Solving the "No Fever" Covid Mystery
A hypothesis why some people had a form of Covid19 but never got a fever or tested positive for the virus or antibodies
Thanks to those who responded tonight. In my website wanderings, I came across some really interesting information that supported a hypothesis I've had for about 2 years, to explain why some people get very ill with covid and others not at all, or mildly. It's been a big mystery. I'll put it down here just for the record.
Intro: I observed that long covid patients, including myself, chiefly suffered symptoms that involved nerves and surfaces covered with collagen—tongue, upper respiratory, esophagus, intestines, brain, eyes.
Also that there seemed to be a very high number of people with autoimmune conditions in the long covid study (of about 3700 patients). This includes many conditions that are, or are comorbid with, a connective tissue disorder (which I have). Half of them did not test positive for the virus or suffer a high fever or serious lung involvement.
Third, that my own covid symptoms mimicked some of my previously diagnosed GI symptoms, such as chest pains and "air hunger," caused by stimulation of the vagus nerve where the protective collagen sheathing has been eroded by stomach acid. The same treatment that worked for the one also worked for the other (simethecone).
So it seems logical to posit that those who give up collagen easily did not test positive for the virus or get high fevers, but still had GI, vascular, and neurological symptoms that persisted.
Because of the HIV discussion tonight, I looked up the gene that is required for HIV to replicate itself: CCR5 coreceptor. Had anyone checked to see if that was also a factor in SARS-CoV-2? Yes.
Which led me to this paper:
A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infection
Early in the pandemic, it was discovered that SARS-CoV-2 infection is dependent on the ACE2 receptor for cell entry and the serine protease TMPRSS2 for spike protein priming55,56,57,58. Indeed, a rare variant located close to ACE2 was found, by GWAS, to confer protection against SARS-CoV-2 infection, possibly by decreasing ACE2 expression59. Furthermore, although their impact on infection is unknown, some human ACE2 polymorphisms bind the SARS-CoV-2 spike protein with different affinities in vitro60. In a genome-wide CRISPR knockout screen for infection with SARS-CoV-2 and other coronaviruses, TMEM41B was identified as a requirement for permissive infection with the virus61. TMEM41B is an endoplasmic reticulum transmembrane protein that is also required by flaviviruses62. Its impact on SARS-CoV-2 infection remains to be established, but an allele common in East and South Asians has been shown to be associated with a lower capacity to support flavivirus infection in vitro.
Transmembrane proteins...you mean like in collagen? So I looked up collagen and flaviviruses.
Cotranslational prolyl hydroxylation is essential for flavivirus biogenesis
For example, we find that both Zika and dengue use the collagen proline hydroxylation machinery to mediate cotranslational modification of conserved proline residues in the viral polyprotein. Genetic or pharmacological inhibition of proline hydroxylation impairs nascent viral polyprotein folding and induces its aggregation and degradation. Notably, such interventions prevent viral polysome remodelling and lower virus production.
This is really exciting, because I have a friend who had dengue 45 years ago and never got Covid, never took the vax. Others have noted that previous dengue infection appears to confer protection against Covid.
My hypothesis is that when the SARS-CoV-2 viral particle invades a person with this genetic collagen machinery located near ACE2 receptors, the collagen binds with the spike protein rather than the spike protein docking with the ACE2 receptor. Thus the viral particles never make it to the immune system, so IgM and IgG antibodies never form, or only in very small amounts.
It's true that I never tested positive for the virus or the antibodies (three virus tests, one antibody test in 2020).
Note: During my repeating cycles of covid, I noticed lots of loose chewy little rubber balls in my mouth as I developed first strawberry tongue and then geographic tongue and theorized that something was grabbing the collagen. This still occurs every single day, and I have had to develop strategies to deal with it. I surmise that the virus is entrenched in a reservoir near the olfactory bulb, and continues to replicate, causing a repeating cycle of symptoms that do not trigger the manufacture of antibodies. This may indeed be a viable explanation for my observation and experience, as well as that of others.
Food for further thought: This may also be related to the known relationship between malaria and tuberculosis...that populations with resistance to the one are vulnerable to the other.
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