Use of a Live Attenuated Vaccine as an Immune-based Preventive Against COVID-19-associated Sepsis
Condition: Sepsis Syndrome
MeSH terms: COVID-19; Sepsis; Toxemia; Systemic Inflammatory Response Syndrome
Study type: Interventional
Phase: Phase 3

Summary: 
      The objective of this randomized clinical trial is to test whether administration of live
      attenuated MMR vaccine (measles mumps rubella; Merck) to eligible adults at highest risk for
      contracting COVID-19 (healthcare workers, first responders), can induce non-specific trained
      innate immune leukocytes that can prevent/dampen pathological inflammation and sepsis
      associated with COVID-19-infection, if exposed.
    

Detailed description: 
      Clinical Design. Eligible healthcare workers (HCW) or first responders in the greater New
      Orleans area (n=60) meeting eligibility criteria will be enrolled into a 12 month study by
      the Louisiana State University Health Sciences Center Clinical & Translational Research
      Center (LSUHSC CTRC) clinical staff affiliated with the Louisiana Clinical and Translational
      Research Science (LA CaTS) Center and blindly randomized to receive the live attenuated
      M-M-R® II vaccine or placebo (sterile saline) via subcutaneous injection in the arm at a
      baseline visit following informed consent. Subjects will be recruited from local hospitals
      and EMS stations throughout the greater New Orleans area by distributing recruitment flyers
      at the local facilities. The flyers will have contact information for HCWs and EMS first
      responders to call for more information or to schedule an appointment. Additionally, subjects
      may be referred to the study by other HCWs or first responders aware of study activities.
      Subject consenting, interviewing, vaccine administration and biospecimen collection will be
      performed by the CTRC staff, under full Personal Protective Equipment (PPE) protection.
      Following informed consent, subjects will be asked to complete the Baseline Demographic &
      History Questionnaire disclosing their demographic information, employment, medication,
      vaccination, and medical history. Specifically, the medical history will place emphasis on
      the presence of diabetes, hypertension, heart disease, and their treatments/medications.
      Subjects will then have their height, weight, body mass index (BMI), vital signs, and pulse
      oximetry measured. Subjects will also have their body composition and fat percentage measured
      using the BOD POD Body Composition Tracking System. Female subjects of childbearing potential
      will be given a urine-based pregnancy test. Approximately 10cc of blood will be collected
      along with a nasopharyngeal swab for baseline laboratory analysees (serology, RNA, flow
      cytometry). When available, a finger prick blood sample will be obtained in addition to the
      other biospecimens for COVID-19 serological analysis. Those subjects that satisfy the
      inclusion and exclusion criteria (Eligibility Criteria) will be blindly randomized to receive
      the live attenuated M-M-R® II vaccine or placebo (sterile saline) via subcutaneous injection.
      Repeat biosampling will occur on days 14, 30, 60, and at 12 months post-vaccination. At each
      follow-up, anthropometric measurements, vital signs measurement, and symptom assessment for
      the presence of symptoms related to COVID-19 infection (fever, headache, myalgia, cough, loss
      of taste or smell, breathing problems), general well-being (i.e., pain, dental concerns,
      sleep patterns, general stress level, fatigue), and any changes in medications, medical
      status, and employment will be collected utilizing the Follow-up Symptom & History
      Questionnaire. Telephone follow-up calls utilizing the Follow-up Symptom Assessment & History
      Questionnaire will be made on a monthly basis between the 60-day follow-up visit and the
      12-month endpoint visit. Should a subject develop symptoms potentially associated with
      COVID-19 infection at any point during the 12-month study period, that subject will be seen
      in the clinic by the Infectious Disease (ID) Co-investigator, and a repeat collection of
      blood and nasopharyngeal biospecimens will be performed for analysis, and the subject will be
      asked to complete the Follow-up Symptom & History Questionnaire and get another body
      composition analysis via BOD POD. Subjects will be asked to report the development of any
      potential COVID-19 infection-related symptoms or positive COVID-19 infection testing outside
      of the study, as well as any symptoms potentially related to MMR vaccination. Should a
      subject become admitted to the hospital related to COVID-19 infection, in-patient information
      will be obtained via the electronic medical record (EMR) when available.

      Primary outcome measures will be peripheral blood monocytic MDSCs (M-MDSC) and/or
      granulocytic MDSCs (G-MDSC) determined by flow cytometry from whole blood samples.
      Specifically, documented increases in the MDSCs per subject from baseline through 30-60 days
      post-vaccination is expected in the MMR group compared to placebo group. Measles antibody are
      also expected to increase in the MMR group and will serve as a control for the MMR
      vaccination. Stationary levels of MDSCs and measles antibodies are expected in the MMR group
      over the 12-month period.

      The investigators will perform the COVID-19 RNA testing at baseline, 14, 30, and 60 days
      post-vaccination, and at any point over the 12-month period that symptoms arise. All patients
      that are COVID-19+ at baseline or become COVID-19+ through the study will be included for
      secondary outcome analyses. The Secondary outcome measures will be COVID-19 antibodies
      (seropositive) as evidence of infection, sepsis/lung inflammation, ICU/ventilator usage,
      in-patient health related co-morbidities and self-reporting mental status (such as general
      fatigue/stress level) over the 12-month period post-vaccination. In-patient information will
      be obtained through the EMR when available. Out-patient information will be obtained via
      self-reporting utilizing the Follow-up Symptom & History Questionnaire.
    

Intervention name(s): MMR vaccine
Intervention type(s): Biological
Intervention description(s): Merck MMR-II vaccine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: MMR vaccine vs placebo
Masking: Single (Participant)
Primary purpose: Prevention
Keywords: MMR vaccine; COVID-19; Sepsis; trained innate immunity; myeloid-derived suppressor cells; inflammation