concomitant need for strong inducers/inhibitors of p-gp or CYP3A4

• Whole blood specimen collected in EDTA anticoagulant tubes
• Subject is considered to have severe or critical illness per below: Severe Illness 1. SpO2 < 94% on room air at sea level; 2. Ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) < 300 mmHg; 3. Respiratory frequency > 30 breaths/min; 4. Or lung infiltrates >50% Critical Illness a) Respiratory failure; b) Septic shock; c) And/or multiple organ dysfunction d) At least one criteria of severe illness
• Subject confirmed to be COVID-19 positive by an EUA RT-PCR test
• Subject is 18+ years of age
• Minimum volume of 100µL for Symphony IL-6 testing
• Specimen is available for testing within 12 hours from collection
• Subject is receiving an anti-IL-6 treatment
• Subject is receiving corticosteroids
• Hemolyzed specimens

• Subject is willing and able to provide informed consent
• > 18 years of age
• Whole blood specimen collected in EDTA anticoagulant tubes
• Minimum volume of 100µL for Symphony IL-6 testing
• Specimen is available for testing within 12 hours from collection
• C-Reactive Protein (CRP) < 10 mg/L
• Subjects presenting with a fever
• Subjects with a diagnosis of COVID-19 or other respiratory illness at the time of collection
• Subjects otherwise self-reported as unhealthy
• Hemolyzed specimens