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1/ Those who follow me know that I think too much and ask too many questions. In my curiosity, I recently stumbled upon a story of a bat cave of coronaviruses, sudden unexplained death, and mysterious poison mushrooms
Buckle up it’s a weird one #medhistory #SARS #Covid_19 
Buckle up it’s a weird one #medhistory #SARS #Covid_19
2/ It all started with that foolish preprint that was again claiming that SARS-CoV-2 was made in a lab. A claim that no respected scientist or clinician supports, given the lack of evidence, including: @K_G_Andersen @angierasmussen @CT_Bergstrom #COVID19 https://twitter.com/angie_rasmussen/status/1307473817527230465?s=20
3/ So, I go back to what evidence we actually have. Because #science is awesome, we have a ridiculous amount of viral genomes that have continued to be tracked from early on in the pandemic:
- 4,678 @nextstrain @trevorbedford
- 84,932 @CovidGenomicsUK https://microreact.org/project/cogconsortium-2020-09-19/76399ee3/
- 4,678 @nextstrain @trevorbedford
- 84,932 @CovidGenomicsUK https://microreact.org/project/cogconsortium-2020-09-19/76399ee3/
4/ We also have amazing scientists who are out in the field (ie bat caves
etc) testing other animals for possible emerging pathogens. I don’t even know how you get into jobs like this but it's another reason why I love #ScienceTwitter! #COVID19 #coronavirus
etc) testing other animals for possible emerging pathogens. I don’t even know how you get into jobs like this but it's another reason why I love #ScienceTwitter! #COVID19 #coronavirus
5/ From a large amount of genetic data, the closest known ancestor to SARS-CoV-2 is a virus found in a horseshoe bat in Tongguan, a town North of Pu’er City in Yunnan Province, China in 2013 dubbed “RaTG13.” 
6/ Here are 2 excellent Nature articles on the origins of SARS-CoV-2:
https://www.nature.com/articles/s41564-020-0771-4 @robertson_lab @arambaut @maciekboni
https://www.nature.com/articles/s41591-020-0820-9 @K_G_Andersen
https://www.nature.com/articles/s41564-020-0771-4 @robertson_lab @arambaut @maciekboni
https://www.nature.com/articles/s41591-020-0820-9 @K_G_Andersen
7/ If you are interested in the most recent and exhaustive study of bat-CoVs in China, please check out this impressive paper by the bat man himself @PeterDaszak and colleagues, preprint, although cited by THE Dr. Fauci :)
https://www.biorxiv.org/content/10.1101/2020.05.31.116061v1.full.pdf
https://www.biorxiv.org/content/10.1101/2020.05.31.116061v1.full.pdf
8/ THE BAT CAVE. After the original SARS epidemic in 2002-2003 @PeterDaszak & his team were tracking viruses similar to #SARS in bats. They discovered a cave in Yunnan province inhabited by bats with a “rich gene pool of SARS-related coronaviruses.” https://pubmed.ncbi.nlm.nih.gov/29190287/#affiliation-1
https://pubmed.ncbi.nlm.nih.gov/29190287/#affiliation-1
9/ In the lab, they were able to infect human cells and then mice with these viruses causing a “SARS-like” disease. Blood samples from people living near the caves found that 2.7% developed antibodies to the viruses, revealing prior infection @PeterDaszak https://link.springer.com/article/10.1007/s12250-018-0012-7
10/ The 2005 paper: Bats are natural reservoirs of SARS-like coronaviruses (which included both @PeterDaszak & “Bat Woman” Dr. Zhengli-Li Shi at the Wuhan Institute of Virology) reported the first evidence that bats harbored coronaviruses closely related https://science.sciencemag.org/content/310/5748/676
11/ But the #US researchers ran out of funding!
NOOOOO!!!
So, they flagged the strains that most resembled SARS as most high risk to authorities in #China and the @WHO.
NOOOOO!!!
So, they flagged the strains that most resembled SARS as most high risk to authorities in #China and the @WHO.
12/ Through collaboration with WIV, over 8 years they have sampled over 10,000 bats, found some 500 novel coronaviruses, about 50 of which fall relatively close to the #SARS virus on the family tree, including RaTG13. @PeterDaszak
13/ They continue to published their ongoing results in a number of accredited academic journals and have even argued for the viruses to be added to the @WHO’s top pathogens of high risk to human health. @PeterDaszak
14/ In this paper from 2013, "results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs.” https://pubmed.ncbi.nlm.nih.gov/24172901/
15/ In 2019: Dr. Shi published another work stressing the importance of Bat Coronaviruses in #China
“Two bat origin CoVs caused large-scale epidemics in China over 14 years, highlighting the risk of a future bat CoV outbreak in this nation.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466186/
“Two bat origin CoVs caused large-scale epidemics in China over 14 years, highlighting the risk of a future bat CoV outbreak in this nation.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466186/
16/ In 2020, @PeterDaszak and team even looked at risk factors for these more vulnerable populations in rural China.
A qualitative study of zoonotic risk factors among rural communities in southern #China https://pubmed.ncbi.nlm.nih.gov/32040190/
A qualitative study of zoonotic risk factors among rural communities in southern #China https://pubmed.ncbi.nlm.nih.gov/32040190/
17/ So, we have caves full of bats in #China that we’ve known about for 15 years, potentially infected with any of several hundreds or thousands of coronaviruses, some of which have also been shown to have the capacity to infect human cells, mice, & actual humans, like #SARS 
18/ And these infected animals could extend to other countries outside of China, because they are BATS and can FLY.
So that seems concerning...
OK enough about bats, but what about the sudden unexplained death (SUD) and those poison mushrooms?
I AM SO GLAD YOU ASKED!!!
So that seems concerning...
OK enough about bats, but what about the sudden unexplained death (SUD) and those poison mushrooms
?I AM SO GLAD YOU ASKED!!!
19/ Since the 1970s, during the rainy season, villagers in Yunnan province have been dying suddenly of cardiac arrest. From 1975-2009, there were 395 sudden unexplained deaths (SUD), w/ 61 villages were affected with SUD clusters and 18 villages had single SUD cases reported.
20/ The phenomenon was called Yunnan Sudden Death Syndrome. Deaths increased gradually by year to reach an average of 21 per year from 1990 to 2005.
Following warnings in 2006 to villagers about eating unfamiliar mushrooms deaths decrease abruptly.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355161/#pone.0035894-Yang1
Following warnings in 2006 to villagers about eating unfamiliar mushrooms deaths decrease abruptly.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355161/#pone.0035894-Yang1
21/ The deaths almost always during rainy season (late June-early September) & at an altitude of 5900-7900ft in remote hamlets on the outskirts of rural villages. Deaths occurred over a week, with the highest risk was among young and middle aged adults. https://www.bbc.com/news/10630155
22/ 2/3 of victims in the hours before death, experienced symptoms such as heart palpitations, nausea, dizziness, seizures, and fatigue.
Initial syncope and coma occurred primarily during diurnal activities and rarely while sleeping. Fever and other signs of infection were rare
Initial syncope and coma occurred primarily during diurnal activities and rarely while sleeping. Fever and other signs of infection were rare
23/ Unlike sudden unexplained nocturnal death (SUND) in nearby Southeast Asian countries and the Philippines and inherited conduction and structural heart defects, the pattern of Yunnan SUD pointed to brief exposure to an environmental agent. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355161/#pone.0035894-Yang1
24/ An investigation was launched in 2005 and after 5 years the Chinese CDC in Beijing implicated a previously undescribed mushroom , Trogia venenata (Mycobank registration number MB 561711). @kasson_wvu #FungiTwitter
, Trogia venenata (Mycobank registration number MB 561711). @kasson_wvu #FungiTwitter
25/ Apparently Yunnan province is well known for its wild mushrooms, but these had no commercial value, so the villagers would eat them.
Some people reported that eating it caused diarrhea, which they could avoid if they ate small amounts at a time or dried it first.
Some people reported that eating it caused diarrhea, which they could avoid if they ate small amounts at a time or dried it first.
26/ A history of eating this mushroom in 5 clusters. In the 6th cluster a substantial amount of T. venenata was found in the kitchen, however, the only survivors were two young children who could not tell us if they or their deceased family members had eaten the mushrooms.
27/ At the 7th remaining cluster, at a village they did not find T. venenata, but found ARVC on the autopsy of both victims, a married couple.
Among all SUD cases the median time from last eating T. venenata to death was 4 days (range 16 hr-15 days).
Among all SUD cases the median time from last eating T. venenata to death was 4 days (range 16 hr-15 days).
28/ In contrast to other known causes of fatal mushroom poisoning, people exposed to T. venenata were either asymptomatic or had mild transient symptoms before losing consciousness and dying. Typical fatal mushroom poisonings have characteristic syndromes of progressing severity
29/ and often incapacitation over 1+ days before death.
Among the 13 SUD cases with exposure to T. venenata:
- 12 were previously in good health
- 12 suddenly lost consciousness during daily activities
--> 7 died within 10 minutes
--> 5 became comatose & died within 1 day
Among the 13 SUD cases with exposure to T. venenata:
- 12 were previously in good health
- 12 suddenly lost consciousness during daily activities
--> 7 died within 10 minutes
--> 5 became comatose & died within 1 day
30/
- 7 had >1 episodes of syncope and dizziness just preceding the acute, fatal episode
- 5 had a variety of transient, recurrent symptoms that did not interfere with their daily activities for 3–5 days before the acute, fatal episode
- 1 person died while sleeping
- 7 had >1 episodes of syncope and dizziness just preceding the acute, fatal episode
- 5 had a variety of transient, recurrent symptoms that did not interfere with their daily activities for 3–5 days before the acute, fatal episode
- 1 person died while sleeping
31/ Postmortem exams on 4 SUD cases with exposure to T. venenata @drjudymelinek
*ALL had microscopic, localized dissolution, disruption, or necrosis of heart muscle fibers with focal lymphocytic infiltration
@drjudymelinek *ALL had microscopic, localized dissolution, disruption, or necrosis of heart muscle fibers with focal lymphocytic infiltration
32/ Additional acute lesions: @drjudymelinek
- 3 localized lymphocytic infiltration of the liver
- 2 pulmonary alveolar edema
- 1 acute kidney tubular necrosis
- 1 hepatocyte necrosis
- 1 congestion of the liver
- 1 congestion of the lung
- 1 congestion the spleen
- 3 localized lymphocytic infiltration of the liver
- 2 pulmonary alveolar edema
- 1 acute kidney tubular necrosis
- 1 hepatocyte necrosis
- 1 congestion of the liver
- 1 congestion of the lung
- 1 congestion the spleen
33/ Notably, the brain 
was not examined due to cultural taboo.
Underlying conditions in 1 patient each:
- 1 ARVC
- 1 patent foramen ovale
- 1 75% stenosis of the artery of the AV node
was not examined due to cultural taboo.Underlying conditions in 1 patient each:
- 1 ARVC
- 1 patent foramen ovale
- 1 75% stenosis of the artery of the AV node
34/ Another autopsy series from 1991-2006 (N=29)
- 16 males
- 13 females
- Mean age 32yo (8-69)
*11 (38%) with lymphocytic myocarditis accompanied with focal myocardial necrosis or degeneration
@drjudymelinek @Bob_Wachter @EricTopol @ErinMichos https://pubmed.ncbi.nlm.nih.gov/18001532/
- 16 males
- 13 females
- Mean age 32yo (8-69)
*11 (38%) with lymphocytic myocarditis accompanied with focal myocardial necrosis or degeneration
@drjudymelinek @Bob_Wachter @EricTopol @ErinMichos https://pubmed.ncbi.nlm.nih.gov/18001532/
35/ - 3 cases (10%) with neutrophil myocarditis accompanied with focal myocytolysis or coagulation necrosis
- 4 cases (14%) with arrhythmogenic right ventricle cardiomyopathy (ARVC) in which fatty infiltration of myocardium was the only pathological finding
@drjudymelinek
- 4 cases (14%) with arrhythmogenic right ventricle cardiomyopathy (ARVC) in which fatty infiltration of myocardium was the only pathological finding
@drjudymelinek
36/ - 2 cases (7%) with ischemic heart disease in which fresh or old foci of myocardial infarction were found but coronary stenosis was shown only in one case @tmprowell
- 2 cases (7%) with left ventricle hypertrophy & obstructive muscle bundle in the outflow of left ventricle
- 2 cases (7%) with left ventricle hypertrophy & obstructive muscle bundle in the outflow of left ventricle
37/ - 2 cases (7%) with allergic bronchitis or chronic bronchitis and pulmonary emphysema.
- 5 cases (17%) without any pathological finding that could explain sudden death.
- Focal but not diffuse inflammatory infiltration was the prominent histological feature of myocarditis
- 5 cases (17%) without any pathological finding that could explain sudden death.
- Focal but not diffuse inflammatory infiltration was the prominent histological feature of myocarditis
38/
- 2 cases were detected to suffer from acute hemorrhage in His bundle and its left branching site
- Pulmonary edema, acute respiratory infection and congestive or ischemic liver necrosis were found in some cases simultaneously. @drjudymelinek @EricTopol @tmprowell
- 2 cases were detected to suffer from acute hemorrhage in His bundle and its left branching site
- Pulmonary edema, acute respiratory infection and congestive or ischemic liver necrosis were found in some cases simultaneously. @drjudymelinek @EricTopol @tmprowell
39/ Testing showed the mushrooms did contain toxins, although not enough to be deadly. Dr. Robert Fontaine, a #US epidemiologist reported "What's happening in Yunnan isn't expected from any other mushroom toxin. What we have here is a toxin that is picking off vulnerable people”
40/ Given what we know about #SARSCoV2 & the capacity of #COVID19 to be a pan-body disease utilizing the ACE-2 receptor to gain cell entry, the complications of thrombus/clotting as well as damage to the heart and lungs specifically in Yunnan SUD are curious...
41/ As usual, I have a few questions.
1.) #FungalTwitter can mushrooms cause lymphocytic infiltrate of the heart muscle, or any of the above pathologic findings? @kasson_wvu @FungalDoc
1.) #FungalTwitter can mushrooms cause lymphocytic infiltrate of the heart muscle, or any of the above pathologic findings? @kasson_wvu @FungalDoc
42/ Is it possible, that these sudden deaths over the last 40 years, were due to emerging coronaviruses from bats?
The seasonality is strange, but it is the rainy season and from the very little I do know, bats don’t like flying in the rain.
@PeterDaszak
The seasonality is strange, but it is the rainy season and from the very little I do know, bats don’t like flying in the rain.
@PeterDaszak
43/ Mushroom gatherers would also likely be under tree cover in rainy weather (these poison ones were found on dead trees) & if bats were in those trees, could the mushrooms be contaminated with bat feces creating a risk for direct fecal oral transmission? @PeterDaszak
@PeterDaszak
44/ Let me again be crystal clear that I am not a virologist, a bat scientist, a mycologist, an epidemiologist, or physician. I am a NP that was intrigued by such an interesting and strange series of events. We don't know the true origins yet. Everything is still circumstantial.
45/ It is very clear that there is not enough large-scale support or funding to finance efforts to prevent pandemics from occurring in the future. This was recently reiterated by the American Journal of Tropical Medicine and Hygieneand Dr. Fauci himself
http://www.ajtmh.org/content/journals/10.4269/ajtmh.20-0849;jsessionid=K3EmYmBTHnemgdqJDD8QEHtL.ip-10-241-1-122
http://www.ajtmh.org/content/journals/10.4269/ajtmh.20-0849;jsessionid=K3EmYmBTHnemgdqJDD8QEHtL.ip-10-241-1-122
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