INTRODUCTION
Background: The first case of severe acute respiratory coronavirus syndrome (SARS-CoV-2) was reported in late November 2019 in Wuhan, China. By then, many patients had been admitted to the hospital for acute pneumonia of unknown origin. On March 11, the World Health Organization (WHO) announced the outbreak of COVID-19 and declared it to be an epidemic (1, 2). The virus is transmitted through respiratory droplets or aerosols (3). One of the theories concerning the coronavirus pathogenesis is that the virus binds to host cells through angiotensin-converting enzyme 2 (ACE2). ACE2 is expressed by the epithelial cells of the lung, intestine, kidney, and blood vessels (4). Diabetes, ACE inhibitors, and angiotensin II receptor blockers (ARBs), which are used for hypertension control, increase ACE2 expression and COVID-19 risk (4). The symptoms of COVID-19 include dry coughs; malaise; fever; dyspnea; multiorgan failure; acute respiratory distress syndrome (ARDS) requiring mechanical ventilation and oxygen therapy in the intensive care unit (ICU); coagulopathy with thrombosis; systemic manifestations such as sepsis, septic shocks, and multiorgan dysfunction syndrome; and mucocutaneous involvement (5, 6). Therefore, COVID-19 is considered a disease with a thousand faces (7, 8).
Diversity in the clinical manifestations of COVID-19 is related to the interaction between the coronavirus and the immune system (6, 9). Inflammatory responses, cytokine storms, and chemokines are critical issues allied to the complications of COVID-19 (10, 11). About 33% of the patients with COVID-19 require ICU admission, with a mortality rate of 20% reported in some investigations (12, 13). Additionally, a mortality rate of 49.0% has been reported among critical patients with comorbid cardiovascular diseases, hypertension, diabetes, chronic respiratory diseases, or cancer (12). Polymerase chain reaction (PCR) tests of the upper respiratory tract samples, lung computed tomography (CT) scans, and blood tests are accepted by the WHO for the diagnosis of COVID-19 (3, 14). N-acetylcysteine (NAC) is a multipotential drug suggested by the literature for the prevention and treatment of COVID-19 (1, 15-24). NAC is antioxidant glutathione with a wide variety of use in different medical conditions, including loosening thick mucus and treating a wide range of diseases such as acetaminophen overdose, pulmonary disorders, cystic fibrosis, idiopathic pulmonary fibrosis, ARDS, bronchitis, chronic obstructive pulmonary disease, and pneumonia (6, 24). Evidence indicates the important roles of NAC in the prevention and treatment of COVID-19 by regulating oxidative and apoptotic responses, boosting the immune system, reducing cytokines and interleukins in the wake of COVID-19 infection, suppressing viral replication (especially via the mucolytic properties of NAC, diluting the viral load in the respiratory system), preventing and alleviating pulmonary disorders, augmenting oxygenation, supporting the therapeutic course of patients with sepsis hospitalized in the ICU, diminishing comorbidities, decreasing the likelihood of non-pulmonary end-organ damage or failure and liver failure, and facilitating oxygenation and circulation (24-26). COVID-19 can manifest itself through neurological disorders such as Guillain–Barre syndrome, seizure, headache, and stroke (27). NAC is capable of exerting protective effects on the nervous system and helps prevent or treat these manifestations (5). Liver failure can develop in patients with COVID-19 for several reasons, including metabolic acidosis and complications induced by certain drugs such as remdesivir, which is one of the most commonly used drugs in these patients. In this regard, one of the most well-known effects of NAC is the prevention and treatment of hepatotoxicity (28-30).