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I’ve been exposed. Is there a treatment that can keep me from getting sick?

Treatments

A: Not currently. But there’s hope in the clinical trial pipeline.

For many viral diseases, treatment with a prescribed “post-exposure prophylaxis” (PEP) can block an exposure from developing into a full-blown infection. Tamiflu is perhaps the best-known example. TL;DR about PEP prospects for COVID-19:

✔️ Several older drugs repurposed for COVID-19 PEP have failed in clinical trials (Here’s looking at you, HCQ)*

✔️Newer treatments in the clinical trial pipeline offer hope

✔️But PEP treatments are often tricky to administer in “real world” settings

✔️So, avoiding exposure to the virus remains the best protection we’ve got. #StaySMART

Boston-based infectious disease physician, former hospital epidemiologist, and clinical researcher Dr. Westyn Branch-Elliman has kindly answered a few background questions about PEP for our Dear Pandemic community. Warmest thanks to her! (And for our fellow hardcore Nerds, please note that she’s provided an a-mazing reading list in the references section!)

Q: How does PEP work?

A: PEP is when we give medications after someone has already been exposed to an infectious agent. It is a “last line of defense,” but a strategy that can be effective in many clinical settings, especially for viruses. Here’s how it works: To prevent infection, it is important to “get ahead” of the virus, before the infection overwhelms our bodies and medications are less able to impact the clinical course. PEP helps us do that.

Q: What can we learn from PEP successes with other viruses?

A: There is a long history of PEP for different viral infections, including prevention of HIV and influenza (we also have strategies for prevention of other viruses like chickenpox and hepatitis B, but it is done a little differently). We don’t have PEP for SARS-COV-2 yet.

For other types of viruses, PEP – when administered early (within 1-2 days after exposure) – reduces the risk of infection by about 70-90 percent. That’s a lot (and the kind of intervention that could really help control the pandemic)! Another benefit is that people who receive medication for influenza (oseltamivir or inhaled zanamivir) are probably less infectious – and less likely to spread the infection- than people who do not receive medications. Reducing infectiousness is also an important tool for reducing spread, and would help us to bring the pandemic under control.

Q: What are the main limitations of PEP?

A: The bad news is that for most infections, PEP really only works well when administered soon after the exposure, so in order for this strategy to really work, we would need better access to high-quality testing with a rapid turnaround time. Without that, we will probably be too far behind the 8-ball for a PEP strategy to be effective.

Q: Are there any antivirals that can be used to treat SARS-CoV-2?

A: The antiviral used to treat SARS-CoV-2 is called remdesivir, and the early clinical trial was in patients who required hospitalization. The clinical trial testing this intravenous antiviral medication found that it had its strongest effect in patients who were sick enough to require hospitalization and needed oxygen support, but not sick enough to require intensive care. We think this is because the antiviral might work better earlier in the disease when than later in the course, when the disease is driven more by inflammation caused by your body’s immune response than a direct viral effect. Because the medication seems to work best when given early, there is reason to hope it might work as PEP, but we don’t know yet.

Q: What options are coming down the pipeline?

A: Currently, most SARS CoV-2 treatments are administered intravenously, which makes them hard to provide to people who are not in the hospital and is a big challenge for implementing a post-exposure prophylaxis strategy. But, we have reason to be hopeful! Gilead is testing the safety and efficacy of its antiviral medication, remdesivir, for outpatients with early and mild disease. Currently, remdesivir is only available via infusion, but the company is working on an inhaled formulation that would be much easier to administer to non-hospitalized patients.

[Editorial comment: Please see reference section for today’s news re: disappointing results from a WHO trial including remdesivir. We’ll keep the community posted as more info emerges.]

Another promising option—fluvoxamine, which is a pill– comes from a totally different class of medications (it is actually usually used to treat anxiety, but also might reduce inflammation in the lungs caused by SARS-CoV-2). Recently released clinical trial data suggests that it might work for outpatients with confirmed infections so using it for post-exposure prophylaxis might work too (but we don’t know yet – we need more studies!).

Q: What’s the take-away message for the Dear Pandemic community?

A: We haven’t gotten there yet, but we have lots of reasons to be hopeful that

EP will be an option in the not-too-distant future. If it is, we may be able to help slow the spread of SARS-CoV-2 and prevent people who are exposed from getting too sick. Both would really help to control the pandemic!
In the meantime, please be sure to #StaySMART to prevent exposures from happening in the first place. And since no approved PEP currently exists, good quarantine etiquette and self-care like sleep, nutrition, and hydration, and hand hygiene are always important.

S Space: 6 feet or more.

M Mask: Keep it on.

A Airflow: Stay outside or in well-ventilated indoor spaces

R Restrict: Keep your circle small.

T Time: Keep it short.

REFERENCES/FURTHER READING:

Failed trial repurposing HCQ for COVID PEP

Earlier PEP and anti-viral successes:

HIV

Influenza 1

Influenza 2

Influenza 3

Influenza 4

Influenza 5

Influenza 6

Influenza 7

Chicken pox (varicella)

Hepatitis B

Remdesivir clinical trial results:

NEJM Final report

NEJM Earlier report

Trial protocols for inhaled administration 1

Trial protocols for inhaled administration 2

Today’s disappointing news re: WHO Solidarity trial

COVID-19 disease course – why antivirals matter early on

Fluvoxamine – preliminary results (abstract)

NIH COVI19 treatment guidelines (updated regularly), including PEP recommendations

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