6  Clinical characteristics of COVID-19
Given the lack of knowledge regarding the manifestations of COVID-19 and the unclear targets for its prevention, efforts have been expedited to extract the clinical data from the first 41 cases, who were unanimously recruited from Wuhan [52]. To depict the clinical characteristics at the national level, a study was performed to analyze 1099 laboratory-confirmed cases from 552 hospitals across mainland China [39]. The most common symptoms were fever and cough on admission, while gastrointestinal illnesses such as nausea, vomiting, and diarrhea were uncommon (<5%). The median incubation period was 4 d (interquartile range: 2–7 d). The case-fatality rate was 1.4%, which was comparable to the national official statistics in China as of 16 February 2020 [39]. However, the case-fatality rate cannot be precisely calculated due to the unclear total number of infected individuals. Importantly, fever was not present on admission in around half of the individuals, suggesting that fever cannot be the sole diagnostic standard for population-based screening of COVID-19. The fact that lymphopenia was common and more prominent in patients with greater disease severity has inspired clinicians to perform clinical trials to validate the effectiveness of interventions against lymphopenia. Furthermore, children are not immune to COVID-19 and most infected children have been found to have a history of recent infections in their families [53], [54].
Multiple comorbidities have been found to be associated with the severity of disease and progression in SARS and MERS [55], [56], [57]. Similarly, recent studies have shown that COVID-19 patients with diabetes, chronic obstructive pulmonary disease (COPD), cardiovascular diseases (CVD), hypertension, malignancies, and other comorbidities had a markedly higher mortality rate. Elevated levels of ACE2 that were proposed to be associated with an increased susceptibility have been observed in COVID-19 patients with diabetes, COPD, and CVD [58]. Persons suffering from hypertension may also have increased ACE2 levels induced by heavy dosages of ACE2 inhibitors and angiotensin receptor blockers (ARBs) during treatment. However, there has been no evidence that ACE inhibitors or ARBs affects the severity of COVID-19 [59], [60], [61], [62]. Apart from hypertension, patients with cancer were found to be more susceptible due to their systemic immunosuppressive state [63]. Patients with cancer had a significantly higher risk of ICU admission, requiring invasive ventilation, and death [63], [64]. Therefore, patient triage should be based on the presence and spectrum of comorbidities, which would allow for more intensive monitoring among patients at higher risk of developing severe clinical outcomes. Meanwhile, radiotherapy and chemotherapy may be postponed for cancer patients who are clinically stable in order to minimize the risk of acquiring nosocomial infections.
The presence of systemic symptoms varied considerably among different countries. A recent meta-analysis of 29 studies, mainly from China, demonstrated that anorexia was present in 21%, nausea and/or vomiting in 7%, diarrhea in 9%, and abdominal pain in 3% of the cases, respectively. However, in a study from the United States, the systemic symptoms of anorexia (34.8%), diarrhea (33.7%), and nausea (26.4%) were found to be more common [14].
It is noteworthy that a small proportion of patients remained asymptomatic throughout the course of the disease [65]. Because of the atypical manifestations, contact tracing of asymptomatic patients is necessary after a positive viral RNA test [66], [67]. The first report of an asymptomatic patient was anecdotal, based on a chest CT scan of an infected child in a familial cluster of cases. Further studies demonstrated that the proportion of asymptomatic patients ranged from 20% to 78% of positive cases [66], [68]. Of the 166 new cases identified on 1 April 2020 in China, 130 (78%) were asymptomatic. Unlike symptomatic patients, hyposmia and nasal congestion were frequent among asymptomatic patients—regardless of whether they had positive CT scan findings or not—but uninfected patients could be excluded by RT-PCR. Asymptomatic patients remained contagious; viral shedding was found to be most prominent before symptom onset, and the duration of shedding might be extended in comparison with symptomatic patients [69], [70]. However, the population of asymptomatic individuals may be highly heterogeneous, as such individuals may be in the earlier stages of the disease or could remain asymptomatic throughout the course of the disease.