Hypothesis: Alpha-1-antitrypsin is a promising treatment option for COVID-19

Bai, Xiyuan; Hippensteel, Joseph A.; Leavitt, Alida; Maloney, James P.; Beckham, J. David; Garcia, Cindy; Li, Qing; Freed, Brian M.; Ordway, Diane; Sandhaus, Robert A.; Chan, Edward D.

doi:10.1016/j.mehy.2020.110394

Cited by 52 publications

(56 citation statements)

References 72 publications

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“…The effects of NE may be modulated by protease inhibitors such as serum alpha-1-antitrypsin (serpinA1) to prevent tissue injury and virus activation. Increased serum NE activity was detected during severe COVID-19, despite the functional inhibitory activity of serpinA1 against exogenous soluble NE [ 59 ], thereby revealing a mechanism of resistance of NET-derived NE to serpinA1 that may be relevant during COVID-19 [ 86 ].…”

Section: Nets’ Impact At the Cellular Levelmentioning

confidence: 99%

Patients with COVID-19: in the dark-NETs of neutrophils

et al. 2021

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SARS-CoV-2 infection poses a major threat to the lungs and multiple other organs, occasionally causing death. Until effective vaccines are developed to curb the pandemic, it is paramount to define the mechanisms and develop protective therapies to prevent organ dysfunction in patients with COVID-19. Individuals that develop severe manifestations have signs of dysregulated innate and adaptive immune responses. Emerging evidence implicates neutrophils and the disbalance between neutrophil extracellular trap (NET) formation and degradation plays a central role in the pathophysiology of inflammation, coagulopathy, organ damage, and immunothrombosis that characterize severe cases of COVID-19. Here, we discuss the evidence supporting a role for NETs in COVID-19 manifestations and present putative mechanisms, by which NETs promote tissue injury and immunothrombosis. We present therapeutic strategies, which have been successful in the treatment of immunο-inflammatory disorders and which target dysregulated NET formation or degradation, as potential approaches that may benefit patients with severe COVID-19.

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Section: Nets’ Impact At the Cellular Levelmentioning

confidence: 99%

Patients with COVID-19: in the dark-NETs of neutrophils

et al. 2021

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“…One of them, alpha-1-antitrypsin (AAT) represents an established treatment for AAT deficiency which is manifest in lung damage. A recent paper outlines several reasons why AAT might be an effective treatment in COVID-19 including (among others) the inhibitory effect of AAT on neutrophil elastase [147,148]. Consequently, several clinical trials have been approved to study the efficacy of AAT in COVID-19 related lung disease.…”

Section: Treatmentmentioning

confidence: 99%

Circulating Calprotectin as a Biomarker of COVID-19 Severity

Mähler

Meroni

Infantino

et al. 2021

Expert Review of Clinical Immunology

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Introduction: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although demographic and clinical parameters such as sex, age, comorbidities, genetic background and various biomarkers have been identified as risk factors, there is an unmet need to predict the risk and onset of severe inflammatory disease leading to poor clinical outcomes. In addition, very few mechanistic biomarkers are available to inform targeted treatment of severe (auto)-inflammatory conditions associated with COVID-19. Calprotectin, also known as S100A8/S100A9, MRP8/14 (Myeloid-Related Protein) or L1, is a heterodimer involved in neutrophil-related inflammatory processes. In COVID-19 patients, calprotectin levels were reported to be associated with poor clinical outcomes such as significantly reduced survival time, especially in patients with severe pulmonary disease. Areas covered: Pubmed was searched using the following keywords: Calprotectin + COVID19, S100A8/ A9 + COVID19, S100A8 + COVID-19, S100A9 + COVID-19, MRP8/14 + COVID19; L1 + COVID-19 between May 2020 and 8 March 2021. The results summarized in this review provide supporting evidence and propose future directions that define calprotectin as an important biomarker in COVID-19. Expert opinion: Calprotectin represents a promising serological biomarker for the risk assessment of COVID-19 patients.

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“…In conclusion our study does not suggest any increased risk of SARS-CoV-2 infection or death associated with AATD, but additional prospective studies are needed for severe AATD before definitive conclusions can be made. Ongoing studies, that are exploring the usefulness of AAT augmentation for treatment of SARS-CoV-2 infection, will shed further light on the importance of AAT in this setting 8 , 9 .…”

mentioning

confidence: 99%