Tag: long covid pathomechanism

Lowered oxygen saturation and increased body temperature in acute COVID-19 largely predict chronic fatigue syndrome and affective symptoms due to LONG COVID: a precision nomothetic approach

Abstract:

Background: Long coronavirus disease 2019 (LC) is a chronic sequel of acute COVID-19. The exact pathophysiology of the affective, chronic fatigue and physiosomatic symptoms labeled as physio-affective phenome of LC has remained elusive. Objective: The current study aims to delineate the effects of oxygen saturation (SpO2) and body temperature during the acute phase on the physio-affective phenome of LC.

Method: We recruited 120 LC patients and 36 controls. For all participants, we assessed the lowest SpO2 and peak body temperature during acute COVID-19, and the Hamilton Depression and Anxiety Rating Scale (HAMD/HAMA) and Fibro Fatigue (FF) scales 3 to 4 months later.

Results: Lowered SpO2 and increased body temperature during the acute phase and female sex predict 60.7% of the variance in the physio-affective phenome of LC. Using unsupervised learning techniques we were able to delineate a new endophenotype class, which comprises around 26.7% of the LC patients and is characterized by very low SpO2 and very high body temperature, and depression, anxiety, chronic fatigue, and autonomic and gastro-intestinal symptoms scores. Single latent vectors could be extracted from both biomarkers, depression, anxiety and FF symptoms or from both biomarkers, insomnia, chronic fatigue, gastro-intestinal and autonomic symptoms.

Conclusion: The newly constructed endophenotype class and pathway phenotypes indicate that the physio-affective phenome of LC is at least in part the consequence of the pathophysiology of acute COVID-19, namely the combined effects of lowered SpO2, increased body temperature and the associated immune-inflammatory processes and lung lesions.

Source: Dhurgham Shihab Al-Hadrawi, Haneen Tahseen Al-Rubaye, Abbas F. Almulla, Hussein Kadhem Al-Hakeim, Michael F. Maes. Lowered oxygen saturation and increased body temperature in acute COVID-19 largely predict chronic fatigue syndrome and affective symptoms due to LONG COVID: a precision nomothetic approach. medRxiv 2022.04.10.22273660; doi: https://doi.org/10.1101/2022.04.10.22273660 https://www.medrxiv.org/content/10.1101/2022.04.10.22273660v1 (Full text as PDF file)

Neurocognitive and psychiatric post-coronavirus disease 2019 conditions: pathogenic insights of brain dysfunction following severe acute respiratory syndrome coronavirus 2 infection

Abstract:

Purpose of review: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), can trigger a myriad of neuropsychiatric manifestations. As a 2-year-old disease (at the writing of this manuscript), its long-term cognitive and neuropsychiatric implications, known as post-COVID-19 conditions, are incompletely recognized and mechanistically obscure.

Recent findings: Fatigue, anxiety, depression, posttraumatic stress disorder, and cognitive dysfunction are reported more frequently in COVID-19 survivors than in matching, non-COVID-19 population. Risk factors are unclear, including comorbidities, age at COVID-19 onset, or disease severity; women, however, have been reported to be at increased risk than men. Although the frequency of these symptoms decreases over time, at least one in five will have persistent cognitive and neuropsychiatric manifestations one year after recovering from COVID-19.

Summary: Neurocognitive and psychiatric post-COVID-19 long-term conditions are frequent and complex multifactorial sequelae. Several acute and chronic factors such as hypoxemia, cerebral thrombotic and inflammatory endothelial damage, and disruption of the blood-brain barrier (leading to parenchymal translocation of pro-inflammatory molecules, cytokines, and cytotoxic T lymphocytes) are involved, leading to microglial activation and astrogliosis. As an evolving topic, evidence derived from prospective studies will expand our understanding of post-COVID-19 these long-term outcomes.

Source: García-Grimshaw M, Sankowski R, Valdés-Ferrer SI. Neurocognitive and psychiatric post-coronavirus disease 2019 conditions: pathogenic insights of brain dysfunction following severe acute respiratory syndrome coronavirus 2 infection. Curr Opin Neurol. 2022 Mar 11. doi: 10.1097/WCO.0000000000001046. Epub ahead of print. PMID: 35283463. https://pubmed.ncbi.nlm.nih.gov/35283463/

Early clues regarding the pathogenesis of long-COVID

Abstract:

Intense investigation into the predictors and determinants of post-acute sequelae of SARS-CoV-2 infection (PASC), including ‘long COVID’, is underway. Recent studies provide clues to the mechanisms that might drive this condition, with the goal of identifying host or virus factors that can be intervened upon to prevent or reverse PASC.

Source: Peluso MJ, Deeks SG. Early clues regarding the pathogenesis of long-COVID. Trends Immunol. 2022 Apr;43(4):268-270. doi: 10.1016/j.it.2022.02.008. Epub 2022 Mar 8. PMID: 35272932; PMCID: PMC8901423. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8901423/ (Full text)

The immunology and immunopathology of COVID-19

Abstract:

Considerable research effort has been made worldwide to decipher the immune response triggered upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, identify the drivers of severe and fatal COVID-19, and understand what leads to the prolongation of symptoms after disease resolution. We review the results of almost 2 years of COVID-19 immunology research and discuss definitive findings and remaining questions regarding our understanding of COVID-19 pathophysiology. We discuss emerging understanding of differences in immune responses seen in those with and without Long Covid syndrome, also known as post-acute sequelae of SARS-CoV-2. We hope that the knowledge gained from this COVID-19 research will be applied in studies of inflammatory processes involved in critical and chronic illnesses, which remain a major unmet need.
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Source: Merad M, Blish CA, Sallusto F, Iwasaki A. The immunology and immunopathology of COVID-19. Science. 2022 Mar 11;375(6585):1122-1127. doi: 10.1126/science.abm8108. Epub 2022 Mar 10. PMID: 35271343. https://www.science.org/doi/full/10.1126/science.abm8108 (Full text)

Post-acute COVID-19 syndrome presented as a cerebral and systemic vasculitis: a case report

To the Editor,

Post-acute Coronavirus Disease of 2019 (COVID-19) syndrome is defined as the appearance of symptoms or an organ dysfunction, which occurs at least 4 weeks after the first COVID-19 manifestations and cannot be explained by any alternative diagnosis []. Neurological complications are also well recognized, and include acute cerebrovascular events, encephalopathy, meningoencephalitis, Guillain–Barre syndrome, demyelination, dementia, parkinsonism, and others []. On the other hand, cerebral vasculitis is one of the causes which can lead to brain damage related to COVID-19 infection []. We present a 69-year-old male with systemic vasculitis and central nervous system (CNS) involvement as a manifestation of post-acute COVID-19 syndrome.

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Source: Ivanovic, Jovana et al. “Post-acute COVID-19 syndrome presented as a cerebral and systemic vasculitis: a case report.” Acta neurologica Belgica, 1–3. 13 Mar. 2022, doi:10.1007/s13760-022-01923-2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8918071/ (Full text)

Chronic cerebral aspects of long COVID, post-stroke syndromes and similar states share their pathogenesis and perispinal etanercept treatment logic

Abstract:

The chronic neurological aspects of traumatic brain injury, post-stroke syndromes, long COVID-19, persistent Lyme disease, and influenza encephalopathy having close pathophysiological parallels that warrant being investigated in an integrated manner. A mechanism, common to all, for this persistence of the range of symptoms common to these conditions is described. While TNF maintains cerebral homeostasis, its excessive production through either pathogen-associated molecular patterns or damage-associated molecular patterns activity associates with the persistence of the symptoms common across both infectious and non-infectious conditions.

The case is made that this shared chronicity arises from a positive feedback loop causing the persistence of the activation of microglia by the TNF that these cells generate. Lowering this excess TNF is the logical way to reducing this persistent, TNF-maintained, microglial activation. While too large to negotiate the blood-brain barrier effectively, the specific anti-TNF biological, etanercept, shows promise when administered by the perispinal route, which allows it to bypass this obstruction.

Source: Clark IA. Chronic cerebral aspects of long COVID, post-stroke syndromes and similar states share their pathogenesis and perispinal etanercept treatment logic. Pharmacol Res Perspect. 2022 Apr;10(2):e00926. doi: 10.1002/prp2.926. PMID: 35174650; PMCID: PMC8850677. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8850677/ (Full text)

A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications

Abstract:

Post-acute sequelae of COVID (PASC), usually referred to as ‘Long COVID’ (a phenotype of COVID-19), is a relatively frequent consequence of SARS-CoV-2 infection, in which symptoms such as breathlessness, fatigue, ‘brain fog’, tissue damage, inflammation, and coagulopathies (dysfunctions of the blood coagulation system) persist long after the initial infection. It bears similarities to other post-viral syndromes, and to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Many regulatory health bodies still do not recognize this syndrome as a separate disease entity, and refer to it under the broad terminology of ‘COVID’, although its demographics are quite different from those of acute COVID-19. A few years ago, we discovered that fibrinogen in blood can clot into an anomalous ‘amyloid’ form of fibrin that (like other β-rich amyloids and prions) is relatively resistant to proteolysis (fibrinolysis). The result, as is strongly manifested in platelet-poor plasma (PPP) of individuals with Long COVID, is extensive fibrin amyloid microclots that can persist, can entrap other proteins, and that may lead to the production of various autoantibodies. These microclots are more-or-less easily measured in PPP with the stain thioflavin T and a simple fluorescence microscope.

Although the symptoms of Long COVID are multifarious, we here argue that the ability of these fibrin amyloid microclots (fibrinaloids) to block up capillaries, and thus to limit the passage of red blood cells and hence O2 exchange, can actually underpin the majority of these symptoms. Consistent with this, in a preliminary report, it has been shown that suitable and closely monitored ‘triple’ anticoagulant therapy that leads to the removal of the microclots also removes the other symptoms. Fibrin amyloid microclots represent a novel and potentially important target for both the understanding and treatment of Long COVID and related disorders.

Source: Kell DB, Laubscher GJ, Pretorius E. A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications. Biochem J. 2022 Feb 17;479(4):537-559. doi: 10.1042/BCJ20220016. PMID: 35195253. https://portlandpress.com/biochemj/article/479/4/537/230829/A-central-role-for-amyloid-fibrin-microclots-in (Full text)