jmb

J. Microbiol. Biotechnol. (2020), 30(3), 313–324

https://doi.org/10.4014/jmb.2003.03011

Review

Current Status of Epidemiology, Diagnosis, Therapeutics, and Vaccines

for Novel Coronavirus Disease 2019 (COVID-19)
Dae-Gyun Ahn1†, Hye-Jin Shin1†, Mi-Hwa Kim1,2†, Sunhee Lee1, Hae-Soo Kim1, Jinjong Myoung3, Bum-Tae
Kim1*, and Seong-Jun Kim1*
1
Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea
2
Bioenvironmental Science and Toxicology Division, Gyeongnam Branch Institute, Korea Institute of Toxicology, Jinju 52834, Republic of Korea
3
Korea Zoonosis Research Institute and Genetic Engineering Research Institute, Jeonbuk National University, Jeollabuk-do 54896, Republic of Korea

Received: March 6, 2020

Revised: March 20, 2020 Coronavirus disease 2019 (COVID-19), which causes serious respiratory illness such as
Accepted: March 20, 2020
pneumonia and lung failure, was first reported in Wuhan, the capital of Hubei, China. The
First published online: etiological agent of COVID-19 has been confirmed as a novel coronavirus, now known as
March 21, 2020 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is most likely
*Corresponding authors originated from zoonotic coronaviruses, like SARS-CoV, which emerged in 2002. Within a few
S.J.K. months of the first report, SARS-CoV-2 had spread across China and worldwide, reaching a
Phone: +82-42-860-7477
E-mail: sekim@krict.re.kr pandemic level. As COVID-19 has triggered enormous human casualties and serious economic
B.T.K. loss posing global threat, an understanding of the ongoing situation and the development of
Phone: +82-42-860-7023
E-mail: btkim@krict.re.kr
strategies to contain the virus’s spread are urgently needed. Currently, various diagnostic kits
to test for COVID-19 are available and several repurposing therapeutics for COVID-19 have
shown to be clinically effective. In addition, global institutions and companies have begun to
develop vaccines for the prevention of COVID-19. Here, we review the current status of
pISSN 1017-7825, eISSN 1738-8872 epidemiology, diagnosis, treatment, and vaccine development for COVID-19.
Copyright © 2020 by
The Korean Society for Microbiology Keywords: 2019-nCoV, COVID-19, SARS-CoV-2, coronavirus, outbreak
and Biotechnology

Introduction CoV-2” by the International Committee on Taxonomy of

Viruses (ICTV) and other virologists [2].
In December 2019, cases of serious illness causing Coronaviruses are enveloped, positive-sense single-
pneumonia and death were first reported in Wuhan, the stranded viruses ((+)ssRNA virus) belonging to the family
capital of Hubei, China. Soon after, the number of cases Coronaviridae. Most coronaviruses have 8-10 open reading
soared dramatically, spreading across China and worldwide. frames (ORFs). ORF1a and ORF1b are translated into
As of March 25, more than 400,000 cases of the disease have polyprotein 1a (pp1a) and pp1ab, which are processed by
been confirmed with over 18,000 deaths. The causative agent viral proteases to produce 16 non-structural proteins
of the disease has been confirmed as a novel coronavirus containing RNA-dependent RNA polymerase enzyme
(CoV). The World Health Organization (WHO) announced (RdRp). The viral RNA is replicated through transcription
the official name of the disease as “coronavirus disease of a minus-strand template by RdRp. During replication,
2019 (COVID-19)” and now publicly refers to the virus as coronaviruses generate 6-9 subgenomic mRNAs (sgmRNAs),
“the COVID-19 virus” (formerly known as “2019-nCoV”, which lead to translation of accessory and structural
or "Wuhan Coronavirus"). Analysis of the viral genome has proteins from downstream ORFs [3]. Spike (S), envelope (E),
revealed that the new coronaviruse is phylogenetically membrane (M), and nucleocapsid (N) proteins, necessary
close to severe acute respiratory syndrome coronavirus for completion of a viral replication cycle, are translated
(SARS-CoV) [1], the causative agent of a viral outbreak in from sgmRNAs [4].
2002. Thus, the new coronavirus has been named “SARS- Many coronaviruses are known to infect humans and

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314 Ahn et al.

various animals. In general, 15-30% of common colds are

caused by human coronaviruses (HCoVs) including HCoV-
229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1 [5].
However, some coronaviruses from animal reservoirs can
be transmitted to humans causing outbreaks in the human
population. The SARS-CoV outbreak in 2002 originated
from bats in China [6] and the Middle East respiratory
syndrome coronavirus (MERS-CoV) outbreak in 2012 from
dromedary camels, though also likely transmitted from
bats, in the Middle East [7]. Although the origin of the
SARS-CoV-2 outbreak has not yet been identified, it has Fig. 1. Cumulative confirmed cases of COVID-19 in China, as
been reported that SARS-CoV-2 might be transmitted by of 15 March, 2020.
bats [8], snakes [9], or pangolins [10, 11]. Unlike HCoVs, Sudden increase of the cases in China on February 17 is due to the
these zoonotic viruses infect both humans and various change in COVID-19 diagnostic criteria.
animals and cause severe respiratory illnesses such as acute
respiratory distress syndrome (ARDS) and pneumonia, Epidemiology
leading to death [12, 13]. The symptoms of COVID-19 are
more severe in older age groups with comorbidities, while The number of COVID-19 cases reported to the WHO has
allergic diseases, asthma, and chronic obstructive pulmonary been growing since the first report of COVID-19 in December
disease (COPD) are also risk factors [14, 15]. 2019 from the WHO China Country Office [19]. The infection
Since 2000, various zoonotic coronaviruses have been began to spread from the Huanan seafood wholesale market
circulating in the animal reservoir [11, 16]. Particularly, in Wuhan, China, while the exact infection route of the first
MERS became endemic in Saudi Arabia and other Middle case remains unclear. The number of confirmed cases in
Eastern countries [17, 18]. At this point, we cannot exclude the China grew until mid-February 2020. Then, the number of
possibility of other coronavirus outbreaks in the future. The daily new cases in China started to decrease from late-
following is a review of the current status of epidemiology, February 2020 (Fig. 1). A sudden increase of the cases in
diagnosis, therapeutics, and vaccines against COVID-19 China on February 17 is due to the change in COVID-19
and related coronaviruses. diagnostic criteria. At the time of writing (March 19, 2020),

Fig. 2. Global distribution of COVID-19 confirmed cases, as of 15 March, 2020.

Distribution of the confirmed cases of COVID-19 in each country is presented in the diagram.

J. Microbiol. Biotechnol.
 Overview of Outbreak of Novel Coronavirus Disease 2019 (COVID-19) 315

COVID-19 cases continue to be reported globally from over

170 countries. As of March 15, 2020, 153,517 laboratory-
confirmed COVID-19 cases with 5,735 deaths (approximately
3.8% mortality) have been reported according to WHO [20,
21] (Fig. 2).
In the early stages of the global COVID-19 spread, the
cases identified outside of China were mostly travelers
who were infected in China and then traveled to areas
outside of China. Countries outside of China that reported
travel-associated COVID-19 cases were Singapore, Japan,
Republic of Korea, Malaysia, Vietnam, Australia, United
States of America, Germany, etc. [22]. Unfortunately, Fig. 4. Cumulative confirmed cases of COVID-19 in South
COVID-19 has begun to spread domestically in South Korea, as of 15 March, 2020.
Korea, Italy, Iran, and Japan from mid-February 2020 [23] Blue bar represents the cumulative confirmed cases before the
(Fig. 3). Particularly, in the Republic of Korea, the spread of indicated date. Red bar represents the newly confirmed cases at the
COVID-19 had been well managed until mid-February. The indicated date.
number of confirmed cases in South Korea was 31 on
February 18, 2020 [24] and most of these cases were or have mild infections [28-30]. These features may
travelers from China or their close contacts. However, explain the sudden epidemic spreading of the virus.
COVID-19 infections among a religious group in the Daegu
metropolitan area and a nearby hospital triggered a sudden Diagnosis
spread to other major domestic cities in South Korea in
mid-February (Fig. 4). As a result, a week later, the To detect this novel coronavirus, molecular-based
confirmed cases soared to 763 and 74.6% of those cases approaches are the first line of methods to confirm
were tied to the event (as of February 24, 2020) [23]. On suspected cases. Nucleic acid testing is the main technique
March 1, the total number of confirmed cases reached for laboratory diagnosis. Other methods such as virus
3,526, among which 59.5% belonged to the religious group- antigen or serological antibody testing are also valuable
related cases [25]. assays with a short turnaround time for the detection of
The mortality rate of SARS-CoV-2 (3.8%) [20] is lower novel coronavirus infection [31, 32]. As with other emerging
than that of SARS-CoV (10%) [26] or MERS-CoV (37.1%) viruses, the development of methods to detect antibodies
[27], but the number of relative infection cases is more than and viral antigens are started after the identification of the
10 times higher. Accumulating reports revealed that SARS- viral genome.
CoV-2 can be transmitted from people who are asymptomatic The genomic sequence of SARS-CoV-2 was released

Fig. 3. Cumulative confirmed cases of COVID-19 outside of China, as of 15 March, 2020.

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316 Ahn et al.

Fig. 5. A representative diagram showing currently available diagnostic primer sets on SARS-CoV-2 genome.
Numbers represent genome positions according to SARS-CoV-2 isolate Wuhan-Hu-1 (GenBank: MN908947.3). Each primer set for the diagnosis
was indicated by grey arrows.

immediately to public databases after the start of the (N) have become key diagnostic targets for SARS-CoV-2
outbreak in Wuhan, China on January 10, 2020 (Wuhan- identification. Some countries hosting institutions have
Hu-1, GenBank Accession No. MN908947) [33]. The World shared their protocols and provided specific sequences of
Health Organization (WHO) currently recommends that all target primers on the WHO public database [36].
patient samples with suspected SARS-CoV-2 should be In the Republic of Korea, since the first confirmed case of
isolated from respiratory tract specimens (including nasal SARS-CoV-2 on January 20, 2020, the Korea Centers for
and pharyngeal swabs, sputum, or bronchoalveolar lavage Disease Control and Prevention (KCDC) rapidly applied
fluid) then shipped to authoritative laboratories for nucleic WHO recommended RT-PCR assays and approved various
acid amplification diagnostic testing. During international in vitro diagnostic test kits. The diagnostic test kits have
health emergencies, the real-time RT-PCR assay has shown been distributed to public health departments and hospitals
to be a sensitive and specific method to detect respiratory to prevent the COVID-19 spread in communities.
pathogens in patients with an acute respiratory infection
[34]. The presence of SARS-CoV-2 in respiratory specimens Antiviral Therapies
was detected by real-time RT-PCR and next-generation
sequencing. For the rapid development of real-time RT- During the COVID-19 outbreak, some potential antiviral
PCR diagnostic tests, the genome sequence was used to drugs are being urgently administered to patients with
design specific primers and probes to detect the SARS- COVID-19 (Table 1). Those drugs are described in detail
CoV-2 [35]. All assays can use viral RNA extracted from below.
SARS-CoV as positive control. The primers and probes
targeting specific genes of SARS-CoV-2 were used in real- Nucleoside Analogs
time RT-PCR assays as diagnostic tests (Fig. 5). The first
open reading frames (ORF 1a and 1b), RNA-dependent RNA Nucleoside analogs have been used as antiviral agents.
polymerase gene (RdRp), envelope (E), and nucleocapsid Nucleoside analogs generally interfere with cellular

J. Microbiol. Biotechnol.
 Overview of Outbreak of Novel Coronavirus Disease 2019 (COVID-19) 317

Table 1. List of candidate therapeutic agents for SARS-CoV-2 treatment.

Candidate therapeutic Market name Manufacturer Target disease EC50 (COVID-19) Status of clinical trials
Favipiravir Avigan Toyama Influenza 61.88 µM [41] Under clinical trial for COVID-19
(T-705) (ChiCTR2000029548)

Remdesivir Gilead Ebola 0.77 µM [41] Phase II clinical trial for Ebola
(GS-5734) (NCT03719586);
Under phase III clinical trials for
COVID-19 (NCT04252664)

Chloroquine Aralen/Plaquenil Sanofi Malaria 1.13 µM [41] Under clinical trials for
/Hydroxychloroquine COVID-19 (a)

Lopinavir and Ritonavir Kaletra Abbott HIV −b Under clinical trials for SARS [59]
Under clinical trial for COVID-19
(ChiCTR2000029539)

Pegylated interferon Virazole Valeant HBV, HCV 109 µM [41] Under clinical trial for COVID-19
with ribavirin (ChiCTR2000029387)

a
ChiCTR2000029939, ChiCTR2000029935, ChiCTR2000029899, ChiCTR2000029898, ChiCTR2000029868, ChiCTR2000029837, ChiCTR2000029826, ChiCTR2000029803,
ChiCTR2000029762, ChiCTR2000029761, ChiCTR2000029760, ChiCTR2000029740, ChiCTR2000029609, ChiCTR2000029559, and ChiCTR2000029542
b
Undetermined

nucleotide synthesis pathways and cause termination of antiviral agents such as interferon-α (ChiCTR2000029600)
viral genome replication by the accumulating mutations or baloxavir marboxil (ChiCTR2000029544).
and by blocking the entry of incoming natural nucleotides. Among the approved nucleotide analogs, ribavirin is
In a broad spectrum of RNA viruses, nucleoside analogs also a guanine analogue for treatment against hepatitis C
act as inhibitors of viral RNA synthesis. Nucleoside virus (HCV) and respiratory syncytial virus (RSV) infection
analogs target the RNA-dependent RNA polymerase that is and has been used to treat patients with SARS or MERS
responsible for the replication of viral RNA [37-39]. [42-44]. However, the drug showed side effects such as
Favipiravir (T-705) is a guanine analog approved for anemia in high dose treatment. The efficacy and safety of
treatment against influenza virus infection in Japan and the drug are uncertain [43, 44]. For COVID-19 treatment,
also can effectively inhibit replication of Ebola, yellow ribavirin was used in combination therapy with pegylated
fever, chikungunya, norovirus, and enterovirus [40]. A interferon (ChiCTR2000029387) to stimulate innate antiviral
recent study suggested that favipiravir is a potential responses, which was given in much lower doses to
candidate for treatment of SARS-CoV-2 infection showing minimize side effects. The combination therapies with
effective antiviral activities in Vero E6 cells (EC50 = interferon should be monitored carefully.
61.88 μM) [41]. For the treatment of patients with COVID- Remdesivir (GS-5734) is an adenine analog that has a
19, favipiravir was used in combination therapy with other similar chemical structure compared with tenofovir

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318 Ahn et al.

alafenamide, an approved HIV reverse transcriptase cleaved by viral proteases for viral gene expression and
inhibitor [45]. Remdesivir also showed antiviral activity replication. Protease inhibitors prevent viral gene replication
against MERS-CoV (IC50 = 0.074 μM) and SARS-CoV (IC50 by binding to enzymes that are responsible for proteolytic
= 0.069 μM) in human airway epithelial (HAE) cell, and, cleavage [56, 57].
can inhibit MERS-CoV replication in mice [46]. This drug Both lopinavir and ritonavir are protease inhibitors,
has been developed for the treatment of Ebola virus approved as HIV drugs, and have been reported to have
infection and the therapeutic efficacy was confirmed in a antiviral activities against SARS and MERS [58, 59]. For
phase III clinical trial [47]. In the USA, the first SARS-CoV- treatment of SARS-CoV-2, clinical trials (ChiCTR2000029539)
2-infected patient was reported and administered have been initiated to test the antiviral activity of HIV
remdesivir [48]. For the inhibition of SARS-CoV-2, the protease inhibitors in patients. However, the antiviral
antiviral activity of remdesivir was tested in Vero cells efficacy of HIV protease inhibitors in coronavirus proteases
(EC50 = 0.77 μM) [41]. Remdesivir has emerged as the most is debatable.
promising candidate for the treatment of SARS-CoV-2 There is no specific antiviral agent against emerging
infection. Recently, two phase III clinical trials were novel coronavirus even though great efforts to develop
initiated to test remdesivir in patients with SARS-CoV-2 effective antiviral drugs have been made by targeting of
(NCT04252664 and NCT04257656). The therapeutic efficacy virus protease, polymerase, and host proteins following the
and safety of favipiravir and remdesivir still need to be MERS and SARS epidemics.
confirmed by clinical research in patients with SARS-CoV-2. In the Republic of Korea after initial reports of an
emerging novel coronavirus, experts from the government
Chloroquine and academy initiated projects for the screening of potential
antiviral drugs against SARS-CoV-2. These projects are
An approved small-molecule agent, chloroquine is a cheap supported by the Ministry of Science and ICT (MSIT) of
and safe drug for the treatment of malaria and sequesters Republic of Korea [60]. To identify novel treatments for
protons into lysosomes to increase the intracellular pH. patients infected with COVID-19, repurposing of FDA-
Chloroquine also has potential broad-spectrum antiviral approved drugs is also a realistic approach.
activities by inhibiting endosomal acidification, which is
required for virus-host cell fusion [49, 50]. Previous studies Current Status of COVID-19 Vaccine Development
determined the antiviral activity of chloroquine against
SARS, MERS, HIV, Ebola, Hendra, and Nipah viruses in Vaccines are the most effective strategy for preventing
vitro [51-54]. Chloroquine also showed inhibitory effects infectious disease since they are more cost-effective than
against SARS by interfering with glycosylation of the treatment, and reduce morbidity and mortality without
cellular receptor of SARS [52]. A recent in vitro study long-lasting effects [61, 62]. Preventive and therapeutic
revealed that chloroquine is a promising candidate antiviral vaccines will be of fundamental value as the most obvious
agent against SARS-CoV-2 infection in Vero E6 cells way to protect global health [62, 63].
(EC50 = 1.13 μM) [41]. To meet urgent clinical demand, Over the past two decades, three human coronaviruses
chloroquine is now being evaluated in clinical trials (SARS-CoV, MERS-CoV, and SARS-CoV-2) emerged
(ChiCTR2000029609). For the treatment of COVID-19 cases worldwide, causing considerable threat to global health
in China, patients were treated with chloroquine to test the [64]. However, there is still no approved vaccines for
efficacy and safety of this antiviral agent candidate against human coronaviruses. Research groups around the world
SARS-CoV-2 infection. The results of trials demonstrated are accelerating the development of COVID-19 vaccines
that chloroquine inhibits the exacerbation of COVID-19 using various approaches. Precise recognition mechanisms
[55]. Based on this finding, the experts from the government between the virus surface proteins and the host receptors are
and organizer of clinical trials suggested that chloroquine important for understanding of cross-species transmission
is a promising antiviral agent against SARS-CoV-2. and host tropism and for the establishment of animal
models for vaccine development [65]. The spike (S) protein
Protease Inhibitors of coronaviruses is an important target for vaccine
development because it mediates the infection mechanism
Protease inhibitors are attractive candidates for antiviral through receptor binding of host cells [65-67]. The S protein
drugs. The viral genome encodes polyproteins which are of human infectious coronaviruses recognizes various host

J. Microbiol. Biotechnol.
 Overview of Outbreak of Novel Coronavirus Disease 2019 (COVID-19) 319

Table 2. Host tropisms and receptors of coronaviruses. response by introducing GSK’s adjuvant system to S-
Virus Host Cellular receptor Reference Trimer [73].
Alphacoronavirus The University of Queensland is developing subunit
HCoV-229E Human APNa [96] vaccines using the “molecular clamp,” a transformative
HCoV-NL63 Human ACE2b [97] technology [74]. A molecular clamp is a polypeptide that
FCoV Feline APN [98]
stabilizes a surface protein and improves recognition of the
correct antigen, thereby inducing stronger immune
CCoV Canine APN [98]
responses. This vaccine platform can be readily applicable
TGEV Porcine APN [99]
to a wide range of enveloped viruses and their product can
Betacoronavirus
be rapidly manufactured [74]. The University of Queensland
SARS-CoV Human ACE2 [100]
has applied GSK’s adjuvant system for the development of an
MERS-CoV Human DPP4c [101] effective vaccine and entered partnership with CEPI [73, 75].
HCoV-OC43 Human 9-O-acetylated sialic acid [102]
HCoV-HKU1 Human 9-O-acetylated sialic acid [103] DNA Vaccine
MHV Mouse CEACAM d
[104] DNA vaccines represent an innovative approach by direct
a
Aminopeptidase N injection of plasmids encoding the antigens, accompanied
b
Angiotensin-converting enzyme 2 (ACE2) with a wide range of immune responses [76]. These
c
Dipeptidyl peptidase 4 (DPP4/CD26) advantages are applied with prophylactic vaccines and
d
Carcinoembryonic antigen-related cell adhesion molecules (CEACAM) therapeutic vaccines. Recently, various DNA vaccine
platforms have been developed to improve the efficacy of
receptors, including ACE2, APN, and DPP4 (Table 2). vaccines by using electroporation to deliver plasmids and
SARS-CoV-2 and SARS-CoV use ACE2 as a receptor. The adding adjuvant to enhance the immune responses [77].
homology between SARS-CoV-2 and SARS-CoV is Inovio Pharmaceuticals, in collaboration with Beijing
approximately 75% for the spike (S) protein-RBD [68]. The Advaccine Biotechnology, has started pre-clinical trials for
S1 subunit of S protein contains a receptor-binding domain DNA vaccine (INO-4800) against COVID-19 [78]. INO-4800
(RBD) and the S2 subunit is necessary for membrane fusion induces activation of T cells by delivering DNA plasmids
between host cells and viruses [12, 69]. The following that express the SARS-CoV-2 spike [79]. This vaccine platform
describes the current status of vaccine development against has advantages that can produce therapeutic antibodies
COVID-19 through various approaches. and activate immune cells by delivering the vaccines
intradermally into the patient. Inovio Pharmaceuticals is
Recombinant Subunit Vaccine preparing for phase I trials in the U.S.A. and China with
In general, subunit vaccines are advantageous over other support from the Coalition for Epidemic Preparedness
types of vaccines in that they are highly safe and have Innovations (CEPI) [80].
fewer side effects by inducing the immune system without
introducing infectious viruses [12]. Subunit-based vaccine mRNA Vaccine
development studies have also reported enhancement of T mRNA vaccines are rapidly developing technologies to
cell immune responses and generation of high titer treat infectious diseases and cancers. mRNA-based vaccines
neutralizing antibodies in vivo [70, 71]. contain mRNAs encoding the antigens, which are translated
Clover Biopharmaceuticals is pre-clinical testing a at the host cellular machinery by vaccination [61, 81]. mRNA
recombinant subunit vaccine based on the trimeric S vaccines have advantages over conventional vaccines, by
protein (S-Trimer) of the SARS-CoV-2 [72]. The S protein the absence of genome integration, the improved immune
contains three S1 heads and a trimeric S2 stalk [67]. Clover responses, the rapid development, and the production of
Biopharmaceuticals confirmed the generation of a native- multimeric antigens [81].
like trimeric viral spike in mammalian cell culture-based Moderna, Inc. has started phase I clinical trials for
expression system and the detection of antigen-specific mRNA-1273, an mRNA vaccine, encoding viral spike (S)
neutralizing antibodies in the sera of fully-recovered protein of SARS-CoV-2. It was designed in collaboration
COVID-19 patients [72]. Recently, Clover Biopharmaceuticals with the National Institute of Allergy and Infectious
and GSK announced a partnership to improve immune Diseases (NIAID) [82]. In contrast to conventional vaccines

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320 Ahn et al.

which are produced in a cell culture system, Moderna’s Summary

mRNA vaccine is designed in silico, which enables the
rapid development and evaluation of vaccine efficacy [83]. Despite tremendous global efforts to contain SARS-CoV-2,
Moderna Inc. is preparing a phase I study with financial the virus’s spread has reached a pandemic level. Although
support from CEPI [75]. the development of therapeutics and vaccines for the
treatment of COVID-19 is still in its early stage, there has
Other Vaccine Approaches been some significant progress in the research area from
Genexine Inc. is developing a COVID-19 vaccine using complete genome sequencing of SARS-CoV-2 to the
Hyleukin-7 platform technology [84]. Hyleukin-7 platform beginning of clinical trials with COVID-19 vaccines.
enhances the immune responses by fusion of interlekin-7 Continued international efforts are required to solve the
(IL-7) to hyFc, designed to hybridize IgD and IgG4 for remaining unanswered questions about the novel
long-acting effects of Fc fusion proteins [84, 85]. IgD has a coronavirus, including the animal sources of infection,
flexible hinge structure that maximizes biological activity transmissibility, and virulence of the virus.
of Fc-fusion protein. IgG4 has an unexposed junction site Rapid complete genome analysis of SARS-CoV-2 and
that minimizes adverse immunogenicity by preventing international sharing of the information have so far allowed
antibody-dependent cellular cytotoxicity (ADCC) and us to produce faster and more accurate diagnostic tools.
complement-dependent cytotoxicity (CDC) [86, 87]. Genexine Currently, most of the developed diagnostic tools are qRT-
Inc. has reported the improved vaccine efficacy showing PCR-based diagnostic tools, which require longer sample
the accumulation of pulmonary T cells and the increase of preparation and analysis time, delaying necessary actions
plasmacytoid dendritic cells by treatment of Fc-fused IL-7 for COVID-19 patients in the field. As COVID-19 spreads
in influenza A virus infection model [88]. continuously all over the world, the development of rapid
Together with the vaccine technologies described above, diagnostic methods, which can be tested in the field, is
some known hurdles also must be overcome for successful urgently required.
vaccine development. Antibody-dependent enhancement It has been reported that some drugs are known to be
(ADE) of disease is a phenomenon in which virus-specific effective for the treatment of COVID-19 patients. However,
antibodies facilitate virus entry into the host cell via the Fc- the lack of clinical evidence may lead to unpredictable
receptor pathway, leading to enhanced virus infection [89]. clinical prognosis. At the moment, quick screening of
In other words, the antibodies generated by vaccination therapeutic agents for the repurposing of FDA-approved
can promote viral infectivity. ADE effects have been and well-characterized drugs may be a more practical
reported in some vaccines against Dengue and Zika viruses approach in epidemics. Considering the seriousness of the
[90]. Although the occurrence of ADE of SARS-CoV-2 has recent outbreaks of zoonotic coronaviruses, therapeutic
not yet been clearly demonstrated, potential ADE of MERS- agents for pan-coronaviruses should be developed to cope
CoV and SARS-CoV was observed in an in vitro model with future outbreaks.
system [91, 92]. Various approaches have been introduced Together with the development of diagnostics and
in vaccine development to avoid adverse effects by ADE. therapeutics, various pharmaceutical companies and
For example, nucleocapsid (N) protein maybe an alternative institutions have announced the beginning of vaccine
target to overcome ADE. Since N protein is not a virus development as well. However, enormous funds and long-
surface protein, antibodies induced by N protein-based term studies are required for clinical research for the
vaccine will not be able to facilitate virus entry. DNA development of vaccines against infectious diseases. Despite
vaccine candidates targeting SARS-CoV N protein as an the serious public health threat caused by viral outbreaks,
immunogen can generate N-specific humoral and cellular the commercial markets for vaccines, particularly against
immune response [93]. Another major hurdle for vaccine emerging infectious diseases, are quite limited due to the
development is higher mutation rates of RNA viruses high cost and time required for vaccine development and the
compared to DNA viruses, resulting in higher genetic uncertainty of profitability. This development environment
diversity [94]. Moreover, the RBD of the S protein is the of vaccines has created a huge gap between academic
most variable region in the coronavirus genome [95]. research and commercial markets. Thus, well-organized,
Therefore, the ADE and the higher genetic diversity should long-term research programs should be established with
be considered as important factors for vaccine design and internationally supported projects for the development of
antibody-based drug development against SARS-CoV-2. vaccines against emerging infectious diseases. For this reason,

J. Microbiol. Biotechnol.
 Overview of Outbreak of Novel Coronavirus Disease 2019 (COVID-19) 321

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Korean government (MSIP) (No. CRC-16-01-KRICT). Clinical course and outcomes of critically ill patients with
SARS-CoV-2 pneumonia in Wuhan, China: a single-
Conflict of Interest centered, retrospective, observational study. Lancet Respir.
Med. pii: S2213-2600(20)30079-5.
The authors have no financial conflicts of interest to 15. Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, et
declare. al. 2020. Clinical characteristics of 140 patients infected
with SARS-CoV-2 in Wuhan, China. Allergy doi: 10.1111/
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