Interleukin-8 as a Biomarker for Disease Prognosis of Coronavirus Disease-2019 Patients

Li, Lili; Li, Jie; Gao, Meiling; Fan, Huimin; Wang, Yanan; Xu, Xin; Chen, Chunfeng; Liu, Junxiao; Kim, Jocelyn T.; Aliyari, Roghiyh; Zhang, Jicai; Jin, Yujie; Li, Xiaorong; Ma, Feng; Shi, Minxin; Cheng, Genhong; Yang, Heng

doi:10.3389/fimmu.2020.602395

Cited by 119 publications

(139 citation statements)

References 44 publications

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“…In particular, we found the upregulation of CXCL8 , CXCL10 , CCL2 , MMP3 , CCL5 , and PTGS2 encoding for IL-8, IP-10, MCP-1, MMP3, RANTES and COX2, respectively ( Table 2 ). IL-8, IP-10, MCP-1 and MMP-3 serum levels were suggested as biomarkers for COVID-19 disease [ 73 , 74 , 75 ]. RANTES and COX-2 increased in SARS-CoV-2 infection [ 76 , 77 ].…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Infected Pediatric Cerebral Cortical Neurons: Transcriptomic Analysis and Potential Role of Toll-like Receptors in Pathogenesis

Chiricosta

Calcaterra

Biasin

et al. 2021

IJMS

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Different mechanisms were proposed as responsible for COVID-19 neurological symptoms but a clear one has not been established yet. In this work we aimed to study SARS-CoV-2 capacity to infect pediatric human cortical neuronal HCN-2 cells, studying the changes in the transcriptomic profile by next generation sequencing. SARS-CoV-2 was able to replicate in HCN-2 cells, that did not express ACE2, confirmed also with Western blot, and TMPRSS2. Looking for pattern recognition receptor expression, we found the deregulation of scavenger receptors, such as SR-B1, and the downregulation of genes encoding for Nod-like receptors. On the other hand, TLR1, TLR4 and TLR6 encoding for Toll-like receptors (TLRs) were upregulated. We also found the upregulation of genes encoding for ERK, JNK, NF-κB and Caspase 8 in our transcriptomic analysis. Regarding the expression of known receptors for viral RNA, only RIG-1 showed an increased expression; downstream RIG-1, the genes encoding for TRAF3, IKKε and IRF3 were downregulated. We also found the upregulation of genes encoding for chemokines and accordingly we found an increase in cytokine/chemokine levels in the medium. According to our results, it is possible to speculate that additionally to ACE2 and TMPRSS2, also other receptors may interact with SARS-CoV-2 proteins and mediate its entry or pathogenesis in pediatric cortical neurons infected with SARS-CoV-2. In particular, TLRs signaling could be crucial for the neurological involvement related to SARS-CoV-2 infection.

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Infected Pediatric Cerebral Cortical Neurons: Transcriptomic Analysis and Potential Role of Toll-like Receptors in Pathogenesis

Chiricosta

Calcaterra

Biasin

et al. 2021

IJMS

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“…21,22 Serum levels of IL-8 have been consistently found increased in patients with mild and severe COVID-19, although there was not a clear correlation with the disease severity. 18 In contrast, a possible association between serum IL-8 levels and disease duration has been suggested. 23 Interleukin-6 levels suggest that neuroinflammation might play a critical role in the development of pathological pain.…”

Section: Discussionmentioning

confidence: 99%

“…The dysregulated production of IL‐6 has been attributed to autoimmunity and chronic inflammation 17 . IL‐8, a proinflammatory cytokine produced by blood cells and many types of tissue, might be increased in COVID‐19, although its diagnostic and predictive role is still debated 18 …”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal fluid and serum interleukins 6 and 8 during the acute and recovery phase in COVID‐19 neuropathy patients

Manganotti

Bellavita

Tommasini

et al. 2021

Journal of Medical Virology

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This case series describes three patients affected by severe acute respiratory syndrome coronavirus 2, who developed polyradiculoneuritis as a probable neurological complication of coronavirus disease 2019 (COVID‐19). A diagnosis of Guillain Barré syndrome was made on the basis of clinical symptoms, cerebrospinal fluid analysis, and electroneurography. In all of them, the therapeutic approach included the administration of intravenous immunoglobulin (0.4 gr/kg for 5 days), which resulted in the improvement of neurological symptoms. Clinical neurophysiology revealed the presence of conduction block, absence of F waves, and in two cases, a significant decrease in amplitude of compound motor action potential cMAP. Due to the potential role of inflammation on symptoms development and prognosis, interleukin‐6 (IL‐6) and IL−8 levels were measured in serum and cerebrospinal fluid during the acute phase, while only serum was tested after recovery. Both IL‐6 and IL‐8 were found increased during the acute phase, both in the serum and cerebrospinal fluid, whereas 4 months after admission (at complete recovery), only IL‐8 remained elevated in the serum. These results confirm the inflammatory response that might be linked to peripheral nervous system complications and encourage the use of IL‐6 and IL‐8 as prognostic biomarkers in COVID‐19.

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“…Specifically, NB-UVA treatment significantly reduced secreted levels of IL-6 and TNF-α by at least 50%. These are two major cytokines associated with the activation of the systemic immune system and inflammatory responses [28] , and are strongly correlated with COVID-19 severity and patient survival [ 10 , 29 ]. Immune-mediated clearance of viral infections involves several orchestrated and well-balanced steps, starting with recognition of the pathogen, followed by cell recruitment and resolution of the damage [28] .…”

Section: Discussionmentioning

confidence: 99%

“…Chemokines are relatively small bioactive molecules which mediate the activation and recruitment of immune cells to the site of infection, and further amplify the inflammatory response. Reduction in the levels of these biomarkers are associated, in most cases, with clearance of the infection and a subsequent return to homeostasis, including in COVID-19 patients [29] . These findings are supported by our results which suggest that repeated NB-UVA treatment results in an overall improvement in the inflammatory state in CoV-229E transfected endotracheal cells, resulting in increased cell survival [12] .…”

Section: Discussionmentioning

confidence: 99%

Ultraviolet-A light reduces cellular cytokine release from human endotracheal cells infected with Coronavirus

Leite¹,

Pimentel²,

Mathur

et al. 2021

Photodiagnosis and Photodynamic Therapy

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Background An important clinical feature of coronavirus disease 2019 (COVID-19) is hypercytokinemia (cytokine storm). We previously showed that narrow band ultraviolet-A (NB-UVA) treatment salvages coronavirus (CoV)-229E-infected human tracheal cells, and that daily endotracheal NB-UVA therapy reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) levels in human subjects, with improved clinical outcomes. Here, we examined NB-UVA effects on cytokine release during CoV-229E infection. Methods Primary human tracheal epithelial cells were transfected with CoV-229E, then exposed to 2 mW/cm 2 NB-UVA for 20 minutes every 24h, either 3 or 4 times. Secreted cytokine/chemokine levels were analyzed in supernatants harvested from CoV-229E-infected/UVA-exposed cells 24h after the last UVA treatment, and from matched non-infected/UVA-exposed controls, CoV-229E-infected/non-exposed controls, and non-infected/non-exposed (naïve) controls. Metabolic pathway/downstream prediction analyses were also performed. Results Pro-inflammatory cytokines interleukin(IL)-6 and tumor necrosis factor (TNF), and chemokines IL-8, monocyte chemoattractant protein-1 (MCP1), and interferon gamma-induced protein 10 (IP-10), were significantly increased in CoV-229E-infected cells, and significantly decreased following NB-UVA treatment. Interferon(IFN)-α2, IFN-γ, and IL-10 were not upregulated in response to CoV-229E. Metabolic pathway predictions indicated hypercytokinemia as the top inflammatory response in CoV-229E-infected cells, whereas the top predicted pathway in CoV-229E-infected/UVA-exposed cells was the recovery stage of severe acute respiratory syndrome. Conclusions Human tracheal epithelial cells infected with CoV-229E showed reduced cytokine secretions including IL-6, TNF, IL-8, and MCP-1, following NB-UVA exposure. This reduction of cytokine levels in vitro , coupled with previously identified reduced cell death in CoV-229E-infected/UVA-exposed cells, suggests that determining UVA effects on cytokine storm in human SARS-Co-V2 patients is warranted.

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Interleukin-8 as a Biomarker for Disease Prognosis of Coronavirus Disease-2019 Patients

Cited by 119 publications

References 44 publications

SARS-CoV-2 Infected Pediatric Cerebral Cortical Neurons: Transcriptomic Analysis and Potential Role of Toll-like Receptors in Pathogenesis

SARS-CoV-2 Infected Pediatric Cerebral Cortical Neurons: Transcriptomic Analysis and Potential Role of Toll-like Receptors in Pathogenesis

Cerebrospinal fluid and serum interleukins 6 and 8 during the acute and recovery phase in COVID‐19 neuropathy patients

Ultraviolet-A light reduces cellular cytokine release from human endotracheal cells infected with Coronavirus

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