Fluoxetine to Reduce Intubation and Death After COVID19 Infection
Condition: COVID-19; Cytokine Storm
MeSH terms: COVID-19; Cytokine Release Syndrome
Intervention: Fluoxetine
Intervention description: Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration
Intervention MeSH terms: Fluoxetine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: All patients who enter the study will be monitored daily for symptoms of COVID-19. Patients may choose to take fluoxetine or to have treatment as usual. Patients may also choose to have blood drawn and stored for a future analysis of cytokines.
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: IL-6; fluoxetine; cytokine storm; NF-KB; COVID-19

Summary:

      This project will test the efficacy of fluoxetine to prevent serious consequences of COVID-19
      infection, especially death. Becoming sick with COVID-19 virus or any other serious
      respiratory condition is not fun. However, the dramatic effects of the COVID-19 pandemic on
      human society stem from its significant mortality, not the number of individuals who become
      sick. This project aims to prevent serious outcomes such as hospitalization, respiratory
      failure and death during the time it takes to develop vaccinations and other strategies to
      prevent COVID-19 infectionPoor outcomes with COVID-19 infection such as hospitalization,
      respiratory failure, organ failure and death are associated with a dysfunctional exaggerated
      immune response, called a cytokine storm, that is triggered by Interleukin-6 expression
      (IL-6) and seems to occur around day 5 to 7 of symptoms. Fluoxetine has extraordinarily
      strong evidence in its action as a blocker of IL-6 and cytokine storms in both animal models
      of infection and in human illness such as rheumatoid arthritis and others. This action of
      fluoxetine is an entirely separate pathway than the serotonergic pathway that allows
      fluoxetine to act as an antidepressant. This pathway has been demonstrated in cell culture,
      in animal models, in human illness and by novel bioinformatics analyses of protein
      transcripts to be relatively unique for fluoxetine and appears to be a novel pathway. This
      project aims to inhibit the increase in IL-6 expression and thereby prevent the cytokine
      storm that causes poor outcomes. Patients who have tested positive or are presumptively
      positive for COVID-19 will be entered into the study and given the option to start the
      medication fluoxetine, which is demonstrated to prevent IL-6 surges in infectious and
      inflammatory conditions. Participants will be monitored daily for COVID-19 symptoms and
      weekly for side effects and tolerance of fluoxetine. A subset of patients will have blood
      drawn weekly and stored to monitor IL-6 and other cytokine levels at a later date.

      This project aims to reduce the serious outcomes of COVID-19 infection by preventing or
      inhibiting the cytokine storm associated with organ failure, respiratory failure and death.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients aged 18 and above, able to give informed consent or with legally authorized
             representative

          -  COVID-19 test positive or presumptive positive awaiting COVID testing or results by
             following criteria: fever, cough and shortness of breath or presumptive positive by
             one of these 3 criteria (fever, cough or shortness of breath) and known exposure to
             COVID-19 positive individual in past 2 weeks

        Overall Study Exclusion Criteria :

          -  Unable to give informed consent and no legal representativ

          -  Prisoner/ institutionalized patient

          -  Under age 18

        Exclusion from Fluoxetine Arm:

          -  Active bleeding requiring blood products

          -  Bipolar disorder not on mood stabilizing medication*

          -  Known allergy or hypersensitivity to fluoxetine

          -  Currently taking the following medications : MAO I, pimozide, thioridine

          -  Currently taking hydroxychloroquine

          -  Pregnant or breastfeeding

          -  For hospitalized patients : QTc greater than 500 ms

          -  *Hospitalized patient may be on hydroxychloroquine if QTc<500 and the primary
             attending approves

        Exclusion from Blood Sample Provision:

          -  Pregnant

          -  Self-report of under 110 pounds