IL-6 and other biomarkers as predictors of severity in COVID-19

Broman, Niklas; Rantasärkkä, Kaisa; Feuth, Thijs; Valtonen, Mika; Waris, Matti; Hohenthal, Ulla; Rintala, Esa; Karlsson, Antti; Marttila, Harri; Peltola, Ville; Vuorinen, Tytti; Oksi, Jarmo

doi:10.1080/07853890.2020.1840621

Cited by 106 publications

(92 citation statements)

References 10 publications

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“…However, the study performed on our patients indicates significantly higher concentrations of ferritin and IL-6 in patients with COVID-19 requiring intensive care comparing with those hospitalized in non-ICU departments. With our results, we confirm observations made by other groups showing that IL-6 allows distinguishing between severe and nonsevere COVID-19 [ 38 , 39 , 40 , 41 , 42 ].…”

Section: Discussionsupporting

confidence: 92%

Cell Population Data and Serum Polyclonal Immunoglobulin Free Light Chains in the Assessment of COVID-19 Severity

Małecka‐Giełdowska

Fołta

Wiśniewska

et al. 2021

Viruses

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Distinguishing between severe and nonsevere COVID-19 to ensure adequate healthcare quality and efficiency is a challenge for the healthcare system. The aim of this study was to assess the usefulness of CBC parameters together with analysis of FLC serum concentration in risk stratification of COVID-19. Materials and methods: CBC was analyzed in 735 COVID ICU, COVID non-ICU, and non-COVID ICU cases. FLC concentration was analyzed in 133 of them. Results: COVID ICU had neutrophils and lymphocytes with the greatest size, granularity, and nucleic acid content. Significant differences in concentrations of κ and λ FLCs were shown between COVID ICU and COVID non-ICU. However, no difference was found in the κ/λ ratio between these groups, and the ratio stayed within the reference value, which indicates the presence of polyclonal FLCs. FLC κ measurement has significant power to distinguish between severe COVID-19 and nonsevere COVID-19 (AUC = 0.7669), with a sensitivity of 86.67% and specificity of 93.33%. The κ coefficients’ odds ratio of 3.0401 was estimated. Conclusion: It can be concluded that the results obtained from the measure of free light immunoglobulin concentration in serum are useful in distinguishing between severe and nonsevere COVID-19.

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Section: Discussionsupporting

confidence: 92%

Cell Population Data and Serum Polyclonal Immunoglobulin Free Light Chains in the Assessment of COVID-19 Severity

Małecka‐Giełdowska

Fołta

Wiśniewska

et al. 2021

Viruses

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“…The phenotypes of MC degranulation-induced epithelial inflammation and lung injury in our study is concordant with the immunological and histopathological findings of COVID-19 patients and infected animals 45,70,71 , indicating that SARS-CoV-2-induced MC degranulation is a major cause that triggers hyper-inflammation and lung injury. We find that MC degranulation induces extremely high level of productions of pro-inflammatory cytokines and chemokines, including IL-6 which has been shown to be an independent risk factor for disease severity and death of COVID-19 14,18,21–23 .…”

Section: Discussionmentioning

confidence: 80%

“…Known inflammatory cytokines and chemokines that produced in excess in patients with severe diseases include IL-6, IL-8, IL-1β, TNF-α, IFN-γ, MIP1α and 1β, CCL2, CCL5, CCL20, CXCL1, CXCL2, CXCL8, CXCL10 and CXCL17 10,14–21 . Among them, elevated IL-6, TNF-α and C-reaction protein (CRP) levels have been shown to be independent risk factors for the severity of COVID-19 disease 14,18,21–23 .…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2-Triggered Mast Cell Rapid Degranulation Induces Alveolar Epithelial Inflammation and Lung Injury

Liu

Sun

et al. 2021

Preprint

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SARS-CoV-2 infection-induced hyper-inflammation links to the acute lung injury and COVID-19 severity. Identifying the primary mediators that initiate the uncontrolled hypercytokinemia is essential for treatments. Mast cells (MCs) are strategically located at the mucosa and beneficially or detrimentally regulate immune inflammations. Here we showed that SARS-CoV-2-triggeed MC degranulation initiated alveolar epithelial inflammation and lung injury. SARS-CoV-2 challenge induced MC degranulation in ACE-2 humanized mice and rhesus macaques, and a rapid MC degranulation could be recapitulated with Spike-RBD binding to ACE2 in cells; MC degranulation alterred various signaling pathways in alveolar epithelial cells, particularly, led to the production of pro-inflammatory factors and consequential disruption of tight junctions. Importantly, the administration of clinical MC stabilizers for blocking degranulation dampened SARS-CoV-2-induced production of pro-inflammatory factors and prevented lung injury. These findings uncover a novel mechanism for SARS-CoV-2 initiating lung inflammation, and suggest an off-label use of MC stabilizer as immunomodulators for COVID-19 treatments.

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“…A compiled representation of multiple molecular markers from over 450 individuals accumulated and reanalyzed from different studies and case reports on COVID-19 is depicted in Fig. 2 (Huang et al 2020;Broman et al 2020;Hashemian et al 2020). This shows the contribution of molecular representatives in determining potential candidates for clinical trial and/or drug development investigations.…”

Section: Ai-enabled Multiomics In Disease Severity Clinical Trial Rementioning

confidence: 99%

“…While age and symptoms matter in COVID-19 patient care, they are not necessarily accurate predictors of disease severity and deaths. Molecular biomarkers like C-reactive protein, interleukin-6 (IL-6), eosinophils and chest X-ray/ computed tomography (CT) findings like lung consolidation, lung lesions and fibrosis have shown significant associations with COVID-19 disease severity as evidenced by several studies (Huang et al 2020;Yun et al 2021;Broman et al 2020;Hashemian et al 2020).…”

Section: Introductionmentioning

confidence: 99%

Host-dependent molecular factors mediating SARS-CoV-2 infection to gain clinical insights for developing effective targeted therapy

Shafi¹,

Desai²,

Srinivasan³

et al. 2021

Mol Genet Genomics

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Coronavirus disease 2019 (COVID-19), a recent viral pandemic that first began in December 2019, in Hunan wildlife market, Wuhan, China. The infection is caused by a coronavirus, SARS-CoV-2 and clinically characterized by common symptoms including fever, dry cough, loss of taste/smell, myalgia and pneumonia in severe cases. With overwhelming spikes in infection and death, its pathogenesis yet remains elusive. Since the infection spread rapidly, its healthcare demands are overwhelming with uncontrollable emergencies. Although laboratory testing and analysis are developing at an enormous pace, the high momentum of severe cases demand more rapid strategies for initial screening and patient stratification. Several molecular biomarkers like C-reactive protein, interleukin-6 (IL6), eosinophils and cytokines, and artificial intelligence (AI) based screening approaches have been developed by various studies to assist this vast medical demand. This review is an attempt to collate the outcomes of such studies, thus highlighting the utility of AI in rapid screening of molecular markers along with chest X-rays and other COVID-19 symptoms to enable faster diagnosis and patient stratification. By doing so, we also found that molecular markers such as C-reactive protein, IL-6 eosinophils, etc. showed significant differences between severe and non-severe cases of COVID-19 patients. CT findings in the lungs also showed different patterns like lung consolidation significantly higher in patients with poor recovery and lung lesions and fibrosis being higher in patients with good recovery. Thus, from these evidences we perceive that an initial rapid screening using integrated AI approach could be a way forward in efficient patient stratification.

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IL-6 and other biomarkers as predictors of severity in COVID-19

Cited by 106 publications

References 10 publications

Cell Population Data and Serum Polyclonal Immunoglobulin Free Light Chains in the Assessment of COVID-19 Severity

Cell Population Data and Serum Polyclonal Immunoglobulin Free Light Chains in the Assessment of COVID-19 Severity

SARS-CoV-2-Triggered Mast Cell Rapid Degranulation Induces Alveolar Epithelial Inflammation and Lung Injury

Host-dependent molecular factors mediating SARS-CoV-2 infection to gain clinical insights for developing effective targeted therapy

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