4. Discussion
The current study provides evidence regarding the efficacy and safety of pentoxifylline in the recovery of hospitalized COVID-19 patients. A total number of 150 patients were selected from two hospitals, Rasool Akram Medical Complex and Firoozgar hospital in Tehran, affiliated to the Iran University of Medical Sciences. Both hospitals were tertiary COVID-19 centers and were following the same protocol in the treatment of COVID positive patients. The trial was conducted during the same period (3-month period) of the second wave of the pandemic in both centers. Responsible physicians were also affiliated with the IUMS. All patients were PCR positive for COVID-19 and hospitalized in the infectious floor and not in ICU.
Demographic characteristics of the patients between the intervention and control groups were similar and no significant differences were detected except for the sex in which the number of male patients was significantly greater in the control group (P=.012); the latter might be due to the higher rate of hospitalization and severe forms of COVID-19 infection in males [23, 24].The socioeconomic statuses of all patients were in the same triers of the society. Regarding the severity of the disease, both groups of patients were struggling with moderate to severe COVID-19 infection at the time of admission. The treatment protocol in both centers was the same except for pentoxifylline that was added to the therapeutic regimen for the intervention group.
A statistically significant drop of proinflammatory biomarkers such as LDH, CRP, and ESR as well as non-statistically significant decreases in CPK were reported at discharge in the intervention group; Since PTX is a methylxanthine derivative, it may reduce the severity of cytokines storm and their consequences [25-27]. Noteworthy, that LDH is a hallmark of COVID-19 severity and disease prognosis. Therefore, decreased LDH in the treatment group can imply the ability of PTX in the reduction of tissue damage [28]. AST level was increased in the intervention group at discharge time; noteworthy, that PTX was extremely metabolized by liver cells and this might be the reason for AST build up in patients who received PTX [29, 30].
The infection signs such as fever, pulse rate, and blood pressure declined after the initiation of the standard protocols for the treatment of COVID infection in both groups; however, the course of decline was more significant in the intervention group treated with pentoxifylline.
Oxygenation and O2 saturation were significantly improved compared before and after the treatment in both intervention and control groups. The anti-inflammatory and immunomodulatory properties of PTX decrease the risk of ARDS in COVID-19 patients with significant lung involvement [26, 31, 32]. On top of that, pentoxifylline was reported to be beneficial in controlling the hypercoagulable state resulting from virus-induced injury to the epithelium [26, 31, 33].
Regarding hospitalization, a significant shorter hospital stay was reported in the treatment group; a mean of 7 vs. 10 days in the intervention and control groups, respectively. Thus, PTX may hasten the recovery process in moderate to severe COVID-19 because of the lower need for intubation and less serious dysregulation of the immune response [34]. Moreover, the mortality rate in the treatment group was statistically lower than the control group; only 4% vs. 32% of patients expired in the treatment and control groups, respectively. The reason can be the beneficial effects of PTX on the respiratory system and lowering tissue damage to heart, kidney, liver, and the brain [33].
CT score for the severity of lung involvement was higher in expired patients of the control group. The CT score was suggested by other studies to be directly related to the mortality of COVID positive patients [35, 36]. In the meanwhile, GCS was significantly more declined during the therapy in the control group, which implied the poorer prognosis and higher morbidity in this group [37, 38].
Overall, PTX is considered being a safe modality in the treatment of various medical conditions. The most common adverse effects reported with PTX were gastrointestinal upset (nausea, vomiting, and abdominal pain) and dizziness [39-41]. Finally, regarding the efficacy of medical agents in the treatment of COIVD-19, it is strongly recommended to prioritize vaccination in respect of their possible side effects because some new subvariants may be emerged with severe consequences even more than the primary subvariants [42-45].