MIS-C, Sepsis and the puzzle between

Eventually the road leads to Rome...

The coming sepsis "pandemic"

A spur of the moment article, since there are many “minor” aspect that doesn’t necessarily entail or fit a comprehensive article, but fit on the overall “puzzle”. Significantly in regards to MIS, Multisystem Inflammatory Syndrome, something that has been one of my interests for a couple of years now, ironically overlaps so close to sepsis, as of right now the two are indistinguishable.

They present with very similar initial symptoms, and sepsis symptoms are so easy to miss there is now a global effort for “awareness”. In July the WHO reported dozens of baby deaths due to sepsis, and in a recent retrospective study on Pediatric patients who died of a sepsis-related cause have a pediatric PICS phenotype nearly one-half of the time, but when it comes to mortality, sepsis is a “very young or very old” disease, but when it comes to lasting damage, it is an “everybody disease”.

I will write about PICS in due time, it is the very definition of complex, and of a doom loop, and shares many similarities with topics covered this year in this Substack.

For my own data tracking and analysis, I weekly search for sepsis on Google News and some other sites, it is much faster than the retroactive “waiting next year for some sprinkles of data”. The incidence and increasing number of sepsis was already a trend back in late 2021, and this trend will only increase as time goes by. Understanding both conditions is paramount to avoid long-term dysfunction and damage. Another interest of mine has been the improper salt intake, pushed by Western medicine (there is a massive, long history of corruption and data manipulation on the vilification of salt), and improper “salt” levels are a trend among many inflammatory diseases, and coincidentally MIS-C and sepsis.

Hyponametria is common in pediatric COVID-19 and MIS-C. Hyponatremia was associated with lower albumin and higher square root CRP levels. This may suggest an association of inflammation with lower serum sodium levels.

Hyponametria has been proposed to be a novel biomarker for Covid-19. The same was proposed after a territory-wide study in Hong Kong.

And sepsis.

Early hyponatremia predicts higher in-hospital mortality in severe sepsis or septic shock requiring ICU admission when Na-serum level is less than 130 mEq/L, but not when Na-serum is between 131 to 135 mEq/L. Early hyponatremia does not predict a longer length of hospital stay.

In May 2022 I wrote about a remarkable paper that found parts of the pathway that participate in the overactive inflammatory response of MIS-C. Children suffering from MIS had higher levels of IFN-Gamma and a protein called BAFF (B cell-activating factor), with the complex role of autoantibodies.

The role of BAFF in sepsis has yet to be uncovered, but it is known BAFF is “abundant” in sepsis, and blocking it positively affects (lowers) the inflammation and intestinal barrier dysfunction (leaky gut) in endotoxemia.

It is very hard to decode this aspect of inflammatory conditions because you are often faced with a “chicken or the egg” situation, there are always factors before, and during this hyper responses that affect the assessment, yet “salt” plays a significant role. Coincidentally to our interest, on rare occasions as a long-term complication, HHV-6 is associated with hyponametria, and the condition is also predictive of encephalitis in regards to Herpes simplex virus type 1 (HSV-1).

• An abnormal sodium level before or at the onset of human herpesvirus 6 (HHV-6) encephalitis is seen in 94% of cases.

• Hyponametria accounts for 85% of cases of sodium imbalance with HHV-6 encephalitis.

Also implicated with CNS infections

Source

On rare occasions, specific infections can induce MIS in children after a Covid infection, and the diagnosed underlying infections are rather… interesting. One child had dengue, the other salmonella and the other two had staphylococcus aureus, with the last case (4) developing sepsis. It has been proposed one of the possible causes of MIS-C (and in my assessment) is a long-term dysfunction being a byproduct of exposure to toxins and superantigens, both present in the Spike Protein, but especially pertinent to Staph.

Post-COVID Kawasaki-like Multisystem Inflammatory Syndrome Complicated by Herpes Simplex Virus-1 in a Two-Year-Old Child

Patients with MIS-C and KD appear to be prone to opportunistic infections such as HSV-1, either from iatrogenic immunosuppressive therapies or environmental exposures, sequelae of the infection itself, or abnormal immune responses. Differentiating HSV-1 infections from orolabial involvement of MIS-C or KD is imperative, as missing this diagnosis could have resulted in administering additional immunosuppressive treatment and worsening the infection.

The causes of both MIS and KD are yet to be elucidated, yet among the proposed causes lies superantigens, this paper also has a section dedicated to this hypothesis.

HHV-6 and -7 reactivation is frequent in KD patients. HHV-6 reactivation might exacerbate the severity of KD. In 2020 a team published the following “We describe here a case of KD with a concomitant primary EBV infection. To the best of our knowledge, this is the first case in western country that describes KD with acute EBV infection as confirmed by PCR.”

If young adults and older people get afflicted by sepsis and its complex complications, children get afflicted by similar heightened inflammatory responses towards certain toxins, with the “cause” being unique to each condition, especially since all these conditions aren’t fully understood so far. A rather interesting converging point among all these diseases and pathogens. Various studies propose Aspirin to treat or ameliorate Herpesviruses recurrence, and Aspirin is among the primary choices among IVIG, and so does sepsis, septic shock, and aspirin also has anti-staphylococcal action.

Understanding the complex effects SARS-CoV-2 induces on our immune system, how it changes many of the most important functions, how it relates to bacteria, endotoxins, fungi, and long-term change in receptor function and expression, therefore attempting to understand the many causes of Long Covid will help solve large parts of this puzzle, and create both treatments and mitigate long-term damage.

And every single condition covered here shares one specific immune response. The Interferon-Gamma pathway, and higher levels of Interleukin-17. All roads eventually lead to Rome.

Be sure to consume enough salt, but by no means just start consuming 10 grams of salt per day out of nowhere, the same applies to using aspirin, do not start using aspirin “just because”.