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].