Hello everyone,
This newsletter is focused on COVID-19 resources, with answers to questions we’ve collected from the group, and also on promising efforts to combat/treat SARS-co-V-2, the virus that causes COVID-19.

As you all know by now, humans do not have any innate immunity to SARS-co-V-2. We also have no current vaccination to protect against this virus. This means that we are all susceptible to infection. Current aggressive measures to maintain social distance (actually physical distance—we can be as social as we want, just have to do it virtually) are in place to slow the rate of infection so that our healthcare systems do not become overwhelmed, resulting in preventable deaths from COVID-19. This is called ‘flattening the curve’ a phrase we are all familiar with at this point.

Since we do not have a universal approach to this in the United States, but are leaving decisions about management up to each state, there is a lot of conflicting guidance based on where you live and the current situation with the virus in each state. Please be aware that it is very challenging for the media to get complete and accurate information during this stressful time. For instance, we are hearing a lot about New York City with regard to their very high infection rate, but there are some smaller states whose total infected number is lower, but that actually have higher per capita infection rates than New York. This is important, because the focus on total number of cases, may lead people to think the virus is not as active where they live. This is misleading.

Some states are taking a very relaxed approach, not requiring adequate physical distancing. Individuals with PCD in states taking this approach may have additional fears about their safety and may feel unsupported by their local communities when they try to do the right thing for PCD.  Let’s be sure these families get lots of support from their PCD community!

COVID-19 Question and Answer with Dr. Thomas Ferkol
In preparation for our virtual town hall next week, we asked Dr. Tom Ferkol from Washington University St. Louis , and Co-PI of the Genetic Disorders of Mucociliary Clearance Consortium to answer some common questions coming up in the group.
1. Should we stockpile azithromycin and albuterol in case of shortage?  

No, and it is likely that insurers and pharmacies will not allow you to do so during the pandemic.

2. Is it dangerous to go into the clinic for PCD flare ups?  

I think the answer depends on the community and numbers of people with COVID-19. If a region has large numbers of infected people, it’s likely that many will be in clinics, emergency departments, and on hospital wards. Because there is no treatment for COVID-19, prevention is key. So, if you are well, stay at home and avoid potential infectious exposures.

If you have developed symptoms consistent with an exacerbation, it is possible that you could be treated with aggressive airway clearance and possibly begin empirical oral or inhaled antibiotics. Many centers have created “virtual” visits, where patients and families can talk with their physician and discuss treatment options.
That all being said, if you feel you need to be seen, be seen. I am sure that your center will make every effort to reduce risk of exposure.

3. Are people with PCD immunocompromised? (This is a tricky one—we know that PCD itself does not compromise the immune system, but the term is being used broadly in the lay press to refer anyone at higher risk, which confuses the issue). 

 An interesting question. People with PCD are not immunocompromised in the same way that those with primary immunodeficiencies. However, because of their abnormal ciliary function, they do not clear bacteria and other airborne particles from their upper and lower airways, which leads to chronic respiratory infections.

It has been reported that people with pre-existing diseases have greater risk for more severe forms of COVID-19, but it is unknown how people with PCD will fare with COVID-19.

4. Related to above, what can I do to strengthen my immune system? Are there supplements, etc?  

Nothing that has been clearly shown to prevent or reduce severity of viral infections, like SARS-CoV-2, the causative virus of COVID-19

5. How will I know if increased symptoms are just regular PCD or could be COVID-19?  

That’s difficult to answer, because clinical features vary between individuals. The typical features of COVID-19 are new cough, shortness of breath, and fever greater than 100.5 degrees Fahrenheit (38.0 degrees Celsius), but there are some people who have been nearly asymptomatic.
6. Should I wear a mask and gloves when I go out?

Not necessarily, remember that you can still be infected despite these barriers, especially if they are used incorrectly.  The most effective way of preventing infection is just good common sense — social distancing, good hand washing, and frequent cleaning and disinfecting surfaces in the home.

7. Does hydroxycholoroquine w/azithromycin cure COVID-19? 

No. There have been anecdotal reports that suggested some benefit, but no proof.  Better studies are needed.
8. Would now be a good time for patients who have been hesitating to go on azithromycin prophylactic therapy to do so, just in case? 

If physicians wish to prescribe alternate-day azithromycin, it should be on the basis of the results from a large though still unpublished European clinical trial showing a modest reduction in exacerbation frequency. There is not data showing that azithromycin is effective in COVID-19.

9. Can we use NSAIDS (non-steroidal anti-inflammatories like ibuprofen and naproxen)? 

Again, there have been anecdotal reports suggesting that these agents were associated with worse disease, but no conclusive proof. We need more evidence.

10. What is convalescent serum? Are there other therapies or medications that might help? 

The concept is passive immunizations, where antibodies from previously patients are infused into an uninfected person. It is an idea that has not been tested yet, and it is likely that person would need repeat (e.g., monthly) injections as long as COVID-19 is in the community, and possibly during subsequent seasons.

Studies testing active immunizations have begun, but it is too early to tell whether they will be effective.  We’ll see.
Resources and Good News!
With so much negative news right now, we think it’s important to share some positive developments. There are clinical trials underway right now on vaccinations for SARS-co-V-2, as well as potential therapies. By ‘flattening the curve’ and slowing the rate of acquisition of this virus, we are also buying time for researchers to find interventions that may make us less susceptible to the virus or less likely to become severely ill or die. Here are some of those possible interventions:


Novel SARS-co-V-2 vaccine: https://www.nih.gov/news-events/news-releases/nih-clinical-trial-investigational-vaccine-covid-19-begins  (note novel vaccines take a long time to develop and test because both safety and efficacy can be issues—getting this vaccine to trial as quickly as they did is impressive, but we are still looking at 12-18 months minimum).

Existing TB vaccine: https://www.sciencealert.com/australia-is-trialling-a-tb-vaccine-for-coronavirus-and-health-workers-get-it-first (note–this is also being evaluated in Germany. it has the advantage of already being approved in many countries (not the US yet) for TB, so safety is already established. If it proves to be of benefit against SARS-co-V-2—and we do not know yet if it will work—it could be available sooner than a novel vaccine).

Convalescent serum, aka plasma therapy: https://www.nature.com/articles/d41586-020-00895-8 (this is a very old therapy first used in the 1918 flu pandemic. It consists of infusing plasma from people who have recovered to provide some short-term preventative/possibly therapeutic benefit).

Hydroxychloroquine w/azithromycin

The data on this drug combo for the treatment of COVID-19 is inconsistent and largely anecdotal. Please be aware that there are serious flaws in the French paper being used to justify this therapy. In the middle of a crisis, it can be hard to get good clinical trial data, but in the case of this paper, the flaws go beyond just what would be expected in a crisis situation.

A very small Chinese study did not include a lot of patients but did have better study design and control. This paper showed no benefit to the group treated with hydroxychloroquine over the group that did not get treated. The authors caution against drawing any conclusions based on such a small sample.

Both of these drugs are known to exacerbate the same cardiac rhythm defect, called a long Q-T interval, so they are not without risk.  True benefit must be established prior to taking the risk for mild/moderate disease that could be managed without them. The US FDA has authorized clinical trials for this drug combo on an urgent basis, so we should have better data very soon.
Here is a nice overview of the current status of investigation into this drug combo: https://www.forbes.com/sites/tarahaelle/2020/03/25/chloroquine-use-for-covid-19-shows-no-benefit-in-first-small-but-limited-controlled-trial/#7f042d734c86

Anti-viral therapy:

There no anti-viral drugs that specifically work against coronaviruses. However, based on preliminary data that show some benefit when used against other types of RNA viruses, the World Health Organization announced clinical trials of four anti-viral agents against SARS-co-V-2. More info here: https://www.sciencemag.org/news/2020/03/who-launches-global-megatrial-four-most-promising-coronavirus-treatments.