COVID19 update, June 8, 2020: timeline pushed back to October 2019?; leaked German Interior Ministry internal report; hydroxychloroquine prophylactic use study

Just a few quick updates today, as things were busy at work.

(1) The time line for the epidemic keeps getting pushed back further? According to an ABC exclusive report , satellite imagery of parking lots of Wuhan hospitals in October 2019, compared to the same month the previous year, indicate unusual levels of activity. Moreover, internet searches on Baidu at the time supposedly had a number of queries for flu/SARS like symptoms. I am not wholly convinced, but who knows?

 

(2) An internal German report from “Referat KM4” of the BMI (Federal Interior Ministry), that was strongly critical of the “overreaction” of the German government to the pandemic, was leaked to the press. A PDF of the full text is here: (accompanying provenance info): Powerline has a summary in English. A little googling turned up an organigram in which KM4 shows up as “Schutz kritischer Infrastrukturen” (protection of critical infrastructures), one of six Referate (idiomatically: desks, sub-departments) in the department Krisenmanagement und Bevolkungsschutz (Crisis Management and Population Protection).

The report argues that mortality is a small fraction of the annual all-cause mortality in Germany [of course, this argument is open to the “well, that is so because we took action quickly” argument], and indeed, worldwide excess mortality at the time of writing (May 11) was one-sixth of that during the 2017/8 seasonal flu epidemic.

I haven’t waded through the entire report, which is nearly 100 pages long, but it is preceded by a 2-page Kurzfassung (“short version”, idiomatically “Executive Summary”). Item 3 of the Executive Summary speaks of a “Fehlalarm” (false alarm) and laments:  

The fact that the suspected false alarm remained undetected for weeks has a major reason
that the existing framework for action of the crisis unit and the
crisis management in a pandemic do not include appropriate detection tools that
automatically trigger an alarm and initiate the immediate cancellation of measures
as soon as either a pandemic warning turned out to be a false alarm or
it is foreseeable that collateral damage — particularly in terms of destruction of human lives — threatens to become larger than the health consequences and especially the lethal potential of the disease under consideration.

The report explicitly distances itself from economic cost-benefit calculations and, in item 4, argues that collateral damage in lives is larger than the damage of the original epidemic. 

Probably the most inflammatory sentence of the executive summary is “One reproach [from the public] might be that, in the Corona crisis, the State has shown itself to be one of the greatest producers of fake news” (Ein Vorwurf könnte lauten: Der Staat hat sich in der Coronakrise als einer der größten fake-news-Produzenten erwiesen.)”

German governmental authorities have tried to dismiss this report as “one person’s opinion”, but — agree with the report or not — it seems to be a good deal more than that. 

(3) Dr. Seheult looks at another hydroxychloroquine clinical trial: this time it looks at a prophylactic regime.

https://doi.org/10.1056/NEJMoa2016638

A group of about 800 patients who reported high-risk contact (nearer than 6th for more than 10 minutes) with a known COVID-19 carrier was split into two arms. One arm was given a 5-day hydroxychloroquine (HOcq) regimen, the other a placebo. Interestingly, and noted by Dr. Seheult, again no zinc!

The percentage of people who developed COVID19 was somewhat lower in the HOcq arm (11.8%) than in the placebo arm (14.3%), but with this sample size, there is about one chance in three the difference is due to chance. (What he didn’t highlight is that, even with high-risk contacts, the risk of contagion is much lower than you might intuitively expect.) 

A fairly large proportion of test subjects in the HOcq arm reported gastrointestinal complaints, but interestingly, no severe adverse events were reported. (HOcq is known to lead to QT-prolongation: in combination with other drugs that do this, such as the macrolide antibiotic azithromycin, the cumulative effect may lead to heart arrhythmias.)

Anyway, let Dr. Seheult explain it himself:

 

(4) Dr. Mike Hansen discusses differences between autopsy reports of COVID19 deaths and deaths from seasonal flu

COVID19 update, Yom HaAtzma’ut edition: “Coronahotels” for mild cases in Israel; pathology professor discusses what can be learned about COVID19 from autopsies

Happy Independence Day/Yom Atzmaut Sameach to my fellow citizens of Israel

(1) In the video below, you see an interview with IDF soldiers staffing a “CoronaHotel”. As our hotels are basically shutdown anyhow, the government requisitioned a number of them to create a third option for people not sick enough to need hospital care, yet whose living conditions do not permit safe home isolation (e.g., because they might infect family members or roommates): the “CoronaHotels”. 

These places are operated by (mostly female) IDF soldiers in their mandatory service: here is a video interview with one of them

No, the hotel is not on a dark, deserted highway 😉 — the one in the video is the Dan Panorama in Jerusalem, normally an upscale tourist and business hotel.

But can you check out? This is not in the hands of the IDF but of doctors, under the overall authority of the Health Ministry.

As I scraped together from different sources:

  • if you tested positive but never showed symptoms, you get retested after two weeks, and if you are negative for the virus then you can go home. If you still test positive, you are retested a week or so later.
  • If you did get a mild flu-like illness, you are tested after you get better.
  • Of course, if your condition worsens, you are transferred to a hospital. In this manner, hospital beds are only used for COVID19 patients who actually need hospital care.

According to the latest Ministry of Health update, https://govextra.gov.il/ministry-of-health/corona/corona-virus/

1,726 people are currently in CoronaHotels, 4,540 mild or suspected cases are in home isolation, and just 352 people are in hospital. Of the latter, 120 are in grave condition (91 of them on artificial respiration), 85 in moderate condition,  and the remainder currently in mild condition (presumably convalescent after more severe episodes). 212 people have died, 7,929 have officially recovered. Out of 15,782 documented infections, that leaves 7,641 active cases, down from their peak of 9,808 on April 15.

(2) Moving from Israel to Germany, DIE WELT has a long (and for me enlightening!) interview with two pathologists at the U. Of Hannover medical school, one of them a lung pathology professor. They perform numerous autopsies on patients deceased from COVID19. Normally they spend 5% of their time doing autopsies and 95% analyzing tissue samples from living patients, mostly for suspected tumors or to help establish optimal cancer treatment plans for confirmed tumors. Nowadays — mostly COVID19 dead. Below follows a mixture of paraphrased summaries and (in quotation marks) hand-corrected machine translations from the original German.

The pathologists broadly hint that invasive respiration (“ventilators”) does more harm than good, and exposes the patients to all sorts of secondary infections [by antibiotic-resistant “hospital bugs”]. 

Primary infection is via nose and throat. 80% of cases are mild [and get better without treatment]. Of the remaining 20%, one-third end up in intensive care with severe lung involvement.

“Jonigk: Blood clotting occurs in the lung [capillaries], which are in the walls of the lung alveoli that serve to absorb oxygen and remove CO2. The damage causes protein to escape from the blood into the alveoli. Oxygen must somehow be transported from the air we breathe into the capillary network. That’s how we breathe. Anything that lengthens that route ensures that the patient can no longer supply himself with sufficient oxygen. It’s like playing soccer when you’ve skinned your knee: First a brown-red crust of protein and blood develops. We have a similar situation in the air bubbles. And breathing through them is massively difficult. The patient has a feeling of breathlessness, too little oxygen gets into the organism. It is more likely to be secondary to an inflammatory reaction. A downward spiral begins, which ends in a so-called shock lung. The lung and with it the patient fight for their lives.[…]”

Q: [which pre-existing conditions?]

A: “Older people with previous damage to the lungs. Patients who are dependent on medication that diminishes the immune system. And smokers, for example. Or people who live in an area with high particulate matter pollution and therefore already have pre-damaged lungs. So they are already not well before that. If an acute infection such as SARS-CoV-2 is then added, this can be enough to put the already sick patient’s life in danger.”

“Classic pneumonia is a bacterial infection with purulent sputum. The pus is yellow because it is made up of fatty granulocytes. Their task is to fight the enemy, the pathogen, in the body. But SARS-CoV-2 is a virus. It attacks cells directly and reprograms them. After an initial unspecific reaction, the response to this infection consists of specific T-lymphocytes, a subtype of white blood cells. These can recognize and attack virus-infected cells. We now have a large number of lymphocytes in the basic structure of the lung, which collect in the walls of the alveoli and develop their inflammatory activity there.”

Q: [what about other organs?]

“Up to 25 percent of intensive care patients have disorders of liver and kidney functions. In addition, blood coagulation often appears to be permanently disturbed. Small, local blood clots form at many sites because the inflammatory cells beat around to destroy the virus-infected cells, which include vascular cells. No matter where this occurs, it always has considerable consequences for the organ — strokes occur and sometimes extremities have to be amputated. In many organs, the occlusion of a blood vessel can be compensated. But if you have many occlusions, the blood does not flow properly, organ damage occurs, inflammatory cells do not get where they actually want to go, and the heart is also put under strain.”

Q: [is this just a COVID19-thing?]

“When you have a nasty cold with a fever, there’s always the recommendation: “Don’t go to the gym.” The basic idea behind this is that any virus can, in principle, infect any organ. Normally you have a resting heart rate of 65 or 70, but if you want to be a tough guy and go to the gym and treadmill and give it all you’ve got, you have a pulse of 150, so your heart is pumping properly. The chance of the virus infecting the heart suddenly increases dramatically. When you are infected, the body fights most viral infections with lymphocytes that go to the heart muscles and kill the infected cells. And this heart muscle inflammation is the most common reason for heart transplants in people under the age of 25.”

“At the moment when [the blood flow in] small vessels in the lungs is disturbed, the heart has to apply increased pressure to pump the blood through the lungs at all. This places an enormous strain on the right ventricle, which is normally only responsible for a low pressure. If the pressure requirements increase, it is quickly overtaxed, resulting in acute right heart failure. The left ventricle does not pump the blood into the lungs, but into the rest of the organism. It is capable of producing a pressure four to ten times greater than the pulmonary circulation. Regardless of whether it is caused by Covid or some other infection: as soon as the pressure in the pulmonary circulation is increased and the right heart is put under pressure, the patient can quickly die. […] So when the lungs are infected, the right heart has to run at full throttle for 1.5–2 weeks and is stressed far beyond normal levels. A young, fit person is more likely to cope with this than someone who already has a previous injury. But the virus is apparently also able to damage the heart itself. And the blood clots can of course also appear in vessels in the heart. So you have a heart that is pumping strongly, and suddenly the blood supply to the heart itself goes down. Then you have two hard strains, which can already be too much for the damaged heart.”

Q: [what about pre-existing conditions?]

“There is the old saying: A healthy patient is only a patient who has not been examined well enough. For example, high blood pressure is a classic disease of old age. In Germany, this will be about 35 percent of the total population. Up to now, mainly elderly people in Germany have died of Covid-19, which means that most Covid-19 deaths have had hypertension. Us being Germans, we also drink a lot of alcohol, so many citizens are overweight and have a fatty liver. The patient over 60 who has no previous illness – statistically there are only few. The important thing is not that there are pre-existing conditions, but which ones. And in what context do these have an influence on the probability of survival in the case of Covid-19 disease? It’s not enough to say, “This patient had something.” Rather, the previous illnesses must be systematically uncovered in relation to the population.”

You have to separate whether someone died of, or with, a Covid-19 infection. It’s already affecting statistics. As far as we know, in Italy a corona test was carried out on every person who died and everyone who was found to have the virus was considered to have died of corona. In the case of pre-existing conditions, a distinction must also be made between diseases that generally shorten life expectancy and diseases that specifically increase the risk of corona infection and possible complications. This is somewhat muddled in the public discussion.”

Q: [brain involvement]
A [paraphrased]: we cannot conclusively rule out direct virus involvement, but the brain is so sensitive to disturbances in blood flow that blood clots quickly lead to headaches, then strokes.

[Paraphrased] “Overall, we know a lot about what happens at the cellular level with the virus, but relatively little about what happens at the organ level. Cell cultures can only tell you so much. So here is where autopsies come in.”