Persistence of SARS CoV-2 S1 Protein in CD16+ Monocytes in Post-Acute Sequelae of COVID-19 (PASC) Up to 15 Months Post-Infection

Bk, Patterson; Eb, Francisco; Yogendra, Ram; Long, Emily; Pise, Amruta; Rodrigues, Hallison; Hall, Eric W.; Herrara, M; Parikh, Purvi; Guevara-Coto, José; Tj, Triche; Scott, Paul T.; Hekmati, Saboor; Maglinte, Dennis T.; Chang, Xaiolan; Mora-Rodriguez, RA; Mora, Javier

doi:10.1101/2021.06.25.449905

Cited by 17 publications

(26 citation statements)

References 27 publications

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“…More recently, elevated NC. Mono was reported to persist up to 16 months post infection among post-acute sequelae SARS-CoV-2 or long-COVID-19 patients in the presence of TNF (70,82). Indeed we observed higher levels of TNF-a that can promote the survival of NC.…”

Section: Discussionsupporting

confidence: 45%

Data-Driven Analysis of COVID-19 Reveals Persistent Immune Abnormalities in Convalescent Severe Individuals

et al. 2021

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Severe SARS-CoV-2 infection can trigger uncontrolled innate and adaptive immune responses, which are commonly associated with lymphopenia and increased neutrophil counts. However, whether the immune abnormalities observed in mild to severely infected patients persist into convalescence remains unclear. Herein, comparisons were drawn between the immune responses of COVID-19 infected and convalescent adults. Strikingly, survivors of severe COVID-19 had decreased proportions of NKT and Vδ2 T cells, and increased proportions of low-density neutrophils, IgA+/CD86+/CD123+ non-classical monocytes and hyperactivated HLADR+CD38+ CD8+ T cells, and elevated levels of pro-inflammatory cytokines such as hepatocyte growth factor and vascular endothelial growth factor A, long after virus clearance. Our study suggests potential immune correlates of “long COVID-19”, and defines key cells and cytokines that delineate true and quasi-convalescent states.

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Section: Discussionsupporting

confidence: 45%

Data-Driven Analysis of COVID-19 Reveals Persistent Immune Abnormalities in Convalescent Severe Individuals

et al. 2021

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“…These efficiently express RNAse L inhibitors and hence interfered with prompt interferon responses 37 . Linking to SARs-CoV-2, the subunit 1 (S1) persists for up to 15 months post infection and is related to post-acute inflammatory sequalae presenting with neurological complications 38 . 75% of Patients with persistent RNAemia also present long COVID 39 .…”

Section: Hypothetical Viral: Mrna Vaccine Interactionsmentioning

confidence: 99%

Differences in Vaccine and SARS-CoV-2 Replication Derived mRNA: Implications for Cell Biology and Future Disease

McKernan¹

2021

Preprint

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Codon optimization describes the process used to increase protein production by use of alternative but synonymous codon changes. In SARS-CoV-2 mRNA vaccines codon optimizations can result in differential secondary conformations that inevitably affect a protein’s function with significant consequences to the cell. Importantly, when codon optimization increases the GC content of synthetic mRNAs, there can be an inevitable enrichment of G-quartets which potentially form G-quadruplex structures. The emerging G-quadruplexes are favorable binding sites of RNA binding proteins like helicases that inevitably affect epigenetic reprogramming of the cell by altering transcription, translation and replication. In this study, we performed a RNAfold analysis to investigate alterations in secondary structures of mRNAs in SARS-CoV-2 vaccines due to codon optimization. We show a significant increase in the GC content of mRNAs in vaccines as compared to native SARS-CoV-2 RNA sequences encoding the spike protein. As the GC enrichment leads to more G-quadruplex structure formations, these may contribute to potential pathological processes initiated by SARS-CoV-2 molecular vaccination.

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“…437  Another "vascular" hypothesis has focused on the possible role of non-classical monocytes rendered dysfunctional and long lived from persistent intracellular SARS CoV-2 S1 protein. 438 The high CCL5/RANTES levels secreted by these monocytes may foster endothelial dysfunction and inappropriate vasodilation. The proponents of this hypothesis claim to have successfully treated "thousands" of Long Covid patients with a therapy including an CCL5 antagonist.…”

Section: Covid-19 To the Rescuementioning

confidence: 99%

Broken Connections: The Evidence for Neuroglial Failure in ME/CFS

Renz‐Polster¹

2021

Preprint

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In spite of decades of research, the pathobiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is still poorly understood. Several pathomechanisms have been identified, yet, it remains unclear how they are related and which of them may be upstream or downstream.. In this paper, we present a theoretical strategy that may help clarify the causal chain of pathophysiological events in ME/CFS. We propose to focus on the common final histological pathway of ME/CFS and suggest to ask: Which cellular compartment may explain the pathological processes and clinical manifestations observed in ME/CFS? Any functional unit consistently identified through this search may then be a plausible candidate for further exploration.For this "histological" approach we have compiled a list of 22 undisputed clinical and pathophysiological features of ME/CFS that need to be plausibly and most directly explained by the dysfunctional cellular unit in question. For each feature we have searched the literature for pathophysiological explanations and analyzed if they may point to the same functional cellular unit.Through this search we have identified the CNS neuroglia - microglia and astroglia - as the one functional unit in the human body which may best explain all and any of the clinical and pathological features, dysfunctions and observations described for ME/CFS. While this points to neuroinflammation as the central hub in ME/CFS, it also points to a novel understanding of the neuroimmune basis of ME/CFS. After all, the neuroglial cells are now understood as the functional matrix of the human brain connectome which operates beyond and above specific brain centers, receptor units or neurotransmitter systems and integrates innate immune functions with CNS regulatory functions pertaining to autonomous regulation, cellular metabolism and the stress response.

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Persistence of SARS CoV-2 S1 Protein in CD16+ Monocytes in Post-Acute Sequelae of COVID-19 (PASC) Up to 15 Months Post-Infection

Cited by 17 publications

References 27 publications

Data-Driven Analysis of COVID-19 Reveals Persistent Immune Abnormalities in Convalescent Severe Individuals

Data-Driven Analysis of COVID-19 Reveals Persistent Immune Abnormalities in Convalescent Severe Individuals

Differences in Vaccine and SARS-CoV-2 Replication Derived mRNA: Implications for Cell Biology and Future Disease

Broken Connections: The Evidence for Neuroglial Failure in ME/CFS

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