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The persistence or emergence of long-term symptoms following resolution of primary SARS-CoV-2 infection is referred to as long COVID or post-acute sequelae of COVID-19 (PASC). PASC predominantly affects the cardiovascular, neurological, respiratory, gastrointestinal, reproductive, and immune systems. Among these, the central nervous system (CNS) is significantly impacted, leading to a spectrum of symptoms, including fatigue, headaches, brain fog, cognitive impairment, anosmia, hypogeusia, neuropsychiatric symptoms, and peripheral neuropathy (neuro-PASC). However, the risk factors and pathogenic mechanisms responsible for neuro-PASC remain unclear. This review hypothesis discusses the leading hypotheses regarding the pathophysiological mechanisms involved in long COVID/PASC, focusing on neuro-PASC. We propose vascular dysfunction mediated by activation of astrocytes and pericytes followed by blood–brain barrier (BBB) disruption as underlying pathophysiological mechanisms of neurological manifestations. Additionally, we provide insights into the role of spike protein at the blood–brain interface. Finally, we explore the potential pathogenic mechanisms initiated by the interaction between the spike protein and cellular receptors at the brain endothelial and tissue levels. [ABSTRACT FROM AUTHOR]

This review presents modern domestic and foreign published data on the effect of the SARS-CoV-2 virus on red blood cells in COVID-19 and on the effect of the resulting erythrocyte degradation products on the body. The mechanisms of detoxification of these products and the possibility of considering them as biomarkers of this severe disease, as well as therapeutic targets for combating it, are considered in detail. [ABSTRACT FROM AUTHOR]

The persistence or emergence of long-term symptoms following resolution of primary SARS-CoV-2 infection is referred to as long COVID or post-acute sequelae of COVID-19 (PASC). PASC predominantly affects the cardiovascular, neurological, respiratory, gastrointestinal, reproductive, and immune systems. Among these, the central nervous system (CNS) is significantly impacted, leading to a spectrum of symptoms, including fatigue, headaches, brain fog, cognitive impairment, anosmia, hypogeusia, neuropsychiatric symptoms, and peripheral neuropathy (neuro-PASC). However, the risk factors and pathogenic mechanisms responsible for neuro-PASC remain unclear. This review hypothesis discusses the leading hypotheses regarding the pathophysiological mechanisms involved in long COVID/PASC, focusing on neuro-PASC. We propose vascular dysfunction mediated by activation of astrocytes and pericytes followed by blood–brain barrier (BBB) disruption as underlying pathophysiological mechanisms of neurological manifestations. Additionally, we provide insights into the role of spike protein at the blood–brain interface. Finally, we explore the potential pathogenic mechanisms initiated by the interaction between the spike protein and cellular receptors at the brain endothelial and tissue levels.

A major problem in SARS-CoV-2-infected patients is the massive tissue inflammation in certain target organs, including the lungs. Mast cells (MC), basophils (BA), and eosinophils (EO) are key effector cells in inflammatory processes. These cells have recently been implicated in the pathogenesis of SARS-CoV-2 infections. We explored coronavirus receptor (CoV-R) expression profiles in primary human MC, BA, and EO, and in related cell lines (HMC-1, ROSA, MCPV-1, KU812, and EOL-1). As determined using flow cytometry, primary MC, BA, and EO, and their corresponding cell lines, displayed the CoV-R CD13 and CD147. Primary skin MC and BA, as well as EOL-1 cells, also displayed CD26, whereas primary EO and the MC and BA cell lines failed to express CD26. As assessed using qPCR, most cell lines expressed transcripts for CD13, CD147, and ABL2, whereas ACE2 mRNA was not detectable, and CD26 mRNA was only identified in EOL-1 cells. We also screened for drug effects on CoV-R expression. However, dexamethasone, vitamin D, and hydroxychloroquine did not exert substantial effects on the expression of CD13, CD26, or CD147 in the cells. Together, MC, BA, and EO express distinct CoV-R profiles. Whether these receptors mediate virus–cell interactions and thereby virus-induced inflammation remains unknown at present. [ABSTRACT FROM AUTHOR]

Perfluorooctanoic acid (PFOA), a ubiquitous environmental toxicant from the Per- and polyfluoroalkyl substances (PFAS) family has been implicated in toxicity of various organs. Several epidemiological studies have linked PFOA to different lung injuries and diseased conditions. However, the implication of PFOA in affecting epigenetic regulators and SARS-CoV-2 infection pathways in the lung are unknown. The present work explores the accumulation of PFOA in lungs and changes in mRNA expression of DNA methylation regulator genes DNA methyltransferases (Dnmts) and ten-eleven translocation (Tets) along with the membrane proteins angiotensin converting enzyme 2 (Ace2) and transmembrane Serine Protease 2 (Tmprss2) genes involved in the SARS-CoV-2 virus infection. CD1 mice were orally exposed to 5 and 20 mg/kg/day PFOA for 10 days and the lung tissues were analyzed using LCMS, qPCR, and pyrosequencing techniques. PFOA was shown to accumulate in the lung tissues and increase in a dose-dependent manner. Dnmts and Tets were significantly downregulated upon at least one of the PFOA dosing concentration, whereas Ace2 and Tmprss2 show significant increase in their expression level. Further, CpG islands in the promotor region of Tmprss2 exhibited significant hypomethylation in PFOA treated groups, which supports its increased gene expression level. Current study reveals the implication of PFOA induced DNA methylation changes in lungs and their possible role in upregulation of Ace2 and Tmprss2. It is possible that increased expression of these membrane receptors due to PFOA exposure can lead to higher susceptibility of SARS-CoV-2 infections.

With the worldwide spread of the novel severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) resulting in declaration of a pandemic by the World Health Organization (WHO) on March 11, 2020, the SARS‐CoV‐2‐induced coronavirus disease‐19 (COVID‐19) has become one of the main challenges of our times. The high infection rate and the severe disease course led to major safety and social restriction measures worldwide. There is an urgent need of unbiased expert knowledge guiding the development of efficient treatment and prevention strategies. This report summarizes current immunological data on mechanisms associated with the SARS‐CoV‐2 infection and COVID‐19 development and progression to the most severe forms. We characterize the differences between adequate innate and adaptive immune response in mild disease and the deep immune dysfunction in the severe multiorgan disease. The similarities of the human immune response to SARS‐CoV‐2 and the SARS‐CoV and MERS‐CoV are underlined. We also summarize known and potential SARS‐CoV‐2 receptors on epithelial barriers, immune cells, endothelium and clinically involved organs such as lung, gut, kidney, cardiovascular, and neuronal system. Finally, we discuss the known and potential mechanisms underlying the involvement of comorbidities, gender, and age in development of COVID‐19. Consequently, we highlight the knowledge gaps and urgent research requirements to provide a quick roadmap for ongoing and needed COVID‐19 studies. [ABSTRACT FROM AUTHOR]