Increased levels of plasma cytokines and correlations to organ failure and 30-day mortality in critically ill Covid-19 patients

Anderberg, Sara Bülow; Luther, Tomas; Berglund, Malin; Larsson, Rolf; Rubertsson, Sten; Lipcsey, Miklós; Larsson, Anders; Frithiof, Robert; Hultström, Michael

doi:10.1016/j.cyto.2020.155389

Cited by 67 publications

(79 citation statements)

References 40 publications

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“… 4 Moreover, increased levels of neutrophil-associated cytokines originating from NLRP3 inflammasome is correlated with organ damage in COVID-19 patients. 5 A pattern of 25 granulocyte-associated markers has been proposed recently to predict critical illness and mortality in COVID-19. 6 …”

Section: Introductionmentioning

confidence: 99%

High expression of neutrophil and monocyte CD64 with simultaneous lack of upregulation of adhesion receptors CD11b, CD162, CD15, CD65 on neutrophils in severe COVID-19

Karawajczyk

Håkansson

Lipcsey

et al. 2021

Therapeutic Advances in Infection

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Background and Aims: The pronounced neutrophilia observed in patients with coronavirus disease 2019 (COVID-19) infections suggests a role for these leukocytes in the pathology of the disease. Monocyte and neutrophil expression of CD64 and CD11b have been reported as early biomarkers to detect infections. The aim of this study was to study the expression of receptors for IgG (CD64) and adhesion molecules (CD11b, CD15s, CD65, CD162, CD66b) on neutrophils and monocytes in patients with severe COVID-19 after admission to an intensive care unit (ICU). Methods: The expression of receptors was analyzed using flow cytometry. EDTA blood from 23 patients with confirmed COVID-19 infection was sampled within 48 h of admission to the ICU. Leukocytes were labeled with antibodies to CD11b, CD15s, CD65s, CD162, CD64, and CD66b. Expression of receptors was reported as mean fluorescence intensity (MFI) or the percentage of cells expressing receptors. Results: Results are presented as comparison of COVID-19 patients with the healthy group and the receptor expression as MFI. Neutrophil receptors CD64 (2.5 versus 0.5) and CD66b (44.5 versus 34) were increased and CD15 decreased (21.6 versus 28.3) when CD65 (6.6 versus 4.4), CD162 (21.3 versus 21.1) and CD11b (10.5 versus 12) were in the same range. Monocytes receptors CD64 (30.5 versus 16.6), CD11b (18.7 versus 9.8), and CD162 (38.6 versus 36.5) were increased and CD15 decreased (10.3 versus 17.9); CD65 were in the same range (2.3 versus 1.96). Conclusion: Monocytes and neutrophils are activated during severe COVID-19 infection as shown by strong upregulation of CD64. High monocyte and neutrophil CD64 can be an indicator of a severe form of COVID19. The adhesion molecules (CD11b, CD162, CD65, and CD15) are not upregulated on otherwise activated neutrophils, which might lead to relative impairment of tissue migration. Low adhesion profile of neutrophils suggests immune dysfunction of neutrophils. Monocytes maintain upregulation of some adhesion molecules (CD11b, CD162) suggesting the persistence of an increased ability to migrate into tissues, even during a severe stage of COVID-19. Future research should focus on CD64 and CD11b kinetics in the context of prognosis.

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Section: Introductionmentioning

confidence: 99%

High expression of neutrophil and monocyte CD64 with simultaneous lack of upregulation of adhesion receptors CD11b, CD162, CD15, CD65 on neutrophils in severe COVID-19

Karawajczyk

Håkansson

Lipcsey

et al. 2021

Therapeutic Advances in Infection

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“…The mechanisms of plasma sTNFR involvement in AKI as a consequence of COVID-19 have not been previously explored. However, TNFα levels are associated with AKI in COVID-19 [8] , and may exert its effects on membrane bound sTNFR 1 and 2 in the kidney as suggested by experimental data [16] .…”

Section: Discussionmentioning

confidence: 98%

“…There is evidence suggesting that the pro-inflammatory response seen in severe COVID-19 is driven by activation of monocyte-derived macrophages [6] . Systemic levels of macrophage-related cytokines, such as tumor necrosis factor alpha (TNFα) and interleukin-10 (IL-10), are increased in severe cases compared to non-severe cases and have been shown to be associated with increased disease severity, organ failure and death [7] , [8] .…”

Section: Introductionmentioning

confidence: 99%

Soluble TNF receptors predict acute kidney injury and mortality in critically ill COVID-19 patients: A prospective observational study

et al. 2022

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Background Although pneumonia is the hallmark of coronavirus disease 2019 (COVID-19), multiple organ failure may develop in severe disease. TNFα receptors in their soluble form (sTNFR) are involved in the immune cascade in other systemic inflammatory processes such as septic shock, and could mediate the inflammatory activation of distant organs. The aim of this study is to analyse plasma levels of sTNFR 1 and 2 in association with organ failure and outcome in critically ill patients with COVID-19. Methods After informed consent, we included 122 adult patients with PCR-confirmed COVID-19 at ICU admission. Demographic data, illness severity scores, organ failure and survival at 30 days were collected. Plasma sTNFR 1 and 2 levels were quantified during the first days after ICU admission. Twenty-five healthy blood donors were used as control group. Results Levels of sTNFR were higher in severe COVID-19 patients compared to controls (p < 0.001). Plasma levels of sTNFR were associated to illness severity scores (SAPS 3 and SOFA), inflammation biomarkers such as IL-6, ferritin and PCT as well as development of AKI during ICU stay. sTNFR 1 higher than 2.29 ng/mL and? sTNFR 2 higher than 11.7 ng/mL were identified as optimal cut-offs to discriminate survivors and non-survivors 30 days after ICU admission and had an area under the curve in receiver operating characteristic curve of 0.75 and 0.67 respectively. Conclusion Plasma levels of sTNFR 1 and 2 were higher in COVID-19 patients compared to controls and were strongly associated with other inflammatory biomarkers, severity of illness and acute kidney injury development during ICU stay. In addition, sTNFR 1 was an independent predictor of 30-day mortality after adjustment for age and respiratory failure.

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“… Widespread systemic inflammation: A significant increase in inflammatory cytokines plays a role in SARS symptoms, with inflammation persisting even after the viral clearance, and a similar ramped up an innate immune response in the form of ‘cytokine storm’ is behind COVID-19 as well [ 16 , 34 , 61 ]. Highly circulating amounts of Interleukins and other mediators (including IL-6, IL-1β, and TNF, and others) resulting in a pro-inflammatory status are commonly found in COVID-19 patients [ 62 , 63 ]. This amplified immune response may cause increased vascular permeability and vasculopathy arising from disseminated intravascular coagulation (DIC).…”

Section: Causalitymentioning

confidence: 99%

SARS-CoV-2 and the Brain: What Do We Know about the Causality of ‘Cognitive COVID?

Awan

Diwan

Aamir

et al. 2021

JCM

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The second year of the COVID-19 (coronavirus disease) pandemic has seen the need to identify and assess the long-term consequences of a SARS-CoV-2 infection on an individual’s overall wellbeing, including adequate cognitive functioning. ‘Cognitive COVID’ is an informal term coined to interchangeably refer to acute changes in cognition during COVID-19 and/or cognitive sequelae with various deficits following the infection. These may manifest as altered levels of consciousness, encephalopathy-like symptoms, delirium, and loss of various memory domains. Dysexecutive syndrome is a peculiar manifestation of ‘Cognitive COVID’ as well. In the previous major outbreaks of viruses like SARS-CoV, MERS-CoV and Influenza. There have been attempts to understand the underlying mechanisms describing the causality of similar symptoms following SARS-CoV-2 infection. This review, therefore, is attempting to highlight the current understanding of the various direct and indirect mechanisms, focusing on the role of neurotropism of SARS-CoV-2, the general pro-inflammatory state, and the pandemic-associated psychosocial stressors in the causality of ‘Cognitive COVID.’ Neurotropism is associated with various mechanisms including retrograde neuronal transmission via olfactory pathway, a general hematogenous spread, and the virus using immune cells as vectors. The high amounts of inflammation caused by COVID-19, compounded with potential intubation, are associated with a deleterious effect on the cognition as well. Finally, the pandemic’s unique psychosocial impact has raised alarm due to its possible effect on cognition. Furthermore, with surfacing reports of post-COVID-vaccination cognitive impairments after vaccines containing mRNA encoding for spike glycoprotein of SARS-CoV-2, we hypothesize their causality and ways to mitigate the risk. The potential impact on the quality of life of an individual and the fact that even a minor proportion of COVID-19 cases developing cognitive impairment could be a significant burden on already overwhelmed healthcare systems across the world make it vital to gather further evidence regarding the prevalence, presentation, correlations, and causality of these events and reevaluate our approach to accommodate early identification, management, and rehabilitation of patients exhibiting cognitive symptoms.

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Increased levels of plasma cytokines and correlations to organ failure and 30-day mortality in critically ill Covid-19 patients

Cited by 67 publications

References 40 publications

High expression of neutrophil and monocyte CD64 with simultaneous lack of upregulation of adhesion receptors CD11b, CD162, CD15, CD65 on neutrophils in severe COVID-19

High expression of neutrophil and monocyte CD64 with simultaneous lack of upregulation of adhesion receptors CD11b, CD162, CD15, CD65 on neutrophils in severe COVID-19

Soluble TNF receptors predict acute kidney injury and mortality in critically ill COVID-19 patients: A prospective observational study

SARS-CoV-2 and the Brain: What Do We Know about the Causality of ‘Cognitive COVID?

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