Anakinra after treatment with corticosteroids alone or with tocilizumab in patients with severe COVID-19 pneumonia and moderate hyperinflammation. A retrospective cohort study

Millán, Ismael Francisco Aomar; Salvatierra, Juan; Torres-Parejo, Úrsula; Faro-Míguez, Naya; Callejas‐Rubio, José Luis; Ceballos-Torres, Ángel; Cruces-Moreno, María Teresa; Gómez-Jiménez, Francisco Javier; Hernández-Quero, José; Anguita-Santos, Francisco

doi:10.1007/s11739-020-02600-z

Cited by 33 publications

(26 citation statements)

References 52 publications

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“…To our knowledge, this is the first report describing the use of a blocker of IL-1 receptor, anakinra, in MIS-A, with a very good outcome. Anakinra has been largely used and studied in the treatment of COVID-19 and is part of several clinical trials for this disease [ 13 , 14 , 15 ]; furthermore, its use has been described in a series of MIS-C cases, with good results [ 16 ]. Interestingly, successful use of anakinra in two cases of MIS-C refractive to IVIG and systemic glucocorticoids has also recently been described [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Multisystem Inflammatory Syndrome in an Adult (MIS-A) Successfully Treated with Anakinra and Glucocorticoids

et al. 2021

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During the current SARS-CoV-2 pandemic, a novel syndrome termed “multisystem inflammatory syndrome in children” (MIS-C) has emerged. MIS-C was linked to COVID-19 and shared some features with Kawasaki disease and Toxic Shock Syndrome, with a common pathogenetic substrate of hyperinflammation and cytokine storm. Lately, MIS was also described in adults (≥21 years of age) and named “MIS-A”. There is no consensus about the treatment of MIS-A; successful use of glucocorticoids and immunoglobulins has been reported in case series, but more solid evidence is lacking. Furthermore, the role of biologic agents with proven benefits against COVID-19, MIS-C, or Kawasaki disease is still unexplored. In this report, we detail the clinical picture and the diagnostic process that led to the diagnosis of MIS-A in a 27-year-old man, focusing on its treatment with anakinra and glucocorticoids, which resulted in full recovery. To our knowledge, this is the first report of the successful use of anakinra for MIS-A, a drug that has already proven useful in the treatment of refractive cases of MIS-C. Anakinra may also play a pivotal role for the treatment of MIS-A.

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Section: Discussionmentioning

confidence: 99%

Multisystem Inflammatory Syndrome in an Adult (MIS-A) Successfully Treated with Anakinra and Glucocorticoids

et al. 2021

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“…In the absence of an effective treatment option against COVID-19, the steadily increased mortality among infected subjects and the delay in the widespread vaccination of the general population, it seems that immunomodulatory agents might be crucial for the management of the disease. However, it remains unclear which one should be preferred, although they could be administered sequentially in refractory cases [3,4].…”

mentioning

confidence: 99%

Anakinra or tocilizumab for prevention of COVID-19 death? A big dilemma

Patoulias

Dimosiari

Michailidis

2021

European Journal of Internal Medicine

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“…A head-to-head comparison of Anakinra to Tocilizumab found no difference in patient outcomes [260], which in light of the lack of Tocilizumab benefits, indicates a lack of Anakinra benefits, as well. Anakinra plus Tocilizumab, however, reduced the need for ventilation and overall mortality [261], as might be expected, since the combination addressed two sets of cytokines rather than just one (Figure 12). Targeting a broader range of cytokines receptors might be more therapeutically effective but, also, much more difficult to deliver than targeting key TLR and NLR and, at present, extremely expensive.…”

Section: Implications Of Innate Receptor Activation Profiles For Tretmentioning

confidence: 57%

Innate Receptor Activation Patterns Involving TLR and NLR Synergisms in COVID-19, ALI/ARDS and Sepsis Cytokine Storms: A Review and Model Making Novel Predictions and Therapeutic Suggestions

Root‐Bernstein

2021

IJMS

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Severe COVID-19 is characterized by a “cytokine storm”, the mechanism of which is not yet understood. I propose that cytokine storms result from synergistic interactions among Toll-like receptors (TLR) and nucleotide-binding oligomerization domain-like receptors (NLR) due to combined infections of SARS-CoV-2 with other microbes, mainly bacterial and fungal. This proposition is based on eight linked types of evidence and their logical connections. (1) Severe cases of COVID-19 differ from healthy controls and mild COVID-19 patients in exhibiting increased TLR4, TLR7, TLR9 and NLRP3 activity. (2) SARS-CoV-2 and related coronaviruses activate TLR3, TLR7, RIG1 and NLRP3. (3) SARS-CoV-2 cannot, therefore, account for the innate receptor activation pattern (IRAP) found in severe COVID-19 patients. (4) Severe COVID-19 also differs from its mild form in being characterized by bacterial and fungal infections. (5) Respiratory bacterial and fungal infections activate TLR2, TLR4, TLR9 and NLRP3. (6) A combination of SARS-CoV-2 with bacterial/fungal coinfections accounts for the IRAP found in severe COVID-19 and why it differs from mild cases. (7) Notably, TLR7 (viral) and TLR4 (bacterial/fungal) synergize, TLR9 and TLR4 (both bacterial/fungal) synergize and TLR2 and TLR4 (both bacterial/fungal) synergize with NLRP3 (viral and bacterial). (8) Thus, a SARS-CoV-2-bacterium/fungus coinfection produces synergistic innate activation, resulting in the hyperinflammation characteristic of a cytokine storm. Unique clinical, experimental and therapeutic predictions (such as why melatonin is effective in treating COVID-19) are discussed, and broader implications are outlined for understanding why other syndromes such as acute lung injury, acute respiratory distress syndrome and sepsis display varied cytokine storm symptoms.

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Anakinra after treatment with corticosteroids alone or with tocilizumab in patients with severe COVID-19 pneumonia and moderate hyperinflammation. A retrospective cohort study

Cited by 33 publications

References 52 publications

Multisystem Inflammatory Syndrome in an Adult (MIS-A) Successfully Treated with Anakinra and Glucocorticoids

Multisystem Inflammatory Syndrome in an Adult (MIS-A) Successfully Treated with Anakinra and Glucocorticoids

Anakinra or tocilizumab for prevention of COVID-19 death? A big dilemma

Innate Receptor Activation Patterns Involving TLR and NLR Synergisms in COVID-19, ALI/ARDS and Sepsis Cytokine Storms: A Review and Model Making Novel Predictions and Therapeutic Suggestions

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