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Review 2: "IL-6 and IL-10 as predictors of disease severity in COVID 19 patients: Results from Meta-analysis and Regression"

This pre-print says that higher levels of cytokines IL-6 and IL-10 are associated with increased severity of COVID-19. Reviewer consensus suggests this well-conducted study provides scientific evidence of potential prognostic markers that could be useful in clinical care.

Published onSep 30, 2020
Review 2: "IL-6 and IL-10 as predictors of disease severity in COVID 19 patients: Results from Meta-analysis and Regression"
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key-enterThis Pub is a Review of
IL-6 and IL-10 as predictors of disease severity in COVID 19 patients: Results from Meta-analysis and Regression

Aims: SARS-CoV-2, an infectious agent behind the ongoing COVID-19 pandemic, induces high levels of cytokines such as IL-1, IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ etc in infected individuals which contribute towards the underlying disease patho-physiology. Nonetheless, exact association and contribution of every cytokine towards COVID-19 pathology remains poorly understood. Delineation of the role of the cytokines during COVID-19 holds the key of efficient patient management in clinics. This study performed a comprehensive meta-analysis to establish association between induced cytokines and COVID-19 disease severity to help in prognosis and clinical care. Main methods: Scientific literature was searched to identify 13 cytokines (IL-1β, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-17, TNF-α and IFN-γ) from 18 clinical studies. Standardized mean difference (SMD) for selected 6 cytokines IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ between severe and non-severe COVID-19 patient groups were summarized using random effects model. A classifier was built using logistic regression model with cytokines having significant SMD as covariates. Key findings: Out of 13 cytokines, IL-6 and IL-10 showed statistically significant SMD across the studies synthesized. Classifier with mean values of both IL-6 and IL-10 as covariates performed well with accuracy of ~ 92% that was significantly higher than accuracy reported in literature with IL-6 and IL-10 as individual covariates. Significance: Simple panel proposed by us with only two cytokine markers can be used as predictors for fast diagnosis of patients with higher risk of COVID-19 disease deterioration and thus can be managed well for a favourable prognosis.

RR:C19 Evidence Scale rating by reviewer:

  • Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.



This study aimed to establish a link between induced and COVID-19 disease severeness and the cytokines levels as predictors for prognosis and clinical treatment. The authors revealed that IL-6 and IL-10 out of 13 investigated cytokines showed good accuracy of 92%, considerably higher than the accuracy of individual covariates reported in the literature.

The importance of the study is linked to the use of such a simple panel with only two cytokine markers as diagnostic predictors for high-risk patients with COVID-19.

The study claims are justified very well by the data and analytical methods employed. There is little question of the results and conclusions of the study mirror the hypothesis of the aim of the research. The main conclusions of the study are conclusive and unreservedly valuable.

The study provides sufficient evidence of its capacity for its central claims, with an option for future reviews.

The findings contribute to broader research understandings regarding the cytokine storm in COVID-19. The evidence and arguments presented support advancement of COVID-19 understanding within society. The manuscript cites current literature and discuss limitations. This paper will impact the current understanding and can influence the implementation of policy and therapy protocols. The authors pay attention to ethics, diversity, and inclusion; they adequately discussed the results from different angles. It is well-structured and well-written, with an ability to speak to key audiences.

I strongly recommend the paper for publishing.

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