Cytokine storm induced by SARS-CoV-2 infection: The spectrum of its neurological manifestations

Thepmankorn, Parisorn; Bach, John R.; Lasfar, Ahmed; Zhao, Xilin; Souayah, S.; Chong, Zhao Zhong; Souayah, Nizar

doi:10.1016/j.cyto.2020.155404

Cited by 72 publications

(76 citation statements)

References 156 publications

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“…Despite emerging evidence for the immune regulatory functions of Neuropilin-1, its exact molecular pathways remain not fully understood. Nevertheless, it is likely that Neuropilin-1 could be also involved in the cytokine storm and the subsequent hyper-inflammatory state observed in COVID-19 patients [84][85][86], although further dedicated studies in this sense are necessary.…”

Section: Discussionmentioning

confidence: 99%

miR-24 Targets the Transmembrane Glycoprotein Neuropilin-1 in Human Brain Microvascular Endothelial Cells

Mone

Gambardella

Wang

et al. 2021

ncRNA

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Neuropilin-1 is a transmembrane glycoprotein that has been implicated in several processes including angiogenesis and immunity. Recent evidence has also shown that it is implied in the cellular internalization of the severe acute respiratory syndrome coronavirus (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). We hypothesized that specific microRNAs can target Neuropilin-1. By combining bioinformatic and functional approaches, we identified miR-24 as a regulator of Neuropilin-1 transcription. Since Neuropilin-1 has been shown to play a key role in the endothelium-mediated regulation of the blood-brain barrier, we validated miR-24 as a functional modulator of Neuropilin-1 in human brain microvascular endothelial cells (hBMECs), which are the most suitable cell line for an in vitro blood–brain barrier model.

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Section: Discussionmentioning

confidence: 99%

miR-24 Targets the Transmembrane Glycoprotein Neuropilin-1 in Human Brain Microvascular Endothelial Cells

Mone

Gambardella

Wang

et al. 2021

ncRNA

View full text Add to dashboard Cite

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“…Several other mechanisms have been postulated and proposed in the immune-mediated muscle injury observed in COVID-19 infection. An alternate or co-existing mechanism for myositis in COVID-19 pathogenesis may include the induction of a hyper-inflammatory state with a rise in TNF-alpha, interferon-alpha, interleukin-1, and interleukin-6 among other cytokines [ 46 ]. The stimulation of inflammation following the positing of antigen-antibody complexes is one of the mechanisms proposed [ 17 ••, 47 •].…”

Section: Proposed Pathogenesis Of Covid-19-triggered Muscle Inflammationmentioning

confidence: 99%

COVID-19 and Myositis: What We Know So Far

et al. 2021

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Purpose Myositis as a rare manifestation of COVID-19 is only recently being reported. This review examines the current literature on COVID-19-induced myositis focusing on etiopathogenesis, clinical presentations, diagnostic practices, and therapeutic challenges with immunosuppression, and the difficulties experienced by rheumatologists in established myositis in the COVID-19 era. Recent Findings COVID-19 is associated with a viral myositis attributable to direct myocyte invasion or induction of autoimmunity. COVID-19-induced myositis may be varied in presentation, from typical dermatomyositis to rhabdomyolysis, and a paraspinal affliction with back pain. It may or may not present with acute exponential elevations of enzyme markers such as creatine kinase (CK). Virus-mediated muscle inflammation is attributed to ACE2 (angiotensin-converting enzyme) receptor–mediated direct entry and affliction of muscle fibers, leading on to innate and adaptive immune activation. A greater recognition of the stark similarity between anti-MDA5-positive myositis with COVID-19 has thrown researchers into the alley of exploration — finding common etiopathogenic basis as well as therapeutic strategies. For patients with established myositis, chronic care was disrupted during the pandemic with several logistic challenges and treatment dilemmas leading to high flare rates. Teleconsultation bridged the gap while ushering in an era of patient-led care with the digital transition to tools of remote disease assessment. Summary COVID-19 has brought along greater insight into unique manifestations of COVID-19-related myositis, ranging from direct virus-induced muscle disease to triggered autoimmunity and other etiopathogenic links to explore. A remarkable shift in the means of delivering chronic care has led patients and caregivers worldwide to embrace a virtual shift with teleconsultation and opened doorways to a new era of patient-led care.

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“… 12 Based on multiple study observations including our own, the metabolic sequelae of SARS-CoV-2 infection are complex, engaging multiple-organ dysfunction presumed to be driven by immunopathological events including, for example, cytokine storms. 13 , 14 Related coronavirus diseases, Middle East respiratory syndrome (MERS) and SARS, have also been shown to induce long-term metabolic changes in recovered patients pertaining to hypertriglyceridemia, disorders of glucose metabolism, and liver function, further underlying the considerable need to support recovery and repair of the body during the post-COVID period. 15 , 16 The similarities between the SARS-CoV-1 and SARS-CoV-2 outbreaks also extend to the neurological consequences, with 54% of patients experiencing fatigue and 60% experiencing sleep disturbances 6 months post infection.…”

Section: Introductionmentioning

confidence: 99%

Incomplete Systemic Recovery and Metabolic Phenoreversion in Post-Acute-Phase Nonhospitalized COVID-19 Patients: Implications for Assessment of Post-Acute COVID-19 Syndrome

et al. 2021

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We present a multivariate metabotyping approach to assess the functional recovery of nonhospitalized COVID-19 patients and the possible biochemical sequelae of “Post-Acute COVID-19 Syndrome”, colloquially known as long-COVID. Blood samples were taken from patients ca. 3 months after acute COVID-19 infection with further assessment of symptoms at 6 months. Some 57% of the patients had one or more persistent symptoms including respiratory-related symptoms like cough, dyspnea, and rhinorrhea or other nonrespiratory symptoms including chronic fatigue, anosmia, myalgia, or joint pain. Plasma samples were quantitatively analyzed for lipoproteins, glycoproteins, amino acids, biogenic amines, and tryptophan pathway intermediates using Nuclear Magnetic Resonance (NMR) spectroscopy and mass spectrometry. Metabolic data for the follow-up patients ( n = 27) were compared with controls ( n = 41) and hospitalized severe acute respiratory syndrome SARS-CoV-2 positive patients ( n = 18, with multiple time-points). Univariate and multivariate statistics revealed variable patterns of functional recovery with many patients exhibiting residual COVID-19 biomarker signatures. Several parameters were persistently perturbed, e.g., elevated taurine ( p = 3.6 × 10 –3 versus controls) and reduced glutamine/glutamate ratio ( p = 6.95 × 10 –8 versus controls), indicative of possible liver and muscle damage and a high energy demand linked to more generalized tissue repair or immune function. Some parameters showed near-complete normalization, e.g., the plasma apolipoprotein B100/A1 ratio was similar to that of healthy controls but significantly lower ( p = 4.2 × 10 –3 ) than post-acute COVID-19 patients, reflecting partial reversion of the metabolic phenotype (phenoreversion) toward the healthy metabolic state. Plasma neopterin was normalized in all follow-up patients, indicative of a reduction in the adaptive immune activity that has been previously detected in active SARS-CoV-2 infection. Other systemic inflammatory biomarkers such as GlycA and the kynurenine/tryptophan ratio remained elevated in some, but not all, patients. Correlation analysis, principal component analysis (PCA), and orthogonal-partial least-squares discriminant analysis (O-PLS-DA) showed that the follow-up patients were, as a group, metabolically distinct from controls and partially comapped with the acute-phase patients. Significant systematic metabolic differences between asymptomatic and symptomatic follow-up patients were also observed for multiple metabolites. The overall metabolic variance of the symptomatic patients was significantly greater than that of nonsymptomatic patients for multiple parameters (χ 2 p = 0.014). Thus, asymptomatic follow-up patients including those with post-acute COVID-19 Syndrome displayed a ...

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Cytokine storm induced by SARS-CoV-2 infection: The spectrum of its neurological manifestations

Cited by 72 publications

References 156 publications

miR-24 Targets the Transmembrane Glycoprotein Neuropilin-1 in Human Brain Microvascular Endothelial Cells

miR-24 Targets the Transmembrane Glycoprotein Neuropilin-1 in Human Brain Microvascular Endothelial Cells

COVID-19 and Myositis: What We Know So Far

Incomplete Systemic Recovery and Metabolic Phenoreversion in Post-Acute-Phase Nonhospitalized COVID-19 Patients: Implications for Assessment of Post-Acute COVID-19 Syndrome

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