Effect of Pentoxifylline on Prognosis of Coronavirus Disease 2019 (COVID- 19) Infection
Condition: Covid19; Corona Virus Infection; Cytokine Storm
MeSH terms: Infections; Communicable Diseases; COVID-19; Coronavirus Infections; Cytokine Release Syndrome
Study type: Interventional

Summary: 
      Coronavirus disease 2019 (COVID-19) remains a threatening pandemic, due to its rapid
      transmission, uncertain risk factors for progression that lead to its lethality and yet
      unsatisfactory antiviral therapy or prophylaxis. The respiratory system remains the most
      frequently affected by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2), with
      patients either presenting mild illness as well as more severe complications such as acute
      respiratory distress syndrome (ARDS) that necessitates admission in Intensive Care Units
      (ICU). Unfortunately, the remaining patients progress to a second phase-called the
      inflammatory stage-featuring ARDS, thromboembolic events, and myocardial acute injury. These
      clinical exacerbation latter predicts poor prognosis associated with an exacerbation of the
      immune system cascade; a phenomenon known as "cytokine storm". In the context of COVID-19,
      the hyper inflammation diagnostic criteria are partly defined. Early studies of patients with
      COVID-19 established independent associations between biomarkers of inflammation, such as
      C-reactive protein, interleukin [IL]-6, ferritin and D-dimer, and severe disease states that
      require respiratory support or result in death.

      The aim of this study was to identify practical blood immune- inflammatory biomarker / ratio
      that could be used alternatively to IL-6 for predicting severity of coronavirus disease 2019
      (COVID- 19) in clinical practice.

      Another aim is to unveil the association of the pro-inflammatory profile as categorized by
      the IL-6 levels in patients infected by SARS-COV-2, with disease severity and outcomes of
      COVID -19.
    

Detailed description: 
      Recent research confirmed that levels of IL-6 seem are associated with COVID-19 induced
      inflammatory response, respiratory failure, needing for mechanical ventilation and/or
      intubation and mortality. The importance of identifying Il-6 as a biomarker lies in the
      potential use of antibody against IL-6 such as tocilizumab, which is currently used in the
      treatment protocol of covid-19. The authors shared an encouraging experience of utilizing
      tocilizumab medication, particularly in patients at risk of developing chemokine storm
      secondary to COVID-19. IL-6, a chemokine, is an important biomarker of inflammation and has
      been shown in studies as an important predictor of severe COVID-19. IL-6 is responsible for
      elevation of acute phase reactants, such as C-reactive protein, serum amyloid A, fibrinogen,
      and hepcidin, and inhibition of albumin synthesis. The dysregulated production of IL-6 has
      been attributed to autoimmunity and chronic inflammation.

      We performed a systematic review and meta analysis to compare IL-6 in severe and non severe
      patients. In clinical practice, it remains crucial to develop a scoring system that includes
      IL-6 to assist clinicians in early recognition of patients at risk for developing severe
      disease.

      Circulating biomarker like neutrophil (NEU)-to-lymphocyte (LYM) ratio (NLR) as well as other
      ratios are used to represent inflammation and the immune status and are considered a
      potential predictor for the prognosis of COVID-19 patients. Interestingly clinical scores
      like the CALL score (C = comorbidity, A= age, L = lymphocyte count, L = lactate dehydrogenase
      (LDH)) have been used for predicting progression towards clinical worsening.

      Adding IL-6 levels to the CALL score proved to improve its predictive power and make
      treatment more appropriate, especially in patients for whom decision whether to treat or not
      with IL-6 inhibitors such as tocilizumab is required. It should be recognized that the
      CALL-IL-6 score could be difficult to reproduce in low- and medium-income countries due to
      costs of IL-6 dosage.

      Aim of the Study

        1. Identify new blood immune inflammatory biomarker / ratio that could be used
           alternatively to IL-6 for predicting severity of coronavirus disease 2019 (COVID- 19) in
           clinical practice.

        2. Evaluate the influence of the pro-inflammatory profile on clinical outcomes and
           therapeutic efficacy as categorized by the IL-6 levels in patients infected by
           SARS-COV-2.

        3. Assess potential associations with other blood inflammatory biomarker and the impact of
           the inflammatory status on clinical outcomes.
    

Intervention name(s): Pentoxifylline
Intervention type(s): Drug
Intervention description(s): 400 mg of pentoxifylline orally TID with the standard COVID-19 protocol of the Egyptian Ministry of Health
Intervention MeSH terms: Pentoxifylline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: COVID-19; Cytokine Storm; Interleukin-6