**4. General clinical presentation of COVID-19**

With the emergence of the pandemic in earnest at the beginning of 2020, the medical and scientific literature has been flooded with case reports and small clinical series often on a regional (district/country) basis. In general, the clinical presentation of patients with SARS-CoV-2 is very similar to that of other coronavirus infections in humans. For the majority of those infected, individuals are either asymptomatic or have a mild fever, novel dry cough or anosmia (loss of smell).

*Cardiac Diseases - Novel Aspects of Cardiac Risk, Cardiorenal Pathology and Cardiac Interventions*

as on vascular endothelial cells [12]. This is especially important in those individuals with underlying cardiovascular diseases as expression of ACE2 in the vasculature is altered [13]. This will be detailed further in the chapter under cardiovascular involvement. Following internalisation via vesicle entry, the ACE2 surface proteins are downregulated, potentiating the increasing physiological effects of angiotensin

The major route of transmission in the human population is from person-to-person via respiratory droplets when infected individuals cough, sneeze and talk when in close contact with another person [15]. Susceptible individuals inhale droplets shed from an infected individual near one another. The risk of infection depends on the size of the particles and droplets, the extent of viral shedding from the infected individual, the force of expulsion of droplets from an infected individual, the proximity between infected and uninfected individuals as well as environmental factors such as air density, humidity and wind speed [16]. Aerosol transmission is an alternative route of infectivity; however, this has been subject to significant

Aerosol transmission occurs when proteins and pathogens float in the form of aerosols after droplets dry out. This may be possible with SARS-CoV-2 in enclosed areas if individuals are exposed to high levels of infected aerosol material such as in care home settings and hospital wards; thus, pose a risk to healthcare workers and others in close contact with infected individuals over a long period of time. Aerosol transmission is often successful with particles with a diameter of 5–10 μm and can be carried over a large distance, whereas droplets are often larger than 10 μm and fall from the air within 1 metre hence the global adoption of spacing between

Oral-faecal transmission is another potential route of person-to-person transmission [18]. SARS-CoV-2 has been detected in faecal material from known COVID-19 patients [15, 19]. This is unsurprising given the clinical gastrointestinal manifestations in some individuals. This poses as a rapid transmission route in

*Viral entry of SARS-CoV-2 in host cells via the ACE2 surface protein. Following entry ACE2 is downregulated resulting in upregulation of angiotensin II (Ang II) which via its AT1R receptor induces NF-kB signalling pathways to increase expression of inflammatory cytokines such as interleukins (IL-1, IL1*β*, IL-6), matrixmtalloproteinases (MMP-1, MMP-3) and tumour necrosis factor alpha (TNF-*α*). [source: Banu* 

II (**Figure 5**) via proinflammatory mediators [14].

**3.3 Routes of transmission of SARS-CoV-2**

debate and scientific study.

individuals of 1–2 metres [17].

**130**

**Figure 5.**

*et al. [14]].*


#### **Table 1.**

*Clinical characteristics and outcomes in COVID-19. Analysis of 281,461 confirmed cases. 95% CI, confidence interval. [source, data from Li et al. [27]].*

In the small minority of those who are severely affected, the overriding clinical presentation is of respiratory distress however other symptoms are case-dependent.

The reported clinical characteristics and prognosis of COVID-19 patients varies greatly (**Figure 6**). A recent comprehensive meta-analysis has been performed of clinical characteristics, risk factors and outcomes by Li and colleagues [27]. This vast analysis includes 212 studies from 11 countries involving 281,461 laboratory confirmed COVID-19 cases. The mean age of patients was 46.7y (95%CI 42.8y to 50.6y) with 51.9 (95%CI 50.4 to 53.2) males. The mean time of illness onset to hospital admission was 5.5 days (95%CI 4.6 to 6.4 days) with an incubation period of 5.3 days (95%CI 4.5 to 5.9 days). Clinical presentation characteristics and outcome are summarised in **Table 1**. 79% of subjects were febrile and 53% developed a cough. Renal and hepatic injury occurred in 4% and 7% respectively but cardiac injury was higher at 9%. Overall mortality was reported to be 6% but this differed greatly by country. Mortality was significantly associated with age, male sex, the presence of hypertension or diabetes mellitus [27].

### **5. Chest imaging**

Thoracic imaging is an important diagnostic tool in screening, early diagnosis and monitoring of patients with COVID-19. Although computed tomography (CT) is the gold standard, chest x-ray (CXR) is a cheap, readily available and a

**133**

**Figure 7.**

*adapted from Pereira et al. [30]].*

*Coronavirus Disease: Epidemiology, Aetiology, Pathophysiology and Involvement…*

respiratory diseases and a normal CXR are shown in **Figure 7**.

faster alternative. CXR lacks sensitivity for diagnosis in the early presentation of COVID-19 being 55% within two days, increasing to 79% at 11 days from onset of symptoms. Specificity decreased over time from 83–70% at ≤2d and > 11d respectively [28]. In approximately 60% of cases, CXR reveals interstitial and airspace opacities in an IA pattern. This increased over time from 51% at ≤2d vs. 73% at >11d [28]. Normal and mild severity CXR findings were the largest factor behind false-negative CXR and often associated with young age and some ethnic groups. In a real-world reader performance study by Cozzi and colleagues [29], experienced radiologist (>10 y experience) reported CXR with higher specificity than less experienced (<10 y experience) radiologists. Comparative CXR images from different

Computed tomography (CT) is the preferred radiological procedure for diagnosis. A Cochrane review of CT for diagnosis of COVID-19 found that in 84 studies with 8,279 participants; the pooled sensitivity for diagnosis was 86% (95%CI 90–95%) with a very low specificity of 18% (95%CI 4–56%) [31]. A retrospective study of chest CT findings in 121 symptomatic patients in 4 centres in China has been reported [32]. The classical findings were bilateral and peripheral ground-glass

*Comparative chest X-ray findings in (a) normal CXR (b) SARS (c) MERS (d) COVID-19. [source: Images* 

*DOI: http://dx.doi.org/10.5772/intechopen.98210*

*Coronavirus Disease: Epidemiology, Aetiology, Pathophysiology and Involvement… DOI: http://dx.doi.org/10.5772/intechopen.98210*

faster alternative. CXR lacks sensitivity for diagnosis in the early presentation of COVID-19 being 55% within two days, increasing to 79% at 11 days from onset of symptoms. Specificity decreased over time from 83–70% at ≤2d and > 11d respectively [28]. In approximately 60% of cases, CXR reveals interstitial and airspace opacities in an IA pattern. This increased over time from 51% at ≤2d vs. 73% at >11d [28]. Normal and mild severity CXR findings were the largest factor behind false-negative CXR and often associated with young age and some ethnic groups. In a real-world reader performance study by Cozzi and colleagues [29], experienced radiologist (>10 y experience) reported CXR with higher specificity than less experienced (<10 y experience) radiologists. Comparative CXR images from different respiratory diseases and a normal CXR are shown in **Figure 7**.

Computed tomography (CT) is the preferred radiological procedure for diagnosis. A Cochrane review of CT for diagnosis of COVID-19 found that in 84 studies with 8,279 participants; the pooled sensitivity for diagnosis was 86% (95%CI 90–95%) with a very low specificity of 18% (95%CI 4–56%) [31]. A retrospective study of chest CT findings in 121 symptomatic patients in 4 centres in China has been reported [32]. The classical findings were bilateral and peripheral ground-glass

#### **Figure 7.**

*Cardiac Diseases - Novel Aspects of Cardiac Risk, Cardiorenal Pathology and Cardiac Interventions*

Fever 15,921 78.8 76.2 to 81.3 Fatigue 13,680 32.2 28.0 to 36.6 Myalgia 10,728 21.3 18.1 to 24.9 Malaise 2,526 37.9 29.5 to 47.1

Cough 12,782 53.9 50.0 to 57.7 Expectoration 6,072 7.5 5.7 to 9.6 Chest pain 3,512 9.0 6.2 to 13.1 Shortness of breath 11,205 18.9 15.7 to 22.8

Nausea 5,599 6.9 5.3 to 9.1 Vomiting 7,484 4.7 3.8 to 5.8 Diarrhoea 12,142 9.5 7.8 to 11.5

Renal injury 77,679 3.6 1.2 to 10.1 Hepatic injury 77,331 7.9 2.6 to 21.7 Cardiac Injury 1,417 9.4 4.5 to 18.8 Mechanical ventilation 6,152 7.1 4.5 to 11.0 Mortality 52,808 5.6 4.2 to 7.5

**Participants (n) Value (%) 95% CI**

In the small minority of those who are severely affected, the overriding clinical presentation is of respiratory distress however other symptoms are case-dependent. The reported clinical characteristics and prognosis of COVID-19 patients varies greatly (**Figure 6**). A recent comprehensive meta-analysis has been performed of clinical characteristics, risk factors and outcomes by Li and colleagues [27]. This vast analysis includes 212 studies from 11 countries involving 281,461 laboratory confirmed COVID-19 cases. The mean age of patients was 46.7y (95%CI 42.8y to 50.6y) with 51.9 (95%CI 50.4 to 53.2) males. The mean time of illness onset to hospital admission was 5.5 days (95%CI 4.6 to 6.4 days) with an incubation period of 5.3 days (95%CI 4.5 to 5.9 days). Clinical presentation characteristics and outcome are summarised in **Table 1**. 79% of subjects were febrile and 53% developed a cough. Renal and hepatic injury occurred in 4% and 7% respectively but cardiac injury was higher at 9%. Overall mortality was reported to be 6% but this differed greatly by country. Mortality was significantly associated with age, male sex, the

*Clinical characteristics and outcomes in COVID-19. Analysis of 281,461 confirmed cases. 95% CI, confidence* 

Thoracic imaging is an important diagnostic tool in screening, early diagnosis and monitoring of patients with COVID-19. Although computed tomography (CT) is the gold standard, chest x-ray (CXR) is a cheap, readily available and a

presence of hypertension or diabetes mellitus [27].

**132**

**5. Chest imaging**

**Clinical Presentation**

**Respiratory symptoms**

**Gastrointestinal symptoms**

*interval. [source, data from Li et al. [27]].*

**Prognosis**

**Table 1.**

*Comparative chest X-ray findings in (a) normal CXR (b) SARS (c) MERS (d) COVID-19. [source: Images adapted from Pereira et al. [30]].*

#### **Figure 8.**

*Representative characteristic findings of COVID-19 infection on thoracic CT imaging: (a) axial CT image obtained without intravenous contrast. 36y male showing bilateral ground-glass opacities in upper lobes with rounded morphologies (arrows); (b) axial CT image. 65 y female, showing bilateral ground-glass and consolidative opacities with striking peripheral distribution (arrows); (c) axial CT image obtained without intravenous contrast material in a 43 y female, demonstrating crazy-paving pattern manifested by right lower lobe ground-glass opacification with interlobular septal thickening (arrows) with intralobular lines. (d) Axial CT image obtained in a 22y female, showing an area of faint ground-glass opacification in left upper lobe with a ring of denser consolidation or reverse halo sign (arrow). [source: Images modified from Bernheim et al. [32]].*

consolidative opacity. 56% of subjects had normal CT images in the early phase (0 to 2 days) of the disease but more frequent in longer infections with consolidation, bilateral and peripheral and greater total lung involvement. Bilateral involvement occurred in 28%, 76% and 88% of early (0–2 days), intermediate (3–5 days) and late (6–12 days) infection times respectively. Further notable CT findings include linear opacity, crazy-paving patterns and reverse halo sign (**Figure 8**).

Following isolation and treatment, most COVID-19 patients stabilise and become well. Further CT imaging demonstrates regression of infection with absorbed lesions, and some cord-like shadows.

## **6. Gastrointestinal symptoms in COVID-19**

Gastrointestinal (GI) symptoms are emerging in patients with COVID-19. This is due to the presence of the ACE2 receptor expressed in the GI tract [33, 34].

COVID-19 patients present with GI symptoms such as diarrhoea (10% of patients) with nausea and vomiting less common [35]. In a meta-analysis of 35 studies, 29 studies reported gastrointestinal symptoms in 6,064 COVID-19 patients with a pooled prevalence of gastrointestinal comorbidities of 4%. (95% CI 2 to 5%; range 0 to 15%; *I* 2 = 74%). The pooled prevalence of digestive symptoms was 15% (10 to 21%; range: 2 to 57%; *I* 2 = 96%) with nausea or vomiting, diarrhoea, and loss of appetite being the three most common [36].

**135**

**Figure 9.**

*Coronavirus Disease: Epidemiology, Aetiology, Pathophysiology and Involvement…*

In addition to respiratory and gastrointestinal symptoms, cardiovascular involvement is also common amongst patients with COVID-19. The symptoms are wide-ranging in manifestation and severity and are more common in the elderly and those hospitalised with the infection. Previous influenza epidemics have been associated with an increased prevalence of myocardial infarction, myocarditis and chronic/congestive heart failure [37]. Both SARS and MERS were associated with either bradycardia, tachycardia, cardiomegaly, diastolic impairments, cardiac

Patients with cardiovascular risk factors or established cardiovascular disease disproportionately suffer with severe forms of the infection with worse clinical prognosis and outcome. In one of the earliest reports of clinical characteristics of COVID-19 from Wuhan China; 14% of 138 patients demonstrated baseline cardiovascular disease and 31% had hypertension [41]. Similar data has been reported in other population studies from Wuhan, China [42–44]; Italy [45, 46]; Iran [47],

The pathophysiological mechanism of cardiac injury in COVID-19 infection are similar to those associated with other influenza pandemics and human coronavirus diseases (SARS and MERS). Although the pathophysiological mechanisms injury is not fully established in COVID-19 patients, it is likely that the elevation is related to (1) Systemic inflammatory involvement, cytokine storm mediated through T-cell and monocytes resulting in myocarditis. Often patients have concomitant elevations in C-reactive protein (CRP), eosinophil sedimentation rate (ESR) (2) Hypercoagulability.

United Kingdom [48] and the USA [49] to varying cardiac involvement.

*Pathophysiological mechanisms of acute myocardial injury in COVID-19 infection.*

*DOI: http://dx.doi.org/10.5772/intechopen.98210*

**7. Cardiovascular findings in COVID-19**

arrest, cardiomegaly and acute cardiac failure [38–40].

*Coronavirus Disease: Epidemiology, Aetiology, Pathophysiology and Involvement… DOI: http://dx.doi.org/10.5772/intechopen.98210*
