Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms (PolyBio, 2021)

Pyrrhus

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I thought this recent paper probably deserved its own discussion thread...

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://www.frontiersin.org/articles/10.3389/fmicb.2021.698169/full

Excerpt:
Proal and van Elzakker 2021 said:
The novel virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic of coronavirus disease 2019 (COVID-19). Across the globe, a subset of patients who sustain an acute SARS-CoV-2 infection are developing a wide range of persistent symptoms that do not resolve over the course of many months. These patients are being given the diagnosis Long COVID or Post-acute sequelae of COVID-19 (PASC).

It is likely that individual patients with a PASC diagnosis have different underlying biological factors driving their symptoms, none of which are mutually exclusive. This paper details mechanisms by which RNA viruses beyond just SARS-CoV-2 have be connected to long-term health consequences. It also reviews literature on acute COVID-19 and other virus-initiated chronic syndromes such as post-Ebola syndrome or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to discuss different scenarios for PASC symptom development.

Potential contributors to PASC symptoms include consequences from acute SARS-CoV-2 injury to one or multiple organs, persistent reservoirs of SARS-CoV-2 in certain tissues, re-activation of neurotrophic pathogens such as herpesviruses under conditions of COVID-19 immune dysregulation, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation issues, dysfunctional brainstem/vagus nerve signaling, ongoing activity of primed immune cells, and autoimmunity due to molecular mimicry between pathogen and host proteins. The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage care for specific patients with the diagnosis.
 

Pyrrhus

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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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Some symptoms some of us have, not mentioned there:

sore throats........

general body dessication/dryness (mouths throats eyes lungs)

swollen lymph nodes

blurred vision, visual acuity poor

IBS and related digestive issues...

-thinking about those types of symptoms- maybe they relate more to Eppstein Barr type subtypes (but maybe not the IBS and digestive). I think of myself as an Eppstein barr type. but I also have digestive....
 

Violeta

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Thank you for this info, looking forward to reading everything!

Might I add before I read it, very interesting to see Van Elzakker and Amy Proal working together!

I can't believe how comprehensive it is.

Now all we need is a way to clean our nerves of these viruses.
 
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