ABSTRACT The current absence of gold-standard or all-aspect favorable therapies for COVID-19 renders a focus on multipotential drugs proposed to prevent or treat this infection or ameliorate its signs and symptoms vitally important. The present well-designed randomized controlled trial sought to evaluate the efficacy and safety of N-acetylcysteine as adjuvant therapy in hospitalized Iranian patients with COVID-19. Four different diets in 60 patients include; Kaletra (lopinavir/ritonavir) + hydroxychloroquine with/without N-acetylcysteine (600 mg TDS) and atazanavir/ritonavir + hydroxychloroquine with/without N-acetylcysteine (600 mg TDS), were administered in the study. At the end of the study, a further decrease in C-reactive protein was observed in groups with N-acetylcysteine (P =0.008), and no death occurred in the atazanavir/ritonavir + hydroxychloroquine + N-acetylcysteine group, showing that the combination of these drugs may reduce mortality. A significant rise in O2 saturation was observed in atazanavir/ritonavir+hydroxychloroquine+N-acetylcysteine group (P <0.05). Accordingly, oral or intravenous N-acetylcysteine, may enhance O2 saturation, blunt the inflammation trend (by reducing C-reactive protein), and reduce mortality in hospitalized patients with COVID-19. The N-acetylcysteine could be more effective as prophylactic or adjuvant therapy in stable and non-severe cases of COVID-19 with a particularly positive role in the augmentation of O2 saturation and faster reduction of the CRP level and inflammation.

Backgrounds: The absence of a gold-standard treatment for COVID-19 infection encourages clinicians to benefit from multipotential medications in the treatment of COVID-19. The current controlled randomized clinical trial tried to evaluate the efficacy and safety of pentoxifylline (PTX) as an adjuvant therapy in moderate to severe COVID-19 infection. Methods: In this randomized controlled clinical trial, two groups of hospitalized patients with moderate to severe COVID-19 infection were randomized by the block randomization method to either receive standard protocol therapy or standard protocol therapy plus pentoxifylline 400 mg TDS for 14 days. Results: The results showed a greater improvement in the proinflammatory biomarkers in the intervention group. Oxygen saturation, hemoglobin, and platelet levels were also improved to a higher level among pentoxifylline recipients. The mortality rate was reported 4% and 32% in the intervention and control groups, respectively. One out 13 patients with severe COVID-19 infection expired in the intervention group, while 20 out of 28 patients expired in the control group, showing about 10 times higher mortality rate compared to the pentoxifylline recipients. Conclusion: Pentoxifylline increased the survival rate of COVID-19 patients and played as a preventive role for COVID-related mortality and morbidity such as acute respiratory distress syndrome.