The experimental antiviral drug remdesivir (manufactured by Gilead) was granted Emergency Use Authorization by the US-FDA in May 2020 for patients hospitalized with severe COVID-1911. Besides US and much of Europe, licensing agreement with manufacturers in Egypt, India, Pakistan, Philippines and Bangladesh that permit the sale of generic version of the drug12,13,14. But at that time, only two randomized clinical trials (RCTs) were completed that compared a 10-day course of remdesivir with placebo. One of the bigger was the National Institutes of Health–sponsored Adaptive COVID-19 Treatment Trial (ACTT-1) on 1063 patients found that those assigned a 10-day course of remdesivir had a shorter recovery time by 4 days (median, 11 vs 15 days) compared with placebo8,9,15. In this study, the mean duration of ICU stay was 11.78 days in RDV-treated patients whereas 18.13 days in FPV-treated patients who survived and improved. But among the death cases, this duration was 12.11 and 14.13 days respectively.
Favipiravir (T-705) is a synthetic prodrug first discovered antiviral active against the influenza virus in Toyoma Chemicals laboratory and has been approved in Japan in 2014 for the management of emerging pandemic influenza. Favipiravir inhibits 53 types of influenza viruses including seasonal flu, swine flu, avian influenza. Over the past few months, different clinical studies have been performed around the world including China, Japan, USA, Saudi Arabia, India to assess the efficacy of favipiravir against SARS-CoV-28,10,16. In various prospective, open-lebel multi centric trial with favipiravir (1600 mg twice daily followed by 600 mg twice daily up to 10 days revealed clinical recovery at day 7 among moderate COVID-19 patients17,18. The main advantages of favipiravir are that it is administered orally and can be given in patients who are symptomatic but not severe enough to be hospitalized. In this study, severely ill COVID-19 patients in ICU were found treated with favipiravir, that might be due to deterioration of condition or exacerbation of comorbid conditions.
Given that d-dimer, ferritin, CRP, INR, NLR, d-NLR, platelet used as predictive biomarkers to identify and differentiate the severity of COVID-19 patients were limited. Yang et al. revealed eight potential factors to identify the progression of the severity19. The applicable thresholds for NLR, d-NLR, PLR, and LMR were observed using the ROC curve. The optimal threshold at 3.3 for NLR showed a superior prognostic option of clinical symptoms to change from mild to severe, which had the maximum of sensitivity and specificity and the largest of AUC. Several reports on the feasibility of either NLR or PLR in predicting prognosis in patients with SARS-CoV-2 infection have been published. In particular, Qu et al. suggested a possible prognostic role of PLR by analyzing the data of a cohort of 30 patients20. Another study by Qin et al. showed a significantly higher NLR in patients with severe forms of COVID-19 in a cohort of 452 hospitalized patients. A higher NLR at hospital admission was associated with a more severe outcome: in particular, a NLR of > 4 was a predictor of admission to the ICU21. Patients with severe disease presented a significantly higher NLR at admission compared with patients with a milder form of COVID-19, which was is in agreement with the present study, where the mean NLR, d-NLR was much higher in all the critically ill patients in ICU with 7.87 in death cases and 3.31 in improved cases who were treated with favipiravir only.
C-reactive protein (CRP) levels are increased in COVID-19 patients and study revealed strong correlation with disease severity and prognosis with median CRP values of approximately 40 mg/L among survivors, while non-survivors had median values of 125 mg/L22.
Among hematological parameters, lymphopenia is clearly associated with disease severity; patients who have died from COVID-19 have had significantly lower lymphocyte counts than survivors. In fact, repletion of lymphocytes may be an important factor for recovery23. Other blood cells including neutrophils, eosinophils, WBC, platelets and CD8 cell counts were partial predictors in discriminating mild from severe COVID-19.
In the present study, the role of two commonly used antivirals (RDV and FPV) in the treatment of COVID-19 patients in ICU revealed not much hope in improving hematological biomarkers in limiting the disease progression. Some independent biomarkers like NLR (7.48 vs 3.31), d-NLR (5.10 vs 2.51) and d-Dimer (0.32 vs 1.10) showed significant variations (p < .00001) in improved cases between RDV and FPV treated patients for 10-day treatment in ICU.