Talk:Wuhan coronavirus outbreak

Origin of 2019-nCoV?
The genome of 2019-nCoV has been claimed to come from four different sources:
 * 1) Bat coronavirus similar to Bat-SL-CoVZXC21 or Bat_SL-CoVZC45
 * 2) Spike glycoprotein gene from human SARS
 * 3) pShuttle-SN vector used in labs for splicing the genome
 * 4) HIV inserts at the tips of the spikes in the spike glycoprotein

Points 2 and 3 are wrong!

I analyzed the two claims made about inserts. James Lyons-Weiler claims that the 2019-nCoV virus has a unique sequence about 1,378 bp (nucleotide base pairs) long that is not found in related coronaviruses. He published the sequence online. He also claims that the sequence also contains the pShuttle-SN expression vector.

I ran the sequence through an online DNA to protein translator. Reading it in reading frame 2 (i.e leaving out the first "c") gives this amino acid sequence.

SVLHSTQDLFLPFFSN VTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNV VIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLRE FVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSS GWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQ PTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTK LNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNY LYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVG

The sequence is identical to the sequence published in the now withdrawn Indian paper. It corresponds to positions 46 to 504 in the full protein (positions 50 to 508 in the alignment table). The sequence is a close match to the SARS spike protein. There is no place to fit in the pShuttle-SN sequence, unless the pShuttle-SN sequence itself mimics or contains the SARS spike protein. James Lyons-Weiler now admits that this is in fact the case.

James Lyons-Weiler also claimed that the spike glycoprotein of 2019-nCoV is most similar to the SARS spike protein and not to the SARS-like coronavirus in bats. This is not true. The article in The Lancet records a 80.2% match between the spike protein of 2019-nCoV and Bat_SL-CoVZC45 but only 76.2% between 2019-nCoV and SARS. This level of similarity is also shown in the sequence alignment presented in the Indian paper.

The Indian paper makes the mistake of comparing 2019-nCoV to SARS, when in fact it is most related to SARS-like bat virus Bat_SL-CoVZC45 or Bat_SL-CoVZXC21 or some common ancestor. This however does not invalidate their results. There are a near infinite number of current and past viruses in the wild that are ever closer ancestors to 2019-nCoV. Comparing 2019-nCoV to SARS is not fundamentally different to comparing to a bat coronavirus or to some yet to be discovered closer relative.

The paper should be rewritten by comparing 2019-nCoV to Bat_SL-CoVZC45. It would also be interesting to know if the insets match the DNA sequence of the database of known HIV genomes and not only the amino acid sequence. I would do the comparison myself, but I do not yet have access to the 2019-nCoV or Bat_SL-CoVZC45 full genomes.

The spike protein of SARS is 1255 amino acids long, nine more than in Bat_SL-CoVZC45. A transformation from SARS to 2019-nCoV removes four amino acids and adds 22 for a total of 1273. A comparison of Bat_SL-CoVZC45 to 2019-nCoV should see inserts of 31 to 35 amino acids or 93 to 105 nucleotides.

I still think the link to HIV sequences is statistically meaningful. (continued.)


 * http://www.tiem.utk.edu/~gross/bioed/webmodules/aminoacid.htm
 * https://en.wikipedia.org/wiki/HIV
 * https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV
 * https://en.wikipedia.org/wiki/Envelope_glycoprotein_GP120

-- Petri Krohn (talk) 03:57, 5 February 2020 (UTC)

Chinese claims

 * Chinese ambassador to Russia on coronavirus: one day everything secret will be revealed (lit. 'will become explicit'), TASS, in Rus.
 * as robo-translated: ...The Chinese Academy of Sciences has collected data on 93 samples of the COVID-19 genome, published in a worldwide database covering 12 countries on four continents. Thanks to studies, it was discovered that mv1 was the earliest “ancestor” of the virus, it evolved into a set of genes (haplotypes) H13 and H38, and H13 and H38, in turn, jointly generated a second generation haplotype - H3, and H3 again evolved into a haplotype H1. In simple terms, mv1 haplotype is “great-grandfather”, H13 and H38 are “grandfather” and “grandmother”, H3 is “dad”, and H1 is “baby”. The virus that appeared in Wuhan on the seafood market is a virus of the H1 gene population. Prior to the H1 haplotype in Wuhan only the H3 haplotype was discovered, and this haplotype has nothing to do with the seafood market in Wuhan. The older haplotypes H13 and H38 were never found in Wuhan. Strains of these ancient haplotypes were also not found, which is very illogical. This suggests that a sample of the H1 haplotype was brought by a certain infected person to the seafood market, after which an epidemic broke out.
 * phrase haplotype H3 (or N3), etc, occurs in earlier Russian sources on the same subject, in Rus:  гаплотип Н3, Н1  , etc. But I do not see those notations explained or used for the same subject in Western sources. So, I am not exactly sure what is the ambassador talking about. This may be Chinese notations for those ....(haplotypes ?)
 * --Resup (talk) 10:28, 17 April 2020 (UTC)

Synthia?
This is probably a lunacy, but I'd like to look into and have a record on it anyway.
 * New version of the appearance of coronavirus COVID19, February 20, 2020, via-midgard.com (randomly walked into from some other page), robo-translation
 * Synthia (Mycoplasma laboratorium) is an artifical modification of mycoplasma with a synthetic genome which can reproduce itself, created by Craig Venter and Venter Institute in 2010 (true)
 * Mycoplasma pneumonia may cause atypical pneumonia in humans and post-pneumonia complications, eg autoimmune disease (true, but Synthia was based on Mycoplasma genitalium; how much they differ, I cannot say)
 * There was a Deepwater Horizon accident on an oil rig in the Gulf of Mexico in 2010, resulting in a massive oil spill (true)
 * Artificial oil-eating bacteria was used to combat the oil spill -some sort of biodegradation was used, details, and how artificial were they, are sketchy (eg here); also some indigenous microorganisms contributed to oil decomposition.
 * Synthia was that artificial oil -eating bacteria. - I not aware of any evidence that Synthia is oil eating. That part seems to be coming from conspirology websites making similar claims. This does not exclude, per se, that some artificial bacteria was created or tried to reduce oil spill, however I could not find any reliable information that this was the case
 * That bacteria attacked humans as well. In view of the above, it is not supported, however there were reports of various health and breathing problems in human population in the area, in particular due to algae (red tide), and other reasons. Official Texas respirotary data for 2010 and 2011 are pretty confusing. 9115 deaths from respiratory problems of all sorts in 2011, 35.5 per 100,000 people. In 2010, 3,013 deaths, 12.0 per 100,000, from pneumonia and influenza. There may be increased rate in 2011, but data are not in the same format to be certain.
 * As the story goes, fish ate that bacteria and eventually surfaced in Wuhan in 2019, to be a source of a chimera with coronavirus. That is not evidenced and probably is a long shot, but I cannot quickly refute it with certainty; and I have not done sequencing type stuff in practice before. --Resup (talk) 12:10, 22 March 2020 (UTC)

Mycoplasma pneumonia
Strangely, some descriptions of clinical symptoms of COVID 19 resembles those of "walking pneumonia" /mycoplasma pneumonia, like not realizing it is a pneumonia, with a chance (in some cases) to end unexpectedly in a life threatening situation. Also reported autoimmune problems appear similar. There is no microbiological similarity though between COVID19 virus and mycoplasma pneumonia. Whether or nor their biological attack modes are similar (like perhaps targeting same/similar lung cells), I am not sure. --Resup (talk) 06:31, 24 April 2020 (UTC)

Coronavirus with time machine?
I have reviewed the article preprint quoted in this article by China Global Television Network. It is bogus!
 * New study further proves Wuhan seafood market not the source of COVID-19 - CGTN, February 23, 2020 (video)
 * ''A recent study conducted by a group of Chinese scientists have found further genome evidence to prove that the seafood market in Wuhan is not the source of the novel coronavirus – a claim first made in a paper published on The Lancet.
 * ''The study, led by researchers from Xishuangbanna Tropical Botanical Garden of Chinese Academy of Sciences, South China Agricultural University and Chinese Institute for Brain Research, was published on ChinaXiv on Saturday in a pre-print version without peer review.
 * ''Per the study, genetic data suggests the virus was introduced from elsewhere and had already circulated widely among humans in Wuhan before December 2019, probably beginning in mid to late November.
 * ''The crowded seafood market facilitated the virus transmission to buyers and spread to the whole city on a large scale in early December 2019, corresponding to the estimated population expansion time, the study shows.
 * ''Researchers collected the genome-wide data from 93 new coronavirus samples shared on the GISAID EpiFlu, an international database that stores information about influenza virus, to study the evolution and human-to-human transmission of the virus over the past two months.

Did haplotype H3 come before H1? The article preprint claims so:


 * Decoding evolution and transmissions of novel pneumonia coronavirus using the whole genomic data
 * ''H1 and its descendant haplotypes from the Hua Nan market should be derived from the H3 haplotype, which was not linked to the market.

The phylogenetic network alone cannot determine what was the ancestral haplotype. Mutations can have happened both ways. There are three ways of deriving the ancestral node from a phylogenetic network: The ChinaXiV paper is doing this wrong. The known cases of H3 appeared one month later than H1. This is evident from the haplotype timeline included in the article.
 * 1) Date the appearance of each haplotype.
 * 2) Follow known infection patterns.
 * 3) Compare genomes to known distant ancestor (bat-RaTG13-CoV).

Neither have they demonstrated the link to link to bat-RaTG13-CoV through their hypothesized haplotype mv1. Choosing another hypothesized haplotype could as well have produced a link to some other SARS-CoV-2 haplotype. -- Petri Krohn (talk) 14:05, 24 February 2020 (UTC)

A group at the University of Cambridge has redone the work of the Chinese study using mainly the same genomic data and and has come unsurprisingly to the same conclusions.
 * April 12...
 * COVID-19: genetic network analysis provides ‘snapshot’ of pandemic origins - Forster & al., University of Cambridge, April 9, 2020

Group B is now called Group A. Group C has become Group B, and Group D is Group C. Haplotype H13 from Guangdong or haplotype H58 from Washington state are still considered the likely ancestral haplotypes most closely related to bat-RatG-13.

I agree that Group B (now Group A) centered around haplotype H3 is is most likely the ancestral group. Haplotype H1 just happened to cause a super spreader event at the wet market.

I am not sure is either of H13 or H58 came before H3. The phylogenetic tree or graph in the Cambridge paper shows several diamond shapes where one mutation has has been reversed. It is not possible to know which is branch is part of the ancestral tree based on the genetics alone. bat-RatG-13 is some 95% identical to SARS-COV-2. The Cambridge tree contains 229 mutations, 17 of these are included in the jump from bat-RatG-13 to H3 of SARS-COV-2. It is therefor likely that any one mutation may result in a haplotype that is "closer" to bat-RatG-13. Which is thus most likely? I vote for option 3. -- Petri Krohn (talk) 21:15, 12 April 2020 (UTC)
 * 1) H3 evolved from bat-RatG-13 via H13 and independently mutated to H58?
 * 2) H3 evolved from bat-RatG-13 via H58 and independently mutated to H13?
 * 3) H3 evolved from bat-RatG-13 directly and independently mutated to H13 and H58?

Italy likely to have 60,000 COVID-19 infections already
When Wuhan and Hubei were locked down on January 23, 2020 there were only 830 coronavirus infections in all of China. As of today there are 67760 cases in Hubei, almost a 100-fold increase! Yet the lockdown seems to have been effective as the epidemic is now over.

When northern Italy was put under lockdown on March 8, 2020 there were 7,375 cases in Italy, with a daily growth rate of 25%. From these numbers it is possible to estimate the total number of people in Italy already infected with the COVID-19 coronavirus.

The growth rate in China on and around January 23rd was about 50% per day. Going from 830 to 67760 would take about 10.86 days. This number is related to the average incubation period.

Staring from 7,375 with a daily growth rate of 25% for 10.86 days results in a 11.28-fold increase or a total of 60,613 cases.

This estimate is based on the assumption that the daily growth rate at the time of the lockdown was twice as high in China as in Italy. Italians may have already prepared for the coronavirus and practiced better hygiene. The figure 50% for the Chinese growth rate is a rough estimate. Averaging over 10 days before and after January 23rd gives a daily growth rate of 47.6%.

It may also be that the growth rates are similar. Comparing the Italian and Chines numbers side-by-side gives similar growth rates for the same number of patients, the main difference being the Italy started the quarantine and lockdown 6 days later and with nine times the number of cases. If so, the total number of COVID-19 cases in Italy may reach half a million.

-- Petri Krohn (talk) 22:22, 10 March 2020 (UTC)

Carlo Urbani
Carlo Urbani is credited with ending SARS epidemic in Vietnam by introducing strict quarantine measures. He got ill himself, documented his illness, and died on arrival to a conference in Bangkok in 2003. It is said that acute complications from the pneumonia had quick onset of about 3 hours --Resup (talk) 05:03, 15 March 2020 (UTC)

Russian chief pulmanologist interview

 * Interview with Alexand Chucalin, RT, titled "how to treat COVID-19", 25 min.

This is a long interview, with the essence appear to be that this a rather meek virus by itself and is not the killer itself; the real killer is bacterio-viral complications which may develop in some patients. The end stages in that case is Non-cardiogenic pulmonary edema, which require being placed on ventilator (if enough are available). While on ventilator, suppressed immunity may develop and rather mundane microorganisms are the eventual killers in that case.

Non-cardiogenic pulmonary edema ''develops both with direct lung damage (inhalation of toxins / toxic gases, aspiration of the contents of the gastrointestinal tract, water, blood, burns, pneumonia), and with extrapulmonary diseases (shock, severe polytrauma, sepsis, massive blood loss, pancreatitis / pancreatic necrosis, blood transfusion, uremia) is much less common. Another syndrome manifested by non-cardiogenic pulmonary edema and acute respiratory failure is ARDS - acute primary / secondary respiratory distress syndrome (synonymous with wet lung, shock lung). The development of this type of edema is mainly due to a violation of the function / structure of the alveolocapillary membrane.

''According to modern concepts of primary ARDS, the damaging factor directly affects alveolocytes, a surfactant that leads to damage to the alveolar epithelium and impaired integrity of the alveolocapillary membrane, resulting in transfusion of the liquid component of blood into the alveolar spaces. With secondary ARDS, the extrapulmonary factor is the basis for it, which forms against the background of the inflammatory response syndrome in the body (sepsis, bacteremia). Edema of this type (shock lung) does not obey the laws of fluid transport and does not depend on the level of hydrostatic pressure.

''Its peculiarity is a sharp decrease in ventilation / oxygenation of the body, which causes congestion in the lungs, oxygen deficiency of brain and heart tissues with the rapid development of life-threatening conditions. With inadequate / untimely assistance, mortality reaches 65-80%.

--Resup (talk) 05:22, 15 March 2020 (UTC)


 * "How to treat with coronavirus infection" - Cassad coverage of the interview, March 14, 2020

“The disease itself has at least four such outlined stages: the first stage is viremia. A harmless cold, nothing special, seven to nine days approximately in this interval, ”said Chuchalin. According to him, from the ninth to the 14th day of the disease, the situation "changes qualitatively," because it is during this period that viral-bacterial pneumonia forms. “After the epithelial cells of the body are damaged, microorganisms and bacteria are colonized in this anatomical space of the airways,” he explained. According to him, the doctor should "show his skill" to identify the disease in the initial stages. “If this situation is not controlled and the disease progresses, then more serious complications come, we call it acute respiratory distress syndrome, shock, a person cannot breathe on his own. To be precise, we call this non-cardiogenic pulmonary edema, ”said the specialist. According to him, pulmonary edema can be treated with a mechanical ventilation machine (mechanical ventilation). “If a person suffers this phase, then the immunosuppression caused by the defeat of acquired and innate immunity becomes fatal and the patient joins such aggressive pathogens as Pseudomonas aeruginosa, fungi”

Bill Ackman interview

 * Bill Ackman interview, YouTube, March 18, 2020
 * '' "Pershing Square Capital CEO Bill Ackman makes a plea to President Trump to shut the U.S. economy down." --Resup (talk) 20:15, 18 March 2020 (UTC)

Treat COVID-19 with immunosuppressors?
I suggest that immunosuppressants are tried as a treatment for the pneumonia associated with the new coronavirus disease. This idea comes from combining five pieces of information and speculation.


 * 1) Despite over a decade of efforts no one has been able to develop a vaccine for SARS or any other coronavirus. The problem is that the test subjects vaccinated (usually laboratory mice) exhibit a too strong immunoreaction to the virus, sometimes leading to a lethal cytokine storm.
 * 2) COVID-19 patients become highly infectious before symptoms appear, but are no longer infectious as the disease progresses. This shows that the immune system is working and able to kill all viruses outside cells but viruses may still survive inside the lung cells.
 * 3) All symptoms of COVID-19 are identical to the mysterious "vaping illness" that caused and epidemic in the United States in the fall of 2019. In both diseases CT scans show "ground-glass opacities" in the lungs. (The cause of "vaping illness" has never been properly established. It is my suspicion that it is actually caused by a strain of the SARS-CoV-2 virus.)
 * 4) Patients with hypersensitivity pneumonitis, an immune system disorder that affects the lungs show "ground-glass opacities" in CT scans.
 * 5) Immunosuppressors have been used successfully in treating "vaping illness".
 * 6) * Outbreak of Electronic-Cigarette–Associated Acute Lipoid Pneumonia — North Carolina, July–August 2019
 * ''All five patients improved clinically within 24–72 hours after initiation of intravenous methylprednisone (120 mg–500 mg daily). All five patients survived and were discharged home on a taper of oral prednisone.

-- Petri Krohn (talk) 21:17, 20 March 2020 (UTC)

After I wrote the above I noticed that a letter to The Lancet says essentially the same thing. -- Petri Krohn (talk) 23:12, 20 March 2020 (UTC)
 * COVID-19: consider cytokine storm syndromes and immunosuppression - Puja Mehta & al., The Lancet, March 16, 2020
 * ''Accumulating evidence suggests that a subgroup of patients with severe COVID-19 might have a cytokine storm syndrome. We recommend identification and treatment of hyperinflammation using existing, approved therapies with proven safety profiles to address the immediate need to reduce the rising mortality.
 * ''Predictors of fatality from a recent retrospective, multicentre study of 150 confirmed COVID-19 cases in Wuhan, China, included elevated ferritin and IL-6 suggesting that mortality might be due to virally driven hyperinflammation.

My take: there are indeed autoimmune-type forms of pneumonia (or complications after it); whether or not this is the case here is one of the questions to be answered, but apparently present view that it is not, Supposedly autoimmune response will create markers picked by tests, like blood tests, and we would know about it fairly quickly. In presentation of Russian chief pulmanologist, the impression is that ARDS which develops is caused by weaken immune response, not by over-response (but this may need more clarity). He does mention vaping matter, giving an impression that it is not understood, and commenting that 'they die once they are placed on ventilator'; he does not claim that vaping illness and COVID-19 have more in common. -- Resup (talk) 07:56, 21 March 2020 (UTC)

Herd immunity

 * The U.K. backed off on herd immunity. To beat COVID-19, we’ll ultimately need it. - National Geographic, March 20, 2020 --Resup (talk) 10:23, 21 March 2020 (UTC)

If blood plasma/serum of recovered patients is helpful one would have thought that that would support the potential for wider population to gain immunity. However there is some uncertainty whether developing antibodies necessarily confers lasting immunity. --Diagonal (talk) 13:57, 23 April 2020 (UTC)


 * STUDIES: 60% of people naturally RESISTANT to SARS-COV2 - Off-Guardian, June 12, 2020


 * I find the inferences in the above hard to take seriously. Just a layman's opinion but; supposing that there was such a level of natural resistance in the population, the virus surely would not have ever begun to spread rapidly, eg, doubling total infections every three days. After all +60% immunity/resistance is where 'shielding' herd immunity is supposed be realised. If the Off-Guardian piece suggestions are accurate, then why was there ever an accelerating rate of infections? --Diagonal (talk) 15:30, 15 June 2020 (UTC)

Basic reproduction number R0 for COVID-19 is infinite!
I have been trying to find a paper that would give estimates for the all three parameters of the epidemic, the basic reproduction number R0, the daily growth rate and the serial interval. So far I have not found any.

The growth rate in most Western countries is ten-fold every week or one thousand fold every month. The first cases of the Spanish epidemic were discovered on February 25. Now, 31 days later Spain has 57,786 laboratory confirmed cases.

The best estimates for the values are in the latest study by the London‌ Imperial College. Instead of estimating a R0 they give graphs for R(t) and its variation over time. The initial values are somewhere between 7 and 10. The paper also states a mean serial interval of 6,48 days.

An estimate for the future development of the pandemic in Finland by Finnish health officials is not sure what the R0 value for COVID-19 is. They claim that R0 in Lombardy was initially "little over 3" and give two prognosis for Finland based on R0 values of 1.6 and 1.8. The whole estimate is worthless crap!

There is no R0 value for COVID-19. Any real time value of R(t) is a function of social distancing measures. The best surrogate for a R0 value is infinity (∞). Everyone you meet will be infected! Everyone in the same room will be infected. If someone is infected in a concert hall with 1000 people, all one thousand are likely to be infected. The only way to decrease R(t) is by limiting the number of people you meet while infectious.

But even the stringiest social distancing measures cannot avoid a pandemic. As long as people meet and interact, everyone will eventually be infected. The only way of avoiding a pandemic and pushing R(t) under 1 is to isolate infected people before they become infectious. This requires tracing contacts and placing them all under quarantine.

-- Petri Krohn (talk) 23:57, 26 March 2020 (UTC)

Petri, there is another Wuhan-based paper which appears to me (on a very brief glance) more informed and more informative. It has supplements discussing parameters as well as SEIR -type model they use. They say that R(t) you worry about dropped to below 1 after most stringent of measures taken, centralized quarantine. I suppose that means quarantine for family members and all established contacts, totalitarian sort of way (And presumably not something likely to happen in Western pseudo-democracies, a China-Russia advocate would say).

And it was above 1 with only social distancing/isolation, in an earlier period (But noted, my understanding of this being claimed is mostly based on a Russian summary, not a particular place in the paper, which I looked into but in 'turning pages' mode as I could not (yet?) find time to do better).

My understanding is that R(t) (total number of directly ever infected by 1 person, with t dependence coming from changing preventive measures) is finite because a person is infectious for a limited time (recovering, getting isolated, or dying after a while); only direct infections (presumably) are counted, not via another party; and this is indeed affected by social interactions mode but an average (in some sense) is taken.

I also note that in SEIR model important parameter is not R(t) but infection rate parameter (I gather called b in paper I quote) in the dynamical system saying essentially that d I/dt = b/N S* I + other terms, d S/dt = -b/N S* I + other terms, S susceptible, I infected, N population size (I am yet to ascertain fine details here). Recovery of I is modeled by terms including dI/dt = - gamma I (+other terms). R(t) is then computed, taken into account this dynamics, and there is a formula somewhere in supplementary part of the paper I link. (Noted, comments written in a hurry as I do not really have much time; so details could be inaccurate; paper(s) need to be consulted for the accurate account).

I also note that available data is pretty 'dirty', for example in Italy number of deaths of people who had COVID is announced, but that does not mean COVID was the main cause of the death (if they would do this during a normal flu epidemic, results perhaps would appear quite dire too) --Resup (talk) 23:59, 27 March 2020 (UTC)


 * I have read that paper. They state an R0 of 3.88 but it is impossible to confirm, as they do not state a value for the serial interval or the growth rate they use. (The growth rate in the US is something like ten-fold in 8 days.) -- Petri Krohn (talk) 09:32, 28 March 2020 (UTC)

Gain of function research
Some references from Corbett report on this..(mixed bag)
 * Was There Foreknowledge of the Plandemic? Corbett Report April 13, 2019
 * NIH lifts 3-year ban on funding risky virus studies - Jocelyn Kaiser, Science December 19, 2017
 * Gain-of-Function Research: Background and Alternatives - National Academies Press April 13, 2015
 * In most instances, GoF experiments looking at receptor interactions with SARS-CoV and MERS-CoV showed that in in vitro or in vivo models with a civet strain gain human ACE2 receptors but also lose the civet ACE2 receptor

Spanish influenza 1918

 * Johan Hultin, got samples of dead virus in his second expeditions to Alaska, July 1997; first mission in the 1950's failed as virus was dead and PCR method was not yet available
 * Kristy Duncan, led a competing failed expedition to Norway, with wide press coverage leading to extraordinary security measures which took some 4 years of preparation
 * Jeffery Taubenberger --first sequencing
 * Initial Genetic Characterization of the 1918 “Spanish” Influenza Virus- Science, 1997
 * The Origin and Virulence of the 1918 “Spanish” Influenza Virus - Proc. Am. Philos. Soc., 2006

Story line YouTube (in Russ.), Jan 13, 2019

--Resup (talk) 12:29, 4 April 2020 (UTC)

God or man - who created COVID-19?
I was about to write a long piece on why I believe COVID-19 was created in a laboratory. Or at least why the proof offered that it is "zoonotic" is bogus. Here is a draft, partly translated by Google from Finnish.

The closest known relative found in nature to the SARS-COV-2 virus that causes corona disease is the bat SARS virus "RaTG13" found from Chinese bat droppings collected in 2013 and subsequently isolated. The lethality and virulence of the new virus are caused by two "copy-paste" style edits or changes to the genome. For a simple presentation of the changes see this story by the Sydney Morning Herald from two weeks week ago: The perfect virus: two gene tweaks that turned COVID-19 into a killer.


 * 1) The adhesion of the viral spike protein to the human ACE2 receptor has been improved. Better infectivity has been obtained by replacing the RNA sequence of the receptor-binding domain with the corresponding RNA sequence of the SARS virus found in pangolin.
 * 2) In order for the virus to penetrate the cell, the spike protein must be cut into two parts. Coronaviruses often use host cell enzymes for this. MERS virus researchers found that effective penetration is obtained with the human enzyme furin. The motif recognized by furin is found in the MERS spike protein at the cleavage site. A four amino acid long sequence "PRRA" has been added to the cleavage site of the SARS-COV-2 peak protein, which causes furin to cleave the protein when it is attached to the ACE2 receptor.

Both changes are such that a malevolent weapons engineer could have done on the basis of the 2019 science and knowledge. It may also be that they were born through natural evolution, especially if the coronavirus has been able to spread in the human population for some time.

Conspiracy theorists have accused virus and weapons laboratories of developing and releasing COVID-19. The scientific community has had a need to prove and convince the public that the virus is the result of natural evolution. The most notable publication on the subject is the letter sent by Kristian G. Andersen and partners to Nature Medicine. See The proximal origin of SARS-CoV-2. The key conclusions of the publication had however already been proved wrong before they were even published.

Andersen & al. relies on a study published by a group at the University of Minnesota at the end of January: Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on the Decade-Long Structural Studies of SARS Coronavirus.

The group attempted to improve the adhesion of the bat SARS spike protein to the ACE2 receptor with computer simulations. The simulations did not produce anything resembling the SARS-COV-2 receptor-binding domain (RBD). Andersen et al. concluded that weapons engineers could not have created the virus in a laboratory, as computer simulations would unlikely have produced anything like SARS-COV-2.


 * ''Thus, the high-affinity binding of the SARS-CoV-2 spike protein to human ACE2 is most likely the result of natural selection on a human or human-like ACE2 that permits another optimal binding solution to arise. This is strong evidence that SARS-CoV-2 is not the product of purposeful manipulation.

However, as early as February 16, the same research team from the University of Minnesota had produced another study that found the receptor-binding domain (RBD) of the SARS-COV-2 spike protein to be identical to that of a related SARS virus found in pangolins. See: Structural basis of receptor recognition by SARS-CoV-2.

The study was published on March 30 and it overturns the basis for the conclusion of Andersen et al.. SARS-COV-2 is however not derived from the pangolin SARS as it is more closely related to the 2013 bat SARS (RaTG13). There must have been a cut-and-paste type recombination event in which a fragment of the pangolin virus genome has been implanted into the bat virus. The cut-and-paste operation is easy to do in the laboratory, but RNA viruses ''have been found to exchange genetic material in nature.

A group from the University of Minnesota also studied the adhesion of various spike proteins. Synthesized spike protein gene sequences for RaTG13, SARS, and SARS-COV-2 were ordered from the GenScript and then inserted into a Sf9 cell line using pFastBac plasmids. The monoclonal proteins obtained were mixed with human ACE2 receptor proteins in a test tube. The SARS-COV-2 spike protein adhered 4–10-fold more tightly than any of the other spike proteins.

It would therefore be very possible that findings similar to the studies now published would have been made out of the public in a virus laboratory even before the spread of COVID-19. The U.S. biological weapons program has several laboratories around Eurasia. The best known is a laboratory in Georgia named after Senator Dick Lugar. Presumably, U.S. laboratory databases have a much broader collection of forms of SARS virus found in bats and pangolins than is found in open databases. It is likely that the SARS-COV-2 strain and the receptor-binding domain of its spike protein have also been collected.

The other edit is the furin cleavage site. There is a large corpus of studies on the benefits of a furin cleavage site in MERS and SARS-like viruses published over the last 15 years, including studies where a furin cleavage site is artificially inserted into the SARS virus. See for example this study from 2006: Furin cleavage of the SARS coronavirus spike glycoprotein enhances cell–cell fusion but does not affect virion entry


 * ''To investigate whether proteolytic cleavage at the basic amino acid residues, were it to occur, might facilitate cell–cell fusion activity, we mutated the wild-type SARS-CoV glycoprotein to construct a prototypic furin recognition site (RRSRR) at either position.

None of the arguments put forward against the laboratory origin of COVID-19 convince me. The origin of COVID-19 is difficult or impossible to prove. The scientific community has however concluded that COVID-19 was not born from scratch in Wuhan in the fall of 2019.

-- Petri Krohn (talk) 20:23, 14 April 2020 (UTC)


 * I do not know enough to judge but some doubts to register. I doubt one can reliably predict functionality based on edits, or reliably figure out edits needed for particular functionality. Educated guesses, perhaps, followed by trials. For something that long and complex, I do not think there would be a computational method to accurately predict what will happen, only approximate methods + searches not guarantied to succeed. Or pretty accurate dynamics but too short for biological timescale. On the other hand, natural processes or multitude of viruses attacking multitude of hosts for many years can try out lots of possibilities, until a variant with exponential self-replication of unfortunate to humans sort pops out (while zillions of other versions end in oblivion). Like Spanish flu, SARS, MERS before, and while not exact science, I find it kind of "believable" that another thing of such sort can pop up once in a while, and may be nastier then before in some ways. This does not totally exclude that somebody was doing experiments and it accidentally jumped from the lab, but nature would be a strong and possibly much stronger competitor here. Even if it jumped from the lab, almost certainly accidentally, as nobody had vaccine, readiness, or particular benefit, with what's going on out there. So it's still almost like an act of nature, with man designs going awry in this instance. BTW, there were claims that SARS is man-made (not particularly justified), and then SARS disappeared and those theories got forgotten. --Resup (talk) 22:29, 14 April 2020 (UTC)


 * The Wuhan virus lab found the likely origin of SARS in 2017, a bat cave in Yunnan Province in China. See Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. -- Petri Krohn (talk) 19:42, 15 April 2020 (UTC)

This paper from 2011 lends support for a natural origin: -- Petri Krohn (talk) 13:46, 28 April 2020 (UTC)
 * Molecular Epidemiology of Human Coronavirus OC43 Reveals Evolution of Different Genotypes over Time and Recent Emergence of a Novel Genotype due to Natural Recombination - Susanna K. P. Lau & al., Journal of Virology, November 2011
 * ''Coronaviruses are unique in having a high frequency of homologous RNA recombination, which is a result of random template switching during RNA replication that is thought to be mediated by a copy-choice mechanism (28, 46). Their tendency for recombination and high mutation rates may allow them to adapt to new hosts and ecological niches.


 * This article arguing that the sequence for RaTG13 is suspicious was discussed in this video. Its beyond me to assess the details of the argument. But a 7 year gap between the virus  apparently being found and the publishing of its sequence at the end of January 2020, does raise some questions.Diagonal (talk) 13:35, 9 May 2020 (UTC)


 * Richard H Ebright Twitter Stated purpose of PREDICT was to determine and disclose sequences in order, somehow, to prevent pandemics. Withholding sequences seems incompatible with stated purpose.

Reliable data on COVID-19 mortality - finally!
Three new sources of information allow us to make estimates on the infection fatality rate of the new coronavirus.

1) New York City now has about 20,000 deaths from COVID-19 out of a population of 8.4 million. The official data lists 15,400 confirmed and probable deaths. New York Times finds 19,200 excess deaths between March 11th and April 22nd. This means that the mortality so far is 0.24% making the pandemic worse than the 1918 "Spanish" Flu.

2) Data for the whole worldlists 2,733,591 coronavirus cases and 191,185 deaths, giving a case fatality rate of 7.0%. Until now it has been useless to compare the reported numbers as deaths follow new cases by some two weeks and case numbers have been growing exponentially. Now new cases have peaked or slowed down in most countries because of the lockdowns and other measures.

New York City seems to have reached its peak for both deaths and new cases. The peak number of confirmed deaths was 546 on April 7th. The average number of new cases for the week ending April 7th was 5070, which is close to the peak weekly number. Comparing peak to peak we get a case fatality rate of 10.8%. (This is a low estimate, as the peak in deaths should be spread over a longer period than the peak in new cases.)

3) The State of New York has done antibody testing and found that 21.2% of those tested showed antibodies for COVID-19. The semi-random sample was picked to be tested outside supermarkets. As the people doing shopping are less likely to have self-isolated in the past I think it is more reasonable to say that 10% of New Yorkers may have been infected. Also, it is likely that those infected are younger and healthier than the average population.

20,000 deaths out of 840,000 infected gives an infection fatality rate of 2.4%. No, this is not a flu! -- Petri Krohn (talk) 10:56, 24 April 2020 (UTC)


 * I think Chris Martensen found a pattern of a roughly 7% fatality rate of those needing to present to medical services in the U.S. I have seen estimations of +.5% IFR in a couple of studies from Europe (one of french prisoners, IIRC). If those were to be taken as reliable (big ?)that would mean roughly one in twelve of those infected need medical assistance. Confounding factors could be; are different strains, such at the one in NY perhaps, more virulent than others. Also what proportion of excess deaths is directly attributable to Covid 19? eg. I saw reports of high number of cardiac arrests in NY, can they be assumed to be principally due to viral infection?--Diagonal (talk) 14:11, 24 April 2020 (UTC)


 * Some have argued that excess mortality seen in the pandemic may be largely attributable to a deleterious impact of the lockdown measures on the health of the population. Whilst differences in how statistics are compiled between countries complicate comparisons, this regional breakdown from Ecuador indicates that there has been negative excess mortality in most regions of Ecuador during the lockdown, less deaths than can be expected normally. With excess deaths mostly concentrated in Guayas. Indicating that other regions have not yet seen many infections. --Diagonal (talk) 12:49, 14 May 2020 (UTC)

2015 Chinese-American gain-of-function study
This piece of sinophobic fear porn needs to be put to rest.


 * 2015 Scientific Paper Proves US & Chinese Scientists Collaborated to Create Coronavirus that Can Infect Humans - Peter R. Breggin, April 15, 2020
 * ''In 2015, American researchers and Chinese Wuhan Institute of Virology researchers collaborated to transform an animal coronavirus into one that can attack humans. Scientists from prestigious American universities and the US Food and Drug Administration (FDA) worked directly with the two coauthor researchers from Wuhan Institute of Virology, Xing-Yi Ge and Zhengli-Li Shi. Funding was provided by the Chinese and US governments. The team succeeded in modifying a bat coronavirus to make it capable of infecting humans.
 * ''The research was published in December 2015 in the prestigious British journal, Nature Medicine (volume 21, pages1508–1513). The paper by Vineet D. Menachery et al., “A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence” is available here as a PDF as well as on-line.
 * ''Footnotes to the scientific paper disclose that the research was funded by both the Chinese and US Governments, including grants from the NIH’s National Institute of Allergy & Infectious Disease.
 * ''Footnotes also document that the two Chinese researchers were active in their own laboratories as part of this coronavirus project.
 * ''At the bottom of the first page, the affiliation of both Chinese coauthors is listed as “Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.” The Chinese were being aided by the American government, American universities and American researchers in developing a potential military weapon with the capacity to cause a pandemic intentionally or accidentally.

No! It was the Americans who were being aided by the Chinese government and Chinese researchers in developing a potential military weapon with the capacity to cause a pandemic intentionally or accidentally.

From the Contributions section of the 2015 article (Chinese participation in bold):
 * ''V.D.M. designed, coordinated and performed experiments, completed analysis and wrote the manuscript. B.L.Y. designed the infectious clone and recovered chimeric viruses; S.A. completed neutralization assays; L.E.G. helped perform mouse experiments; T.S. and J.A.P. completed mouse experiments and plaque assays; X.-Y.G. performed pseudotyping experiments; K.D. generated structural figures and predictions; E.F.D. generated phylogenetic analysis; R.L.G. completed RNA analysis; S.H.R. provided primary HAE cultures; A.L. and W.A.M. provided critical monoclonal antibody reagents; and Z.-L.S. provided SHC014 spike sequences and plasmids. R.S.B. designed experiments and wrote manuscript.

There is no indication here that the Chinese were ever involved in any gain-of-function studies. Dr. Zhengli-Li Shi from the Wuhan virus laboratory provided the virus sample her team had collected. It was appropriate for the Americans to credit her in the authors list. This is not always done. The most famous example is when Luc Montagnier from the Pasteur Institute in France sent a sample of the HI virus to Robert Gallo in the US. Or maybe the French virus contaminated Gallo's lab. It took 10 years to figure out.

As Doctor Breggin notes, the article in Nature Medicine created controversy at the time. It was immediately criticized in the sister publication Nature by Declan Butler on November 12, 2015, three days after the original article was published. See Engineered bat virus stirs debate over risky research. On the same day, Jef Akst in The Scientist explains the context.


 * Lab-Made Coronavirus Triggers Debate
 * ''In October 2013, the US government put a stop to all federal funding for gain-of-function studies, with particular concern rising about influenza, SARS, and Middle East respiratory syndrome (MERS). “NIH [National Institutes of Health] has funded such studies because they help define the fundamental nature of human-pathogen interactions, enable the assessment of the pandemic potential of emerging infectious agents, and inform public health and preparedness efforts,” NIH Director Francis Collins said in a statement at the time. “These studies, however, also entail biosafety and biosecurity risks, which need to be understood better.”
 * ''Baric’s study on the SHC014-chimeric coronavirus began before the moratorium was announced, and the NIH allowed it to proceed during a review process, which eventually led to the conclusion that the work did not fall under the new restrictions, Baric told Nature.

The US bioweapons program has a network of laboratories throughout Eurasia collecting natural viruses for American researchers. The most famous may be the Lugar Center in Georgia’s capital Tbilisi. As Dilyana Gaytandzhieva notes:


 * ''This military facility is just one of the many Pentagon biolaboratories in 25 countries across the world. They are funded by the Defense Threat Reduction Agency (DTRA) under a $ 2.1 billion military program – Cooperative Biological Engagement Program (CBEP), and are located in former Soviet Union countries such as Georgia and Ukraine, the Middle East, South East Asia and Africa.

-- Petri Krohn (talk) 08:36, 25 April 2020 (UTC)

US origin?
That New Jersey mayor (mainpage), unlikely. Nobody else among his contacts is known to have it; on the other hand, bad flu or bad pneumonia could well happen; people do get very sick or day from those. As for the test, this is what convinced him, but reality is that perhaps false positives or non-specific positive is not exceedingly unlikely, in real world tests. As many people get tested, a few false postives are to be expected.

Also reminds of a Russian socialite Ksenia Sobchak claim that she had COVID very early (November?)--for the reason that she felt very sick. That claim is not convincing. --Resup (talk) 01:03, 5 May 2020 (UTC)

Biological origin?
I might have classed this paper as potentially lending support to Sars Cov 2 being a product of synthetic modification...doesn't it undermine the plausibility of a natural evolution?
 * SARS-CoV-2 is well adapted for humans. What does this mean for re-emergence? (PDF)
 * e.g.
 * However, no precursors or branches of evolution stemming from a less human-adapted SARS-CoV-2-like virus have been detected....
 * and
 * the majority of the non-synonymous substitutions in SARS-CoV-2 S are distributed across the gene at low frequency and have not been reported to confer adaptive benefit (Figure 4). Yet, the SARS-CoV-2 S has been demonstrated to bind more strongly to human ACE2 and has a superior plasma membrane fusion capacity compared to the SARS-CoV S (32,33). The only site of notable entropy in the SARS-CoV-2 S, D614G, lies outside of the RBD and is not predicted to impact the structure or function of the protein

--Diagonal (talk) 11:09, 18 May 2020 (UTC)


 * Yes, I agree. I put it under Biological origin? in Possible cases before Wuhan outbreak as we did not have another section for this point of view.


 * As for D614G or "Clade G", it makes the virus more infectious. All cases in northern France stem from the German Webasto executive that returned from Shanghai and was diagnosed on January 28 as Germany's first COVID-19 patient. -- Petri Krohn (talk) 21:12, 18 May 2020 (UTC)


 * This paper(pdf) concludes that they find no evidence of increased transmissibility from mutations including D614G. (Beyond me to evaluate this)
 * A much discussed mutation in the context of demographic confounding is D614G, a nonsynonymous change in the SARS-CoV-2 Spike protein. D614G emerged early in the pandemic and is found at high frequency globally, with 4,744 assemblies carrying the associated mutation in the data we analysed (Table S3). Korber et al. suggest that D614G increases transmissibility, and reported experimental evidence consistent with higher viral loads but with no measurable effect on patient infection outcome [14]. In our analysis D614G (nucleotide position 23,403) has at least 12 independent emergences. However, in line with the vast majority of other recurrent mutations we analysed, it does not appear to be associated with increased viral transmission. Consistent with our findings for D614G, our results support a wider narrative where the vast majority of the nearly 7,000 mutations we detect in SARS-CoV-2 are either neutral or even weakly deleterious.

--Diagonal (talk) 07:47, 23 May 2020 (UTC)

More bullshit from Sir Richard Dearlove
The Telegraph has published yet another attack on China and the Wuhan virus laboratory. A summary is available on Sputnik. Allegedly COVID-19 started as an accident at the Wuhan virus laboratory. The manuscript quoted has been published online on the QRB Discovery site. It reads like marketing material for a synthetic vaccine the team is developing.
 * Exclusive: Coronavirus began 'as an accident' in Chinese lab, says former MI6 boss - Bill Gardner, The Telegraph, June 3, 2020 (reader)


 * Biovacc-19: A Candidate Vaccine for Covid-19 (SARS-CoV-2) Developed from Analysis of its General Method of Action for Infectivity - B. Sørensen, A. Susrud and A.G. Dalgleish, QRB Discovery, June 2, 2020
 * 'Conclusions
 * ''We have offered a rationale for the design methodology and the necessary design parameters of a successful and safe vaccine against SARS-CoV-2. It is not included in any of the eight vaccine design routes identified in a recent Nature summary graphic. (Callaway, 2020) We have shown in this paper why a comprehensive analysis of the aetiology of the target virus is prerequisite, not optional. From the HIV experience, we have illustrated the risks of not so doing.
 * ''Next, we explained why, unlike in conventional vaccine design procedures, the choice of adjuvant is not to be seen as an afterthought but as integral from the beginning. We have deliberately chosen an adjuvant which has been shown to activate the innate and cell-mediated immune responses which are crucial to the successful presentation of the relevant epitopes. We have shown how Biovacc-19 has employed our understanding of the general method of action for infectivity and pathogenicity of the target virus to optimise action and to minimise risk, especially Antibody Dependent Enhancement; and we have presented the Non Human-Like epitopes in the SARS-CoV-2 Spike from which Biovacc-19 has been down-selected.

According to The Telegraph the team claim to have identified "inserted sections placed on the SARS-CoV-2 Spike surface" that shed light on how the virus finds its way into human cells. The claim is little different from the allegation by the Indian team that the genome contains "HIV inserts".

Nothing in the article says the group did any forensic research on the origins of the genome or of the spike protein. They have included a comparison table of coronavirus genomes which is based on the article by Zheng-Li Shi's group published in Nature on February 3, 2020. They make no mention of Bat CoV RaTG13 or the pangolin origins of the receptor binding domain of the spike protein.

There is allegedly another paper in the works by London professor Angus Dalgleish named A Reconstructed Historical Aetiology of the SARS-CoV-2 Spike. Maybe it contains something, maybe. There is however no reason to believe the chimeric virus was created in Wuhan and not, say at Fort Detrick in the USA.

-- Petri Krohn (talk) 00:22, 5 June 2020 (UTC)


 * It seems to me that although this article makes the case for zoonotic recombinations, it has to acknowledge some features that look difficult to explain away when making the case for a natural origin.


 * Emergence of SARS-CoV-2 through recombination and strong purifying selection - Science Advances, May 29, 2020


 * As you say there is not a clear reason to reject an origin elsewhere than Wuhan. One potential issue that would need explaining in the case of a leak and cluster in Maryland/Virginia would be that any cluster of cases could be expected to have become an epidemic in the US within weeks, allowing that the transmissibility of the virus was equal with what it is now thought to be.


 * We know the US carried out such research elsewhere but also projects on bat coronaviruses at WIV. This article says researchers often chose China for this kind of ethically dubious chimeric research.

--Diagonal (talk) 11:38, 5 June 2020 (UTC)

Barcelona waste water and a conspiracy theory
I read the preprint on the Barcelona waste water study.


 * Sentinel surveillance of SARS-CoV-2 in wastewater anticipates the occurrence of COVID-19 cases
 * ''SARS-CoV-2 was detected in Barcelona sewage long before the declaration of the first COVID-19 case, indicating that the infection was present in the population before the first imported case was reported.
 * ''In order to elucidate the evolution of COVID-19 in Barcelona, 24-h composite raw sewage samples from two large wastewater treatment plants were weekly analyzed for the presence of SARS-CoV-2 from April 13, in the peak of the epidemics, to May 25. In addition, for WWTP2, frozen archival samples from 2018 (January-March), 2019 (January, March, September-December) and 2020 (January-March) were also assayed.
 * ''Most COVID-19 cases show mild influenza-like symptoms and it has been suggested that some uncharacterized influenza cases may have masked COVID-19 cases in the 2019-2020 season. This possibility prompted us to analyze some archival WWTP samples from January 2018 to December 2019 (Figure 2). All samples came out to be negative for the presence of SARS-CoV-2 genomes with the exception of March 12, 2019, in which both IP2 and IP4 target assays were positive. This striking finding indicates circulation of the virus in Barcelona long before the report of any COVID-19 case worldwide.

There were only 9 frozen waste water samples available. The March 2019 sample is the only one that corresponds to the 2018-2019 flu season.

All samples were tested with five different probes targeting five different fragments of the SARS-CoV-2 genome. Diagnostic tests usually target only two or three gene sequences. The five probes used were the three (IP2, IP4, E) included in the French test (Institut Pasteur) and the two (N1, N2) included in the American test (Centers for Disease Control and Prevention).

When testing fresh samples drawn directly from sewers in May 2020, no single sample was positive for more than four probes. None of tests could detect the presence of the E gene. When testing mixed water from the waste water treatment plants the different probes gave different results. The IP2 and IP4 gene fragments were most likely to be present.


 * ...the conspiracy theory

I have previously voiced a suspicion that the CDC test is intentionally flawed. It is made to differentiate between the Wuhan strain of COVID-19 and any COVID strains in circulation before the Wuhan outbreak. This would explain why it took so long to produce and why testing was initially restricted.

If so, the Barcelona study is consistent with what one would see if COVID-19 had been circulation in Barcelona in the winter of 2019. The frozen sample from March 12, 2019 tested positive IP2 and IP4 gene fragments. The E gene has shown to be elusive in waste water tests. If the CDC test cannot detect pre-Wuhan nucleoprotein N, then the negative results are as expected.

More proof is needed. What the scientific community now wants is the sequencing of the genetic material in the March 12, 2019 sample. It is not necessary to produce a complete viral genome. What is needed is enough of the genome to place it into the phylogenetic tree. The tests may have destroyed the whole sample, making sequencing impossible. There should however be two test tubes with genetic material 107 and 108 base pairs long. Of these base pairs 58 and 56 come from the probes and primers used in the PT-PCR test. The remaining 101 base pairs came from the waste water time machine.

-- Petri Krohn (talk) 21:24, 30 June 2020 (UTC)

Hypothesis: Herd Immunity threshold at 10%-20% seroprevalence?
Some commentators - e.g. James Todaro,Chris Martenson, Real Clear Science - are speculating that due to levels of pre-existing or T-Cell (non-antibody generated) immunity, that once reported Sars-Cov 2 cases have spread through a formerly naive population to the extent of roughly 15%, then the rate of new infections drops off as 'herd immunity' for that population may have been effectively realized. If 40%/50% have such T-Cell immunity when 10%/20% acquire antibody based immunity a protective 60%/70% level of herd immunity is realized.

The hypothesis will be discredited if we see examples of cities where case counts are near or greater than 15% of the population and the daily rate of new infections has not fallen significantly.

According to John Hopkins via Martin Armstrong: Countries with highest recorded rates of infections The highest rate is in Chile.

According to Worldometer Qatar has the highest case count per capita. Qatar has a population of 2.6 million. Has had 113,646 cases, of those tested (524,466) that is 21.6%. It reached 100,000 cases (per capita 3.8%) over a month ago. New cases have slowed subsequently, but still remain a concern. If we were to assume that its positive test rate reliably indicates prevalence in the population, then Qatar would seemingly be close to the hypothesised threshold.

Extrapolating from these stats on excess deaths in Guayas, Ecuador is difficult because we don't have a reliable indicator of the infection fatality rate for the period. If we take a 1% IFR for Guayas then its 14,308 excess deaths in a population 4,387, 434 would give a figure of +30% per capita infections. Whereas assuming an IFR of 6% (based on official stats for Ecuador) leaves a nearer 5% per capita infection rate. According to El Universo new daily cases in Guayas are less than 10% of the peak numbers as officialy recorded.

A confounding factor in testing this hypothesis is the question of whether mild cases (mostly unreported) should be taken as counting amongst levels of pre-existing immunity or should be factored into case counts.

According to some quite extensive seroprevalence surveys Madrid was taken to have >10% antibody prevalence rate back in May. We would according to the hypothesis expect daily new cases there to remain low, but it looks like there are increasing daily cases there now, (if not drastic). This was reported a week ago: ''A total of 61% of residents in senior homes in Madrid and 30% of workers at these centers have developed IgC antibodies to the coronavirus. That’s according to the results of 18,500 blood samples taken by the regional health department in different social service centers in the region.''

According to James Todaro high rates of antibodies amongst the elderly would not be a counter example as T-Cell immunity declines with age.

Madrid Update August 21: Increased hospital admissions for Covid 19 are reported over the previous weeks. Hence the rise in new cases can't be written off as merely the consequence of increased rate of testing. It should be noted that the rise is less drastic than in March. However the 12 de Octubre Hospital that was close to collapse in the first wave has seen a notable rise in admissions, according to the new stats. Cases such as this look hard to explain away for those suggesting low herd immunity thresholds. The area the hospital serves was presumably hit hard during the first wave and is seeing increased admissions currently --Diagonal (talk) 10:40, 22 August 2020 (UTC)

Sao Paolo: At the end of June a seroprevelance survey estimated a 9.5% infection rate in Sao Paolo. By August there is no sign that the rate of new cases was decling. Noting that the area where the survey was carried out likely smaller than the region.

Serology tests are unreliable, but given a sufficiently extensive and representative section of population, the seroprevalence survey's should be in the right ball park. On the face of it the Madrid and Sao Paolo recent figures dont seem to support the hypothesis. Confounding factors: The unreliabilty of the seroprevalence surveys, patchiness between the areas might account for discrepencies.

Peru: The Iquitos, Loreto region (Thread - Priya Sampathkumar) Reached 70% seroprevalence according to preliminary results not considered conclusive. Apparently cases fell subsequently. Such high rates are dismissed by Todaro as being down to reduced T-cell immunity caused by malnutrition. The extrapolated IFR is low (just 0.7%), whilst the case fatality rate was ~14%. Due to either low recording of cases or over estimations of seroprevalence/infections. We would expect to see a higher IFR if malnutrition was a factor.

Some cities, countries to check: New York, Sao Paolo, Madrid, Guayaquil, Belgium

--Diagonal (talk) 12:23, 12 August 2020 (UTC)
 * Hi, Diagonal. I think I panned this same article, not that I published it. It cites falling deaths in Sweden, some 30% infected estimates, revised to 7.5%, and Diamond Princess ship where infections fell during cabin lockdown despite just 20% infected? If so, no on both. Classic model is most people infected = slower spread, less re-spread - 60% infected/immune WITH vaccine often works - this is extra-contagious and no vaccine, so maybe 70-80-90% mobile populace needs to be exposed/immune to work. Sweden: safe at 7.5%? No. Deaths fell like they do everywhere, mainly because people likely to die wise up. D.P. cruise ship: presumes it's airborne and should keep spreading unless people got immune. But agreement is - supported by this - it's not airborne like that. Spread stopped during cabin lockdown BECAUSE cabin lockdown. No virus knows 20% of other people in other cabins have been infected and decides to be less contagious in this cabin. That has no logic. The authors didn't seem to even get HOW herd immunity works. (fuller explanations available)


 * So anyway, if any derivative analysis seems to support something that doesn't even make sense ... maybe there's another reason for that appearance/something else at work. If it's okay with you, I'll try and come back soon to your analysis in whatever detail. I like analysis stuff, but not ATM> --Caustic Logic (talk) 14:38, 12 August 2020 (UTC)
 * Thanks CL, I'll have to look at the Diamond Princess data. Falling deaths can largely be attributed to better standard of care now the action of the virus is better understood. Maybe the virus will remain circulating and even some reinfections but we won't see large second waves in areas already hard hit. Although, it's hard to get why (if the theory is valid) cases could have seen exponential growth if there was already ~50% immunity, but adding just 10% or 15% means it grinds out. --Diagonal (talk) 17:20, 12 August 2020 (UTC)
 * Before I dig in, I notice you said "The hypothesis will be discredited if we see examples of cities where case counts are near or greater than 15% of the population and the daily rate of new infections has not fallen significantly." The article I'm thinking of (will see first if this is it) acknowledges some places (Bergamo, a prison) where it must've kept going, showing antibodies in 50-60% of the people - and antibodies often decrease or fade over time, so the percent exposed is even higher. (note: antibody lapse doesn't SEEM to allow re-infection, for which I've seen no proof. That supports the t+b-cell hypothesis).
 * Real Clear Science is the one I panned as lame. They should've noticed it was a bit too "clear." The herd prosperity one and Todaro I hadn't seen, but they sound wrong too. Sounds like you have better background knowledge here and are doing ok - you notice level don't stay down that easily, prone to rise again. I haven't even looked into most of these studies - good work. As for t-cell immunity, are they taking it as something people already HAVE that keep them from getting it? So far it seemed like the way you get immune AFTER you've gotten it, and AFAIK everyone's susceptible to start with. If that's already been covered, sorry.

--Caustic Logic (talk) 10:23, 13 August 2020 (UTC)
 * Leaving aside the issue of reinfections for now. I think the theory, according to Martenson (who has generally been a good source imo), is that there is some level of pre-existing immunity as under 10yo seem to have, plus a good proportion develop T-cell immunity easily (the science on that is beyond me). Whether or not it counts as pre-existing or as the result of an infection makes it harder to evaluate the data.


 * About the studies obviously you have to be careful with what you infer from the headlines (once you look at the the methodologies often the headline isn't supported). I've just thought to look at some hotspots to see if trends look to fit, so haven't delved in to them much here. Where the curves do support the hypothesis, they could also be explained by factors like NPI's, so it's quite murky to weigh up in a lot of ways. Cheers! --Diagonal (talk) 11:19, 13 August 2020 (UTC)


 * I do not have time now for the issue, but a brief comment, without having time to really investigate. Simple models do not do a good job of dealing with recovery (or death, or isolation0 after some time delay; they operate with instantaneous sub-population numbers, and try to do something sensible with that. As a consequence, they tend to say that in effect somebody infected will keep infecting for a long time, and even if chances are small, total number of infected may eventually be over 1 per infected person. It probably overestimates for how long this may, in effect, occur. It is conceivable that doing this better will predict that with proportion of already exposed (immune) above some threshold, expected new infections is under 1, per infected person, and so subpopulation of those infected will be extinct after a while. FWIW. The problem with all this is that by changing models you may change outcomes, and there is a danger to assume whatever will lead to conclusion one wants to draw. (But I have not spent time on it). --Resup (talk) 17:06, 12 August 2020 (UTC)

New blog post: On The Long March to Covid-19 Herd Immunity pans the 10-20% notion, finding several places in India and Italy hitting up to 57% seroprevalence, an rates to 68% and even 98% in prisons and a nursing home. I should have reviewed this and added Diagonal's notes on Madrid, and maybe try for some estimate for Guayas/Guayaquil (I haven't found any more specific information). Bergamo cases graphic below. --Caustic Logic (talk) 13:56, 27 August 2020 (UTC)


 * Just for the sake of running a possible (non-expert)line of defence of T-Cell immunity claims to examples of high seroprevalence. Perhaps the incidences of high seroprevalence could be explained by the extent of exposure to the virus. e.g. in environments where unmitigated transmission occurs such as prison or prior to social distancing measures those with the T-cell defense may be repeatedly exposed to the virus and hence develop the antibodies on top of the t-cell defenses. Whereas in a city like Stockholm in spring/summer there will be less repeated or prolonged exposure to the virus. But still a lot of work for low HI enthusiasts to do, I think.


 * It's sometimes more apt to think about things probablisticly e.g. perhaps most people being on a gradient from low exposure to high exposure, rather than binary logic of either infected or not. The chances of developing Covid-19 in relation to your level of exposure to Sars-Cov2 (the innoculum or dose you receive over time)will probably be non-linear. So the increase in your chances of a good outcome will be greater than the % reduction in viral load. Similarly as with the effectiveness of masks. Nassim Taleb has pointed pointed out that if two people are wearing masks that are each only 50% effective then the risk of transmission between them is reduced by 75%. So if the masks are both 60% effective then the risk is mitigated by 96%.


 * Caustic Logic, you may well have raised an important issue of the mortality for those who seemingly recovery from the main line symptoms of Covid and it will certainly need to be something that isn't overlooked --Diagonal (talk) 19:00, 27 August 2020 (UTC)