Interleukin 6, soluble interleukin 2 receptor alpha (CD25), monocyte colony-stimulating factor, and hepatocyte growth factor linked with systemic hyperinflammation, innate immunity hyperactivation, and organ damage in COVID-19 pneumonia

Quartuccio, Luca; Fabris, Martina; Sonaglia, Arianna; Peghin, Maddalena; Domenis, Rossana; Cifù, Adriana; Curcio, Francesco; Tascini, Carlo

doi:10.1016/j.cyto.2021.155438

Cited by 45 publications

(38 citation statements)

References 37 publications

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“…In contrast, a reduced or delayed mucosal response in adults, evidenced by the decreased expression of transcripts associated with innate pathways in their NP swabs, may lead to an inability to escape viral immune evasion and a more vigorous adaptive response ( 13 , 14 ). The latter contributes to high systemic levels of other inflammatory cytokines (e.g., IL-6 and TNF) and an increased risk of acute respiratory distress syndrome, which was also observed with SARS-CoV-1 ( 15 – 18 ). Other studies have found an impaired innate response to SARS-CoV-2 in adults compared with their response to other respiratory viral infections ( 19 ).…”

Section: Discussionmentioning

confidence: 95%

Natural mucosal barriers and COVID-19 in children

Pierce¹,

Sy²,

Galen³

et al. 2021

JCI Insight

131

177

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Background: COVID-19 is more benign in children compared to adults for unknown reasons. This contrasts with other respiratory viruses where disease manifestations are often more severe in children. We hypothesize that a more robust early innate immune response to SARS-CoV-2 protects against severe disease. Methods: Clinical outcomes, SARS-CoV-2 viral copies and cellular gene expression were compared in nasopharyngeal swabs obtained at the time of presentation to the Emergency Department from 12 children and 27 adults using bulk RNA sequencing and quantitative reverse transcription PCR. Total protein, cytokines and anti-SARS-CoV-2 IgG and IgA were quantified in nasal fluid.Results: SARS-CoV-2 copies, ACE2 and TMPRSS2 gene expression were similar in children and adults, but children displayed higher expression of genes associated with interferon signaling, NLRP3 inflammasome, and other innate pathways. Higher levels of IFN-2, IFN-, IP-10, IL-8, and IL-1 protein were detected in nasal fluid in children versus adults. Children also expressed higher levels of genes associated with immune cells whereas expression of those associated with epithelial cells did not differ in children versus adults. Anti-SARS-CoV-2 IgA and IgG were detected at similar levels in nasal fluid from both groups. None of the children required supplemental oxygen whereas 7 adults did (p=0.03); four adults died.Conclusions: These findings provide direct evidence of a more vigorous early mucosal immune response in children compared to adults and suggest that this contributes to favorable clinical outcomes.

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Section: Discussionmentioning

confidence: 95%

Natural mucosal barriers and COVID-19 in children

Pierce¹,

Sy²,

Galen³

et al. 2021

JCI Insight

131

177

View full text Add to dashboard Cite

show abstract

“…Moreover, as described in many studies, SARS-CoV-2 is able to activate in different ways the immune system; in particular, it can induce interleukin-6 (IL-6)-dependent pathways leading to cytokine storm and macrophage activation syndromes; in addition, it might alter interferon signalling in some cases [ 19 , 54 , 55 , 56 , 57 , 58 ].…”

Section: Discussionmentioning

confidence: 99%

Post-COVID-19 Arthritis and Sacroiliitis: Natural History with Longitudinal Magnetic Resonance Imaging Study in Two Cases and Review of the Literature

Colatutto

Sonaglia

Zabotti

et al. 2021

Viruses

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Severe acute respiratory coronavirus-2 syndrome (SARS-CoV-2) is a well-known pandemic infectious disease caused by an RNA virus belonging to the coronaviridae family. The most important involvement during the acute phase of infection concerns the respiratory tract and may be fatal. However, COVID-19 may become a systemic disease with a wide spectrum of manifestations. Herein, we report the natural history of sacroiliac inflammatory involvement in two females who developed COVID-19 infection with mild flu-like symptoms. After the infection they reported inflammatory back pain, with magnetic resonance imaging (MRI) studies showing typical aspects of sacroiliitis. Symptoms improved with NSAIDs therapy over the following months while MRI remained positive. A literature review was performed on this emerging topic. To our knowledge, this is the first MRI longitudinal study of post-COVID-19 sacroiliitis with almost one year of follow-up. Predisposing factors for the development of articular involvement are unclear but a long-lasting persistence of the virus, demonstrated by nasopharyngeal swab, may enhance the probability of altering the immune system in a favourable background.

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“…The excited macrophages trigger multi-immune cell proteins, including interferons, proinflammatory cytokines, monocyte chemo-attractant proteins, and tumor necrosis factors. Stimulation of T-lymphocytes incites complement activation (C5a/C5aR1), causing extensive organ injury [233][234][235].…”

Section: Dysregulated Immune Response As a Crucial Pathogenic Factor For Organ Disordermentioning

confidence: 99%

Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses

et al. 2021

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The pathogenesis of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still not fully unraveled. Though preventive vaccines and treatment methods are out on the market, a specific cure for the disease has not been discovered. Recent investigations and research studies primarily focus on the immunopathology of the disease. A healthy immune system responds immediately after viral entry, causing immediate viral annihilation and recovery. However, an impaired immune system causes extensive systemic damage due to an unregulated immune response characterized by the hypersecretion of chemokines and cytokines. The elevated levels of cytokine or hypercytokinemia leads to acute respiratory distress syndrome (ARDS) along with multiple organ damage. Moreover, the immune response against SARS-CoV-2 has been linked with race, gender, and age; hence, this viral infection’s outcome differs among the patients. Many therapeutic strategies focusing on immunomodulation have been tested out to assuage the cytokine storm in patients with severe COVID-19. A thorough understanding of the diverse signaling pathways triggered by the SARS-CoV-2 virus is essential before contemplating relief measures. This present review explains the interrelationships of hyperinflammatory response or cytokine storm with organ damage and the disease severity. Furthermore, we have thrown light on the diverse mechanisms and risk factors that influence pathogenesis and the molecular pathways that lead to severe SARS-CoV-2 infection and multiple organ damage. Recognition of altered pathways of a dysregulated immune system can be a loophole to identify potential target markers. Identifying biomarkers in the dysregulated pathway can aid in better clinical management for patients with severe COVID-19 disease. A special focus has also been given to potent inhibitors of proinflammatory cytokines, immunomodulatory and immunotherapeutic options to ameliorate cytokine storm and inflammatory responses in patients affected with COVID-19.

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Interleukin 6, soluble interleukin 2 receptor alpha (CD25), monocyte colony-stimulating factor, and hepatocyte growth factor linked with systemic hyperinflammation, innate immunity hyperactivation, and organ damage in COVID-19 pneumonia

Cited by 45 publications

References 37 publications

Natural mucosal barriers and COVID-19 in children

Natural mucosal barriers and COVID-19 in children

Post-COVID-19 Arthritis and Sacroiliitis: Natural History with Longitudinal Magnetic Resonance Imaging Study in Two Cases and Review of the Literature

Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses

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