Clinical effectiveness of lopinavir in the management of Covid-19 infection and prevention.

COVID-19 also known as Coronavirus 2019, is currently declared by WHO as a new pandemic
disease caused by a single-stranded RNA zoonotic virus termed severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) (Lu et al. 2020). The complete viral genome analysis shows that the
virus shares 88% sequence identity to two bat-derived severe acute respiratory syndrome (SARS)-
like coronaviruses, but more distant from severe acute respiratory syndrome coronavirus (SARSCoV) (Lu et al. 2020). Coronavirus is an enveloped and single-stranded ribonucleic acid named
for its solar corona like appearance due to 9-12 nm-long surface spikes (Buja et al. 2020). There
are four major structural proteins encoded by the coronaviral genome on the envelope, one of
which is the spike (S) protein which binds to the angiotensin-converting enzyme 2 (ACE2)
receptor and mediates subsequent fusion between the envelope and host cell membranes to aid
viral entry into the host cell (Bao et al. 2020; Page et al. 2020). The spectrum of COVID-19 ranges
from a mild respiratory illness to a severe disease requiring hospitalization in up to a third of
patients, with frequent progression to acute respiratory distress syndrome (ARDS) and a high
mortality (Guan et al. 2020). Current reports suggest that COVID-19 patients can have a biphasic
clinical course with deterioration following initial improvement, consistent with a delayed and
exaggerated immune activation (Guan et al. 2020; Shi et al. 2020). A virus-induced
hyperinflammatory response has been associated to be a major pathogenic mechanism of ARDS in
these patients through modulation of pulmonary macrophages, dendritic cells and/or neutrophils
(Huang et al. 2020). Indeed, patients with COVID-19 have elevated blood levels of multipleinflammatory cytokines and chemokines (IL-1β, IL-6, IL-7, IL-8, IL-9, IL-10, G-CSF, GM-CSF,
IFN-γ, IP-10, MCP-1, and MIP-1α), and those requiring admittance to an intensive care unit have
even higher levels (Huang et al. 2020; Zhu et al. 2020). The hyperinflammatory response in
COVID-19 shares biological characteristics with macrophage activation syndrome, suggesting that
targeting the innate immune system may be an effective strategy (Bracaglia et al. 2017). Currently,
real-time reverse-transcription–polymerase-chain-reaction (RT-PCR) assay for COVID-19 has
been developed and used in clinics. Although RT-PCR remains the reference standard to make a
definitive diagnose of COVID-19 infection, the high false negative rate which might be associated
with possible virus mutation, and unavailability of RT-PCR assay in many developing countries
might be responsible for future uncontrollable outbreak in the disease. Other tests that play
important role is radiological examinations, especially thin slice chest CT (Zhu et al. 2019). Chest
CT can identify the early phase lung infection and prompt larger public health surveillance and
response systems.