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].