Inflammatory biomarkers as independent prognosticators of 28-day mortality for COVID-19 patients admitted to general medicine or ICU wards: a retrospective cohort study

Pitre, Tyler; Jones, Aaron; Su, Johnny; Helmeczi, Wryan; Xu, Grace; Lee, Catherine; Shamsuddin, Adib; Mir, Adhora; MacGregor, Sarah; Duong, MyLinh; Ho, Terence; Beauchamp, Marla K.; Costa, Andrew P.; Kruisselbrink, Rebecca; Ciccotelli, William; Corriveau, Sophie; Farjou, George; Giilck, Stephen; Girolametto, Carla; Griffith, Lauren; Guy, Brent; Haider, Shariq; Hanmiah, Rajendar; Hosek, Paul; Junek, Mats; Kapralik, Jessica; Law, Cindy Cin Yee; Liu, Theresa T; Marcucci, Maura; Martin, Leigh R.; Neary, John; Patel, Ameen; Raghavan, Natya; Raina, Parminder; Raza, Samir; Schumacher, Connie; Tong, Catherine; Tsnlrang, Jennifer; Wald, Joshua

doi:10.1007/s11739-021-02637-8

Cited by 25 publications

(28 citation statements)

References 33 publications

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“…Given this heterogeneity, anti-inflammatory therapies may benefit certain groups, while harming others (38). Although there is no gold standard definition of hyperinflammation, hyperthermic slow resolvers demonstrated several abnormalities consistent with a hyperinflammatory state (39)(40)(41)(42)(43). CRP and ferritin have been commonly used to define COVID-19-associated hyperinflammation, and hyperthermic slow resolvers had the highest levels of both biomarkers (40).…”

Section: Discussionmentioning

confidence: 99%

Coronavirus Disease 2019 Temperature Trajectories Correlate With Hyperinflammatory and Hypercoagulable Subphenotypes

Bhavani

Verhoef

Maier

et al. 2022

Critical Care Medicine

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OBJECTIVES: Body temperature trajectories of infected patients are associated with specific immune profiles and survival. We determined the association between temperature trajectories and distinct manifestations of coronavirus disease 2019.DESIGN: Retrospective observational study. SETTING:Four hospitals within an academic healthcare system from March 2020 to February 2021. PATIENTS:All adult patients hospitalized with coronavirus disease 2019. INTERVENTIONS:Using a validated group-based trajectory model, we classified patients into four previously defined temperature trajectory subphenotypes using oral temperature measurements from the first 72 hours of hospitalization. Clinical characteristics, biomarkers, and outcomes were compared between subphenotypes. MEASUREMENTS AND MAIN RESULTS:The 5,903 hospitalized coronavirus disease 2019 patients were classified into four subphenotypes: hyperthermic slow resolvers (n = 1,452, 25%), hyperthermic fast resolvers (1,469, 25%), normothermics (2,126, 36%), and hypothermics (856, 15%). Hypothermics had abnormal coagulation markers, with the highest d-dimer and fibrin monomers (p < 0.001) and the highest prevalence of cerebrovascular accidents (10%, p = 0.001). The prevalence of venous thromboembolism was significantly different between subphenotypes (p = 0.005), with the highest rate in hypothermics (8.5%) and lowest in hyperthermic slow resolvers (5.1%). Hyperthermic slow resolvers had abnormal inflammatory markers, with the highest C-reactive protein, ferritin, and interleukin-6 (p < 0.001). Hyperthermic slow resolvers had increased odds of mechanical ventilation, vasopressors, and 30-day inpatient mortality (odds ratio, 1.58; 95% CI, 1.13-2.19) compared with hyperthermic fast resolvers. Over the course of the pandemic, we observed a drastic decrease in the prevalence of hyperthermic slow resolvers, from representing 53% of admissions in March 2020 to less than 15% by 2021. We found that dexamethasone use was associated with significant reduction in probability of hyperthermic slow resolvers membership (27% reduction; 95% CI, 23-31%; p < 0.001). CONCLUSIONS:Hypothermics had abnormal coagulation markers, suggesting a hypercoagulable subphenotype. Hyperthermic slow resolvers had elevated inflammatory markers and the highest odds of mortality, suggesting a hyperinflammatory subphenotype. Future work should investigate whether temperature subphenotypes benefit from targeted antithrombotic and anti-inflammatory strategies.

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Section: Discussionmentioning

confidence: 99%

Coronavirus Disease 2019 Temperature Trajectories Correlate With Hyperinflammatory and Hypercoagulable Subphenotypes

Bhavani

Verhoef

Maier

et al. 2022

Critical Care Medicine

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“…ere are also some investigations that have assessed the relationship between LWR and several diseases [18,19]. In a research of 336 COVID-19 patients, the investigators discovered that high LWR was related to the lowest increased risk of short-outcome (28-day mortality) [18].…”

Section: Discussionmentioning

confidence: 99%

“…Our work also found that lymphocyte count was lower in the nonsurvivor group compared with the survivor group, while it was not significant. There are also some investigations that have assessed the relationship between LWR and several diseases [ 18 , 19 ]. In a research of 336 COVID-19 patients, the investigators discovered that high LWR was related to the lowest increased risk of short-outcome (28-day mortality) [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of Lymphocyte-to-White Blood Cell Ratio for In-Hospital Mortality in Infective Endocarditis Patients

Zhang

Qiao

et al. 2022

International Journal of Clinical Practice

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Background. The prognosis of Infective endocarditis (IE) is poor, and we conducted this investigation to evaluate the worth of admission lymphocyte-to-white blood cell ratio (LWR) for prediction of short-term outcome in IE patients. Methods. We retrospectively assessed the medical records of 147 IE patients from January 2017 to December 2019. Patients were divided into the survivor group and nonsurvivor group. Univariate and multivariate analyses were applied to estimate the independent factors contribution to in-hospital death, and receiver-operator characteristic (ROC) curve was utilized to check the performance. Results. The levels of LWR (0.17 ± 0.08 vs. 0.10 ± 0.06) were significantly increased among the survivor group compared with the nonsurvivor group ( P = 0.001). Multivariate analysis displayed that LWR (hazard ratio (HR): 1.755, 1.304–2.362, P < 0.001) was not interfered by other confounding factors for early death. Moreover, ROC analysis suggested that LWR (cutoff value = 0.10) performed the best among assessed indexes for the forecast of primary outcome (area under curve (AUC) = 0.750, 95% confidence interval (CI) = 0.634–0.867, P < 0.001, sensitivity = 70.0%, specificity = 76.4%), and the proportion of in-hospital mortality was remarkably inferior in patients with LWR > 0.10 than in those with LWR ≤ 0.10. (5.83% vs. 31.8%, P < 0.001). Conclusions. LMR is an independent, simple, universal, inexpensive, and reliable prognostic parameter to identify high-risk IE patients for in-hospital mortality.

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“…IL-6 receptor blockers have immunosuppressive effects that may be important in COVID-19 patients with immune system dysfunction and inflammation (3)(4)(5). The RECOVERY trial found that tocilizumab reduces mortality and ventilation, particularly among patients receiving corticosteroids (6) and REMAP-CAP showed tocilizumab and sarilumab to reduce mortality and improve organ-support free days (7).…”

Section: Introductionmentioning

confidence: 99%

Tocilizumab and sarilumab alone or in combination with corticosteroids for COVID-19: A systematic review and network meta-analysis

Zeraatkar

Cusano

Martínez

et al. 2021

Preprint

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Objective: To compare the effects of interleukin-6 (IL-6) receptor blockers, with or without corticosteroids, on mortality in patients with COVID-19. Design: Systematic review and network meta-analysis Data sources: WHO COVID-19 database, a comprehensive multilingual source of global covid-19 literature, and two prospective meta-analyses Study selection: Trials in which people with suspected, probable, or confirmed COVID-19 were randomized to IL-6 receptor blockers (with or without corticosteroids), corticosteroids, placebo, or standard care. Results: We assessed the risk of bias of included trials using a modification of the Cochrane risk of bias 2.0 tool. We performed a Bayesian fixed effect network meta-analysis and assessed the certainty of evidence using the GRADE approach. We identified 45 eligible trials (20,650 patients), 36 (19,350 patients) of which could be included in the network meta-analysis. 27 of 36 trials were rated at high risk of bias, primarily due to lack of blinding. Tocilizumab (20 more per 1000, 15 fewer to 59 more; low certainty) and sarilumab (11 more per 1000, 38 fewer to 55 more; low certainty) alone may not reduce the risk of death. Tocilizumab, in combination with corticosteroids, probably reduces the risk of death compared to corticosteroids alone (35 fewer per 1000, 52 fewer to 18 more; moderate certainty) and sarilumab, in combination with corticosteroids, may reduce the risk of death compared to corticosteroids alone (43 fewer, 73 fewer to 12 more; low certainty). Tocilizumab and sarilumab, both in combination with corticosteroids, may have similar effects (8 more per 1000, 20 fewer to 35 more; low certainty). Conclusion: IL-6 receptor blockers, when added to standard care that includes corticosteroids, in patients with severe or critical COVID-19, probably reduce mortality. Tocilizumab and sarilumab may have similar effectiveness.

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Inflammatory biomarkers as independent prognosticators of 28-day mortality for COVID-19 patients admitted to general medicine or ICU wards: a retrospective cohort study

Cited by 25 publications

References 33 publications

Coronavirus Disease 2019 Temperature Trajectories Correlate With Hyperinflammatory and Hypercoagulable Subphenotypes

Coronavirus Disease 2019 Temperature Trajectories Correlate With Hyperinflammatory and Hypercoagulable Subphenotypes

Prognostic Value of Lymphocyte-to-White Blood Cell Ratio for In-Hospital Mortality in Infective Endocarditis Patients

Tocilizumab and sarilumab alone or in combination with corticosteroids for COVID-19: A systematic review and network meta-analysis

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