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Source: SARS-CoV-2 Viral Persistence   Dec 25, 2021  28 days ago
BREAKING! U.S. NIH Study Shockingly Reveals SARS-CoV-2 Viral Persistence Throughout Human Body And In The Brain Even In Those Who Were Asymptomatic!
BREAKING! U.S. NIH Study Shockingly Reveals SARS-CoV-2 Viral Persistence Throughout Human Body And In The Brain Even In Those Who Were Asymptomatic!
Source: SARS-CoV-2 Viral Persistence   Dec 25, 2021  28 days ago
SARS-CoV-2 Viral Persistence: A new study by scientists from the U.S. National Institute of Health (NIH) has found alarming evidence of SARS-CoV-2 viral persistence in the human host body and also in the brain even in those individuals that only had mild symptoms initially during infection and even in the asymptomatic who were deemed as ‘recovered’! The study team even detected SARS-CoV-2 RNA in multiple anatomic sites, including regions throughout the brain, for up to 230 days following symptom onset!

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The study findings have enormous implications for the definition of COVID-19 recovery and also current diagnostic methods used to verify of COVID-19 recovery and also the issues surrounding Long-COVID or PASC (Post-Acute Sequelae of COVID-19.)
 
SARS-CoV-2 infections are 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.

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The study team from the U.S. NIH 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.
 
The SARS-CoV-2 Viral Persistence study findings shockingly showed 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 extrapulmonary tissues early in infection.
 
The study findings also showed detection of 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, the study team observed a paucity of inflammation or direct viral cytopathology outside of the lungs.
 
The study findings prove that the SARS-CoV-2 coronavirus causes systemic infection and can persist in the body for months. />  
The study findings were published on a preprint server called Research Square and is current under peer review for publication into the journal: Nature. https://www.researchsquare.com/article/rs-1139035/v1
 
It is also strangely surprising for the U.S. NIH to finally conduct a study and release the findings about SARS-CoV-2 viral persistence two years after the COVID-19 crisis first broke out despite  being fully aware about the issues of viral persistence in Long COVID. And its also interesting that the study was published on the preprint server of researchsquare and not medRxiv or bioRxiv which are the normal preprint servers that the NIH normally post to unless they want less coverage of these studies!
 
The study findings showed how 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.

The study team detected sgRNA in at least one tissue in over half of cases (14/27), suggesting that prolonged viral replication may occur in extra pulmonary tissues as late as 99 days. 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, the study rules out both theories.
 
Only 12 cases had detectable SARS-CoV-2 RNA in a perimortem plasma sample, and of these only two early cases also had SARS-CoV-2 sgRNA in the plasma, which occurred at Ct levels higher than nearly all of their tissues with sgRNA.
 
Hence, residual blood contamination cannot account for RNA levels within tissues. Furthermore, blood contamination would not account for the SARS-CoV-2 sgRNA or virus isolated from tissues. Contamination of additional tissues during procurement, is likewise ruled out by ISH demonstrating widespread SARS-CoV-2 cellular tropism across the sampled organs, by IHC detecting viral protein in the brain, and by several cases of virus genetic compartmentalization in which spike variant sequences that were abundant in extrapulmonary tissues were rare or undetected in lung samples.
 
Utilizing both ddPCR and sgRNA analysis to inform the selection of tissue for virus isolation and ISH staining allowed the study team to describe a number of novel findings.
 
Past studies have reported SARS-CoV-2 RNA within the heart, lymph node, small intestine, and adrenal gland.
 
The study findings of this current research demonstrate conclusively that SARS-CoV-2 is capable of infecting and replicating within these tissues.
 
Current literature has also reported absent or controversial expression of ACE2 and/or TMPRSS2 in several extrapulmonary tissues, such as the colon, lymphoid tissues, and ocular tissues, calling into question if these tissues can become infected by SARS-CoV-2.
 
This new study findings however found high levels of SARS-CoV-2 RNA and evidence of replication within these organs, as well as SARS-CoV-2 RNA via ISH in colonic mucosal epithelium and mononuclear leukocytes within the spleen, thoracic cavity lymph nodes, and GI lymphoid aggregates.

It is believed that these ISH positive cells represent either infection or phagocytized virus in resident macrophages.
 
Furthermore, the study team isolated virus from a mediastinal lymph node and ocular tissue from two early cases.
 
The study findings collectively show while that the highest burden of SARS-CoV-2 is in the airways and lungs, the virus can disseminate early during infection and infect cells throughout the entire body, including widely throughout the brain.
 
While others have posited this viral dissemination occurs through cell trafficking due to a reported failure to culture virus from blood, this new study findings support an early viremic phase, which seeds the virus throughout the body following pulmonary infection.
 
Another recent study in which SARS-CoV-2 virions were pelleted and imaged from COVID-19 patient plasma, supports this mechanism of viral dissemination.
 
Although the study cohort is primarily made up of severe cases of COVID-19, two early cases had mild respiratory symptoms (fatal pulmonary embolism occurred at home) or no symptoms (diagnosed upon hospitalization for ultimately fatal complications of a comorbidity), yet still had SARS-CoV-2 RNA widely detected across the body, including brain, with detection of sgRNA in multiple compartments.

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The study findings therefore, suggest viremia leading to body-wide dissemination, including across the blood-brain barrier, and viral replication can occur early in COVID-19, even in asymptomatic or mild cases.
 
Among the cohort was one juvenile patient with no evidence of multisystem inflammatory syndrome, this suggests that infected children without severe COVID-19 can also experience systemic infection with SARS CoV-2.
 
Finally, a major contribution of the study findings is a greater understanding of the duration and locations at which SARS-CoV-2 can persist. 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 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, the study team 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.
 
The stud team detected sgRNA in tissue of over 60% of the cohort. While less definitive than viral culture, multiple studies have shown that sgRNA levels correlate with acute infection and can be detected in respiratory samples of immunocompromised patients experiencing prolonged infections.
 
The study findings coupled with ISH suggest that SARS-CoV-2 can replicate within tissue for over 3 months after infection in some individuals, with RNA failing to clear from multiple compartments for up to 230 days or maybe even far longer!
 
This persistence of viral RNA and sgRNA may represent infection with defective virus, which has been described in persistent infection with the measles virus which is another single-strand enveloped RNA virus, in cases of subacute sclerosing panencephalitis.
 
The mechanisms contributing to Long COVID or PASC are still being investigated; however, ongoing systemic and local inflammatory responses have been proposed to play a role.
 
The study findings provide evidence for delayed viral clearance, but do not support significant inflammation outside of the respiratory tract even among patients who died months after symptom onset. Understanding the mechanisms by which SARS-CoV-2 persists and the cellular and subcellular host responses to viral persistence promises to improve the understanding and clinical management of Long COVID or PASC.
 
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For the latest about SARS-CoV-2 Viral Persistence, keep on logging to Thailand Medical News.
 
 
 

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