ABSTRACT
COVID-19 is a rapidly growing pandemic with its first case identified during December 2019 in Wuhan, Hubei Province, China. Due to the rampant rise in the number of cases in China and globally, WHO declared COVID-19 as a pandemic on 11th March 2020. The disease is transmitted via respiratory droplets of infected patients during coughing or sneezing and affects primarily the lung parenchyma. The spectrum of clinical manifestations can be seen in COVID-19 patients ranging from asymptomatic infections to severe disease resulting in mortality. Although respiratory involvement is most common in COVID-19 patients, the virus can affect other organ systems as well. The systemic inflammation induced by the disease along with multisystem expression of Angiotensin Convertin Enzyme 2 (ACE2), a receptor which allows viral entry into cells, explains the manifestation of extra-pulmonary symptoms affecting the gastrointestinal, cardiovascular, hematological, renal, musculoskeletal, and endocrine system. To date, many biomarkers reflecting the main pathophysiological characteristics of the disease have been identified and associated with the risk of developing severe disease. Proteolytic enzymes, or proteases, are known to play important roles in the maintenance of pulmonary homeostasis. However, during disease, proteolytic activity can become dysregulated and cause damage to the lung, contributing to the pathology of conditions like cystic fibrosis, chronic obstructive pulmonary disease, asthma, pulmonary fibrosis and ARDS. we first evaluated the status of CTSS in the context of ARDS and models of ARDS. These investigations revealed that CTSS levels and activity were elevated in the lungs of patients with ARDS, and that elevated CTSS activity was also detectable in the plasma of these patients. Altogether, these findings support a role for CTSS in the pathogenesis of ARDS and the fact that Corona virus infects the respiratory system and the severity of the infection increases with the increase in the severity of the inflammation.