Potential role of methylxanthines as an adjuvant to COVID-19 treatment:
A review of Pentoxifylline and caffeine as the case of any port in the
storm
Abstract
COVID-19 pandemic presents an unprecedented challenge to identify
effective drugs for treatment. Despite multiple clinical trials using
different agents, there is still a lack of specific treatment for
COVID-19. Having the possible role in suppressing inflammation, immune
modulation, antiviral and improving respiratory symptoms, this review
discusses the potential role of methylxanthine drugs like pentoxifylline
and caffeine in the management of COVID-19 patients. COVID-19
pathogenesis for clinical features like severe pneumonia, acute lung
injury (ALI) / acute respiratory distress syndrome (ARDS), and
multi-organ failures are excessive inflammation, oxidation, and cytokine
storm by the exaggerated immune response. Drugs like pentoxifylline have
already shown improvement of the symptoms of ARDS and caffeine has been
in clinical use for decades to treat apnea of prematurity (AOP) in
preterm infants and improve respiratory function. Both pentoxifylline
and caffeine are well-known anti-inflammatory and anti-oxidative
molecules that have already shown to suppress Tumor Necrosis Factor
(TNF-α) as well as other inflammatory cytokines in pulmonary diseases,
and this may be beneficial for better clinical outcomes in COVID-19
patients. Pentoxifylline enhances blood flow, improves microcirculation
and tissue oxygenation, and caffeine also efficiently improves
microcirculation, reduces cardiovascular disease, and an effective
analgesic. There are significant shreds of evidence that proved the
properties of pentoxifylline and caffeine against virus-related diseases
as well. Along with the aforementioned evidences and high safety
profiles, both pentoxifylline and caffeine offer a glimpse of
considerations for future use as a potential adjuvant to COVID-19
treatment. However, additional clinical studies are required to confirm
this speculation.