Coronavirus

[Cosmacelf]

Another data point. Basically, all major ski resorts are closing. My guess this is due to corporate concerns about legal liability, nonetheless it is happening. In Canada too. I was only able to find two ski hills in Canada (none in the US) that are staying open this week. I am left wondering if golf courses are going to follow.

 

[bkp_duke]

Two points:
Guam has a large economy due to tourism as well. It's not just DOD.
Bahamas and Bermuda: 0 cases to date (last I looked)...hhmm probably the smart gov't right? No it was shutting down and Isolating the countries further than they are (which I'll buy was a smart move, one which the libs will say the President should have done, but then had he done it they would have gone high and right critical and probably died of a stroke).
Dzm

You are comparing . . . tomatoes to . . . Teslas.

Shutting down the border of a country the size of a small island is relatively easy. Closing the border for the USA . . . not so much.

 

[KSilver2000]

 

[Lessmog]

College wrestling championships were held over the weekend.

From the Washington Post:
https://www.washingtonpost.com/spor...-than-fear-college-wrestling-tournament-went/
https://www.washingtonpost.com/spor...-than-fear-college-wrestling-tournament-went/

At the bottom of the article, the Liberty University Coach is quoted as saying the virus (or the ‘scare’, not clear which) was created to impeach the President.

I went to the Liberty University web site. They celebrate their showing at the wrestling championship. The web site shares that classes are open as usual. They mention the 100.4 degree fever mentioned in the article.

Wrestlers with a temperature above 100.4 were to be disqualified, but no temperatures were taken at the event.

Also, wrestlers were not allowed to use the competition mats to reduce the risk of infection, so all competitors shared a single practice mat.

The organizers stressed faith over fear, and the use of common sense.

I gave this a Funny icon, because what else is there? Can't find the Weep.
Liberty U must be fudamentally science based, right? /s

 

[upkerry14]

In the Fire Dept they're making us mask and suit up like that doctor pictured above, having the pt sit on the front steps if possible, only one medic out of the four of us approaches the pt and NO ONE getting involved with ANY hands on pt care except the primary medic unless necassry. It's like something out of The Hot Zone. It takes 30 minutes to run a simple flu-like symptoms call.

 

[GaryW]

Two points:
Guam has a large economy due to tourism as well. It's not just DOD.
Bahamas and Bermuda: 0 cases to date (last I looked)...hhmm probably the smart gov't right? No it was shutting down and Isolating the countries further than they are (which I'll buy was a smart move, one which the libs will say the President should have done, but then had he done it they would have gone high and right critical and probably died of a stroke).
Dzm

I’m wondering if we can limit the trash talking?

Aren’t there a number of web sites where you can talk about ‘libs’ to your hearts content?

edit: typo

 

[sparcs]

You are comparing . . . tomatoes to . . . Teslas.

Shutting down the border of a country the size of a small island is relatively easy. Closing the border for the USA . . . not so much.

Especially when you have many Americans who likely are stuck waiting for flights in a foreign country and want to come home.

 

[Sean Wagner]

According to an article in the NYT [Kindle edition], massive testing capacities will be rolled out this week in the US.

From memory [!], 2000 private labs with automated analysis.

If this has been posted already, please indulge me - I think this is highly significant.

 

[Cherry Wine]

Thanks for that. I was following discussions I had read elsewhere. FWIW, I trust myself on things epidemiological, specifically including morbidity/mortality, and generally think I do well when considering analogies. However, my treatment comments are obviously derivative and I should not have made them.

BTW, it is also true that some of the more recent developments, Netherlands and France as examples, appear to have significant deviations in typical morbidity patterns. Both seem possibly to have significant COVID-19 cases outside of the typical risk grouping. Thus far I have seen no data, just anecdotes, so it enough to make me thirst for data. We do know that the Brazilian man (who was infected when he travelled with Bolsonaro and met Trump etc) was early 40's in good health but had traveled to Lombardy the prior week. It does seem that commencing with the Lombardy cases many victims were atypical. If such events become patterns all the past historical expectations might be erroneous.

One major caution suggesting atypical character is the presence of numerous cases that have had apparent recovery followed by rapid decline and sometimes death. The first such case of which i read was that of a 29 year-old MD from Wuhan, otherwise healthy, who had been treating cases and was herself seemingly recovered, tested negative twice then suddenly relapsed and died. It is entirely possible that the testing has been deficient. It is also seemingly logical to assume that the scarring and other pulmonary damage might enable the virus to escape detection in small concentrations.

The very proof of risk is that we still have no definitive was to understand any of the core recognition, diagnosis nor treatment methods. Without those we can be sure that prevention (e.g. vaccines) will be more than a year away. Even then every flu vaccine is a bet on an unknown evolution of viruses. We all want a panacea.

How I long for the time a couple of months ago when I could wander carelessly in my Tesla.

Your post underscores for me the importance of buying time through containment / mitigation not only for health care saturation, but for research. There are troubling anecdotes that are difficult to interpret - are they outliers (likely), or warning signs? We need more data, and therefore more time.

Longing for better days indeed.

 

[Cosmacelf]

Especially when you have many Americans who likely are stuck waiting for flights in a foreign country and want to come home.

I believe the travel restrictions for coming back to the US don’t apply to American citizens and green card holders.

 

[MXLRplus]

One of my employees arrived back from a C19 area. We are going to pay him 2 weeks pay to stay home.

 

[adiggs]

According to an article in the NYT [Kindle edition], massive testing capacities will be rolled out this week in the US.

From memory [!], 2000 private labs with automated analysis.

If this has been posted already, please indulge me - I think this is highly significant.

This is indeed good news. My take though is that we've been hearing about how testing will expand dramatically in the US for more than a week, with no actual meaningful change in the scale of testing.]

So I do keep an eye on what's being said, but I view it as aspirational until it's followed up with actual changes in the scale of available testing.

 

[skivi]

Switzerland has now a complete lock down till 19th of april 2020.

Edit: Not complete lock down like Iataly but maybe to 90 %. So supermarket, gas station, pharmacie, banks and offices stay open.

I hope that works to flatten the curve.

 

[dfwatt]

And yet another article that circles back to the UNPUBLISHED Chinese data.

I'll get behind this if/when the Chinese publish their data AND do follow up studies.

The longer they don't publish it, the more skeptical we all should become. And it is notable that no one else has published in vivo (i.e. patient data) for Chloroquine use with COVID-19. That sets off an alarm bell there for me.

Hi BKP

Not sure if you've seen this but this Lancet piece is a compelling read. Parenthetically it's nice to see the Journals step up and make recent publications on Covid 19 public domain.

Here's my take on this - And of course one has to confess up front that at the beginning of any scientific puzzle what you know by definition is way less than what you don't. I think the central scientific puzzle and certainly one with the greatest clinical value is the mortality puzzle – what characterizes the highly vulnerable to those fatal outcomes. Of course everyone has jumped on the age factor, but the question is what does that mean? You may disagree with my assessment of this admittedly incomplete picture, but of course a spirited and respectful scientific debate can never be a bad thing. And preliminary hypotheses of course are always valuable because they can be falsified and then you can move on to better ideas.

I might tentatively hypothesize that the increased mortality in older groups is another finding related to the work on "inflammaging". This concept has been around for decades (and shows decisive relevance in relationship to Alzheimer's disease in my professional opinion) but in a nutshell it attempts to articulate an age-related tilt in the immune system in which upregulated and even disinhibited innate immunity Is a partial but ultimately unsuccessful compensation for declining adaptive immunity. And I believe it puts the lie to simpleminded notions about inflammation as a unidimensional volume control. It's highly differential and multicomponent, and it looks like in the patients with poorer outcomes there may be a stronger and disinhibited innate immunity response, one that's not only unsuccessful in containing the virus but that may create sepsis and organ failure. The data set in the Lancet piece of course is not conclusive for that because the only cytokine that they indexed is IL-6 which of course is one of the most important ones but they're at least another six or seven that they could've looked at. Of course this exaggerated innate immune response may emerge from greater penetration of the virus into lung and cardiac tissue (which might index another currently completely unknown vulnerability factor possibly even genotypic), and cardiac tissue looks increasingly like it's a target along with vascular tissue, as the biomarkers in the graphic below including not just troponins but also D-dimer might indicate. Intriguingly, the failing patients do not activate lymphocyte production to nearly the same degree and unfortunately they did not index B cell versus T-cell but in any case both are more involved in adaptive immunity than innate immunity. In any case and this part of course is not surprising, the poorer outcomes had sepsis and organ failure in a much higher percentage. A really tempting hypothesis is that the patients with fatal outcomes failed to mount an effective antibody response as their immune systems ramped up to the pathogen, while those with better outcomes gradually achieved increasing and viable adaptive immune resistance. In other words, patients with poor outcomes may be stuck in mostly in innate immunity response with increased damage to bystander tissues, steadily escalating pro-inflammatory cytokines and eventual sepsis, but of course this is just a speculation at this point without adequate date.

Here's the text from the article Discussion Section that's also quite informative in this regard:

"This retrospective cohort study identified several risk factors for death in adults in Wuhan who were hospitalised with COVID-19. In particular, older age, d-dimer levels greater than 1 μg/mL, and higher SOFA score on admission were associated with higher odds of in-hospital death. Additionally, elevated levels of blood IL-6, high-sensitivity cardiac troponin I, and lactate dehydrogenase and lymphopenia were more commonly seen in severe COVID-19 illness. Sustained viral detection in throat samples was observed in both survivors and non-survivors. Previously, older age has been reported as an important independent predictor of mortality in SARS and MERS.

The current study confirmed that increased age was associated with death in patients with COVID-19. Previous studies in macaques inoculated with SARS-CoV found that older macaques had stronger host innate responses to virus infection than younger adults, with an increase in differential expression of genes associated with inflammation, whereas expression of type I interferon beta was reduced. The age-dependent defects in T-cell and B-cell function and the excess production of type 2 cytokines could lead to a deficiency in control of viral replication and more prolonged proinflammatory responses, potentially leading to poor outcome.

SOFA score is a good diagnostic marker for sepsis and septic shock, and reflects the state and degree of multi-organ dysfunction. Although bacterial infections are usually regarded as a leading cause of sepsis, viral infection can also cause sepsis syndrome. Previously, we determined that sepsis occurred in nearly 40% of adults with community-acquired pneumonia due to viral infection. In the current study, we found that more than half of patients developed sepsis. Additionally, we found that more than 70% of patients had white blood cell count below 10·0 × 109 per L or procalcitonin below 0·25 ng/mL, and no bacterial pathogens were detected in these patients on admission. Sepsis was a common complication, which might be directly caused by SARS-CoV-2 infection, but further research is needed to investigate the pathogenesis of sepsis in COVID-19 illness. Cardiac complications, including new or worsening heart failure, new or worsening arrhythmia, or myocardial infarction are common in patients with pneumonia. Cardiac arrest occurs in about 3% of inpatients with pneumonia. Risk factors of cardiac events after pneumonia include older age, pre-existing cardiovascular diseases, and greater severity of pneumonia at presentation. Coronary heart disease has also been found to be associated with acute cardiac events and poor outcomes in influenza and other respiratory viral infections.

In this study, increased high-sensitivity cardiac troponin I during hospitalisation was found in more than half of those who died. The first autopsy of a 53-year-old woman with chronic renal failure in Jinyintan Hospital showed acute myocardial infarction (data not published; personal communication with a pathologist from the Chinese Academy of Science). About 90% of inpatients with pneumonia had increased coagulation activity, marked by increased d-dimer concentrations. In this study, we found d-dimer greater than 1 μg/mL is associated with fatal outcome of COVID-19. High levels of d-dimer have a reported association with 28-day mortality in patients with infection or sepsis identified in the emergency department. Contributory mechanisms include systemic pro-inflammatory cytokine responses that are mediators of atherosclerosis directly contributing to plaque rupture through local inflammation, induction of procoagulant factors, and haemodynamic changes, which predispose to ischaemia and thrombosis.

In addition, angiotensin converting enzyme 2, the receptor for SARS-CoV-2, is expressed on myocytes and vascular endothelial cells so there is at least theoretical potential possibility of direct cardiac involvement by the virus. Of note, interstitial mononuclear inflammatory infiltrates in heart tissue has been documented in fatal cases of COVID-19, although viral detection studies were not reported."

What do you think? Sorry for the long post!

 

[Cherry Wine]

Spanish flu - Wikipedia
-----------------------
The second wave of the 1918 pandemic was much deadlier than the first. The first wave had resembled typical flu epidemics; those most at risk were the sick and elderly, while younger, healthier people recovered easily. By August, when the second wave began in France, Sierra Leone, and the United States,[92] the virus had mutated to a much deadlier form. October 1918 was the deadliest month of the whole pandemic.[93]

This increased severity has been attributed to the circumstances of the First World War.[94] In civilian life, natural selection favors a mild strain. Those who get very ill stay home, and those mildly ill continue with their lives, preferentially spreading the mild strain. In the trenches, natural selection was reversed. Soldiers with a mild strain stayed where they were, while the severely ill were sent on crowded trains to crowded field hospitals, spreading the deadlier virus. The second wave began, and the flu quickly spread around the world again. Consequently, during modern pandemics, health officials pay attention when the virus reaches places with social upheaval (looking for deadlier strains of the virus).[95]
-----------------------

In normal circumstances, "flus" get milder with time, not more severe. World War I unintentionally inverted the selective factors.

Regardless, the more time that passes, the further along antiviral development, vaccine development, and hospital preparation will be. You do not want to be among those who get it in the near term when the risk of hospital overload is highest and the available treatments are limited.

Thank you. The speculation around a "second, deadlier wave" comes up so often that I really want to delve into some literature on the issue. From a layman's perspective, I don't understand why it should be considered a given, or even likely, for a virus to temporarily recede within the population only to return in a more virulent form.

 

[bkp_duke]

Hi BKP

Not sure if you've seen this but this Lancet piece is a compelling read. Parenthetically it's nice to see the Journals step up and make recent publications on Covid 19 public domain.

Here's my take on this - And of course one has to confess up front that at the beginning of any scientific puzzle what you know by definition is way less than what you don't. I think the central scientific puzzle and certainly one with the greatest clinical value is the mortality puzzle – what characterizes the highly vulnerable to those fatal outcomes. Of course everyone has jumped on the age factor, but the question is what does that mean? You may disagree with my assessment of this admittedly incomplete picture, but of course a spirited and respectful scientific debate can never be a bad thing. And preliminary hypotheses of course are always valuable because they can be falsified and then you can move on to better ideas.

I might tentatively hypothesize that the increased mortality in older groups is another finding related to the work on "inflammaging". This concept has been around for decades (and shows decisive relevance in relationship to Alzheimer's disease in my professional opinion) but in a nutshell it attempts to articulate an age-related tilt in the immune system in which upregulated and even disinhibited innate immunity Is a partial but ultimately unsuccessful compensation for declining adaptive immunity. And I believe it puts the lie to simpleminded notions about inflammation as a unidimensional volume control. It's highly differential and multicomponent, and it looks like in the patients with poorer outcomes there may be a stronger and disinhibited innate immunity response, one that's not only unsuccessful in containing the virus but that may create sepsis and organ failure. The data set in the Lancet piece of course is not conclusive for that because the only cytokine that they indexed is IL-6 which of course is one of the most important ones but they're at least another six or seven that they could've looked at. Of course this exaggerated innate immune response may emerge from greater penetration of the virus into lung and cardiac tissue (which might index another currently completely unknown vulnerability factor possibly even genotypic), and cardiac tissue looks increasingly like it's a target along with vascular tissue, as the biomarkers in the graphic below including not just troponins but also D-dimer might indicate. Intriguingly, the failing patients do not activate lymphocyte production to nearly the same degree and unfortunately they did not index B cell versus T-cell but in any case both are more involved in adaptive immunity than innate immunity. In any case and this part of course is not surprising, the poorer outcomes had sepsis and organ failure in a much higher percentage. A really tempting hypothesis is that the patients with fatal outcomes failed to mount an effective antibody response as their immune systems ramped up to the pathogen, while those with better outcomes gradually achieved increasing and viable adaptive immune resistance. In other words, patients with poor outcomes may be stuck in mostly in innate immunity response with increased damage to bystander tissues, steadily escalating pro-inflammatory cytokines and eventual sepsis, but of course this is just a speculation at this point without adequate date.

View attachment 522382

Here's the text from the article Discussion Section that's also quite informative in this regard:

"This retrospective cohort study identified several risk factors for death in adults in Wuhan who were hospitalised with COVID-19. In particular, older age, d-dimer levels greater than 1 μg/mL, and higher SOFA score on admission were associated with higher odds of in-hospital death. Additionally, elevated levels of blood IL-6, high-sensitivity cardiac troponin I, and lactate dehydrogenase and lymphopenia were more commonly seen in severe COVID-19 illness. Sustained viral detection in throat samples was observed in both survivors and non-survivors. Previously, older age has been reported as an important independent predictor of mortality in SARS and MERS.

The current study confirmed that increased age was associated with death in patients with COVID-19. Previous studies in macaques inoculated with SARS-CoV found that older macaques had stronger host innate responses to virus infection than younger adults, with an increase in differential expression of genes associated with inflammation, whereas expression of type I interferon beta was reduced.
The age-dependent defects in T-cell and B-cell function and the excess production of type 2 cytokines could lead to a deficiency in control of viral replication and more prolonged proinflammatory responses, potentially leading to poor outcome.

SOFA score is a good diagnostic marker for sepsis and septic shock, and reflects the state and degree of multi-organ dysfunction. Although bacterial infections are usually regarded as a leading cause of sepsis, viral infection can also cause sepsis syndrome. Previously, we determined that sepsis occurred in nearly 40% of adults with community-acquired pneumonia due to viral infection. In the current study, we found that more than half of patients developed sepsis. Additionally, we found that more than 70% of patients had white blood cell count below 10·0 × 109 per L or procalcitonin below 0·25 ng/mL, and no bacterial pathogens were detected in these patients on admission. Sepsis was a common complication, which might be directly caused by SARS-CoV-2 infection, but further research is needed to investigate the pathogenesis of sepsis in COVID-19 illness. Cardiac complications, including new or worsening heart failure, new or worsening arrhythmia, or myocardial infarction are common in patients with pneumonia. Cardiac arrest occurs in about 3% of inpatients with pneumonia. Risk factors of cardiac events after pneumonia include older age, pre-existing cardiovascular diseases, and greater severity of pneumonia at presentation. Coronary heart disease has also been found to be associated with acute cardiac events and poor outcomes in influenza and other respiratory viral infections.

In this study, increased high-sensitivity cardiac troponin I during hospitalisation was found in more than half of those who died. The first autopsy of a 53-year-old woman with chronic renal failure in Jinyintan Hospital showed acute myocardial infarction (data not published; personal communication with a pathologist from the Chinese Academy of Science). About 90% of inpatients with pneumonia had increased coagulation activity, marked by increased d-dimer concentrations. In this study, we found d-dimer greater than 1 μg/mL is associated with fatal outcome of COVID-19. High levels of d-dimer have a reported association with 28-day mortality in patients with infection or sepsis identified in the emergency department. Contributory mechanisms include systemic pro-inflammatory cytokine responses that are mediators of atherosclerosis directly contributing to plaque rupture through local inflammation, induction of procoagulant factors, and haemodynamic changes, which predispose to ischaemia and thrombosis.

In addition, angiotensin converting enzyme 2, the receptor for SARS-CoV-2, is expressed on myocytes and vascular endothelial cells
so there is at least theoretical potential possibility of direct cardiac involvement by the virus. Of note, interstitial mononuclear inflammatory infiltrates in heart tissue has been documented in fatal cases of COVID-19, although viral detection studies were not reported."

What do you think? Sorry for the long post!

Reading now. One thing - the number of patients in the retrospective analysis is 191. I would have liked to have seen a much larger number given how many were hospitalized in Wuhan in the time frame.


EDIT - ok, done.

I concur with the conclusion of the authors:
"Older age, elevated d-dimer levels, and high SOFA score could help clinicians to identify at an early stage those patients with COVID-19 who have poor prognosis."

This study helps identify lab variables, and age, (i.e. prognostic indicators) upon hospital admission which can help clinicians clue in to which patients are the sickest and need the closest monitoring and greatest intervention.

EDIT 2 - the results, unfortunately, don't give us any therapeutic intervention data which might guide treatment to reduce morbidity and mortality. But this early in the pandemic I did not expect to really see that data yet. It will come and the number of cases climbs and different interventions are tried.

 

[Cherry Wine]

Coronavirus vaccine test opens as US volunteer gets 1st shot

SEATTLE (AP) — U.S. researchers gave the first shot to the first person in a test of an experimental coronavirus vaccine Monday -- leading off a worldwide hunt for protection even as the pandemic surges.

With a careful jab in a healthy volunteer’s arm, scientists at the Kaiser Permanente Washington Research Institute in Seattle begin an anxiously awaited first-stage study of a potential COVID-19 vaccine developed in record time after the new virus exploded from China and fanned across the globe.

“We’re team coronavirus now,” Kaiser Permanente study leader Dr. Lisa Jackson said on the eve of the experiment. “Everyone wants to do what they can in this emergency.”

The Associated Press observed as the study’s first participant, an operations manager at a small tech company, received the injection inside an exam room. Several others were next in line for a test that will ultimately give 45 volunteers two doses, a month apart.

 

[dfwatt]

It's a bad flu. Old and imunosuppressed people are at high risk.

See my previous posts on this. From a scientific standpoint your statement is wrong, or at least it is so misleading as to be virtually wrong. Older people are not necessarily immunosuppressed. It's not that simple. That's a simpleminded and therefore appealing but ultimately misleading concept.

 

[nwdiver]

It's a bad flu.

It's ~20x more lethal, more contagious, no one has immunity, there's no vaccine and anti-virals don't work. That's far more than just a 'bad flu'.

The only 'saving grace' is people under 20 appear to be ~immune but the lethality doubles for every 10 years of age up to >10% for anyone >70.

 

[SageBrush]

I woke up thinking about vaccination and the US. If the country's public health officials (not the trump sociopath) come to the conclusion that Asian approaches to controlling the epidemic are not possible/effective here due to population behavior/other political choices; and a boutique vaccine is too far away to matter in the next 6 months, then it is not unreasonable in my opinion to consider an attenuated virus vaccine for the 20 - 60 year demographic. It may well be the quickest route to herd immunity with the least morbidity/mortality.

Just a thought, but it sure has historical precedence and support.