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Cathelicidins are a ubiquitous family of host defence antimicrobial peptides in vertebrate animals. Unlike other antimicrobial peptide families, it is defined by a large and relatively well conserved proregion rather than by the mature bioactive peptides themselves, which are highly diverse and conform to at least five different structural types, resulting in distinct modes of action. Cathelicidin-derived host defence peptides have a pleiotropic role in immunity, displaying both a direct antimicrobial activity and the ability to boost other host responses to infection and injury. The presence of a relatively well conserved proregion attached to a vast repertoire of structurally and functionally diverse peptides allows mining the increasing number of vertebrate genomes for lead sequences to potentially useful new anti-infective and/or immunomodulatory agents. This should increase the number of cathelicidin-based peptides entering clinical trials, which has been limited to date, despite considerable efforts in the last 2 decades.

COVID-19, the severe acute respiratory syndrome, is one of the major emergencies that have affected health care systems. Drugs and oxygen are only partially effective in saving lives in patients with severe COVID-19, and the most important protection from death is vaccination. The widespread use of COVID-19 adenovirus-based vaccines has provided evidence for the occurrence of rare venous thrombotic events including cerebral venous thrombosis and splanchnic venous thrombosis in recipients of Vaxzevria and Jcovden vaccines and the review focus on them. One year ago, thromboses in Vaxzevria recipients have been associated with thrombocytopenia in the presence of antibodies to platelet factor 4 and have been called vaccine-induced immune thrombotic thrombocytopenia (VITT). The incidence of VITT is equal to 9-31 events per one million doses of vaccines as evaluated by health agencies worldwide and is higher in female and young vaccine recipients. More recently, by using the European EudraVigilance database, it has been demonstrated that the incidence of thrombosis in recipients of adenovirus-based vaccines is 5–10 fold higher than that of VITT and 7–12 fold higher than observed in the recipients of Comirnaty, an mRNA-based vaccine, suggesting that adenovirus-based vaccines cause not only VITT but also thrombosis without thrombocytopenia (non-VITT thrombosis). The incidence of the vaccine-dependent non-VITT thrombosis is different in the adenovirus-based vaccines and the VITT/non-VITT incidence ratio depends on the severity of thrombosis and is inversely related to the age of the recipients. The possible causes and clinical implications of non-VITT thrombosis in vaccine recipients are discussed.

The spread of antibiotic resistant-pathogens is driving the search for new antimicrobial compounds. Pulmonary infections experienced by cystic fibrosis (CF) patients are a dramatic example of this health-care emergency. Antimicrobial peptides could answer the need for new antibiotics but translating them from basic research to the clinic is a challenge. We have previously evaluated the potential of the small membranolytic peptide BMAP-18 to treat CF-related infections, discovering that while this molecule had a good activity in vitro it was not active in vivo because of its rapid degradation by pulmonary proteases. In this study, we synthesized and tested the proteases-resistant all-D enantiomer. In spite of a good antimicrobial activity against Pseudomonas aeruginosa and Stenotrophomonas maltophilia clinical isolates and of a tolerable cytotoxicity in vitro, D-BMAP18 was ineffective to treat P. aeruginosa pulmonary infection in mice, in comparison to tobramycin. We observed that different factors other than peptide degradation hampered its efficacy for pulmonary application. These results indicate that D-BMAP18 needs further optimization before being suitable for clinical application and this approach may represent a guide for optimization of other anti-infective peptides eligible for the treatment of pulmonary infections.