BPIFB4 Circulating Levels and Its Prognostic Relevance in COVID-19.
J Gerontol A Biol Sci Med Sci
; 76(10): 1775-1783, 2021 09 13.
Article
in English
| MEDLINE | ID: covidwho-1358442
ABSTRACT
Aging and comorbidities make individuals at greatest risk of COVID-19 serious illness and mortality due to senescence-related events and deleterious inflammation. Long-living individuals (LLIs) are less susceptible to inflammation and develop more resiliency to COVID-19. As demonstrated, LLIs are characterized by high circulating levels of BPIFB4, a protein involved in homeostatic response to inflammatory stimuli. Also, LLIs show enrichment of homozygous genotype for the minor alleles of a 4 missense single-nucleotide polymorphism haplotype (longevity-associated variant [LAV]) in BPIFB4, able to counteract progression of diseases in animal models. Thus, the present study was designed to assess the presence and significance of BPIFB4 level in COVID-19 patients and the potential therapeutic use of LAV-BPIFB4 in fighting COVID-19. BPIFB4 plasma concentration was found significantly higher in LLIs compared to old healthy controls while it significantly decreased in 64 COVID-19 patients. Further, the drop in BPIFB4 values correlated with disease severity. Accordingly to the LAV-BPIFB4 immunomodulatory role, while lysates of SARS-CoV-2-infected cells induced an inflammatory response in healthy peripheral blood mononuclear cells in vitro, the co-treatment with recombinant protein (rh) LAV-BPIFB4 resulted in a protective and self-limiting reaction, culminating in the downregulation of CD69 activating-marker for T cells (both TCD4+ and TCD8+) and in MCP-1 reduction. On the contrary, rhLAV-BPIFB4 induced a rapid increase in IL-18 and IL-1b levels, shown largely protective during the early stages of the virus infection. This evidence, along with the ability of rhLAV-BPIFB4 to counteract the cytotoxicity induced by SARS-CoV-2 lysate in selected target cell lines, corroborates BPIFB4 prognostic value and open new therapeutic possibilities in more vulnerable people.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Intercellular Signaling Peptides and Proteins
/
COVID-19
/
Longevity
Type of study:
Diagnostic study
/
Observational study
/
Prognostic study
Topics:
Long Covid
/
Variants
Limits:
Female
/
Humans
/
Male
Country/Region as subject:
Europa
Language:
English
Journal:
J Gerontol A Biol Sci Med Sci
Journal subject:
Geriatrics
Year:
2021
Document Type:
Article
Affiliation country:
Gerona
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