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COVID-19: What has been learned and to be learned about the novel coronavirus disease

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The outbreak of Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), has thus far killed over 3,000 people and infected over 80,000 in China and elsewhere in the world, resulting in catastrophe for humans. Similar to its homologous virus, SARS-CoV, which caused SARS in thousands of people in 2003, SARS-CoV-2 might also be transmitted from the bats and causes similar symptoms through a similar mechanism. However, COVID-19 has lower severity and mortality than SARS but is much more transmissive and affects more elderly individuals than youth and more men than women. In response to the rapidly increasing number of publications on the emerging disease, this article attempts to provide a timely and comprehensive review of the swiftly developing research subject. We will cover the basics about the epidemiology, etiology, virology, diagnosis, treatment, prognosis, and prevention of the disease. Although many questions still require answers, we hope that this review helps in the understanding and eradication of the threatening disease.
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Int. J. Biol. Sci. 2020, Vol. 16
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International Journal of Biological Sciences
2020; 16(10): 1753-1766. doi: 10.7150/ijbs.45134
Review
COVID-19: what has been learned and to be learned
about the novel coronavirus disease
Ye Yi, Philip N.P. Lagniton, Sen Ye, Enqin Li and Ren-He Xu
Institute of Translational Medicine, and Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Taipa, Macau, China.
Corresponding author: Ren-He Xu, Faculty of Health Sciences, University of Macau, Taipa, Macau, China. Tel: 853-8822-4993; Fax: 853-8822-8345; Email
address: renhexu@um.edu.mo.
© The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).
See http://ivyspring.com/terms for full terms and conditions.
Received: 2020.02.20; Accepted: 2020.02.29; Published: 2020.03.15
Abstract
The outbreak of Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome (SARS)
coronavirus 2 (SARS-CoV-2), has thus far killed over 3,000 people and infected over 80,000 in China and
elsewhere in the world, resulting in catastrophe for humans. Similar to its homologous virus, SARS-CoV, which
caused SARS in thousands of people in 2003, SARS-CoV-2 might also be transmitted from the bats and causes
similar symptoms through a similar mechanism. However, COVID-19 has lower severity and mortality than
SARS but is much more transmissive and affects more elderly individuals than youth and more men than
women. In response to the rapidly increasing number of publications on the emerging disease, this article
attempts to provide a timely and comprehensive review of the swiftly developing research subject. We will
cover the basics about the epidemiology, etiology, virology, diagnosis, treatment, prognosis, and prevention of
the disease. Although many questions still require answers, we hope that this review helps in the understanding
and eradication of the threatening disease.
Key words: Coronavirus, pneumonia, outbreak, SARS-CoV-2, COVID-19
Introduction
The Spring Festival on January 25, 2020 has
become an unprecedented and unforgettable memory
to all Chinese who were urged to stay indoors for all
the holiday and for many weeks after due to the
outbreak of a novel viral disease. The virus is highly
homologous to the coronavirus (CoV) that caused an
outbreak of severe acute respiratory syndrome
(SARS) in 2003; thus, it was named SARS-CoV-2 by
the World Health Organization (WHO) on February
11, 2020, and the associated disease was named CoV
Disease-19 (COVID-19) [1]. The epidemic started in
Wuhan, China, and quickly spread throughout the
entire country and to near 50 others all over the world.
As of March 2, 2020, the virus has resulted in over
80,000 confirmed cases of COVID-19, with more than
40,000 patients discharged and over 3,000 patients
who died. WHO warns that COVID-19 is “public
enemy number 1” and potentially more powerful
than terrorism [2].
According to PubMed (https://www.ncbi.nlm.
nih.gov/pubmed/), in less than two months, over 200
papers have been published on COVID-19 including
its virology, epidemiology, etiology, diagnosis, and
treatment since the first report on January 7, 2020 that
determined the sequence of the virus isolated from
multiple patients [3]. This review attempts to
summarize the research progress in the new and
swiftly developing subject area. Whenever possible,
we will try to compare COVID-19 with SARS and
another CoV-caused disease, Middle East respiratory
syndrome (MERS, an outbreak in 2012). We will also
discuss what we have learned so far regarding the
prevention and prognosis of the disease as well as
some remaining yet urgent questions.
The outbreak
CoVs have been traditionally considered
nonlethal pathogens to humans, mainly causing
approximately 15% of common colds [4]. However, in
this century, we have encountered highly pathogenic
human CoVs twice, i.e., SARS-CoV and MERS-CoV,
which caused an outbreak originally in China in 2003
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and Saudi Arabia in 2012, respectively, and soon
spread to many other countries with horrible
morbidity and mortality [5]. Therefore, the current
COVID-19 is the third CoV outbreak in the recorded
history of humans.
As shown in Fig. 1, clusters of pneumonia that
had unknown origins were first reported from Wuhan
on December 31, 2019 to the China National Health
Commission [6]. Seven days later the sequence of the
CoV was released [7]. On January 15, 2020 the first
fatal case from Wuhan was reported [6]. Meanwhile,
the epidemic rapidly spread to the neighboring cities,
provinces, and countries. On January 20, the infection
of health-care providers was reported, suggesting that
human-to-human transmission was possible [8]. On
January 23, the city of Wuhan was locked down with
all its public transportation stopped. On January 24
the first clinical study on the disease reported that, out
of 41 patients with confirmed cases, only 21 had direct
contact with the Wuhan seafood market that was
considered the starting site of the infection from an
unknown animal source [6]. On January 30, WHO
declared the outbreak a global health emergency. By
the time of this report, the disease has already spread
throughout China and near 50 other countries all over
the world (Fig. 2). As the situation is rapidly evolving,
the final scope and severity of the outbreak remain to
be determined.
Figure 1. Major events that occurred thus far during the outbreak of COVID-19.
Figure 2. Worldwide distribution of COVID-19 cases on 26 Feb. 2020, according to a coronavirus monitoring system of Johns Hopkins University [9,10].
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On February 11, 2020, a multi-center study on
8,866 patients including 4,021 confirmed COVID-19
patients presented a more updated illustration of the
epidemic as follows (https://mp.weixin.qq.com/s/
UlBi-HX_rHPXa1qHA2bhdA).
SARS-CoV-2 infected people of all ages, but
mainly at the age of 30-65. Almost half (47.7%) of
the infected individuals were over 50 years old,
very few were under 20, and only 14 infected
individuals were under the age of 10.
SARS-CoV-2 infected more men (0.31/100,000)
than women (0.27/100,000).
COVID-19 expanded in clusters mainly in and
around Hubei.
COVID-19 took an average of 5 (2-9) days from
onset to diagnosis. The average incubation
period was 4.8 (3.0-7.2) days. The average time
from onset to death was 9.5 (4.8-13) days.
The basic reproductive number (R0) was 3.77 (95%
CI: 3.51-4.05), and the adjusted R0 was 2.23-4.82.
The number of infected people increased
exponentially before 23 Jan. 2020, matching the
time of massive transportation before the Spring
Festival in China.
The mortality of patients with confirmed cases
was 1.44% (95% CI: 1.10-1.86%), and the adjusted
mortality of all the patients was 3.06% (95% CI:
2.02-4.59%).
Three major risk factors for COVID-19 were sex
(male), age (≥60), and severe pneumonia.
SARS-CoV-2
Etiology
CoVs are a subfamily of large and enveloped
viruses containing a single strand of sense RNA. They
can be divided into four genera, i.e., alpha, beta,
gamma, and delta, of which alpha- and beta-CoVs are
known to infect humans [11]. The envelope spike (S)
glycoprotein binds to its cellular receptors
angiotensin-converting enzyme 2 (ACE2) and
dipeptidyl peptidase 4 (DPP4) for SARS-CoV and
MERS-CoV, respectively, and then membrane fusion
occurs [12]. The viral RNA genome is released into the
cytoplasm; after replication of the viral genome,
genomic RNA accompanied by envelope
glycoproteins and nucleocapsid proteins forms
virion-containing vesicles, which then fuse with the
plasma membrane to release the virus [13].
The first genomic sequence of SARS-CoV-2 was
reported on January 10, 2020 [3]. SARS-CoV-2 was
found to be a new type of beta-CoV with more than
99.98% genetic identity among 10 sequenced samples
collected from the original site of the outbreak, the
Huanan Seafood Market in Wuhan. SARS-CoV-2 is
genetically more similar to SARS-CoV than to
MERS-CoV [14-16]. Through transmission electron
microscopy, SARS-CoV-2 particles were found in
ultrathin sections of human airway epithelium [17].
Human ACE2 was found to be a receptor for SARS-
CoV-2 as well as SARS-CoV [16,18,19]. However, the S
protein of SARS-CoV-2 binds to human ACE2 more
weakly than that of SARS-CoV, which is coincident
with the fact that SARS-CoV-2 causes less severe
infection in patients than SARS-CoV [14].
SARS-CoV-2 can also form a novel short protein
encoded by orf3b and a secreted protein encoded by
orf8. The orf3b of SARS-CoV-2 may play a role in the
viral pathogenicity and inhibit the expression of IFNβ;
however, orf8 does not contain any known functional
domain or motif [20]. On February 18, 2020, Zhou, et
al., reported the cryo-EM structure of the full-length
human ACE2 at 2.9 Å resolution in complex with the
amino acid transporter B0AT1 [21]. They found that
the complex, which had open and closed
conformations, was assembled as a dimer and the
ACE2-B0AT1 complex can bind two S proteins, which
provides evidence for CoV recognition and infection.
B0AT1 may become a therapeutic target for drug
screening to suppress SARS-CoV-2 infection.
The origin and intermediate host
It has been known that both SARS-CoV and
MERS-CoV originated from bats and were
transmitted to humans via civet cats and camels,
respectively. Through a phylogenetic comparison of
SARS-CoV-2 with other CoVs, bats were considered
the native host of SARS-CoV-2 as the new virus is 96%
identical to two SARS-like CoVs from bats called
bat-SL-CoVZX45 and bat-SL-CoVZX21 [14-16,19].
However, what intermediate host helped the virus
cross the species barrier to infect humans remains
unknown, and the transmission route is yet to be
elucidated. Ji, et al., proposed snakes as a carrier of the
virus from bats to humans which involved
homologous recombination within the S protein [22].
According to a study, researchers in Guangzhou,
China, suggested that pangolins long-snouted, ant-
eating mammals often used in traditional Chinese
medicine are the potential intermediate host of
SARS-CoV-2 based on 99% genetic homology in a
CoV discovered in pangolins and SARS-CoV-2 [23].
However, 1% difference spread all over two genomes
is still a big difference; thus, conclusive results for
concrete evidence are awaited (Fig. 3).
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Figure 3. The origins and intermediate hosts of SARS-CoV-2, SARS-CoV, and MERS-CoV.
Figure 4. Immune response of the host to coronavirus infection [4, 32-34].
Physicochemical properties
The physicochemical properties of SARS-CoV-2
are largely not yet known. SARS-CoV and MERS-CoV
can survive in vitro for 48 hours in a dry environment
and up to 5 days under 20 °C and 40%-50% humidity
[24-26]. SARS-CoV-2 may possess similar properties.
It has been reported that SARS-CoV-2 is sensitive to
ultraviolet rays and heat at 56 °C for 30 minutes; ether,
75% ethanol, chlorine-containing disinfectant,
peracetic acid, chloroform, and other fatty solvents,
but not chlorhexidine, can effectively inactivate the
virus [27].
Immune responses to CoVs
The entire human population generally lacks
immunity to SARS-CoV-2 and hence is susceptible to
the novel virus. Currently, no detailed study has been
reported regarding the immunological response to
SARS-CoV-2. Thus, we can only refer to previous
studies on other CoVs, especially SARS-CoV and
MERS-CoV (Fig. 4). In general, after a virus invades
the host, it is first recognized by the host innate
immune system through pattern recognition receptors
(PRRs) including C-type lectin-like receptors, Toll-like
receptor (TLR), NOD-like receptor (NLR), and RIG-I-
like receptor (RLR) [28]. Through different pathways,
the virus induces the expression of inflammatory
factors, maturation of dendritic cells, and synthesis of
type I interferons (IFNs) which limit the spreading of
the virus and accelerate macrophage phagocytosis of
viral antigens [28]. However, the N protein of SARS-
CoV can help the virus escape from the immune
responses [29].
Soon, the adaptive immune response joins the
fight against the virus. T lymphocytes including CD4+
and CD8+ T cells play an important role in the
defense. CD4+ T cells stimulate B cells to produce
virus-specific antibodies, and CD8+ T cells directly kill
virus-infected cells. T helper cells produce
proinflammatory cytokines to help the defending
cells. However, CoV can inhibit T cell functions by
inducing apoptosis of T cells. The humoral immunity
including complements such as C3a and C5a and
antibodies is also essential in combating the viral
infection [30,31]. For example, antibodies isolated
from a recovered patient neutralized MERS-CoV [32].
On the other hand, an overreaction of the immune
system generates a large number of free radicals
locally that can cause severe damages to the lungs and
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other organs, and, in the worst scenario, multi-organ
failure and even death [33].
Clinical features
The incubation periods
The SARS-CoV-2 infection, featured by
clustering onset, is more likely to affect elderly people
with comorbidities and pregnant women [8]. It is
common that for people who are exposed to a large
number of viruses or whose immune functions are
compromised, they have higher chance to be infected
than others. The estimated mean incubation period of
SARS-CoV-2 is 1-14 days, mostly 3-7 days based on a
study of the first 425 cases in Wuhan [36]. However, a
study on 1,099 cases demonstrates that the incubation
period was 3 days on average and ranged from 0 to 24
days [8]. A more recent study, as described above,
demonstrates that the incubation period was 4.8
(3.0-7.2) days based on the demography of 8,866 cases
[37]. It is very important for health authorities to
adjust the effective quarantine time based on the most
accurate incubation period, thus preventing infected
but symptomless people from transmitting the virus
to others [38]. As a common practice, individuals
exposed to, or infected by, the virus are usually
required to be quarantined for 14 days. Should the
quarantine time be extended to 24 days?
Symptoms
Fever is often the major and initial symptom of
COVID-19, which can be accompanied by no
symptom or other symptoms such as dry cough,
shortness of breath, muscle ache, dizziness, headache,
sore throat, rhinorrhea, chest pain, diarrhea, nausea,
and vomiting. Some patients experienced dyspnea
and/or hypoxemia one week after the onset of the
disease [8]. In severe cases, patients quickly
progressed to develop acute respiratory syndrome,
septic shock, metabolic acidosis, and coagulopathy.
Patients with fever and/or respiratory symptoms and
acute fever, even without pulmonary imaging
abnormalities, should be screened for the virus for
early diagnosis [39-41].
A demographic study in late December of 2019
showed that the percentages of the symptoms were
98% for fever, 76% for dry cough, 55% for dyspnea,
and 3% for diarrhea; 8% of the patients required
ventilation support [42]. Similar findings were
reported in two recent studies of a family cluster and
a cluster caused by transmission from an
asymptomatic individual [43,44]. Comparably, a
demographic study in 2012 showed that MERS-CoV
patients also had fever (98%), dry cough (47%), and
dyspnea (55%) as their main symptoms. However,
80% of them required ventilation support, much more
than COVID-19 patients and consistent with the
higher lethality of MERS than of COVID-19. Diarrhea
(26%) and sore throat (21%) were also observed with
MERS patients. In SARS patients, it has been
demonstrated that fever (99%-100%), dry cough
(29%-75%), dyspnea (40%-42%), diarrhea (20-25%),
and sore throat (13-25%) were the major symptoms
and ventilation support was required for
approximately 14%-20% of the patients [45].
By February 14, the mortality of COVID-19 was
2% when the confirmed cases reached 66,576 globally.
Comparably, the mortality of SARS by November
2002 was 10% of 8,096 confirmed cases [46]. For
MERS, based on a demographic study in June 2012,
the mortality was 37% of 2,494 confirmed cases [47].
An earlier study reported that the R0 of SARS-CoV-2
was as high as 6.47 with a 95% confidence interval
(CI) of 5.71-7.23 [48], whereas the R0 of SARS-CoV
only ranged from 2 to 4 [49]. A comparison of SARS-
CoV-2 with MERS-CoV and SARA-CoV regarding
their symptoms, mortality, and R0 is presented in
Table 1. The above figures suggest that SARS-CoV-2
has a higher ability to spread than MERS-CoV and
SARS-CoV, but it is less lethal than the latter two [6].
Thus, it is much more challenging to control the
epidemic of SARS-CoV-2 than those of MERS-CoV
and SARS-CoV.
Table 1. Comparison of SARS-CoV-2 with SARS-CoV and MERS-CoV
Comparison items
SARS-CoV-2
MERS-CoV
SARS-CoV
Characteristics
Date extracted from
Dec. 2020 Feb. 2020
Sept. 2012
Dec. 2003
Place of origin
Wuhan, China
Jeddah, Saudi Arabia
Guangdong China
Age range
56 (22-92)
56 (14-94)
39.9 (1-91)
Male/Female sex ratio
1:3:1
3.3:1
1.1.25
Mortality rate
2%
34%
9.6%
Confirmed cases (Global)
24554
2494
8096
R0
4.7 6.6
0.45 0.91
0.86 1.88
Incubation period (day)
7 14
5.0 6.9
4.4 6.9
Symptoms
Fever
258 (93%)
98%
99-100%
Dry cough
194 (70%)
47%
29-75%
Dyspnea
96 (35%)
72%
40-42%
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Comparison items
SARS-CoV-2
MERS-CoV
SARS-CoV
Diarrhea
17 (6%)
26%
20-25%
Sore throat
10 (4%)
21%
13-25%
Diagnosis
Patient history
Clustered onset often happens in the same
family or from the same gathering or vehicle such as a
cruise ship. Patients often have a history of travel or
residence in Wuhan or other affected areas or contact
with infected individuals or patients in the recent two
weeks before the onset [50]. However, it has been
reported that people can carry the virus without
symptoms longer than two weeks and cured patients
discharged from hospitals can carry the virus again
[51], which sends out an alarm to increase the time for
quarantine.
Laboratory results
Patients have normal or reduced number of
peripheral white blood cells (especially lymphocytes)
at the early stage. For example, lymphopenia with
white blood cell count < 4×109/L including
lymphocyte count < 1×109/L, and elevated aspartate
aminotransferase levels and viremia were found in
1,099 COVID-19 patients [8]. The levels of liver and
muscle enzymes and myoglobin were increased in the
blood of some patients, and C-reactive protein and
erythrocyte sedimentation were increased in the
blood of most patients [52]. In patients with severe
cases, the level of D-dimer, a fibrin degradation
product present in the blood, was elevated, and
lymphocyte count was progressively reduced [34].
Radiography
Abnormalities in chest radiography are found in
most COVID-19 patients and featured by bilateral
patchy shadows or ground glass opacity in the lungs.
Patients often develop an atypical pneumonia, acute
lung injury, and acute respiratory distress syndrome
(ARDS) [34]. When ARDS happens, uncontrolled
inflammation, fluid accumulation, and progressive
fibrosis severely compromise the gas exchange.
Dysfunction of type-I and type-II pneumocytes
decreases the surfactant level and increases surface
tension, thus reducing the ability of the lungs to
expand and heightening the risk of lung collapse [53,
54]. Therefore, the worst chest radiographic findings
often parallel the most severe extent of the disease
[55].
Pathology
On February 18, 2020, the first pathological
analysis of COVID-19 demonstrated the
desquamation of pneumocytes, hyaline membrane
formation, and interstitial lymphocyte infiltration,
and multinucleated syncytial cells in the lungs of a
patient who died of the disease, consistent with the
pathology of viral infection and ARDS [56] and
similar to that of SARS and MERS patients [57,58].
Nuclear acid assays
The detection of SARS-CoV-2 RNA via reverse-
transcriptase polymerase chain reaction (RT-PCR)
was used as the major criteria for the diagnosis of
COVID-19. However, due to the high false-negative
rate, which may accelerate the epidemic, clinical
manifestations started to be used for diagnosis (which
no longer solely relied on RT-PCR) in China on
February 13, 2020. A similar situation also occurred
with the diagnosis of SARS [59]. Therefore, a
combination of disease history, clinical
manifestations, laboratory tests, and radiological
findings is essential and imperative for making an
effective diagnosis. On February 14, 2020, the Feng
Zhang group described a protocol of using the
CRISPR-based SHERLOCK technique to detect SARS-
CoV-2, which detects synthetic SARS-CoV-2 RNA
fragments at 20 × 10-18 mol/L to 200 × 10-18 mol/L
(10-100 copies per microliter of input) using a dipstick
in less than an hour without requiring elaborate
instrumentation [60]. Hopefully, the new technique
can dramatically enhance the sensitivity and
convenience if verified in clinical samples.
Treatment
Due to the lack of experience with the novel
CoV, physicians can mainly provide supportive care
to COVID-19 patients, while attempting a variety of
therapies that have been used or proposed before for
the treatment of other CoVs such as SARS-CoV and
MERS-CoV and other viral diseases (Table 2). These
therapies include current and potential treatments
with antiviral drugs, immunosuppressants, steroids,
plasma from recovered patients, Chinese medicine,
and psychological support. Even plasma from
recovered patients was proposed to be used for
treatment [61]. Pharmaceutical companies are racing
to develop antibodies and vaccines against the virus
[62].
Supportive care
SARS-CoV-2 mainly attacks the lungs in the
beginning and probably also attacks, to a lesser
degree, other organs that express ACE2, such as the
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gastrointestinal system and the kidneys. Nevertheless,
respiratory dysfunction and failure are the major
threat to the patients and the major cause of death.
Thus, respiratory support is critical to relieve the
symptoms and save lives and includes general oxygen
therapy, high-flow oxygen, noninvasive ventilation,
and invasive mechanical ventilation depending on the
severity of the disease. Patients with severe
respiratory symptoms have to be supported by
extracorporeal membrane oxygenation (ECMO), a
modified cardiopulmonary bypass technique used for
the treatment of life-threatening cardiac or respiratory
failure. In addition, the maintenance of electrolyte
balance, the prevention and treatment of secondary
infection and septic shock, and the protection of the
functions of the vital organs are also essential for
SARS-CoV-2 patients [7].
Table 2. Treatments of COVID-19
Treatment
Efficacy
References
General oxygen therapy,
high-flow oxygen/noninvasive
ventilation, and invasive
mechanical ventilation,
conservation fluid management,
management of septic shock,
infection control
Respiratory supports
[7]
Antiviral therapy
Reduce the viral load
[63]
Remdesivir
-
[64]
Steroids
Reduce the severity of
inflammatory damage
[65]
Psychological supports
Relieve stress and improve
mental health
[66]
Tackling cytokine storms
It has been known that a cytokine storm results
from an overreaction of the immune system in SARS
and MERS patients [33]. Cytokine storm is a form of
systemic inflammatory response featured by the
release of a series of cytokines including TNFα, IL-1β,
IL-2, IL-6, IFNα, IFNβ, IFNγ, and MCP-1. These
cytokines induce immune cells to release a vast
number of free radicals which are the major cause of
ARDS and multiple organ failure [67].
Immunosuppression is essential in the treatment of
cytokine storms, especially in severe patients.
Corticosteroids and tocilizumab, an anti-IL6
monoclonal antibody, have been used to treat
cytokine storm [68]. Other immunosuppression
treatments for cytokine storm include the modulation
of T cell-directed immune response; the blockade of
IFN-γ, IL-1, and TNF; JAK inhibition [69];
blinatumomab [70]; suppressor of cytokine signaling
4 [71]; and HDAC inhibitors [72].
Steroids, as immunosuppressants, were widely
used in the treatment of SARS to reduce the severity
of inflammatory damage [65]. However, steroids at
high dosages were not beneficial to severe lung injury
in SARS and COVID-19 patients [59,73]. Instead, they
may cause severe side effects, especially avascular
osteonecrosis, dramatically affecting the prognosis
[74]. Nevertheless, short courses of corticosteroids at
low-to-moderate doses have been recommended to be
used prudently for critically ill COVID-19 patients
[75].
Antiviral therapy
At the time of writing, no effective antiviral
therapy has been confirmed. However, intravenous
administration with remdesivir, a nucleotide analog,
has been found to be efficacious in an American
patient with COVID-19 [64]. Remdesivir is a novel
antiviral drug developed by Gilead initially for the
treatment of diseases caused by Ebola and Marlburg
viruses [76]. Later, remdesivir also demonstrated
possible inhibition of other single stranded RNA
viruses including MERS and SARS viruses [77,78].
Based on these, Gilead has provided the compound to
China to conduct a pair of trials on SARS-CoV-2-
infected individuals [79], and the results are highly
anticipated.
In addition, baricitinb, interferon-α, lopinavir/
ritonavir, and ribavirin have been suggested as
potential therapies for patients with acute respiratory
symptoms [80,81]. Diarrhea, nausea, vomiting, liver
damage, and other adverse reactions can occur
following combined therapy with lopinavir/ritonavir
[80]. The interaction of these treatments with other
drugs used in the patients should be monitored
carefully.
Plasma from recovered patients and antibody
generation
The collection of the blood from patients who
recovered from a contagious disease to treat other
patients suffering from the same disease or to protect
healthy individuals from catching the disease has a
long history [82]. Indeed, recovered patients often
have a relatively high level of antibodies against the
pathogen in their blood. Antibodies are an
immunoglobulin (Ig) produced by B lymphocytes to
fight pathogens and other foreign objects and they
recognize unique molecules in the pathogens and
neutralize them directly [83]. Based on this, plasma
was collected from the blood of a group of patients
who recovered from COVID-19 and was injected into
10 seriously ill patients. Their symptoms improved
within 24 hours, accompanied by reduced
inflammation and viral loads and improved oxygen
saturation in the blood. However, verification and
clarification are necessary to propose the method for
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large-scale use before specific therapies are not yet
developed.
In addition, given the therapeutic effects, some
disadvantages associated with the plasma should be
considered carefully. For example, antibodies can
overstimulate the immune response and cause
cytokine release syndrome, which is potentially a
life-threatening toxicity [84]. The concentration of
antibodies in the blood is usually low, and the
demand for the plasma is large to treat critically ill
patients. It is difficult to develop and produce specific
antibodies rapidly enough to fight against a global
epidemic [62]. Thus, it is more critical and practical to
isolate B cells from recovered patients and identify the
genetic codes encoding effective antibodies or screen
for effective antibodies against essential proteins of
the virus. This way, we can readily scale up the
production of the antibodies.
Traditional Chinese medicine (TCM)
TCM has been used to treat a variety of diseases
in China for thousands of years. However, its effects
largely rely on a combination of multiple components
in a formula that varies depending on the diagnosis of
a disease based on the theories of TCM. Most of the
effective components remain unknown or are vague
as it is difficult to extract and verify such components
or their optimal combinations. Currently, due to the
lack of effective and specific therapy for COVID-19,
TCM has become one of the major alternative
treatments for patients with light to moderate
symptoms or for those who have recovered from
severe stages [85]. For example, Shu Feng Jie Du
capsules and Lian Hua Qing Wen capsules were
found to be effective for COVID-19 treatment [86].
Top cure rates in the treatment of COVID-19 patients
were observed in several provinces in China that used
TCM in 87% of their patients, including Gansu
(63.7%), Ningxia (50%), and Hunan (50%), whereas
Hubei province, which used TCM in only
approximately 30% of its COVID-19 patients, had the
lowest cure rate (13%) [87]. However, this is quite a
rough comparison as many other impact factors such
as the number and severity of the patients should be
included in the evaluation.
On February 18, 2020, Boli Zhang and coworkers
published a study to compare western medicine
(WM) treatment alone with combined treatment of
WM and TCM [88]. They found that the times needed
for body temperature recovery, symptom
disappearance, and hospitalization were remarkably
shorter in the WM+TCM group than in the WM only
group. Most impressively, the rate for symptomatic
worsening (from light to severe) was remarkably
lower for the WM+TCM group than for the WM only
group (7.4% versus 46.2%) and the mortality was
lower in the WM+TCM group than WM only group
(8.8% versus 39%). Nevertheless, the efficacy and
safety of TCM still await more well-controlled trials at
larger scales and in more centers. It would also be
intriguing to characterize the mechanism of actions
and clarify the effective components of TCM
treatments or their combinations if possible.
Mental health care
Patients with suspected or confirmed COVID-19
mostly experience great fear of the highly contagious
and even fatal disease, and quarantined people also
experience boredom, loneliness, and anger.
Furthermore, symptoms of the infection such as fever,
hypoxia, and cough as well as adverse effects of the
treatments such as insomnia caused by corticosteroids
can lead to more anxiety and mental distress. In the
early phase of the SARS outbreak, a range of
psychiatric morbidities including persistent
depression, anxiety, panic attacks, psychomotor
excitement, psychotic symptoms, delirium, and even
suicidality were reported [89,90]. Mandatory contact
tracing and quarantine, as a part of the public health
responses to the COVID-19 outbreak, can make
people more anxious and guilty about the effects of
the contagion, quarantine, and stigma on their
families and friends [66].
Thus, mental health care should be provided to
COVID-19 patients, suspected individuals, and
people in contact with them as well as the general
public who are in need. The psychological support
should include the establishment of multidisciplinary
mental health teams, clear communications with
regular and accurate updates about the SARS-CoV-2
outbreak and treatment plans and the use of
professional electronic devices and applications to
avoid close contact with each other [66].
Vaccination
Effective vaccines are essential for interrupting
the chain of transmission from animal reservoirs and
infected humans to susceptible hosts and are often
complementary to antiviral treatment in the control of
epidemics caused by emerging viruses. Efforts have
been made to develop S protein-based vaccines to
generate long-term and potent neutralizing antibodies
and/or protective immunity against SARS-CoV [81,
91]. Live-attenuated vaccines have been evaluated in
animal models for SARS [92]. However, the in vivo
efficacy of these vaccine candidates in elderly
individuals and lethal-challenge models and their
protection against zoonotic virus infection have yet to
be determined before a clinical study is initiated. This
is probably because SARS died down 17 years ago
Int. J. Biol. Sci. 2020, Vol. 16
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1761
and no new case has been reported since.
In contrast, sporadic cases and clusters of MERS
continue to occur in the Middle East and spread to
other regions owing to the persistence of zoonotic
sources in endemic areas. Vaccination strategies have
been developed for MERS by using inactivated virus,
DNA plasmids, viral vectors, nanoparticles, virus-like
particles and recombinant protein subunits and some
have been evaluated in animal models [93]. The
development of a safe and effective vaccine against
SARS-CoV-2 for non-immune individuals is an urgent
and critical task for controlling the ongoing epidemic.
However, it is challenging to overcome the difficulty
because of the long period of time (averaged 18
months) needed for vaccine development and the
dynamic variations of CoVs.
Prognosis
Prognosis of patients
As a novel disease, COVID-19 has just started to
manifest its full clinical course throughout thousands
of patients. In most cases, patients can recover
gradually without sequelae. However, similar to
SARS and MERS, COVID-19 is also associated with
high morbidity and mortality in patients with severe
cases. Therefore, building a prognosis model for the
disease is essential for health-care agencies to
prioritize their services, especially in resource-
constrained areas. Based on clinical studies reported
thus far, the following factors may affect or be
associated with the prognosis of COVID-19 patients
(Table 3):
Age: Age was the most important factor for the
prognosis of SARS [99], which is also true for
COVID-19. COVID-19 mainly happened at the
age of 30-65 with 47.7% of those patients being
over 50 in a study of 8,866 cases as described
above [37]. Patients who required intensive care
were more likely to have underlying
comorbidities and complications and were
significantly older than those who did not (at the
median age of 66 versus 51) [34], suggesting age
as a prognostic factor for the outcome of
COVID-19 patients.
Sex: SARS-CoV-2 has infected more men than
women (0.31/100,000 versus 0.27/100,000), as
described above [37].
Comorbidities and complications: Patients with
COVID-19 who require intensive care are more
likely to suffer from acute cardiac injury and
arrhythmia [34]. Cardiac events were also the
main reason for death in SARS patients [55,65,99].
It has been reported that SARS-CoV-2 can also
bind to ACE2-positive cholangiocytes, which
might lead to liver dysfunctions in COVID-19
patients [100]. It is worth noting that age and
underlying disease are strongly correlated and
might interfere with each other [55].
Abnormal laboratory findings: The C-reactive
protein (CRP) level in blood reflects the severity
of inflammation or tissue injury and has been
proposed to be a potential prognostic factor for
disease, response to therapy, and ultimate
recovery [101]. The correlation of CRP level to
the severity and prognosis of COVID-19 has also
been proposed [101]. In addition, elevated lactate
dehydrogenase (LDH), aspartate amino-
transferase (AST), alanine aminotransferase
(ALT), and creatine kinase (CK) may also help
predict the outcome. These enzymes are
expressed extensively in multiple organs,
especially in the heart and liver, and are released
during tissue damage [102,103]. Thus, they are
traditional markers for heart or liver
dysfunctions.
Major clinical symptoms: Chest radiography
and temporal progression of clinical symptoms
should be considered together with the other
issues for the prediction of outcomes and
complications of COVID-19.
Use of steroids: As described above, steroids are
immunosuppressant commonly used as an
adjunctive therapy for infectious diseases to
reduce the severity of inflammatory damage
[104]. Since a high dosage of corticosteroids was
widely used in severe SARS patients, many
survivors suffered from avascular osteonecrosis
with life-long disability and poor life quality
[105]. Thus, if needed, steroids should be used at
low dosage and for a short time in COVID-19
patients.
Mental stress: As described above, during the
COVID-19 outbreak many patients have suffered
from extraordinary stress as they often endured
long periods of quarantine and extreme
uncertainty and witnessed the death of close
family members and fellow patients. It is
imperative to provide psychological counseling
and long-term support to help these patients
recover from the stress and return to normal life
[66].
Prognosis of the epidemic
According to demographic studies so far,
COVID-19 seems to have different epidemiological
features from SARS. In addition to replicating in the
lower respiratory tract, SARS-CoV-2 can efficiently
replicate in the upper respiratory tract and causes
Int. J. Biol. Sci. 2020, Vol. 16
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1762
mild or no symptoms in the early phase of infection,
similar to other CoVs that cause common colds [106].
Therefore, infected patients at the early phase or
incubation period can produce a large amount of
virus during daily activities, causing great difficulty
for the control of the epidemic. However, the
transmission of SARS-CoV was considered to occur
when the patients are severely ill, while most
transmission did not happen at the early phase [107].
Thus, the current outbreak of COVID-19 is much
more severe and difficult to control than the outbreak
of SARS.
Table 3. Prognostic factors for COVID-19 in comparison with
SARS and MERS
Disease
Laboratory
results
Chest
radiography
Others
Reference
COVID-19
CRP
AST
ALT
CK
LDH
D-dimer
Lymphopenia
Chest
radiography
Age
Gender
Pregnancy
Viral load
Underlying
disease
SARS
CRP
AST
ALT
CK
LDH
D-dimer
Low platelet
Plasma
electrolyte
Chest
radiography
Age
Gender
Pregnancy
Underlying
diseases
[55, 59, 65,
94]
MERS
Neutrophilia
Lymphopenia
Serum
creatinine
LDH
The diffuse or
brochopneumonia
Age,
Chronic
kidney
disease,
Hypertension,
Viral load
[95-98]
Figure 5. Comparison of epidemic of COVID-19, SARS, and MERS.
Great efforts are currently underway in China
including the lockdown of Wuhan and surrounding
cities and continuous quarantine of almost the entire
population in hopes of interrupting the transmission
of SARS-CoV-2. Although these actions have been
dramatically damaging the economy and other sectors
of the country, the number of new patients is
declining, indicating the slowdown of the epidemic.
The most optimistic estimate is that the outbreak will
end by March and the downswing phase will last for
3-4 months [108]. However, some other experts are
not that optimistic. Paul Hunter, et al., estimated that
COVID-19, which seems substantially more infectious
than SARS, will not end in 2020 [109]. Ira Longini, et
al., established a model to predict the outcome of the
epidemic and suggested that SARS-CoV-2 could
infect two-thirds of the global population [110].
A Canadian group reported that SARS-CoV-2
was detected in both mid-turbinate and throat swabs
of patients who recovered and left the hospital 2
weeks earlier [111], which indicates that the newly
identified virus could become a cyclical episode
similar to influenza. However, promising signs have
occurred in China based on the declining number of
new cases, indicating the current strategies might
have been working. Ebola was originally predicted to
cause up to a million cases with half a million deaths.
However, via strict quarantine and isolation, the
disease has eventually been put under control [112,
113]. It is possible, similar to SARS-CoV, that SARS-
CoV-2 might become weaker in infectivity and
eventually die down or become a less pathogenic
virus co-existent with humans. A comparison of the
epidemic of COVID-19 with that of SARS and MERS
is provided below (Fig. 5).
Prevention
SARS-CoV-2 is highly transmittable through
coughing or sneezing, and possibly also through
direct contact with materials contaminated by the
virus [12]. The virus was also found in feces, which
raises a new possibility of feces-to-mouth
transmission [114]. A recent study on 138 cases
reported that 41% of the cases were possibly caused
by nosocomial infections, including 17 patients with
other prior diseases and 40 health-care providers
[115]. Thus, great precaution should be used to
protect humans, especially health-care providers,
social workers, family members, colleagues, and even
bystanders in contact with patients or infected people.
Personal role
The first line of defense that could be used to
lower the risk of infection is through wearing face
masks; both the use of surgical masks and N95
respirator masks (series # 1860s) helps control the
spread of viruses [116]. Surgical face masks prevent
liquid droplets from a potentially infected individual
Int. J. Biol. Sci. 2020, Vol. 16
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1763
from traveling through the air or sticking onto
surfaces of materials, where they could be passed on
to others [117]. However, only N95 (series # 1860s)
masks can protect against the inhalation of virions as
small as 10 to 80 nm, with only 5% of the virions being
able to penetrate completely; SARS-CoV-2 is similar to
SARS-CoV in size and both are approximately 85 nm
[117]. Since particles can penetrate even five surgical
masks stacked together, health-care providers in
direct contact with patients must wear N95 (series #
1860s) masks but not surgical masks [118].
In addition to masks, health-care providers
should wear fitted isolation gowns in order to further
reduce contact with viruses. Viruses can also infect an
individual through the eyes. On January 22, 2020, a
doctor was infected with SARS-CoV-2 although he
wore an N95 mask; the virus might have entered his
body through his inflammatory eyes [119]. Thus,
health-care providers should also wear transparent
face shields or goggles while working with patients.
For the general public in affected or potentially
affected areas, it is highly suggested that everybody
wash their hands with disinfectant soaps more often
than usual, try to stay indoors for self-quarantine and
limit contact with potentially infected individuals.
Three feet is considered an appropriate distance for
people to stay away from a patient [120]. These
actions are effective methods to lower the risk of
infection as well as prevent the spread of the virus.
Governmental role
Although SARS-CoV-2 came as a new virus to
the human world, its high homology to SARS-CoV as
reported on 7 January 2020 [3] should have caused
high alert to China based on her deep memory of the
SARS outbreak in 2003. However, not until 19 January
2020 did the director of the Center of Disease Control
of Wuhan comfort the citizens by saying that the
novel virus has low contagiousness and limited
reproductivity from human to human and that it is
not a problem to prevent and contain the disease. This
message remarkably relaxed the alarm of the public,
especially when the entire country was preparing for
the Spring Festival, and the critical time was missed to
contain the disease at its minimal scale in Wuhan.
The disease control agencies in China may take
this hard lesson and make critical improvements in
the future. For example, these agencies should be (1)
more careful when making public announcements as
every word counts to citizens and can change their
attitude and decisions; (2) more sensitive and reactive
to unusual information from clinics rather than
waiting for formal reports from doctors or officials; (3)
more restrictive to contain a potential epidemic at its
early stage rather than attempting to comfort the
public; and (4) more often to issue targeted and
effective drills to increase the public’s awareness
about epidemic diseases and to test and improve the
response system of the society periodically.
Concluding remarks
The outbreak of COVID-19 caused by the novel
virus SARS-CoV-2 started in the end of December
2019. In less than two months, it has spread all over
China and near 50 other countries globally at the time
of this writing. Since the virus is very similar to
SARS-CoV and the symptoms are also similar
between COVID-19 and SARS, the outbreak of
COVID-19 has created a sense of SARS recurring.
However, there are some remarkable differences
between COVID-19 and SARS, which are essential for
containing the epidemic and treating the patients.
COVID-19 affects more elderly individuals than
youth and more men than women, and the
severity and death rate are also higher in elderly
individual than in youth.
SARS has higher mortality than COVID-19 (10.91%
versus 1.44%).
COVID-19 patients transmit the virus even when
they are symptomless whereas SARS patients do
so usually when they are severely ill, which
causes much greater difficulty to contain the
spread of COVID-19 than SARS. This partially
explains why SARS-CoV-2 spread much faster
and broader than SARS-CoV.
The regular RNA assay for SARS-CoV-2 can be
negative in some COVID-19 patients. On the
other hand, cured patients can be positive for the
virus again. These findings dramatically increase
the risk of virus spreading.
Given such rapid progress in research on
COVID-19, several critical issues remain to be solved,
as follows:
Where did SARS-CoV-2 come from? Although
96% genetic homolog was found between SARS-
CoV-2 and two bat SARS-like CoVs, we still
cannot conclude that SARS-CoV-2 is from bats.
What animal was the intermediate species to
transmit the virus from the original host, say bats,
to humans? Without knowing answers to #1 and
2, we cannot efficiently cut the transmission, and
the outbreak can relapse at any time.
Although molecular modeling and biochemical
assays have demonstrated that SARS-CoV-2
binds to ACE2, how exactly does the virus enter
the airway cells and cause subsequent
pathological changes? Does the virus also bind
ACE2-expressing cells in other organs [121]?
Int. J. Biol. Sci. 2020, Vol. 16
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1764
Without clear answers to these questions, we
cannot achieve fast and accurate diagnosis and
effective treatment.
How long will the epidemic last? How is the
virus genetically evolving during transmission
among humans? Will it become a pandemic
worldwide, die down like SARS or relapse
periodically like the flu?
It is essential but may take some time to search
for answers to the above and many other questions.
However, with whatever expense it may demand, we
have no other choice but to stop the epidemic as soon
as possible and bring our life back to normal.
Acknowledgments
This work was supported by University of
Macau Research Committee funds MYRG
#2016-00070-FHS, and #2017-00124-FHS, Macau
Science and Technology Development Fund (FDCT)
#095/2017/A1 and 0112-2018-A3, and FDCT-
National Natural Science Foundation of China joint
grant #0008-2019-AFJ to R.X.
Author contributions
Y.Y. and R.X. conceived and designed the
manuscript. Y.Y., P.L., S.Y., E.L. and R.X. wrote the
manuscript. R.X gave the final approval of the
manuscript.
Competing Interests
R.X. is a founder of ImStem Biotechnology, Inc.,
a stem cell company. The other authors declare no
competing financial interests.
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... Whereas, there is a general fluidity of emerging information around COVID-19 as we learn more about this virus and pandemic daily [6], there appears to be some consistency in its disproportionate burdens on older individuals and those with some underlying medical conditions such as obesity, diabetes and heart disease [7,8]. To the extent that older people appear to be more vulnerable to COVID-19, and more likely to die after contracting the disease, it is conceivable that countries with relatively younger populations may have lower case fatality rates (CFRs) compared to countries with older populations. ...
... Median age by country is an important index that summarizes the age distribution of a country by dividing the population into two numerically equal-sized groups such that, half of the people are younger than this age and half are older [19]. Since available evidence suggests a higher mortality burden from COVID-19 among older individuals [7,8], median age by country was included in this study to evaluate the effect of age on COVID-19 CFR at the population level for the purposes of cross-country and regional analyses. ...
Research
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Aim COVID-19 has exerted distress on virtually every aspect of human life with disproportionate mortality burdens on older individuals and those with underlying medical conditions. Variations in COVID-19 incidence and case fatality rates (CFRs) across countries have incited a growing research interest regarding the effect of social factors on COVID-19 case-loads and fatality rates. We investigated the effect of population median age, inequalities in human development, healthcare capacity, and pandemic mitigation indicators on country-specific COVID-19 CFRs across countries and regions. Subject and methods Using population secondary data from multiple sources, we conducted a cross-sectional study and used regional analysis to compare regional differences in COVID-19 CFRs as influenced by the selected indicators. Results The analysis revealed wide variations in COVID-19 CFRs and the selected indicators across countries and regions. Mean CFR was highest for South America at 1.973% (± 0.742) and lowest for Oceania at 0.264% (± 0.107), while the Africa sub-region recorded the lowest scores for pandemic preparedness, vaccination rate, and other indicators. Population Median Age [0.073 (0.033 0.113)], Vaccination Rate [−3.3389 (−5.570.033 −1.208)], and Inequality-Adjusted Human Development Index (IHDI) [−0.014 (−0.023 −0.004)] emerged as statistically significant predictors of COVID-19 CFR, with directions indicating increasing Population Median Age, higher inequalities in human development and low vaccination rate are predictive of higher fatalities from COVID-19. Conclusion Regional differences in COVID-19 CFR may be influenced by underlying differences in sociodemographic and pandemic mitigation indicators. Populations with wide social inequalities, increased population Median Age and low vaccination rates are more likely to suffer higher fatalities from COVID-19.
... Tampoco fue posible dimensionar las consecuencias e impactos sociales, ambientales, económicos y políticos que produciría. La enfermedad de COVID-19 se convirtió en unos meses en pandemia, cuyos efectos fueron devastadores para todos los integrantes de la sociedad (Yi et al., 2020). De un momento a otro, las escuelas y universidades de todo el mundo cerraron sus puertas, lo cual afectó a 1 570 millones de estudiantes en 191 países (unesco e iesalc, 2020). ...
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... In the beginning, snakes charged as an adapter host of SARS-CoV-2 transmission [11]. Later, pangolins were proposed as potential transitional hosts for SARS-CoV-2 as the genetic symmetry with CoVs in pangolins is high, and the difference is less than 1% [12]. The epidemiology of COVID-19 can be divided into three stages [13]. ...
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... The virus attacks the vital organs of the body and leads to fatal respiratory distress. SARS-CoV-2 belongs to a group of viruses known as human coronaviruses [1]. Human coronavirus is a member of the Coronaviridae family that infects the respiratory tract of humans. ...
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Various mutations have accumulated since the first genome sequence of SARS-CoV2 in 2020. Mutants of the virus carrying the D614G and P681R mutations in the spike protein are increasingly becoming dominant all over the world. The two mutations increase the viral infectivity and severity of the disease. This report describes an in silico design of SARS-CoV-2 multi-epitope carrying the spike D614G and P681R mutations. The designed vaccine harbors the D614G mutation that increases viral infectivity, fitness, and the P681R mutation that enhances the cleavage of S to S1 and S2 subunits. The designed multi-epitope vaccine showed an antigenic property with a value of 0.67 and the immunogenicity of the predicted vaccine was calculated and yielded 3.4. The vaccine construct is predicted to be non-allergenic, thermostable and has hydrophilic nature. The combination of the selected CTL and HTL epitopes in the vaccine resulted in 96.85% population coverage globally. Stable interactions of the vaccine with Toll-Like Receptor 4 were tested by docking studies. The multi-epitope vaccine can be a good candidate against highly infecting SARS-CoV-2 variants.
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Viral infections are the culprit of many diseases, including inflammation of the heart muscle, known as myocarditis. Acute myocarditis cases have been described in scientific literature, and viruses, such as parvovirus B19, coxsackievirus B3, or more recently, SARS-CoV-2, were the direct cause of cardiac inflammation. If not treated, myocarditis could progress to dilated cardiomyopathy, which permanently impairs the heart and limits a person’s lifespan. Accumulated evidence suggests that certain viruses may persist in cardiac tissue after the initial infection, which could open up the door to reactivation under favorable conditions. Whether this chronic infection contributes to, or initiates, cardiac damage over time, remains a pressing issue in the field of virus-induced heart pathology, and it is directly tied to patients’ treatment. Previously, large case studies found that a few viruses: parvovirus B19, coxsackievirus, adenovirus, human herpesvirus 6, cytomegalovirus and Epstein–Barr virus, are most commonly found in human endomyocardial biopsy samples derived from patients experiencing cardiac inflammation, or dilated cardiomyopathy. SARS-CoV-2 infection has also been shown to have cardiovascular consequences. This review examines the role of viral persistence in cardiac inflammation and heart disease, and discusses its implications for patients’ outcomes.
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We are now entering the third decade of the 21st Century, and, especially in the last years, the achievements made by scientists have been exceptional, leading to major advancements in the fast-growing field of Public Health Education and Promotion. Frontiers has organized a series of Research Topics to highlight the latest advancements in science in order to be at the forefront of science in different fields of research. This editorial initiative of particular relevance, led by Dr. Marcelo Demarzo, Associate Editor of the Public Health Education and Promotion section, is focused on new insights, novel developments, current challenges, latest discoveries, recent advances and future perspectives in the field of Public Health Education and Promotion. The Research Topic solicits brief, forward-looking contributions from the editorial board members that describe the state of the art, outlining, recent developments and major accomplishments that have been achieved and that need to occur to move the field forward. Authors are encouraged to identify the greatest challenges in the sub-disciplines, and how to address those challenges. The goal of this special edition Research Topic is to shed light on the progress made in the past decade in the Public Health Education and Promotion field and on its future challenges to provide a thorough overview of the status of the art of the Public Health Education and Promotion field. This article collection will inspire, inform and provide direction and guidance to researchers in the field.
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Background: Over 43% of the world's population regularly consumes alcohol. Although not commonly known, alcohol can have a significant impact on the respiratory environment. Living in the time of the COVID-19 pandemic, alcohol misuse can have a particularly deleterious effect on SARS-CoV-2-infected individuals and, in turn, the overall healthcare system. Patients with alcohol use disorders have higher odds of COVID-19-associated hospitalization and mortality. Even though the detrimental role of alcohol on COVID-19 outcomes has been established, the underlying mechanisms are yet to be fully understood. Alcohol misuse has been shown to induce oxidative damage in the lungs through the production of reactive aldehydes such as malondialdehyde and acetaldehyde (MAA). MAA can then form adducts with proteins, altering their structure and function. One such protein is surfactant protein D (SPD), which plays an important role in innate immunity against pathogens. Methods and results: In this study, we examined whether MAA adduction of SPD (SPD-MAA) attenuates the ability of SPD to bind SARS-CoV-2 spike protein, reversing SPD-mediated virus neutralization. Using ELISA, we show that SPD-MAA is unable to competitively bind spike protein and prevent ACE2 receptor binding. Similarly, SPD-MAA fails to inhibit entry of wild-type SARS-CoV-2 virus into Calu-3 cells, a lung epithelial cell line, as well as ciliated primary human bronchial epithelial cells isolated from healthy individuals. Conclusions: Overall, MAA adduction of SPD, a consequence of alcohol overconsumption, represents one mechanism of compromised lung innate defense against SARS-CoV-2, highlighting a possible mechanism underlying COVID-19 severity and related mortality in patients who misuse alcohol.
Chapter
Since the emergence of a novel coronavirus (severe acute respiratory syndrome coronavirus 2) in Wuhan, China, at the end of December 2019, coronavirus disease 2019 has been associated with severe morbidity and mortality and has left world governments, health care systems, and providers caring for vulnerable populations, such as pregnant women, wrestling with the optimal management strategy. Unique physiologic and ethical considerations negate a one-size-fits-all approach when caring for critically ill pregnant women with coronavirus disease 2019 (especially those with underlying cardiac disease), and few resources exist to guide the multidisciplinary team through decisions regarding optimal maternal-fetal surveillance, intensive care procedures, and delivery timing.
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Background: Present concepts of the novel coronavirus infection prognosis in haemodialysis (HD) patients are rather controversial. There is little information on therapy efficiency and safety in such patients. We studied COVID-19 course specifics, prognostic factors associated with fatal outcomes, therapy efficiency and its transformation at different stages of the pandemic first year. Materials and methods: Single-centre retrospective uncontrolled study included 653 COVID-19 HD-patients treated at Moscow City Nephrology Centre from April 1 to December 31, 2020. Results: This period mortality rate was 21.0%. Independent predictors of COVID-19 unfavourable outcome in HD patients were pulmonary lesion extension (CT grades 34), high comorbidity index, and mechanical ventilation. Approaches to COVID-19 treatment modified significantly at different periods. Immunomodulatory drugs (monoclonal antibodies to IL-6, corticosteroids) were used largely at later stages. With tocilizumab administration, mortality was 15.1%, tocilizumab together with dexamethasone 13.3%; without them 37.8% (р0,001). Tocilizumab administration in the first 3 days after hospitalization of patients with CT grades 12 was associated with more favourable outcomes: 1 out of 29 died vs 6 out of 20 (tocilizumab administered at later periods); p0.04. There was no significant difference in death frequency in patients with CT grades 34 depending on tocilizumab administration time. Conclusion: COVID-19 in HD patients can manifest in a severe course with unfavourable outcome. It is urgent to identify reliable disease outcome predictors and develop efficient treatment in this population.
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Background: Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods: We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results: The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions: During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.).
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The outbreak of 2019-nCoV in the central Chinese city of Wuhan at the end of 2019 poses unprecedent public health challenges to both China and the rest world. The new coronavirus shares high sequence identity to SARS-CoV and a newly identified bat coronavirus. While bats may be the reservoir host for various coronaviruses, whether 2019-nCoV has other hosts is still ambiguous. In this study, one coronavirus isolated from Malayan pangolins showed 100%, 98.2%, 96.7% and 90.4% amino acid identity with 2019-nCoV in the E, M, N and S genes, respectively. In particular, the receptor-binding domain of the S protein of the Pangolin-CoV is virtually identical to that of 2019-nCoV, with one amino acid difference. Comparison of available genomes suggests 2019-nCoV might have originated from the recombination of a Pangolin-CoV-like virus with a Bat-CoV-RaTG13-like virus. Infected pangolins showed clinical signs and histopathological changes, and the circulating antibodies reacted with the S protein of 2019-nCoV. The isolation of a coronavirus that is highly related to 2019-nCoV in the pangolins suggests that these animals have the potential to act as the intermediate host of 2019-nCoV. The newly identified coronavirus in the most-trafficked mammal could represent a continuous threat to public health if wildlife trade is not effectively controlled.
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In December 2019 and January 2020, novel coronavirus (2019-nCoV) - infected pneumonia (NCIP) occurred in Wuhan, and has already posed a serious threat to public health. ACE2 (Angiotensin Converting Enzyme 2) has been shown to be one of the major receptors that mediate the entry of 2019-nCoV into human cells, which also happens in severe acute respiratory syndrome coronavirus (SARS). Several researches have indicated that some patients have abnormal renal function or even kidney damage in addition to injury in respiratory system, and the related mechanism is unknown. This arouses our interest in whether coronavirus infection will affect the urinary and male reproductive systems. Here in this study, we used the online datasets to analyze ACE2 expression in different human organs. The results indicate that ACE2 highly expresses in renal tubular cells, Leydig cells and cells in seminiferous ducts in testis. Therefore, virus might directly bind to such ACE2 positive cells and damage the kidney and testicular tissue of patients. Our results indicate that renal function evaluation and special care should be performed in 2019-nCoV patients during clinical work, because of the kidney damage caused by virus and antiviral drugs with certain renal toxicity. In addition, due to the potential pathogenicity of the virus to testicular tissues, clinicians should pay attention to the risk of testicular lesions in patients during hospitalization and later clinical follow-up, especially the assessment and appropriate intervention in young patients' fertility.
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The current outbreak of the novel coronavirus Covid‐19 (coronavirus disease 2019; previously 2019‐nCoV), epi‐centered in Hubei Province of the People's Republic of China, has spread to many other countries. On January 30, 2020, the WHO Emergency Committee declared a global health emergency based on growing case notification rates at Chinese and international locations. The case detection rate is changing hourly and daily and can be tracked in almost real time on website provided by Johns Hopkins University [1] and other websites. As of early February 2020, China bears the large burden of morbidity and mortality, whereas the incidence in other Asian countries, in Europe and North America remains low so far.
Preprint
Angiotensin-converting enzyme 2 (ACE2) is the surface receptor for SARS coronavirus (SARS-CoV) through interaction with its spike glycoprotein (S protein). ACE2 is also suggested to be the receptor for the new coronavirus (2019-nCoV), which is causing a serious epidemic in China manifested with severe respiratory syndrome. B ⁰ AT1 (SLC6A19) is a neutral amino acid transporter whose surface expression in intestinal cells requires ACE2. Here we present the 2.9 Å resolution cryo-EM structure of full-length human ACE2 in complex with B ⁰ AT1. The complex, assembled as a dimer of ACE2-B ⁰ AT1 heterodimers, exhibits open and closed conformations due to the shifts of the peptidase domains of ACE2. A newly resolved Collectrin-like domain (CLD) on ACE2 mediates homo-dimerization. The extended TM7 in each B ⁰ AT1 clamps CLD of ACE2. Structural analysis suggests that the ACE2-B ⁰ AT1 complex can bind two S proteins simultaneously, providing important clues to the molecular basis for coronavirus recognition and infection.