Immune Pathogenesis of COVID-19 Intoxication: Storm or Silence?

Kiselevskiy, Mikhail; Шубина, И. Ж.; Chikileva, Irina O.; Ситдикова, С. М.; Samoylenko, Igor; Anisimova, Natalia; Киргизов, К. И.; Сулейманова, А. М.; Gorbunova, Tatyana; Варфоломеева, С. Р.

doi:10.3390/ph13080166

Cited by 18 publications

(17 citation statements)

References 116 publications

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“…Finally, human coronavirus can lie dormant in the leukocytes for a long period and may manifest as delayed or persistent central nervous system infection, later giving rise to movement disorders 87 . Indeed, immune dysregulation brought about by SARS‐CoV‐2 infection 88 may lead to neurodegeneration 89 and potentially neurodegenerative movement disorders might manifest later. Notwithstanding, movement disorders are being increasingly documented because of the higher reporting frequency of COVID‐19 cases worldwide.…”

Section: Discussionmentioning

confidence: 99%

De Novo Movement Disorders and COVID‐19: Exploring the Interface

Ghosh

Biswas

Roy

et al. 2021

Movement Disord Clin Pract

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Section: Discussionmentioning

confidence: 99%

De Novo Movement Disorders and COVID‐19: Exploring the Interface

Ghosh

Biswas

Roy

et al. 2021

Movement Disord Clin Pract

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“…We analyzed nonhuman RNA presence within each sample using KRAKEN2 tools and a database of thousands of transcriptomes from bacteria/plants/viruses/fungi. Three patients (13,28,36) have higher values of mapped bacterial RNA, four (12,14,18,25,28) with higher plant RNA, and two (27 and 25) with high viral RNA (Figure 6A). Multiple patients carried elevation of bacterial species such as Photobacterium 6B).…”

Section: Secondary Infectionsmentioning

confidence: 99%

“…In choosing the right treatment strategy for the immunemediated complications of coronavirus infection, neutralizing the "cytokine storm" is often the putative goal. Still, it is vital to recognize immune incompetence that turns into immunoparalysis with increased vulnerability to secondary infections (14). In addition to acute complications, the global activation of the immune system may be related to poorly understood chronic problems in survivors of COVID-19 (15,16) that are beginning to surface in COVID-19 "long-haulers."…”

Section: Introductionmentioning

confidence: 99%

High-Density Blood Transcriptomics Reveals Precision Immune Signatures of SARS-CoV-2 Infection in Hospitalized Individuals

et al. 2021

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The immune response to COVID-19 infection is variable. How COVID-19 influences clinical outcomes in hospitalized patients needs to be understood through readily obtainable biological materials, such as blood. We hypothesized that a high-density analysis of host (and pathogen) blood RNA in hospitalized patients with SARS-CoV-2 would provide mechanistic insights into the heterogeneity of response amongst COVID-19 patients when combined with advanced multidimensional bioinformatics for RNA. We enrolled 36 hospitalized COVID-19 patients (11 died) and 15 controls, collecting 74 blood PAXgene RNA tubes at multiple timepoints, one early and in 23 patients after treatment with various therapies. Total RNAseq was performed at high-density, with >160 million paired-end, 150 base pair reads per sample, representing the most sequenced bases per sample for any publicly deposited blood PAXgene tube study. There are 770 genes significantly altered in the blood of COVID-19 patients associated with antiviral defense, mitotic cell cycle, type I interferon signaling, and severe viral infections. Immune genes activated include those associated with neutrophil mechanisms, secretory granules, and neutrophil extracellular traps (NETs), along with decreased gene expression in lymphocytes and clonal expansion of the acquired immune response. Therapies such as convalescent serum and dexamethasone reduced many of the blood expression signatures of COVID-19. Severely ill or deceased patients are marked by various secondary infections, unique gene patterns, dysregulated innate response, and peripheral organ damage not otherwise found in the cohort. High-density transcriptomic data offers shared gene expression signatures, providing unique insights into the immune system and individualized signatures of patients that could be used to understand the patient’s clinical condition. Whole blood transcriptomics provides patient-level insights for immune activation, immune repertoire, and secondary infections that can further guide precision treatment.

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“…Previous studies have shown that patients with severe COVID-19 have acute lymphopenia and damage to lymphatic tissues such as the spleen and lymph nodes, leading to immune paralysis that interferes with the clearance of virus [ 49 ]. The enhanced ratio of neutrophils to lymphocytes was observed in severe COVID-19 patients with lymphopenia, which is considered a clear sign of systemic inflammation and poor prognosis [ 50 ]. In COVID-19 patients, the T cell and NK cell counts are reduced, and significantly lower in the critically ill cases [ 51 – 53 ].…”

Section: Cytokine Storm Accounts For the Severity Of Covid-19mentioning

confidence: 99%

Natural products provide a new perspective for anti-complement treatment of severe COVID-19: a review

Fan

Wang

et al. 2021

Chin Med

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Exaggerated immune response and cytokine storm are accounted for the severity of COVID-19, including organ dysfunction, especially progressive respiratory failure and generalized coagulopathy. Uncontrolled activation of complement contributes to acute and chronic inflammation, the generation of cytokine storm, intravascular coagulation and cell/tissue damage, which may be a favorable target for the treatment of multiple organ failure and reduction of mortality in critically ill patients with COVID-19. Cytokine storm suppression therapy can alleviate the symptoms of critically ill patients to some extent, but as a remedial etiological measure, its long-term efficacy is still questionable. Anti-complement therapy has undoubtedly become an important hotspot in the upstream regulation of cytokine storm. However, chemosynthetic complement inhibitors are expensive, and their drug resistance and long-term side effects require further investigation. New complement inhibitors with high efficiency and low toxicity can be obtained from natural products at low development cost. This paper puts forward some insights of the development of natural anti-complement products in traditional Chinese medicine, that may provide a bright perspective for suppressing cytokine storm in critically ill patients with COVID-19.

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Immune Pathogenesis of COVID-19 Intoxication: Storm or Silence?

Cited by 18 publications

References 116 publications

De Novo Movement Disorders and COVID‐19: Exploring the Interface

De Novo Movement Disorders and COVID‐19: Exploring the Interface

High-Density Blood Transcriptomics Reveals Precision Immune Signatures of SARS-CoV-2 Infection in Hospitalized Individuals

Natural products provide a new perspective for anti-complement treatment of severe COVID-19: a review

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