COVID19 update, May 2, 2020 edition: Remdesivir gets FDA approval; detailed German statistics

(1) The top news item of the day is probably that Gilead Scientific’s antiviral drug remdesivir was given FDA Emergency Approval for use in COVID19 patients. Remdesivir is not a “magic bullet”, but it’s a start.

(2) Roger Seheult MD, pulmonologist and medical school instructor, gives a 1.5 hour recap video on what we know about COVID19.

(3) Miscellaneous updates:

  • the Ma`ayanei haYeshua [Wellsprings of Salvation] hospital in Bnei Brak, Israel (a COVID19 hotspot) has deployed an Israeli-developed UV-C room sterilization system. This is of broader relevance than COVID19, and if successful, will prove very helpful in the protracted and increasingly worrying struggle against hospital “superbugs” — bacteria resistant to every known antibiotic. (Such bacteria tend to develop in hospitals and long-term care settings through “Darwinian selection”, as both infections and treatment with aggressive antibiotics are frequent.)
  • Die Welt has a detailed video (in English, with German subtitles) on significant progress with a vaccine in the USA
  • worrisome reports about some peculiar COVID19-like pediatric syndrome noted in earlier updates: these now appear to have been identified as Kawasaki’s disease, which is of uncertain origin but some sort of autoimmune etiology is suspected. Coincidence or new cases triggered by COVID19 infection?
  • disturbing reports of COVID19 “reinfections” in South Korea appear to have been false positives in the test
  • Abbott’s new rapid COVID19 test, which claims 99% accuracy, has been approved for use in Europe.
  • if you give people perverse incentives to cook the books, and don’t balance that out with a deterrent for the act of cooking — well, don’t be surprised if books get cooked. NYC funeral director on candid recording about people who obviously died from otehr causes being coded as COVID19. Mind you, I am sure the un-inflated COVID19 mortality in NYC would be quite bad enough (“thanks” to very high pollution density and the subway as “the mother of all superspreaders”) — but those numbers struck me as anomalously high from the start. (As discussed in previous updates, numbers from Italy and Belgium are inflated for different reasons.)

(4) In contrast, countries like South Korea and Germany have rather more scrupulous reporting standards. I’ve linked previously to the daily Korean CDC reports: here is the detailed daily update (in English) from the Robert Koch-Institute (Germany’s infectious diseases authority, named after the discoverer of the tuberculosis pathogen). A few highlights from the daily report:

  • Only 19% of all cases occurred in persons aged 70 years or older — but these account for 87% of deaths.
  • cases per 100,000 people in age cohorts are fairly homogenous across age cohorts 20-29 through 70-79, climb sharply in the highest age cohorts, and drop steeply for ages 10-19 and especially 0-9.
  • mortality in age cohorts 0-9 and 10-19 are ONE (1) patient each, while age cohorts 20-29 and 30-39 account for just 6 and 14 deceased out of a total of 6,472. Yes, Virginia, ages below forty account for just 0.3% of all dead, and all ages below fifty for just 1%. Fifty-somethings add another 3.2%, sixty-somethings another 9.0%.
  • Their technique of estimating the effective reproductive number R consists of dividing the 4-day moving average of new cases by the one 4 days earlier. At present it is R=0.79, with a 95% confidence interval of 0.66–0.90. Any R value below 1 implies that the epidemic will wither away, while any value over 1 implies slower or faster exponential growth.
  • the report points to a European Union website with all-causes excess mortality graphs. These serve as a useful “sanity check” on COVID19 death reporting criteria for different countries.

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.”