The novel immunomodulatory biologic LMWF5A for pharmacological attenuation of the “cytokine storm” in COVID-19 patients: a hypothesis

Abstract

Background: A common complication of viral pulmonary infections, such as in the ongoing COVID-19 pandemic, is a phenomenon described as a "cytokine storm". While poorly defined, this hyperinflammatory response results in diffuse alveolar damage. The low molecular weight fraction of commercial human serum albumin (LMWF5A), a novel biologic in development for osteoarthritis, demonstrates beneficial in vitro immunomodulatory effects complimentary to addressing inflammation, thus, we hypothesize that LMWF5A could improve the clinical outcomes of COVID-19 by attenuating hyperinflammation and the potential development of a cytokine storm.Presentation of the hypothesis: A variety of human in vitro immune models indicate that LMWF5A reduces the production of pro-inflammatory cytokines implicated in cytokine storm associated with COVID-19. Furthermore, evidence suggests LMWF5A also promotes the production of mediators required for resolving inflammation and enhances the barrier function of endothelial cultures. Testing the hypothesis: A randomized controlled trial, to evaluate the safety and efficacy of nebulized LMWF5A in adults with Acute Respiratory Distress Syndrome (ARDS) secondary to COVID-19 infection, was developed and is currently under review by the Food and Drug Administration. Implications of hypothesis: If successful, this therapy may attenuate the cytokine storm observed in these patients and potentially reduce mortality, increase ventilation free days, improve oxygenation parameters and consequently lessen the burden on patients and the intensive care unit. Conclusions: In conclusion, in vitro findings suggest that the immunomodulatory effects of LMWF5A make it a viable candidate for treating cytokine storm and restoring homeostasis to the immune response in COVID-19.

A Novel CD206 Targeting Peptide Inhibits Bleomycin Induced Pulmonary Fibrosis in Mice

“…Furthermore, we observed significant decreases in CD206 expression by immunofluorescence ( Figure 4D). M2 macrophages are responsible for pro-inflammatory and pro-fibrosis cytokines in the lung commonly known as the "cytokine storm" [22,23] To determine if RP-832c affects these cytokines, we performed RT-PCR on mRNA extracted from naïve, BLM only, and RP-832c treated lungs. Interestingly, we observed significant decreases in TNF-α, IL-10, IL-6, CXCL1, and CXCL2 ( Figure 4E).…”

Escaping Cytokine Storm for the Poor

“…The other day when this author was surfing you tube, one thing surprised her was that so many people including many professionals do not know how to wash hands. The right way to wash hands is as follows: First, you need to lather the hand up after test the water temperature [24,25]. Do not burn yourself.…”

Insights into pediatric multi-system inflammatory syndrome and COVID-19

“…We have recently reviewed the effects of both PGE 2 and PGJ 2 (and its derivatives) in severe inflammatory disease and have argued that the pro-and anti-inflammatory effects of these prostaglandins are so complex that, for clinical use, it would be better to use compounds that stimulate the natural progression of PGE 2 synthesis followed by inhibition of its synthesis, and then appearance of the PGJ 2 and its derivatives, in order to mimic the body's natural sequence of events when severe inflammation arises [13]. KD and the newly described syndrome associated with COVID-19 are logical diseases to consider using this approach.…”

“…Furthermore, evidence suggests LMWF5A also promotes the production of mediators required for resolving inflammation and enhances the barrier function of endothelial cultures. A more detailed description of the nebulized form trial protocol and rationale was recently published [13]. Although a nebulized form of LMWF5A has been proposed to treat COVID-19 respiratory disease, it seems more likely that intravenous therapy, either alone or as a supplement to IVIG therapy would be a more reasonable approach for a trial in KD patients and the recently observed SARS-CoV-2 associated disease.…”

“…LMWF5A, obtained from removing the >5 kDa fraction which includes albumin, contains at least 3 separate anti-inflammatory compounds [18] . The full panoply of anti-inflammatory results found in a large number of cell types was recently published [13] . What we want to emphasize here is that LMWF5A is unique among non-steroidal anti-inflammatory compounds.…”