VIP plasma levels associate with survival in severe COVID-19 patients, correlating with protective effects in SARS-CoV-2-infected cells

Abstract

Infection by SARS‐CoV‐2 may elicit uncontrolled and damaging inflammatory responses. Thus, it is critical to identify compounds able to inhibit virus replication and thwart the inflammatory reaction. Here, we show that the plasma levels of the immunoregulatory neuropeptide VIP are elevated in patients with severe COVID‐19, correlating with reduced inflammatory mediators and with survival on those patients. In vitro, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase‐activating polypeptide (PACAP), highly similar neuropeptides, decreased the SARS‐CoV‐2 RNA content in human monocytes and viral production in lung epithelial cells, also reducing cell death. Both neuropeptides inhibited the production of proinflammatory mediators in lung epithelial cells and in monocytes. VIP and PACAP prevented in monocytes the SARS‐CoV‐2‐induced activation of NF‐kB and SREBP1 and SREBP2, transcriptions factors involved in proinflammatory reactions and lipid metabolism, respectively. They also promoted CREB activation, a transcription factor with antiapoptotic activity and negative regulator of NF‐kB. Specific inhibition of NF‐kB and SREBP1/2 reproduced the anti‐inflammatory, antiviral, and cell death protection effects of VIP and PACAP. Our results support further clinical investigations of these neuropeptides against COVID‐19.

VIP/VPAC Axis Expression in Immune-Mediated Inflammatory Disorders: Associated miRNA Signatures

“…More studies are needed to strongly test this hypothesis with a larger number of patients in the remaining pathologies studied. A recently published study corroborates this finding in COVID-19 patients, where the plasma VIP levels were raised in patients with severe COVID-19, correlating with reduced inflammatory mediators and with survival in these patients [ 27 ].…”

Bioinformatics and systems biology approaches to identify the effects of COVID-19 on neurodegenerative diseases: A review

“…This may be a consequence of the intrinsic regulation of inflammatory mediators and TFs directly and indirectly involved in viral replication by VIP. [ 103 ] VIP prevented in monocytes the SARS-CoV-2-induced activation of NF-kB and SREBP1 and SREBP2, TFs involved in the pro-inflammatory response and lipid metabolism, respectively, and the activation of CREB (CREB is a transcription factor with anti-apoptotic activity and a transcription factor with NF-kB negative regulator). [ 104 ] Specific inhibition of NF-kB and SREBP1/2 by VIP recapitulates anti-inflammatory, anti-viral and cell death protective effects.…”

“…[ 104 ] Specific inhibition of NF-kB and SREBP1/2 by VIP recapitulates anti-inflammatory, anti-viral and cell death protective effects. [ 103 , 105 , 106 ] VIP exerts protective effects in cellular and animal models of different ND. In AD models, VIP prevents Aβ-induced neurodegeneration, inhibits the secretion of pro-inflammatory interleukins and neurotoxic drugs in microglia and induces Aβ phagocytosis.…”

Role of endocrine PACAP in age-related diseases

“…Elderly with Coronavirus disease 2019 suffered more severe cases and complications therefore this population showed increased morbidity and mortality ( 124 – 126 ). A recent study examined the possible protective and biomarker role of PACAP and VIP during SARS‐CoV‐2 infection, but no significant differences were found between PACAP plasma levels and the groups analyzed, inflammatory markers, viral load ( 127 ).…”