Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19

Herold, Tobias; Jurinović, Vindi; Arnreich, Chiara; Lipworth, Brian J.; Hellmuth, Johannes C.; Bergwelt‐Baildon, Michael von; Klein, Matthias; Weinberger, Tobias

doi:10.1016/j.jaci.2020.05.008

Cited by 926 publications

(947 citation statements)

References 34 publications

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“…This is consistent with our ndings in relation to CRP and IL-6 which were signi cantly higher in non-frail patients compared to frail patients; it is possible that frail older adults are not able to mount strong immune responses to COVID-19 infection due to immunosenescence [36]. Higher in ammatory responses to COVID-19 have been associated with severe disease and poorer outcomes [37], and dexamethasone, an immunosuppressant therapy, has been proven to reduce mortality in patients with COVID-19 requiring oxygen therapy or mechanical ventilation [38]. Therefore, if immune reactions differ in frail compared to non-frail older adults this may suggest the pathogenesis of COVID-19 differs by frailty and will have implications for the likely effectiveness of different treatments.…”

Section: Discussionsupporting

confidence: 91%

Clinical features and inpatient trajectories of older inpatients with COVID-19: a retrospective observational study.

Osuafor

Davidson

Mackett

et al. 2020

Preprint

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Background: A comprehensive description of the clinical characteristics, inpatient trajectory and relationship with frailty of older inpatients admitted with COVID-19 is essential in the management of older adults during the COVID-19 pandemic. The aim of this study was to describe the clinical features and inpatient trajectory of older inpatients with confirmed COVID -19.Methods: This was a retrospective observational study of hospitalised older adults. Subjects include unscheduled medical admissions of older inpatients to a University Hospital with laboratory and clinically confirmed COVID-19. The primary outcome was death during the inpatient stay or within 14 days of discharge after a maximum follow up time of 45 days. The characteristics of the cohort were described in detail as a whole and by frailty status.Results: 214 patients were included in this study with a mean length of stay of 11 days (Range 6 to 18 days), of whom 140 (65.4%) patients were discharged and 74 (34.6%) patients died in hospital. 142 (66.4%) patients were frail with median Clinical Frailty Scale (CFS) score of 6. Frail patients were more likely to present with atypical symptoms including new or worsening confusion compared to non-frail patients (20.8% vs 45.1%, p<0.001) and were more likely to die in hospital or within 14 days of discharge (66% vs 16%, p=0.001). Older age, being male, presenting with high illness acuity and high frailty were all independently associated with higher risk of death and a dose response association between higher frailty and higher mortality was observed.Conclusions: Older adult inpatients with COVID-19 infection are likely to present with atypical symptoms, experience delirium and have a high mortality, especially if they are also living with frailty. Clinicians should have a low threshold for testing for COVID-19 in older and frail patients presenting to hospital as an emergency during periods when there is community transmission of COVID-19 and, when diagnosed, this should prompt early advanced care planning with the patient and family.

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Section: Discussionsupporting

confidence: 91%

Clinical features and inpatient trajectories of older inpatients with COVID-19: a retrospective observational study.

Osuafor

Davidson

Mackett

et al. 2020

Preprint

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“…Model predictions were validated with clinical data from healthy humans and severe COVID-19 patients [34][35][36] . Figure 2A Subsequently, we focused on the clinically observed phenotypes of COVID-19.…”

Section: Resultsmentioning

confidence: 99%

In silico dynamics of COVID-19 phenotypes for optimizing clinical management

Voutouri

Nikmaneshi

Hardin

et al. 2020

Preprint

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Understanding the underlying mechanisms of COVID-19 progression and the impact of various pharmaceutical interventions is crucial for the clinical management of the disease. We developed a comprehensive mathematical framework based on the known mechanisms of the SARS-CoV-2 virus infection, incorporating the renin-angiotensin system and ACE2, which the virus exploits for cellular entry, key elements of the innate and adaptive immune responses, the role of inflammatory cytokines and the coagulation cascade for thrombus formation. The model predicts the evolution of viral load, immune cells, cytokines, thrombosis, and oxygen saturation based on patient baseline condition and the presence of co-morbidities. Model predictions were validated with clinical data from healthy people and COVID-19 patients, and the results were used to gain insight into identified risk factors of disease progression including older age, co-morbidities such as obesity, diabetes, and hypertension, and dysregulated immune response 1,2. We then simulated treatment with various drug classes to identify optimal therapeutic protocols. We found that the outcome of any treatment depends on the sustained response rate of activated CD8+ T cells and sufficient control of the innate immune response. Furthermore, the best treatment –or combination of treatments – depends on the pre-infection health status of the patient. Our mathematical framework provides important insight into SARS-CoV-2 pathogenesis and could be used as the basis for personalized, optimal management of COVID-19.

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“…There is a substantial body of evidence linking the IL-6 concentration to the severity of disease and unfavorable outcome of Covid-19 [11,12,13,14,15,16,18,19,20]. However, to our knowledge, this study is the rst study which evaluated the ability of IL-6 to predict the need for supplementary oxygen administration as a surrogate marker of severe Covid-19 requiring hospital admission in the population of high risk elderly patients.…”

Section: Discussionmentioning

confidence: 97%

“…It also suggests clinical implications for intervention procedures for Covid-19 outbreak in LTCF. Han et al examined the predictive value of various cytokines and concluded that IL-6 is the best predictor of severe Covid-19 [16]. A metanalysis of 9 studies concluded that increased IL-6 is highly associated with severe disease.…”

Section: Discussionmentioning

confidence: 99%

“…Various biomarkers, especially in ammatory markers like C-reactive protein (CRP), ferritin, brinogen, D-dimer and Interleukin 6 (IL-6) are associated with Covid-19 progression [10,11]. According to known evidence, IL-6 is superior to CRP and other markers of in ammation in predicting respiratory failure in Covid-19 [16,17]. IL-6 appears to be the most important driver of immune dysregulation and ARDS in Covid-19 [18,19,20,21].…”

Section: Introductionmentioning

confidence: 99%

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Role of interleukin 6 as a predictive factor for a severe course of Covid-19: retrospective data analysis of patients from a Long-term Care Facility during Covid-19 Outbreak

Sabaka

Koščálová

Straka³

et al. 2020

Preprint

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Background: Covid-19 is a disease with high morbidity and mortality among elderly residents of long-term care facilities (LTCF). During an outbreak of SARS-CoV-2 infection in the LTCF an effective screening tool is essential to identify the patients at risk for severe illness and death. We explored the role of interleukin 6 (IL-6) as a predictor for severe disease during the outbreak of Covid-19 in one LTCF in Slovakia.Methods: We conducted a retrospective data analysis of cases of COVID-19, diagnosed during the outbreak in one LTCF in Slovakia between April 11, 2020, and May 5, 2020. Within 24 hours after the diagnosis of Covid-19, clinical and laboratory screening was performed in the LTCF to identify patients in need of hospitalization. Patients with oxygen saturation below 90% were immediately referred to the hospital. Patients staying in the LFTC were monitored daily and those that developed hypoxemia were transferred to the hospital. We analyzed the association between the IL-6 at the initial assessment and development of hypoxemia during follow up and determined the cut-off of the IL-6 able to predict the development of hypoxemia requiring oxygen therapy.Results: Fifty-three patients (11 men, 42 women) with diagnosed Covid-19 were included in the analysis. 19 (53%) patients developed hypoxemia during the disease. Patients with hypoxemia had significantly higher concentrations of IL-6, C-reactive protein, procalcitonin, fibrinogen, total bilirubin, aspartate aminotransferase and alanine aminotransferase at initial screening. ROC analyses identified IL-6 as the most robust predictor of hypoxemia. The concentration of IL-6 > 24 pg/mL predicted the development of hypoxemia with the sensitivity of 100% and specificity of 88.9%. The positive and negative predictive values were 76.9%, and 100% respectively.Conclusions: The concentration of IL-6 > 24 pg/mL at initial assessment predicted the development of hypoxemia requiring hospitalization with excellent sensitivity and good specificity. IL-6 appears as a potential predictor for the development of the severe Covid-19 and might serve for early identification of patients in need of hospitalization. Further studies are needed to evaluate the robustness of the use of IL-6 as an effective screening tool for the severe course of Covid-19.

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Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19

Cited by 926 publications

References 34 publications

Clinical features and inpatient trajectories of older inpatients with COVID-19: a retrospective observational study.

Clinical features and inpatient trajectories of older inpatients with COVID-19: a retrospective observational study.

In silico dynamics of COVID-19 phenotypes for optimizing clinical management

Role of interleukin 6 as a predictive factor for a severe course of Covid-19: retrospective data analysis of patients from a Long-term Care Facility during Covid-19 Outbreak

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