The novel coronavirus disease (COVID-19) is caused by a virus (SARS-Cov-2) and is known for inducing multisystem organ dysfunction associated with significant morbidity and mortality. Current therapeutic strategies for COVID-19 have failed to effectively reduce mortality rate, especially for elderly patients. A newly developed vaccine against SARS-Cov-2 has been reported to induce the production of neutralizing antibodies in young volunteers. However, the vaccine has shown limited benefit in the elderly, suggesting an age-dependent immune response. As a result, exploring new applications of existing medications could potentially provide valuable treatments for COVID-19. N-acetylcysteine (NAC) has been used in clinical practice to treat critically ill septic patients, and more recently for COVID-19 patients. NAC has antioxidant, anti-inflammatory and immune-modulating characteristics that may prove beneficial in the treatment and prevention of SARS-Cov-2. This review offers a thorough analysis of NAC and discusses its potential use for treatment of COVID-19.

Short-term intubation in healthy patients resulted in significant tracheal inflammation. Involvement of the innate immune system as documented in the present study provides information that may help to better understand the pathophysiologic characteristics of subglottic stenosis and other endotracheal injuries secondary to endotracheal intubation.

In the absence of infection, the pathophysiology of endotracheal tube-induced sore throat pain is unclear. Activated neutrophils release elastase, reactive oxygen species, and inflammatory cytokines known to contribute to neuropathic pain. Sterile tissue injury can cause the release of damage-associated molecular patterns such as mitochondrial DNA that promote neutrophil activation. We hypothesized that endotracheal tube-induced sore throat pain is linked to mitochondrial DNA-mediated neutrophil inflammation. A nonrandomized prospective survey for sore throat pain was conducted in 31 patients who required short-term intubation and had no evidence of upper airway infection. Patterns of neutrophil abundance, activation, and mitochondrial DNA levels were analyzed in tracheal lavage fluid following intubation and prior to extubation. Thirteen of 31 patients reported sore throat pain. Sore throat patients had high neutrophilia with elevated adhesion molecule and TLR9 expression and constitutive reactive oxygen species generation. Tracheal lavage fluid from sore throat patients accumulated mitochondrial DNA and stimulated neutrophils to release mediators associated with pain in a TLR9- and DNAse-dependent fashion. Endotracheal tube-induced sore throat is linked to the release of mitochondrial DNA and can drive TLR9-mediated inflammatory responses by neutrophils reported to cause pain. Mitigating the effects of cell-free mitochondrial DNA may prove beneficial for the prevention of endotracheal tube-mediated sore throat pain.

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Tracheitis secondary to placement of an endotracheal tube (ETT) is characterized by neutrophil accumulation in the tracheal lumen, which is generally associated with epithelial damage. Mitochondrial DNA (mtDNA), has been implicated in systemic inflammation and organ dysfunction following trauma; however, less is known about the effects of a foreign body on local trauma and tissue damage. We hypothesized that tracheal damage secondary to the ETT will result in local release of mtDNA at sufficient levels to induce TLR9 and NF‐κB activation. In a swine model we compared the differences between uncoated, and chloroquine (CQ) and N‐acetylcysteine (NAC) coated ETTs as measured by tracheal lavage fluids (TLF) over a period of 6 h. The swine model allowed us to recreate human conditions. ETT presence was characterized by neutrophil activation, necrosis, and release of proinflammatory cytokines mediated by TLR9/NF‐κB induction. Amelioration of the tracheal damage was observed in the CQ and NAC coated ETT group as shown in tracheal tissue specimens and TLF. The role of TLR9/NF‐κB dependent activity was confirmed by HEK‐Blue hTLR9 reporter cell line analysis after coincubation with TLF specimens with predetermined concentrations of NAC or CQ alone or TLR9 inhibitory oligodeoxynucleotide (iODN). These findings indicate that therapeutic interventions aimed at preventing mtDNA/TLR9/NF‐κB activity may have benefits in prevention of acute tracheal damage.