Thread by @rplenge

The immune system is critical in the fight against SARS-CoV-2 infection. But what happens when the immune system turns against the body itself? Read this blog.thread to learn more, including repurposing anti-inflammatory drugs to prevent cytokine storm. plengegen.com/blog/repurposi…

To start, there is a lot that is *not* known about how the immune system responds to SARS-CoV-2, and how the immune system evolves during the course of the disease, COVID-19. We know a little, however, which helps with drug repurposing.

That most infected people are asymptomatic or have mild disease is prima facie evidence that the immune system is sufficient to attack the virus and eradicate it from patients.

In some patients the immune system cannot control the virus – or even worse, the immune system goes berserk and turns against the body itself, leading to systemic inflammation (aka cytokine storm)

thelancet.com/journals/lance…

An over-exuberant immune response may compromise organ function, leading to lung injury [acute respiratory distress syndrome (ARDS)] or damage to the heart (myocardial dysfunction).

nytimes.com/2020/04/01/hea…

A “maladaptive immune response” appears to be a turning point in COVID-19 disease progression, when a patient goes from mild to severe disease, which may require ICU care and mechanical ventilation.

npr.org/sections/healt…

To treat the maladaptive immune response – and prevent progression to severe disease – it may be possible to “repurpose” anti-inflammatory drugs used to treat autoimmune diseases such as lupus or rheumatoid arthritis.

biocentury.com/clinical-vacci…

The idea is to give these anti-inflammatory medicines after the immune system has started to clear the infection, but before the immune system goes berserk, thereby preventing progression to severe COVID-19.

Decreasing the number of COVID-19 patients that require intensive care treatment is a big deal, as ICU beds and ventilators appear to be a limiting factor in caring for patients – hence the importance of “flattening the curve”.

covid19.healthdata.org/united-states-…

There are a lot of ongoing clinical trials where anti-inflammatory drugs are being repurposed to treat the maladaptive immune response in COVID-19 - and the list is growing daily.

https://twitter.com/jbrafel/status/1247058257341972482

Many ongoing trials are small, observational studies. Appropriately powered, randomized control trials (RCT) will be required to definitively demonstrate repurposed drugs are safe and effective – a difficult but essential task in the midst of a crisis.

RCTs are essential!

It is important to distinguish repurposed anti-inflammatory drugs from vaccines and passive immune therapy, both of which must be tailored to coronavirus, but, if successful, may cure or greatly diminish COVID-19.

wsj.com/articles/insid…

It is also important to distinguish repurposed anti-inflammatory drugs from repurposed antiviral drugs such as remdesivir, which if given early in SARS-CoV-2 infection may reduce COVID-19 disease severity.

statnews.com/2020/04/06/gil…

An advantage of repurposed drugs over those tailored to the virus itself is that repurposed drugs are available now - often with sufficient clinical supply to meet demand if RCTs are successful - whereas novel therapies will take at least a year to develop de novo.

A disadvantage of repurposed drugs over those tailored to the virus is that repurposed drugs are very unlikely to cure disease. Either a vaccine and/or herd immunity is required to overcome the coronavirus pandemic. (Sadly, both will take time.)

I want to repeat that there is a lot that is NOT known about the immune response in COVID-19, which limits the ability to repurpose anti-inflammatory drugs. More research is needed (e.g., human genetics).

wired.com/story/why-does…

Finally, repurposed drugs will not minimize the importance of public health measures such as physical distancing, hand washing, and masks. These measures will remain our frontline defense against the virus in the near-term.

To conclude: repurposed anti-inflammatory drugs, available now, may dampen the maladaptive immune response, preventing severe COVID-19 and keeping pts out of the ICU / off ventilators. Appropriately powered RCTs are essential to confirm safety / efficacy. plengegen.com/blog/repurposi…