BPIFB4 Circulating Levels and Its Prognostic Relevance in COVID-19

• Published in: The journals of gerontology. Series A, Biological sciences and medical sciences Biological sciences and medical sciences, 2021-10, Vol.76 (10), p.1775-1783
• Main Authors: Ciaglia, Elena, Lopardo, Valentina, Montella, Francesco, Sellitto, Carmine, Manzo, Valentina, De Bellis, Emanuela, Iannaccone, Teresa, Franci, Gianluigi, Zannella, Carla, Pagliano, Pasquale, Di Pietro, Paola, Carrizzo, Albino, Vecchione, Carmine, Conti, Valeria, Filippelli, Amelia, Puca, Annibale Alessandro
• Format: Article
• Language: English
• Subjects: Aging; Animal models; CD69 antigen; Cell lines; COVID-19; Cytokines; Cytotoxicity; Gene polymorphism; Haplotypes; IL-1β; Immunomodulation; Inflammation; Interleukin 1; Interleukin 18; Leukocytes (mononuclear); Lymphocytes T; Lysates; Monocyte chemoattractant protein 1; Pandemics; Patients; Peripheral blood mononuclear cells; Senescence; Severe acute respiratory syndrome coronavirus 2; Single-nucleotide polymorphism; THE JOURNAL OF GERONTOLOGY: Biological Sciences
• ISSN: 1079-5006; 1758-535X
• DOI: 10.1093/gerona/glab208

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.