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SARS-CoV-2 infection and persistence throughout the human body and brain

re: COVID
re: Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms

Seems credible, based on my own 18-month ordeal.

Not yet peer-reviewed. Though peer review these days is a farce.

SARS-CoV-2 infection and persistence throughout the human body and brain

2021-12-20, emphasis added.

COVID-19 is known to cause multi-organ dysfunction in acute infection, with prolonged symptoms experienced by some patients, termed Post-Acute Sequelae of SARS- CoV-2 (PASC).

However, the burden of infection outside the respiratory tract and time to viral clearance is not well characterized, particularly in the brain. We performed complete autopsies on 44 patients with COVID-19 to map and quantify SARS-CoV-2 distribution, replication, and cell-type specificity across the human body, including brain, from acute infection through over seven months following symptom onset.

We show that SARS-CoV-2 is widely distributed, even among patients who died with asymptomatic to mild COVID-19, and that virus replication is present in multiple pulmonary and extrapulmonary tissues early in infection.

Further, we detected persistent SARS-CoV-2 RNA in multiple anatomic sites, including regions throughout the brain, for up to 230 days following symptom onset. Despite extensive distribution of SARS-CoV-2 in the body, we observed a paucity of inflammation or direct viral cytopathology outside of the lungs. Our data prove that SARS-CoV-2 causes systemic infection and can persist in the body for months.

Main text:

Infection with severe acute respiratory syndrome coronavirus (SARS-CoV-2), the
causative agent of coronavirus disease (COVID-19), has well described pulmonary and
extrapulmonary manifestation, including multiorgan failure and shock among severe and fatal cases.

Some survivors experience Post-Acute Sequelae of SARS-CoV-(PASC) – also known as Long COVID—with cardiovascular, pulmonary, and neurological manifestations with or without functional impairment. While autopsy studies of fatal COVID-cases support the ability of SARS-CoV to infect multiple organs, extra-pulmonary organs often lack histopathological evidence of direct virally-mediated injury or inflammation. The paradox of extra-pulmonary infection without injury or inflammation raises many pathogen and host-related questions.

These questions include, but are not limited to: What is the burden of infection within versus outside of the respiratory tract? What cell types are infected across extra-pulmonary tissues, and do they support SARS-CoV-infection and replication? In the absence of cellular injury and inflammation in extra-pulmonary tissues, does SARS-CoV-persist, and if so, over what interval? Does SARS-CoV-evolve as it spreads to and persists in different anatomical compartments?

...

Spike RNA was found in neurons, glia and ependyma, as well as endothelium of vessels
across all lobes of the brain
of early, mid, and late cases. Within the cerebellum specifically, 226 neurons, Purkinje cells, and endothelium of vasculature also contained spike protein via IHC.

...Overall, these 190 findings suggested no need for alterations in receptor utilization to permit extrapulmonary 191 dissemination of SARS-CoV-2, while also revealing genetic compartmentalization between 192 viruses in the lung lobes and those in extrapulmonary sites, including the brain... These differences may indicate differential selective pressure on spike by antiviral antibodies in brain versus other sites, though further studies will be needed to confirm this speculation...

...All but five cases were considered to have died from COVID-19 (Extended Data Table 5), and, of these, 37 (94.5%) had either acute pneumonia or diffuse alveolar damage at the time of death...

...We show SARS-CoV-2 disseminates across the human body and brain early in infection at high levels, and provide evidence of virus replication at multiple extrapulmonary sites during the first week following symptom onset. We detected sgRNA in at least one tissue in over half of 270 cases (14/27) beyond D14, suggesting that prolonged viral replication may occur in extra- pulmonary tissues as late as D99. While others have questioned if extrapulmonary viral presence is due to either residual blood within the tissue or cross-contamination from the lungs during tissue procurement, our data rule out both theories.

...While the respiratory tract was the most common location in which SARS-CoV-2 RNA tends to linger, ≥50% of late cases also had persistence in the myocardium, thoracic cavity lymph nodes, tongue, peripheral nerves, ocular tissue, and in all 333 sampled areas of the brain, except the dura mater. Interestingly, despite having much lower levels of SARS-CoV-2 in early cases compared to respiratory tissues, we found similar levels between pulmonary and the extrapulmonary tissue categories in late cases. This less efficient viral clearance in extrapulmonary tissues is perhaps related to a less robust innate and adaptive immune response outside the respiratory tract.

...SARS-CoV-2 can replicate within tissue for over 3 months after infection in some individuals, with RNA failing to clear from multiple 343 compartments for up to D230...

...

DIGLLOYD: this is very good work to start! And it’s fairly “hard” science, or so it looks.

But the 44 autopsies occurred on a non-representative sample: most had multiple comorbidities, 70% were male, average age was 59 years, etc. In other words, what COVID does to young healthy people does not look to have been answered, and cannot be unless a similar study is done where death occurs from unnatural causes (eg traffic accidents).

Moreover, the study is looking at people whose bodies were least able to fight off the infection; those who died in relatively short order. So it tells us little if anything about healthy people who fight off COVID. But it does show that at least in some people, viral clearance takes a long time. And that is worrisome for the mRNA vaccines, which generate the same spike protein.

Also of interest is that the virus mutates within the same body in different types of tissue! Hmmm... could being vaccinated could drive more mutations, by applying survival pressure?

My feeling after initial recovery from my April 2020 infection was that my entire body/brain/neurological system were damaged. And took 18 months to get to some reasonably normal place. However, since I had overcome the infection in ~2.5 weeks and resumed training (albeit feeling somewhat off and with ongoing minor issues) and only 6 weeks later had the massive hit appears to have been Epstein Barr Virus “piling on”, perhaps it was a multi-viral thing at work: lingering COVID, EBV, and HHV-6 (I tested positive for both EBV and HHV-6 even a year later). The body is an extremely complex ecosystem!

Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms

If spike RNA is found all over the place in the body for months, why wouldn’t the mRNA vaccines cause the same kind of intrusive contamination/damage as COVID itself? Since the mRNA vaccines are themselves de facto virii (hijacking the body’s cells to make spike protein to cause the immune system to react to the spike protein its own cells have made). Science still has no idea what the effects will be over time of the mRNA vaccines, or COVID itself.

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