Monday, April 6, 2020

Timeline of COVID March-April 8


Now we're into the stock market rising as investors are becoming optimistic that we're seeing a global flattening of the curve.  Perhaps it's time to take advantage of some relatively discounted stocks.  But as the future may look brighter to them, the death rates are peaking and will likely be at a plateau for the next week or two.  It's buckle-down time.

I did go out to Braums yesterday morning–the first that I donned one of the n95 masks I've got around.  Braums is a small convenience store attached to a fast food joint.  They make their own milk and I figured in the morning it would be relatively uncrowded.  I was right.  There were only two other shoppers and a cashier.  One of them was wearing a mask and that eased my awkward feeling of being the other one with a mask on.  After I left, I quickly doffed my mask; doffing means I removed it by the straps only making sure I didn't touch the filter.  I think I did okay though the mask did some pirouettes as I took it off.  Later I learned that I should've removed one strap at a time starting with the top.  Damn, I felt like one wrong move and that's it, I'm hosed.  At least I had my wash station in the RAV.  It was the third time I used the station.  The two other times were 2 weeks before yesterday.   My station consists of a flexible 5 gallon plastic container with a faucet that we use for camping and a liquid soap dispenser in the door pocket.  It's quite handy and I use it anytime after I touch anything public, or merchandise.

Upon coming back home, I took the products out of the bag, one at a time, to disinfect on our mobile cutting board in the garage.  Then each one goes into another bag to be brought inside.  I also took the vegetables and fruit inside to be rinsed.  The first time I did this I washed the fruits and veggies with soap but I've heard that's not advisable as soap could be absorbed.  As I'm doing this I wonder how long this will go on.  No longer do we go out on weekends and I'm the only one going out.  Also, I go in the mornings and to smaller stores.  Will this go on even after everything opens up?  I suspect I may for quite some time.

Now the latest thoughts.   I'm seeing some good news
This story shows promising research in developing an all-encompassing anti-viral medication that can be taken orally.  Called EIDD-2801(named after Emory Institute for Drug Development) has been successfully used on mice and is now going to clinical trials.  Another anti-viral called Remdesivir is another in trials.  Either one can be subject to resistant viruses but the combination can be much more powerful.  Here's to successful clinical trials.

Another good news item:  There are several stories of centenarians surviving this virus.  I see an article somewhere in the news every time another one survives.  One of them survived the 1918 flu pandemic.  How encouraging!

How about decreasing air pollution as good news?  Well, I have chosen to call this good news.  As shutdowns spread globally, air pollution has remarkably decreased.  The most noticeable areas were the most polluted areas.  This picture from northern India where residents could see the Himalayas for the first time in 30 years is so poignant to me.  How is it that 30 years could go by without people in Pathankot being able to view the mountains?  Imagine residents living there from birth to adulthood seeing the mountains for the first time?  It's analogous to residents of cities traveling out into the countryside and seeing the Milkyway for the first time.  I cannot imagine what that's like.

These stories have been coming out since early March when China's pollution decreased.

Then in mid-March, it was Italy's turn to be in the news about decreasing pollution.
Imagine how many lives were saved just on the account of having a couple months of clean air.  Would there be thousands living by the end of the year that might otherwise not be?  It's quite conceivable.

Other good news comes from Germany where they have been quite successful in their testing. I think only Iceland has exceeded Germany's testing rate.  The result is a much better idea of fatality rates as well as helping to flatten the growth curve.

Now for troubling news.  This virus is tremendously infectious. And it's only because it takes advantage of our proclivity to spread droplets and aerosols far and wide  This story of a Belgian-Dutch study shows that I've got to be 10 m or more away from other runners and bikers because of the wakes we leave behind.  My take on this is 'know the wind direction' and stay out of people's wakes.  The youtube link below is even more distressing.  Using laser beams, Japanese researchers filmed the spray of particles emanating people's sneezes, coughs and even just talking.  They modeled the dispersion of these particles and showed how far and wide they travel in a closed room.  This makes me not want to ever show up to a conference again.

Perhaps even more disturbing is that blacks in the US are so worried about wearing masks that they would choose to risk being infected than to be mislabeled as a threat.  So here's yet another consequence of racism and fear.  Black people are more likely to suffer from infection and also die from COVID-19.  Blacks and Hispanics are more likely than others to not be able to telework or have health insurance.  Add that to the fear of facial protection and we're starting to see how this disease disproportionately exacts a toll on the same people like with so many other threats.

Finally, Modley resigned a day after he spent $244k to fly down to Guam to berate the crew for their loyalty to a Captain that may have saved many lives.  Yay!  Now reinstate Capt Crozier after he hopefully recovers well!


Villains in the news regarding COVID:
Our Secretary of the NAVY Thomas Modley berates Aircraft Carrier, Capt Brett Crozier, for appealing for help to unload his ship when his crew became sick.  True, Capt Crozier didn't follow through chain of command.  But I can't imagine anybody reaching his rank not knowing that.  Something forced him to e-mail 30 NAVY officers outside classified channels.  In so doing, he was removed from his post while contracting the disease himself.  Thomas Modley's erratic, expletive-laden rebuke in front of the Aircraft Carrier's crew did nothing but further alienate the crew from the NAVY's leadership.  I put Modley in the list of villains – shameful.

Another villain, or ill-advised, Dr. Drew, who spread disinformation about the virus, claiming that it was nothing to worry about, now admits his mistake.  How much damage have these people caused (45 included)?
He learned what it's like to be on the wrong side of the asymmetric penalty function of a warning.

COVID timeline:
Business Insider has an excellent timeline of this pandemic.  It starts December 31 with the Chinese notification to the WHO of a new disease.

But now there are stories that COVID-19 may have been in the US in December.  I've heard of people suffering from weeks of severe coughs and fever.  It certainly was spreading in Wuhan province since late November.

Heroes:  Grocery Store employees.
I didn't want to hear about this but it was inevitable.  Store employees are becoming sick and some are dying.  I have an amazing new outlook on the danger they face when dealing with a broad spectrum of shoppers, some adhering to social distancing while others literally sneeze in cashier's faces with perceived impunity.  Many employees demanded stores add various measures to mitigate transmission.

Two weeks ago was the last time I shopped at Sprouts in Norman.  At the time, I only saw two shoppers with masks.  One store employee greeted me at the entrance with a cart and a wipe.  I thanked him much.  I went in the morning and so the store was quiet. What shoppers there were kept distances from each other.  One shopper had to get by me in a narrow aisle.  I turned to face the merchandise and heard her speed up to get by me, much like a cat does when trying to run through a constriction.   I bought my groceries and proceeded to the checkout.   I talked with the cashier and thanked her for wiping down the conveyor belt.  She wore a mask, to which I was grateful.  At the time I didn't have one for I followed the advice of professionals that I didn't need one in a store.  Case counts weren't as high as they are today.  Anyway, I asked the cashier how shoppers were.  Her main complaint was that shoppers tended to violate the six-foot rule at checkout; markers were taped on the floor at six-foot intervals.  But she didn't mention any more severe violations of social distancing.

When I go shopping soon, I will be masked and I heard a majority of others are doing the same.

Mitigation measures:
For weeks we've been reducing our exposure to public spaces.  Even since March 16, after we got over our flu-A (yes we had the vaccine), I decided not to fly to my mother's 90th birthday family reunion; Daphne asked that I quarantine myself for five days upon coming back.  Daphne hasn't left the house in over two weeks while my outings were limited to a grocery store, the Lowes outside garden center, and Marcum's nursery.  Even there, I waited till the checkout cleared out before checking out myself.

Next time I go out I'll be wearing a mask.  But now I see that virus particles linger for quite some time on them.  But how many that are left after a day are not viable?  Who knows.

20200404 -
Popular culture-
Somebody just showed us that all of our new cultural behavioral changes have been summed up in various MASH episodes.  We've known all along.

The mask hunt
A shortage of masks has resulted in an international hunt for them, sometimes using less than honorable methods.  I just heard Canada may retaliate after Trump redirected 3M to keep all masks within the US.  So instead of helping each other, we turn into packs of wolves.

Crazy conspiracists:
Now, 5G cellphone towers are being attacked because of a certain claim that millimeter-wave radiation is dangerous for the immune system.  This article sets the record straight.  However I've not known conspiracists to be convinced they're wrong based on one article.  Hopefully, anybody wavering on the fence will lean toward rationality.

The aftermath
What about all the PTSD from going through this crisis?  Some stories come from patients in ICU that they're not the same coming out the other end.

Today's report from Jason Persoff
COVID Update 4/3

So the CDC wants people to wear masks now?  I'm uncertain about this switch in position when considering the evidence.

First off, if you're sick, YOU wearing a mask makes a HUGE difference.  Masks of any kind reduce the amount of viral particles shed into the air via droplets (main mode of transmission), but does nothing to stop aerosolized particles.  This study: Rengasamy S, Eimer B, Shaffer RE. Simple respiratory protection—evaluation of the filtration performance of cloth masks and common fabric materials against 20-1000 nm size particles.Ann Occup Hyg 2010 Jun 28;54(7):789-98, looked at the issue and concluded the following:

"The National Institute for Occupational Safety and Health (NIOSH) conducted a study of the filter performance on clothing materials and articles, including commercial cloth masks marketed for air pollution and allergens, sweatshirts, t-shirts, and scarfs.

Filter efficiency was measured across a wide range of small particle sizes (0.02 to 1 µm) at 33 and 99 L/min. N95 respirators had efficiencies greater than 95% (as expected). For the entire range of particles tested, t-shirts had 10% efficiency, scarves 10% to 20%, cloth masks 10% to 30%, sweatshirts 20% to 40%, and towels 40%. All of the cloth masks and materials had near zero efficiency at 0.3 µm, a particle size that easily penetrates into the lungs."

But if you're sick, wearing a mask does reduce the particle counts, just not outstandingly.  Every bit helps.  But do aerosolized particles that are <0.3 microns matter in COVID?  This appears to be answered by an excellent study in Nature Medicine.

This study by Leung NH, et al, (h/t Alan Schenkel) found some pretty big news.  Here is the quote and I'll follow that with a summary:

"Our findings indicate that surgical masks can efficaciously reduce the emission of influenza virus particles into the environment in respiratory droplets, but not in aerosols...This has important implications for control of COVID-19, suggesting that surgical face masks could be used by ill people to reduce onward transmission.  Among the samples collected without a face mask, we found that the majority of participants with influenza virus and coronavirus infection did not shed detectable virus in respiratory droplets or aerosols...For those who did shed virus in respiratory droplets and aerosols, viral load in both tended to be low... Given the high collection efficiency of the G-II and given that each exhaled breath collection was conducted for 30min, this might imply that prolonged close contact would be required for transmission to occur, even if transmission was primarily via aerosols, as has been described for rhinovirus colds...Our results also indicate that there could be considerable heterogeneity in contagiousness of individuals with coronavirus...."

What this study shows is that by ill people wearing masks, they do reduce the risk of disease transmission.  But, just talking to someone in a room masked or not, appears not to be a big risk for others to catch the virus since the viral loads in these droplets and aerosols are pretty low.  This does *not* account for people coughing or sneezing where viral loads are very high.

So how should this apply to the issue of masks. I offer this:

#) If everyone wears some kind of mask, it WILL decrease the frequency of spreading the disease by keeping asymptomatic infected people from having a way to easily transmit it.

#) Wearing a mask to protect yourself from the disease offers very little protection unless it's a surgical or N95 (or higher grade) mask.  BUT, it does still offer SOME protection, even if it's made out of cloth.  

#) Masks may give people a FALSE SENSE of security, but they must be used properly to work at all.  You still need to socially distance.  Period.  Second, removing a mask properly requires you to know how to doff a mask.  In short--you never ever touch the front of the mask, only remove the mask with the ties in the back or elastics.  Never let your hand or any part of your body come in contact with the front of the mask.  That front side of the mask should always be treated as if it is teaming with germs.  Wash your hands thoroughly after any contact with your mask--do not doff your mask someplace you can't immediately disinfect.

#) YOU should not be using a surgical mask or N95 mask if possible--right now tons of healthcare providers NEED these.  If you wish to donate yours (which is the correct answer right now), our hospital will take those donations at  Any amount helps preserve our PPE supplies and helps us fight the disease while you stay home.

#) The fear that there is tons of coronavirus in the air is FALSE.  The study from the NEJM (which I've previously nitpicked about its artificiality in a room with no air turnover) does not fly in real life.  Studies done on real patients with COVID show very low infectivity with simple talking in the same room.  This should mean that you're safe walking about a store for short periods of time, and there's NOT a ton of virus to be found in the air in real life.  But run from anyone who sneezes or coughs ;). 

#) If you are ill with anything these days, start wearing a mask if you can tolerate it to decrease your spread to others, and STAY AT HOME.  Ideally 10 days following your last fever without the use of anti-fever medications like acetaminophen (Tylenol).

#) Better yet, just stay home except for necessities or to get some outdoor exercise. And WASH YOUR HANDS!!!  ALL THE TIME!!

Our lost chances for taking action:
Here's another excellent report on how we lost our chance to take action.  The White House was completely inept at personalizing the threat and doing something about it.  

What we need to do now to prepare for the next round
We can't stay locked up forever and neither can we afford to reach herd immunity.  So how do we snake our way from being immobile to getting somewhere where we can manage the outbreak until a vaccine appears?  You know that as soon as we go back to work once case numbers go down there will be another outbreak.  We can't get away with it as long as there are a vulnerable population and viruses lingering.  The CDC has to get out of their asses, come up with a plan to deal with spot outbreaks, and be given a blank check to do what it takes.

I am hearing that the CDC is testing antibody tests.

Updates from Jason Persoff 
Several developments that may be of concern...

#) First off, the connection to NSAIDs and worsening of disease was incorrect.  It was a ramped up rumor mill not connected to any science, but attributed to the WHO.  The WHO has no concerns about NSAIDs, so use them as before.

#) The connections with ACE inhibitors and ARBs is still not clear.  Jury's out.  However, that's not likely a connection, more of a theoretical risk.

#) We have been seeing younger people coming in and ending up on the ventilator rapidly.  We're talking late teens/early 20s.  This is puzzling given the Chinese data, and worrisome to me.  Sure, these could be just a couple of aberrant cases, but I also heard Children's Hospital has a couple of kids on ventilators there too.  So, while kids, teens, and young adults largely do well, that doesn't mean you should discount the possibility of these age groups getting very sick, very rapidly.

I'm attaching an internal document on the science of NSAIDs and ACEI/ARBs below from one helluva smart pharmacist of ours if you want the details.  More to follow....

Clinical Pearl - Ibuprofen, ACEi, ARBs, and Steroids in the midst of COVID-19

By Kyle Molina, PharmD

In regard to NSAIDs, specifically ibuprofen, there is a report that went viral online yesterday (3/18) that World Health Organization (WHO) is recommending against use the use of ibuprofen for patients with COVID-19. Initially, there was no mention of this on the WHO website or within their media releases. This claim was from external media websites and, stems from the minster of WHO, not a formal recommendation by the WHO1. The WHO minister reportedly made the claim on twitter over the weekend, as mentioned in forwarded BMJ article, based on reports of 4 young healthy French patients who had taken ibuprofen and progressed severe disease. It is important to note that although this is a BMJ article, it is a new piece which has not undergone peer review, and there are calls for retraction of the piece based on the sources of these claims. The reported incidents are attributed to an uncited infectious diseases doctor in the South of France, which per BBC reporting yesterday morning is a social media hoax.2 There is apparently a similar claim floating around on Whatsapp and twitter originating from Ireland which cite similar story, however, the Infectious Diseases Society of Ireland has confirmed that the doctor cited in this claim is not even a real person. The other claim, has been that NSAIDS have previously been shown to exacerbate viral illnesses (most people have been citing the link between NSAID use and severe cutaneous varicella complications). It is not clear to me we can extrapolate this to cutaneous varicella to COVID-19 infection. The final line of arguement, stems from a lancet publication3 examining the link of ACE expression in the role of COVID infection, and cites animal evidence that ibuprofen increase ACE expression – I address the ACE theories below. The Europeans Medicine Agency released guidance yesterday saying there is a lack of a scientific link between ibuprofen use and COVID at this time.4 In addition, WHO has provided explicit clarification that they ARE NOT recommending against the use of ibuprofen – this was posted on their official twitter this morning and represents the WHO’s first official communication on the issue.5

With respect to ACE/ARBs, given that ACE appears to be a critical site for SARS-COV entry, many are speculating on the role of the enzyme in COVID pathogenesis.  Early COVID studies showed a significant number of deaths occurred in those with hypertension, coronary heart disease, and diabetes, disease states associated with higher circulating levels of ACE and frequently an indication for ACE inhibitor or ARB. However, upon multivariate analysis of risk factors associated with in-hospital death from China, hypertension, diabetes, and coronary heart disease did not maintain their univariate association and may be just markers for advance age. Advanced age was a risk factor for in-hospital mortality (OR 1.1; 95% CI 1.03-1.17, P=0.0043) in multivariate analysis.6 ACE inhibitors are not known to prevent transmission or viral replication and may or may not bind the same epitope as SARS-COV-2 does for entry. It is unlikely that these agents prevents transmission via direct inhibition of the enzyme given these agents have not been identified in high throughput screens of related SARS-CoV previously. Another argument being made is that RAAS inhibition, ibuprofen, and TZDs may cause upregulation of circulating ACE, causing patients to be more susceptible to infection or more severe disease. Lines of evidence suggested include that Italians in general use ACEs, whereas South Koreans tend to use other antihypertensive medications, and this may relate to the difference in mortality rates seen between countries. I think we need to be skeptical as there are national differences in age, percentage of smokers, likely comorbidities. In addition, early infection prevention approaches differed significantly between the two countries, and I think we have all read about the burden on the Italian healthcare system this week. There are additionally conflicting animal models with previous SARS infections. The aforementioned Lancet article additionally proposes genetic differences between the ACE polymorphisms which might have a role, but it’s unclear at this time. The American Heart Association, the Heart Failure Society of America, and the American College of Cardiology issued a statement yesterday recommending “continuation of RAAS antagonists for those patients who are currently prescribed such agents for indications for which these agents are known to be beneficial, such as heart failure, hypertension, or ischemic heart disease”.7 With that said, Anthony Fauci, the Director of National Institutes of Allergy and Infectious Diseases, did say yesterday in an interview with JAMA that he found these theories at least biologically plausible and should be investigated in studies before we make any changes in the use of these agents.8 There is not currently enough information to change practice, and we have no information whether modifying these drug regimens will do more harm than good.

Steroids have been an additional subject of discussion this week. A study published in JAMA last week indicated that use of methylprednisolone resulted in lower likelihood of death among those who developed ARDS.8 Notably, this was an unadjusted analysis and not the intent of the study, thus is subject to significant confounding. However, there is other RCT level evidence patients with moderate-to-severe ARDS benefit from early dexamethasone administration, therefore it is at least plausibly beneficial for our sickest patients with COVID and ARDS.9 The concern with routine use of corticosteroids in those with COVID is that steroids may diminish humoral immunity and allow for more rapid viral replication, prolonged viral shedding, as seen in some studies of other respiratory viruses including influenza and respiratory syncytial virus.10,11  In contrast, corticosteroids are likely still beneficial among COVID patients with a compelling indication (e.g., asthma, COPD, septic shock, likely ARDS). The risks and benefits of corticosteroids should be carefully weighed for each patient.

This is all to say we have extremely limited data to suggest we need to change our current practices with use of these medication. In this present time, be very cautious and skeptical of information being reported as it is susceptible to false claims or based on limited evidence. Please critically evaluate recommendations for data support and authenticity.

I’ll provide updates if any of this information changes and if you have any questions please let me know.

9. Wu C, et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. Published online March 13, 2020. doi:10.1001/jamainternmed.2020.0994

10. Villar et al. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Resp Medicine.

11. Nelson L , et al . Viral Loads and Duration of Viral Shedding in Adult Patients Hospitalized with Influenza, The Journal of Infectious Diseases, Volume 200, Issue 4, 1 August 2009, Pages 492–500,

12. Moreno G, et al. Corticosteroid treatment in critically ill patients with severe influenza pneumonia: a propensity score matching study. Intensive Care Med 44, 1470–1482 (2018).  

A whole suite of websites brings the grim realizations to us.
The latest site shows in stark terms when each state will go through its own surge and how unprepared they will be.  Oklahoma looks to be short 200 ICU rooms.

Epidemiologists are the experts in a new spotlight.
We've had epidemiologists who've thwarted other outbreaks come out to give us a picture of what's coming.

Our lost chances of taking action:
This article shows how Asian countries learned how to respond to a new outbreak when SARS erupted onto the scene in 2003.