The Plague's Lord Garden - "Quad-demic"

Nurgle's smiled that day

Title explanation in the comment section.

Although it would make more “narrative” sense to separate the subjects covered here, it fits an overall arching theme, so hopefully I do a good job at stitching it together. The science of this article is present in the articles of the last few weeks, and these will point you towards the last couple of years.

If you pay attention to the entire system and its non-linear dynamics, rather than focusing on specific regions, you may find yourself being able to forecast within probabilistic thresholds coming trends else. A fancy way to say, what happens in the Southern Hemisphere in Winter may repeat in the Northern Hemisphere in the Northern Winter (hypersimplified).

If you desire fewer data points, and not a high level of complexity in data analysis, you can just pay attention to China. What happens in China will often cascade into the Nothern Hemisphere within 2 to 4 months. Shortly ago, a peculiar piece of narrative went viral, not entirely fabricated, but most certainly “aligned” with the media. The “quad-demic”

What to know about 'quad-demic' of COVID, flu, RSV and norovirus in US

Norovirus levels are hitting highs not seen in six years, according to CDC data.

At some point, a good perspective to adopt into your analytical framework is the one I started presenting in the Language - The Genocidal Organ, as in Language being the DNA-Helix that forms culture and memes, thus specific words and terms are exactly like that, becoming memes which act as viruses of the mind. Quademic is a term that originated in the UK, last year and given its apparent virality, it stuck and spread elsewhere. Using linguistic analysis can also help you forecast overall trends although some intuition goes into it. This paragraph is just a little tidbit about the origins of certain memes =).

Manufactured term, but observable world dynamics. The UK experienced an absurd increase in the same infections, with RSV rising as much as 342%. In the closing days of 2024, Japan experienced one of its largest flu outbreaks in history. “To understand the future, you must understand the past” and thus looking at the past we shall.

China experienced significant outbreaks of respiratory viruses, especially in children in late 2023, SARS-CoV-2, Influenza, RSV, at different times, but late in the year “Mycoplasma Pneumoniae”, which is well known to cause both chronic and latent infections (it can persist in the respiratory tract for months…), fast-forward a little bit, Europe starts suffering a similar outbreak, in a year the US experiences the same.

What about one of the worst offenders in the last 12 months, Norovirus. 2023 in China, Fast forward a few months, and Europe and the US experience sustained outbreaks, with the most recent one hitting the news (within seasonality, in a sense). Similar trend with Group A Strep, which causes Scarlet fever.

Surge in scarlet fever cases in China: An atypical epidemiological pattern in Beijing

Rapid expansion and international spread of M1_UK in the post-pandemic UK upsurge of Streptococcus pyogenes

The opposite also remains true, China experienced a massive surge in a imported clade of RSV in the winter of 2023.

Quoting one of my favorite characters, again, when you discard the impossible, whatever remains however improbable, must be the truth. There is only one variable that can account for this disproportional shift in everything, from other pathogens, to their evolution, seasonality to how we respond to them. SARS-CoV-2. While odd “outbreaks” and diseases occurred in late 2021 and 2022, the rather easy-to-spot trend started in 2023. Covid 0 policy in China ended in January 2023.

One of my most recent articles talks about the long-term consequences of a SARS-COV-2 (mostly Omicron) infection and a few other articles are able to explain these “outbreaks we can’t explain” and “quade-emic”. Looking into Mycoplasma as an initial model to understand already gives you answers.

Patients with SMPP (severe M. pneumoniae pneumonia) had lower lymphocytes, CD3⁺ T cells, CD4⁺ T cells, CD8⁺ T cells, B cells, and higher IL-4, IL-6, IL-10 levels than those with non-SMPP.

That looks pretty much like a biased Th2 response (allergic, inflammatory) with fewer T cells, and one of mycoplasma hallmarks severity is the imbalance between Th17 cells and T Regulatory. Hum, I wonder… RSV ? Depletion of Circulating Regulatory T Cells during Severe Respiratory Syncytial Virus Infection in Young Children. Regulatory T Cells are necessary for forming Memory T cells after Influenza. Mycoplasma ? An imbalance of circulating Th17 cells and Tregs is associated with the deterioration of pulmonary injury in patients with MP infections.

China is now experiencing another “outbreak of unknown disease”, soon to be uncovered as Human Metapneumovirus, hMPV for short. The disease has grown so aggressively in China that Western health organizations are already sending out alerts for hospitals, and clinicians to be prepared in case of surges around our region. So, let us dig into the immune response, and see if we can find any meaningful information.

• Symptomatology induced by hMPV-infection is caused by a typical Th17-like immune response, characterized by the secretion of interleukin (IL)-6 and TNF-α in the lungs

• (Part of the paper above)…promotes a delay in the Th1-like immunity and triggers the secretion of cytokines related to a Th2-like profile…

• Skewed balance of regulatory T cell and inflammatory T cell in IL-17 defect with human metapneumovirus infection

• Human Metapneumovirus Establishes Persistent Infection in the Lungs of Mice and Is Reactivated by Glucocorticoid Treatment

Hidden trends in complexity (pun intended) are clearly emerging, an outrageously drastic and complex immunological shift induced by SARS-CoV-2, causing our bodies to not fight many pathogens properly, thus fueling their evading mechanisms, which in turn affects consequential infections, and our bodies are having trouble keeping latent pathogens in check, be their Herpes viruses or “forgotten” respiratory infections.

A counter-argument by a perceptive reader would be “But you never mentioned the impact of SARS-CoV-2 on T-Reg cells directly”, this wouldn’t be entirely the effect on other cells, would it ?

Despite this, one year after recovery, the decreased subpopulations of regulatory T cells had not yet reached the levels observed in healthy donors.

Alas, another published paper on the long-term effects of SARS-CoV-2 and here one of the most important subtypes of T-cells remains low for almost a year, it recovers, but never to the prior levels, and shows an impact in the thymus. An article I wrote in 2022 has now more significance.

SARS-CoV-2, thymic atrophy and impaired T cell development

SARS-CoV-2 variants impact the thymus and bone marrow differently

There I argue one of the reasons Omicron causes a milder version of thymic atrophy is because of the attenuation of its superantigenic sequence. It is known that injecting SEB induces thymic atrophy and results in thymocyte death. The generation of regulatory T (TReg) cells in the thymus are crucial for immune homeostasis and self-tolerance.

Omicron also impacts in a long-lasting manner the microbiome.

Akkermansia plays a direct and significant role in glucose metabolism, Kynurenine, and Tryptophan pathway, T reg cells, and the integrity of your gut walls (thus lack of it will contribute to dysbiosis). Not only does the “Quad-demic” have an explanation, it also has multiple immunological pathways and causes. Understanding these trends will be very important for the rest of the year (perhaps the next few).

And now I leave you with homework.

Receptor shedding. To fully understand not only what is going on with SARS-CoV-2 long-lasting changes, Long Covid, but with other pathogens, that is a concept that will need to be researched and thus I plan on writing about it. It may as well be the word of the year when it comes to my work, such as superantigens being last year’s word.

It is also funny, looking into my notes from 2015-2017, back in my Intelligence days, I had often made remarks, in many pages of the odd outbreaks and odd distribution of diseases in many areas, clearly affected by air travel, but with a red annotation “unknown variable”. Your intuition, if well attuned, will seldom let you down… would be a shame if a synthetic pathogen affected that huh…

I am grateful for your support, it enables the continuation of my research !