SARS-CoV-2 infection: The role of cytokines in COVID-19 disease

Costela‐Ruiz, Víctor J.; Illescas‐Montes, Rebeca; Puerta-Puerta, José Manuel; Ruíz, Concepción; Melguizo‐Rodríguez, Lucia

doi:10.1016/j.cytogfr.2020.06.001

Cited by 995 publications

(1,039 citation statements)

References 180 publications

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“…This is consistent with increased disease progression when COVID-19 patients were stratified based on age. A previous study found that peripheral VEGF concentrations were significantly higher in COVID-19 patients than in healthy controls (81). We also find this effect in our human samples ( Figure 8B) where people with COVID-19 that are older than 60 years of age have more VEGF protein in their peripheral blood.…”

Section: Neutrophil Degranulation and Ifn Pathways Overlap Between Cosupporting

confidence: 82%

IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection

Rosa

Ahmed

Singh

et al. 2020

Preprint

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The novel virus SARS-CoV-2 has infected more than 14 million people worldwide resulting in the Coronavirus disease 2019 (COVID-19). Limited information on the underlying immune mechanisms that drive disease or protection during COVID-19 severely hamper development of therapeutics and vaccines. Thus, the establishment of relevant animal models that mimic the pathobiology of the disease is urgent. Rhesus macaques infected with SARS-CoV-2 exhibit disease pathobiology similar to human COVID-19, thus serving as a relevant animal model. In the current study, we have characterized the transcriptional signatures induced in the lungs of juvenile and old rhesus macaques following SARS-CoV-2 infection. We show that genes associated with Interferon (IFN) signaling, neutrophil degranulation and innate immune pathways are significantly induced in macaque infected lungs, while pathways associated with collagen formation are downregulated. In COVID-19, increasing age is a significant risk factor for poor prognosis and increased mortality. We demonstrate that Type I IFN and Notch signaling pathways are significantly upregulated in lungs of juvenile infected macaques when compared with old infected macaques. These results are corroborated with increased peripheral neutrophil counts and neutrophil lymphocyte ratio in older individuals with COVID-19 disease. In contrast, pathways involving VEGF are downregulated in lungs of old infected macaques. Using samples from humans with SARS-CoV-2 infection and COVID-19, we validate a subset of our findings. Finally, neutrophil degranulation, innate immune system and IFN gamma signaling pathways are upregulated in both tuberculosis and COVID-19, two pulmonary diseases where neutrophils are associated with increased severity. Together, our transcriptomic studies have delineated disease pathways to improve our understanding of the immunopathogenesis of COVID-19 to facilitate the design of new therapeutics for COVID-19.

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Section: Neutrophil Degranulation and Ifn Pathways Overlap Between Cosupporting

confidence: 82%

IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection

Rosa

Ahmed

Singh

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Secondly, acute in ammation caused by SARS-CoV-2 might alter lipid metabolism as well. Severe and critical patients with COVID-19 were commonly accompanied with largely excessive release of proin ammatory cytokines, such as IL-1, IL-6, IL-12, IFN -γ and TNF-α, as the disease progressed over time and gradually got worse [30]. It was shown that tumor necrosis TNF-α, IL-1β, and IL-6 could decrease synthesis and/or secretion of apolipoproteins in hepatic cell lines in dose-dependent way [31].…”

Section: Discussionmentioning

confidence: 99%

“…However, there are no clinical and experimental studies on the protective effect of HDL and Apo-AI in COVID-19. In severe and critical COVID-19 patients, clinical outcome can be signi cantly worsened by excessive release of pro-in ammatory cytokines [30]. HDL and Apo-AI may help in preventing in ammatory injury and improving the clinical outcome with anti-in ammatory and antioxidative properties.…”

Section: Discussionmentioning

confidence: 99%

Changes in lipid metabolism in patients with severe COVID-19

Li¹,

Zhang²,

Dai³

et al. 2020

Preprint

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Background: Dyslipidemia plays an important role in the pathogenesis and evolution of critical illness, but limited information exists regarding the lipid metabolism of severe coronavirus disease 2019 (COVID-19) patients. The aim of this study was to investigate role of dyslipidemia in patients with severe COVID-19Methods: We retrospectively reviewed 216 severe COVID-19 patients with clarified outcomes (discharged or deceased), admitted to the West Court of Union Hospital in Wuhan, China, between February 1 and March 31, 2020. The dynamic changes of lipid profiles and their relationships with disease severity and clinical outcomes were analyzed.Results: A total of 216 severe COVID-19 patients, including 24 non-survivors and 192 survivors, were included in the final analyses. The levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein AI (Apo-AI) on admission were significantly lower in non-survivors compared to survivors. During hospitalization, low-density lipoprotein cholesterol (LDL-C), total cholesterol(TC), HDL-C and Apo-AI were shown an increasing trend in survivors, but maintained lower levels or shown downward trend in non-survivors. The serum levels of HDL-C and Apo-AI were inversely correlated with C-reactive protein (CRP), length of hospital stay of survivors and disease severity. The receiver operating characteristic (ROC) curve analysis identified a CRP/ HDL-C ratio cut-off value of 62.54 as the predictor for in-hospital mortality (AUC=0.823, Sensitivity=83.3%, Specificity=70.8%). Logistic regression analysis demonstrated that hypertension, neutrophils-to-lymphocytes ratio(NLR), platelet count and high CRP/ HDL-C ratio (>62.54) were independent factors to predict in-hospital mortality.Conclusions: The results demonstrated that dyslipidemia was associated with the inflammatory response, disease severity and poor prognosis of COVID-19. High CRP/ HDL-C ratio may serve as an independently potential predictor for hospital mortality among patients with severe COVID-19.

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“…We next determined if SARS-CoV-2 infection of K18 hACE2 transgenic mice resulted in a cytokine storm, as described during the development of severe COVID-19 disease in humans (reviewed in [22][23][24][25][26] ). Multiple tissues were analyzed to define local and systemic inflammatory, TH1, TH17, and TH2 responses.…”

Section: Sars-cov-2 Infection Of K18 Hace2 Transgenic Mice Drives a Lmentioning

confidence: 99%

Lethality of SARS-CoV-2 infection in K18 human angiotensin converting enzyme 2 transgenic mice

Oladunni

Park

Tamayo

et al. 2020

Preprint

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Vaccine and antiviral development against SARS-CoV-2 infection or COVID-19 disease currently lacks a validated small animal model. Here, we show that transgenic mice expressing human angiotensin converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18 hACE2) represent a susceptible rodent model. K18 hACE2-transgenic mice succumbed to SARS-CoV-2 infection by day 6, with virus detected in lung airway epithelium and brain. K18 ACE2-transgenic mice produced a modest TH1/2/17 cytokine storm in the lung and spleen that peaked by day 2, and an extended chemokine storm that was detected in both lungs and brain. This chemokine storm was also detected in the brain at day 4. K18 hACE2-transgenic mice are, therefore, highly susceptible to SARS-CoV-2 infection and represent a suitable animal model for the study of viral pathogenesis, and for identification and characterization of vaccines (prophylactic) and antivirals (therapeutics) for SARS-CoV-2 infection and associated severe COVID-19 disease.

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SARS-CoV-2 infection: The role of cytokines in COVID-19 disease

Cited by 995 publications

References 180 publications

IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection

IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection

Changes in lipid metabolism in patients with severe COVID-19

Lethality of SARS-CoV-2 infection in K18 human angiotensin converting enzyme 2 transgenic mice

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