Coronavirus Disease 2019 (COVID-19): A Perspective from China

Introduction

An ongoing outbreak of pneumonia associated with a novel coronavirus, severe acute respiratory syndrome (SARS) coronavirus 2, was reported in Wuhan, Hubei Province, China, in December 2019 (1–3). In the following weeks, infections spread across China and other countries around the world (4–6). The Chinese public health, clinical, and scientific communities took action to allow for timely recognition of the new virus and shared the viral gene sequence to the world (2,7). On January 30, 2020, the World Health Organization (WHO) declared the outbreak a Public Health Emergency of International Concern (8). On February 12, 2020, the WHO named the disease caused by the novel coronavirus “coronavirus disease 2019” (COVID-19) (9). A group of international experts, with a range of specializations, have worked with Chinese counterparts to try to contain the outbreak (10).

At present, a real-time reverse-transcription polymerase chain reaction (RT-PCR) assay for COVID-19 has been developed and used in clinics. Although RT-PCR remains the reference standard for making a definitive diagnosis of COVID-19 infection (11), the high false-negative rate (12) and the unavailability of the RT-PCR assay in the early stage of the outbreak restricted prompt diagnosis of infected patients. Radiologic examinations, especially thin-slice chest CT, play an important role in fighting this infectious disease (13). Chest CT can help identify the early phase lung infection (14,15) and prompt larger public health surveillance and response systems (16). Currently, chest CT findings have been recommended as major evidence for confirmed clinical diagnosis in Hubei, China. The addition of chest CT for diagnosis resulted in 14 840 confirmed new cases (13 332 clinically diagnosed cases) reported on February 13, 2020. Comprehensive and timely review of the role of radiology in fighting COVID-19 remains urgent and mandatory.

Etiology

In a preliminary report, complete viral genome analysis revealed that the virus shared 88% sequence identity to two bat-derived SARS-like coronaviruses, but more distant from SARS coronavirus (17). Hence, the virus was temporarily called 2019 novel coronavirus (2019-nCoV). Coronavirus is an enveloped and single-stranded ribonucleic acid named for its solar corona-like appearance due to 9–12-nm-long surface spikes (18). There are four major structural proteins encoded by the coronaviral genome on the envelope, one of which is the spike protein (S) that binds to angiotensin-converting enzyme 2 receptor and mediates subsequent fusion between the envelope and host cell membranes to aid viral entry into the host cell (19,20). On February 11, 2020, the Coronavirus Study Group of the International Committee on Taxonomy of Viruses finally designated it as SARS coronavirus 2 based on phylogeny, taxonomy, and established practice (21). Shortly thereafter, the WHO named the disease caused by this coronavirus COVID-19 (9). On the basis of current data, it seems that SARS coronavirus 2 might be initially hosted by bats and might have been transmitted to humans by means of pangolin (22) or other wild animals (17,23) sold at the Huanan Seafood Market but subsequently spread by means of human-to-human transmission.

Epidemiology

In December 2019, the earliest symptoms of patients confirmed to have COVID-19 appeared (24). At first, the morbidity remained low. However, it reached a tipping point in the middle of January 2020. During the second half of that month, there was a remarkable increase in the number of infected patients in affected cities outside Hubei Province because of the population movement before the lunar Chinese New Year (25). Followed by an exponential growth until January 23, 2020, the outbreak spread to the other countries, attracting extensive attention around the world (Fig 1). Evidence of clusters of infected family members and medical workers confirmed the presence of human-to-human transmission (12) by droplets, contact, and fomite (26,27). Thus far, there is no definite evidence of intrauterine transmission (28). Current estimates are that COVID-19 has a median incubation period of 3 days (range, 0–24 days), with potential transmission from asymptomatic individuals (26,29). At the end of January 2020, the WHO confirmed that there were more than 10 000 cases of COVID-19 across China (30). On February 13, 2020, 13 332 new clinically diagnosed cases were first reported from Hubei. Official reports included clinically diagnosed cases and laboratory-confirmed cases because chest CT findings were recommended as the major evidence for clinically confirmed cases in the Diagnosis and Treatment Program of 2019 New Coronavirus Pneumonia (trial version 5) by the National Health and Health Commission of China in February 2020 (13). As of February 19, 2020, the total number of confirmed cases rose to 74 280 in China and to 924 in 25 countries outside China; there was a total of 2009 deaths globally (10) (Fig 2). To control COVID-19, effective prevention and control measurements must include early detection, diagnosis, treatment, and quarantine to block human-to-human transmission and reduce secondary infections among close contacts and health care workers (10).

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Clinical Symptom Spectrum

Understanding the clinical symptoms of COVID-19 is important, although the clinical symptoms are indicated nonspecific. Common symptoms include fever, cough, myalgia, and fatigue. Patients may initially present with diarrhea and nausea a few days before developing a fever, which suggests that fever is dominant but not the premier symptom of infection. A small number of patients can have headache or hemoptysis (26,31) and be relatively asymptomatic (12). Affected older men with comorbidities are more likely to have respiratory failure due to severe alveolar damage (32). Disease onset may show rapid progression to organ dysfunction (eg, shock, acute respiratory distress syndrome, acute cardiac injury, and acute kidney injury) and even death in severe cases (1,31). Meanwhile, patients might have normal or lower white blood cell counts, lymphopenia, or thrombocytopenia, with extended activated thromboplastin time and increased C-reactive protein level (1,26,31,32). In short, COVID-19 should be suspected in a patient with fever and upper respiratory tract symptoms with lymphopenia or leukopenia, especially in those with Wuhan exposure or a history of close contact with people from Wuhan or patients confirmed to have COVID-19.

Diagnosis of COVID-19 Infection

The first task for the clinical diagnostic workflow is to confirm a history of Wuhan exposure or close contact with people from Wuhan or patients confirmed to have COVID-19 during the past 2 weeks. However, the number of patients with unknown exposure history is increasing due to the rapid and extensive spread of the disease. The National Health Commission of China (33,34) formulated the Diagnosis and Treatment Program of 2019 New Coronavirus Pneumonia (trial version 6) (Table 1) based on WHO recommendations for SARS and Middle East respiratory syndrome (35–37). A patient with one exposure history and two clinical conditions is considered as suspected case. If there is no clear exposure history, patients suspected of having COVID-19 should meet three clinical conditions (Table 1). Based on trial version 5 (13), chest CT findings of viral pneumonia are regarded as evidence of clinical diagnosis of COVID-19 infection. However, the WHO did not accept CT findings without RT-PCR confirmation until February 17, 2020 (38), and the most recently published Diagnosis and Treatment Program of 2019 New Coronavirus Pneumonia (trial version 6) has deleted the term clinical diagnosis (34). The final etiologic diagnosis of COVID-19 is necessary and can be further confirmed with a positive real-time RT-PCR assay for COVID-19 using respiratory or blood samples or by means of viral gene sequencing of respiratory or blood samples that are highly homologous with COVID-19. Patients confirmed to have COVID-19 are classified as having mild, moderate, severe, or critical disease according to clinical manifestations (Table 2) (13,34,39).

Table 1: Case Definition for Surveillance of COVID-19 by Chinese Health Commission

Table 2: Criteria for Clinical Severity of Confirmed COVID-19 Pneumonia

Role of Radiology in the Detection of COVID-19

Radiologic examinations are of great importance in the early detection and management of COVID-19. Because chest radiography has lower density resolution and may demonstrate normal findings in the early stage of infection (16), it is not recommended as the first-line imaging modality for COVID-19. However, bilateral multifocal consolidation (Fig 3) can be seen in patients with severe disease, partially fused into massive consolidation with small pleural effusions and even manifesting as “white lung” (11). Thin-slice chest CT is more effective in the early detection of COVID-19 pneumonia (12,16). The largest sample study to date showed that, among 3665 patients with confirmed COVID-19, pneumonia was diagnosed in 3498 (95.5%) (25). Pan et al (40) reviewed 21 patients with COVID-19 who underwent repeat CT at approximately 4-day intervals and found that four patients had negative findings at an early stage (0–4 days after onset of the initial symptoms). However, repeat chest CT showed lung abnormalities in all four of these patients.

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To date, only five case series studies (16,40–43) and some case reports (44–54) have investigated the chest CT features of COVID-19 pneumonia. COVID-19 pneumonia has nonspecific and various features at chest CT. The typical chest CT findings include multifocal bilateral ground-glass opacities (GGOs) with patchy consolidations, prominent peripherally subpleural distribution, and posterior part or lower lobe predilection (Figs 4–9) (14,55,56). GGO is a hazy increase in attenuation that appears in a variety of interstitial and alveolar processes, with preservation of the bronchial and vascular margins (57), whereas consolidation is an area of opacification obscuring the margins of vessels and airway walls (58). In patients with COVID-19 pneumonia, focal or multifocal pure GGO (Figs 4a, 5, 6b) and GGO with reticular and/or interlobular septal thickening as typical crazy-paving pattern (Fig 6a) were often observed, whereas pure consolidation (Fig 7) was relatively less common or absent (16,40–42). Pure GGO lesions (Figs 4a, 5, 9b) can be an early feature of COVID-19 pneumonia. In the study by Chung et al (41), one patient had normal chest CT findings on the initial scan but showed a new solitary, rounded peripheral GGO lesion 3 days later. The reversed CT halo sign, defined as a rounded area of ground glass surrounded by a complete or almost complete ring of consolidation, can also be observed (16,49). Pleural effusion, lung cavitation, lymphadenopathy, and calcification are rarely reported (40–44,49,50). Table 3 summarizes the characteristic chest CT features of COVID-19 pneumonia.

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Table 3: Chest CT Features of COVID-19 Pneumonia

Other diseases mimic COVID-19 pneumonia and should be differentiated, including other coronavirus infections and community-acquired pneumonia such as Streptococcus, mycoplasma, and Chlamydia-related pneumonia. Differential diagnosis is very important so that patients with fever who are suspected of having COVID-19 can be quarantined to reduce cross infection. Table 4 shows typical clinical and CT findings of conditions that mimic COVID-19, such as the common cold, influenza, and other coronavirus diseases including SARS and Middle East respiratory syndrome (34,59–63). Wuhan exposure history or close contact with patients confirmed to have or suspected of having COVID-19 is an essential clue for the diagnosis. However, for patients with unknown epidemiologic history, typical clinical and imaging appearance can indicate suspected COVID-19; the RT-PCR test should be performed in these patients. In summary, the diagnosis of COVID-19 should combine epidemiologic history, clinical and imaging manifestations, and RT-PCR test results (the reference standard).

Table 4: Comparison of Symptoms and CT Findings of the Common Cold, Influenza, SARS, MERS, and COVID-19

Value of Radiology in the Prevention and Control of COVID-19

Although chest CT findings are nonspecific for COVID-19 detection, CT findings have been recommended as major evidence of clinical diagnosis in Hubei Province by the National Health and Health Commission of China (13). A positive finding for COVID-19 at RT-PCR remains the reference standard (11), but RT-PCR results can be affected by sampling errors and low virus load (61,64,65). Previous SARS studies (66–68) showed that RT-PCR lacked sensitivity during the first 5 days of the disease. Current reports show that chest CT may demonstrate pneumonia while multiple RT-PCR tests of nasopharyngeal or throat swabs show negative findings (12,53,69,70). Fang et al (71) compared the detection rate of initial chest CT examination and RT-PCR and reported a higher detection rate for initial CT examination (50 of 51 patients, 98%) than for the first RT-PCR test (36 of 51 patients, 71%) (P < .001). Xie et al (69) evaluated 167 patients and found that 3% (five patients) had initially negative findings at RT-PCR but positive findings at chest CT. Both RT-PCR and CT findings were concordant for COVID-19 in 155 of the 167 patients (92.8%). Furthermore, RT-PCR results must be checked by the Centers for Disease Control and Prevention in the early stage of an outbreak, which prolongs the time to confirm the final diagnosis (25). Thin-slice chest CT is easy to perform, fast, and depicts early COVID-19 pneumonia with high sensitivity, providing valuable information for further diagnosis while aiding prevention and control of COVID-19.

CT can also help assess the severity of COVID-19 to guide clinical management. Clinical observations (1) showed that patients admitted to the intensive care unit often had bilateral multiple lobular and subsegmental consolidation, whereas those not admitted to the intensive care unit had bilateral GGOs and subsegmental consolidation. In patients with severe disease, CT can demonstrate diffuse heterogeneous consolidation with GGOs in bilateral lungs with air bronchial sign and bronchiectasis (Fig 9), manifesting as “white lung” when most lung lobes are affected (15). Patients may also have thickening of interlobar septa and bilateral pleura with a small pleural effusion (11,56).

In addition, CT enables surveillance of the disease time course of COVID-19. Chung et al (41) found that seven of the eight patients who underwent follow-up CT showed mild or moderate progression that manifested as increasing number, extent, and attenuation of GGOs (Figs 4, 9). Pan et al (40) reviewed 21 patients with COVID-19 who underwent repeat CT at approximately 4-day intervals and summarized four stages of the disease: early, progressive, peak, and absorption. They found that GGOs will grow rapidly, demonstrating consolidation and crazy-paving pattern as the disease progresses. The lesions will absorb without crazy-paving pattern in the absorption stage, suggesting that crazy-paving pattern can be used as another index to evaluate the disease course. Song et al (42) concluded that greater consolidation was indicative of disease progression. Some case reports showed that smaller size, extent, and absorption of these lesions was indicative of improvement (32,42,51–53).

Conclusion

Characteristic chest CT features and history of Wuhan exposure or close contact with a patient with coronavirus disease 2019 (COVID-19) are highly suggestive of COVID-19 pneumonia, although reverse-transcription polymerase chain reaction remains the reference standard. Typical CT features of COVID-19 pneumonia include multifocal bilateral ground-glass opacities with patchy consolidations, prominent peripherally subpleural distribution, and posterior part or lower lobe predilection. Thin-slice chest CT can help prompt diagnosis, guide clinical decision making, and monitor disease progression, playing a crucial role in the early prevention and control of COVID-19. Special attention should be paid to the role of radiologists in fighting this new infectious disease. A full translation of this article in Chinese is provided in Appendix E1 (online).