There has been a lot lately related to H5N1. It’s VERY concerning that it has shown up in more mammal species because that means the virus is more adapted to the mammalian respiratory tract, but also because of the impacts of the virus on both poultry and cattle. The CDC has a page about the history of H5N1 since 2020.
There is a LOT to unpack in this story. First, most people don’t know the dark side of the egg industry. Chickens are bred either to be layers or broilers for eating. Male layers obviously can’t lay eggs and aren’t profitable as a human food source. What gets done to them might disturb a lot of people. This includes gassing them to death with carbon dioxide, manually breaking their necks, or running them through a macerator. The video is rather graphic, so skip it if you would be bothered by it.
What happens to the ground up chicks and eggshells? It varies by country and laws, but in general, they become a component of pet food, large animal food, or organic fertilizer.
Something similar happens with butchered pigs and cattle. The portions that aren’t used for human consumption go through a rendering process. One of the products of rendering is bone meal. It is used in human dietary supplements, as an organic fertilizer, and as animal feed.
Some of the above has been banned in other countries, but the agriculture industry has a very strong lobbying presence in the US.
Many diseases can be transmitted through livestock feeding practices. One that eventually impacted humans was a disease in sheep called scrapie, which got its name for the characteristic behavior of inflicted sheep which would rub their sides against objects, leading to bald patches where wool would normally be.
Mad cow disease was identified in Britain in 1986. In the early 90s, a health advisory board in Britain proclaimed that cattle were a “dead-end host.” Eventually that assessment was proven wrong, and the first death related to BSE transmitted to humans occurred in 1995. It was called new variant CJD (nvCJD or vCJD were both used).
We are already seeing cracks (pun intended) in the egg supply chain. Realistically, this will likely result in the culling of over 2 million chickens.
The simple take away is that we are stepping into uncharted waters in relationship between the food supply and H5N1. I would really urge people to take emergency preparedness seriously. I generally point people to https://www.do1thing.com/ because of their approach of ongoing preparedness.
COVID and Workplace Fatalities
Most of my week has been consumed with H5N1, but I had an idea about where to look for more data suggesting impacts from COVID in industry. I realized that fatal work injuries might tell something of a story about risks of death in the workplace from brain fog and other neurological injury from COVID. In the last two years, the rate of workplace deaths either matched or exceeded the prior highest rate since the start of this data set in 2012.
I’ve decided to write a weekly summary of my thoughts on publications and news sources around COVID and other public health/public policy interests during each week. Some of these might seem familiar to those who follow me on social media.
This is concerning for many reasons. First, given that we have seen it in ruminants in multiple states, this implies that this strain of H5N1 is already widespread. Most likely, it is in waterfowl flocks spreading it across North America. I suspect that the fecal-oral transmission is the most likely cause. Waterfowl land in water sources and defecate where ruminants later use for drinking. This means that containing spread is almost impossible.
Second, influenza viruses undergo genetic shift and drift quite regularly. This is part of the reason we need new human influenza boosters each year. While the current strain of the virus infecting ruminants appears to only cause illness for 7-10 days, it is also likely that this virus will mutate. That could make things better, or perhaps much worse, which could have devastating impacts on food supplies.
My biggest concern is those with migration routes including NW Canada and Alaska. That is because it shares space with waterfowl from SE Asia. Introducing this strain into waterfowl from that region increases the risk to humans considerably.
SE Asia has the densest human, waterfowl, and pig populations in the world. The problem lies in introducing this virus into pig populations in that area. The reason is that pigs are more unique in that their physiology is much more similar to humans than other animals. In addition, they can be easily infected by both human and avian influenza strains.
Influenza is a promiscuous virus. It will incorporate genetic sequences into its genome from the environment and is a very sloppy replicator, which introduces mutations readily. This also means that a pig can act as a petri dish to mix the genes from a human virus that makes influenza readily transmissible among humans and mix it with the genes of an avian strain that could make the virus much more deadly to humans as well. In 2013, H5N1 was repeatedly entering human populations and had a 60% fatality rate.
Soft cheeses, such as Brie and Camembert, and Mexican-style soft cheeses such as Queso Fresco, Panela, Asadero, and Queso Blanco made from unpasteurized milk
Yogurt made from unpasteurized milk
Pudding made from unpasteurized milk
Ice cream or frozen yogurt made from unpasteurized milk
Problems with Possible COVID Links
Group A Strep in Japan
Group A strep is responsible for strep throat which can normally be easily treated with antibiotics. If it spreads systemically through a bloodstream infection, it can cause streptococcal toxic shock syndrome (STSS), which can cause organ failure and leads to about a 30% mortality rate, hence the need to treat strep throat early.
There have been a LOT of airline incidents related to maintenance and manufacturing this year that have received plenty of media attention, as well as some that haven’t.
In addition, there was also the container ship that hit the Francis Scott Key bridge in Baltimore.
In the study, “We observed significant cognitive impairment only in the ROCF, a drawing task test used to assess visuospatial abilities, executive functions and memory. The deficits observed in the ROCF could not be explained by socio-demographic factors, ophthalmologic deficits or psychiatric symptoms, suggesting cognitive deficit secondary to SARS-CoV-2 infection. Other factors which may influence performance, such as motor coordination, spatial neglect, visual attention, semantic knowledge, intelligence and executive functions were not likely to explain the observed difficulties, since we did not find any significant differences in other non-verbal (Trail Making Test and Five Points Test) and verbal tests (verbal fluency, digit span) also related to these processes.
Visuoconstructive deficits are usually defined as an atypical difficulty in using visual and spatial information to guide complex behaviors like drawing, assembling objects or organizing multiple pieces of a more sophisticated stimuli. In drawing a complex figure, as in the ROCFT, the patient must organize visual and spatial information in a planned manner to execute the drawing per se, a processes that demand several more specific cognitive abilities related to perceiving, processing, storing and recalling visuospatial information, both regarding shape and position, as well the planning and execution of the drawing per se.”
People that have visuospatial deficits could have difficulties estimating speeds, directions, and other variables that are important in operating transportation, especially in circumstances where quick action is required. This is why I have concerns about public and commercial transportation as well as shipping.
It’s not just an issue in the US either. Other countries have a similar trend in the aggregate. What is particularly interesting though is how much the US contributes to the aggregate numbers. It’s not surprising given that we already have a distracted driving problem here as well as unmitigated COVID. I worry that these kinds of problems are only going to become more prevalent.
This is weekly US COVID admissions. The dotted lines that drop in June last year is due to the requirement for reporting suspected admissions, so after that time, this data is only representing about 1/3 of the actual numbers.
This means that there are about 45,000 COVID admissions/week up to 3/17. About 1% of COVID cases need hospitalization, suggesting around 450,000 cases/week. However, this is also a gross undercount. This image shows the percentage of patients being screened from a sample of hospitals. Note the caveat on the chart, but we can then assume that the figures are closer to double that.
It also suggests that there are about 900,000 new cases/week based on hospital data alone. However, with better treatments including drugs like Paxlovid in play, the 1% hospitalization rate is likely a bit of an overestimate compared to the past.
I’ll ballpark that this means that there are about 150,000-200,000 new cases/day in the US. I’m old enough to remember when there was a big push to use NPIs because these numbers seemed insane. Now the country seems to give a big collective shrug. That doesn’t end well, especially for those who have gotten repeat infections.
There have been many reports of unusually high case counts of pneumonia in children and some of this appears to be related to Mycoplasma pneumoniae. Some are calling this white lung syndrome. h/t to @celestial_bean_ for this list of different locations.
The review article Infection with and Carriage of Mycoplasma pneumoniae in Children provides an excellent background on this problem (Meyer Sauter et al., 2016).
An eight-year study beginning in the 1960s in Seattle found carriage rates that varied between endemic (2%) and epidemic (35%) periods (Foy et al., 1979). One study found that 21% of asymptomatic children carried M. pneumoniae in their upper respiratory tract at a single study site (Spuesens et al, 2013). In a separate study, 24% of children with pharyngitis were found to have M. pneumoniae on testing as well (Esposito et al., 2014).
A 2023 study of children with recurrent respiratory tract infections found that 68% carried M. pneumoniae (Koenen et al., 2023). Why is this rate doubled of that a few years ago? Could COVID be a driving factor?
This organism is more likely to cause severe disease in an immunocompromised host (Yacoub et al., 2016). One problem is that colonization may not drive a mucosal antibody response (de Groot et al., 2022). I have a number of studies linked on this page indicating immune system damage from COVID.
Think of the immune system as a chemical defense system against pneumonia. Another defense system is mechanical. “Mucociliary clearance (MCC) is the primary innate defense mechanism of the lung. The functional components are the protective mucous layer, the airway surface liquid layer, and the cilia on the surface of ciliated cells. The cilia are specialized organelles that beat in metachronal waves to propel pathogens and inhaled particles trapped in the mucous layer out of the airways.” (Bustamante-Marin and Ostrowski, 2016).
In a hamster model, “SARS-CoV-2 infection is followed by a severe loss of cilia.” (Schreiner et al., 2022). Part of the mechanism of spread to other cells in the respiratory epithelium has been described and illustrated (Su et al., 2023).
“The step-by-step model of SARS-CoV-2 penetrating the mucus barrier and infecting human nasal epithelium. Air-liquid interface culture of primary human nasal epithelial cells to form nasal epithelial organoids composed of ciliated, goblet, and basal cells. Firstly, small amount of virus penetrates the peri-ciliary layer, along the cilia, after binding to ACE2 on cilia. Activation of various kinases such as PAK1/4 and phosphorylation of several actins such as EZR occur in the infected ciliated cells immediately. The microvilli then form dome-shaped alienated structures and high degree of extension. Cytoplasmic vesicle-encapsulated viral progeny pass through the PCL layer along alienated microvilli and exit at the mucus layer. Mucus flow, which depends on ciliary movement, assists the spread of viral progeny to other surrounding cells.”
“SARS-CoV-2 ORF10 impairs ciliogenesis by enhancing the activity of the E3 ligase CUL2ZYG11B. (A) The CUL2ZYB11B RING E3 ligase complex contributes to cellular protein degradation via ubiquitination. (B) Upon SARS-CoV-2 infection, the viral protein ORF10 binds the E3 adapter ZYG11B, increasing the ubiquitination activity of the complex, and inducing the proteasomal degradation of ciliary proteins, including IFT46. (C) ORF10 overexpression in serum-starved NIH3T3 and MRC-5 cells blocks primary cilium biogenesis and maintenance. (D) The lentiviral transfer of ORF10 is sufficient to induce cilia loss in human ACE2 knock-in mice and in primary human nasal epithelial cells, highlighting the role of this viral protein in SARS-CoV-2-mediated cilia disruption.”
This damage can clearly be seen in both transmission and scanning electron microscopy.
This damage has been seen with other coronaviruses. “Transmission electron micrograph of nasal epithelium before and after coronavirus inoculation. a) Transmission electron micrograph day 0. This shows normal tissue with an intact well-ciliated surface and minimal disruption. b) Transmission electron micrograph day 3. This shows abnormal tissue with severely disrupted cell surface. Marked loss of cilia is seen. Internal scale bars=2.9 µm.” (Chilvers et al., 2001).“A Scanning electron microscopy (SEM) image of a massively infected cell at 2 dpi (left) with a lack of cilia and an accumulation of viral particles at the surface of membrane ruffles (enlarged in right panel). B SEM image of an infected cell at 2 dpi with few remaining cilia (left) and scattered viral particles (vp) at the plasma membrane (right). C, D SEM images of infected cells at 2 dpi showing cilia abnormalities, including shortened misshapen cilia (D left, enlarged in middle panels) and crescent-shaped proximal axonemes (E). E SEM image of pleiomorphic SARS-CoV-2 viral particles.” (Robinot et al., 2021)
The authors also showed the impact of infection on the ability of the cilia to sweep away low density 30 µm-sized polystyrene microbeads. The first video is of mock-infected cells where “beads deposited on mock-treated epithelia moved generally in the same direction, consistent with coordinated beating of the underlying cilia.”
“In contrast, beads deposited on infected epithelia were mostly immobile or showed randomly-oriented limited movements, indicating an impairment of the mucociliary clearance function.”
It’s clear that both immune system dysfunction and respiratory epithelial damage could be contributing to the M. pneumoniae problem in the pediatric population. The question then becomes one of why this seems to be surging now. Could it be that a new variant is driving this? The answer seems that this seems to be a distinct possibility. “Omicron variants dramatically accelerate spread via the ciliary transport/microvilli reprogramming pathway, which explains the increase in its attack rate compared to previous variants.” (Wu et al., 2022).
What variants do the impacted countries have in common currently? 23F (EG.5) and its sublineages (HV.1 is one of them).
However, the HV.1 sublineage seems to be what is becoming dominant in the US which correlates with the M. pneumoniae cases. It’s interesting that the EG.5 is dominant in the world.
Of course, this could all be correlation with the variants. It’s possible that there is ascertainment bias and that much of the pneumonia in pediatric populations is a combination of COVID, RSV, influenza, and M. pneuomoniae which are all on the rise. Even more concerning is the possibility that this is a new virus. The rapid rise in cases would certainly suggest that. It’s also worth learning about the concepts of sufficient and necessary causes in epidemiology if one has that level of interest in this topic.
Mainly though, I hope to impress on people that COVID not only is a causal pathway for a number of chronic diseases, but I think I’ve made a case that it is also causal for infectious diseases as well, with a special focus here on respiratory ones. We need to be doing far more to protect children.
When cells die, their contents are released into the surrounding tissue. Parts of the DNA of the cell are also released and can be detected in the bloodstream. That’s what is meant by cell-free DNA (cfDNA). Epigenetic liquid biopsies study the cfDNA and can determine the type of cells that it came from, based on characteristic molecular structures. The authors state “Patients with severe COVID-19 had a massive elevation of circulating cell-free DNA (cfDNA) levels, which originated in lung epithelial cells, cardiomyocytes, vascular endothelial cells and erythroblasts, suggesting increased cell death or turnover in these tissues.”
Cardiomyocytes are the muscle cells of the heart that contract to provide the heartbeat. When a large area of these become damaged, it is called a myocardial infarction, or commonly called a heart attack. This is normally due to either fatty plaques forming in the blood vessels that feed the heart or a clot that enters one of them. Keep that in mind for the part on vascular endothelial cell damage.
Endothelial cells line the inside of tissue. Epithelial cells line the outer surface. Damaged lung epithelium means that the cells that take up oxygen in the air sacs of the lungs (alveoli) which gets diffused into the bloodstream and carbon dioxide to flow into the alveoli no longer function. Erythroblasts are the cells that become red blood cells when mature. The damage to these just these two cell types means that other tissues will be supplied less oxygen, but that is just part of the widespread damage.
The damage to the vascular endothelium is really one of the most critical things to understand about COVID. It is the layer of cells lining blood vessels.
Capillaries become small enough that they only allow for a single red blood cell to pass at a time, as illustrated video.
That is the problem with endothelial damage. When that occurs, capillaries can be occluded, which would lead to reduced (or no) oxygen flow to the tissue supplied by the capillary. These blockages are what are referred to as microthrombi.
An important finding of this study is “Patients with severe COVID-19 have a higher concentration of cfDNA, originating in affected tissues.” When endothelial damage occurs and microthrombi form on a large scale, such as in severe COVID, it leads to acute organ damage and potentially organ failure.
The damage of clot formation is evident in a stroke. (The other common type of stroke, where a blood vessel ruptures, is called a hemorrhagic stroke). When a clot causes a stroke, it’s called an ischemic stroke, because the clot deprives the downstream brain tissue of oxygen, as illustrated in this animation.
There was an autopsy study of patients who had died of COVID. “151 autopsies were included, and 91 cases presented microthrombi in the lung (73%), heart (11.2%), kidney (24%), and liver (16.3%). The age range was between 27 and 96 years.” Clearly the COVID microthrombi risk is real across many organs.
Endothelial damage is not only dangerous due to clot formation, but also because the endothelial cells are responsible for the transfer of oxygen from red blood cells into the surrounding tissue, which can also lead to that tissue being starved of oxygen and potential death of those cells, which is called ischemia.
The preprint also refers to erythropoiesis, which is simply the production of new red blood cells. Why would this increase? Because the body recognizes that parts of it are starving for oxygen.
There is more to the study, but this is the basic biology that is important to understand in how COVID causes damage.
I suspect that part of the reason that COVID seems less damaging in younger or healthier populations is that they can more easily handle some tissue damage since the surrounding unaffected tissue can take on some of the load of the damaged tissue. However, as that unaffected tissue ages, it won’t work quite as efficiently as when it was young and healthy, and the impacts of the COVID infection will start manifesting themselves as a number of chronic diseases. The fact that we are seeing many of these in such a short time is extremely concerning. It suggests that we will see massive amounts of chronic diseases among people who had COVID infections in the future. You can find information on some of these broken down by organ system on this page. Click the link of the system to see some of the studies.
There is another round of disinformation around COVID vaccines related to the Amish, originating from people like Steve Kirsch, who doesn’t have a science or medicine background and makes false vaccine claims, which are easily debunked.
What does a real source say about COVID in this population?
Closed religious communities also resist epidemiological surveillance. The same factors that put these communities at high risk for infectious disease outbreaks—lack of trust in medicine and the state, reluctance to receive routine and preventative healthcare, and closed communication networks—also make their members less likely to avail themselves of testing for COVID-19. Even among those tested, it may be difficult to connect their tests back to their religious communities without information about religious affiliation. Moreover, it is difficult to distinguish their COVID-19 transmission and death rates from surrounding communities.
CRCs are sectarian groups in tension with their environment’s dominant culture. This tension leads these communities to erect boundaries between themselves and outsiders, limiting interaction.
These communities warrant close monitoring, given their history of infectious disease outbreaks. However, some community members distrust state officials and medical providers, which undermine efforts to monitor public health. Additionally, since some groups prefer natural remedies to modern medicine, their members avoid routine medical care and are less likely to be tested for COVID-19. After a COVID-19 outbreak in an Amish community in Ohio, the local health department set up a testing site to track the spread. According to Ali et al, more traditional community members did not participate in the testing clinic, implying they won’t seek testing independently.
Our findings reflect the older Amish and Mennonites’ vulnerability in the population, as the average age of death is consistently higher after June 2020. The results indicate the average age of death during the first wave (March through May) was lower than the baseline average, suggesting the initial two waves of COVID-19 may have impacted people in the population with underlying health risks. In general, the Amish and the Mennonites were subject to government guidelines in March and April limiting religious gatherings. Many groups complied with the CDC’s recommendations to limit contact. However, when restrictions were lifted during the summer of 2020, many of these communities resumed church services. The importance of face-to-face rituals in CRCs and Amish groups’ general resistance to mask-wearing and other CDC guidelines makes them especially vulnerable to COVID-19. Indeed, we see the number of excess deaths spike in October and November when many governmental restrictions relaxed and many of the Amish and Mennonite groups were engaging in face-to-face interactions.
The large number of excess deaths among the Amish and Mennonite community is concerning, as it indicates not only the presence, but the impact of COVID-19 on this community.
Oddly, there is still a lot of vaccine hesitancy and conspiracy theories even though that has all been debunked. What’s even more puzzling are the number of people who will claim that it hasn’t been tested adequately (it’s been tested far more than any other vaccine at launch), but then they will go on to take drugs like hydroxychloroquine and ivermectin, that hadn’t been tested much for COVID initially, and after they have been tested and found not to provide any benefit, they still insist that it’s a cover up. Another study was published in JAMA this week indicating that ivermectin is no better than placebo.
So are vaccines better at preventing COVID infection, hospitalizations, and death? The data paints a very cleart picture.
Infection
This graphs represents cases by vaccination status per 100,000 people.
At first glance, the green line at the bottom right doesn’t seem to any benefit from the bivalent boosters. However, this is due to the big surge of cases at the start of 2022, which changes the scale of the y-axis. This is a view of just the part of the graph when the bivalent data became available.
Of course, there were legitimate concerns about the safety of the vaccine in adolescents and children. Views of the data can be found in the link in the sources section below. This is what the case data looks like for the <5 year old cohort, suggesting efficacy among this age group as well
Hospitalization
This is hospitalizations per 100,000 among the >18 year old population by vaccination status.
Hospitalization data isn’t available in their visualization tool for the <5 age group, but this is how hospitalizations look for 5-11 year olds by vaccination status.
Deaths
This represents deaths per 100,000 among those over 18 by vaccination status.
Again, it’s useful to zoom in to see the imapact of the bivalent boosters.
Last evening I came across a post on Twitter with a great illustration on a single page of how to build a C-R box. I messaged the author for permission to add it here. Thank you Shiven Taneja.
