PANDEMIC | 1. Germany's Low Virus Death Rate

The following is the first in a series of posts on this topic. See also posts of March 20 (#2, on infection rates), March 21 (#3, includes Italy). Virus Deaths Tracker.

March 19, 2020 – The data in the table below show a column for death rate ("case fatality rate") with a global ratio of 4.1 deaths per 100 cases of the COVID-19 disease as of this morning, using the Johns Hopkins database (jhu.edu). It's not hard to see that Germany stands out for its low death rate, 0.2 per cent. What's behind these numbers, and are there any lessons we can learn from them?

Why Is German Death Rate So Low?

Information on testing rates might be a clue. But data on testing rates, posted by Oxford University's Martin School's OWID, exclude Germany. The reason may be that Germany's automated testing system is so widespread within the country and distributed to such a wide number of labs, that they can't keep accurate track of all the tests that are being done.

Country (Rank by Cases)	Rank by Death Rate	Cases	Deaths	Death Rate	Recovered	Tests	Tests /Million Pop.	Comment
World	Total	222,642	9,115	4.1	84,506			See updates at JHU.edu
Germany (5)	1	13,093	31	0.2	113	-	-	Automated community testing.
Korea, S. (8)	2	8,565	91	1.1	1,540	286,716	5,566	High community testing.
Switzerland (9)	3	3,067	33	1.1	15	4,000	461	Testing number as of March 7
USA (6)	4	9,415	150	1.6	106	41,552	124	Inadequate, late testing; testing only those with symptoms.
France (7)	5	9,058	243	2.7	12	11,071	168	Number of tests as of March 10
Netherlands (11)	6	2,056	59	2.9	2	6,000	349	Testing number as of March 7
UK (10)	7	2,644	103	3.9	67	50,442	749	Updated at least daily. Data show number of people tested.
China (1)	8	81,154	3,249	4.0	70,535	320,000	2,824	Tests as of Feb. 24, Guangdong
Spain (4)	9	15,014	640	4.3	1,081	-		No data on testing
Iran (3)	10	18,407	1,284	7.0	5,710	-		Questions about transparency
Italy (2)	11	27,980	2,158	7.7	4,025	148,657	2,514	Unclear if people or tests. World’s 2nd highest elderly pop.
All Other		32,189	1,074	3.3	1,300
Comment						Some test numbers are for people, some for specific tests (x2). Community testing includes non-symptomatic cases.
Source	This blog	Johns Hopkins University JHU jhu.edu		This blog	JHU	Oxford University Martin School, OWID, ourworldindata.org/coronavirus

What is the story? 

Germany was the first to design a test differently from other countries; it has a rapid testing system. Germany has therefore probably diagnosed a much larger proportion of those who have been infected, and also a higher proportion of their population.

One factor is the number of independent labs throughout the country. Christian Drosten, the director of the Institute for Virology at Berlin's Charite hospital says that this network received both technical information to conduct tests and the approval to bill for them in January, when case numbers in Germany were still in the single digits.

Germany's distributed system helped doctors to determine quick whether suspected cases actually involved the new virus or a common cold, which can have similar symptoms. Drosten said: “Other countries lost a month or even more time because of this,”  Lothar H. Wieler, head of the Robert Koch Institute, Germany's equivalent the the U.S. CDC, said something similar: “We identified people early on with our testing who are infected, but not seriously ill.”

Why Doesn't the United States Adopt the German Test? 

The Germans developed a test for the new coronavirus one week after the genetic sequence for the novel coronavirus first became available in January 2020. That test became the basis for the World Health Organization’s (WHO) test used in countries around the world, including South Korea. However, the Centers for Disease Control and Prevention (CDC) declined to use it. The German test adopted and disseminated by the WHO scanned for three specific viral genes. 

Countries around the world adopted the test. South Korea, for example, quickly started testing around 10,000 people each day and now has tested 250,000 people.

The CDC instead created its own test using the three different genes from the German test. But when state labs tried the test, some found false positive results. The CDC redesigned and remanufactured test kits, but this took time.

Multiple Problems Being Addressed Now

The United States reported its first confirmed case of COVID-19 on January 21. Eight weeks later, there are aren’t enough tests for the virus available. Here are the contributing problems:

• Systemic failure. “The system is not really geared to what we need right now,” said Anthony Fauci, director of the National Institutes of Allergy and Infectious Diseases, at a briefing last week before the Committee on House Oversight and Reform, chaired by Rep. Carolyn B. Maloney (D-NY12). 
• Cuts in CDC, planning for pandemics. Contributing factors reportedly were cuts in the CDC and the termination of the unit planning for pandemics in the White House.
• The PCR is time-consuming. Until last week, the number of tests that could be run per day in the United States was limited to approximately 7,000, because it just takes so long.  The polymerase chain reaction (PCR) test has been around for decades. A doctor swabs a patient’s nose or throat and sends the sample to a lab, which looks for snippets of the virus’s genetic material. The test, however, is too slow. A bitter commentator has described the technology to me as "ancient." 
• Point-of-care testing is required in a pandemic. No one wants to wait for a lab while they decide where to put patients in an overcrowded hospital. "We’re just not quite there yet,” said Catherine Klapperich, director of the Laboratory for Diagnostics and Global Healthcare Technologies at Boston University.
• Shortage of supplies. The PCR swabs are imported and are in short supply.
• Too few labs. For weeks in the US, tests for the virus were being done by hand. A lab technician mixes a patient sample with tiny portions of chemicals in tiny tubes. Contamination can ruin the test. The samples must be repeatedly brought up to high heat and back down in a process called thermocycling, done on a specific machine. It takes a few hours to get results back. Labs that can do the testing have needed special approval to run PCR tests, and permission could take months. (Some of the problems listed here are being fixed.)
• State of emergency slowed FDA approval. Normally, state public health labs and commercial labs would have been able to create their own PCR tests.  But the public health state of emergency meant that any new test had to be approved by the Food and Drug Administration (FDA). That slow process also contributed to delays. On February 29, the agency relaxed the rule.
• FDA approval for machines took time. Machines are available that can run PCR tests automatically. However, it took companies weeks to develop tests for those automated systems and for the FDA to approve them.

Technology for the new tests is still experimental. The PCR test is hard to bring to a patient’s bedside, because thermocycling needed to run the test needs a lot of electricity. Another approach, isothermal amplification, is simpler and can work at a fixed temperature. Dozens of companies are now developing point-of-care tests for the novel coronavirus. The Verge cites three promising approaches: 

• The University of California, San Diego is evaluating a system that they say could return results in one hour. 
• Mammoth Biosciences is developing a bedside test that would work similarly to a pregnancy test. 
• Cepheid is leveraging a flu detection technology to build a rapid novel coronavirus test.

The question is whether, after a late start, any of these tests can be ready to help stem this pandemic. We should ask the Germans to help us get this done.