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).