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.
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.
Drug: Pentoxifylline
400 mg of pentoxifylline orally TID with the standard COVID-19 protocol of the Egyptian Ministry of Health
Inclusion Criteria:
1. Age 18 to 65 years.
2. COVID-19 hospitalized patients with pneumonia proved by chest X-ray or CT scan.
3. Confirmed infection with COVID-19 virus using RT-PCR or strongly suspected to be
infected with pending confirmation studies.
4. Have acute respiratory distress syndrome (ARDS).
5. Having either peripheral capillary oxygen saturation (SpO2) ≤ 94% ambient air, or a
partial oxygen pressure (PaO2) to fraction of inspired oxygen (FiO2) ratio ≤ 300 mmHg.
Exclusion Criteria:
1. Age greater than 85 years-old
2. Creatinine clearance (CrCl) < 10ml/min.
3. Severe circulatory shock with a dose of norepinephrine higher than 1.0 μg/kg/min.
4. Pregnant women.
Teachers Hospital
Cairo, Please Select, Egypt
Neven Sarhan, PhD, Principal Investigator
Misr International University