Cytokine release syndrome in severe COVID-19

Moore, John B.; June, Carl H.

doi:10.1126/science.abb8925

Cited by 1,771 publications

(1,907 citation statements)

References 12 publications

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“…Programmed death 1 (PD-1) blockade has improved survival in patients in multiple incurable cancers, but there is uncertainty about the potential impactharmful, beneficial, or neitherof immunotherapy in the context of COVID-19 (12). On one hand, PD-1 blockade might theoretically augment the hyperactive immune phase of COVID-19 and worsen outcomes (13). Alternatively, as PD-1 blockade can enhance immunologic control of viral infections, it could theoretically improve outcomes (14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Impact of PD-1 Blockade on Severity of COVID-19 in Patients with Lung Cancers

et al. 2020

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Section: Introductionmentioning

confidence: 99%

Impact of PD-1 Blockade on Severity of COVID-19 in Patients with Lung Cancers

et al. 2020

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“…1), it is tempting to speculate that such mechanisms could be less efficient in SARS-CoV-2 compared to SARS-CoV. Indeed, cytokine production was described to be connected to pathogenesis [21,40,41]. However, the extent to which observations in cell lines and other models are reproducible in animal models and humans will require further investigations [62][63][64].…”

Section: Discussionmentioning

confidence: 99%

“…This response was absent in Caco-2 cells likely due to the reduced expression of pattern-recognition receptors, IFIH1 and DDX58 that activate transcription of target genes via interferon regulatory factors (IRF) and NF-κB signaling [36,37], which supports similar results for SARS-CoV infection [38] (Supplementary data 1). [40,41].…”

Section: Sars-cov-2 Infected Calu-3 Cells Show a Strong Induction Ofmentioning

confidence: 99%

Bulk and single-cell gene expression profiling of SARS-CoV-2 infected human cell lines identifies molecular targets for therapeutic intervention

Wyler

Mösbauer

Franke

et al. 2020

Preprint

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The coronavirus disease 2019 pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing global health threat with more than two million infected people since its emergence in late 2019. Detailed knowledge of the molecular biology of the infection is indispensable for understanding of the viral replication, host responses, and disease progression. We provide gene expression profiles of SARS-CoV and SARS-CoV-2 infections in three human cell lines (H1299, Caco-2 and Calu-3 cells), using bulk and single-cell transcriptomics. Small RNA profiling showed strong expression of the immunity and inflammation-associated microRNA miRNA-155 upon infection with both viruses. SARS-CoV-2 elicited approximately two-fold higher stimulation of the interferon response compared to SARS-CoV in the permissive human epithelial cell line Calu-3, and induction of cytokines such as CXCL10 or IL6. Single cell RNA sequencing data showed that canonical interferon stimulated genes such as IFIT2 or OAS2 were broadly induced, whereas interferon beta (IFNB1) and lambda (IFNL1-4) were expressed only in a subset of infected cells. In addition, temporal resolution of transcriptional responses suggested interferon regulatory factors (IRFs) activities precede that of nuclear factor-κB (NF-κB). Lastly, we identified heat shock protein 90 (HSP90) as a protein relevant for the infection. Inhibition of the HSP90 charperone activity by Tanespimycin/17-N-allylamino-17-demethoxygeldanamycin (17-AAG) resulted in a reduction of viral replication, and of TNF and IL1B mRNA levels. In summary, our study established in vitro cell culture models to study SARS-CoV-2 infection and identified HSP90 protein as potential drug target for therapeutic intervention of SARS-CoV-2 infection.

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“…Furthermore, a large proportion of obesity cases in Mexico live in geographical areas of increased social vulnerability, which poses a structural inequality that might also increase mortality for COVID-19 associated to both diabetes and obesity [11]. Chronic inflammation in obesity might worsen the acute inflammatory response triggered by SARS-CoV-2 infection, which might be associated to a cytokine release syndrome [5,12]. Here, we investigate the role of both diabetes and obesity in determining propensity for SARS-CoV-2 infection and its associated clinical outcomes including disease severity and COVID-19 lethality; using these associations, we further construct a clinically useful predictive model for COVID-19 mortality using national epidemiological surveillance data from Mexico.…”

Section: Introductionmentioning

confidence: 99%

Predicting mortality due to SARS-CoV-2: A mechanistic score relating obesity and diabetes to COVID-19 outcomes in Mexico

Bello‐Chavolla

Bahena-López

Antonio-Villa

et al. 2020

Preprint

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WORDS)BACKGROUND: The SARS-CoV-2 outbreak poses challenge to healthcare systems due to high complication rates in patients with cardiometabolic diseases. Here, we identify risk factors and propose a clinical score to predict COVID-19 lethality, including specific factors for diabetes and obesity and its role in improving risk prediction. METHODS:We obtained data of confirmed and negative COVID-19 cases and their demographic and health characteristics from the General Directorate of Epidemiology of Mexican Ministry of Health. We investigated specific risk factors associated to COVID-19 positivity and mortality and explored the impact of diabetes and obesity on modifying COVID-19 related lethality. Finally, we built a clinical score to predict COVID-19 lethality. RESULTS:Among 177,133 subjects at May 18 th , 2020, we observed 51,633 subjects with SARS-CoV-2 and 5,332 deaths. Risk factors for lethality in COVID-19 include early-onset diabetes, obesity, COPD, advanced age, hypertension, immunosuppression, and CKD; we observed that obesity mediates 49.5% of the effect of diabetes on COVID-19 lethality. Earlyonset diabetes conferred an increased risk of hospitalization and obesity conferred an increased risk for ICU admission and intubation. Our predictive score for COVID-19 lethality included age ≥ 65 years, diabetes, early-onset diabetes, obesity, age <40 years, CKD, hypertension, and immunosuppression and significantly discriminates lethal from non-lethal COVID-19 cases (c-statistic=0.823). RESULTS:Here, we propose a mechanistic approach to evaluate risk for complications and lethality attributable to COVID-19 considering the effect of obesity and diabetes in Mexico.Our score offers a clinical tool for quick determination of high-risk susceptibility patients in a first contact scenario.

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Cytokine release syndrome in severe COVID-19

Abstract: Lessons from arthritis and cell therapy in cancer patients point to therapy for severe disease

Cited by 1,771 publications

References 12 publications

Impact of PD-1 Blockade on Severity of COVID-19 in Patients with Lung Cancers

Impact of PD-1 Blockade on Severity of COVID-19 in Patients with Lung Cancers

Bulk and single-cell gene expression profiling of SARS-CoV-2 infected human cell lines identifies molecular targets for therapeutic intervention

Predicting mortality due to SARS-CoV-2: A mechanistic score relating obesity and diabetes to COVID-19 outcomes in Mexico

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