Comparative Study of Cytokine Storm Treatment in Patients with COVID-19 Pneumonia Using Immunomodulators

Abstract

(1) Background: In patients hospitalized with COVID-19 pneumonia, especially moderate and severe forms, a cytokine storm may occur, characterized by the worsening of symptoms and the alteration of biological parameters on days 8–12 of the disease. The therapeutic options for cytokine storms are still controversial, requiring further clarification; (2) Methods: Our study included 344 patients with moderate and severe pneumonia admitted to the internal medicine department who developed a cytokine storm (diagnosed by clinical and biochemical criteria). In group A, 149 patients were treated with Remdesivir and Tocilizumab (together with other drugs, including corticosteroids, antibiotics and anticoagulants), and in group B, 195 patients received Remdesivir and Anakinra. Patients were monitored clinically and by laboratory tests, with the main biochemical parameters being CRP (C-reactive protein), LDH (lactic dehydrogenase) and ferritin; (3) Results: Patients were followed up from a clinical point of view and also by the measurement of CRP, LDH and ferritin at the beginning of therapy, on days three to four and on the tenth day. In both groups, we registered a clinical improvement and a decrease in the parameters of the cytokine storm. In group A, with the IL-6 antagonist Tocilizumab, the beneficial effect occurred faster; in group B, with the IL-1 antagonist Anakinra, the beneficial effect was slower. (4) Conclusions: The use of the immunomodulators, Tocilizumab and Anakinra, in the cytokine storm showed favorable effects, both clinical and biochemical.

Role of Innate and Adaptive Cytokines in the Survival of COVID-19 Patients

“…IL-6 is considered pivotal for the onset of innate immune-inflammatory responses [ 16 , 17 ]. The biological activity of IL-6 is antagonized by a combination of sIL-6R and sgp130, which are soluble IL-6 receptors [ 42 , 43 , 44 ]. In agreement with previous studies, we found that severe COVID-19 patients had elevated serum levels of IL-1α, IL-1β IL-6 and IL-18 [ 18 , 25 , 26 , 32 , 37 ].…”

“…Supporting this relevance of IL-6, although the non-surviving severe COVID-19 patients had significantly higher levels of IL-6, there were no significant differences between the two groups of patients in the levels of sIL-6R and sgp130, indicating limited control of IL-6 activity. Furthermore, circulating IL-6 and sIL-6R complexes (also called hyper-IL-6) may amplify inflammation, with the potential involvement of somatic non-immune cells that ubiquitously express the gp-130 receptor, through a non-classic form of activation called trans-signaling and in the absence of the regulatory mechanism of the sgp130 soluble factor [ 43 , 44 ]. Clearly, in the absence of sIL-6R, cells are not able to respond to IL-6; thus, treatment with anti-IL-6R has been shown to be efficient in the treatment of severe patients [ 45 ].…”

In silico prediction of COVID-19 cytokine storm in lung cancer types

“…Surprisingly, some of the clinically proven essential cytokines in the case of COVID-19, such as IL-6, which served as a biomarker for COVID-19 infection [ 31 , 32 ] was negatively correlated in LUAD ( P < 0.0001) compared to LUSC with ACE2 gene expression, where it has shown a non-significant correlation. Various other essential cytokines which constitute “cytokine storm” such as IL-2R, TGFβ1, TGFβ2, IFNα1, IFNβ1, IFNγ, CXCL10 and MCP2 [ 4 , 17 , 33 ] were also negatively correlated in LUAD ( Fig. 3 and Supplementary Table 1 ).…”

“…This pandemic's critical and devastating feature is not only limited to the discovery of new viruses but also diversifying and hyperinflammatory unpredictable immune response. According to current literature actual killer is not the virus but the immunologic complications such as hyper-proinflammatory status called the “cytokine storm” [ 2 ], leading to the development of acute respiratory distress syndrome and multiple organ dysfunction/failure, making the disease more grievous for COVID-19 patients [ 3 , 4 ].…”

“…Two receptors, i.e., angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) are the crucial players in SARS-CoV-2 entry into host cells, thereby providing a platform to replicate and damage host cells and organs [ 3 , 4 ]. ACE2 acted as a functional “receptor” by facilitating the entry of the virus through the binding of spike glycoprotein (S-glycoprotein) of novel coronavirus SARS-CoV-2.…”