Weekly Update: November 12th - November 17th

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Welcome to the AccessMedicine COVID-19 channel. This week we have a study examining the risk of disease progression in patients randomized to fluvoxamine versus placebo, information about autoantibodies to Interferon-γ (IFN-γ) in patients with severe COVID-19, and new mask recommendations from the CDC.

Fluvoxamine was associated with a reduced risk of progression of COVID-19 in outpatients with mild disease. This is a double-blind, study of 152 outpatients (72% women, average age 46) randomized to fluvoxamine (100mg TID for 15 days) or placebo within seven days of onset of their symptoms. Patients had to have an oxygen saturation of 92% or greater at the onset of the study, be community dwelling and with a confirmed diagnosis of COVID-19. The outcomes included “shortness of breath or hospitalization for shortness of breath or pneumonia, and oxygen saturation of <92%, or need for supplemental oxygen to maintain an oxygen saturation of 92% or greater.”
Twenty-four percent of enrollees did not complete the trial. Zero of 80 patients in the fluvoxamine group met the criteria for clinical deterioration versus six of 72 in the placebo group; four of the six were hospitalized. The NNT was 11.

As with most studies, there are caveats. First, only 13.5% of the patients screened were included in the study. This does not mean that fluvoxamine was not useful in the group studied, only that the applicability cannot be generalized to “all comers”. Additionally, this was a relatively young population and 72% were women (who tend to have better outcomes as a group than do men). As pointed out by the authors, this data should be treated as preliminary and should prompt a larger study. 

Why fluvoxamine? It targets the σ-1 receptor (S1R) which modulates the immune response. Fluvoxamine has been shown to reduce the inflammatory response in animal models of sepsis.

  • Lenze EJ, Mattar C, Zorumski CF, et al. Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19: A Randomized Clinical Trial. JAMA. Published online November 12, 2020. doi:10.1001/jama.2020.22760

The CDC has updated information about mask use to reflect data that masks protect the wearer. One of the reasons given for not wearing a mask has been that the mask does not protect the wearer. The CDC points out that multiple layers of cloth can reduce inhaled particles by 50%. For those interested, they present a summary of the data of “real world effectiveness” of mask wearing in preventing SARS-CoV-2 transmission. They recommend multi-layer cloth masks without valves The full article can be found here.

Autoantibodies to immune mediators are found in at least some patients sick with COVID-19. Last week we reported on a paper that found anticardiolipin antibodies in patients with COVID-19. This is a report of the presence of autoantibodies that impair type I interferons in 987 patients hospitalized with severe COVID-19, 663 mildly symptomatic or asymptomatic patients with COVID-19 and in 1227 healthy controls. They found IgG autoantibodies against interferon-γ (IFN-γ) in 10.2% of those with COVID-19 pneumonia versus zero percent in those with mild or asymptomatic disease (2.6% of women, 12.5% of men). These antibodies seem to be genetically determined rather than a specific response to SARS-CoV-2. They hypothesize that the absence of functioning IFN-γ causes an immunodeficient state leading to worse COVID-19 outcomes.
According to the authors, this explains at least some of the predominance of severe disease in men. They suggest therapies such as plasmapheresis or autoantibody-resistant recombinant Type I interferons as possible useful therapies in the future. The full paper can be found here.

  • Bastard et al., Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science Oct 2020;6515. eabd4585
    DOI: 10.1126/science.abd4585

 

 

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