SARS-CoV-2 infection and persistence in the human body and brain at autopsy, 2022, Stein et al

[Andy]

Preprint

Abstract

COVID-19 is known to cause multi-organ dysfunction1-3 in acute infection, with prolonged symptoms experienced by some patients, termed Post-Acute Sequelae of SARS-CoV-2 (PASC)4-5. However, the burden of infection outside the respiratory tract and time to viral clearance is not well characterized, particularly in the brain3,6-14. 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 extrapulmonary tissues early in infection. Further, we detected 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.

Open access, https://www.researchsquare.com/article/rs-1139035/v1

 

[rvallee]

If anyone is able to read through this, did they specifically look for SARS-CoV-2? Or would their methods also find other viruses or pathogens? With so many infections that are known to infect most humans, it's hard to think this would be the only one to do this.

 

[hibiscuswahine]

If anyone is able to read through this, did they specifically look for SARS-CoV-2? Or would their methods also find other viruses or pathogens? With so many infections that are known to infect most humans, it's hard to think this would be the only one to do this.

They used ISH to detect SARS-CoV-2 in the brain tissue. Technique described here in this article https://www.ncbi.nlm.nih.gov/probe/docs/techish/

In Situ Hybridization (ISH)
is a technique that allows for precise localization of a specific segment of nucleic acid within a histologic section. The underlying basis of ISH is that nucleic acids, if preserved adequately within a histologic specimen, can be detected through the application of a complementary strand of nucleic acid to which a reporter molecule is attached.

Visualization of the reporter molecule allows to localize DNA or RNA sequences in a heterogeneous cell populations including tissue samples and environmental samples. Riboprobes also allow to localize and assess degree of gene expression. The technique is particularly useful in neuroscience.

It is used for many different situations.
https://www.sciencedirect.com/topic...s-and-molecular-biology/in-situ-hybridization

including EBV associated lymphomas
https://academic.oup.com/jid/article/200/7/1078/905519

 

[zzz]

Merged thread

Study finds coronavirus can persist for months in almost every organ system

Study finds coronavirus can persist for months in almost every organ system: a step towards understanding long COVID-19
https://www.pennlive.com/nation-wor...step-towards-understanding-long-covid-19.html
Here's a link to the actual study, which has not yet been peer reviewed:
SARS-CoV-2 infection and persistence throughout
the human body and brain

 

[Three Chord Monty]

A few interesting Twitter threads on this:



Amy Proal also quote-tweeted that in a thread where she brings up possible relevance to ME/CFS, which I'll link in the larger "ME/CFS following Covid" thread.

Zoe Hyde (who has 65,000 followers as compared to Amy Proal's approx 12,000) also tweeted about it here



which inspired a more critical thread that I include here because, in spite of the importance of the implications raised by this preprint, contains interesting points about the importance of presenting scientific information to the lay public in context:

 

[Joan Crawford]

Merged thread

Published in Nature today

https://www.nature.com/articles/s41586-022-05542-y

Abstract

Coronavirus disease 2019 (COVID-19) is known to cause multi-organ dysfunction1,2,3 during acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some patients experiencing prolonged symptoms, termed post-acute sequelae of SARS-CoV-2 (refs. 4,5). However, the burden of infection outside the respiratory tract and time to viral clearance are not well characterized, particularly in the brain3,6,7,8,9,10,11,12,13,14. Here we carried out complete autopsies on 44 patients who died with COVID-19, with extensive sampling of the central nervous system in 11 of these patients, to map and quantify the distribution, replication and cell-type specificity of SARS-CoV-2 across the human body, including the brain, from acute infection to more than seven months following symptom onset.

We show that SARS-CoV-2 is widely distributed, predominantly among patients who died with severe COVID-19, and that virus replication is present in multiple respiratory and non-respiratory tissues, including the brain, early in infection. Further, we detected persistent SARS-CoV-2 RNA in multiple anatomic sites, including throughout the brain, as late as 230 days following symptom onset in one case. Despite extensive distribution of SARS-CoV-2 RNA throughout the body, we observed little evidence of inflammation or direct viral cytopathology outside the respiratory tract. Our data indicate that in some patients SARS-CoV-2 can cause systemic infection and persist in the body for months.

 

[Hutan]

Patient 42 died at 230 days after onset of symptoms, had only mild or no respiratory symptoms, and died with, not from, COVID-19. Viral RNA was found in this patient's spinal cord and basal ganglia. A young person, who probably died due to a pre-existing seizure disorder, didn't show an inflammatory response. There wasn't much evidence of infection in the brains with virus present - they note vascular congestion was observed.

However, two cases (P36 and P42) reported only mild or no respiratory symptoms and died with, not from, COVID-19, yet had SARS-CoV-2 RNA widely detected across the body and brain. Additionally, P36 was a juvenile with an underlying neurological condition, but without evidence of multisystem inflammatory syndrome in children, suggesting that children may develop systemic infection with SARS-CoV-2 without developing a generalized inflammatory response.

We observed SARS-CoV-2 RNA and protein in ... cervical spinal cord and basal ganglia of late cases (P42 and P40, respectively)

In the examination of 11 brains, we found few histopathologic changes, despite substantial viral burden. Vascular congestion was an unusual finding that had an unclear aetiology and could be related to the haemodynamic changes incurred with infection. Global hypoxic–ischaemic change was seen in two cases, one of which was a juvenile (P36) with a seizure disorder who was found to be SARS-CoV-2 positive on hospital admission, but who probably died of seizure complications unrelated to viral infection.

Specifically, only 12 of our cases had detectable SARS-CoV-2 RNA in a perimortem plasma sample

I assume the following means that they found virus in different parts of people's bodies, with some genetic variation in different parts of the body (but presumably still close enough that it's unlikely that this was due to multiple infections). They seem to be suggesting that the rate of mutation was less than they might have expected. I wonder if the virus just holes up in some tissues, not replicating much, and so not mutating much.

HT-SGS of SARS-CoV-2 spike demonstrates homogeneous virus populations in many tissues, while also revealing informative virus variants in others. Low intra-individual diversity of SARS-CoV-2 sequences has been observed frequently in previous studies19,20,21, and probably relates to the intrinsic mutation rate of the virus as well as lack of early immune pressure to drive virus evolution.

We note several cases in which brain-derived virus spike sequences showed nonsynonymous changes relative to sequences from other non-CNS tissues. Further studies will be needed to understand whether these cases might represent stochastic seeding of the CNS or differential selective pressure on spike by antiviral antibodies in the CNS, as others have suggested23,24,25.

 

[CRG]

Characteristics of the study population - 52.3% obesese, 61.4% with 3 or more comorbidities, 61.4% with hypertension, 68.2% over the age of 55 - whatever this study tells us about SARS COVID 19, it has only limited application to how the virus impacts younger/healthier populations.

 

[John Mac]

Sure feels like this is reasonably likely given this finding in ME/CFS too, its just a question of which virus it is and the recent autopsies suggest its EBV often alongside HHV6.

The ME/CFS study discussed here:
https://www.s4me.info/threads/tissu...n-me-cfs-2022-prusty-et-al.30763/#post-450013

 

[SNT Gatchaman]

Also discussed a year prior as a preprint in thread https://www.s4me.info/threads/prepr...uman-body-and-brain-2021-chertow-et-al.23957/

 

[Midnattsol]

Characteristics of the study population - 52.3% obesese, 61.4% with 3 or more comorbidities, 61.4% with hypertension, 68.2% over the age of 55 - whatever this study tells us about SARS COVID 19, it has only limited application to how the virus impacts younger/healthier populations.

Seeing that obesity and non-communicable diseases are common globally, also increasingly in the young, we need studies that look at this population. It encompasses a lot of people.