Inclusion Criteria:

• Adults > 18 years of age regardless of medical condition.
• SARS-CoV-2 nasopharyngeal PCR testing prior to gastrointestinal endoscopy as part of routine clinical care. 
• Undergoing an upper gastrointestinal endoscopic procedure (e.g, EGD, EUS, ERCP, upper enteroscopy), lower endoscopy (colonoscopy, flexible sigmoidoscopy, lower EUS), or ERCP.
• Ability to understand study procedures and to comply with them for the entire length of the study.

Exclusion Criteria:

• Inability or unwillingness of individual or legal guardian/representative to give written informed consent.  

Note: Additional inclusion/exclusion criteria may apply, per protocol.

Eligibility last updated 6/8/22. Questions regarding updates should be directed to the study team contact.

• Male or female adults ages 21 and older at the time of enrollment.
• Received at least one COVID-19 vaccination (Johnson &Johnson, Pfizer, Moderna, Novavax; subjects with any number of prior vaccine doses are eligible) and would like to receive an mRNA booster vaccine.
• No immunosuppression or immunodeficiency.
• Determined by medical history and clinical judgment to be eligible for the study, by being generally healthy, with no autoimmune or immunosuppressive conditions and having stable current medical conditions (subjects with preexisting stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease 12 weeks before receipt of the booster vaccine, will be eligible. A change in dose or therapy within a category (e.g., change from one nonsteroidal anti-inflammatory drug to another) is allowed. A change to a new therapy category (e.g., surgery or addition of a new pharmacological class) is only allowed if it is not caused by worsening disease. A change to a new therapy category caused by worsening disease is considered significant and therefore ineligible for enrollment.
• Patients with diabetes mellitus are eligible for inclusion if they have had a hemoglobin A1c measurement of < 8.0 within the past 6 months prior to enrollment. These hemoglobin A1c measurements are recommended at least twice yearly by the American Diabetes Association (ADA), and the target levels here are representative of the goals of the ADA. These hemoglobin A1c levels will ensure that these participants have good glycemic control. (American Diabetes Association. American Diabetes Association Position Statement: Standards of Medical Care in Diabetes— 2015. Diabetes Care 2015;38(Suppl. 1): S1–S94).
• Able to follow study procedures in the opinion of the investigator.
• Expected to be available for the duration of the study.
• Weighs > 110 lbs.

• Known or suspected immunodeficiency or receiving treatment with immunosuppressive therapy including cytotoxic agents (e.g., for cancer, HIV, or autoimmune disease).
• Subjects on corticosteroids will be excluded if ≥ 20mg of Prednisone (or equivalent drug) has been (or will be) administered daily for 2 weeks or more. Subjects will be eligible if corticosteroid therapy has been discontinued for at least 30 days.
• Serious chronic medical conditions including metastatic malignancy, severe chronic obstructive pulmonary disease requiring supplemental oxygen, end-stage renal disease with or without dialysis, clinically unstable cardiac disease, or any other disorder that, in the investigator’s opinion, precludes the subject from participating in the study. Diabetic patients will be excluded if they do not have a hemoglobin A1c measurement within the past 6 months or if they had a hemoglobin A1c measurement of an A1c  > 8.0.
• Receipt of any blood products, including immunoglobulin, within 6 months of study enrollment.
• Current anticoagulant therapy or a history of bleeding diathesis that would contraindicate intramuscular (IM) injection:
  • Note: antiplatelet drugs such as aspirin and clopidogrel are permitted.
• Receipt of any COVID-19-specific monoclonal antibodies within the past 90 days prior to enrollment.
• Any acute illness within the last 30 days.
• Blood donation within the last 56 days prior to study enrollment and within 56 days following the last study visit.
• Pregnancy, Nursing or trying to conceive at the time of the study or for 28 days following the baseline visit.
• Currently taking antibiotics to treat a serious infection. Preventative use of antibiotics (i.e. oral surgery) is not an exclusion criterion.
• Diagnosis of a cognitive disorder (e.g., Alzheimer’s, Dementia).
• Anemia.
• Any medical condition that would, in the opinion of the investigator, interfere with the evaluation of the study objectives.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 1/25/23. Questions regarding updates should be directed to the study team contact.

• 18 years of age or older at time of consent.
• Identified with one of 3 Post-Covid Syndrome (PASC) phenotypes at Mayo Clinic Rochester:  
  • fatigue-predominant  (N=20);
  • pain-predominant  (N=20); 
  • orthostasis-predominant  (N=20).
• Not pregnant by subject self-report at time of consent.
• Have the ability to provide informed consent.
• Have the ability to complete all aspects of this trial.
• Have access to an iPhone, iPad, or Android device.  
• Have no contraindicating comorbid health condition which would interfere with the proper use of the Muse-S™ system, as determined by the clinical investigators.

• Individuals < 18 years old.
• Used an investigational drug within the past 30 days.
• Anyone that is not on a stable dose of medication for anxiety, depression or sleep.
• Currently (within the past 3 weeks) been practicing mindfulness training on a weekly/regular basis.
• Currently (within 3 weeks) has been enrolled in another clinical or research program which intervenes on the patients’ QOL, or stress.
• An unstable medical or mental health condition as determined by the physician investigator.

Eligibility last updated 2/1/22. Questions regarding updates should be directed to the study team contact.

• Male or female, ≥ 18 years of age.
• Prior positive SARS-CoV-2 testing.
• Persistent symptoms meeting diagnosis of PoCoS.
• Access to electronic platform (email, device, internet).
• English speaking.

• Individual, < 18 years of age.
• Acute COVID infection.
• No prior positive COVID testing.

Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this
study:
1. At the time of randomization, requires supplemental oxygen ≥2 LPM due to hypoxemia.
Hypoxemia can be defined by meeting at least one of the following criteria:
 
•SpO2 <92% on or off supplemental oxygen
  - Respiratory failure necessitating mechanical or non-invasive ventilation (CPAP or Bi-PAP)
  - Written declaration from Investigator that subject is clinically hypoxemic and removal of oxygen supplementation would not be considered clinically appropriate for the purpose of measuring SpO2 while on room air
   Note: Documentation of hypoxemia prior to or during the most recent oxygen supplementation must be available in source.
   Note: Subjects who also require invasive mechanical ventilation (MV) or non-invasive positive pressure ventilation (CPAP or bi-PAP) are eligible, although ventilator support is not mandatory
2. Immunocompromised, as defined by one or more of the following:
  - Received an autologous or allogeneic hematopoietic stem cell transplantation (HSCT) at any time in the past
 
•Received a solid organ transplant at any time in the past
  - Has been or is currently being treated with chemotherapy for hematologic malignancies (e.g., leukemia, myeloma, lymphoma) and/or solid tumor malignancies (e.g., lung, breast, brain cancer) at any time in the past
 
•Has an immunodeficiency due to congenital abnormality (only applicable to subjects age < 18 years old) or pre-term birth (only applicable to subjects age ≤ 2 years old)
3. Has, within 3 days prior to randomization, a confirmed LRTI with a sialic acid dependent respiratory virus (SAD-RV, see definition). This can be confirmed by:
 
•bronchoalveolar lavage (BAL) positive for SAD-RV
 
•lung biopsy positive for SAD-RV
 
•chest imaging with a new or worsening finding of pulmonary infiltrate, bronchiolitis, or pneumonitis temporally associated with an upper respiratory tract sample (e.g., tracheal aspirate, sputum, nasopharyngeal swab (NPS), nasopharyngeal wash) positive for SADRV
   Note: These requirements can be fulfilled by results from samples and/or chest imaging that are collected/performed locally as per standard of care within 3 days prior to randomization.
   Note: For all subjects, after obtaining informed consent but within 3 days prior to randomization, a separate nasopharyngeal swab sample will be collected and sent to thecentral laboratory for confirmation of a SAD-RV. The results from the central lab analysis are not required to initiate the subject on study treatment.
4. If female, subject must meet one of the following conditions:
 
•Not be of childbearing potential, defined as one or more of the following conditions:
     - Premenarchal
     - Postmenopausal for at least 1 year
     - Surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy;
 
•Be of childbearing potential and meet all of the following criteria:
     - Has a negative urine or serum pregnancy test (beta-human chorionic gonadotropin) at screening
     - Agrees to practice an acceptable method of contraception (or meets criteria for waiving contraception) from screening until at least 30 days after last dose of study medication (see Section 8.10.1 for details)
Additional contraception requirements may need to be followed according to local regulations and/or requirements.
5. Non-vasectomized males are required to practice effective birth control methods (see Section 8.10.1) from screening until at least 30 days after last dose of study medication
6. Capable of understanding and complying with procedures as outlined in the protocol as judged by the Investigator and able to sign informed consent form prior to the initiation of any screening or study-specific procedures. Subjects must have the ability to return to the hospital to comply with required procedures if they are discharged during the study.
   Note: For subjects, including minors and patients with medical incapacity or impaired consciousness such that they are not able to give fully informed voluntary consent, the subjects' legal representative (parent, guardian or surrogate) must sign an institutional review board (IRB)/independent ethical committee (IEC)-approved informed consent document prior to the initiation of any screening or study-specific procedures. Minor subjects must also sign an IRB/IEC-approved assent form unless not required per local and institution regulations
 

 Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study:
1. Subjects may not be on hospice care or, in the opinion of the investigator, have a low chance of survival during the first 10 days of treatment
2. Subjects with Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), or Alkaline Phosphatase (ALP) ≥3x ULN and Total Bilirubin (TBILI) ≥2x ULN
Note: Subjects with ALT/AST/ALP ≥ 3x ULN AND TB ≥2x ULN that have been chronically stable (for >1 year on more than one assessments) due to known liver pathology including malignancy (primary or metastasis), chronic medications, transplantation, or chronic infection will not be excluded
3. Female subjects breastfeeding or planning to breastfeed at any time through 30 days after the last dose of study drug
4. Subjects taking any other investigational drug used to treat pulmonary infection.
5. Psychiatric or cognitive illness or recreational drug/alcohol use that, in the opinion of the principal investigator, would affect subject safety and/or compliance
6. Subjects with known hypersensitivity to DAS181 and/or any of its components

7. Subjects with severe sepsis due to either their baseline SAD-RV infection or a concurrent viral, bacterial, or fungal infection and meet at least one of the following criteria:
   - Has evidence of vital organ failure outside of the lung (e.g., liver, kidney)
   - Requires vasopressors to maintain blood pressure

• Adult partipicipants, ≥ 18 years of age.
• Participants from the partnering African-American (AA) churches.

• Individuals less than 18 years of age.

• Member of identified high risk population; i.e., employees of long-term care facilities, first responders, health care workers, and day care providers.

• Known clinically-diagnosed COVID-19 infection.

• Has provided informed consent (signed by study patient or legally acceptable representative).
• Male or female adult ≥ 18 years of age (or country’s legal age of adulthood) at randomization.
• Laboratory-confirmed SARS-CoV-2 infection as determined by a RT-PCR result from any specimen (or other commercial or public health assay) ≤ 72 hours from randomization and no alternative explanation for current clinical condition.
• COVID-19 symptom onset ≤ 7 days.
• Hospitalized for COVID-19 illness for < 72 hours with at least 1 of the following at randomization; patients meeting more than one criterion will be categorized in the most severely affected category:
  • Cohort 1: Maintains O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device;
  • Cohort 2: High-intensity oxygen therapy without mechanical ventilation, where high-intensity is defined as receiving supplemental oxygen delivered by 1 of the following devices:
    • Non-rebreather mask (with an SpO2 ≤ 96% while receiving an oxygen flow rate of at least 10 L/min).
    • High-flow device (e.g., AIRVO™ or Optiflow™) with at least 50% FiO2.
    • Non-invasive ventilator, including continuous positive airway pressure (CPAP), to treat hypoxemia (excluding isolated use for sleep-disordered breathing).
  • Cohort 3: On mechanical ventilation

• Phase 1 only: Patients maintaining O2 saturation > 94% on room air.
• In the opinion of the investigator, unlikely to survive for > 48 hours from screening.
• Receiving extracorporeal membrane oxygenation (ECMO).
• Has new-onset stroke or seizure disorder during hospitalization.
• Initiated on renal replacement therapy due to COVID-19.
• Has circulatory shock requiring vasopressors at randomization.
  • Note: Patients who require vasopressors for sedation-related hypotension or reasons other than circulatory shock may be eligible in this study.
• Patients who have received convalescent plasma or IVIG in the past 5 months or plan to receive during the study period for any indication.
• Participation in a clinical research study, including any double-blind study, evaluating an investigational product within 30 days and less than 5 half-lives of the investigational product prior to the screening visit.
  • Note: The use of remdesivir, hydroxychloroquine, or other treatments (except for COVID- 19 convalescent plasma or IVIG) being used for COVID-19 treatments in the context of the local standard-of-care or an open-label study or compassionate use protocol is permitted.
• Any physical examination findings, history of illness, and/or concomitant medications that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the patient by their participation in the study.
• Known allergy or hypersensitivity to components of study drug.
• Pregnant or breastfeeding women.
• Continued sexual activity in women of childbearing potential (WOCBP)* or sexually active men who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose.
• Highly effective contraceptive measures in women include:
  • Stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening;
  • Intrauterine device (IUD);
  • Intrauterine hormone-releasing system (IUS);
  • Bilateral tubal ligation;
  • Vasectomized partner,† and/or;
  • Sexual abstinence‡,§;
  • Male study participants with WOCBP partners are required to use condoms unless they are vasectomized† or practice sexual abstinence.‡,§.

* WOCBP are defined as women who are fertile following menarche until becoming postmenopausal, unless permanently sterile. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to determine the occurrence of a postmenopausal state. The above definitions are according to Clinical Trial Facilitation Group (CTFG) guidance. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.

† Vasectomized partner or vasectomized study participant must have received medical assessment of the surgical success.

‡ Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drugs. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient.

§ Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method (LAM) are not acceptable methods of contraception. Female condom and male condom should not be used together.

• Mayo Clinic patients with a previously confirmed infection with the novel SARS-CoV-2 virus who have been seen in the PCOC, CARP, Pulmonary for post COVID clinic, Neurology, or approval by MAGPIES research group.
• Aged  5 years and older.
• All racial and ethnic groups are eligible.
• Women with a previously confirmed infection with the novel SARS-CoV-2 virus of childbearing potential and pregnant women will be offered enrollment because there is no risk to an unborn child in this investigation. 

• Lacking the capacity to consent.
• Prisoners and institutionalized individuals.
• Non-English speakers will be enrolled into the study but will not be specifically targeted.

• Mayo Clinic patients with a previously confirmed infection with the novel SARS-CoV-2 virus who have been seen in the PCCOC, CARP, Pulmonary for post COVID clinic, Neurology, or approval by MAGPIES research group.
• Aged 5 years and older.
• All racial and ethnic groups are eligible.

• Lacking the capacity to consent.
• Prisoners and institutionalized individuals.

Eligibility last updated 9/8/21. Questions regarding updates should be directed to the study team contact.

.

• Aged 18 years of age or older.
• Patients who have had a recent episode of COVID-19 and who present to the Post COVID-19 Clinic at Mayo Clinic Rochester.   
• Access to smartphone (iOS or Android operating systems).
• Ability to complete study questionnaires and provide voice samples using a smartphone application.

• Known history of voice disorder either primary or secondary to neuromuscular or other pathology.
• Cognitively impaired patients.
• Prisoners.
• Non-English speakers.
• Currently on another study assessing depression or quality of life.

Eligibility last updated 2/22/23. Questions regarding updates should be directed to the study team contact.

• Adults 18 years of age and older who are capable of providing informed consent or have a proxy capable of giving consent for them. See Section 10.1 for details on the consenting process for subjects with COVID-19.
• Virologic confirmation of SARS-CoV-2 infection via any diagnostic test for SARS-CoV- 2 authorized by US FDA or other national regulatory agency or ministry of health (e.g., qualitative SARS-CoV-2 real time polymerase chain reaction (RT-PCR), nucleic acid amplification (molecular) test, etc.) assessed locally per institution standard of care, prior to randomization.
• Pneumonia diagnosed by chest x-ray or computed tomography (CT) revealing infiltrates consistent with pneumonia. Note that a CT scan may be used if available, but is not required.
• Subject must have an SpO2 ≤ 94% on room air and/or require supplemental oxygen (including high-flow oxygen support or NPPV) to be eligible.
• Subject is hospitalized and has not required invasive mechanical ventilation during this hospitalization.
• Subject has not participated in other clinical trials for COVID-19 using an immunomodulating monoclonal antibody or kinase inhibitor. Subjects on corticosteroids, convalescent plasma, remdesivir or other anti-virals and/or hydroxychloroquine with or without azithromycin are not excluded from the study. Agents that have received emergency use authorization or approval from the FDA or are considered by the study site to be standard of care treatment at the institution for COVID-19 are permitted provided the agent is not an immunomodulating monoclonal antibody or kinase inhibitor. Participation in clinical trials with remdesivir or convalescent plasma is permitted provided the subject meets all other eligibility criteria.
• Females of childbearing potential must have a negative urine or serum pregnancy test at screening/baseline. Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for 5 months following their last dose of study drug. A negative urine pregnancy test or serum beta human chorionic gonadotropin (β-hCG) is required for all women of childbearing potential within 1 week prior to receiving first dose of study drug.

• Subject requires invasive mechanical ventilation or extracorporeal membrane oxygenation (i.e., category 2 on the ordinal scale).
• Confirmed diagnosis of bacterial pneumonia or other active/uncontrolled fungal or viral infections at screening/baseline.
• Known active tuberculosis (TB), history of incompletely treated TB or suspected or known extrapulmonary TB.
• Currently receiving treatment for hepatitis A, hepatitis B, hepatitis C or HIV infection.
• History of pulmonary alveolar proteinosis (PAP).
• Women of childbearing potential who are pregnant or breastfeeding.
• Known hypersensitivity to lenzilumab or any of its components.
• Use of any FDA approved anti-IL-6 (e.g., tocilizumab, sarilumab, sitlukimab), anti-IL-1 (e.g., anakinra, canakinumab) or kinase inhibitor (e.g., baracitinib, ibrutinib, acalabrutinib) therapy to treat COVID-19 within 8 weeks prior to randomization. Use of any neutralizing monoclonal antibodies such as bamlanivimab (LY-CoV555) or REGNCOV2 within 8 weeks prior to randomization. Subjects receiving other FDA-approved immunomodulators to treat underlying autoimmune disorders such as rheumatoid arthritis, psoriasis, ankylosing spondylitis, asthma, COPD, atopic dermatitis, multiple sclerosis, etc., would not be excluded unless there is a potential drug interaction with lenzilumab. Note: Subjects receiving convalescent plasma or corticosteroids are not excluded from the study. Note: Subjects receiving remdesivir or other anti-virals and/or hydroxychloroquine with or without azithromycin are not excluded from the study.
• Use of GM-CSF agents (e.g., sargramostim) within 2 months prior to randomization.
• Expected survival < 48h in the opinion of the investigator or subjects with Do Not Resuscitate or Do Not Intubate orders at baseline.
• Any condition that, in the opinion of the investigator, is likely to interfere with the safety and efficacy of the study treatment or puts the subject at unacceptably high risk from the study.

• Admission to the hospital at any point during illness.
• ≤ 25 years of age (as of October 15, 2020 only patients < 21 years of age are eligible).
• Hospitalization is associated with SARS-CoV-2 with either:
  • SARS-CoV-2 positive test (PCR or antibody) prior to, on admission or during hospitalization; OR
  • Strong clinical suspicion (with confirmed exposure) that complications are due to COVID-19 despite negative SARS-CoV-2 test.
• (as of October 15, 2020) Symptoms or signs of disease thought to be due to COVID-19 or MIS-C OR an asymptomatic patient with BCH coordinating site approval.

• Never tested for SARS-CoV-2.
• Hospitalization is associated with a non-COVID-related acute disorder that may result in significant changes in their immune response (e.g., burns, crush injury, major trauma) (exclusion criteria 3-6 added for patients enrolled October 15th, 2020 onwards).
• Nosocomial SARS-CoV-2 infection.
• Acquired immune compromise at baseline (HIV; on active chemotherapy; active cancer; on immune modulating therapy for rheumatologic, immune, or oncologic disorders or after transplantation to prevent rejection).
• Limitations on life support due to poor prognosis.
• End stage lung disease awaiting transplant or needing chronic mechanical ventilator support.

• Female or male patients with histologically confirmed HER2+ breast cancer who have completed chemotherapy in combination with P+H IV and are currently receiving or will be receiving maintenance P+H IV, PH FDC SC, or trastuzumab SC (regardless of remaining treatment cycles [e.g., only 1 cycle remaining]).
• HER2+ status must have been previously determined and is defined as 3+ by immunohistochemistry (IHC) and/or positive by HER2 amplification by in situ hybridization (ISH) with a ratio of ≥ 2 for the number of HER2 gene copies to the number of chromosome 17 copies.
• Patients are not restricted from restarting therapy at any time, per investigator’s discretion. However, upon re-initiation of chemotherapy patients will be discontinued from this study.
• Signed Informed Consent Form by patient or the patient’s legally-authorized representative.
• Age ≥ 18 years at time of signing Informed Consent Form.
• Ability to comply with the study protocol, in the investigator’s judgment.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Intact skin at planned site of subcutaneous (SC) injections (thigh).
• Baseline and most recent (within 3 months) LVEF ≥ 50% measured by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA).
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating eggs, as defined below:
  • Women must remain abstinent or use non-hormonal contraceptive methods with a failure rate of < 1% per year, or 2 effective non-hormonal contraceptive methods during the study treatment periods and for 7 months after the last dose of study treatment. Women must refrain from donating eggs during this same period;
  • A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a post-menopausal state (post-menopausal defined as ≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements;
  • Examples of non-hormonal contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization (with appropriate post-vasectomy documentation of the absence of sperm in the ejaculate) and copper intrauterine devices (IUDs);
  • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception.
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below:
  • With female partners of childbearing potential or pregnant female partners,men must remain abstinent or use a condom during the study treatment periods and for seven months after the last dose of study treatment to avoid exposing the embryo. Men must refrain from donating sperm during this same period;
  • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of preventing drug exposure.

• Current or prior history of active malignancy (other than current breast cancer) within the last 5 years. Appropriately treated non-melanoma skin cancer; in situ carcinomas, including cervix, colon, or skin; or Stage I uterine cancer within the last 5 years are allowed.
• Investigational treatment within 4 weeks of enrollment.
• Patients with any severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infections should not be enrolled in the trial (in the current situation, this also applies to patients with suspected or confirmed COVID-19 infection).
  • Patients with suspected or confirmed COVID-19 may be re-screened for eligibility following physician-prescribed COVID-19 treatment and/or quarantine and following a negative COVID-19 real-time reverse transcription polymerase chain reaction (rRT-PCR) test.
• Patients who may have had a recent episode of thromboembolism and are still trying to optimize the anticoagulation dose and/or have not normalized their INR.
• Serious cardiac illness or medical conditions including, but not confined to, the following:
  • History of NCI CTCAE v5.0 Grade ≥ 3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) Class ≥ II;
  • High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate ≥ 100/min at rest, significant ventricular arrhythmia [ventricular tachycardia], or higher-grade atrioventricular [AV]-block, such as second-degree AV-block Type 2 [Mobitz II] or third-degree AV-block);
  • Serious cardiac arrhythmia or severe conduction abnormality not controlled by adequate medication;
  • Angina pectoris requiring anti-angina medication;
  • Clinically significant valvular heart disease;
  • Evidence of transmural infarction on electrocardiogram (ECG);
  • Evidence of myocardial infarction within 12 months prior to enrollment;
  • Poorly controlled hypertension (e.g., systolic > 180 mm Hg or diastolic > 100mmHg).
• History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease (e.g., severe left ventricular systolic dysfunction [LVSD], left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome.
• Inadequate bone marrow function, defined by any of:
  • Absolute neutrophil count (ANC) < 1.0 x 10^9/L;
  • Platelet count < 100 x 10^9/L;
  • Hemoglobin < 9 g/dL.
• Impaired liver function, defined by any of:
  • Serum (total) bilirubin > 1.25 x upper limit of normal (ULN). In case of Gilbert’s syndrome: a total bilirubin of 2 x ULN is permitted;
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels as defined below:
  • Patients with early breast cancer: AST and ALT > 1.5 x ULN;
  • Patients with metastatic breast cancer: AST and ALT > 2.5 x ULN;
  • Patients with liver metastases: AST and ALT > 5 x ULN;
  • Albumin < 25g/L.
• Renal function with creatinine clearance < 50 mL/min using the Cockroft-Gault formula.
• Major surgical procedure unrelated to breast cancer within 28 days prior to study entry or anticipation of the need for major surgery during the course of study treatment.
• Current severe, uncontrolled systemic disease that may interfere with planned treatment (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound-healing disorders).
• Pregnant or breastfeeding, or intending to become pregnant during the study or within seven months after the last dose of study treatment.
• Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator’s judgment, precludes the patient’s safe participation in, and completion of, the study.
• Known active liver disease, for example, active viral hepatitis infection (i.e., hepatitis B or hepatitis C), autoimmune hepatic disorders, or sclerosing cholangitis.
• Concurrent, serious, uncontrolled infections, or known infection with human immunodeficiency virus (HIV).
  • Patients with known HIV who have adequate and stable CD4 counts on highly active antiretroviral therapy (HARRT) are allowed.
• Known hypersensitivity to any of the study drugs, excipients, and/or murine proteins or a history of severe allergic or immunological reactions; e.g., difficult to control asthma.
• Previously experienced severe injection related reactions with P + H IV, PH FDC SC and/or trastuzumab SC.
• Current chronic daily treatment with corticosteroids (dose > 10 mg methylprednisolone or equivalent excluding inhaled steroids).

Eligibility last updated 2/17/22. Questions regarding updates should be directed to the study team contact.

Up to 500 patients will be recruited for this study. Patients presenting for drive-through or walk-in tent specimen collection for RT-PCR testing for SARS-CoV-2 at one or more of the following SE or SW Minnesota testing sites would be enrolled:

SWMN

Mankato Eastridge

101 Martin Luther King Jr. Drive

SWMN

New Prague

212 10th Ave NE

SWMN

Fairmont

800 Medical Center Drive

SEMN

Owatonna

2200 26th St NW

SEMN

Austin

510 2nd St NW

SEMN

Albert Lea

1705 SE Broadway Ave

SEMN

Red Wing

1407 West 4th Street

The drive-thru or tent collection sites would be selected based upon testing volumes and percent positive tests in the week preceding study commencement, in order to maximize the number of positive SARS-CoV-2 PCR results.

• Adults ≥ 18 years of age.
• Asymptomatic subjects presenting for SARS-CoV-2 screening as part of their routine pre-procedural testing.

• Individuals < 18 years of age.
• Symptomatic subjects.
• Subjects who are not undergoing routine SARS-CoV-2 PCR screening.

• 18 years or older.
• Patients with post-viral olfactory dysfunction > 4 weeks.
• History of positive COVID-19 PCR.

• Less than 18 years of age.
• Active sinus infection.
• New diagnosis of untreated CRS.
• Prior diagnosis of dementia or Parkinson’s disease.
• Prior head trauma or neurosurgical procedure resulting in olfactory loss.
• Patients who do not speak or read English.
• Patients unable to understand and sign the study consent.

• Admitted to a hospital or awaiting admission in the ED with symptoms suggestive of COVID-19.
• Subject (or legally authorized representative) provides informed consent prior to initiation of any study procedures.
• Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.
• Male or non-pregnant female adults ≥ 18 years of age at time of enrollment.
• Has laboratory-confirmed (within 14 days prior to enrollment) SARS-CoV-2 infection as determined by PCR or other commercial or public health assay in any specimen.
• Ongoing illness of any duration, and at least one of the following:
  • Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.).
  • Blood oxygen saturation (SpO2) ≤ 94% on room air.
  • Requiring supplemental oxygen.
  • Requiring mechanical ventilation or ECMO.
• Women of childbearing potential must agree to either abstinence or use at least one primary form of contraception not including hormonal contraception from the time of screening through Day 60.
• Agrees to not participate in another intervention trial for the treatment of COVID-19 through Day 60.

• ALT or AST > 5 times the upper limit of normal.
• Estimated glomerular filtration rate (eGFR) < 30 mL/min (including patients receiving hemodialysis or hemofiltration).
• Neutropenia (absolute neutrophil count < 1000 cells/μL) (<1.0 x 10^3/μL or < 1.0 GI/L).
• Lymphopenia (absolute lymphocyte count < 200 cells/μL) (< 0.20 x 10^3/μL or < 0.20 GI/L).
• Pregnancy or breast feeding.
• Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours.
• Known Allergy to any study medication.
• Received cytotoxic or biologic treatments (such as anti-interleukin-1 [IL-1], anti-IL-6 [tocilizumab or sarilumab], IL-17, or T-cell or B-cell targeted therapies (e.g., rituximab), tyrosine kinase inhibitors including baricitinib, TNF inhibitors, or interferon within 4 weeks or 5 half-lives prior to screening. Steroid dependency defined as need for prednisone at a dose > 10 mg (or equivalent) for > 1 month within 2 weeks of screening is exclusionary.
  • Note 1: Dexamethasone (at a dose of 6 mg per day for up to 10 days) is permitted for the treatment of COVID-19 in patients who are already mechanically ventilated and in patients who require supplemental oxygen at screening, but who are not mechanically ventilated in accordance with national guidelines.
  • Note 2: Infusion of convalescent plasma is also allowed.
• Based on medical history and concomitant therapies that would suggest infection, have suspected clinical diagnosis of current active tuberculosis (TB) or, if known, latent TB treated for less than 4 weeks with appropriate anti-tuberculosis therapy per local guidelines (by history only, no screening required).
• Based on medical history and concomitant therapies that would suggest infection, suspected serious, active bacterial, fungal, viral (including, but not limited to, active HBV, HCV, or HIV/AIDS).
• Have received any live vaccine (that is, live attenuated) within 3 months before screening, or intend to receive a live vaccine (or live attenuated) during the study.
  • Note: Use of non-live (inactivated) vaccinations is allowed for all participants.
• Severe hepatic impairment (defined as liver cirrhosis Child stage C).
• Current severe heart failure (New York Heart Association [NYHA] III-IV).
• In the Investigator's judgment, the patient has any advanced organ dysfunction that would not make participation appropriate.

• ≥ 18 years of age.
• No additional confounding cardiorespiratory, metabolic, or musculoskeletal conditions.   
• All inclusion criteria will be at the discretion of the principal investigator.

• < 18 years of age.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 1/31/23. Questions regarding updates should be directed to the study team contact.

• Adult patients ≥ 18 years old.
• COVID-19+ and COVID-19- individuals (controls), as determined by qPCR.

• Individuals < 18 years of age.
• Pregnant women.
• Individuals with ambiguous COVID-19 result by qPCR.
• Individuals who have received one, or both doses of the Covid 19 vaccine.
• Individuals who are recieving a monoclonal antibody infusion.

• Participants must be ≥ 18 years of age at the time of signing the informed consent.
• Confirmed positive by PCR or antigen test for SARS-CoV-2 with sample collection ≤ 10 days prior to the day of randomization. PCR is the preferred method; however other tests for SARS-CoV-2 are allowed if authorized for use in the country.
• Covid-19 illness of any duration of symptoms.
• Participant capable of understanding the study and giving informed consent. Participant capable of signing and dating the written ICF. Participant must understand and agree to comply with planned study procedures for the duration of the study. The study visits beyond Day 28 will be optional and require a separate consent.
• Hospitalized for Covid-19 illness for ≤ 5 days with mild to moderate Covid-19 symptoms, including:
  • Mild: Symptoms of Covid-19 including fever, rhinorrhea, mild cough, sore throat, headache, muscle pain, malaise but not requiring supplemental oxygen;
  • Moderate: Lower respiratory symptoms: shortness of breath (SOB) or signs of pneumonia or lung infiltrates based on X-ray or computed tomography (CT) scan < 50% present; and
  • Meets the criteria for:
  • Category 4
    •Hospitalized, not requiring supplemental oxygen
    •requiring ongoing medical care (Covid-19 related or otherwise); OR
  • Category 5
    •Hospitalized, requiring supplemental oxygen; OR
  • Category 6
    •Hospitalized, on non-invasive ventilation or high flow oxygen devices per 8-point ordinal scale.
• Adequate organ function, as defined by:
  • CBC: ANC >1000/mm^3;
  • Platelets > 75,000mm^3;
  • Hgb > 9 gm/100 cc;
  • Calculated creatinine clearance based on ideal body weight per Cockcroft-Gault formula or 24-hour urine ≥ 30 mL/min;
  • Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 5 × upper limit of normal (ULN);
  • D-dimer < 10,000 ng/mL.
• Eligible participants of child-bearing age (male or female) must agree to use at least 1 medically accepted method of contraception (e.g., barrier contraceptives [condom, or diaphragm with a spermicidal gel], hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], or intrauterine devices), or agree to abstinence for 6 weeks. Female participants or the female partners of male participants who become pregnant during the study or within the protocol-specified period after their last CPI-006 administration should immediately inform their treating physicians.

• Signs of acute respiratory distress syndrome (ARDS) or respiratory failure necessitating mechanical ventilation at the time of screening (and randomization) or anticipated impending need for mechanical ventilation.
• History of severe chronic respiratory disease and requirement for long-term oxygen therapy.
• Any uncontrolled active systemic infection or hemodynamic instability requiring admission to an intensive care unit (ICU).
• Patients with malignant tumor receiving treatment, or other serious systemic diseases affecting life expectancy within 29 days of Screening.
• Receipt of cancer chemotherapy or immunomodulatory drugs including (but not limited to) biologics such as anti-CD20, anti-TNF, anti-IL6; alkylating agents (e.g., cyclophosphamide); antimetabolites (e.g., azathioprine); or chronic corticosteroid use equivalent to prednisone > 10 gm/day, during preceding 2 months.
  • Note: Steroids for treatment of Covid-19 is acceptable.
• Patients who are participating in other clinical trials including participants in an extended access program (EAP).
• Active deep vein thrombosis or pulmonary embolism as confirmed by the investigator within last 6 months.
• Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours of admission as confirmed by the investigator.
• Any active uncontrolled co-morbid disease that might interfere with study conduct or interpretation of findings.
• Known to be positive for HIV or positive test for chronic HBV infection (defined as positive hepatitis B surface antigen [HBsAg]) or positive test for hepatitis C antibody.
• Convalescent plasma (CCP) or anti-SARS-CoV-2 monoclonal antibodies administered less than 24 hours prior to randomization. Patient must have recovered from any adverse events related to CCP treatment. Received chloroquine or hydroxychloroquine within last 7 days or during the study.
• Pregnancy or breast feeding.

• Participants must be 18 years or older.
• Participants must understand and cooperate with requirements of the study in the opinion of the investigators and must be able to provide written informed consent.
• Individuals who had no known COVID-19 exposure (for controls) or had PCR or antibody confirmed COVID-19 who present with neurological symptoms in the months after infection and fit one of the following criteria during the acute phase of the infection:
  • ambulatory with no or mild symptoms;
  • hospitalized but on no oxygen; or
  • hospitalized but on oxygen administered via a nasal cannula, mask or non-invasive ventilation; i.e., individuals with WHO Ordinal Scale40 scores 0-5. 
• English or Spanish speaking (based on self-stated primary language).
• Clear of any contraindications for MRI.

• Patients under 18 years of age.
• Medical conditions likely to interfere with the study, including chronic neurologic conditions, restless leg syndrome, structural abnormalities such as subdural hematoma, intracranial neoplasms, end-stage renal disease, severe chronic obstructive pulmonary disease (COPD) needing oxygen, end-stage liver disease, active psychiatric illness, active drug abuse, stroke unrelated to COVID-19 or heart attack 6 months before study enrollment, active cancer, concurrent illnesses or treatments interfering with cognitive function such as dementia or normal pressure hydrocephalus.
• Individuals who had COVID-19 and required mechanical ventilation.
• Pregnant women.
• Inability to undergo MRI scanning, including but not limited to claustrophobia, unable to remain still in an MRI scanner for more than 30 minutes, presence of paramagnetic substances or pacemakers in body, weight over 300 lbs.
• Inability to adhere to study protocol for whatever reason.

Inclusion Criteria: Adults patients (> 18 years old) being seen in colon and rectal surgery clinic for a surgical condition requiring an inpatient operation.

Exclusion Criteria: 

Children (age < 18 years old)

Patients with surgical conditions requiring an outpatient operation

• Male or female, age ≥ 18 years as of April 2020.
• Patient at Mayo Clinic (Arizona, Florida or Minnesota) or Mayo Clinic Health System.
• Has not utilized telehealth services since April 2020 but attended face-to-face appointments only for non-emergent outpatient clinical care.

• Anyone not meeting inclusion criteria.

• Participants < 21 years AND meets one or more of the following criteria:
  • SARS-CoV-2 detection from a respiratory specimen; and/or
  • Meets criteria for MIS-C; and/or
  • Meets criteria for MIS-C, except has involvement of only 1 organ system.
• Cases meeting clinical criteria for MIS-C but without known SARS-CoV-2 exposure, and who are being treated as MIS-C by the treating physician, but with negative SARS-CoV-2 PCR and pending or negative antibody testing, may be enrolled as participants. If subsequent antibody testing is positive, cases will be labelled as confirmed MIS-C.
• If SARS-CoV-2 antibody testing is negative, participants will be labeled at the end of the study as suspected/not confirmed MIS-C.

• Participant and/or parent/guardian who is not able to understand or be willing to provide informed consent and where applicable assent.
  • Note, for this observational cohort study, participation in other COVID-19 studies is not an automatic exclusionary criterion.
  • Nonetheless, blood draw restrictions will be strictly adhered to.

• Age, 18-65 years.
• Diagnosis of BD-I or BD-II, or SCZ-BD by DSM-IV (SCID confirmed). Participants of the Bipolar Biobank (IRB # 08-008794) are patients with existing SCID results and participants enrolling to the MoStGEN protocol (IRB # 20-001658) are required to complete a SCID; thus they will not be required to repeat the SCID assessment. Only patients without a previous SCID will be interviewed to complete it.
• Subjects willing to provide consent to be blood-tested for SARS-CoV-2 IgG/IgM on each of the three visits.

• Inability to understand English.
• Inability or unwillingness to provide informed consent or scoring less than 80% on the comprehension assessment (CA) form.
• Unwilling to consent to providing bio-specimens to be stored in the biobank for an indefinite amount of time and to be used in future research studies of as yet unknown design.
• Actively psychotic (i.e., paranoia, perceptual disturbances, delusional ideas, impaired judgment) or active suicidal behavior (including suicidal ideation or planning).
• Involuntary patients.
• Women with known pregnancy. (Due to the lack of conclusive data regarding the quality of antibody response during pregnancy, we considered it appropriate the exclusion of women with known pregnancy from this study).

• Adults, ≥ 18 years if age.
• Subjects who have respiratory tract specimens positive for the SARS-CoV-2 virus.

• Individuals < 18 years of age.
• Unable to provide consent.

• Pregnant females age 18-45 years and their infants.
• Willing and able to provide written informed consent.
• Pregnant and planning to deliver at Mayo Clinic.

• Positive for HIV, HBV or TB.
• Delivery not planned at Mayo Clinic.