Exploring the immunogenic properties of SARS-CoV-2 structural proteins: PAMP:TLR signaling in the mediation of the neuroinflammatory and neurologic sequelae of COVID-19

Frank, Marion E.; Fleshner, Monika; Maier, Steven F.

doi:10.1016/j.bbi.2023.04.009

Cited by 10 publications

(3 citation statements)

References 110 publications

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“…For instance, long COVID appears to share with what could be termed long Lyme disease the increased frequency of the MDD and other common psychiatric disorders. 84 , 85 Our reasoning here is entirely consistent with the outcome of recent studies 98 that focused on the details of the PAMP activity of certain structural proteins of SARS‐CoV‐2 in this same context. Their conclusions also plausibly apply to the psychiatric disorders recorded in Lyme disease, above.…”

Section: Psychiatric Consequences Of Any Excessive Cerebral Increase ...supporting

confidence: 87%

Autocrine positive feedback of tumor necrosis factor from activated microglia proposed to be of widespread relevance in chronic neurological disease

Clark,

Vissel

2023

Pharmacology Res & Perspec

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Over a decade's experience of post‐stroke rehabilitation by administering the specific anti‐TNF biological, etanercept, by the novel perispinal route, is consistent with a wide range of chronically diminished neurological function having been caused by persistent excessive cerebral levels of TNF. We propose that this TNF persistence, and cerebral disease chronicity, largely arises from a positive autocrine feedback loop of this cytokine, allowing the persistence of microglial activation caused by the excess TNF that these cells produce. It appears that many of these observations have never been exploited to construct a broad understanding and treatment of certain chronic, yet reversible, neurological illnesses. We propose that this treatment allows these chronically activated microglia to revert to their normal quiescent state, rather than simply neutralizing the direct harmful effects of this cytokine after its release from microglia. Logically, this also applies to the chronic cerebral aspects of various other neurological conditions characterized by activated microglia. These include long COVID, Lyme disease, post‐stroke syndromes, traumatic brain injury, chronic traumatic encephalopathy, post‐chemotherapy, post‐irradiation cerebral dysfunction, cerebral palsy, fetal alcohol syndrome, hepatic encephalopathy, the antinociceptive state of morphine tolerance, and neurogenic pain. In addition, certain psychiatric states, in isolation or as sequelae of infectious diseases such as Lyme disease and long COVID, are candidates for being understood through this approach and treated accordingly. Perispinal etanercept provides the prospect of being able to treat various chronic central nervous system illnesses, whether they are of infectious or non‐infectious origin, through reversing excess TNF generation by microglia.

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Section: Psychiatric Consequences Of Any Excessive Cerebral Increase ...supporting

confidence: 87%

Autocrine positive feedback of tumor necrosis factor from activated microglia proposed to be of widespread relevance in chronic neurological disease

Clark,

Vissel

2023

Pharmacology Res & Perspec

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“…The proposed mechanisms for PASC [ 433 , 434 , 435 , 436 , 437 , 438 ] include persistent reservoirs of pathogens or pathogen remnants (e.g., SARS-CoV-2 structural proteins such as spike protein or spike protein fragments such as the S1 subunit); the development of autoimmunity due to molecular mimicry between pathogen and host proteins; the reactivation of other latent pathogens; dysbiosis from SARS-CoV-2–host-microbiome interactions; and resultant organ system or tissue damage from the infection and associated immunopathology, including vasculopathy, coagulopathy, and clotting issues. These potential contributors may act independently or in combination to cause persistent symptoms.…”

Section: Resultsmentioning

confidence: 99%

Microbes and Mental Illness: Past, Present, and Future

Bransfield,

Mao,

Greenberg

2023

Healthcare

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A review of the association between microbes and mental illness is performed, including the history, relevant definitions, infectious agents associated with mental illnesses, complex interactive infections, total load theory, pathophysiology, psychoimmunology, psychoneuroimmunology, clinical presentations, early-life infections, clinical assessment, and treatment. Perspectives on the etiology of mental illness have evolved from demonic possession toward multisystem biologically based models that include gene expression, environmental triggers, immune mediators, and infectious diseases. Microbes are associated with a number of mental disorders, including autism, schizophrenia, bipolar disorder, depressive disorders, and anxiety disorders, as well as suicidality and aggressive or violent behaviors. Specific microbes that have been associated or potentially associated with at least one of these conditions include Aspergillus, Babesia, Bartonella, Borna disease virus, Borrelia burgdorferi (Lyme disease), Candida, Chlamydia, coronaviruses (e.g., SARS-CoV-2), Cryptococcus neoformans, cytomegalovirus, enteroviruses, Epstein–Barr virus, hepatitis C, herpes simplex virus, human endogenous retroviruses, human immunodeficiency virus, human herpesvirus-6 (HHV-6), human T-cell lymphotropic virus type 1, influenza viruses, measles virus, Mycoplasma, Plasmodium, rubella virus, Group A Streptococcus (PANDAS), Taenia solium, Toxoplasma gondii, Treponema pallidum (syphilis), Trypanosoma, and West Nile virus. Recognition of the microbe and mental illness association with the development of greater interdisciplinary research, education, and treatment options may prevent and reduce mental illness morbidity, disability, and mortality.

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“…Indeed, severe acute respiratory syndrome induced by SARS-CoV-2 induces proinflammatory immune responses in the periphery and/or in the brain via classical TL receptor inflammatory pathway and this event is crucial for the onset of acute and chronic neuroinflammation and sickness-related behavior ( 210 ). Dysregulated immune responses resulting in lymphopenia and increased proinflammatory cytokine production seems to be the principal cause of the pathophysiology in COVID-19 and patients.…”

Section: Avoidance Resistance and Tolerance To Virusesmentioning

confidence: 99%

Genes, inflammatory response, tolerance, and resistance to virus infections in migratory birds, bats, and rodents

Pereira,

Diniz,

da Costa

et al. 2023

Front. Immunol.

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Normally, the host immunological response to viral infection is coordinated to restore homeostasis and protect the individual from possible tissue damage. The two major approaches are adopted by the host to deal with the pathogen: resistance or tolerance. The nature of the responses often differs between species and between individuals of the same species. Resistance includes innate and adaptive immune responses to control virus replication. Disease tolerance relies on the immune response allowing the coexistence of infections in the host with minimal or no clinical signs, while maintaining sufficient viral replication for transmission. Here, we compared the virome of bats, rodents and migratory birds and the molecular mechanisms underlying symptomatic and asymptomatic disease progression. We also explore the influence of the host physiology and environmental influences on RNA virus expression and how it impacts on the whole brain transcriptome of seemingly healthy semipalmated sandpiper (Calidris pusilla) and spotted sandpiper (Actitis macularius). Three time points throughout the year were selected to understand the importance of longitudinal surveys in the characterization of the virome. We finally revisited evidence that upstream and downstream regulation of the inflammatory response is, respectively, associated with resistance and tolerance to viral infections.

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Exploring the immunogenic properties of SARS-CoV-2 structural proteins: PAMP:TLR signaling in the mediation of the neuroinflammatory and neurologic sequelae of COVID-19

Cited by 10 publications

References 110 publications

Autocrine positive feedback of tumor necrosis factor from activated microglia proposed to be of widespread relevance in chronic neurological disease

Autocrine positive feedback of tumor necrosis factor from activated microglia proposed to be of widespread relevance in chronic neurological disease

Microbes and Mental Illness: Past, Present, and Future

Genes, inflammatory response, tolerance, and resistance to virus infections in migratory birds, bats, and rodents

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