Cytokine storm and immunomodulatory therapy in COVID-19: Role of chloroquine and anti-IL-6 monoclonal antibodies

Zhao, Ming

doi:10.1016/j.ijantimicag.2020.105982

Cited by 250 publications

(245 citation statements)

References 15 publications

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“…22 In COVID-19 patients the severity of the disease is associated with a cytokine storm with markedly increased expression of interleukin 6 (IL-6) in the serum of severe cases. 23 Interestingly, IL-6 can activate mTOR in a STAT3 dependent or independent manner. 24 Whether our proposed drugs can be indeed repurposed for COVID-19 therapies now needs to be carefully tested in in vitro SARS-CoV-2 infection models and in in vivo COVID-19 disease models.…”

Section: Discussionmentioning

confidence: 99%

Dysregulation in mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells

Appelberg

Gupta

Ambikan

et al. 2020

Preprint

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26How Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infections engage 27 cellular host pathways and innate immunity in infected cells remain largely elusive. We 28 performed an integrative proteo-transcriptomics analysis in SARS-CoV-2 infected HuH7 cells to 29 map the cellular response to the invading virus over time. We identified four pathways, ErbB, 30 HIF-1, mTOR and TNF signaling, among others that were markedly modulated during the course 31 of the SARS-CoV-2 infection in vitro. Western blot validation of the downstream effector 32 molecules of these pathways revealed a significant reduction in activated S6K1 and 4E-BP1 at 72 33 hours post infection. Unlike other human respiratory viruses, we found a significant inhibition of 34 HIF-1α through the entire time course of the infection, suggesting a crosstalk between the SARS-35

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Section: Discussionmentioning

confidence: 99%

Dysregulation in mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells

Appelberg

Gupta

Ambikan

et al. 2020

Preprint

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“…The HCQ has also been reported for COVID-19 and potentially could be an alternative agent for the treatment of COVID-19. 13,20 Our small case report showed HCQ with or without AZ tested negative for the virus on an oropharyngeal swab on day 7. We found the tested negative is variate.…”

Section: Discussionmentioning

confidence: 74%

The Urgent Countermeasures in Infection Control for Diagnosis of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Taiwan

Lee

Tsao

et al. 2020

Preprint

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The emergence of the coronavirus disease 2019 (COVID-19) caused a large-scale outbreak and has rapidly spread across China and multiple countries. We reported countermeasures in infection control for diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) infection and the experiences of point of care diagnostics and medical quarantine for presumed SARS-CoV-2-infected subjects. We conducted a retrospective cohort study on subjects came to Chung Shan Medical University Hospital with suspicion of SARS-CoV-2 infection during January to March, 2020. We performed the real-time reverse-transcription polymerase chain reaction testing (rRT-PCR) for SARS-CoV-2-infection and reported the results of testing and treatment. A total of 212 participants were enrolled due to suspicion of SARS-CoV-2 infection. Five of those were confirmed COVID-19 cases after monitoring for a period of 14 days and were cured. The time to rRT-PCR test conversion after treatment is variate. The infection control measures of home quarantine and mandatory medical quarantine combined with rapid diagnosis seem to postpone the speed of transmission of SARS-CoV-2 infection at once in Taiwan. Due to lack of vaccination and confirmed antiviral therapy, it is important to strictly abide by the infection control measures.

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“…Recent studies indicated that patients with severe COVID-19 had higher C-reactive protein (CRP) and lactate dehydrogenase (LDH) levels than patients with non-severe COVID-19 (13). Moreover, in comparison with patients with mild COVID-19, the levels of IL-10 and IFNγ in patients with severe COVID-19 were signi cantly increased in the early stage of the disease, and most detected cytokines peaked in the serum 3-6 days after the onset (21,22). Therefore, NLR, CRP, LDH, interleukin-10(IL-10), and interferon γ(IFNγ) were selected as the six variables for the multivariable logistic regression analysis.…”

Section: Resultsmentioning

confidence: 99%

A Composite Index Predicts Disease Progression in Early Stages of COVID-19: a Propensity Score-matched Cohort Study

et al. 2020

Preprint

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Background: Thus far, studies on COVID-19 have focused on the epidemiology of the disease and clinical characteristics of patients (14-19), as well as on the risk factors associated with mortality during hospitalization in critical COVID-19 cases. However, no research has been performed on the prediction of progression in patients in the early stages of the disease. The aim of this work was to identify the early predictors of COVID-19 progression.Methods: The study included 338 patients with COVID-19 treated at two hospitals in Wuhan, Chian, from December, 2019 to March, 2020. Predictors of the progression of COVID-19 from mild to severe stages were selected by the logistic regression analysis. The predictive accuracy was evaluated further in the propensity score-matched cohort.Results: COVID-19 progression to severe and critical stages was confirmed in 78(23.1%) patients. The average value of the neutrophil-to-lymphocyte ratio (NLR) was higher in patients in the disease progression group than in the improvement group. Multivariable logistic regression analysis revealed that elevated NLR, LDH, and IL-10, were independent predictors of disease progression. The optimal cut-off value of NLR for predicting the progression of COVID-19 was 3.75. In the propensity score-matched cohort, NLR ≥ 3.75 was still an independent predictor of COVID-19 progression after multivariate analysis.Conclusions: The performed analysis demonstrates that NLR qualiﬁes as an independent predictor of disease progression in COVID-19 patients at the early stage of the disease. The combined evaluation of NLR and LDH improved the accuracy of the prediction of COVID-19 progression. Assessment of predictors might facilitate early identification of COVID-19 patients at high risk for disease progression and ensure timely administration of appropriate treatment to prevent mild cases from becoming severe.

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Cytokine storm and immunomodulatory therapy in COVID-19: Role of chloroquine and anti-IL-6 monoclonal antibodies

Cited by 250 publications

References 15 publications

Dysregulation in mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells

Dysregulation in mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells

The Urgent Countermeasures in Infection Control for Diagnosis of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Taiwan

A Composite Index Predicts Disease Progression in Early Stages of COVID-19: a Propensity Score-matched Cohort Study

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