Relationship Between IL-6 and COVID-19: to Be Considered During Treatment

Vatansever, Hafize Seda; Becer, Eda

doi:10.2217/fvl-2020-0168

Cited by 57 publications

(48 citation statements)

References 36 publications

(40 reference statements)

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“…For example, SARS-CoV and Middle East respiratory syndrome-coronavirus (MERS-CoV) both induce aberrant pro-inflammatory cytokine and chemokine response, resulting in acute lung injury (ALI), and ARDS (5,6). During SARS-CoV-2 infection, elevated IL-6, TNF-α, IL-1β, and inflammatory chemokines including IL-8, IP-10 were correlated with the disease severity and the corresponding agonists were used as therapeutic options for COVID-19 (4,7). Importantly, IL-6, TNF-α have been reported to predict the severity of COVID-19 patients (8).…”

Section: Introductionmentioning

confidence: 99%

The Characterization of Disease Severity Associated IgG Subclasses Response in COVID-19 Patients

et al. 2021

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Increasing evidence suggests that dysregulated immune responses are associated with the clinical outcome of coronavirus disease 2019 (COVID-19). Nucleocapsid protein (NP)-, spike (S)-, receptor binding domain (RBD)- specific immunoglobulin (Ig) isotypes, IgG subclasses and neutralizing antibody (NAb) were analyzed in 123 serum from 63 hospitalized patients with severe, moderate, mild or asymptomatic COVID-19. Mild to modest correlations were found between disease severity and antigen specific IgG subclasses in serum, of which IgG1 and IgG3 were negatively associated with viral load in nasopharyngeal swab. Multiple cytokines were significantly related with antigen-specific Ig isotypes and IgG subclasses, and IL-1β was positively correlated with most antibodies. Furthermore, the old patients (≥ 60 years old) had higher levels of chemokines, increased NAb activities and SARS-CoV-2 specific IgG1, and IgG3 responses and compromised T cell responses compared to the young patients (≤ 18 years old), which are related with more severe cases. Higher IgG1 and IgG3 were found in COVID-19 patients with comorbidities while biological sex had no effect on IgG subclasses. Overall, we have identified diseases severity was related to higher antibodies, of which IgG subclasses had weakly negative correlation with viral load, and cytokines were significantly associated with antibody response. Further, advancing age and comorbidities had obvious effect on IgG1 and IgG3.

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Section: Introductionmentioning

confidence: 99%

The Characterization of Disease Severity Associated IgG Subclasses Response in COVID-19 Patients

et al. 2021

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“… 155 According to the literature, high levels of IL-6 are associated with severe COVID-19 patients, as it is a crucial mediator of respiratory failure and multiorgan dysfunction. 156 , 157 Some reports in the literature have introduced interesting paper-based methodologies for detecting this relevant biomarker.…”

Section: Paper-based Devices For Covid-19 Associated Inflammatory Response and Disease Severity Monitoringmentioning

confidence: 99%

Paper-Based Biosensors for COVID-19: A Review of Innovative Tools for Controlling the Pandemic

et al. 2021

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The appearance and quick spread of the new severe acute respiratory syndrome coronavirus disease, COVID-19, brought major societal challenges. Importantly, suitable medical diagnosis procedures and smooth clinical management of the disease are an emergent need, which must be anchored on novel diagnostic methods and devices. Novel molecular diagnostic tools relying on nucleic acid amplification testing have emerged globally and are the current gold standard in COVID-19 diagnosis. However, the need for widespread testing methodologies for fast, effective testing in multiple epidemiological scenarios remains a crucial step in the fight against the COVID-19 pandemic. Biosensors have previously shown the potential for cost-effective and accessible diagnostics, finding applications in settings where conventional, laboratorial techniques may not be readily employed. Paper- and cellulose-based biosensors can be particularly relevant in pandemic times, for the renewability, possibility of mass production with sustainable methodologies, and safe environmental disposal. In this review, paper-based devices and platforms targeting SARS-CoV-2 are showcased and discussed, as a means to achieve quick and low-cost PoC diagnosis, including detection methodologies for viral genomic material, viral antigen detection, and serological antibody testing. Devices targeting inflammatory markers relevant for COVID-19 are also discussed, as fast, reliable bedside diagnostic tools for patient treatment and follow-up.

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“…Both IL-6 and PAI-1 Levels correlate with Ang II and are the highest in individuals with the ACE DD genotype[ 67 - 70 ]. IL-6 can inhibit EPO secretion in the kidney[ 71 ], is a prognosticator of COVID-19 disease severity, progress to severe disease and mortality[ 72 , 73 ]. Similarly, elevated PAI-1 is an independent risk factor for poor ARDS outcomes in COVID-19[ 74 ] and IL-6 induced significantly elevated PAI-1 Levels in critically ill COVID-19 patients[ 74 , 75 ].…”

Section: The Ace D Allele / Dd Genotype and Epo Interplay: Implications For Covid-19mentioning

confidence: 99%

Age and genotype dependent erythropoietin protection in COVID-19

Papadopoulos

Sutheesophon

Manipalviratn³

et al. 2021

WJSC

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Erythropoietin (EPO) is the main mediator of erythropoiesis and an important tissue protective hormone that appears to mediate an ancestral neuroprotective innate immune response mechanism at an early age. When the young brain is threatened-prematurity, neonatal hyperbilirubinemia, malaria- EPO is hyper-secreted disproportionately to any concurrent anemic stimuli. Under eons of severe malarial selection pressure, neuroprotective EPO augmenting genetic determinants such as the various hemoglobinopathies, and the angiotensin converting enzyme (ACE) I/D polymorphism, have been positively selected. When malarial and other cerebral threats abate and the young child survives to adulthood, EPO subsides. Sustained high ACE and angiotensin II (Ang II) levels through the ACE D allele in adulthood may then become detrimental as witnessed by epidemiological studies. The ubiquitous renin angiotensin system (RAS) influences the α-klotho/fibroblast growth factor 23 (FGF23) circuitry, and both are interconnected with EPO. Here we propose that at a young age, EPO augmenting genetic determinants through ACE D allele elevated Ang II levels in some or HbE/beta thalassemia in others would increase EPO levels and shield against coronavirus disease 2019, akin to protection from malaria and dengue fever. Human evolution may use ACE2 as a “bait” for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to gain cellular entry in order to trigger an ACE/ACE2 imbalance and stimulate EPO hypersecretion using tissue RAS, uncoupled from hemoglobin levels. In subjects without EPO augmenting genetic determinants at any age, ACE2 binding and internalization upon SARS-CoV-2 entry would trigger an ACE/ACE2 imbalance, and Ang II oversecretion leading to protective EPO stimulation. In children, low nasal ACE2 Levels would beneficially augment this imbalance, especially for those without protective genetic determinants. On the other hand, in predisposed adults with the ACE D allele, ACE/ACE2 imbalance, may lead to uncontrolled RAS overactivity and an Ang II induced proinflammatory state and immune dysregulation, with interleukin 6 (IL-6), plasminogen activator inhibitor, and FGF23 elevations. IL-6 induced EPO suppression, aggravated through co-morbidities such as hypertension, diabetes, obesity, and RAS pharmacological interventions may potentially lead to acute respiratory distress syndrome, cytokine storm and/or autoimmunity. HbE/beta thalassemia carriers would enjoy protection at any age as their EPO stimulation is uncoupled from the RAS system. The timely use of rhEPO, EPO analogs, acetylsalicylic acid, bioactive lipids, or FGF23 antagonists in genetically predisposed individuals may counteract those detrimental effects.

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Relationship Between IL-6 and COVID-19: to Be Considered During Treatment

Cited by 57 publications

References 36 publications

The Characterization of Disease Severity Associated IgG Subclasses Response in COVID-19 Patients

The Characterization of Disease Severity Associated IgG Subclasses Response in COVID-19 Patients

Paper-Based Biosensors for COVID-19: A Review of Innovative Tools for Controlling the Pandemic

Age and genotype dependent erythropoietin protection in COVID-19

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