Efficacy of Tocilizumab Therapy in Different Subtypes of COVID-19 Cytokine Storm Syndrome

Oliynyk, Oleksandr; Barg, Wojciech; Ślifirczyk, Anna; Oliynyk, Yanina; Гуріанов, В. Г.; Rorat, Marta

doi:10.3390/v13061067

Cited by 10 publications

(4 citation statements)

References 33 publications

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“…Regarding IL-6 blockade with tocilizumab in COVID-19-associated MAS, the results are controversial. Some studies have reported that treatment with tocilizumab contributes to reduced mortality and favorable outcomes [144,145]. Conversely, another study noted that tocilizumab demonstrated limited efficacy for COVID-19-related MAS [146].…”

Section: Therapeutic Optionsmentioning

confidence: 99%

Macrophage Activation Syndrome in Viral Sepsis

Papageorgiou,

Gogos,

Akinosoglou

2024

Viruses

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Macrophage activation syndrome (MAS) is a life-threatening systemic hyperinflammatory syndrome triggered by various infections, particularly viral infections, autoimmune disorders, and malignancy. The condition is characterized by an increased production of proinflammatory cytokines resulting in a cytokine storm and has been associated with poor clinical outcomes. During the COVID-19 pandemic, patients with severe manifestations developed features similar to those of MAS, although these characteristics remained well defined within the lung. Additionally, other viral infections including EBV, the herpes family of viruses, hepatitis viruses, influenza, HIV, and hemorrhagic fevers can be complicated by MAS. The diagnosis and management of the condition remain challenging due to the lack of consensus on specific guidelines, especially among the adult population. Currently, therapeutic options primarily rely on medications that are typically used to treat primary hemophagocytic lymphohistiocytosis, such as corticosteroids and etoposide. In addition, cytokine-targeted therapies present promising treatment options. The objective of this review is to discuss the emergence of MAS in the context of viral infections including, but not limited to, its occurrence in COVID-19.

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Section: Therapeutic Optionsmentioning

confidence: 99%

Macrophage Activation Syndrome in Viral Sepsis

Papageorgiou,

Gogos,

Akinosoglou

2024

Viruses

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“…This, in turn, drives the overexpression of proinflammatory cytokines such as IL-6 [ 511 ], and chemokines such as IL-8 (aka CXCL8 [C-X-C motif chemokine ligand 8]) [ 512 , 513 ]. The lymphopenia usually appears within the first week of infection, whereas the cytokine storm, typically associated with macrophage activation, typically occurs later as the disease progresses [ 514 ]. Nevertheless, there may be a link between these two processes, as it has been demonstrated that neutralization of IL-6 helped to restore circulatory T-cell counts [ 515 ].…”

Section: Antibodies For Palliative Therapymentioning

confidence: 99%

Passive Immunotherapy Against SARS-CoV-2: From Plasma-Based Therapy to Single Potent Antibodies in the Race to Stay Ahead of the Variants

Strohl

et al. 2022

BioDrugs

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The COVID-19 pandemic is now approaching 2 years old, with more than 440 million people infected and nearly six million dead worldwide, making it the most significant pandemic since the 1918 influenza pandemic. The severity and significance of SARS-CoV-2 was recognized immediately upon discovery, leading to innumerable companies and institutes designing and generating vaccines and therapeutic antibodies literally as soon as recombinant SARS-CoV-2 spike protein sequence was available. Within months of the pandemic start, several antibodies had been generated, tested, and moved into clinical trials, including Eli Lilly’s bamlanivimab and etesevimab, Regeneron’s mixture of imdevimab and casirivimab, Vir’s sotrovimab, Celltrion’s regdanvimab, and Lilly’s bebtelovimab. These antibodies all have now received at least Emergency Use Authorizations (EUAs) and some have received full approval in select countries. To date, more than three dozen antibodies or antibody combinations have been forwarded into clinical trials. These antibodies to SARS-CoV-2 all target the receptor-binding domain (RBD), with some blocking the ability of the RBD to bind human ACE2, while others bind core regions of the RBD to modulate spike stability or ability to fuse to host cell membranes. While these antibodies were being discovered and developed, new variants of SARS-CoV-2 have cropped up in real time, altering the antibody landscape on a moving basis. Over the past year, the search has widened to find antibodies capable of neutralizing the wide array of variants that have arisen, including Alpha, Beta, Gamma, Delta, and Omicron. The recent rise and dominance of the Omicron family of variants, including the rather disparate BA.1 and BA.2 variants, demonstrate the need to continue to find new approaches to neutralize the rapidly evolving SARS-CoV-2 virus. This review highlights both convalescent plasma- and polyclonal antibody-based approaches as well as the top approximately 50 antibodies to SARS-CoV-2, their epitopes, their ability to bind to SARS-CoV-2 variants, and how they are delivered. New approaches to antibody constructs, including single domain antibodies, bispecific antibodies, IgA- and IgM-based antibodies, and modified ACE2-Fc fusion proteins, are also described. Finally, antibodies being developed for palliative care of COVID-19 disease, including the ramifications of cytokine release syndrome (CRS) and acute respiratory distress syndrome (ARDS), are described. Supplementary Information The online version contains supplementary material available at 10.1007/s40259-022-00529-7.

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“…40,41 A recent double-blind placebo-controlled study of seven days of sildenafil in acutely ill patients with COVID-19 found five-fold decreased mortality and halving in ITU admissions in the PDE5I group, suggesting an important role in acute COVID infection and a need for further studies. 42…”

Section: Prevention Of Diabetic Peripheral Neuropathymentioning

confidence: 99%