Summary Understanding Covid‐19 pathophysiology is crucial for a better understanding of the disease and development of more effective treatments. Alpha‐1‐antitrypsin (A1AT) is a constitutive tissue protector with antiviral and anti‐inflammatory properties. A1AT inhibits SARS‐CoV‐2 infection and two of the most important proteases in the pathophysiology of Covid‐19: the transmembrane serine protease 2 (TMPRSS2) and the disintegrin and metalloproteinase 17 (ADAM17). It also inhibits the activity of inflammatory molecules, such as IL‐8, TNF‐α, and neutrophil elastase (NE). TMPRSS2 is essential for SARS‐CoV‐2‐S protein priming and viral infection. ADAM17 mediates ACE2, IL‐6R, and TNF‐α shedding. ACE2 is the SARS‐CoV‐2 entry receptor and a key component for the balance of the renin‐angiotensin system, inflammation, vascular permeability, and pulmonary homeostasis. In addition, clinical findings indicate that A1AT levels might be important in defining Covid‐19 outcomes, potentially partially explaining associations with air pollution and with diabetes. In this review, we focused on the interplay between A1AT with TMPRSS2, ADAM17 and immune molecules, and the role of A1AT in the pathophysiology of Covid‐19, opening new avenues for investigating effective treatments.
The ongoing outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or 2019 novel coronavirus (2019-nCoV) infection was declared as a public health emergency of international concern by the World Health Organization (WHO) on 30 th January 2020. However, the pandemic started in 2019 in the city of Wuhan, Hubei Province, China 1 , and since then it has had consequences for health systems and the international economy 2 . Several measures to reduce the person-to-person transmission of COVID-19 have been taken by several countries to control the current outbreak 3 . The main measures being implemented differently by many countries around the world are the following: social distancing by closing public places as well as schools and universities 4 , travel restrictions or block traffic outside of defined areas 2,4 , quarantine of confirmed and possibly infected individuals and separation of persons with contagious diseases from the healthy ones, defined as isolation 5 .The epidemic of SARS-CoV-2 has become a great public health challenge in several countries around the world. Clinical activities are decreasing after implementation of measures to control the viral transmission, meaning that only dental care remains for urgent patients under the premise of suitable protection measures 6 . Reduced clinical activities can have diagnostic consequences, especially for cancer diagnosis, as an exponential increase in delayed diagnoses also increases in mortality rates 6 .
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