Interleukin-6 and severe COVID-19: a systematic review and meta-analysis

Mojtabavi, Helia; Saghazadeh, Amene; Rezaei, Nima

doi:10.1684/ecn.2020.0448

Cited by 90 publications

(93 citation statements)

References 20 publications

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“…Normal plasma levels of IL-6 in adults range between 1 and 10 pg/ml; whereas in a systemic inflammation this amount increases to several ng/ml [197] and even higher concentrations were reported in COVID-19 patients [198]. Indeed, cytokine release syndrome (CRS) is common in COVID-19 patients and increased levels of serum IL-6 have been identified to be significantly associated with acute respiratory distress syndrome (ARDS), respiratory failure, and poor disease outcome in numerous studies [192,[199][200][201]. Studies suggest that new onset depression is most probably caused by inflammation initiated during the active phase of the infection leading to a cytokine surge [202].…”

Section: Elevated Levels Of Il-6 In Patients With Covid-19 Infectionmentioning

confidence: 99%

On inflammatory hypothesis of depression: what is the role of IL-6 in the middle of the chaos?

Roohi

Jaafari

Hashemian

2021

J Neuroinflammation

119

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Many patients with major depressive disorder (MDD) are reported to have higher levels of multiple inflammatory cytokines including interleukin 6 (IL-6). Recent studies both pre-clinical and clinical have advocated for the functional role of IL-6 in development of MDD and suggested a great potential for targeting this cytokine to open new avenues in pharmacotherapy of depression. The purpose of the present narrative review was to provide an integrated account of how IL-6 may contribute to development of depression. All peer-reviewed journal articles published before July 2020 for each area discussed were searched by WOS, PubMed, MEDLINE, Scopus, Google Scholar, for original research, review articles, and book chapters. Publications between 1980 and July 2020 were included. Alterations in IL-6 levels, both within the periphery and the brain, most probably contribute to depression symptomatology in numerous ways. As IL-6 acts on multiple differing target tissues throughout the body, dysregulation of this particular cytokine can precipitate a multitude of events relevant to depression and blocking its effects can prevent further escalation of inflammatory responses, and potentially pave the way for opening new avenues in diagnosis, treatment, and prevention of this debilitating disorder.

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Section: Elevated Levels Of Il-6 In Patients With Covid-19 Infectionmentioning

confidence: 99%

On inflammatory hypothesis of depression: what is the role of IL-6 in the middle of the chaos?

Roohi

Jaafari

Hashemian

2021

J Neuroinflammation

119

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“…Several retrospective case-control, single-armed studies and randomized clinical trials declared promising results of tocilizumab treatment in SARS CoV-2 infection. Nevertheless, some systematic reviews and meta-analyses showed an unclear risk of bias and reported debatable results about tocilizumab's benefit as a treatment 6,[8][9][10][11][12][13] . We performed a systematic review and meta-analysis to research the risks and benefits of tocilizumab and investigate outcomes from different baseline criteria for administration of tocilizumab as a treatment for severe and critically ill COVID-19 patients.…”

Section: Introductionmentioning

confidence: 99%

Optimal use of tocilizumab for severe and critical COVID-19: a systematic review and meta-analysis

et al. 2021

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Background: Several studies have revealed the potential use of tocilizumab in treating COVID-19 since no therapy has yet been approved for COVID-19 pneumonia. Tocilizumab may provide clinical benefits for cytokine release syndrome in COVID-19 patients. Methods: We searched for relevant studies in PubMed, Embase, Medline, and Cochrane published from March to October 2020 to evaluate optimal use and baseline criteria for administration of tocilizumab in severe and critically ill COVID-19 patients. Research involving patients with confirmed SARS-CoV-2 infection, treated with tocilizumab and compared with the standard of care (SOC) was included in this study. We conducted a systematic review to find data about the risks and benefits of tocilizumab and outcomes from different baseline criteria for administration of tocilizumab as a treatment for severe and critically ill COVID-19 patients. Results: A total of 26 studies, consisting of 23 retrospective studies, one prospective study, and two randomised controlled trials with 2112 patients enrolled in the tocilizumab group and 6160 patients in the SOC group, were included in this meta-analysis. Compared to the SOC, tocilizumab showed benefits for all-cause mortality events and a shorter time until death after first intervention but showed no difference in hospital length of stay. Upon subgroup analysis, tocilizumab showed fewer all-cause mortality events when CRP level ≥100 mg/L, P/F ratio 200-300 mmHg, and P/F ratio <200 mmHg. However, tocilizumab showed a longer length of stay when CRP <100 mg/L than the SOC. Conclusion: This meta-analysis demonstrated that tocilizumab has a positive effect on all-cause mortality. It should be cautiously administrated for optimal results and tailored to the patient's eligibility criteria.

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“…It is evident that augmented levels of IL-6 were observed in patients infected with SARS-CoV-2 and correlated with disease severity (Zhang, Peihua et al, 2020; Aziz et al, 2020 ; Mojtabavi et al, 2020 ; Ji et al, 2020 ; Udomsinprasert et al, 2020 ). Levels of IL-6 seem to be associated with inflammatory response, respiratory failure, needing for mechanical ventilation and/or intubation and mortality in COVID-19 patients ( Herold et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Recent updates in the clinical trials of therapeutic monoclonal antibodies targeting cytokine storm for the management of COVID-19

Patel

Saxena

Mehta

2021

Heliyon

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Clinical studies have identified a cytokine storm in the third stage of disease progression in critical ill patients with coronavirus disease 2019 . Hence, effectively suppressing the uncontrolled immune response of the host towards the invaded viruses in a cytokine storm is a critical step to prevent the deterioration of patient conditions and decrease the rate of mortality. Therapeutic monoclonal antibodies (mAbs) are found to be effective for the management of acute respiratory distress syndrome in patients with COVID-19. In this review, we compiled all therapeutic mAbs targeting cytokine storm, which are in clinical trials for its repurposing in the management of COVID-19. Compilation of clinical trial data indicated that therapeutic monoclonal antibodies targeting interleukins (IL-6, IL-1ra, IL-8, IL-1β, IL-17A, IL-33), interferon-gamma, tumor necrosis factor-alpha, Pselectin, connective tissue growth factor, plasma kallikrein, tumor necrosis factor superfamily 14, granulocyte macrophage colony stimulating factor, colony stimulating factor 1 receptor, C-C chemokine receptor type 5, cluster of differentiation 14 and 147, vascular endothelial growth factor, programmed cell death protein-1, Angiopoietin -2, human factor XIIa, complementary protein 5, natural killer cell receptor G2A, human epidermal growth factor receptor 2, immunoglobulin-like transcript 7 receptor, complement component fragment 5a receptor and viral attachment to the human cell were under investigation for management of severely ill patients with COVID-19. Among these, about 65 clinical trials are targeting IL-6 inhibition as the most promising one and Tocilizumab, an IL-6 inhibitor is considered to be the potential candidate to treat cytokine storm associated with the COVID-19. OverviewCoronavirus disease 2019 (COVID-19) is the infectious disease, which affects primarily the lungs, caused by newly identified coronavirus termed as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patient infected with SARS-CoV-2 was initially discovered at Wuhan, China in December 2019 and is still spreading across the globe (Singhal, 2020). The COVID-19 outbreak was declared as pandemic on March 11, 2020 by the world health organization (WHO) (Coperchini et al., 2020). By September 9, 2020 the number of deaths raised to 896K amongst 27.5 million confirmed cases of COVID-19. The majority of the patients infected with SARS-CoV-2 in this COVID-19 pandemic are clinically asymptomatic or develop mild clinical manifestations like cough, mild fever, or muscle soreness. However, nearly 10-20% of patients (especially geriatric and patients with other co-morbidity) will develop pneumonia and acute respiratory distress syndrome (ARDS) (Soy et al., 2020). This COVID-19 pandemic created global crises of both public health as well as economic and thus emerged the need for rapid development of vaccines and therapeutic countermeasures (Sempowski et al., 2020). One approach for finding appropriate therapeutics for treating COVID-19 is rapid repurposing of existin...

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Interleukin-6 and severe COVID-19: a systematic review and meta-analysis

Cited by 90 publications

References 20 publications

On inflammatory hypothesis of depression: what is the role of IL-6 in the middle of the chaos?

On inflammatory hypothesis of depression: what is the role of IL-6 in the middle of the chaos?

Optimal use of tocilizumab for severe and critical COVID-19: a systematic review and meta-analysis

Recent updates in the clinical trials of therapeutic monoclonal antibodies targeting cytokine storm for the management of COVID-19

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