Capturing Cytokines with Advanced Materials: A Potential Strategy to Tackle COVID‐19 Cytokine Storm

Abstract

as 2019-nCoV), [1] has caused more than 83 million infections and 1.8 million deaths globally as of January 1, 2021. [2] In the past 200 years, multiple epidemics induced by emerging viruses, such as SARS-CoV, Zika virus, Ebola virus, and recently SARS-CoV-2, have posed unprecedented threats to global public health. [3] Although several vaccine candidates have been approved by the U.S. Food and Drug Administration (FDA) for emergency prevention of SARS-CoV-2 infection, so far there is still absence of effective therapeutic options for patients with COVID-19. [4] Thus, it is of paramount importance to develop therapeutic approaches for COVID-19 and other potential pandemics.Similar to SARS-CoV infection, SARS-CoV-2 relies on spike proteins and angiotensin-converting enzyme 2 (ACE2) receptors for cell infection. [5][6][7] Once the virus enters human body, macrophages and monocytes secrete abundant proinflammatory cytokines, promoting pathogen elimination and tissue recovery. However, an exaggerated release of cytokines, known as a "cytokine storm" (or "cytokine release syndrome"), may worsen inflammatory status and result in immune-system-initiated organ damage. [8] Clinically, the majority of patients with COVID-19 appear asymptomatic or mildly symptomatic, while ≈20% of COVID-19 cases developThe COVID-19 pandemic, induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused great impact on the global economy and people's daily life. In the clinic, most patients with COVID-19 show none or mild symptoms, while approximately 20% of them develop severe pneumonia, multiple organ failure, or septic shock due to infection-induced cytokine release syndrome (the so-called "cytokine storm"). Neutralizing antibodies targeting inflammatory cytokines may potentially curb immunopathology caused by COVID-19; however, the complexity of cytokine interactions and the multiplicity of cytokine targets make attenuating the cytokine storm challenging. Nonspecific in vivo biodistribution and dose-limiting side effects further limit the broad application of those free antibodies. Recent advances in biomaterials and nanotechnology have offered many promising opportunities for infectious and inflammatory diseases. Here, potential mechanisms of COVID-19 cytokine storm are first discussed, and relevant therapeutic strategies and ongoing clinical trials are then reviewed. Furthermore, recent research involving emerging biomaterials for improving antibody-based and broad-spectrum cytokine neutralization is summarized. It is anticipated that this work will provide insights on the development of novel therapeutics toward efficacious management of COVID-19 cytokine storm and other inflammatory diseases.

Peritoneal M2 macrophage-derived extracellular vesicles as natural multitarget nanotherapeutics to attenuate cytokine storms after severe infections

“…Some therapies aimed at countering or neutralizing a single cytokine ( e.g. , IL-6 or TNF-α blockers) have been developed and have shown certain beneficial effects in preclinical models [ 7 , 8 ], but they have shown controversial results in clinical trials of COVID-19 treatment [ 9 ]. The possible reason is that single cytokine-targeted therapy may function well when this cytokine is the driving factor in this disease, while the mechanisms of cytokine storms are complicated, and many cytokines are involved [ 3 ].…”

Changes in Serum Liver Function for Patients with COVID-19: A 1-Year Follow-Up Study

“…A cytokine storm is characteristic of COVID-19. 26 Significant release of proinflammatory cytokines and changes in the number and function of lymphocytes are related symptoms. 27 We found that the percentage of CD8+ T cells in the first blood test (T1) was a risk factor for stage T3 liver dysfunction.…”

Regulation of Inflammatory Cytokine Storms by Mesenchymal Stem Cells

“…The non-specific biodistribution in vivo and dose-limited side effects further limit the wide application of these free antibodies. The latest developments in biomaterials and nanotechnology ( 85 ) provide many promising opportunities for infectious and inflammatory diseases.Recently, the team of Rao ( 86 ) and other researchers proposed new biomaterials in improving the role of antibody and broad spectrum cytokines. This multi-functional neutralization platform ( 87 ) can solve the problem of multiple cytokines released in different diseases at the same time, which is conducive to the development.…”