Corona and The Future of Hygiene – Part 1 of 4: Corona: The Crown Upon Viruses?

It is 2020: a year already set in every book of history. The world has been taken hostage by a new coronavirus. Or at least by all the measures which ensued. The future has become a fearful image: will this be the new normal? Will we, from now on, always look back on a time before and a time after corona? Or will everything simply blow over? In this series of four episodes we will put views of virologists, epidemiologists, scientists, journalists, academics and politicians side by side. In this first episode: what is the coronavirus and how dangerous is it? To get more details on a specific subject, click on the enclosed links. Part 2 and 3 will focus on the measures taken to diminish the impact of the coronavirus, vaccines and medicines. Part 4 will aim to portray the future.

 

A jacket of fat with protein around it

History knows many epidemics and pandemics. At the core: a virus is nothing more than a piece of genetic material (DNA or RNA) in a jacket of fat with protein around it. Contrary to a bacteria (a micro-organism with DNA-genome) which can multiply by itself when it finds itself in the right circumstances, a virus needs a live host to do so. We often fight bacteria with antibiotics.[1] When it comes to viruses, we use vaccines to prevent them, and antiviral medicines to fight them. Viruses cause mild illnesses like colds and cold sores, but also serious diseases like HIV, SARS and hepatitis.[2] We talk about an infection when a virus or bacteria has invaded any living being.

 

Viruses are smart

All viruses came from wild birds, says Ron Fouchier from the Virology laboratory at the Erasmus University in Rotterdam, The Netherlands.[3] The birds usually don’t mind the virus. Some viruses jump to mammals or humans, when they come in close contact with each other. At times, serious problems occur, like with the Ebola virus. What happens when we become infected with a virus? Our immune system is put to work. We have an innate immune system with an nonspecific defence which rebels against everything unknown.[4] And we also have an adaptive immune system, fighting against a specific intruder.[5] Our bodies produce antibodies, which are used by our immune system to recognize the intruder when he attacks in the future. Viruses continuously adapt. In a new form, they cause new infections. Every year, new variations to the known viruses emerge. The flu, which is responsible for a great number of deaths each year, consists of multiple, ever-changing, flu viruses.[6] Coronaviruses are not uncommon: these RNA viruses are widespread amongst people and animals.[7] In the range of viruses causing respiratory illnesses, 7 to 15% of coronaviruses are usually involved.[8]

All viruses originate from wild birds

 

Corona: the upgrade

At the end of last year, a new coronavirus surfaced. Also this new virus could have circulated amongst birds, especially bats, for a while before it became known to us. Perhaps it has even come into contact with people before.[9] Until now, however, the virus has missed the right ‘key’ to ‘open’ human cells. After mutation, the virus has changed so that the protein on her jacket of fat suddenly fits exactly on receptors of cells in the human mucous membrane.[10] After discovery, Chinese scientist took a sample from the lower respiratory tract of a patient and used it to determine the RNA (the genetic code, existing of about 300.000 signs) of the virus.[11] What can we do with this RNA? It doesn’t provide us with information on how dangerous the virus is, but it is used to analyse the virus, to find out how it could evolve, and to create a vaccine.

 

After mutation, the virus has changed so that the protein on her jacket of fat suddenly fits exactly on receptors of cells in the human mucous membrane

 

Discussion: origins of the new virus

How did the new coronavirus come to be? This question is important to answer in order to prevent future outbreaks. As of yet, the experts don’t agree. The animal market in Wuhan is mentioned as a point of origin, also both laboratories working with viruses in Wuhan have entered the picture. Some experts believe to have found proof of the natural evolution of the virus in the RNA, while others claim to find evidence for human intervention there.

 

Discussion: origins of the new virus

The first report of the China CDC on the 21st of January 2020 states, after analysing the RNA of the virus, that transmission from wild animals being sold illegally on the market in Wuhan is the most probable cause of the outbreak.[12] On the 24th of January, a Chinese report is published after analysing the first patients: it concludes that the first patient, as well as two of the three cases following, did not have a direct link to the Wuhan market.[13] From the first 41 patients, 27 had directly come into contact with the market.[14] On the 31st of January, Indian scientists are heavily criticized after publishing a paper concluding they found sequences in the new virus with an identity of HIV-1-protein, which could not have gotten there through natural evolution of the virus.[15] After the critique, they withdraw their paper. In February, two Chinese scientists write that bats, according to the municipal reports and statements of residents and visitors, are not sold on the Wuhan-market: instead they live in caves and trees 900 km away from the market.[16] There are two laboratories in Wuhan (one of which only 280 meters from the market) that work with bats, and also with coronaviruses: the Wuhan Institute of Virology (WIV) and the Wuhan Center for Disease Control and Prevention (Wuhan CDC).[17]

 

From a laboratory?

On the 17th of March, researchers publish an article in Nature Medicine magazine in which they explain why it is unlikely that the new virus was created by humans.[18] The press is having a field day with the study.[19] On the 3rd of April, a Czech molecular geneticist and virologist states that these researchers have only examined the structural part of the RNA, which shows likenesses with the viruses in host animals.[20] Instead, they should have examined the regulatory part, she says, because this is the part responsible for the mutations in the virus. According to her, this is also where the pieces of DNA were found which could not have occurred naturally. The Washington Post says to conclude, based on expert opinions, that the Wuhan-market-story is ‘shaky’.[21] On the 18th of April, French virologist Luc Montagnier, the Nobel prize winner who discovered hiv, states that he has examined the RNA-code of the new coronavirus together with his colleague, bio mathematician Jean-Claude Perez. He says that the Indian scientists were right: the new coronavirus contains fragments of an hiv-virus which could not have come from a patient.[22] ‘You can only insert hiv into a genome with the help of molecular instruments,’ says Montagnier on the French news station CNews.[23] ‘It is very precise work which can only be carried out in a highly secured laboratory.’ Also Montagnier is not spared by the critics.[24] Virologist Steven van Gucht says on the first of May: ‘We know that there are many possibilities in which this virus could have jumped from nature to man.’[25]

 

Human intervention in viruses: a myth?

Human intervention in any virus is not as strange an idea as it might sound. ‘Gain-of-function’ research, like the name suggests, focuses on expanding existing characteristics of a virus or introducing new ones into it. Human intervention in the RNA of a virus. This type of research is being conducted to discover how a virus might evolve and how a vaccine might be created. Ron Fouchier of the Virology laboratory at the Erasmus University in Rotterdam, The Netherlands, explains how he himself conducts this type of research: ‘I can rebuild these pieces of genetic material [from the virus] in a lab. Then, I alter the gen in a specific way. I put it back into the virus, creating a new virus with my mutations. After which I can of course investigate the consequences of the mutations.’[26] Is that normal? ‘No other organism works as fast,’ says Fouchier. ‘Genetic modification of a plant takes months or years. When it comes to humans, we have decided we won’t do it at all.’ Fouchier altered the bird flu virus with characteristics of previous pandemics in 2011, to see if he could change the virus in such a way that it could also attach itself to human cells. He succeeded, but criticism ensued. The American government asked Fouchier to keep his research results a secret. After all, he had just created a possible biological weapon. The Dutch government heeded the American advice.[27]

 

Was this type of research being conducted with coronaviruses?

In 2015, researchers generated a virus with the protein of the horseshoe bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone.[28] This virus caused illness in mice and could replicate efficiently in human cells in the respiratory tract.[29] The researchers found clues that the virus could jump directly from bats to humans and cause illness in humans.[30] The research was conducted in a collaboration between universities and institutes in America, Switzerland, and the Wuhan Institute of Virology (WIV) in China.[31] At the time, the study caused a stir. Amerika had announced to put a stop to ‘gain-of-function’ research due to biosafety and biosecurity risks in 2013.[32] This specific study had started before that announcement, and was continued upon review because it was thought not to fall under the new restrictions.[33] After the Americans stopped the financing, the WIV in China took over the lead of the study.[34] This doesn’t necessarily mean that the new coronavirus emerged from a Wuhan laboratory. An official international investigation might shed more light onto the question in the future.[35]

 

Viruses are mutated so that they become more dangerous than before in so called ‘gain-of-function’ studies

 

How dangerous is the new coronavirus?

As stated above, the RNA, the genetic material, of the new coronavirus does not determine how dangerous the virus actually is. We have to judge the virus based on its epidemiologic data. Such as: how many people have been infected with the virus? How many of them have become ill, how quickly have they recovered, and which percentage has died? Based on the (estimated) answers, the government introduces new measures. We try to answer these questions by testing, measuring, collecting the data and analysing it. Worldwide, 5.64 million cases of corona were reported as of the 28th of May, and 349.100 deaths.[36] In the Netherlands, there were 46.257 people who tested positive, 11.727 people hospitalized and 5.951 deaths as of the 30th of May.[37] What can we conclude from these numbers? Not so much yet.

 

The danger of any virus needs to be determined by its epidemiological data

 

Measuring means knowing?

This is because a lot depends on how you are testing, how much you are testing, and who you are testing. Two types of tests are mostly used to determine if anyone is carrying a specific virus. The two tests measure different things, so we can answer different types of questions based on the results. Both tests have their advantages and disadvantages where practicability and reliability is concerned.

 

The PCR-test

There are many different corona tests, with different degrees of reliability. Two tests are widely used. The first is a PCR test. This test detects genetic material (RNA) of the virus in your nose or mouth, confirming whether you have been infected. The test is specific and sensitive.[38] What does that mean? It means that it can check whether the virus is in your body, and how much of the virus is there. A limiting factor of this test is that scientists have to look for the specific virus.[39] To find it, they don’t look for the entire 300.000 character long RNA-code: they choose a part of the genetic code, a part of which they suspect it will not mutate.[40] If the match between the part that they decide to look for, and the virus in the patient, is a bad one, the patient could get a negative result while the virus is in fact inside him.[41] This is not only a theoretic mistake. Some people have actually been tested six times and get positive results the seventh time.[42] According to an article in The Wall Street Journal, about 30% of the people who has the virus, gets a negative result.[43] The other way around is also a possibility: because the technique is so sensitive, small amounts of a virus can be found that are not necessarily the cause of any illness.[44] This is because the PCR-test cannot tell if the virus is intact, says analytical bio scientist Willem Engel.[45] If the immune system has already defeated the virus, little pieces of virus garbage can remain in the body for months. The PCR-test is so sensitive that it can still pick up these little pieces.[46] If the virus has left the body entirely, the PCR-test cannot detect whether you have been infected with the virus in the past.[47]

 

The serologic test

The other widely used test is the serologic test: this one checks for antibodies of the coronavirus in your blood.[48] Antibodies remain in the blood for a long time, providing a kind of map of viruses you have been infected with in the past. According to analytical bio scientist Willem Engel there is also a disadvantage of this type of test: the antibodies measured in your blood might not be the antibodies of the new coronavirus, but of an old one.[49] If there are antibodies in your blood from former coronaviruses, which, as stated above, form a normal part of the existing seasonal flu viruses, they might be genetically similar to the antibodies of the new virus: so similar in fact, that the test cannot always distinguish between the two. This could explain how people who are tested positive can still contract the new coronavirus at a later point in time.[50] Other people have come to this same conclusion.[51] The corona tests have not been evaluated for their reliability yet. The Dutch Governmental Institute of Health and Environment, which is also in the process of evaluating these tests[52], has started a study to find out how many people in the Netherlands have antibodies of the new coronavirus in their blood. They will check 6.000 people. With the results, they wish to find out more about how the virus is spreading and if herd immunity is being built.[53] The people taking part in the study are people whose blood has been tested before: that way, current blood samples can be compared with earlier ones.[54]

 

How many people have been tested?

The number of people who have been tested positive for corona in itself is no indication of total amount of infected people. This depends instead upon the total number of tested people. Existing data is insufficient to compare contamination data from different countries. Should a first country test half its population, and a second country test only a third, it would appear that the first country has more infected people, while in fact, they have only tested more people. In South Korea for example, the number of infected people suddenly skyrocketed with 200% when people started to be tested on a large scale.[55] It also works the other way around: when you stop testing, there are no more corona cases.

 

The number of contaminated people suddenly skyrocketed with 200% when people started to be tested on a grand scale in South Korea

 

Who did we test?

It also matters who we test. The testing policy roughly up until now has mainly been aimed at logically dividing scarce medical supplies. This makes sense of course, but it also makes for unreliable statistics. On the whole, people have been tested when they showed certain symptoms and/or when they worked in a specific profession.[56] This group of people naturally has a higher chance of being infected, says German pulmonologist Wolfgang Wodarg.[57] When you test the entire population of a certain country at the height of a flu epidemic, you will find a virus infection in 7 to 10% of these people, says Wodarg. If you only test the people in the GP’s waiting rooms, the percentage increases. If you only test people in a hospital, the percentage further increases. The most effective strategy to prevent selection bias and distortions in the data is therefore to test a random selection of the population.[58] This is also the strategy of the ongoing study of the Dutch government.[59]

 

Case Fatality Rate vs. Infection Fatality Rate

But there are several studies which have already focused on analysing a random selection of people. These studies try to estimate the percentage of infected people and the fatality rate to give us an idea of how widely spread, how dangerous, and how deadly the virus really is. Experts do not agree amongst each other which fatalities should be included in these calculations.[60] Some include everyone who dies after a positive diagnosis, even if they were also suffering from underlying illnesses which might have caused them to die; and how to calculate the people who die without having been tested (and could have been tested positive)?[61] Furthermore, the data that can be collected after an epidemic has ended might provide different answers than the answers that are given during the course of one.[62] Based on former experiences, the numbers could turn out to be higher[63] but also lower.[64] If we want to know which people have been included in a certain study, we look at these terms: Infection Fatality Rate (IFR) and Case Fatality Rate (CFR). IFR is the number of fatalities amongst a group of infected people, also including asymptomatic and non-tested people.[65] This is usually seen as the most reliable method.[66] CFR is the number of fatalities amongst the number of positively diagnosed people.[67] The WHO initially estimated the CFR of the new coronavirus to be 3.4%.[68]

 

Clues from a finished study: Diamond Princess

The first situation in which an entire, contained group of people was tested, happened to be on the cruise ship Diamond Princess. The ship was quarantined with 3.711 passengers on board. About 700 people were infected and six people died.[69] Based on the data of the cruise ship, scientists estimated the CFR in that case to be 2.3%, and the IFR to be 1.2%.[70] Adjusted to the average age of a population (the cruise ship contained a relatively high percentage of elderly people) this would amount to rates of 1.1% (CFR) and 0.5% (IFR) in China[71] and 0.125% in the US.[72] Much lower than the 3.4% mentioned by the WHO.

 

Other finished studies: New York and Gangelt

John Ioannidis is a professor of medicine, epidemiology, and health at Stanford University. He is specialised in pointing out mistakes in research methods. Ioannidis was one of the researchers who tested and analysed 3.330 residents of Santa Clara County, US, on antibodies of the new coronavirus last April.[73] 50 people tested positive, which is 1.5%.[74] The most important implication of the New York study, according to the researchers, is that the total number of infected people is much higher than the number of reported cases. Following this data, the IFR would much sooner be somewhere around 0.17%.[75] A third study took place in Germany. A team at the University of Bonn tested a random group of 1.000 residents of the city of Gangelt, one of the epicentres of the virus outbreak.[76] They concluded that about 15% of the population was or had been contaminated, and they calculated the IFR to be 0.37%.[77]

 

Flu numbers

The fatality rate of the seasonal flu in the US is estimated to be somewhere around 0.10%.[78] Some mild or ‘normal’ coronaviruses have in previous years even caused fatality rates of 8% with elderly in care homes.[79] Often, these people are not tested for flu viruses, however: they fall under the general number of 60 million people which die each year from unspecified causes.[80]

 

Case study: Flu numbers in the Netherlands

The excess mortality rate during the 18 weeks of the flu season in 2017/2018 in the Netherlands amounted to an estimated 9.444 fatalities.[81] About 900.000 Dutch citizens were floored by the flu that year: 40 hospitals stopped taking patients.[82] Also in that period, there were a lot more cases of pneumonia: a peak of 40.000 compared to the average 13.000, with the notable difference that patients remained on the ICU shorter than they do now.[83] Ted van Essen, retired GP-researcher and chairman of the Dutch Influenza Foundation recalls: ‘A disaster happened in our country, 9,500 people died. But no-one addressed the government at that time. There was no further investigation at all.’[84] The number of corona fatalities in the Netherlands is calculated to be 5.951 on the 30th of May.[85] The excess mortality rate in the first nine weeks of the corona epidemic is estimated to be almost 9.000.[86]

 

Corona: just another flu?

These studies conclude that the fatality rate of the new coronavirus is much lower than initially thought, much closer to the normal rates of the seasonal flu.[87] In the Netherlands, the excess mortality rate of the new corona virus is of yet nothing out of the ordinary. Two years ago, there was a higher excess mortality rate during the flu season. We cannot yet draw any conclusions from these numbers. The new virus differs from previous viruses in several ways. The WHO explains how the normal flu and the new coronavirus differ from one another.[88] For example: the flu spreads faster and spreads even before you have symptoms, contrary to the new coronavirus. The most important difference is that the symptoms of the new coronavirus appear to be worse. The new coronavirus seems to infect more people and cause more serious symptoms. While the flu forms a higher risk for children, pregnant women, elderly and people with underlying chronic illnesses, the new virus mainly poses a threat to elderly and people with underlying illnesses.

 

 

Corona: just another flu?

 

 

Conclusion: the danger of corona

It seems that we can only really know what happened when we compare the number of deaths to the number of deaths in previous years, after the year has ended. Countries are planning to investigate the medical reports of the people who died to determine how big a share the coronavirus can really take credit for.[89] The excess mortality of 2017/2018 might be surpassed in the Netherlands, but that depends on what will happen in the next months.[90] Even then, however, it is difficult to draw conclusions. What has been the effect of the measures that the governments have taken everywhere around the globe? Have they prevented more deaths? Or have they made treatment of patients with other types of illnesses like heart disease, strokes, or bleeding, more difficult?[91] And what will be the effect of social distancing on depression and suicide?[92] The next episodes of these series will focus on the measures following the epidemic, vaccines and medicines, as well as life after corona.

What will be the effect of social distancing on depression and suicide?

[1] University Medical Centre Leiden, the Netherlands, https://www.lumc.nl/org/mm/patientenzorg/Microbiologie/

[2] Ibid.

[3] VPRO Tegenlicht, ‘Virus van Morgen’, https://www.vpro.nl/programmas/tegenlicht/kijk/afleveringen/2019-2020/virus-van-morgen.html

[4] https://nl.wikipedia.org/wiki/Immuunsysteem

[5] Ibid.

[6] Dutch Governmental Institute for Health and Environment, https://www.rivm.nl/griep-griepprik/griep

[7] Richman DD, Whitley RJ, Hayden FG, eds. Clinical virology, 4th edn. Washington: ASM Press 2016.

[8] Sema Nickbakhsh et al., ‘Virus-virus interactions impact the population dynamics of influenza and the common cold’, 26 December 2019, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936719

[9] Joep Engels, ‘Wat dit coronavirus zo bijzonder maakt,’ Trouw, 21 March 2020, https://www.trouw.nl/wetenschap/wat-dit-coronavirus-zo-bijzonder-maakt~bab00f5c/

[10] Ibid.

[11] Tan W, Zhao X, Ma X, et al., ‘A novel coronavirus genome identified in a cluster of pneumonia cases’, 21 January 2020, http://weekly.chinacdc.cn/en/article/id/a3907201-f64f-4154-a19e-4253b453d10c

[12] Ibid.

[13] Chaolin Huang et al., ‘Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China’, Lancet, 24 January 2020, https://www.thelancet.com/action/showPdf?pii=S0140-6736%2820%2930183-5

[14] Ibid.

[15] Pashant Pradhan et al., ‘Uncanny similarity of unique inserts in the 2019-nCoV spike protein to HIV-I gpI20 and Gag’, 31 January 2020, https://www.biorxiv.org/content/10.1101/2020.01.30.927871v1

[16] Botao Xiao en Lei Xiao, ‘The possible origins of 2019-nCoV coronavirus’, 6 February 2020, https://img-prod.tgcom24.mediaset.it/images/2020/02/16/114720192-5eb8307f-017c-4075-a697-348628da0204.pdf

[17] Botao Xiao en Lei Xiao, ‘The possible origins of 2019-nCoV coronavirus’, 6 February 2020, https://img-prod.tgcom24.mediaset.it/images/2020/02/16/114720192-5eb8307f-017c-4075-a697-348628da0204.pdf

[18] Kristian Andersen et al., ‘The proximal origin of SARS-SoV-2’, 17 March 2020, https://www.nature.com/articles/s41591-020-0820-9

[19] See f.e. Luc de Roy, ‘Nieuwe coronavirus is het product van natuurlijke evolutie’, Vrt Nws, 18 March 2020, https://www.vrt.be/vrtnws/nl/2020/03/18/coronavirus-sars-cov-2-is-het-product-van-natuurlijke-evolutie/

[20] Ostap Carmody, ‘Он ведет себя необычно”. Биолог об особенностях коронавируса’, 3 April 2020, https://www.svoboda.org/a/30525376.html

[21] David Ignatius, ‘How did covid-19 begin? It’s original origin story is shaky’, 3 April 2020, https://www.washingtonpost.com/opinions/global-opinions/how-did-covid-19-begin-its-initial-origin-story-is-shaky/2020/04/02/1475d488-7521-11ea-87da-77a8136c1a6d_story.html

[22] ‘Nobelprijswinnaar en ontdekker van hiv: ‘Coronavirus werd ontwikkeld in Chinees laboratorium’, Het Nieuwsblad, 18 April 2020, https://m.nieuwsblad.be/cnt/dmf20200418_04926817

[23] Ibid.

[24] ‘Ontdekker van hiv en Nobelprijswinnaar oogst kritiek na claim dat coronavirus in labo in Wuhan werd gemaakt,’ 18 April 2020, https://www.hln.be/wetenschap-planeet/wetenschap/ontdekker-van-hiv-en-nobelprijswinnaar-oogst-kritiek-na-claim-dat-coronavirus-in-labo-in-wuhan-werd-gemaakt~ad32eb26/?referer=https%3A%2F%2Fwww.google.com%2F

[25] Vrt Nws, ‘Komt coronavirus uit Chinees lab?’, 1 May 2020, https://www.vrt.be/vrtnws/nl/2020/04/21/ontstond-het-coronavirus-in-een-lab-in-wuhan-zo-sprong-een-inte/

[26] VPRO Tegenlicht, ‘Virus van Morgen’, https://www.vpro.nl/programmas/tegenlicht/kijk/afleveringen/2019-2020/virus-van-morgen.html

[27] Ibid.

[28] Vineet D Menachery et al., ‘A Sars-like cluster of circulating bat coronaviruses shows potential for human emergence’, Nature Medicine, Vol. 21, No. 12, December 2015, https://www.nature.com/articles/nm.3985

[29] Ibid.

[30] Ibid.

[31] Ibid.

[32] Jef Akst, ‘Lab-Made Coronavirus Triggers Debate’, The Scientist, 16 November 2015, https://www.the-scientist.com/news-opinion/lab-made-coronavirus-triggers-debate-34502

[33] Jef Akst, ‘Lab-Made Coronavirus Triggers Debate’, The Scientist, 16 November 2015, https://www.the-scientist.com/news-opinion/lab-made-coronavirus-triggers-debate-34502

[34] Duurzaam nieuws, ‘Experimenten met coronavirus als in 2013 afgewezen, nieuwe risico’s in beeld,’ 3 May 2020, https://www.duurzaamnieuws.nl/experimenten-met-coronavirus-al-in-2013-afgewezen-wegens-risicos-voor-volksgezondheid/

[35] Bob van Huet, ‘China bepaalt nog steeds hoe en wanneer WHO oorsprong coronavirus gaat onderzoeken,’ AD, 20 May 2020, https://www.ad.nl/buitenland/china-bepaalt-nog-steeds-hoe-en-wanneer-who-oorsprong-coronavirus-gaat-onderzoeken~a17d9e0f/?referrer=https://www.google.com/

[36] Financial Times, https://www.ft.com/content/a26fbf7e-48f8-11ea-aeb3-955839e06441

[37] Dutch Governmental Institute for Health and Environment, https://www.rivm.nl/coronavirus-covid-19/actueel

[38] Ibid.

[39] Leids University Medical Centre, the Netherlands, https://www.lumc.nl/org/mm/patientenzorg/Microbiologie/

[40] James Gallagher, ‘Are coronavirus tests flawed?’, BBC news, 13 February 2020, https://www.bbc.com/news/health-51491763

[41] James Gallagher, ‘Are coronavirus tests flawed?’, BBC news, 13 February 2020, https://www.bbc.com/news/health-51491763

[42] Ibid.

[43] Christopher Weaver, ‘Questions About Accuracy of Coronavirus Tests Sow Worry’, 2 April 2020, https://www.wsj.com/articles/questions-about-accuracy-of-coronavirus-tests-sow-worry-11585836001

[44] Ibid.

[45] ‘Een crisis in de wetenschap, lockdown is een schande,’ Cafe Weltschmerz, 29 May 2020, https://www.cafeweltschmerz.nl/een-crises-in-de-wetenschap-lockdown-is-een-schande-willem-engel-en-ramon-bril/

[46] Ibid.

[47] Alexander Edwards, ‘COVID-19 tests: how they work and what’s in development’, The Conversation, 24 March 2020, https://theconversation.com/covid-19-tests-how-they-work-and-whats-in-development-134479

[48] Dutch Governmental Institute of Health and Environment, ‘Testen op COVID-19’, https://www.rivm.nl/coronavirus-covid-19/testen

[49] ‘Een crisis in de wetenschap, lockdown is een schande,’ Cafe Weltschmerz, 29 May 2020, https://www.cafeweltschmerz.nl/een-crises-in-de-wetenschap-lockdown-is-een-schande-willem-engel-en-ramon-bril/

[50] ‘Een crisis in de wetenschap, lockdown is een schande,’ Cafe Weltschmerz, 29 May 2020, https://www.cafeweltschmerz.nl/een-crises-in-de-wetenschap-lockdown-is-een-schande-willem-engel-en-ramon-bril/

[51] Norman Fenton et al., ‘Coronavirus: country comparisons are pointless unless we account for these biases in testing’, The Conversation, 2 April 2020, https://theconversation.com/coronavirus-country-comparisons-are-pointless-unless-we-account-for-these-biases-in-testing-135464

[52] Dutch Governmental Institute of Health and Environment, ‘Testen op COVID-19’, https://www.rivm.nl/coronavirus-covid-19/testen

[53] Dutch Governmental Institute of Health and Environment, ‘RIVM start onderzoek naar groepsimmuniteit nieuw coronavirus’, 31 March 2020, https://www.rivm.nl/nieuws/rivm-start-groot-onderzoek-naar-groepsimmuniteit-coronavirus

[54] Ibid.

[55] Christopher Weaver, ‘Questions About Accuracy of Coronavirus Tests Sow Worry’, 2 April 2020, https://www.wsj.com/articles/questions-about-accuracy-of-coronavirus-tests-sow-worry-11585836001

[56] See f.e. the testing criteria of the Dutch government: RIVM, ‘Testen op COVID-19’, https://www.rivm.nl/coronavirus-covid-19/testen

[57] Luuk Koelman, ‘Corona is vooral een politiek virus’, https://koelman.com/corona-is-vooral-een-politiek-virus/

[58] Norman Fenton et al., ‘Coronavirus: country comparisons are pointless unless we account for these biases in testing’, The Conversation, 2 April 2020, https://theconversation.com/coronavirus-country-comparisons-are-pointless-unless-we-account-for-these-biases-in-testing-135464

[59] Dutch Governmental Institute of Health and Environment, ‘RIVM start onderzoek naar groepsimmuniteit nieuw coronavirus’, 31 March 2020, https://www.rivm.nl/nieuws/rivm-start-groot-onderzoek-naar-groepsimmuniteit-coronavirus

[60] Glenn Kessler, ‘Those covid-19 death figures are incomplete’, The Washington Post, 27 March 2020, https://www.washingtonpost.com/politics/2020/03/27/those-covid-19-death-toll-figures-are-incomplete/

[61] Norman Fenton et al., ‘Coronavirus: country comparisons are pointless unless we account for these biases in testing’, The Conversation, 2 April 2020, https://theconversation.com/coronavirus-country-comparisons-are-pointless-unless-we-account-for-these-biases-in-testing-135464

[62] Glenn Kessler, ‘Those covid-19 death figures are incomplete’, The Washington Post, 27 March 2020, https://www.washingtonpost.com/politics/2020/03/27/those-covid-19-death-toll-figures-are-incomplete/

[63] Ibid.

[64] Deborah Blum, ‘Interpreting the Covid-19 Death Rate: You Asked, We Answered’, 23 April 2020, https://undark.org/2020/04/23/reader-questions-coronavirus-antibody-testing/

[65] https://en.wikipedia.org/wiki/Case_fatality_rate

[66] University of Bonn, Germany, ‘Heinsberg Study results published’, 4 May 2020, https://www.uni-bonn.de/news/111-2020

[67] https://en.wikipedia.org/wiki/Case_fatality_rate

[68] WHO, WHO Director-General’s opening remarks at the media briefing on COVID-19, 3 March 2020, https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19—3-march-2020

[69] Smriti Mallapaty, ‘What the cruise-ship outbreaks reveal about COVID-19’, 26 March 2020, https://www.nature.com/articles/d41586-020-00885-w

[70] Timothy Russell et al., ‘Estimating the infection and case fatality ratio for COVID-19 using age-adjusted data from the outbreak on the Diamond Princess cruise ship’, 9 March 2020, https://www.medrxiv.org/content/10.1101/2020.03.05.20031773v2

[71] Ibid.

[72] John P.A. Ioannidis, ‘A fiasco in the making? As the coronavirus pandemic takes hold, we are making decisions without reliable data’, 17 March 2020, https://www.statnews.com/2020/03/17/a-fiasco-in-the-making-as-the-coronavirus-pandemic-takes-hold-we-are-making-decisions-without-reliable-data/

[73] Eran Bendavid et al., ‘COVID-19 Antibody Seroprevalence in Santa Clara County, California’, 30 April 2020, https://www.medrxiv.org/content/10.1101/2020.04.14.20062463v2.full.pdf

[74] Ibid.

[75] Ibid.

[76] University of Bonn, Germany, ‘Heinsberg Study results published’, 4 May 2020, https://www.uni-bonn.de/news/111-2020

[77] Ibid.

[78] WHO, ‘Q&A: Influenza and COVID-19 – similarities and differences’, 17 May 2020, https://www.who.int/emergencies/diseases/novel-coronavirus-2019/question-and-answers-hub/q-a-detail/q-a-similarities-and-differences-covid-19-and-influenza?gclid=EAIaIQobChMIjsfzvOrd6QIVF_lRCh1mtA82EAAYASAAEgK90_D_BwE

[79] John P.A. Ioannidis, ‘A fiasco in the making? As the coronavirus pandemic takes hold, we are making decisions without reliable data’, 17 March 2020, https://www.statnews.com/2020/03/17/a-fiasco-in-the-making-as-the-coronavirus-pandemic-takes-hold-we-are-making-decisions-without-reliable-data/

[80] Ibid.

[81] RIVM, ‘Monitoring sterftecijfers Nederland’, 28 May 2020, https://www.rivm.nl/monitoring-sterftecijfers-nederland

[82] De Volkskrant, ‘Waarom corona zelfs de griep van ’17-’18 overtreft’, https://www.volkskrant.nl/nieuws-achtergrond/waarom-corona-zelfs-de-griep-van-17-18-overtreft~ba9c1f10/?utm_campaign=shared_earned&utm_medium=social&utm_source=whatsapp

[83] Ibid.

[84] Ibid.

[85] RIVM, https://www.rivm.nl/coronavirus-covid-19/actueel

[86] CBS, ‘Bijna 9 duizend meer mensen overladen in eerste 9 weken corona-epidemie’, 15 May 2020, https://www.cbs.nl/nl-nl/nieuws/2020/20/bijna-9-duizend-meer-mensen-overleden-in-eerste-9-weken-corona-epidemie

[87] Michael Schulson, ‘On Covid-19, a Respected Science Watchdog Raises Eyebrows’, 24 April 2020, https://undark.org/2020/04/24/john-ioannidis-covid-19-death-rate-critics/

[88] WHO, ‘Q&A: Influenza and COVID-19 – similarities and differences’, 17 March 2020, https://www.who.int/emergencies/diseases/novel-coronavirus-2019/question-and-answers-hub/q-a-detail/q-a-similarities-and-differences-covid-19-and-influenza?gclid=EAIaIQobChMIjsfzvOrd6QIVF_lRCh1mtA82EAAYASAAEgK90_D_BwE

[89] In the Netherlands, for example, this kind of study is being prepared. See: Nu.nl, ‘Wat is oversterfte en waarom is het belangrijk voor begrijpen coronavirus?’, 15 May 2020, https://www.nu.nl/coronavirus/6046684/wat-is-oversterfte-en-waarom-is-het-belangrijk-voor-begrijpen-coronavirus.html

[90] Ibid.

[91] John P.A. Ioannidis, ‘A fiasco in the making? As the coronavirus pandemic takes hold, we are making decisions without reliable data’, 17 March 2020, https://www.statnews.com/2020/03/17/a-fiasco-in-the-making-as-the-coronavirus-pandemic-takes-hold-we-are-making-decisions-without-reliable-data/

[92] RTL nieuws, ‘Als corona je tot wanhoop drijft,’ 30 April 2020, https://www.rtlnieuws.nl/nieuws/artikel/5106571/wanhoop-door-corona-zelfdoding-113-hulp-vragen-ondernemers