The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system

Coperchini, Francesca; Chiovato, Luca; Croce, Laura; Magri, Flavia; Rotondi, Mario

doi:10.1016/j.cytogfr.2020.05.003

Cited by 1,220 publications

(1,313 citation statements)

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“…CXCL8 and its receptors contribute to pathogen elimination, through the transient activation of ERK, AKT, SRC and FAK leading to activation of neutrophils 26 . The expression of CXCL8, which is present in COVID-19 patients, is considered a potential prognostic factor in acute respiratory distress syndrome (ARDS) 29 and lung injury 30 .…”

Section: Discussionmentioning

confidence: 99%

Increased expression of hypoxia-induced factor 1α mRNA and its related genes in myeloid blood cells from critically ill COVID-19 patients

Taniguchi‐Ponciano

Vadillo

Mayani

et al. 2020

Preprint

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Since its emergence, in December 2019, COVID-19 has resulted in more than 12 million people infected and has killed more than 570000. Hypoxemia has been identified as one of the main clinical manifestations of this disease, especially in severe cases. We have previously reported that in critically ill COVID-19 patients there is a shift towards an immature myeloid profile in peripheral blood cells, including band neutrophils, immature monocytes, metamyelocytes, monocyte-macrophages, monocytoid precursors, and promyelocytes-myelocytes, which, together with mature monocytes and segmented neutrophils, comprise the vast majority of blood cells in these patients. Such an immature myeloid profile may be the result of a physiological response known as emergency myelopoiesis. In the present study, we performed scRNAseq from leukocytes from five critically ill COVID-19 patients and characterized the expression of hypoxia-inducible factor1α (HIF1α) mRNA and its transcriptionally regulated genes. HIF1α is a master transcription factor involved in the cellular response to hypoxia. We herein report that these cellular subsets express high levels of HIF1α mRNA and several of their transcriptional targets, including those related to inflammation, such as CXCL8, CXCR1, CXCR2, and CXCR4; those potentially involved in virus sensing, such as TLR2 and TLR4; and those related to metabolism, such as SLC2A3, PFKFB3, PGK1, GAPDH and SOD2. The up-regulation and participation of HIF1α in relevant events such as inflammation, immunometabolism, and TLR make it a potential molecular marker for COVID-19 severity and, interestingly, could represent a potential target for molecular therapy.

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Section: Discussionmentioning

confidence: 99%

Increased expression of hypoxia-induced factor 1α mRNA and its related genes in myeloid blood cells from critically ill COVID-19 patients

Taniguchi‐Ponciano

Vadillo

Mayani

et al. 2020

Preprint

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“…Mc Gonagle et al illustrated that lung pathology seen in patients with COVID-19 shows marked alveolar and interstitial in ammation [17] It is currently believed that lung injury in COVID-19 not only associates with direct viral injury but also COVID-19 triggers immune response which leads to activation of immune cells and cytokine storm [18]. Cytokine storm extensively damages vascular endothelium and alveolar epithelium which increases vascular permeability leading to pulmonary edema and hyaline formation [19,20], similar to our ndings previous studies also reported aggravation of symptoms during 5-7 days after the disease onset [21], therefore it is important to control the in ammatory response and cytokine storm in this phase, however, by the systematic review, Nicola Veronese concluded that the routine use of corticosteroids in COVID-19 couldn't be encouraged, but methylprednisolone therapy could lower mortality rate in more severe forms of this condition, such as in severe respiratory failure.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Efficacy of Methylprednisolone Pulse Therapy in Treatment of Covid-19 Adult Patients with Severe Respiratory Failure: Randomized, Clinical Trial

Farahani

Mosaed

Nezami-Asl

et al. 2020

Preprint

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Background: Covid-19 is now global concern and widely spread to the world due to high mortality among the nations we tried to evaluate the efficacy of methylprednisolone pulse in COVID-19 patients with severe respiratory failure.Methods: This study was phase2, double-blind, randomized, clinical trial in adults with COVID-19 (aged ≥18 years old) admitted to the intensive care unit (ICU) of *. Patients with intermediate or severe COVID-19 with PaO2/FiO2 less than 300 and progressive disease unresponsive to standard treatments admitted to ICU. Patients were randomly allocated in either control or investigation group. The control group received recommended regimen for COVID-19. The investigation group received the recommended regimen plus Methylprednisolone (1000mg/day for three days) and oral prednisolone 1mg/kg with tapering of dose within ten days. Results: A total of 29 ICU patients with intermediate or severe COVID-19 pneumonia recruited in this study. Fourteen patients (4 female, ten male) allocated in the investigation group, and 15 patients (6 female, nine male) assigned to the control group. The participant’s average age was 64.03±13.545 (case: 61.07±12.83, control: 66.80±14.03). The patients with methylprednisolone pulse had significantly higher systolic (P=0.018) and diastolic (P=0.001) blood pressure, meanwhile, the Glasgow coma scale (GCS) of methylprednisolone group was considerably (P<0.001) higher, and by the improvement in SpO2 of methylprednisolone group none of these patients needed mechanical ventilation.Conclusion: This study demonstrated methylprednisolone pulse in COVID-19 severe respiratory failure dramatically improves the clinical condition of patients including, GCS, and SpO2 of patients.Clinical Trial Registration Number: IRCT20200406046963N1

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“…Mice model study also reveals the surge of chemokines in the lungs on SARS-CoV–2 infection(Shi-Hui-Sun et al 2020; Jason et al 2008). Elevation level was highest for inflammatory chemokines (macrophage inflammatory protein (MIP)-1α/CCL3, secreted (RANTES)/CCL-5, interferon-inducible protein (IP-10)/CXCL10 and monocyte chemotactic protein (MCP)-1/CCL2 upon SARS-Co-V infection and it may be true for other β-coronaviruses family viruses including SARS-CoV-2(Coperchini F, 2020; Zang et al 2020). We postulated that this lack of antiviral cytokine response against a background of intense chemokine upregulation could represent a mechanism of immune evasion by SARS-CoV-2; however, the genomic heterogeneity of S and N protein between SARS-CoV-2 and CARS-CoV-2 is essentially required to understand the immune escape mechanism.…”

Section: Discussionmentioning

confidence: 99%

Genotypic and antigenic study of SARS-CoV-2 from an Indian isolate

Dhar

Sinha²,

Seethy

et al. 2020

Preprint

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Coronaviruses (CoVs) are one of the largest groups of positive-sense RNA virus families within the Nidovirales order, which are further classified into four genera: alpha, beta, gamma, and delta. Coronaviruses have an extensive range of natural hosts and are known to be responsible for a broad spectrum of diseases in multiple species. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) that has unleashed a global threat to public health and the economy. Coronaviruses are extensively present in birds and mammals, with horseshoe bats (Rhinolophus affinis), being the reservoir for the ongoing SARS-CoV-2 that seems to have resulted from a zoonotic spillover to the human host, causing respiratory infections, lung injury and Acute Respiratory Distress Syndrome(ARDS). About six coronavirus serotypes are linked with the disease in humans, namely HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, SARS-CoV, SARS-CoV-2, and MERS-CoV. SARS-CoV-2 is the seventh CoV to infect humans. We analyzed the genome sequence of CoV-2 from isolates derived from China as well from India and encountered minute variations in their sequence. A cladogram analysis revealed the predominant strain circulating in India belongs to the A2a clad. We took one such strain (MT012098) and performed a rigorous in-silico genotypic and antigenic analysis to identify its relatedness to other strains. Further, we also performed a detailed prediction for B and T cell epitopes using BepiPred 2.0 server and NetCTL 1.2 server (DTU Bioinformatics), respectively. We hope this information may assist in an effective vaccine designing program against SARS-CoV-2.

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The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system

Cited by 1,220 publications

References 98 publications

Increased expression of hypoxia-induced factor 1α mRNA and its related genes in myeloid blood cells from critically ill COVID-19 patients

Increased expression of hypoxia-induced factor 1α mRNA and its related genes in myeloid blood cells from critically ill COVID-19 patients

Evaluation of the Efficacy of Methylprednisolone Pulse Therapy in Treatment of Covid-19 Adult Patients with Severe Respiratory Failure: Randomized, Clinical Trial

Genotypic and antigenic study of SARS-CoV-2 from an Indian isolate

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