COVID 1
Rick Hodes, MD, MACP
JDC-Ethiopia
EthiopianSpines@gmail.com
11 April, 2020
To my Ethiopian colleagues:
I am sending recent thoughts on Covid-19. I am happy to help explore ideas; certainly many ideas and recommendations will be changing in coming weeks. At this writing, there are 278 studies researching this disease, and the answers will be very useful.
Spread:A lot of this is asymptomatic. We need mass testing to find out the real story. Testing is only recommended for sick people in the US. Testing is limited in the US due to a) few tests, b) few swabs, c) lack of PPE, so we don’t exactly know number of exposed people. America has tested 2.3 million people (out of 330 million).
Iceland has tested 10% of its entire population. They took names from the telephone directory for randomization. Note: the population of Iceland is 360,000, equal to Tulsa, Oklahoma! Half the disease in Iceland is asymptomatic! In the USA, CDC had estimated that 25% was asymptomatic.
Recall that in polio, for every case of paralytic disease, there are 200 patients without paralysis.
Prevention:
BCG: There are at least 12 studies about BCG, which have been posted (non necessarily peer-reviewed). There is good suggestion that it is protective. It has also been suggested to give it to health workers.
https://www.medrxiv.org/search/BCG%252Bcovid%252B
https://foreignpolicy.com/2020/03/24/coronavirus-vaccine-health-care-workers-bcg/
Vaccination:
There is great push to come up with a vaccine, but most agree that there will be no vaccine this year. One podcast I listened to said they had spoken with CEOs of 3 different biotech companies, and all agreed that there will be no working vaccine in 2020. There are both technical, manufacturing, and safety issues.
In the realm of safety, the Dengue vaccine had a huge problem with ADE – antibody dependent enhancement. In sero-negative children, the vaccine acted like the primary dengue virus infection, causing severe disease in infections later on in 1.4%. Because millions of children are candidates for vaccination, this rate was considered unacceptable.
How much time, and how many doses are needed to rule this out? Will we have to balance the risk of enhancement vs the risk of not getting a speedy vaccine? Recall that dengue is a flavivirus, while COVID-19 is a ribovirus, so that may make it less of an issue.
https://www.virology.ws/2017/12/07/a-problem-with-dengue-virus-vaccine/
https://www.nature.com/articles/d41586-020-00798-8
Treatment Possibilities:
1) Convalescent plasma
Seemed to help 10 recent patients reported in PNAS:
https://www.pnas.org/content/early/2020/04/02/2004168117
2) Hydroxychloroquine +/- azithromycin, normally used for lupus or P. vivax
This is highly controversial. A small, uncontrolled French study is suggestive of efficacy, but needs to be studied in a controlled trial. This has been endorsed by President Trump on numerous occasions. Physicians are less excited, including friends of mine who are actively treating patients and are using it. Turkey, however, is finding that it helps prevent pneumonia.
https://www.ncbi.nlm.nih.gov/pubmed/32265182
https://www.ncbi.nlm.nih.gov/pubmed/32205204
https://www.middleeasteye.net/news/coronavirus-turkey-hydroxychloroquine-malaria-treatment-progress
This is also being studied for prophylactic use among medical staff.
3) Kaletra (lopinovir/ritonavir),these are HIV meds
No benefit was seen in this NEJM study:
https://www.nejm.org/doi/full/10.1056/NEJMoa2001282
4) Remdesiviris an antiviral drug, which is safe, but ineffective against Ebola. It is in good supply. Today, a study posted by NEJM of 61 patients in 9 countries:
68% had improvement in oxygenation. 17/30 patients were extubated, this is really good. I could find no good data on extubation in this disease but in general it is less than half. Mortality was 13% among patients on invasive ventilation with median followup of 18 days. This is promising.
https://www.nejm.org/doi/full/10.1056/NEJMoa2007016?query=featured_coronavirus
5) Anti IL-6 drugs:
The idea of cytokine storm causing ARDS-type lungs is quite popular, with the concept that if you can quiet the storm and inflammation, it may well quiet the disease.
Tocilizumab (Actemra, made by Roche), is a biologic agent used for rheumatoid arthritis and related diseases. It has been credited with a couple of notable patient turnarounds. I think there is great promise here.
6) Non-steroidal anti-inflammatory drugs
There was suggestion that these may be deleterious. However, the emergency medicine doctors I listen to are using NSAIDS without problem. The World Health Organization has not spoken out against them. Because pleuritic chest pain is a strong component of the disease, which is limiting respiration, NSAIDS may be quite helpful, so patient can breath with less pain.
7) Steroids:
I could find nobody advocating this, but it is being discussed.
8) Statins:
Nobody is talking about use of statins, this is my idea. It is known that high dose simvastatin (and probably others as well) have anti-inflammatory effects.
In a subgroup analysis of the HARP-2 study, high dose simvastatin patients who had hypoinflammatory disease (65% of the total) did not improve with simvastatin. For the 35% who had hyperinflammatory subphenotype, they had statistically significantly fewer days on ventilator. They had significantly higher 28 day survival. I have contacted the author to ask her thoughts on the COVID-19 phenotypes.
https://www.ncbi.nlm.nih.gov/pubmed/30078618
9) Prevention of venous thromboembolism
Many centers routinely use preventive measures. Consideration should be given to giving prophylaxis to bedridden patients.
10) Ventilation:
Here is a link to a free, online course by Harvard University on how to run ventilators for physicians who are not ICU-trained:
Concepts:
a) When to intubate:
This is a rapidly changing concept. I have listened to 8 hours of discussion online about this. It seems like there may be 2 subgroups, which are not distinct and patients may go from 1 to the other:
TYPE L – lungs not in bad shape, some VQ mismatch, and some groundglass appearance on x-ray. May be hypoxic
TYPE H: More of a classic ARDS, with poor oxygenation and poor compliance. May have a lot of alveolar collapse.
The old idea (2 weeks ago) was to intubate early. Now they are talking about ignoring hypoxia and making the decision to intubate based on work of breathing, not on the oxygen level. Some might use esophageal manometry if available to make that decision. They are trying to start with high-flow nasal cannula and CPAP, I realize this may not be possible in Ethiopia. And it potentially aerosolizes viral particles, making personal protection of medical staff quite important. Wearing an N-95 mask for hours is not easy and not comfortable, and itself causes shortness of breath to staff.
b) Oxygenation:
At what level should oxygenation be aimed? A recent study in the NEJM (12 March, 2020) found that there was no difference in outcome in “conservative vs liberal” use of oxygen in the ICU.
https://www.nejm.org/doi/exam/10.1056/NEJMcme1903297?ef=article
c) Possibility of extubation:
Once intubated, it seems that less than half of patients will survive.
d) Patient position: Proning
There is general agreement that “Proning” of the patient – putting them on their stomach, may help a lot in this condition. Prone position is otherwise not used very often in the USA, and has some contraindications (high ICP, hemoptysis, DVT, burns…).
One expert said on a podcast that he lets patients choose their position, and even in the ICU may have patients in a variety of positions, including L and R lateral and seated.
Why does prone position help? It probably helps with the V/Q match. It will move the heart off the collapsed left lower lung, applying gravitational traction to the previously collapsed dorsal lung. It may improve blood flow to lower gravity-dependent lung zones.
A 2013 NEJM study of 466 patients with ARDS compared position. Unadjusted 90-day mortality was 23.6% in the prone position, 41% in the supine position.
https://www.nejm.org/doi/full/10.1056/NEJMoa1214103
I can provide more information, if anyone is interested.
d) Protection of medical staff:
More than 100 physicians have died of coronavirus in Italy.
https://www.thelocal.it/20200409/more-than-100-doctors-have-now-died-in-italys-coronavirus-outbreak
It is especially important to DON and DOFF (put on/take off) PPE properly. Some places have 1 full-time staff simply directing this because it is easy to make errors. Here are the CDC recommendations:
https://www.cdc.gov/hai/pdfs/ppe/ppe-sequence.pdf
And here are similar recommendations from U Texas in Galveston:
https://www.utmb.edu/covid-19/health-care-workers/ppe-and-testing-information/don-and-doff-ppe
Resources:
a) American College of Physicians
The ACP is the professional organization of internists in the US. I have the highest status with this group (master) and access to their materials.
They are offering free access to their Coronavirus info:
b) Annals of Internal Medicine
The Annals (journal of the ACP above) is offering free access to all for its coronavirus articles:
https://annals.org/aim/pages/coronavirus-content
c) Pediatrics:guidance of American Heart Association + American Academy of Pediatrics:
A personal note:
Health care personnel are welcome to contact me directly with their questions.
I know this is a very difficult time, and I want to send my appreciation and gratitude to the Ethiopian medical professionals for working so hard to keep Ethiopians as healthy as possible.
We hope to have a podcast in the future so Ethiopian medical staff can hear and interact with American physicians on the front lines.
Sincerely,
Rick
Rick Hodes, MD, MACP
Medical Director, JDC-Ethiopia
Note: These are my personal medical ideas and not those of JDC, which has no recommendations on these detailed topics.