Persistence of RNA viruses is deadly real

Pyrrhus

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There are a few relevant gems in this paper:

NEW PAPER ON LONG COVID:

Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms (Proal and van Elzakker, 2021)
https://forums.phoenixrising.me/thr...te-to-persistent-symptoms-polybio-2021.84761/

Here are a few selected quotes from this excellent paper:
SARS-CoV-2 is a positive-sense single-stranded RNA virus (V’kovski et al., 2021). It is one of seven coronaviruses capable of infecting humans (Corman et al., 2018). Compared with other coronaviruses (e.g., HCoV-NL63, HCoV-229E, and HCoV-OC43) that are pathogenic to humans but generally drive only mild clinical symptoms, SARS-CoV-2 more closely resembles MERS-CoV or SARS-CoV (sometimes called SARS-CoV-1) in that it is capable of causing severe disease (Zhu et al., 2020).
[...]
Like all pathogens, SARS-CoV-2 employs a number of mechanisms to disable and evade the host immune response (Lucas et al., 2001; Bowie and Unterholzner, 2008; Taefehshokr et al., 2020). These include the ability to replicate within double-membrane vesicles that are not detected by host pathogen pattern recognition receptors (Taefehshokr et al., 2020). SARS-CoV-2 also dysregulates the host interferon response (Ribero et al., 2020). Interferons are cytokines secreted by host cells in response to viral infection. They bind to cell surface receptors and act as transcription factors, regulating the expression of hundreds of genes whose protein products target viruses at many levels (Acharya et al., 2020). SARS-CoV-2 expresses at least 10 proteins that allow it to either counteract the induction or escape the antiviral activity of interferons (Ribero et al., 2020), allowing the virus to better survive by rendering the host innate immune response inefficient.
[...]
Autopsy, animal, and organoid model studies show that, like SARS-CoV, SARS-CoV-2 is able to reach and infect cells of the CNS, infect neurons, and produce neuroinflammation (Matschke et al., 2020; Song et al., 2020; Song et al., 2021). Indeed, SARS-CoV-2 may be capable of transport up and down nerves and neuronal axons (Lima et al., 2020; Rangon et al., 2020; Song et al., 2020; Karuppan et al., 2021).
[...]
A growing number of studies show that some patients infected with SARS-CoV-2 do not successfully clear the virus over long periods of time (Liotti et al., 2020; Sun et al., 2020; Vibholm et al., 2021). In such studies, confirmation of SARS-CoV-2 in patient samples is generally assessed via identification of viral RNA and/or proteins. While identification of SARS-CoV-2 RNA could technically represent “inert” RNA, the possibility is unlikely because inert RNA in the human body is rapidly degraded (Houseley and Tollervey, 2009; Fabre et al., 2014). Nearly every human cell type, and human tears, saliva, mucus, perspiration, and extracellular spaces express RNAase enzymes that rapidly degrade inert RNA (Sorrentino, 2010; Gupta et al., 2013).
[...]
Persistence of SARS-CoV-2 in some patients with [Long Covid] symptoms is not unexpected. The literature is replete with examples of single-stranded RNA virus persistence, spanning decades of research on samples obtained from living human patients, autopsy studies, and animal studies (Viola et al., 1978; Riddell et al., 2007; Doi et al., 2016; Randall and Griffin, 2017; Ireland et al., 2020). Persistence of single-stranded RNA viruses in the central nervous system has been documented on multiple occasions. In a 1986 paper on the topic, Kristensson and Norrby explain that “Although it would seem difficult for RNA viruses to persist in the brain under conditions of normal immune defense mechanisms, representatives of at least seven of the established families of RNA viruses have been shown capable of causing persistent infections under these conditions” (Kristensson and Norrby, 1986).
[...]
Dozens of studies show coronaviruses capable of persistence, with some coronaviruses tied to chronic disease development (Arbour et al., 1999; Chan et al., 2004). One study found that in primates infected with two different coronaviruses, the viruses persisted, replicated, and disseminated in the central nervous system, leading to demyelination in the brain (Murray et al., 1992b). Coronavirus RNA and/or antigen have also been found in human multiple sclerosis (MS) brains examined at autopsy, including in both plaque and non-plaque areas of brainstem, cortex, and spinal cord samples (Murray et al., 1992a).
[...]
A number of teams have identified enteroviruses and their proteins in tissue samples obtained from patients with ME/CFS or ME/CFS-like symptoms (Yousef et al., 1988; Dowsett et al., 1990; Chia et al., 2010; Chia et al., 2015). For example, Chia and Chia found enterovirus VP1 protein and RNA in stomach biopsy specimens obtained from 165 ME/CFS patients with chronic abdominal complaints. 82% of ME/CFS specimens stained positive for enterovirus VP1 protein, compared to 20% of control specimens (Chia and Chia, 2008) (Figure 2). A non-cytolytic form of enteroviral infection was cultured from 5 ME/CFS specimens. Positive staining was found in repeat stomach biopsy specimens taken from 6 ME/CFS patients at the onset of symptoms and again 2–8 years later.

Enteroviruses have also been found in ME/CFS brain and muscle tissue (Cunningham et al., 1991; Gow et al., 1991; Richardson, 2001). For example, McGarry et al. (1994) examined the central nervous system of a woman with ME/CFS who died by suicide for the presence of enteroviruses. Positive PCR sequences with similarity to coxsackievirus B3 were identified in brain samples from the hypothalamus and brainstem, and also in muscle and heart samples. No enteroviral sequences were identified in any tissue obtained from four control subjects.
[...]
It is well understood that humans accumulate persistent viruses over the course of a lifetime. These viruses generally persist in dormant, latent, or non-cytolytic forms, but may reactivate under conditions of stress or immunosuppression. Indeed, people regarded as healthy have been shown to harbor a wide range of persistent viruses in blood, saliva (Wylie et al., 2014), or tissue that are capable of activation under such conditions (Virgin et al., 2009).
[...]
Acknowledgments
Thank you to supporters of PolyBio Research Foundation.
 
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Marylib

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Are any of our researchers, such as OMF or PolyBio watching this? @Ben H do you know? Is @PolyBioFoundation on this forum. I officially give up, because this is interesting. We used to call this disease non-HIV AIDS and people may actually be getting result with maraviroc.
 
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Pyrrhus

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Pyrrhus

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All this reminds me of a small talk I gave at U.C. Berkeley back in 2013.

I was asked to speak on West Nile Virus, so I talked about how many people infected with West Nile Virus went on to have persistent, fluctuating, exertion-induced neurological symptoms for years after infection.
I just read this:

Evaluation of Prolonged Fatigue Post–West Nile Virus Infection and Association of Fatigue with Elevated Antiviral and Proinflammatory Cytokines (Garcia et al., 2014)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150370/

...And just for completeness, here's a 2015 review article that attempts to summarize the long-term effects of West Nile Virus infection:

Long-term sequelae of West Nile virus-related illness: a systematic review (Patel et al., 2015)
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(15)00134-6/fulltext


Excerpt:
We systematically reviewed the clinical outlook of West Nile virus (WNV)-related illness in North America and western Europe. As of March, 2015, more than 45 000 cases of WNV-related illness have been reported in North America. Unlike acute morbidity and mortality, the long-term physical, cognitive, and functional sequelae associated with WNV-related illness are not well characterised.

An understanding of WNV-related sequelae and their prognostic factors can support physicians with early diagnosis and tertiary prevention efforts. We searched Ovid Medline, Embase, Scopus, and Environment Complete for studies published between 1999 and 2015. We included 67 studies in our Review.

Although muscle weakness, memory loss, and difficulties with activities of daily living were among the most common physical, cognitive, and functional sequelae, respectively, some population groups were reported to be at greater risk of severe neurological disease or death (ie, older men with underlying illnesses such as cardiovascular disease or cancer).

A high level of heterogeneity was reported among studies included in this Review, suggesting a need for consistent methods for collecting data and reporting findings. Further, more than half of the studies reporting sequelae relied exclusively on subjective assessment and only two studies used matched control groups. Therefore, opportunities exist for more robust primary studies in future research.
 

Pyrrhus

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There is currently a new outbreak of Ebola virus in Guinea, in West Africa, and the journal Science published this article:

New Ebola outbreak likely sparked by a person infected 5 years ago
https://www.sciencemag.org/news/202...ak-likely-sparked-person-infected-5-years-ago
Now published in Nature:

Resurgence of Ebola virus in 2021 in Guinea suggests a new paradigm for outbreaks (Keita et al., 2021)
https://www.nature.com/articles/s41586-021-03901-9

Excerpt:
Keita et al 2021 said:
Seven years after the declaration of the first epidemic of Ebola virus disease in Guinea, the country faced a new outbreak—between 14 February and 19 June 2021—near the epicentre of the previous epidemic. Here we use next-generation sequencing to generate complete or near-complete genomes of Zaire ebolavirus from samples obtained from 12 different patients.

These genomes form a well-supported phylogenetic cluster with genomes from the previous outbreak, which indicates that the new outbreak was not the result of a new spillover event from an animal reservoir. The 2021 lineage shows considerably lower divergence than would be expected during sustained human-to-human transmission, which suggests a persistent infection with reduced replication or a period of latency.

The resurgence of Zaire ebolavirus from humans five years after the end of the previous outbreak of Ebola virus disease reinforces the need for long-term medical and social care for patients who survive the disease, to reduce the risk of re-emergence and to prevent further stigmatization.

Related article:

Resurgence of Ebola Virus Disease in Guinea Linked to a Survivor With Virus Persistence in Seminal Fluid for More Than 500 Days (Diallo et al., 2016)
https://academic.oup.com/cid/article/63/10/1353/2452977
 

sometexan84

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Now published in Nature:

Resurgence of Ebola virus in 2021 in Guinea suggests a new paradigm for outbreaks (Keita et al., 2021)
https://www.nature.com/articles/s41586-021-03901-9

Excerpt:



Related article:

Resurgence of Ebola Virus Disease in Guinea Linked to a Survivor With Virus Persistence in Seminal Fluid for More Than 500 Days (Diallo et al., 2016)
https://academic.oup.com/cid/article/63/10/1353/2452977
Any persistent RNA virus that specifically tries to inhibit IFN Lambda production is suspect, and that includes Ebola.

In the case of Ebola, apparently it's the VP24 viral protein that blocks the IFNλ1.

This is why Peginterferon Lambda works on these!
https://forums.phoenixrising.me/threads/we-can-get-peginterferon-lambda-now.85475/

Ebola and Type III Interferon (Lambda)....

Type III Interferons in Viral Infection and Antiviral Immunity

Ebolavirus protein VP24 interferes with innate immune responses by inhibiting interferon-λ1 gene expression