Fragments of alpha-1-antitrypsin in patients with severe COVID-19 and bacterial pulmonary sepsis

Alpha-1-antitrypsin antagonizes COVID-19: a review of the epidemiology, molecular mechanisms, and clinical evidence

“…When AAT phenotype was analyzed temporally, there was an increase in sialylation of the M0 and M1 AAT glycoforms in all those who died and in 59% of those who survived, suggesting that a shift in sialylation was a counterregulatory response to increase anti-elastase activity in these critically ill COVID-19 patients [ 124 ]. Interestingly, the increased protease:anti-protease ratio seen with COVID-19 may be due to cleavage of AAT by proteases, as evinced by increased AAT fragments C-36 (cleavage product of neutrophil elastase) and C-42 (cleavage product of MMP-12) ( Figure 2 ) [ 125 ]. Additionally, cathepsin B may play a role in the hyperinflammatory response of COVID-19 [ 126 ] and AAT inhibits neutrophil elastase induction of cathepsin B in vivo and in vitro ( Figure 2 ) [ 127 ].…”

Plasma levels of α1-antitrypsin-derived C-terminal peptides in PiMM and PiZZ COPD patients

“…We previously demonstrated that the content of urinary peptides differs between COPD patients with PiMM and PiZZ genotypes [12]. More recent studies found that plasma levels of carboxyl (C)-terminal peptides of AAT are significantly elevated in patients with acute respiratory distress syndrome, severe COVID-19, and bacterial pulmonary sepsis [13][14][15]. Since peptides of AAT are generated under inflammatory conditions and COPD is characterized by the persistent systemic inflammation [16], we aimed to investigate whether peptides of AAT are present in plasma of COPD patients with PiMM and PiZZ genotypes.…”