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. 2021 Jul 15;204(2):224-227.
doi: 10.1164/rccm.202104-0833LE.

Therapeutic Application of Alpha-1 Antitrypsin in COVID-19

Felix Ritzmann  1 , Praneeth Chitirala  1 , Nadine Krüger  2 , Markus Hoffmann  2   3 , Wei Zuo  4 , Frank Lammert  1   5 , Sigrun Smola  6 , Naveh Tov  7 , Noga Alagem  7 , Philipp M Lepper  1 , Stefan Pöhlmann  2   3 , Christoph Beisswenger  1 , Christian Herr  1 , Robert Bals  1 ; AAT-in-COVID-19 Study Group
Collaborators, Affiliations

Therapeutic Application of Alpha-1 Antitrypsin in COVID-19

Felix Ritzmann et al. Am J Respir Crit Care Med. .
No abstract available

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Figures

Figure 1.
Figure 1.
Human airway organoids as models to study SARS-CoV-2 infection. (A) TMPRSS2 and ACE2 are expressed in airway organoids as detected by immunohistochemistry. Representative images of organoids stained for TMPRSS2 and ACE2 with corresponding IgG controls are shown. Scale bars: TMPRSS2 column , 40 μm; ACE2 column, 20 μm. (B) AAT blocks the proteolysis of the synthetic peptide Boc-Gln-Ala-Arg-AMC added to airway organoids in culture. Final levels of fluorescence were compared using ANOVA with Tukey post hoc test and significance levels are displayed (***P < 0.001). Data are from three independent experiments. (C) The slopes of the graphs from B were calculated using a linear regression line model (Microsoft Excel, 2021). The slopes of the control group were significantly steeper as compared with the AAT-treated groups as calculated with ANOVA with Tukey post hoc test (***P = 0.001 and ****P < 0.001). (D) Human lung organoids were pretreated for 2 hours with the indicated concentrations of camostat or AAT, inoculated with SARS-CoV-2, and viral titers determined at 24 hours after infection using plaque assay. The infection of five cultures was analyzed. The experiment was repeated with equivalent results. Error bars indicate SD with **P < 0.01 and ***P < 0.001. AAT = alpha-1 antitrypsin; ACE2 = angiotensin-converting enzyme 2; AFU = artificial fluorescence units; ns = not significant; PFU = plaque-forming units; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; TMPRSS2 = transmembrane protease serine 2.
Figure 2.
Figure 2.
Application of AAT (alpha-1 antitrypsin) to patients with coronavirus disease (COVID-19). (A) Development of the respiratory status in all nine patients after the initiation of AAT treatment over time (arrow), World Health Organization severity class: 3 = no oxygen, 4 = oxygen by mask or nasal prongs, 5 = noninvasive ventilation or high-flow oxygen, and 6 = intubation and mechanical ventilation. (B) Overall CRP serum concentrations were decreasing after AAT application (arrow). The green line represents the mean of all nine patients with AAT treatment, and the red line represents the mean of 18 matched control patients with COVID-19. Time point 1 is the last CRP measurement before the initiation of treatment (in treated patients) or the first available CRP measurement in the control patients. Time points 2, 3, and 4 indicate subsequent measurements during the next 10 days. CRP = C-reactive protein.
See this image and copyright information in PMC

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