Circulating Levels of Interleukin-6 and Interleukin-10, But Not Tumor Necrosis Factor-Alpha, as Potential Biomarkers of Severity and Mortality for COVID-19: Systematic Review with Meta-analysis

Udomsinprasert, Wanvisa; Jittikoon, Jiraphun; Sangroongruangsri, Sermsiri; Chaikledkaew, Usa

doi:10.1007/s10875-020-00899-z

Cited by 84 publications

(88 citation statements)

References 43 publications

(91 reference statements)

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“…Another synthesis over three clinical studies determined the elevated ratio IL-6/IFN-γ in severe patients [ 17 ] with substantial heterogeneity (I 2 = 79%). A recent meta-analysis covering 6242 patients over 24 studies established elevated levels of IL-6 and IL-10 in severe COVID-19 patients with practically no reported heterogeneity for IL-10 [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

IL-6 and IL-10 as predictors of disease severity in COVID-19 patients: results from meta-analysis and regression

Dhar

Vishnupriyan

Damodar

et al. 2021

Heliyon

154

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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 that play a role in the underlying patho-physiology. Nonetheless, exact association and contribution of every cytokine towards COVID-19 pathology remains poorly understood. Delineation of the roles of cytokines during COVID-19 holds the key to 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-

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Section: Introductionmentioning

confidence: 99%

IL-6 and IL-10 as predictors of disease severity in COVID-19 patients: results from meta-analysis and regression

Dhar

Vishnupriyan

Damodar

et al. 2021

Heliyon

154

View full text Add to dashboard Cite

show abstract

“…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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“…Antibody response seems to be essential in viral clearance. Likewise, in severely infected patients, IFN-γ production by CD4 + T cells is significantly lower than controls, 142,143,156,157 and the circulating B lymphocyte number is deficient. The decrease in TH1 and B cells impairs antibody production in these patients.…”

Section: De Sanctis Et Almentioning

confidence: 96%

“…141 Patients who eventually enter the intensive care unit (ICU) have significantly higher plasma levels of IL-6, and IL-10, non-necessarily TNFα and fewer circulating CD4 + and CD8 + T lymphocytes, NK, and B lymphocytes. [141][142][143][144] CD8 and NK cells exhaustion markers indicate progression and prognosis of the viral infection, [142][143][144] and IL-6 appears to be the | 9 of 18 DE SANCTIS ET Al crucial cytokine in the inflammatory process. 144 In animal studies, CS also impaired the development of adequate adaptive immunity against SARS-CoV infection.…”

Section: Inflammasomes and Cytokine Storm (Cs)mentioning

confidence: 99%

Coronavirus infection: An immunologists' perspective

et al. 2021

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Coronaviruses (CoVs) are a collection of enveloped viruses with non-segmented, positive-sense single-stranded RNA genomes with distinctive crown-like spikes that protrude from the capsid of helical symmetry. 1 They have a remarkably long RNA genome and a particular replication strategy. In this complex family, several members attack different species causing several diseases that can end up in death. In November 2002, in China, a severe acute respiratory syndrome coronavirus (SARS-CoV) was identified. It promptly spread to other countries. There were around 8000 confirmed cases, and the mortality rate was 9.6%. 2 Then, another member of the family, Middle East respiratory syndrome coronavirus (MERS-CoV), appeared in Saudi Arabia in 2012 and later emerged in South Korea in 2015. The confirmed cases of MERS-CoV exceeded 2000, with a mortality rate of ∼35%. 2 In 2019, another member of the family was identified, SARS-CoV-2. 3 The number of infected people and the mortality rate still grow continuously. Infected elderly individuals with comorbidities exhibit the worst outcomes. There are now several vaccines against SARS-CoV-2 approved for emergency use by the regulatory offices of different countries.The coronavirus genome is formed by 2 UTR sites, 5′ and 3′, the replicase, the spike (Spike), the envelope E (Envelope), the M (Membrane), the N (Nucleocapsid) and

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Circulating Levels of Interleukin-6 and Interleukin-10, But Not Tumor Necrosis Factor-Alpha, as Potential Biomarkers of Severity and Mortality for COVID-19: Systematic Review with Meta-analysis

Cited by 84 publications

References 43 publications

IL-6 and IL-10 as predictors of disease severity in COVID-19 patients: results from meta-analysis and regression

IL-6 and IL-10 as predictors of disease severity in COVID-19 patients: results from meta-analysis and regression

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

Coronavirus infection: An immunologists' perspective

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