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.