Monday 30 March 2020

An Account from the Frontline

3rd hand info, so classify as RUMINT.

FYI. From a friend:

I am an ER MD in New Orleans. Class of 98. Every one of my colleagues have now seen several hundred Covid 19 patients and this is what I think I know.

Clinical course is predictable.
2-11 days after exposure (day 5 on average) flu like symptoms start. Common are fever, headache, dry cough, myalgias(back pain), nausea without vomiting, abdominal discomfort with some diarrhea, loss of smell, anorexia, fatigue.
Day 5 of symptoms- increased SOB, and bilateral viral pneumonia from direct viral damage to lung parenchyma.
Day 10- Cytokine storm leading to acute ARDS and multiorgan failure. You can literally watch it happen in a matter of hours.
81% mild symptoms, 14% severe symptoms requiring hospitalization, 5% critical.
Patient presentation is varied. Patients are coming in hypoxic (even 75%) without dyspnea. I have seen Covid patients present with encephalopathy, renal failure from dehydration, DKA. I have seen the bilateral interstitial pneumonia on the xray of the asymptomatic shoulder dislocation or on the CT's of the (respiratory) asymptomatic polytrauma patient. Essentially if they are in my ER, they have it. Seen three positive flu swabs in 2 weeks and all three had Covid 19 as well. Somehow this ***** has told all other disease processes to get out of town.
China reported 15% cardiac involvement. I have seen covid 19 patients present with myocarditis, pericarditis, new onset CHF and new onset atrial fibrillation. I still order a troponin, but no cardiologist will treat no matter what the number in a suspected Covid 19 patient. Even our non covid 19 STEMIs at all of our facilities are getting TPA in the ED and rescue PCI at 60 minutes only if TPA fails.

CXR- bilateral interstitial pneumonia (anecdotally starts most often in the RLL so bilateral on CXR is not required). The hypoxia does not correlate with the CXR findings. Their lungs do not sound bad. Keep your stethoscope in your pocket and evaluate with your eyes and pulse ox.
Labs- WBC low, Lymphocytes low, platelets lower then their normal, Procalcitonin normal in 95% CRP and Ferritin elevated most often. CPK, D-Dimer, LDH, Alk Phos/AST/ALT commonly elevated.
Notice D-Dimer- I would be very careful about CT PE these patients for their hypoxia. The patients receiving IV contrast are going into renal failure and on the vent sooner.
Basically, if you have a bilateral pneumonia with normal to low WBC, lymphopenia, normal procalcitonin, elevated CRP and ferritin- you have covid-19 and do not need a nasal swab to tell you that.
A ratio of absolute neutrophil count to absolute lymphocyte count greater than 3.5 may be the highest predictor of poor outcome. the UK is automatically intubating these patients for expected outcomes regardless of their clinical presentation.
An elevated Interleukin-6 (IL6) is an indicator of their cytokine storm. If this is elevated watch these patients closely with both eyes.
Other factors that appear to be predictive of poor outcomes are thrombocytopenia and LFTs 5x upper limit of normal.

I had never discharged multifocal pneumonia before. Now I personally do it 12-15 times a shift. 2 weeks ago we were admitting anyone who needed supplemental oxygen. Now we are discharging with oxygen if the patient is comfortable and oxygenating above 92% on nasal cannula. We have contracted with a company that sends a paramedic to their home twice daily to check on them and record a pulse ox. We know many of these patients will bounce back but if it saves a bed for a day we have accomplished something. Obviously we are fearful some won't make it back.
We are a small community hospital. Our 22 bed ICU and now a 4 bed Endoscopy suite are all Covid 19. All of these patients are intubated except one. 75% of our floor beds have been cohorted into covid 19 wards and are full. We are averaging 4 rescue intubations a day on the floor. We now have 9 vented patients in our ER transferred down from the floor after intubation.
Luckily we are part of a larger hospital group. Our main teaching hospital repurposed space to open 50 new Covid 19 ICU beds this past Sunday so these numbers are with significant decompression. Today those 50 beds are full. They are opening 30 more by Friday. But even with the "lockdown", our AI models are expecting a 200-400% increase in covid 19 patients by 4/4/2020.

worldwide 86% of covid 19 patients that go on a vent die. Seattle reporting 70%. Our hospital has had 5 deaths and one patient who was extubated. Extubation happens on day 10 per the Chinese and day 11 per Seattle.
Plaquenil which has weak ACE2 blockade doesn't appear to be a savior of any kind in our patient population. Theoretically, it may have some prophylactic properties but so far it is difficult to see the benefit to our hospitalized patients, but we are using it and the studies will tell. With Plaquenil's potential QT prolongation and liver toxic effects (both particularly problematic in covid 19 patients), I am not longer selectively prescribing this medication as I stated on a previous post.
We are also using Azithromycin, but are intermittently running out of IV.
Do not give these patient's standard sepsis fluid resuscitation. Be very judicious with the fluids as it hastens their respiratory decompensation. Outside the DKA and renal failure dehydration, leave them dry.
Proning vented patients significantly helps oxygenation. Even self proning the ones on nasal cannula helps.
Vent settings- Usual ARDS stuff, low volume, permissive hypercapnia, etc. Except for Peep of 5 will not do. Start at 14 and you may go up to 25 if needed.
Do not use Bipap- it does not work well and is a significant exposure risk with high levels of aerosolized virus to you and your staff. Even after a cough or sneeze this virus can aerosolize up to 3 hours.
The same goes for nebulizer treatments. Use MDI. you can give 8-10 puffs at one time of an albuterol MDI. Use only if wheezing which isn't often with covid 19. If you have to give a nebulizer must be in a negative pressure room; and if you can, instruct the patient on how to start it after you leave the room.
Do not use steroids, it makes this worse. Push out to your urgent cares to stop their usual practice of steroid shots for their URI/bronchitis.
We are currently out of Versed, Fentanyl, and intermittently Propofol. Get the dosing of Precedex and Nimbex back in your heads.

One of my colleagues who is a 31 yo old female who graduated residency last may with no health problems and normal BMI is out with the symptoms and an SaO2 of 92%. She will be the first of many.

I PPE best I have. I do wear a MaxAir PAPR the entire shift. I do not take it off to eat or drink during the shift. I undress in the garage and go straight to the shower. My wife and kids fled to her parents outside Hattiesburg. The stress and exposure at work coupled with the isolation at home is trying. But everyone is going through something right now. Everyone is scared; patients and employees. But we are the leaders of that emergency room. Be nice to your nurses and staff. Show by example how to tackle this crisis head on. Good luck to us all."

Saturday 28 March 2020

Possible length of infectivity > 25 days after negative test.

Our data suggest the possibility of extended duration of viral shedding in faeces, for nearly 5 weeks after the patients' respiratory samples tested negative for SARS-CoV-2 RNA. Although knowledge about the viability of SARS-CoV-2 is limited,the virus could remain viable in the environment for days, which could lead to faecal–oral transmission, as seen with severe acute respiratory virus CoV and Middle East respiratory syndrome CoV

Prolonged presence of SARS-CoV-2 viral RNA in faecal samples Wu et al, The Lancet, March 2020

Friday 27 March 2020

SARS-CoV-2 Mutation worldwide in pictures


 How various strains spread.

The family tree by geographic location.

And where on the genome the mutations are.

Mutation accumulation in SARS-CoV-2 strains as of 26Mar20 from
The picture above shows the length of the genome (0 to 29,000 bases) and the bars above show how many mutations have been detected at a given nucleotide. The long, color coded bars underneath represent the protein produced by that section of the virus.

Now, the analysis, by someone who knows their onions.

Overall, we’re seeing what you would hope to see in a virus, a lot of broad, non-specific mutation locations. This means there is no particular pressure on the virus to change an aspect of its proteins rapidly.

Overall, we’re looking at wonderful news for people developing treatments and vaccines. While this virus is mutating, it’s not showing anything dangerous or anything that can prevent treatments from working in the near future. The virus will continue to spread, but we’ll continue to monitor it; as the virus accumulates more isolated differences, we’ll even be able to tell where a case was from based on its unique sequence.

There is concern about the ability of this disease to reinfect someone after they recover from an initial bout of COVID-19. I am no virologist and can’t say it won’t happen in the future, but for now it looks like that isn’t possible. While there have been some reports of reinfection in people, it could be that they had false negative test results or just hadn’t quite recovered as much as they thought they had, leading people to be readmitted to the hospital. A trial performed in monkeys showed no signs of a second infection after the monkey was initially exposed, which is great news for us.

 See for a discussion on these experiments.

Thursday 26 March 2020

Local news : a snapshot of the plague year in Canberra.

Starting with the smoke emergency.

A summer marked by hazardous air quality and bushfire smoke may have cost 31 Canberrans their lives, according to a new study published in the Medical Journal of Australia.

The study did not analyse pre-existing conditions but measured what public health experts describe as “excess deaths”, or the factor by which observed mortality rates exceed expected mortality rates when major risks like heatwaves, bushfires, pandemics, famine or war are present.

The study estimated that in the ACT, 229 people were admitted to hospital – 82 for cardiovascular problems, and 147 for respiratory problems – while 89 people attended the emergency department because of asthma-related issues.
There were a total of 417 estimated excess deaths because of the bushfire smoke and 4,456 hospitalisations and emergency department visits across NSW, Queensland, Victoria and the ACT.

Between October 2019 and February 2020, the concentration of PM2.5 – fine particles that irritate the respiratory system – exceeding the 95th percentage of historical daily averages was recorded by at least one air-quality monitoring station on 94 per cent of days.

More than a third of Canberra’s summer was spent with air quality levels above hazardous as bushfire smoke blanketed the ACT. Canberra regularly had the world’s worst air quality levels on days throughout the 2020 bushfires.
The air quality in Canberra reached 22 times the hazardous threshold on New Year’s Day, dragged across from the South Coast by unrelenting easterlies.
 And now to the fast moving situation regarding COVID-19.

One person who was diagnosed with the COVID-19 virus has made a full recovery and is now out of self-isolation.

An ACT Health spokesperson confirmed the good news early this afternoon. The person was first diagnosed on 12 March.

“This person has now shed the virus and is no longer required to self-isolate,” the ACT Health spokesperson said.
However, the number of confirmed cases of COVID-19 in the ACT in the past 24 hours continues to rise, with a further nine people testing positive.

This brings the ACT’s total to 53 people with the virus.

The new cases include six males and three females, aged between 21 and 83.
“ACT Health is undertaking thorough contact tracing but can confirm that eight of the cases are linked to overseas travel, including cruise ships, and one is a close contact of a confirmed case,” ACT Health said in a statement.

ACT Health said there is still currently no evidence of community transmission in the ACT.

There have been 3219 negative COVID-19 tests in the ACT to date. 

There are currently three COVID-19 patients in the Canberra hospital. All are in a stable condition. The rest are isolating at home with ACT Health support.

Wednesday 25 March 2020

Hydroxychloroquine / Azithromycin

Are hydroxychloroquine and azithromycin an effective treatment for COVID-19?

The evidence is pretty poor at the moment, alas.
Aside from not adhering to an intent-to-treat design, here’s where the study is truly revealed to be crap.....

 But like Chicken Soup, it can't hurt, right? Welll..not usually... but sometimes it does hurt.

Hydroxychloroquine (trade name Plaquenil) is a derivative of chloroquine (trade name Aralen), a common antimalarial drug. Indeed, some of you reading this might well have taken chloroquine as prophylaxis to prevent malaria while traveling to tropical regions where the disease is endemic. It is also used to treat amoebic liver abscesses when other drugs used for such infections are not working. These drugs also mildly suppress the immune system, which is why they are used as part of the treatment of some autoimmune disorders, such as lupus erythematosis or rheumatoid arthritis.

One thing that should be understood is that these are not entirely benign drugs. They have a number of side effects and adverse reactions. In addition to more mild side effects, such as nausea, headache, loss of appetite, and diarrhea, there are two more severe potential side effects. One is that long term use of these drugs can damage the retina and lead to macular degeneration, which is why patients taking these drugs long term need regular ophthalmological examinations. They can also affect the heart by prolonging the QT interval and also lead to drug-induced torsade de pointes, a potentially lethal ventricular tachycardia.

The other drug in the combination, azithromycin (trade names Zithromax, Azithrocin, and others), is a common antibiotic, used to treat a number of infections, ranging from ear infections, to strep throat, pneumonia, and a number of sexually transmitted infections, including chlamydia and gonorrhea. It’s commonly prescribed as a “Z-Pak,” to be taken for five days, and it’s widely prescribed. It can also be used to treat malaria. It has few adverse side effects, but it shares one with hydroxychloroquine: QT-segment prolongation. Indeed, the FDA issued a warning in 2013 that azithromycine “can cause abnormal changes in the electrical activity of the heart that may lead to a potentially fatal irregular heart rhythm.” The warning further cautioned that people with certain pre-existing conditions are at particular risk, such as those with QT interval prolongation, low potassium or magnesium levels, a slower than normal heart rate, or those who use certain drugs to treat abnormal heart rhythms.
A number of doctors on Twitter were alarmed at the suggestion that two drugs that can affect heart rhythm be taken together without much stronger evidence that they were effective....

Coronavirus Pandemic Update 42: Immunity to COVID-19 and is Reinfection ...

Tuesday 24 March 2020

Those in power

When asked if he would make the decision to loosen social-distancing recommendations even if it went against the advice of federal public health officials, Trump said: “If it was up to the doctors they might say shut down the entire world.”
Washington Post

The US at time of posting has had over 43,000 cases, some 550 deaths, with 1000 in serious or critical condition.
Q: You’re standing there saying nobody should gather with more than 10 people and there are almost 10 people with you on the stage. And there are certainly more than 10 journalists there asking questions.
A: I know that. I’m trying my best. I cannot do the impossible.
Q: What about the travel restrictions? Trump keeps saying that the travel ban for China, which began 2 February, had a big impact on slowing the spread of the virus to the United States and that he wishes China would have told us 3 to 4 months earlier and that they were “very secretive.” (China did not immediately reveal the discovery of a new coronavirus in late December 2019, but by 10 January, Chinese researchers made the sequence of the virus public.) It just doesn’t comport with facts.
A: I know, but what do you want me to do? I mean, seriously Jon, let’s get real, what do you want me to do?
That was from an interview with Dr Fauci,director of the National Institute of Allergy and Infectious Diseases and apparently nanny to the toddler in chief in Science Magazine
Brazil’s far-right president, Jair Bolsonaro, has accused his political foes and the press of purposefully “tricking” citizens about the dangers of coronavirus, as Latin America braced for a spike in the number of deaths.
The pandemic has claimed nearly 15,000 lives across the globe and looks set to exact a deadly toll on Latin America in the coming weeks, with many regional governments closing borders and shutting down major cities in a desperate bid to limit the damage.
But Bolsonaro has resisted such drastic measures, dismissing media “hysteria” over coronavirus and calling the illness “a little flu”.
In a tetchy television interview on Sunday night Bolsonaro again downplayed the pandemic and attacked the governors of key states including Rio de Janeiro and São Paulo who have ordered residents to stay at home and are imposing quarantines.
“The people will soon see that they were tricked by these governors and by the large part of the media when it comes to coronavirus,” Bolsonaro said, as his own health officials announced 25 deaths and 1,546 cases of coronavirus in Brazil.
The Grauniad

Sunday 22 March 2020

Pharmaceutical Society of Australia (PSA) Letter to Prescribers

Prescribing Hydroxychloroquine for COVID-19

Saturday, 21 March 2020

Open letter to Prescribers

As the National President of the Pharmaceutical Society of Australia (PSA) representing Australia’s 32,000 Pharmacists, we are providing this open letter to all Australian prescribers regarding the Prescribing hydroxychloroquine for COVID-19.

On the background of some promising data showing the effectiveness of hydroxychloroquine for the treatment of COVID-19 and with President Trump’s announcement yesterday, 20 March 2020, that the drug hydroxychloroquine may support the care of patients affected by COVID-19, Australian community pharmacies have seen unprecedented demand for the drug.

PSA is receiving reports from Australian pharmacists that they are receiving prescriptions from: doctors prescribing for other doctors and their families; as well as dentists prescribing to the community and their families; Non-medical prescribers prescribing bulk amounts of the drug. If this medication does indeed have the efficacy that we would desire against COVID-19 then it needs to be prescribed and used judiciously. The stock of this medication needs to be managed effectively and utilised for those who may genuinely need it.

Our strong advice to pharmacists at this point in time, until further advice is available, is to refuse the dispensing of hydroxychloroquine if there is not a genuine need, and that need is for those indications for what it is approved for – inflammatory conditions or the suppression and treatment of malaria The current stock of hydroxychloroquine needs to be managed sensibly, it needs to be available for those who are currently being prescribed this medicine, and it may also be needed for treatment of COVID-19 in the future. We are urging pharmacists to manage their existing stock if they have it sensibly, ensuring those who are currently prescribed the medicine have an existing supply.

PSA will continue to work with the Minister for Health and the Therapeutic Goods Administration (TGA) with regards to the appropriate management of national stockpiles and medicines stock in Australia. PSA would like to keep safe any stock of hydroxychloroquine held in local pharmacies – so it is available to treat patients who genuinely need this medicine. The only way this is possible is for prescribers to not write prescriptions for this medicine as a ‘just in case’ measure and for pharmacists to refuse the supply outside of these indications at this point in time.

While the data may not yet be clear, if hydroxychloroquine is shown to be effective for COVID-19, we want every dose available to treat those who may require it.

Yours sincerely,

Associate Professor Chris Freeman
PSA National President

Podcast 10: Coronavirus | with Dr Norman Swan

Friday 20 March 2020

Exercise Crimson Contagion

From the New York Times :
The outbreak of the respiratory virus began in China and was quickly spread around the world by air travelers, who ran high fevers. In the United States, it was first detected in Chicago, and 47 days later, the World Health Organization declared a pandemic. By then it was too late: 110 million Americans were expected to become ill, leading to 7.7 million hospitalized and 586,000 dead.
That scenario, code-named “Crimson Contagion” and imagining an influenza pandemic, was simulated by the Trump administration’s Department of Health and Human Services in a series of exercises that ran from last January to August.

The simulation’s sobering results — contained in a draft report dated October 2019 that has not previously been reported — drove home just how underfunded, underprepared and uncoordinated the federal government would be for a life-or-death battle with a virus for which no treatment existed.
The draft report, marked “not to be disclosed,” laid out in stark detail repeated cases of “confusion” in the exercise. Federal agencies jockeyed over who was in charge. State officials and hospitals struggled to figure out what kind of equipment was stockpiled or available. Cities and states went their own ways on school closings.

Many of the potentially deadly consequences of a failure to address the shortcomings are now playing out in all-too-real fashion across the country.

Thursday 19 March 2020

Missing the Golden Moment

I'd say "Remember in November", but by then a million Americans (at least) will have died, and holding any Free and Fair election would be impossible. Anything  involving massed crowds in polling booths and lines to get in them would be dangerous lunacy, so if elections are held at all, the way of doing them will have to change radically.

Those who criticised Trump for his action in banning travellers from China were wrong, and should admit it. If they don't,  they are not to be trusted.

Those who now criticise the measures being taken far too late are not to be trusted.

Those who believe the obvious untruths continually being spouted by the GOP and Trump - you are responsible for this being as bad as it's going to be. Not for the first million deaths perhaps, half a million would have died even if everything had been done right. But for the millions after that, because Reality wins in the end, and the Con game finishes eventually.

We were living in trees when they met us. They showed us each in turn

That Water would certainly wet us, as Fire would certainly burn:

But we found them lacking in Uplift, Vision and Breadth of Mind,

So we left them to teach the Gorillas while we followed the March of Mankind.

We moved as the Spirit listed. They never altered their pace,

Being neither cloud nor wind-borne like the Gods of the Market Place,

But they always caught up with our progress, and presently word would come

That a tribe had been wiped off its icefield, or the lights had gone out in Rome.

With the Hopes that our World is built on they were utterly out of touch,

They denied that the Moon was Stilton; they denied she was even Dutch;

They denied that Wishes were Horses; they denied that a Pig had Wings;

So we worshipped the Gods of the Market Who promised these beautiful things.

Tuesday 17 March 2020

We estimate 86% of all infections were undocumented.....

We estimate 86% of all infections were undocumented (95% CI: [82%–90%]) prior to 23 January 2020 travel restrictions. Per person, the transmission rate of undocumented infections was 55% of documented infections ([46%–62%]), yet, due to their greater numbers, undocumented infections were the infection source for 79% of documented cases.
Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV2) li et al, Science 16 Mar 2020: