COVID19 update, May 7, 2020: risk of severe case presentation increases with age too; meat processing plants; fraying lockdowns; Georgia (the country)

Busy day at work, so just some quick updates:

(1) There is a commonly quoted rule of thumb that 80-85% of COVID19 cases are mild, and the rest severe and life-threatening. But how constant is that ratio really?

I was emailed a copy of a report (in Hebrew) by a group that was consulted for our national COVID19 planning. In the section on expected hospital load was a table with a breakdown of hospital and ICU admissions by age bracket, apparently taken from a CDC Morbidity and Mortality Weekly Report, http://dx.doi.org/10.15585/mmwr.mm6912e2. Screenshotting the table here:

* Lower bound of range = number of persons hospitalized, admitted to ICU, or who died among total in age group; upper bound of range = number of persons hospitalized, admitted to ICU, or who died among total in age group with known hospitalization status, ICU admission status, or death.

Needless to say, these are data early in the epidemic (when the group had to make its recommendations). But if we use ICU admissions as a proxy for the number of severe cases, then we see a clear increase with age, the way it is seen for mortality.

(2) Elsewhere on the CDC site, one finds a report about the conditions and challenges at meat processing plants https://dx.doi.org/10.15585/mmwr.mm6918e3
Some quotes:

During April 9–27, aggregate data on COVID-19 cases among 115 meat or poultry processing facilities in 19 states were reported to CDC. Among these facilities, COVID-19 was diagnosed in 4,913 (approximately 3%) workers, and 20 COVID-19–related deaths were reported. Facility barriers to effective prevention and control of COVID-19 included difficulty distancing workers at least 6 feet (2 meters) from one another (2) and in implementing COVID-19-specific disinfection guidelines.* Among workers, socioeconomic challenges might contribute to working while feeling ill, particularly if there are management practices such as bonuses that incentivize attendance. 

 Facility challenges included structural and operational practices that made it difficult to maintain a 6-foot (2-meter) distance while working, especially on production lines, and in nonproduction settings during breaks and while entering and exiting facilities. The pace and physical demands of processing work made adherence to face covering recommendations difficult, with some workers observed covering only their mouths and frequently readjusting their face coverings while working. Some sites were also observed to have difficulty adhering to the heightened cleaning and disinfection guidance recommended for all worksites to reduce SARS-CoV-2 transmission.

Solutions to structural and operational challenges that some facilities adopted included adjusting start and stop times of shifts and breaks to increase physical distance between workers. Outdoor break areas were added at some facilities to decrease contact between workers. Some facilities installed physical (e.g., plexiglass) barriers between workers; however, this was not practical for all worker functions. Symptom and temperature screening of workers was newly instituted in some facilities and improved in others.

Sociocultural and economic challenges to COVID-19 prevention in meat and poultry processing facilities (Table 2) include accommodating the needs of workers from diverse backgrounds who speak different primary languages; one facility reported a workforce with 40 primary languages. This necessitates innovative approaches to educating and training employees and supervisors on safety and health information. In addition, some employees were incentivized to work while ill as a result of medical leave and disability policies and attendance bonuses that could encourage working while experiencing symptoms. Finally, many workers live in crowded, multigenerational settings and sometimes share transportation to and from work, contributing to increased risk for transmission of COVID-19 outside the facility itself. Changing transportation to and from the facilities to increase the number of vehicles and reduce the number of passengers per vehicle helped maintain physical distancing in some facilities.

(3) Lockdowns — useful as they undeniably are in densely populated urban regions — are not something that can be maintained forever. In the “hammer and dance” strategy of Tomas Pueyo, the “hammer” — the lockdown to break the epidemic’s back — is supposed to be hard and short, followed by a maintenance phase — the “dance” — that favors such social distance measures as yield the maximum reduction for minimal economic cost. (Face masks are one example.)
There are increasing signs that lockdowns in the US are fraying. Bethany Mandel, who lives in New York, speaks for many who express a sense that politicians of a certain stripe now keep “moving the goalposts” way beyond the original justification for lockdowns, and that they are completely oblivious to the staggering and still mounting economic costs for those who do not have guaranteed government paychecks. “We are tired of being treated like children,” one reads numerous times in the comments.[*]

Days ago, a hairdresser in Texas who had reopened her business made a tearful plea that she not be punished for wanting to feed her children. She was convicted to seven days in prison and a $7K fine. Now in a dramatic turn of events, not only have both the state Attorney-General and the Governor criticized the “excessive” punishment (the lockdown over hardressing salons ends Friday anyhow), but the state’s Lt.-Gov. donated the money from his own pocket and offered to serve the 7-day sentence himself as a proxy for the woman.

(4) DIE WELT looks at what it calls the “Coronavirus Model Pupil,” Georgia (the country, not the US state). The country, knowing it could ill afford such a calamity, locked down proactively rather than reactively, and is now exiting. (Possibly the most prescient thing it did was cut air links to China before they even saw their first case.) Now, despite a social culture much like Italy, it got a sum total of 610 cases, with just 9 (nine) dead.

(5) Finally, hard-hit Belgium is reopening after a few false starts. Summarizing the report from De Standaard (in Dutch):

  • starting May 10, every household can receive and host four designated people (a fixed list of four). Recommended to sit outdoors. No travel distance limitation
  • May 11, shops will open. One customer per 10m^2 (110 sq.ft.) floor area. Wearing a mask is recommended but not mandatory; generally recommended in situations where 1.5m (5ft) distance cannot be maintained (e.g. on public transit). If lines develop, elderly, handicapped, and care workers get priority
  • public transit in principle reserved for people who have no private means of transportation (cars, motorcycles). In practice, this will not be enforced
  • restaurants, cafés, cultural centers remain closed for now
  • public sports events are put off until July 31

[*] Without engaging in partisan political rhetoric: one reason the lockdown in Israel was largely successful, and saw a compliance well above what one might expect of our garrulous nation, was that we were treated like adults. Economic trade-offs were honestly discussed, including the limits to how long we could lock down before irreparable damage to our economy would ensue — and we were given a realistic time horizon from the start. At no point was there a sense of “bait and switch”.

UPDATE: via the Jerusalem Post, this interesting paper in the Journal of Medical Virology has an interesting theory about why the SARS-nCoV-2 coronavirus may elicit potentially fatal “cytokine storm” so much more often than seasonal influenzaviruses: https://doi.org/10.1002/jmv.25866

We have applied mathematical modeling to investigate the infections of the ongoing COVID‐19 pandemic caused by SARS‐CoV‐2 virus. We first validated our model using the well‐studied influenza viruses and then compared the pathogenesis processes between the two viruses. The interaction between host innate and adaptive immune responses was found to be a potential cause for the higher severity and mortality in COVID‐19 patients. Specifically the timing mismatch between the two immune responses has a major impact on the disease progression. The adaptive immune response of the COVID‐19 patients are more likely to come before the peak of viral load, while the opposite is true for influenza patients. This difference in timing causes delayed depletion of vulnerable epithelial cells in the lungs in COVID‐19 patients while enhancing the viral clearance in influenza patients. Stronger adaptive immunity in COVID‐19 patients can potentially lead to longer recovery time and more severe secondary complications. Based on our analysis, delaying the onset of adaptive immune responses during early phase of infections may be a potential treatment option for high risk COVID‐19 patients. Suppressing the adaptive immune response temporarily and avoiding its interference with the innate immune response may allow the innate immunity to more efficiently clear the virus.

COVID19, April 15, 2020 update: Cytokine storm — the immune system “killing the patient in order to save him/her”

The more I read about the (fairly rare) cases of younger people in generally good health dying or becoming critically ill, the more it sounded to me like “cytokine storm”, a.k.a. https://en.wikipedia.org/wiki/Cytokine_release_syndrome

In plain English, this is what happens when the immune system massively overreacts and does more damage to the patient than the original disease. It is generally assumed that the vast majority of deaths due to the 1918 “Spanish” Flu [*] resulted from cytokine storm, which explains the (for a flu) anomalous age distribution of mortality.

A reader (thanks a lot, Lissa!) forwarded me a story from the San Diego Union Tribune about a doctor in the prime of his life who got infected caring for the first major outbreak in Washington State.  https://archive.is/YBqAq

A 6-foot-3, 250-pound former football star who played for Northwestern in the 1996 Rose Bowl, he wasn’t fazed by much.

“To worry about myself, as a 44-year-old healthy man, didn’t even cross my mind,” he said in an interview Monday.

But on March 12, with his wedding day two months away, Padgett became the patient.

Soon after being admitted to his own hospital with a fever, cough and difficulty breathing, he was placed on a ventilator. Five days after that, his lungs and kidneys were failing, his heart was in trouble, and doctors figured he had a day or so to live.

He owes his survival to an elite team of doctors who tried an experimental treatment pioneered in China and used on the sickest of all COVID-19 patients.

Lessons from his dramatic recovery could help doctors worldwide treat other extremely ill COVID-19 patients.

“This is a movie-like save, it doesn’t happen in the real world often,” Padgett said. “I was just a fortunate recipient of people who said, ‘We are not done. We are going to go into an experimental realm to try and save your life.’”

Once his colleagues at EvergreenHealth realized they had run out of options, they called Swedish Medical Center, one of two Seattle hospitals that has a machine known as an ECMO, which replaces the functions of the heart and lungs.

But even after the hospital admitted him, doctors there had to figure out why he was so profoundly sick.

Based on the astronomical level of inflammation in his body and reports written by Chinese and Italian physicians who had treated the sickest COVID-19 patients, the doctors came to believe that it was not the disease itself killing him but his own immune system.

It had gone haywire and began to attack itself — a syndrome known as a “cytokine storm.”

The immune system normally uses proteins called cytokines as weapons in fighting a disease. For unknown reasons in some COVID-19 patients, the immune system first fails to respond quickly enough and then floods the body with cytokines, destroying blood vessels and filling the lungs with fluid.

The doctors tried a drug called Actemra [US brand name for the immunosuppressor https://en.wikipedia.org/wiki/Tocilizumab] which was designed to treat rheumatoid arthritis [an autoimmune disease] but also approved in 2017 to treat cytokine storms in cancer patients.

“Our role was to quiet the storm,” said Dr. Samuel Youssef, a cardiac surgeon. “Dr. Padgett was able to clear the virus” once his immune system was back in balance.

Dr. Matt Hartman, a cardiologist, said that after four days on the immunosuppressive drug, supplemented by high-dose vitamin C and other therapies, the level of oxygen in Padgett’s blood improved dramatically. On March 23, doctors were able to take him off life support.

Four days later, they removed his breathing tube. He slowly came out of his sedated coma, at first imagining that he was in the top floor of the Space Needle converted to a COVID ward.

There are a number of theories why chloroquine and hydroxychloroquine (HOcq) appear to have at least to some therapeutic benefit in COVID-19 patients: one that it is a zinc metallophore and zinc interferes with RdRa (RNA-dependent RNA polymerase, the enzyme that makes copies of the viral genome); another that it changes the intracellular pH to an extent that interferes with viral reproduction; yet another that it has some protective effect on hemoglobin. But the real answer may have been staring us in the face all the time:  HOcq, aside from being a decades-old antimalarial, also happens to be a mild immunosuppressant, and has been used as such (initially off-label) for many years (under the US brand name Plaquenil) in patients with autoimmune diseases like lupus and rheumatoid arthritis. So its real benefit may be in holding cytokine storm at bay, and stopping the immune system from “killing the patient in order to save him/her”. 

Now a downregulated immune system will result in greater vulnerability to opportunistic bacterial superinfections — which is why the simultaneous administration of an antibiotic like azithromycin (“Z-pak” as it’s popularly known in the US) appears to give added value to the treatment. As for the recommendation of adding zinc: I already commented on that yesterday.

As I am writing these lines, it occurred to me that cytokine storm and “killing the patient in order to save him/her” may be perfect metaphors for extended (6-months and more) economic shutdowns that are sure to kill or irreparably damage an economy. I am perhaps the last person on the planet to dispute the usefulness of lockdowns and social distancing measures where appropriate. My own country has applied them severely, but this makes complete sense given our population density. They should not be applied as blunt instruments in a one-size-fits-all approach, and (at least this is widely discussed here) cannot be kept up for more than a limited time.  To give an example: applying the same standards across a continent-sized country, whether it is thinly populated Wyoming or teeming New York City, makes no sense. New York City and its commuter counties in adjacent states New Jersey and Connecticut account for nearly half the new cases AND mortality in the US — it was pointed out to me by my friend David S. Bernstein that the hardest-hit counties proportionally are not Manhattan (as one might naively expect based on population density) but the commuter counties. I can hardly think of a riskier prospect in a major respiratory epidemic than having to commute half an hour or an hour each way packed like sardines in a subway. (As far as I can tell from the New York Municipal Transit Authority website, the subway is still running, albeit with reduced service.) The same people who would want to apply the “if it only saves one life” standard to justify asinine measures like prohibiting the sale of seeds and gardening tools in Michigan supermarkets should instead direct their energies to New York City — where public transportation is likely responsible for more infections than all the “nonessential purchases” in the rest of the country combined. (But then, of course, they would not be able to make political hay off it…) It makes complete sense to keep NYC under lockdown for a considerable while longer. It makes none at all to do the same for agriculture and food processing — which would add famine to the already staggering economic cost of the pandemic.

POSTSCRIPT: Meanwhile, the Washington Post, in a rare display of journalism, dropped a bombshell (archive copy at http://archive.is/Tg5oo in case it gets “airbrushed”)” It appears that my friend “masgramondou” was not far off the mark with his origin theory for the epidemic.

In January 2018, the U.S. Embassy in Beijing took the unusual step of repeatedly sending U.S. science diplomats to the Wuhan Institute of Virology (WIV), which had in 2015 become China’s first laboratory to achieve the highest level of international bioresearch safety (known as BSL-4). WIV issued a news release in English about the last of these visits, which occurred on March 27, 2018. The U.S. delegation was led by Jamison Fouss, the consul general in Wuhan, and Rick Switzer, the embassy’s counselor of environment, science, technology and health. Last week, WIV erased that statement from its website, though it remains archived on the Internet.

What the U.S. officials learned during their visits concerned them so much that they dispatched two diplomatic cables categorized as Sensitive But Unclassified back to Washington. The cables warned about safety and management weaknesses at the WIV lab and proposed more attention and help. The first cable, which I obtained, also warns that the lab’s work on bat coronaviruses and their potential human transmission represented a risk of a new SARS-like pandemic.

“During interactions with scientists at the WIV laboratory, they noted the new lab has a serious shortage of appropriately trained technicians and investigators needed to safely operate this high-containment laboratory,” states the Jan. 19, 2018, cable, which was drafted by two officials from the embassy’s environment, science and health sections who met with the WIV scientists. (The State Department declined to comment on this and other details of the story.)

The Chinese researchers at WIV were receiving assistance from the Galveston National Laboratory at the University of Texas Medical Branch and other U.S. organizations, but the Chinese requested additional help. The cables argued that the United States should give the Wuhan lab further support, mainly because its research on bat coronaviruses was important but also dangerous.

As the cable noted, the U.S. visitors met with Shi Zhengli, the head of the research project, who had been publishing studies related to bat coronaviruses for many years. In November 2017, just before the U.S. officials’ visit, Shi’s team had published research showing that horseshoe bats they had collected from a cave in Yunnan province were very likely from the same bat population that spawned the SARS coronavirus in 2003.

“Most importantly,” the cable states, “the researchers also showed that various SARS-like coronaviruses can interact with ACE2, the human receptor identified for SARS-coronavirus. This finding strongly suggests that SARS-like coronaviruses from bats can be transmitted to humans to cause SARS-like diseases. From a public health perspective, this makes the continued surveillance of SARS-like coronaviruses in bats and study of the animal-human interface critical to future emerging coronavirus outbreak prediction and prevention.”

The research was designed to prevent the next SARS-like pandemic by anticipating how it might emerge. But even in 2015, other scientists questioned whether Shi’s team was taking unnecessary risks. In October 2014, the U.S. government had imposed a moratorium on funding of any research that makes a virus more deadly or contagious, known as “gain-of-function” experiments.

[…]

There are similar concerns about the nearby Wuhan Center for Disease Control and Prevention lab, which operates at biosecurity level 2, a level significantly less secure than the level-4 standard claimed by the Wuhan Insititute of Virology lab, Xiao said. That’s important because the Chinese government still refuses to answer basic questions about the origin of the novel coronavirus while suppressing any attempts to examine whether either lab was involved.

[*] The reason for the historical name “Spanish Flu” is simple. There were outbreaks in army barracks across the front, but those were hushed up due to wartime censorship. Spain was neutral in WW I, so its press was the first to significantly report on the epidemic. The name “Spanish” has stuck until quite recently.

ADDENDUM: welcome Instapundit readers! Via your intrepid host linking a NYPost article, I found this recent study from MIT showing the major role the NYC subway had in spreading the infection. This is my face. It is shocked.

ADDENDUM 2: I linked an interview with South Korean COVID19 expert Dr. Woo-Joo Kim of Korea University Guro Hospital in an earlier update. Commenter “reactionary” on Instapundit drew my attention to the followup interview, which is highly recommended (remember, South Korea was one of the first countries to get the epidemic under control). He starts discussing cytokines and cytokine storm about 14 minutes into the video (in Korean with English subtitles).

COVID19 update, April 6, 2020: BREAKING: Austrian Chancellor announces “back to normal” schedule; how is the rest of Europe doing? (UPDATED)

German center-right daily Die Welt reports that Austrian Chancellor Sebastian Kurz has announced his country’s return-to-normality schedule.

The country has been on lockdown since March 16, and recent statistics strongly suggest the epidemic is under control in Austria. (At present, the country has 12 008 confirmed infections, 220 dead, and 3,463 recovered.) To wit, I include the following graphs from worldometers:

“Active” refers to patients not yet cured or deceased
As you can see, the number of recoveries exceeds the number of new patients now
  • Summarizing from the German text:
  • Starting April 14 (the Tuesday after Easter), small businesses of all kinds — other than cafés and restaurants, etc. — are allowed to reopen with restrictions, as will larger stores dealing in building/DIY or garden supplies. (Such stores tend to be either outdoors or in very large halls in that part of the world.)
  • Starting May 1, also larger businesses — again, other than cafés, restaurants, etc. — will be allowed to reopen, as will (indoor) shopping malls.
  • Starting May 15, cafés and restaurants will be allowed to reopen

Die Welt adds that Kurz’s Danish colleague Mette Fredriksen has likewise indicated wanting to gradually reopen business in her country after Easter, but has not committed to a specific time table.

DEVELOPING…

ADDENDUM: what about elsewhere in Europe?

  • Italy is seeing its smallest daily new cases count since March 19, and its smallest number of daily deaths since March 20. From the Worldometers data, I calculate their latest daily growth rate as 3.3%, which corresponds to doubling every 3 weeks or so.
  • Belgium yesterday marked the first day that net hospital bed occupancy dropped, according to De Standaard (in Dutch): admissions were less than the sum of discharges and deaths. Daily new cases have been fluctuating around 1,250 since March 26.
  • In Spain, daily deaths have been dropping for 3 days in a row now, and active cases appear to be leveling off. New cases are at the lowest level since March 23.
  • Germany has its lowest number of new cases since March 23. The “new cases” and “new recoveries” lines are on the way to the magic crossover point
  • Norway has its smallest number of new cases since March 19.
  • France has an anomalous spike in daily new cases on April 3, but daily deaths have been going down for 3 days in a row now.
  • The UK still is looking for first light at the end of the tunnel

And from Italy, an amazing human interest story: La Repubblica reports (in Italian) that Ada Zanusso, age 103 [!], beat back COVID-19. 21 other residents of her assisted living facility, 100km from Milan, succumbed the disease, but “somebody up there forgot me”. She stays in touch with her so Giampiero [Italian for John Peter], who says “she still reads without glasses, she is curious, always wants to know what we’re up to.” The spunky lady will turn 104 in August. Let’s raise a glass to her!

UPDATE 2:  Belgian PM presents 10-member GEES (group of experts [for a lockdown] exit strategy) reports De Standaard (in Dutch). This group, a mixture of doctors, epidemiologists, and economists, has been working behind the scenes for some time, apparently. Immunity testing and tracking via phone app are reported to be two cornerstones of the strategy, inspired by the work of a group from Oxford.
https://www.standaard.be/cnt/dmf20200406_04914854
https://www.standaard.be/cnt/dmf20200405_04913914

Israel has informally been talking about “after Passover” through much of the crisis, but no clear time table appears to exist as of yet. The epidemic is clearly slowing down here, but has not yet reached the plateau phase like in Belgium, let alone started receding like in Austria. A variety of creative solutions are being coined by scientists, including this one of an age-stratified exit.

In the UK, sadly, things are still looking glum, with now PM Boris Johnson moved to the ICU.