4.1 Current therapies
The most commonly one involves the use of hydroxychloroquine (HCQ) as
the first-line therapy because of its anti-inflammatory and
immunomodulatory effects (Hu et al., 2017). Based on the international
guidelines, HCQ is reported to be utilized either alone or in
combination with other drugs including, systemic corticosteroids,
Tocilizumab (TCZ), macrolide Aazithromycin, antiviral
Lopinavir/Ritonavir and anticoagulant Enoxaparin (Mehra et al., 2020;
Rosenberg et al., 2020). However, the use of HCQ is lately recorded to
have many restrictions due to increased risk of serious cardiac
arrhythmias. Additionally, either HCQ or CQ is no longer authorized by
FDA to treat COVID-19 (Joyce et al., 2013).
Moreover, current COVID-19 treatment protocol also recommends the use of
oral anti-inflammatory steroids,
however they may paradoxically exaggerate COVID-19-associated
neutrophilia (Fukakusa et al., 2005). In addition, due to their local
and systemic harmful adverse effects, steroids may be inappropriate drug
of choice for vulnerable patients with pre-existing hypertension,
diabetes, or cardiovascular diseases, which represent the most
susceptible group to be infected with COVID-19 (Varga et al., 2020).
That pushed clinicians to search for additional or alternative
anti-inflammatory treatments that can efficiently control the
neutrophilic component of COVID-19 apart from steroid related
complications.
TCZ, a humanized monoclonal antibody acted by blocking IL-6 receptors,
has been suggested for COVID-19 patients to suppress the inflammatory
storm and minimize the mortality (Fu et al., 2020). However, some
studies showed that TCZ may effectively reduce both fever and
inflammatory markers, but with no satisfactory clinical outcomes
inferred for the critically ill COVID-19 patients (Campochiaro et al.,
2020; Dastan et al., 2020). As documented, this medication may also
raise both blood pressure and lipid levels, which are considered the
main risk factors exaggerating the severity in COVID-19 patients of
cardiovascular (CV) diseases (Rao et al., 2015). Furthermore,
anti-interleukin therapy is expected to worse the post-COVID-19
pulmonary fibrosis (George et al., 2020; Silva et al., 2020).
As regards azithromycin, various clinical evidences revealed that it
could exert a great role against both Acute Respiratory Distress
Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), that
prompted scientists to strongly suggest it as a potential treatment for
COVID-19. Azithromycin was detected to possess anti-inflammatory and
immunomodulating actions in addition to antiviral properties because of
its ability to minimize the production of pro-inflammatory cytokines
particularly IL-6 and TNF-α, noxious oxidative radicals as well as to
improve T-helper functions. However, the preliminary studies have
demonstrated that using azithromycin should be in caution due to its
potential arrhythmogenic threat, especially in highly risk COVID-19
patients (Pani et al., 2020).
Moreover, provision should be also taken to mitigate the cardiac risk,
especially after adding lopinavir/ritonavir into the current treatment
protocol for COVID-19 (Gérard et al., 2020). Lopinavir acts as anti-HIV
protease inhibitor via inhibiting the action of 3CLpro, thus disrupting
the viral replication and release from host cells. Recentin-vitro study indicates that lopinavir can also exhibit
antiviral activity against SARS-CoV-2, with which ritonavir can be added
as a booster. However, there is a contradictory survey concluded that
the use of lopinavir/ritonavir shows no significant reduction in the
mortality rate within the severely ill COVID-19 patients (Owa and Owa,
2020).