Introduction
A novel coronavirus, recognized as severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2), is the pathogen resulting in the 2019-2020
viral pneumonia outbreak of coronavirus disease 2019 (COVID-19) (Q. Li
et al., 2020; F. Wu et al., 2020; P. Zhou et al., 2020; N. Zhu et al.,
2020). Since then, the novel coronavirus (COVID-19) has been spread
around the world and has continued to negatively affect the global
public health and economies. COVID-19 is a brand-new respiratory disease
triggered by SARS-CoV-2, a novel enveloped RNA β-coronavirus (N. Zhu et
al., 2020). Coronavirus is a lipid enveloped, positive-sense and
single-stranded RNA virus. Under the electron microscope, the virus has
protrusions that resemble the corona, and looks like a crown, so it is
called coronavirus. The clinical manifestations of SARS-CoV-2 are mainly
fever, cough, occasional dyspnea, invasive bilateral lung pneumonic
infiltrates, and other severe complications(C. Huang et al., 2020).
Acute respiratory distress syndrome (ARDS) is a common complication of
severe viral pneumonia, including severe acute respiratory syndrome
coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus
(MERS-CoV) (Channappanavar & Perlman, 2017), which are the fatal
coronavirus infections that have occurred over the past two decades. A
high sequence identity between SARS-CoV-2 and SARS-CoV is known by gene
sequence (Xiaolong Tian et al., 2020). The genome of SARS-CoV-2
partially resembles SARS-CoV (82%) and MERS-CoV (50%) (Chan et al.,
2020), both of which are of bat origin. Therefore, bats are thought to
be the most probable animal hosts of SARS-CoV-2. However, due to the
existence of natural ecological isolation, the probability of bat
coronovirus ((BatCoV)-ZC45, BatCoV-RmYN02, and BatCoV-RaTG13) infecting
directly to humans is very low, so there may exist other mammalian
species act as intermediate hosts. Pangolins is reported as the possible
intermediate hosts due to approximately 85.5%–92.4% similarity in
their genome with COVID-19 (Lam et al., 2020).
This review summarizes the clinical manifestations, epidemiology, and
the infection mechanism of SARS-CoV-2. We found that hACE2 plays an
important role in the infection process, which also provides new
research directions for potential therapeutic targets. This study
highlights the treatment of COVID-19. There is no vaccine or effective
antiviral treatment against COVID-19 presently. Novel therapeutics
continue to be developed with the emergence of viruses. This article
introduces potential drug therapy (i.e. remdesivir, ribavirin,
Lopinavir/ritonavir, chloroquine, chloroquine phosphate, Arbidol, and
traditional Chinese medicine) and immunotherapy (i.e. IL-6 or vaccines)
for the treatment of COVID-19.
The clinicalmanifestations and
epidemiology of COVID-19
The COVID-19 disease has reached pandemic status with the rapid spread
worldwide. The threat of the SARS-COV-2 virus has developed rapidly
since the first cluster case appeared. However, the result from
phyloepidemiologic analyses suggested that the root of the SARS-COV-2
virus is not the Huanan market; they show that the virus was imported
from elsewhere and then boosted in the market due to the large
population (Peng Zhou et al., 2020). The epidemic curve of COVID-19
shows a mixed epidemic pattern. Because the epidemic caught up with the
Spring Festival, the epidemic began in mid-to-late January. Early cases
suggested that there was a continuing common source. In the South China
seafood wholesale market, there may be a spillover of zoonotic diseases.
Later, the increasing number of infected health care workers suggested
that person-to-person transmission occurs mainly through droplet or
contact transmission (”Clinical and virologic characteristics of the
first 12 patients with coronavirus disease 2019 (COVID-19) in the United
States,” 2020; Phan et al., 2020; Rothe et al., 2020; N. Zhu et al.,
2020). The latest report showed that the SARS-COV-2 virus was detected
positive in the gastrointestinal tract, saliva, and urine.
Most current published data come from China, despite the severe
situations around the world, and provides first-hand information on the
epidemiology of COVID-19. The high-level details of patient from 72,314
cases, including patient characteristics, severity of manifestations and
survival, are reported by the Chinese Center for Disease Control and
Prevention; suspected (22%), clinical diagnosed (15%), asymptomatic
(1%), and confirmed (62%) COVID-19 cases (Wu & McGoogan, 2020). Most
of the confirmed cases (75%) were confirmed in Hubei and were
predominantly identified by the degree of symptoms, most (87%) were
mild, defined by no or mild pneumonia, 14% were severe with significant
infiltrates or signs of dyspnea, and 5% were severe, with distinct
syndromes of respiratory failure (e.g. mechanical ventilation), shock,
or multiple system organ failure.
The resistance capacity of children to infection is better than adults
or are rarely symptomatic. The report showed that 87% of the cases were
between 30-79 years old, 8% were 20-29 years old, 3% were ≥ 80 years
old, 1% were 10 -19 years old, and 1% were ≤ 9 years old (Wu &
McGoogan, 2020). Early data from the U.S. Centers for Disease Control
and Prevention showed that in 4,226 confirmed cases with symptoms or
exposure, only 5% occurred in those ˂ 20 years of age (D. Wang et al.,
2020; Wu & McGoogan, 2020). A study also shows that children are less
susceptible to SARS-CoV-2, which may result from the maturity and
function of ACE2 in children lower than that in adult (Cristiani et al.,
2020). The total case fatality rate of the 44,672 confirmed cases was
2.3%, among which, there are no death cases for patients ≤ 9 years old,
the case fatality rate for patients aged 70 to 79 years was only 8.0%,
and the case fatality rate for 80 years old and above was 14.8%. There
were no reports of death in mild or severe cases, but the fatality rate
of critical cases was 49.0%. Patients with hidden diseases have a high
case fatality rate, of which for cardiovascular disease is 10.5%,
diabetes is 7.3%, chronic respiratory disease is 6.3%, hypertension is
6.0%, and cancer is 5.6%. Therefore these conditions are risk factors
for SARS-CoV-2 infection, which is consistent with the conclusions of
138 cases reported from Wuhan Central South University (Qun Li et al.,
2020). Compared with SARS and MERS, the total mortality of COVID-19 is
higher, which may result from its larger base. The first confirmed case
of COVID-19 in the United States, which has now surpassed other
countries in the absolute number of cases, was confirmed on January 20,
2020. In contrast, the United States shows the reflecting experience
with COVID-19 from a few published data, which is worth learning from.
The commonest symptoms reported were fever (up to 90%), then developing
into cough, fatigue, sputum production, and shortness of breath (Guan,
Ni, Hu, Liang, Ou, He, Liu, Shan, Lei, Hui, Du, Li, Zeng, Yuen, Chen,
Tang, Wang, Chen, Xiang, Li, Wang, Liang, Peng, Wei, Liu, Hu, Peng,
Wang, Liu, Chen, Li, Zheng, Qiu, Luo, Ye, Zhu, & Zhong, 2020). Less
common symptoms, including headache, myalgia, sore throat, nausea,
vomiting, and diarrhea may occur (N. Chen et al., 2020; C. Huang et al.,
2020; D. Wang et al., 2020). However, only 43.8% of COVID-19 patients
developed fever initially, which progressed to 87.9% after
hospitalization (Guan, Ni, Hu, Liang, Ou, He, Liu, Shan, Lei, Hui, Du,
Li, Zeng, Yuen, Chen, Tang, Wang, Chen, Xiang, Li, Wang, Liang, Peng,
Wei, Liu, Hu, Peng, Wang, Liu, Chen, Li, Zheng, Qiu, Luo, Ye, Zhu, &
Zhong, 2020). Therefore, if the surveillance method focuses on fever
detection, patients with no fever or who are asymptomatic may be a
hidden source of infection. A recent study (n = 214) concluded that, in
addition to systemic and respiratory symptoms, of total patients with
COVID-19, 36.4% develop neurological symptoms (Mao et al., 2020). The
latest report from the American Association of Otolaryngology shows that
anosmia and dyspepsia have been highlighted as possible symptoms of the
disease. Additionally, most cases show differential results between
males and females, suggesting that males are more susceptible to
SARS-CoV-2 infection resulting from the innate X-chromosome, sex
hormones, and adaptive immunity (Jaillon, Berthenet, & Garlanda, 2019).
Presently, the common methods for diagnosis of SARS-CoV-2 are chest
radiographs and nucleic acid detection. The chest computed tomography
(CT) was abnormal in 87% of patients at the time of admission, and the
typical chest CT for COVID-19 pneumonia was the initial small pleural
ground glass turbidity gradually becoming larger with insane-paving
pattern and consolidation. The lesions were gradually absorbed after two
weeks of growth, leaving a large number of patients with turbidity and
subpleural parenchyma in the recovery phase. However, the latest report
suggests the complexity of disease control due to patients with normal
imaging performance on initial presentation; which occurs in severe and
non-severe patients.
Moreover, the common lab derangements on admission included lymphopenia,
elevations in C-reactive protein (CRP), lactate dehydrogenase, liver
transaminases, and D-dimer. It is worth noting that procalcitonin is
rarely elevated. The considerable decrease in the total number of
lymphocytes is an effective sign, which developed as an indicator for
the diagnosis of SARS-CoV-2 infection; it indicates the consumption of
immune cells and the impairment of cellular immune function (N. Chen et
al., 2020). Another report noted elevations in other inflammatory
markers, such as ferritin, interleukin (IL)-6, and erythrocyte
sedimentation rate (Arentz et al., 2020; Guo et al., 2020; D. Wang et
al., 2020; C. Wu et al., 2020; F. Zhou et al., 2020).