Just curious, anyone have a plan, or preps for global pandemic?

[Sibiriak]

6 hours ago, macaroni said:

...there is nothing logical about deducing causation from correlation.

Yes,  probabilistic statistical inference is different than strict logical deduction.     Cf.Italy's death toll could be 60% higher than assumed

 

[Gordo]

Georgia just hit 40% unemployment: Reopening reality check: Georgia's jobs aren’t flooding back

[mccoy]

14 hours ago, macaroni said:

Allow me to point out that there is nothing logical about deducing causation from correlation.

Macaroni, I beg to differ. In an environment you know, take the savannah, you see heavily tramped soil and underbrush and broken trees. My mind associates the scenario to elephants having been there. The association is one with very high probability of being real, so the jump to causation is very much justified. That's inferential logic at work. Otherwise I'll have to think about other possible causes, and assign probabilities to them. I'd say the aliens having tramped the underbrush has a near-zero degree of occurrence. 

To get back to our case, if we see a very higher than average mortality during an epidemics, the association suggests the causation with a very high degree of probability. No one raised alternative causes, like a mass intoxication. 

So, in some outbreak places like Italy, there are huge mortality excesses, especially among the elders. This all very much fits into the effects of the Covid-19. No one is suggesting logical, alternative causes of death, there have been no disasters, no mass deaths, nothing but SARS-COV2 can be associated to such spike in all cause mortality.

The bottom line here is that associating SARSCOV2 to such a spike in all-cause mortality is very legitimate from the logical and scientific standpoint.

Furthermore, it has been observed that the official Covid-19 death counts did not allow for all that mortality. Again, the logical inference here is that there has been a significant underestimation in death counts from Covid-19, especially in the early stages of the epidemics. 

[Gordo]

New high in daily confirmed cases worldwide, not looking good for the Southern Hemisphere:

[Dean Pomerleau]

Another antibody study has just been released, this one from the UK. It found that among 1000 randomly sampled adults from across the UK, 5% of them had antibodies to the virus. The number in London was 17%.

Going through the same exercise to compute infection fatality rate (IFR): The UK has a population of 67M, so 5% would mean 67M * 0.05 = 3.35M people have been infected so far. The UK has experienced 36K deaths, so 36K / 3.35M = 1.07% IFR. 

That is slightly above the IFR range from other large-scale serology studies from New York, Spain and France, which have been between 0.5 to 1.0%.

Extrapolating out to herd immunity levels of infection (optimistically 65%), that would equate to 67M * 0.65 * 0.01 = 435K deaths in the UK.

--Dean

[Dean Pomerleau]

A new study [1] out today in The Lancet looked at 14K hospitalized covid-19 patients from 671 hospitals on six continents who were treated with hydroxychloroquine or chloroquine either with or without a macrolide antibiotic (e.g. azithromyacin) and compared them against 81K control patients given standard care. 

After controlling for potential confounders, including disease severity at time of hospitalization, they found that the different drug combinations all raised the risk of mortality by around 33%. The favored combination of hydroxychloroquine and macrolide was the worst of the bunch, with a 44% increase in mortality. This combination also resulted in the highest rate of new heart arrhythmias, 500% higher than in patients receiving standard care.

This pretty much puts to rest the hope that hydroxychloroquine might be an effective treatment for hospitalized patients. But it does still leave open the possibility it could be useful as a prophylactic (as Trump is hoping) or if administered earlier in the disease progression (perhaps with zinc), at least in those without risk of heart rhythm irregularities.

--Dean

---------

[1] The Lancet Published Online May 22, 2020 

https://doi.org/10.1016/ S0140-6736(20)31180-6 

Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis 

Mandeep R Mehra, Sapan S Desai, Frank Ruschitzka, Amit N Patel

Summary

Background Hydroxychloroquine or chloroquine, often in combination with a second-generation macrolide, are being

widely used for treatment of COVID-19, despite no conclusive evidence of their beneit. Although generally safe when

used for approved indications such as autoimmune disease or malaria, the safety and beneit of these treatment

regimens are poorly evaluated in COVID-19.

Methods We did a multinational registry analysis of the use of hydroxychloroquine or chloroquine with or without a

macrolide for treatment of COVID-19. The registry comprised data from 671 hospitals in six continents. We included

patients hospitalised between Dec 20, 2019, and April 14, 2020, with a positive laboratory inding for SARS-CoV-2.

Patients who received one of the treatments of interest within 48 h of diagnosis were included in one of four treatment

groups (chloroquine alone, chloroquine with a macrolide, hydroxychloroquine alone, or hydroxychloroquine with a

macrolide), and patients who received none of these treatments formed the control group. Patients for whom one of

the treatments of interest was initiated more than 48 h after diagnosis or while they were on mechanical ventilation,

as well as patients who received remdesivir, were excluded. The main outcomes of interest were in-hospital mortality

and the occurrence of de-novo ventricular arrhythmias (non-sustained or sustained ventricular tachycardia or

ventricular ibrillation).

Findings 96 032 patients (mean age 53·8 years, 46·3% women) with COVID-19 were hospitalised during the study

period and met the inclusion criteria. Of these, 14 888 patients were in the treatment groups (1868 received

chloroquine, 3783 received chloroquine with a macrolide, 3016 received hydroxychloroquine, and 6221 received

hydroxychloroquine with a macrolide) and 81144 patients were in the control group. 10698 (11·1%) patients died in

hospital. After controlling for multiple confounding factors (age, sex, race or ethnicity, body-mass index, underlying

cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition,

and baseline disease severity), when compared with mortality in the control group (9·3%), hydroxychloroquine

(18·0%; hazard ratio 1·335, 95% CI 1·223–1·457), hydroxychloroquine with a macrolide (23·8%; 1·447, 1·368–1·531),

chloroquine (16·4%; 1·365, 1·218–1·531), and chloroquine with a macrolide (22·2%; 1·368, 1·273–1·469) were each

independently associated with an increased risk of in-hospital mortality. Compared with the control group (0·3%),

hydroxychloroquine (6·1%; 2·369, 1·935–2·900), hydroxychloroquine with a macrolide (8·1%; 5·106, 4·106–5·983),

chloroquine (4·3%; 3·561, 2·760–4·596), and chloroquine with a macrolide (6·5%; 4·011, 3·344–4·812) were

independently associated with an increased risk of de-novo ventricular arrhythmia during hospitalisation.

Interpretation We were unable to conirm a beneit of hydroxychloroquine or chloroquine, when used alone or with

a macrolide, on in-hospital outcomes for COVID-19. Each of these drug regimens was associated with decreased

in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19.

 

[Gordo]

Always hard to tell what is going on in China but it seems things are flaring up there again and there is a weird new monetary incentive for quarantines:

 

In the meantime in the US it seems the white collar job cuts are really gaining traction with IBM announcing deep cuts today (they didn't say exactly how many but 1000's expected).

[Matt]

1 hour ago, Dean Pomerleau said:

Another antibody study has just been released, this one from the UK. It found that among 1000 randomly sampled adults from across the UK, 5% of them had antibodies to the virus. The number in London was 17%.

Going through the same exercise to compute infection fatality rate (IFR): The UK has a population of 67M, so 5% would mean 67M * 0.05 = 3.35M people have been infected so far. The UK has experienced 36K deaths, so 36K / 3.35M = 1.07% IFR. 

That is slightly above the IFR range from other large-scale serology studies from New York, Spain and France, which have been between 0.5 to 1.0%.

Extrapolating out to herd immunity levels of infection (optimistically 65%), that would equate to 67M * 0.65 * 0.01 = 435K deaths in the UK.

--Dean

1.45% IFR outside of London.

This is with the shielding of over 2 million high risk people who are advised to not leave the house for 12 weeks.

This is also without NHS hospitals being overwhelmed.

435K deaths is also close to what the government estimated if the infection wasn't controlled with these measures put in place.

 

[Sibiriak]

On 5/19/2020 at 2:31 AM, TomBAvoider said:

For most of my life, I've had mild thrombocytopenia - the lower level of the platelet count for normal is 150,000, and I often had in the range of 130K - 140K, although the lowest was when I was fasting for 8 days, and it was 94K. But often I'm at the lower end of normal, f.ex. this year (a week ago), I had exactly 150K, and one year I had 175K. So basically, very mild thrombocytopenia - I have never experienced any negative symptoms, bleeding and the like.

Since your platelet count is basically within normal range (150-175K is NOT thrombocytopenia), or very close, stable, most likely congenital,  and not the result of any underlying pathology,   I can't imagine you having any major  concerns.    "Patients rarely spontaneously bleed with platelet counts greater than 10,000."

Quote

So, it occured to me, that if my blood is less prone to coagulation...

 Platelet effect on coagulation etc. is as much a matter of platelet functionality (and other complex factors),  as platelet number alone.   With your  only-very-slightly-lower-to-normal platelet count, it is unlikely you are less prone to coagulation based on that fact alone.

Quote

it transpires that having thrombocytopenia drastically escalates the odds of a severe reaction to COVID-19, and dramatically elevates (by multiple times) the odds of death:

 

From the  first study  (Lippi et al.)  you cite :

Quote

In the presence of this rapidly emerging, novel infection uncharacteristic of the era of modern medicine, identification of biomarkers that could predict disease severity and prognosis are essential to guiding clinical care. Uniquely to COVID-19, a wide range of variability in disease severity is observed ranging from asymptomatic to critical ^[2]. As such, biomarkers are needed to identify severe disease among hospitalized patients. In this study, we found that platelet count may be a simple, economic, rapid and commonly available laboratory parameter, that could straightforwardly discriminate between COVID patients with and without severe disease. Moreover, we observed that thrombocytopenia is also associated with threefold enhanced risk of severe COVID-19.

Thrombocytopenia is commonplace in critically ill patients, and usually suggests serious organ malfunction or physiologic decompensation as opposed to primary hematologic etiology, as well as the development of intravascular coagulopathy, often evolving towards disseminated intravascular coagulation (DIC) ^[20]. In COVID-19 patients, the mechanism for thrombocytopenia patients is likely multifactorial.

In SARS, it was suggested that the combination of viral infection and mechanical ventilation leads to endothelial damage triggering platelet activation, aggregation and thrombosis in the lung, causing vast platelet consumption ^[7]. Moreover, as lung may be a site of platelet release from fully mature megakaryocytes, a decrease or morphologic alternation in the pulmonary capillary bed may lead to deranged platelet defragmentation ^[7].

Coronaviruses may also directly infect bone marrow elements resulting in abnormal hematopoiesis, or trigger an auto-immune response against blood cells ^{[7], [21]}. It also has been suggested that a consistently present low grade DIC may propagate a low platelet count in SARS ^[7]

 

That quote makes it pretty clear that the issue is COVID-19 causing thrombocytopenia,    and the level of thrombocytopenia possibly serving as a biomarker for the severity of the disease.

From the second study   (Xiaobo Yang et al.):
 

Quote

The proportion of patients with thrombocytopenia was smaller than that of patients with severe acute respiratory syndrome (SARS). In patients infected by SARS‐CoV, thrombocytopenia was found in 40% to 50% patients.10-12

SARS‐CoV can induce hematopoiesis after infecting cells in bone marrow. As a coronavirus sharing 79% genomic sequence with SARS‐CoV and the same cell entry receptor of angiotensin‐converting enzyme 2,13 it is possible that SARS‐CoV‐2 may cause thrombocytopenia in a similar way.

In a study on coagulopathy associated with COVID‐19, 71.4% (15 in 21) non‐survivors met the International Society on Thrombosis and Haemostasis criteria of disseminated intravascular coagulopathy,14 which may cause increased consumption of platelets.

SARS‐CoV‐2 infects and causes diffuse alveolar damage, which entraps megakaryocytes and hinders the release of platelets from megakaryocytes.15

Again, the issue, as far as I can tell,  is  COVID-19 causing thrombocytopenia,  not pre-existing thrombocytopenia causing COVID-19 to be more severe.

Since your platelet count is very close to or in normal range, and is not reflecting any underlying pathological condition, alcohol use, drug use etc.,   I doubt very much that your  extremely- mild-to-non-existent thrombocytopenia would make you more likely to have a severe case of COVID-19  were you to contract the virus.

 

 

Edited May 22, 2020 by Sibiriak

[KHashmi316]

About the UK ....

 

[macaroni]

10 hours ago, mccoy said:

Macaroni, I beg to differ. In an environment you know, take the savannah, you see heavily tramped soil and underbrush and broken trees. My mind associates the scenario to elephants having been there. The association is one with very high probability of being real, so the jump to causation is very much justified. That's inferential logic at work. Otherwise I'll have to think about other possible causes, and assign probabilities to them. I'd say the aliens having tramped the underbrush has a near-zero degree of occurrence. 

 To get back to our case, if we see a very higher than average mortality during an epidemics, the association suggests the causation with a very high degree of probability. No one raised alternative causes, like a mass intoxication. 

So, in some outbreak places like Italy, there are huge mortality excesses, especially among the elders. This all very much fits into the effects of the Covid-19. No one is suggesting logical, alternative causes of death, there have been no disasters, no mass deaths, nothing but SARS-COV2 can be associated to such spike in all cause mortality.

The bottom line here is that associating SARSCOV2 to such a spike in all-cause mortality is very legitimate from the logical and scientific standpoint.

Furthermore, it has been observed that the official Covid-19 death counts did not allow for all that mortality. Again, the logical inference here is that there has been a significant underestimation in death counts from Covid-19, especially in the early stages of the epidemics. 

McCoy, causal inference depends on assumptions. These are necessarily judgmental. The data cannot provide nor test them. 

[mccoy]

1 hour ago, macaroni said:

McCoy, causal inference depends on assumptions. These are necessarily judgmental. The data cannot provide nor test them. 

Well, assumptions are based upon prior experience. Our very evident prior here is that there is an epidemic under way, which seems to cause serious pulmonary and CV disease in older people, often fatal. Our discrimination suggests that this is the probable cause of excess mortality observed in the outbreak places. Otherwise, what is it? 

 Bayesian inference, which is a consolidated scientific method, makes ample use of a priori experience.

Last but not least, if you follow Peter Attia, I remember him saying that a very strong association [correlation] in medical studies suggests probable causation. Hazard ratios higher than 5, for example, are interpreted as very probable causation. For example, the association between cigarette smoke and lung cancer. Is it judgmental to decide that this association implies causation as well? No one ever debates that.

[mccoy]

The Euromomo network is publishing interesting graphs based on baseline mortality models for Europe.

The theory is explained, the model is a poissonian time series where the baseline follows a sinusoidal signal and is derived from the periods *fall spring( when no excess mortality is expected. Winter displays spikes in mortality because of cold and flu, summer because of heat waves. The following is the model pooled for all age groups. The Late winter/spring peak is the larger of the peaks from 2016 to date. 

Age 5/14 years, no excess mortality visible

65/74 years, the 2020 peak overwhelms by far any other previous peaks

 

And, by the way, there is this strange association, the huge peak just overlaps with the Covid19 inception in Europe! But it is just an association, and even toddlers know that association is no causation, no, not at all! Guys, this peak may be the nazis reincarnated in aliens randomly hitting people by invisible  ionizing radiations rays, yes, the older people because nazis like eugenics.

[corybroo]

Fact checkers looked at this claim:

Mortality in the U.S. noticeably increased during the first months of 2020 compared to previous years

https://healthfeedback.org/claimreview/mortality-in-the-u-s-noticeably-increased-during-the-first-months-of-2020-compared-to-previous-years/

and found it

Misleading: The author calculated the number of deaths that occurred during a time window in 2020 that was inappropriate for assessing whether the COVID-19 epidemic impacted overall U.S. mortality (70% of the time period is prior to the onset of COVID-19).
Lacks context : The post author neglected to explain that the CDC collects and reports death count data in a manner that results in underestimates in initial reports followed by rapid increases as new data becomes available.

KEY TAKE AWAY

A comparison of the number of deaths from all causes in the U.S. during the first 17 weeks of 2020 reveals a higher mortality than for the same period in any of the previous five years. While the death count was comparable to previous years in the first two months of 2020, it increased rapidly in March and April. Comparisons of mortality are highly sensitive to how the data are gathered and presented, therefore any claims based on the data must always be presented in the appropriate context. Since its outbreak in the U.S., COVID-19 has claimed more lives than diabetes, suicide, or stroke.

[Sibiriak]

5 hours ago, macaroni said:

causal inference depends on assumptions.

Hey Macaroni,   enough of the banal generalities.   What specific assumptions do you find  problematic?

[Clinton]

well ...

at the very least macaroni is a superfood.

Edited May 23, 2020 by Clinton

[mccoy]

8 hours ago, corybroo said:

Mortality in the U.S. noticeably increased during the first months of 2020 compared to previous years

https://healthfeedback.org/claimreview/mortality-in-the-u-s-noticeably-increased-during-the-first-months-of-2020-compared-to-previous-years/

and found it

Misleading: The author calculated the number of deaths that occurred during a time window in 2020 that was inappropriate for assessing whether the COVID-19 epidemic impacted overall U.S. mortality (70% of the time period is prior to the onset of COVID-19).
Lacks context : The post author neglected to explain that the CDC collects and reports death count data in a manner that results in underestimates in initial reports followed by rapid increases as new data becomes available.

Of course, all-cause mortality data are very accurate, provided they are final, since it takes some time to collect them. In the Euromomo project, the modelers have allowed for the delay by making a correction, visible at the far right end, yellow region. It just also be said that the mortality and excess mortality data vary across counties for municipalities, where the outbreak was not serious, there are no peaks, or even negative trends.

 

[mccoy]

Always from the Euromomo site, excess mortality graphs in Europe, which are perhaps even more eloquent than the mortality graphs.

The younger age interval  (blue line in 2020) shows no peaks, rather, a negative trend in march due probably to the lockdown and lesser accident hazards

 

In this older-age interval, the blue line (2020) peaks out at about week 12, which is the beginning of March, when the outbreak started being serious in Italy. Lines of other colors are excess mortalities of previous years. We recognize the 2017 excess of early January (peaking at 1600 excess deaths) but the 2020 excess (peaking at 4000+deaths) dwarfs it.

[mccoy]

Euromomo has also a very interesting dynamic graph, which can be seen as a video clip, showing the evolution of mortality anomalies for every country as zeta scores (the higher, the higher deviation from the average).

This is week 15 2020 (darker colours are higher z-scores= higher deaths than usual)

 

[mccoy]

This is the map at week 18

Anfd this the map at week 20, present-day. For some reason, England is still under fire...

 

[mccoy]

The following graph is the result of the official data analysis of the Italian statistical agency. Those are guys who analyze and process mortality data for a living→ high reliability.

The blue bins in the histogram represent the all-cause excess deaths for males in March in northern Italy (daily deaths minus daily deaths averaged in the previous 4 years). Official Covid19 deaths are yellow bins. This shows that the official Covid19 death count underestimated, in a significant way (over 200 deaths per day at the peak) the real Covid19 deaths.

That's why I insist that the counts of Covid19 deaths are an underestimate, above all in the first period of the outbreak (afterwards, the all cause mortality and Covid19 mortality seem to converge, at least, exhibit less difference.

 

Edited May 23, 2020 by mccoy

[Mike41]

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2766121
 

posted this morning by Al Pater.

The article makes the case that we have been comparing apples 🍎 and oranges 🍊 with regard to CFR of influenza and covid 19. If the articles conclusions are at all accurate than the CFR for Covid 19 is at least 5 times the CFR of influenza.

[Gordo]

Hertz files for Chapter 11 bankruptcy protection
By the end of March, Hertz Global Holdings Inc. had racked up more than $24 billion in debt, according to the bankruptcy filing, with only $1 billion of available cash.

U.S. leveraged loan defaults at 6-year high as coronavirus hits businesses

Many people have been pinning hopes on the idea that the lockdowns will end soon (already ended in many places) and there will be a swift recovery. This is pure fantasy.  If every state opens up right now, the pain will continue and the bankruptcies are just getting started. I saw that IBM announced layoffs yesterday, I checked in with my uncle who works for them, sure enough, he was given 30 days notice this week.  White collar jobs are just starting to get hit.

Even Fauchi is getting worried:
Anthony Fauci warns of 'irreparable damage' if lockdowns are kept in place for too long

[Dean Pomerleau]

16 minutes ago, Mike41 said:

If the articles conclusions are at all accurate than the CFR for Covid 19 is at least 5 times the CFR of influenza.

I thought this was the most interesting conclusion from that paper :

The mean number of counted deaths during the peak week of influenza seasons from 2013-2020 was 752.4 (95% CI, 558.8-946.1).7 These statistics on counted deaths suggest that the number of COVID-19 deaths for the week ending April 21 was 9.5-fold to 44.1-fold greater than the peak week of counted influenza deaths during the past 7 influenza seasons in the US, with a 20.5-fold mean increase (95% CI, 16.3-27.7).

But one has to keep in mind that people are likely to be more attuned to the covid pandemic and therefore more likely to attribute the cause of death to the virus than to the flu during normal times.

--Dean 

[Sibiriak]

  Nouriel Roubini,  aka "Dr. Doom",   is always worth listening to:

Coronavirus: Leading economist warns of 10 years of depression and debt