Discussion
”Epidemiological features” mainly focused on transmission and
surveillance. Although SARS-CoV, MERS-CoV and SARS-CoV-2 mainly induce
respiratory infections, understanding the routes of and factors
affecting transmission is very important for the prevention and control
of epidemics. SARS-CoV and MERS-CoV are transmitted via two routes
(respiratory droplets and close contact) [5]. Although the primary
modes of transmission of SARS-CoV-2 are also respiratory droplets and
contact, fomite transfer and aerosols are possible; furthermore, the
faecal-oral route may also be a route of transmission [11].
Transmission by asymptomatic patients has been reported in many
countries and territories [11-13], and asymptomatic patients as a
source of the spread of the infection have become a key aspect of
prevention and control measures. In addition, vertical transmission may
be possible [1]. The WHO has indicated that there is a risk of women
transmitting SARS-CoV-2 to their babies through breastfeeding [14].
Environmental factors (ambient temperature and humidity) have also been
studied in the attempt to elucidate the transmission of SARS-CoV-2
[15]. The routes of transmission of SARS-CoV-2 are complicated and
diverse. It has been reported that transmission along cold chains is
possible, and transmission along the route by which seafood is
transported over long distances may explain the outbreaks in Beijing,
Qingdao and Dalian in China. This possibility serves as a reminder of
the outbreak at the Huanan seafood market in Wuhan. Traceability
analyses have produced uncertain results, and the paths of transmission
are complex and confusing. With regard to preventive measures, using
face masks, practicing appropriate hand hygiene, maintaining social
distance and ensuring adequate ventilation are effective routine methods
[16, 17]. Reducing virus variation and adaptation may play important
roles in preventing and controlling epidemic situation.
”Biological features” were associated with the pathogenicity of
coronaviruses. The latest studies found that the spike protein on the
SARS-CoV-2 surface binds to its receptor, angiotensin-converting enzyme
2 (ACE2), to enter host cells, and host transmembrane protease serine 2
(TMPRSS2) is essential for viral entry [18]. Notably, the binding
affinity of SARS-CoV-2 for ACE2 is 10- to 20-fold higher than that of
SARS-CoV [6], contributing to its virulence. ACE2 expression and the
renin-angiotensin system (RAS) are abnormal in patients with
hypertension and obesity, and TMPRSS2 is overexpressed when exposed to
androgens, indicating that these factors are involved in the
pathogenicity of SARS-CoV-2 [19]. With regard to the RAS, abnormal
levels of proinflammatory angiotensin II and antiinflammatory
angiotensin 1-7 may reflect the severity of COVID-19 [19]. ACE2 and
TMPRSS2 expression may modulate the infectivity of SARS-CoV-2 and are
therefore promising therapeutic targets for COVID-19.
”Immune response features” included multiple immune-related factors,
although most involved immune cells (particularly T lymphocytes,
macrophages and B lymphocytes) and cytokines (interferons, interleukins,
chemokines, TNF and C-reactive protein). Cytokine storms were a primary
focus during the COVID-19 outbreak. Immune responses play essential
roles in the interactions between coronaviruses and their hosts, and
cytokine storms are directly correlated with the pathogenesis and
disease severity. Evidence indicates that excessive elevations of
inflammatory factors are associated with the deterioration of the
condition of patients with SARS and MERS, and there is growing evidence
that cytokine storms may be involved in the pathogenesis of COVID-19,
causing rapid worsening of the condition of the patient [20].
Clinical features, diagnostic methods and therapies are clinical
practice issues. Keywords that were included in the category ”Age/sex”
mainly involved children, pregnant women and older adults. Older adults
tend to be more severely affected by infections due to their weakened
immunity [1]. Pregnant women and children are unique groups during
the COVID-19 outbreak. They pose difficulties with regard to
surveillance and diagnosis. Pregnant women are more susceptible to
infectious diseases due to immune suppression; moreover, the clinical
symptoms are different in pregnant women than in nonpregnant adults.
Compared with adults, fewer children are infected by SARS-CoV-2, and
their CT images show nonspecific abnormalities (pure ground-glass
opacities or consolidation), unlike in adults [21]. There are
diverse systemic manifestations included in the category
”diseases/symptoms”, possibly due to the wide distribution of the
receptor and presence of systemic inflammation (cytokine storms). The
receptor for SARS-CoV-2 and SARS-CoV, ACE2, is widely distributed among
the organs and tissues (mouth, nasal mucosa, nasopharynx, lung, stomach,
small intestine, colon, skin, lymph nodes, thymus, bone marrow, spleen,
liver, kidney, and brain), and the receptor for MERS-CoV, DPP4 (CD26),
is expressed on the kidney, small intestine, liver, prostate epithelial
cells and activated leukocytes, suggesting that the range of tissue
tropism is relatively broader [7]. The nonspecific symptoms and
manifestations of COVID-19 may cause difficulties with regard to
diagnosis and management. Based on clinical and epidemiological
analyses, older age, male sex and preexisting comorbidities were
identified as important risk factors for the development of severe or
fatal disease in COVID-19 patients, which was similar to the results
found in SARS and MERS patients [22-24]. The five most common
comorbidities were hypertension, diabetes, cardiovascular disease,
chronic obstructive pulmonary disease and tumours, while higher D-dimer
levels, higher neutrophil/lymphocyte ratios, higher levels of C-reactive
protein, lymphopenia, thrombocytopenia and obesity were independent risk
factors for mortality in COVID-19 patients [25-27]. According to
epidemiological studies and large-scale data analyses, diabetes is an
important risk factor for mortality and progression to acute respiratory
distress syndrome (ARDS) in patients hospitalized with COVID-19 [28,
29]. The mortality rate in COVID-19 patients with comorbid diabetes
reached 7.3%, which was 2.3% higher than that in nondiabetic patients
[30]. Diabetic patients hospitalized with COVID-19 who had poor
blood glucose control tended to have a higher risk of mortality and
overall poor prognosis due to their preexisting comorbidities,
complications and the effects of cytokine storms [29].
It has been confirmed that swab tests (PCR nucleic acid detection) and
chest CT scans play important roles in the detection and diagnosis of
coronavirus infections [1]. While sequence variation may contribute
to false negative results in nucleic acid detection of SARS-CoV-2 for
diagnosis of COVID‐19. CT scans are very important for screening for
COVID-19, especially in patients with highly suspicious, asymptomatic
cases with negative nucleic acid test results [13]. With regard to
therapies and preventive measures, vaccines, antibody treatments,
traditional Chinese medicine and targeted drugs are four methods. Safe
and effective vaccines are currently in the clinical trial stage
[31]. High-risk groups (for example, medical workers, children,
pregnant women, older adults and people with preexisting diseases) will
be given priority for vaccination. Widespread availability of vaccines
permits eradication of SARS-CoV-2 from endemicity in humans. Early signs
indicate that plasma containing anti-SARS-CoV-2 antibodies from patients
who have recovered from COVID-19 can reduce mortality in COVID-19
patients [11]. There are a number of therapies undergoing
investigation. Hydroxychloroquine, chloroquine, lopinavir/ritonavir and
remdesivir have antiviral activities that can control SARS-CoV-2 in
vitro [32]; moreover, viral entry inhibitors, ACE2 modulators
(angiotensin receptor blockers) and TMPRSS2 inhibitors (camostat
mesylate) are promising clinical therapies, and in China, it has been
suggested that Shuanghuanglian oral liquid and Lianhuaqingwen are
effective treatments in certain patients with COVID-19 [18, 33, 34].
Given the high levels of cytokines in the host, immunosuppressive drugs
targeting the interleukin-6 (IL-6) receptor, such as tocilizumab, have
been reported to be effective at controlling cytokine storms induced by
infection with SARS-CoV-2 [35], and the application of blood
purification technology (plasma exchange, blood/plasma filtration,
adsorption, perfusion and continuous renal replacement therapy) is
helpful because it removes cytokines and may improve the clinical
outcomes in critically ill patients [20].