Discussion
In such an unprecedent pandemy wich affect the global public health and make a serious crisis in every country around the world, there is an ergent need to assess the efficacy of different repurposed and antiviral drugs for treating the patient infected with Covid-19.
Therefor, in this study we evaluate the efficacy of Oseltamivir as a therapeutic option, for confirmed Covid-19 hospitalized patients with mild to sever disease. Oseltamivir is a repurposed approved antiviral drug recommended by CDC for the prevention and treatment of viral influenza infection (Ishaqui et al., 2020), and is one of the therapeutic options considered for Covid-19 patients((Ding, Zhu, & Yao, 2020),(Jiang et al., 2020)).
In one review study in china, revealed that between 96-virus drug and 78 small molecules and after evaluation and compution a complete genomic sequence similarity of virus and chemical structure similarity of drugs, the predicted top three antiviral drugs against SARS-COV-2 are remedesivir, oseltamivir and zanamivir, and after molecular docking showed that these three drugs have higher molecular binding energies with ACE2(Zhou et al., 2020).
Similarly in another study, showed that neuraminidase inhibitors enhances the survival rate of mice in clinically relevant models of sepsis and regulate neutrophil response by inhibition of neuraminidase-mediated neutrophil dysfunction (overactivation) in vivo, resulting in infection control and suggest oseltamivir as it could be repurposed for the treatment of sepsis or sever infections such as Covid-19, and it raised the requirement of the clinically used of neuraminidase inhibitors in sepsis and Covid-19 to explore this hypothesis (Formiga et al., 2020).
In this study, we showed that oseltamivir in combination therapy within the first hours of admission (group 1), was associated with a decreased incidence of ICU admission and mechanical ventilation in compare with control group (group2) which was not statistically significant, and a significant lower mortality rate especially in moderate to sever conditions (subgroup B, p=0.04).
Similar results obtained from a retrospective single center cohort study including 1190 patients with Covid-19 in wuhan, china showed that administration of oseltamivir was associated with a lower rate of mortality in sever patients (Liu et al., 2020).
In addition there are reassuring safety data for use of oseltamivir in pregnant women that can be prescribe during pregnancy (Louchet et al., 2020).
In some studies the efficacy of oseltamivir treatment for Covid-19 patients remain controversial and further studies requirements for evaluating the efficacy of this drug suggested ((Wu et al., 2020),(Ungogo et al., 2021)). Whereas, in another studies showed that oseltamivir did not have efficacy for treatment of Covid-19 patients and was not recommended ((Lam, Lombardi, & Ouanounou, 2020),(Tan et al., 2020),(Sanders, Monogue, Jodlowski, & Cutrell, 2020)).
Since Covid-19 infection is a viral disease, and like most drugs for acute infections, an antiviral may be much more potent if given early, says Stanley Perlman, a coronavirus researcher at the University of Iowa , and he said although remdesivir is the best antiviral drug in many studies, but the big challenge is how we could give an expensive intravenous drug like that to people who walk in with mild symptoms and considering that 85% of patients won’t develop sever disease and need such a drug like it (Kupferschmidt & Cohen, 2020). Similarly in another study showed that early (within 24 hours of fever onset) administration of oseltamivir in combination with antibiotic help a faster improvement in patient’s symptoms in Covid-19 suspected outpatients without hypoxia (Chiba, 2020).
There for an important consideration in the effective management of Covid-19 as a viral infection is to start an antiviral agent in the first days of infection which is the replication phase of the virus (Iranian Ministry of health and Medical Education , deceber 2020).
In our study, we found patients who were treated with oseltamivir in combination therapy within the first hours of their admission, showed a faster recovery and discharge from hospital and have a shorter length of hospital stay in compare with the control group, which was statistically significant (B=1.89, p<0.001) especially in mild conditions (subgroup A, B=2.2, P<0.001).
This may show that immunomodulatory and probable antiviral effects of hydroxychloroquine ((Yao et al., 2020),(Gautret et al., 2020),(Guastalegname & Vallone, 2020)), and antibiotic therapy with Azithromycin with triple therapeutic effects (anti inflammatory, antiviral, antimicrobial)((Mosquera et al., 2018),(Kakeya et al., 2014)) alone may not be effective in treatment of Covid-19 disease in the absence of an effective antiviral drugs against this viral infection, to start and prescribed as soon as possible. So may be oseltamivir as an oral, nonexpensive antiviaral drug from the repurposed drugs which is already approved for other disease and have acceptable safety profile and a few well-known adverse effects, could consider as a therapeutic option for the initial treatment of Covid-19 patients at the first visit in the office or in the health care centers in combination with an oral antibiotic for prevention of probable secondary bacterial infections and an anti inflammatory agent. Thus, we could have a faster recovery of disease, and in this way we could prevent the transmission of the virus from infected patients and progression of the disease in the society for a better control and management of this disease(Agrawal et al., 2020).
In conclusion, oseltamivir in combination with routine regimen therapy was found to be more efficacious as compared to routine regimen alone, in rapid recovery and earlier discharge of hospital, and was associated with lower mortality rate.
The limitation of our study, is the retrospective nature of this study, incomplete medical records that we had to remove a number of patients, small sample size especially for better results in mortality rate, and the patients were not evaluate at the same time and were reviewed in two consecutive months.
Further prospective studies are required to clarify the clinical benefits of oseltamivir in combination therapy and compare oseltamivir with other antiviral drugs for better management and found a well-established gold standard therapy for the treatment of diagnosed Covid-19.