Ivermectin Affects Neutrophil-Induced Inflammation through Inhibition of Hydroxylysine but Stimulation of Cathepsin G and Phenylalanine Secretion.

The invasion and integrin-dependent adhesion of neutrophils to lung tissues and their secretion lead to the development of pneumonia in various pulmonary pathologies, including acute respiratory distress syndrome in coronavirus disease. We studied the effect of ivermectin, a possible therapeutic agent for inflammation and cancer, on integrin-dependent neutrophil adhesion to fibronectin and the concomitant secretion. Ivermectin did not affect the attachment of neutrophils to the substrate and the reactive oxygen species production but sharply inhibited the adhesion-induced release of hydroxylysine and stimulated the release of phenylalanine and cathepsin G. Hydroxylysine is a product of lysyl hydroxylase, which is overexpressed in tumor cells with an increased ability to invade and metastasize. The inhibition of hydroxylysine release by ivermectin, by analogy, may indicate the suppression of neutrophil invasion into tissue. The increase in the release of phenylalanine in our experiments coincided with the secretion of cathepsin G, which indicates the possible role of this enzyme in the cleavage of phenylalanine. What is the substrate in such a reaction is unknown. We demonstrated that exogenously added angiotensin II (1-8) can serve as a substrate for phenylalanine cleavage. Mass spectrometry revealed the formation of angiotensin II (1-7) in the secretion of neutrophils, which attached to fibronectin in the presence of ivermectin and exogenous angiotensin II (1-8), indicating a possible involvement of ivermectin in the inactivation of angiotensin II.

Experience and perspectives of infection prevention staff of the COVID-19 response in Australian hospitals.

BACKGROUND: Hospital infection prevention and control (IPC) staff have played a key role in adapting and implementing jurisdictional COVID-19 policy during the current pandemic. We aimed to describe the experiences of IPC staff in Australian hospitals during the COVID-19 pandemic to inform future pandemic preparedness plans. METHODS: A cross-sectional study involving an online survey distributed to IPC practitioners employed in Australian hospitals. Survey content was informed by in-depth interviews, and addressed work conditions, redeployed workforce, personal protective equipment, communication, and guidelines. Participants were recruited through the mailing lists of Australasian College of Infection Prevention and Control and the Australasian Society of Infectious Diseases. RESULTS: We received fully or partially completed responses from 160 participants, including 38 (24%) and 122 (76%) with nursing and medical backgrounds, respectively. Respondents reported access to sufficient information about PPE (75%, 114/152), PPE was of sufficient quantity (77%, 117/152) and was of sufficient quality (70%, 106/152). Barriers to infection prevention guideline implementation included frequently changing guidelines (57%, 84/148), timing of updates (65%, 96/148) and contradictory sources of information (64%, 95/148). Respondents described a need for better communication channels from government authorities to hospital IPC teams. All respondents described an increase in workload leading to difficulty completing work (63%, 97/154) and feeling burnt out (48%, 74/154). CONCLUSIONS: These data identify avoidable barriers to implementation of COVID-19 infection prevention guidance in Australian hospitals. These findings can inform future national preparedness strategies.