Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19 A Randomized Clinical Trial. Lenze et al. JAMA (2020)

An SSRI to treat early COVID, supposedly SSRIs can inhibit SARS-CoV-2 and also potentially have anti-inflammatory and immunoregulatory properties. I think also earlier this year there was an observational study showing patients taking SSRIs had lower risk of severe COVID and death (I think a medXriv paper)

Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19A Randomized Clinical Trial. Lenze et al. JAMA (2020)

If you prefer to read a news summary:
Scienmag: JAMA Reports Fluvoxamine As Potential Early Treatment For COVID-19

 

Association between SSRI Antidepressant Use and Reduced Risk of Intubation or Death in Hospitalized Patients with Coronavirus Disease 2019: a Multicenter Retrospective Observational Study. Hoertel et al. medRxiv (2020)

 

The JAMA work was a small but gold standard RCT and it showed efficacy. So similar cohort size to RituxME trial and if that trial showed efficacy would we care if we knew any science behind it?

 

Some scientific background covered here:

The possible immunoregulatory and anti-inflammatory effects of selective serotonin reuptake inhibitors in coronavirus disease patients. Hamed & Hagag. Med Hypotheses (2020)

 

Here was the news report of the JAMA trial from WUSTL (the university that did the trial) back in April. It mentions that they believe some SSRIs can prevent or reduce the cytokine storm.

WUSTL: Study to evaluate antidepressant as potential COVID-19 treatment

 

How does the dosage compare to doses for depressive conditions?

ETA ages ?
Were any side effects observed at particular points in menstrual cycles?
Did any participants gave gut issues ?

Estrogen and seratonin are closely linked, and some gut bacteria can " repackage" compounds including estrogen / influence seratonin levels.

Needs a bit more digging to understand mechanisms

 

Looks like much more of a rationale - or at least no less - than say the rituximab and cyclophosphamide trials for ME.

 

There is no "cytokine storm" to reduce...

 

Aka Luvox,they titrate up to max dose then discontinue
I found Luvox the easiest to tolerate and discontinue from

 

I’m confused, has this been refuted by the scientific community as one of the causes of COVID worsening?

 

Yes. (and from what we knew about SARS-1, it was not a likely hypothesis)

"Is a “cytokine storm” relevant to COVID-19?" June 30, 2020
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2767939
(tl;dr: no)

"Cytokine Levels in Critically Ill Patients With COVID-19 and Other Conditions" September 3, 2020
https://jamanetwork.com/journals/jama/article-abstract/2770484
"The findings of this preliminary analysis suggest COVID-19 may not be characterized by cytokine storm."

"Cytokine elevation in severe and critical COVID-19: a rapid systematic review, meta-analysis, and comparison with other inflammatory syndromes" Octover 16, 2020
https://www.sciencedirect.com/science/article/pii/S2213260020304045

Evidence shows that like SARS-1 and some other coronaviruses, COVID19 is actually associated with an impaired cytokine response (of interferons).
https://www.sciencedirect.com/science/article/pii/S2211124720312237

Lastly, cytokine inhibitors (such as Tocilizumab, a IL-6 inhibitor) have failed to demonstrate efficacy in COVID19

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2772187
https://www.nejm.org/doi/full/10.1056/NEJMoa2028836


Now, all of this is not to say that there are zero cases of cytokine release syndrome associated with COVID19, indeed with over fifty million confirmed SARS-CoV-2 cases, cases of rare syndromes like this will show up. Note that most cytokine release syndrome cases are associated with immunotherapies, such as those that use (engineered) chimeric antigen receptor T-cells as an anti-cancer therapy.

 

This ties in with results from Synairgen, who developed Interferon-1B as a treatment for severe asthma and have done trials on its effect on Covid19.
https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30511-7/fulltext

Sir Stephen Holgate and others at Southapton have developed this.