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COVID-19

Changed by Daniel J Bell, 24 Mar 2020
Back to revision history

Updates to Article Attributes

Body was changed:

For a quick reference guide, please see our COVID-19 summary article.

COVID-19 (coronavirus disease 2019) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), previously known as 2019 novel coronavirus (2019-nCoV), a species of coronavirus. The first cases were seen in Wuhan, China in December 2019 before spreading globally 1,2,10. The current outbreak was recognized as a pandemic on 11 March 2020 44.

The non-specific imaging findings are most commonly of atypical or organising pneumonia, often with a bilateral, peripheral, and basal predominant distribution 32. No effective treatment or vaccine exists currently (March 2020) 20.

Terminology

The World Health Organisation (WHO) originally called this illness "novel coronavirus-infected pneumonia (NCIP)" and the virus itself had been named "2019 novel coronavirus (2019-nCoV)" 1.

On 11 February 2020, the WHO officially renamed the clinical condition COVID-19 (a shortening of COronaVIrus Disease-19) 15. Coincidentally, on the same day, the Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses renamed the virus "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2) 16,22,46. The names of both the disease and the virus should be fully capitalised, except for the 'o' in the viral name, which is in lowercase 16,22,41. 

The official virus name is similar to sudden acute respiratory syndrome (SARS) and its causative virus, SARS-CoV, potentially causing confusion 38. The WHO has stated it will use "COVID-19 virus" or the "virus that causes COVID-19" instead of its official name, SARS-CoV-2, in dealings with the public 45.

Epidemiology

As of 24 March 2020, over 381,000 cases of COVID-19 have been confirmed worldwide, having been diagnosed in 168 territories, in six continents according to an online virus tracker created by the medical journal, The Lancet, and hosted by Johns Hopkins University 5,13. There are seven countries with >10,000 confirmed cases and nineteen countries with between 1000 and 10,000 confirmed cases 5. 

NB: Surveillance methods and capacity vary dramatically between countries, and there is reason to suspect that there may be a significant number of carriers in some countries not diagnosed.

The R0 (basic reproduction number) of SARS-CoV-2 has been estimated between2.2 and 3.28 12,33, that is each infected individual, on average, causes between 2-3 new infections. The incubation period in this group has been calculated to be 5.2 days on average 12.

A paper published by the Chinese Center for Disease Control and Prevention (CCDC) analysed all 44,672 cases diagnosed up to 11 February 2020. Of these, 1.2% were asymptomatic and 80.9% were classed as "mild" 25. 

Another study looked at clinical characteristics in COVID-19 positively tested closed contacts of COVID-19 patients 81. About 29.2% of those COVID-19 positive closed contacts never developed any symptoms or changes on chest CT scans. The remainder showed changes on CT, but apparently, only 21% developed symptoms during their hospital course, none of them developed severe disease 81. This suggests that a high percentage of COVID-19 carriers are asymptomatic.

In an article examining the first 425 infected cases in Wuhan, 56% of the infected were male and the median age was 59 years 12.

Paediatric

Children seem to be relatively unaffected by this virus, or indeed other closely-related coronaviruses 31,47,90, however, there have been cases of critically-ill children with infants under 12 months likely to be more seriously affected 59.

In a large cohort Chinese study which included 44,672 COVID-19 positive patients, 2% of the total were children, and a large Italian series stated that just 1.2% of 22,512 COVID-19 patients were children. In children, male gender does not seem to be a risk factor 59.

In China, only two deaths in children have been reported, one in a 14 year old 59, the other in a 10-month old 9091. No deaths have been reported in Italy for anyone less than 30 years old 90.

In children, the incubation period is about two days 90.

NB: it is important to appreciate that the known epidemiological parameters of any new disease are likely to change as larger cohorts of infected people are studied, although this will only to some extent reflect a true change in the underlying reality of disease activity (as a disease is studied and understood humans will be simultaneously changing their behaviours to alter transmission or prevalence patterns).

Clinical presentation

COVID-19 typically presents with systemic and/or respiratory manifestations. Some individuals infected with SARS-CoV-2 are asymptomatic and can act as carriers 70. Some also experience mild gastrointestinal or cardiovascular symptoms, although these are much less common 18,50. However;

However, itsthe full spectrum of clinical effects of COVID-19 remains to be determined 1,13. Symptoms and signs are non-specific 68:

Common:

  • fever  (85-90%)
  • cough (65-70%)
  • fatigue (35-40%)
  • sputum production (30-35%)
  • shortness of breath (15-20%)

Less common:

Rare:

  • nausea, vomiting, diarrhoea, nasal congestion (<10%)
  • palpitations, chest tightness 50

Anecdotal reports from ENT specialists in the UK 79 suggest that COVID-19 sufferers have high rates of anosmia/hyposmia, however, no peer-reviewed studies supporting this are yet available.

Paediatric

In the main the clinical presentation in children with COVID-19 is more mild than in adults 59,90. Symptoms are similar to any acute chest infection, encompassing most commonly pyrexia, dry cough, sore throat, sneezing, myalgia and lethargy. Wheezing has also been noted 59,90. Other less common (<10%) symptoms in children included diarrhoea, lethargy, rhinorrhea and vomiting 91.

Diagnosis

The definitive test for SARS-CoV-2 is the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test and is believed to be highly specific, but with sensitivity reported as low as 60-70% 32 and as high as 95-97% 56 depending on the country. Thus, false negatives are a real clinical problem and several negative tests might be required in a single case to be confident about excluding the disease.

Multiple radiological organisations have come forward to state that CT should not be relied upon as a primary diagnostic/screening tool for COVID-19 52,57,87,88. On 16 March 2020, an American-Singaporean panel published that CT findings were not part of the diagnostic criteria for COVID-19 56. However, CT findings have been used as a surrogate diagnostic test 2,32,89. 

Laboratory tests

The most common ancillary laboratory findings in a study of 138 hospitalised patients were the following 13,89:

Mild elevations of inflammatory markers (CRP 89 and ESR) and D-dimer are also seen.

Complications

In a study of 138 patients who had been hospitalised, 26% were admitted to the intensive care unit (ICU). The ICU patients tended to be older with more comorbidities 13. Common sequelae included the following:

In a small subgroup of severe ICU cases:

Pathology

Aetiology

On 9 January 2020, the World Health Organisation (WHO) confirmed that SARS-CoV-2 was the cause of COVID-19 (2019-nCoV was the name of the virus at that time) 14,37. It is a member of the Betacoronavirus genus, one of the genera of the Coronaviridae family of viruses. Coronaviruses are enveloped single-stranded RNA viruses, that are found in humans, many other mammals, and birds. These viruses are responsible for pulmonary, hepatic, CNS, and intestinal disease. 

As with many human infections, SARS-CoV-2 is zoonotic. The closest animal coronavirus by genetic sequence is a bat coronavirus, and this is the likely ultimate origin of the virus 11,19,26. The disease can also be transmitted by snakes 24.

Hitherto, six coronaviruses have been known to be responsible for human diseases. Two are zoonoses: the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), both of which may sometimes be fatal. The remaining four viruses are widespread in human society, causing the common cold. 

Pathophysiology

The SARS-CoV-2 virus, like the closely-related MERS and SARS coronaviruses, affects its cellular entry via attachment of its virion spike protein (a.k.a. S protein) to the angiotensin-converting enzyme 2 (ACE 2) receptor. This receptor is commonly found on alveolar cells of the lung epithelium, underlying the development of respiratory symptoms as the commonest presentation of COVID-19 50. It is thought that the mediation of the less common cardiovascular effects is also via the same ACE-2 receptor which is also commonly expressed on the cells of the cardiovascular system 50.

Transmission

Although originating from animals, COVID-19 is not considered a direct zoonosis as its transmission is now primarily human-to-human. It is primarily transmitted in a similar way to the common cold, via contact with droplets of infected individuals' upper respiratory tract secretions, e.g. from sneezing or coughing 19.

A recent Bayesian regression model has found that aerosol and fomite transmission isare plausible 58.

Orofaecal spread was seen with the SARS epidemic, and although it remains unclear if SARS-CoV-2 can be transmitted in this way, there is some evidence for it 19,43.

A recent retrospective study of nine pregnant patients infected by SARS-CoV-2 did not show any evidence of vertical/intrauterine infection 21. More recent published (20 March 2020) guidance from a joint American-Chinese consensus panel stated that it remains unclear if vertical transmission can occur 82.

Considerations for medical imaging departments

Infection precautions

Given that the staff in a medical imaging department are some of the first parties to be in contact with COVID-19 patients, clear infection control guidelines are imperative. At the time of writing (8 March 2020) droplet-type precautions are in place for COVID-19 patients, that is, medical mask, gown, gloves, and eye protection (aerosol-generating procedures require N95 masks and aprons) 39.

Patients requiring general radiography should receive it portably (to limit transporting patients) or in dedicated auxiliary units. Patients that require transport to departments must wear a mask to and from the unit. Machines, including any ancillary equipment used during examinations, should be cleaned after examinations 40. It is recommended that any imaging examinations have two radiographers in attendance using the 'one clean, one in contact with the patient' system to minimize cross-contamination 89. SARS-CoV-2 can exist on surfaces for up to 72 hours, reinforcing the need for protection of equipment with barriers such as covers and thorough cleaning of equipment between patients 58.

Please follow your departmental policies on personal protective equipment (PPE).

Non-urgent care

The Both the American College of Radiology (ACR)and Centresthe Centers for Disease CentralControl and Prevention (USA(CDC) recommend to "reschedule in the United States advise that non-urgent outpatient visits"appointments should be rescheduled 83,84. In addition, theThe British Society of Skeletal Radiologists has recommended: "Intraadvised that intra-articular steroid, soft tissue, and perineural steroid injections may reduce viral immunity and therefore should not be avoidedperformed, whenever possible during the COVID-19 pandemic to reduce the risk of reduced immunity to viral exposure"unless they are unavoidable 85.

CT protocol

Patients requiring CT should receive a non-contrast chest CT (unless iodinated contrast medium is indicated), with reconstructions of the volume at 0.625-mm to 1.5-mm slice thickness (gapless) 57. If iodinated contrast is indicated (for example a CT pulmonary angiogram), a non-contrast scan should be considered prior to contrast administration, as contrast may impact the interpretation of GGO patterns 89.

Radiographic features

The primary findings of COVID-19 on chest radiograph and CT are those of atypical pneumonia 40 or organising pneumonia 32,34. Imaging has limited sensitivity for COVID-19, up to 18% demonstrate normal chest x-rays or CT when mild/early in the disease course but this decreases to 3% in severe disease 89. Bilateral and/or multilobar involvement is common 6,78.

Plain radiograph
  • asymmetric patchy or diffuse airspace opacities 89
CT

The primary findings on CT in adults have been reported 13,17,27,28,36:

The ground-glass and/or consolidative opacities are usually bilateral, peripheral, and basal in distribution 2,32.

A retrospective study of 112 patients found 54% of asymptomatic patients had pneumonic changes on CT 67.

A study published in March 2020, evaluated the ability of Chinese and American radiologists to differentiate COVID-19 from other viral pneumonia on CT 51. The Chinese radiologists demonstrated sensitivities of 72-94% and specificity of 24-94%. The results for the American radiologists were better, including specificity of 100% for two radiologists; however, the American specialists viewed a much smaller dataset than their Chinese colleagues.

In this study, these chest CT findings had the highest discriminatory value (p<0.001) 51:

  • peripheral distribution
  • ground-glass opacity
  • bronchovascular thickening (in lesions)
Atypical CT findings

These findings only seen in a small minority of patients should raise concern for superadded bacterial pneumonia or other diagnoses 2,32,89:

Temporal CT changes

Four stages on CT have been described 17,24,32,86:

  • early/initial stage (0-4 days): normal CT or GGO only
    • up to half of patients have normal CT scans within 2 days of symptom onset
  • progressive stage (5-8 days): increased GGO and crazy paving appearance.
  • peak stage (9-13 days): consolidation
  • absorption stage (> 14 days): with an improvement in the disease course, "fibrous stripes" appear and the abnormalities resolve at 1 month and beyond
Paediatric CT

In a small study of five children that had been admitted to hospital with positive COVID-19 RT-PCR tests and who had CT chest performed, only three children had abnormalities. The main abnormality was bilateral patchy ground-glass opacities, similar to the appearances in adults, but less florid, and in all three cases the opacities resolved as they clinically recovered 48.

On 18 March 2020, the details of a much larger cohort of 171 children with confirmed COVID-19, and evaluated in a hospital setting was published as a letter in the New England Journal of Medicine. Ground-glass opacities were seen in one third of the total, whereas almost 16% children had no imaging features of pneumonia 91.

Ultrasound

Initial work on patients in China suggests that lung ultrasound may be useful in the evaluation of critically ill COVID-19 patients 55. The following patterns have been observed, tending to have a bilateral and posterobasal predominance:

  • multiple B-lines
    • ranging from focal to diffuse with spared areas 64
    • representative of thickened subpleural interlobular septa
  • irregular, thickened pleural line with scattered discontinuities 63
  • subpleural consolidations
    • can be associated with a discrete, localized pleural effusion
    • relatively avascular with colour flow Doppler interrogation
    • pneumonic consolidation typically associated with preservation of flow or hyperemia 65
  • alveolar consolidation
    • tissue-like appearance with dynamic and static air bronchograms
    • associated with severe, progressive disease 
  • restitution of aeration during recovery
Nuclear medicine
PET-CT

An initial small case series published on 22 February 2020 demonstrated that FDG uptake is increased in ground-glass opacities in those with presumed COVID-19 42. A commentary in the same issue of the journal as this paper suggested that those with higher SUVs in lung lesions take longer to heal 77. A further single case detailed in a letter to Radiology corroborated the FDG avidity of COVID lung lesions 75.

Treatment and prognosis

Treatment

No specific treatment or vaccine exists for COVID-19 (March 2020). Therefore resources have been concentrated on public health measures, to prevent further interhuman transmission of the virus. This has required a multipronged approach and for individuals includes meticulous personal hygiene, the avoidance of large crowds/crowded environments and where necessary, self-isolation 11.

In healthcare facilities, concerted efforts are required to effect rapid diagnosis, quarantine infected cases and provide effective supportive therapies. This will encompass empirical treatments with antibiotics, antivirals, and supportive measures. Mechanical ventilation and extracorporeal membrane oxygenation (ECMO) have also been used where clinically necessary. 

Antiviral therapy

Whilst specific antiviral therapies for SARS-2-CoV do not currently exist, the combination of the protease inhibitors, ritonavir, and lopinavir, or a triple combination of these antiviral agents with the addition of ribavirin, showed some success in the treatment of SARS 20, and early reports suggested similar efficacy in the treatment of COVID-19 23. However, a more recent randomized, controlled open-label trial failed to demonstrate any added benefit of lopinavir-ritonavir combination therapy 66.

Remdesivir, a drug originally developed to treat Ebola virus and shown to be effective against MERS-CoV and SARS-CoV, showed promising in vitro results against SARS-CoV-2 29 and is undergoing phase III trials 30. Other antivirals in phase III trials include oseltamivir, ASC09F (HIV protease inhibitor), lopinavir, ritonavir, darunavir, and cobicistat 80.

Early reports demonstrated that treatment with two antimalarial drugs, chloroquine, and its analogue hydroxychloroquine have a beneficial effect on the clinical outcome, and it was also shown that they demonstrate anti-SARS-2-CoV activity in vitro. This was further corroborated by a recent open-label, randomized clinical trial, which demonstrated a significant reduction of viral carriage, and a lower average carrying duration in patients treated with hydroxychloroquine. Furthermore, a combination with the antibiotic azithromycin resulted in a synergistic effect 69. 

Vaccines

The primary target in developing coronavirus vaccines has been the spike protein (S protein) which is on the surface of the virion particle, and in vivo is the most important antigen for triggering an immune response 75. 

Vaccines for the coronaviruses have been under development since the SARS outbreak, but none are yet available for humans 11,26. A phase I trial in humans of a potential vaccine against MERS-CoV has already been performed in the UK 26.

NSAIDs

Emerging expert opinion is that non-steroidal anti-inflammatory drugs (NSAIDs) are relatively contraindicated in those with COVID-19. This is based upon several strands of "evidence" 61:

  • since 2019 the French government National Agency for the Safety of Medicines and Health Products has advised against the routine use of NSAIDs as antipyretic
  • previous research has shown that NSAIDs may suppress the immune system 
  • anecdotal reports from France suggest that young patients on NSAIDs, otherwise previously fit and well, developed more severe COVID-19 symptoms

However, it is important to note that there is currently (March 2020) no published scientific evidence showing that NSAIDs increase the risk of developing COVID-19 or worsen established disease. Also, at least one report shows antiviral activity by indomethacin (an NSAID) against SARS-CoV (cause of SARS) 60.

Prognosis

Progressive deterioration of imaging changes despite medical treatment is thought to be associated with poor prognosis 27. There is an increased risk of death in men over the age of 60 years old 62. The mortality rate is estimated to be 3.6% 89.

Early reports show that in some well patients the RT-PCR test remains falsely positive despite an apparent clinical recovery. This raises the concern that asymptomatic carriage may occur 35.

History and etymology

The first mention in the medical press about the emerging infection was in the British Medical Journal (BMJ) on 8 January 2020 in a news article, which reported "outbreak of pneumonia of unknown cause in Wuhan, China, has prompted authorities in neighbouring Hong Kong, Macau, and Taiwan to step up border surveillance, amid fears that it could signal the emergence of a new and serious threat to public health" 54. The first scientific article about the new disease, initially termed 2019‐new coronavirus (2019‐nCoV) by the World Health Organisation (WHO), was published in the Journal of Medical Virology on 16 January 2020 53.

On 13 January 2020, the first confirmed case outside China was diagnosed, a Chinese tourist in Thailand 10. On 20 January, the first infected person in the United States was confirmed to be a man who had recently returned from Wuhan 9. The infection was declared a Public Health Emergency of International Concern (PHEIC) on 30 January 2020 by the WHO 7. On 28 February 2020, the WHO increased the global risk assessment of COVID-19 to “very high” which is the highest level. On 11 March 2020, COVID-19 was declared a pandemic by the WHO 44.

The WHO originally called this illness "novel coronavirus-infected pneumonia (NCIP)" and the virus itself had been named "2019 novel coronavirus (2019-nCoV)" 1. On 11 February 2020, the World Health Organisation (WHO) officially renamed the clinical condition COVID-19 (a shortening of COronaVIrus Disease-19) 15. On the same day, the Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses renamed the virus "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2) 16,22,46. 

Differential diagnoses

Resources

These lists are in alphabetical order:

See also

  • -<p><em>For a quick reference guide, please see our <a href="/articles/covid-19-summary">COVID-19 summary</a> article.</em></p><p><strong>COVID-19 </strong>(<strong>coronavirus disease 2019</strong>) is an infectious disease caused by <strong>severe acute respiratory syndrome coronavirus 2</strong> (<strong>SARS-CoV-2</strong>), previously known as <strong>2019 novel coronavirus </strong>(<strong>2019-nCoV</strong>), a species of <a href="/articles/human-coronavirus-1">coronavirus</a>. The first cases were seen in Wuhan, China in December 2019 before spreading globally <sup>1,2,10</sup>. The current <a href="/articles/outbreak">outbreak</a> was recognized as a <a href="/articles/pandemic">pandemic</a> on 11 March 2020 <sup>44</sup>.</p><p>The non-specific imaging findings are most commonly of <a href="/articles/atypical-pneumonia">atypical</a> or <a href="/articles/organising-pneumonia">organising pneumonia</a>, often with a bilateral, peripheral, and basal predominant distribution <sup>32</sup>. No effective treatment or vaccine exists currently (March 2020) <sup>20</sup>.</p><h4>Terminology</h4><p>The <a href="/articles/world-health-organisation-who">World Health Organisation (WHO)</a> originally called this illness "novel coronavirus-infected pneumonia (NCIP)" and the virus itself had been named "2019 novel coronavirus (2019-nCoV)" <sup>1</sup>.</p><p>On 11 February 2020, the WHO officially renamed the clinical condition COVID-19 (a shortening of COronaVIrus Disease-19) <sup>15</sup>. Coincidentally, on the same day, the Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses renamed the virus "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2) <sup>16,22,46</sup>. The names of both the disease and the virus should be fully capitalised, except for the 'o' in the viral name, which is in lowercase <sup>16,22,41</sup>. </p><p>The official virus name is similar to <a href="/articles/severe-acute-respiratory-syndrome-1">sudden acute respiratory syndrome (SARS)</a> and its causative virus, SARS-CoV, potentially causing confusion <sup>38</sup>. The WHO has stated it will use "COVID-19 virus" or the "virus that causes COVID-19" instead of its official name, SARS-CoV-2, in dealings with the public <sup>45</sup>.</p><h4>Epidemiology</h4><p>As of 24 March 2020, over 381,000 cases of COVID-19 have been confirmed worldwide, having been diagnosed in 168 territories, in six continents according to an online virus tracker created by the medical journal, The Lancet, and hosted by Johns Hopkins University <sup>5,13</sup>. There are seven countries with &gt;10,000 confirmed cases and nineteen countries with between 1000 and 10,000 confirmed cases <sup>5</sup>. </p><p>NB: Surveillance methods and capacity vary dramatically between countries, and there is reason to suspect that there may be a significant number of carriers in some countries not diagnosed.</p><p>The <a href="/articles/basic-reproductive-number">R<sub>0</sub> (basic reproduction number)</a> of SARS-CoV-2 has been estimated between<strong> </strong>2.2 and 3.28 <sup>12,33</sup>, that is each infected individual, on average, causes between 2-3 new infections. The <a href="/articles/incubation-period">incubation period</a> in this group has been calculated to be 5.2 days on average <sup>12</sup>.</p><p>A paper published by the Chinese Center for Disease Control and Prevention (CCDC) analysed all 44,672 cases diagnosed up to 11 February 2020. Of these, 1.2% were asymptomatic and 80.9% were classed as "mild" <sup>25</sup>. </p><p>Another study looked at clinical characteristics in COVID-19 positively tested closed contacts of COVID-19 patients <sup>81</sup>. About 29.2% of those COVID-19 positive closed contacts never developed any symptoms or changes on chest CT scans. The remainder showed changes on CT, but apparently, only 21% developed symptoms during their hospital course, none of them developed severe disease <sup>81</sup>. This suggests that a high percentage of COVID-19 carriers are asymptomatic.</p><p>In an article examining the first 425 infected cases in Wuhan, 56% of the infected were male and the median age was 59 years <sup>12</sup>.</p><h5>Paediatric</h5><p>Children seem to be relatively unaffected by this virus, or indeed other closely-related coronaviruses <sup>31,47,90</sup>, however, there have been cases of critically-ill children with infants under 12 months likely to be more seriously affected<sup> 59</sup>.</p><p>In a large cohort Chinese study which included 44,672 COVID-19 positive patients, 2% of the total were children, and a large Italian series stated that just 1.2% of 22,512 COVID-19 patients were children. In children, male gender does not seem to be a risk factor <sup>59</sup>.</p><p>In China, only two deaths in children have been reported, one in a 14 year old <sup>59</sup>, the other in a 10-month old <sup>90</sup>. No deaths have been reported in Italy for anyone less than 30 years old <sup>90</sup>.</p><p>In children, the incubation period is about two days <sup>90</sup>.</p><p>NB: it is important to appreciate that the known epidemiological parameters of any new disease are likely to change as larger cohorts of infected people are studied, although this will only to some extent reflect a true change in the underlying reality of disease activity (as a disease is studied and understood humans will be simultaneously changing their behaviours to alter transmission or prevalence patterns).</p><h4>Clinical presentation</h4><p>COVID-19 typically presents with systemic and/or respiratory manifestations. Some individuals infected with SARS-CoV-2 are asymptomatic and can act as carriers <sup>70</sup>. Some also experience mild gastrointestinal or cardiovascular symptoms <sup>18,50</sup>. However, its full spectrum of clinical effects remains to be determined <sup>1,13</sup>. Symptoms and signs are <a href="/articles/non-specific">non-specific</a> <sup>68</sup>:</p><p><strong>Common:</strong></p><ul>
  • +<p><em>For a quick reference guide, please see our <a href="/articles/covid-19-summary">COVID-19 summary</a> article.</em></p><p><strong>COVID-19 </strong>(<strong>coronavirus disease 2019</strong>) is an infectious disease caused by <strong>severe acute respiratory syndrome coronavirus 2</strong> (<strong>SARS-CoV-2</strong>), previously known as <strong>2019 novel coronavirus </strong>(<strong>2019-nCoV</strong>), a species of <a href="/articles/human-coronavirus-1">coronavirus</a>. The first cases were seen in Wuhan, China in December 2019 before spreading globally <sup>1,2,10</sup>. The current <a href="/articles/outbreak">outbreak</a> was recognized as a <a href="/articles/pandemic">pandemic</a> on 11 March 2020 <sup>44</sup>.</p><p>The non-specific imaging findings are most commonly of <a href="/articles/atypical-pneumonia">atypical</a> or <a href="/articles/organising-pneumonia">organising pneumonia</a>, often with a bilateral, peripheral, and basal predominant distribution <sup>32</sup>. No effective treatment or vaccine exists currently (March 2020) <sup>20</sup>.</p><h4>Terminology</h4><p>The <a href="/articles/world-health-organisation-who">World Health Organisation (WHO)</a> originally called this illness "novel coronavirus-infected pneumonia (NCIP)" and the virus itself had been named "2019 novel coronavirus (2019-nCoV)" <sup>1</sup>.</p><p>On 11 February 2020, the WHO officially renamed the clinical condition COVID-19 (a shortening of COronaVIrus Disease-19) <sup>15</sup>. Coincidentally, on the same day, the Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses renamed the virus "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2) <sup>16,22,46</sup>. The names of both the disease and the virus should be fully capitalised, except for the 'o' in the viral name, which is in lowercase <sup>16,22,41</sup>. </p><p>The official virus name is similar to <a href="/articles/severe-acute-respiratory-syndrome-1">sudden acute respiratory syndrome (SARS)</a> and its causative virus, SARS-CoV, potentially causing confusion <sup>38</sup>. The WHO has stated it will use "COVID-19 virus" or the "virus that causes COVID-19" instead of its official name, SARS-CoV-2, in dealings with the public <sup>45</sup>.</p><h4>Epidemiology</h4><p>As of 24 March 2020, over 381,000 cases of COVID-19 have been confirmed worldwide, having been diagnosed in 168 territories, in six continents according to an online virus tracker created by the medical journal, The Lancet, and hosted by Johns Hopkins University <sup>5,13</sup>. There are seven countries with &gt;10,000 confirmed cases and nineteen countries with between 1000 and 10,000 confirmed cases <sup>5</sup>. </p><p>NB: Surveillance methods and capacity vary dramatically between countries, and there is reason to suspect that there may be a significant number of carriers in some countries not diagnosed.</p><p>The <a href="/articles/basic-reproductive-number">R<sub>0</sub> (basic reproduction number)</a> of SARS-CoV-2 has been estimated between<strong> </strong>2.2 and 3.28 <sup>12,33</sup>, that is each infected individual, on average, causes between 2-3 new infections. The <a href="/articles/incubation-period">incubation period</a> in this group has been calculated to be 5.2 days on average <sup>12</sup>.</p><p>A paper published by the Chinese Center for Disease Control and Prevention (CCDC) analysed all 44,672 cases diagnosed up to 11 February 2020. Of these, 1.2% were asymptomatic and 80.9% were classed as "mild" <sup>25</sup>. </p><p>Another study looked at clinical characteristics in COVID-19 positively tested closed contacts of COVID-19 patients <sup>81</sup>. About 29.2% of those COVID-19 positive closed contacts never developed any symptoms or changes on chest CT scans. The remainder showed changes on CT, but apparently, only 21% developed symptoms during their hospital course, none of them developed severe disease <sup>81</sup>. This suggests that a high percentage of COVID-19 carriers are asymptomatic.</p><p>In an article examining the first 425 infected cases in Wuhan, 56% of the infected were male and the median age was 59 years <sup>12</sup>.</p><h5>Paediatric</h5><p>Children seem to be relatively unaffected by this virus, or indeed other closely-related coronaviruses <sup>31,47,90</sup>, however, there have been cases of critically-ill children with infants under 12 months likely to be more seriously affected<sup> 59</sup>.</p><p>In a large cohort Chinese study which included 44,672 COVID-19 positive patients, 2% of the total were children, and a large Italian series stated that just 1.2% of 22,512 COVID-19 patients were children. In children, male gender does not seem to be a risk factor <sup>59</sup>.</p><p>In China, only two deaths in children have been reported, one in a 14 year old <sup>59</sup>, the other in a 10-month old <sup>91</sup>. No deaths have been reported in Italy for anyone less than 30 years old <sup>90</sup>.</p><p>In children, the incubation period is about two days <sup>90</sup>.</p><p>NB: it is important to appreciate that the known epidemiological parameters of any new disease are likely to change as larger cohorts of infected people are studied, although this will only to some extent reflect a true change in the underlying reality of disease activity (as a disease is studied and understood humans will be simultaneously changing their behaviours to alter transmission or prevalence patterns).</p><h4>Clinical presentation</h4><p>COVID-19 typically presents with systemic and/or respiratory manifestations. Some individuals infected with SARS-CoV-2 are asymptomatic and can act as carriers <sup>70</sup>. Some also experience mild gastrointestinal or cardiovascular symptoms, although these are much less common <sup>18,50</sup>. </p><p>However, the full spectrum of clinical effects of COVID-19 remains to be determined <sup>1,13</sup>. Symptoms and signs are <a href="/articles/non-specific">non-specific</a> <sup>68</sup>:</p><p><strong>Common:</strong></p><ul>
  • -</ul><p>Anecdotal reports from ENT specialists in the UK <sup>79</sup> suggest that COVID-19 sufferers have high rates of <a href="/articles/anosmia">anosmia/hyposmia</a>, however, no peer-reviewed studies supporting this are yet available.</p><h5>Diagnosis</h5><p>The definitive test for SARS-CoV-2 is the <strong>real-time reverse transcriptase-polymerase chain reaction</strong> (<strong>RT-PCR</strong>) <strong>test</strong> and is believed to be highly <a href="/articles/specificity">specific</a>, but with <a href="/articles/sensitivity">sensitivity</a> reported as low as 60-70% <sup>32</sup> and as high as 95-97% <sup>56</sup> depending on the country. Thus, false negatives are a real clinical problem and several negative tests might be required in a single case to be confident about excluding the disease.</p><p>Multiple radiological organisations have come forward to state that CT should not be relied upon as a primary diagnostic/screening tool for COVID-19 <sup>52,57,87,88</sup>. On 16 March 2020, an American-Singaporean panel published that CT findings were not part of the diagnostic criteria for COVID-19 <sup>56</sup>. However, CT findings have been used as a surrogate diagnostic test <sup>2,</sup><sup>32,89</sup>. </p><h6>Laboratory tests</h6><p>The most common ancillary laboratory findings in a study of 138 hospitalised patients were the following <sup>13,89</sup>:</p><ul>
  • +</ul><p>Anecdotal reports from ENT specialists in the UK <sup>79</sup> suggest that COVID-19 sufferers have high rates of <a href="/articles/anosmia">anosmia/hyposmia</a>, however, no peer-reviewed studies supporting this are yet available.</p><h6>Paediatric</h6><p>In the main the clinical presentation in children with COVID-19 is more mild than in adults <sup>59,90</sup>. Symptoms are similar to any acute chest infection, encompassing most commonly pyrexia, dry cough, sore throat, sneezing, myalgia and lethargy. <a href="/articles/wheeze">Wheezing</a> has also been noted <sup>59,90</sup>. Other less common (&lt;10%) symptoms in children included diarrhoea, lethargy, rhinorrhea and vomiting <sup>91</sup>.</p><h5>Diagnosis</h5><p>The definitive test for SARS-CoV-2 is the <strong>real-time reverse transcriptase-polymerase chain reaction</strong> (<strong>RT-PCR</strong>) <strong>test</strong> and is believed to be highly <a href="/articles/specificity">specific</a>, but with <a href="/articles/sensitivity">sensitivity</a> reported as low as 60-70% <sup>32</sup> and as high as 95-97% <sup>56</sup> depending on the country. Thus, false negatives are a real clinical problem and several negative tests might be required in a single case to be confident about excluding the disease.</p><p>Multiple radiological organisations have come forward to state that CT should not be relied upon as a primary diagnostic/screening tool for COVID-19 <sup>52,57,87,88</sup>. On 16 March 2020, an American-Singaporean panel published that CT findings were not part of the diagnostic criteria for COVID-19 <sup>56</sup>. However, CT findings have been used as a surrogate diagnostic test <sup>2,</sup><sup>32,89</sup>. </p><h6>Laboratory tests</h6><p>The most common ancillary laboratory findings in a study of 138 hospitalised patients were the following <sup>13,89</sup>:</p><ul>
  • -</li></ul><h4>Pathology</h4><h5>Aetiology</h5><p>On 9 January 2020, the World Health Organisation (WHO) confirmed that SARS-CoV-2 was the cause of COVID-19 (2019-nCoV was the name of the virus at that time) <sup>14,37</sup>. It is a member of the <em>Betacoronavirus</em> genus, one of the genera of the <em>Coronaviridae</em> family of viruses. <a href="/articles/human-coronavirus-1">Coronaviruses</a> are enveloped single-stranded RNA viruses, that are found in humans, many other mammals, and birds. These viruses are responsible for pulmonary, hepatic, CNS, and intestinal disease. </p><p>As with many human infections, SARS-CoV-2 is <a href="/articles/zoonosis">zoonotic</a>. The closest animal coronavirus by genetic sequence is a bat coronavirus, and this is the likely ultimate origin of the virus <sup>11,19,26</sup>. The disease can also be transmitted by snakes <sup>24</sup>.</p><p>Hitherto, six coronaviruses have been known to be responsible for human diseases. Two are zoonoses: the <a href="/articles/sars">severe acute respiratory syndrome coronavirus (SARS-CoV)</a> and <a href="/articles/middle-east-respiratory-syndrome-coronavirus-mers-cov-infection">Middle East respiratory syndrome coronavirus (MERS-CoV)</a>, both of which may sometimes be fatal. The remaining four viruses are widespread in human society, causing the <a href="/articles/common-cold">common cold</a>. </p><h5>Pathophysiology</h5><p>The SARS-CoV-2 virus, like the closely-related MERS and SARS coronaviruses, affects its cellular entry via attachment of its virion spike protein (a.k.a. S protein) to the angiotensin-converting enzyme 2 (ACE 2) receptor. This receptor is commonly found on alveolar cells of the lung epithelium, underlying the development of respiratory symptoms as the commonest presentation of COVID-19 <sup>50</sup>. It is thought that the mediation of the less common cardiovascular effects is also via the same ACE-2 receptor which is also commonly expressed on the cells of the cardiovascular system <sup>50</sup>.</p><h5>Transmission</h5><p>Although originating from animals, COVID-19 is not considered a direct zoonosis as its transmission is now primarily human-to-human. It is primarily transmitted in a similar way to the common cold, via contact with droplets of infected individuals' upper respiratory tract secretions, e.g. from sneezing or coughing <sup>19</sup>.</p><p>A recent Bayesian regression model has found that aerosol and fomite transmission is plausible <sup>58</sup>.</p><p>Orofaecal spread was seen with the <a href="/articles/severe-acute-respiratory-syndrome-1">SARS</a> epidemic, and although it remains unclear if SARS-CoV-2 can be transmitted in this way, there is some evidence for it <sup>19,43</sup>.</p><p>A recent retrospective study of nine pregnant patients infected by SARS-CoV-2 did not show any evidence of vertical/intrauterine infection <sup>21</sup>. More recent published (20 March 2020) guidance from a joint American-Chinese consensus panel stated that it remains unclear if vertical transmission can occur <sup>82</sup>.</p><h4>Considerations for medical imaging departments</h4><h5>Infection precautions</h5><p>Given that the staff in a medical imaging department are some of the first parties to be in contact with COVID-19 patients, clear infection control guidelines are imperative. At the time of writing (8 March 2020) droplet-type precautions are in place for COVID-19 patients, that is, medical mask, gown, gloves, and eye protection (aerosol-generating procedures require N95 masks and aprons) <sup>39</sup>.</p><p>Patients requiring general radiography should receive it portably (to limit transporting patients) or in dedicated auxiliary units. Patients that require transport to departments must wear a mask to and from the unit. Machines, including any ancillary equipment used during examinations, should be cleaned after examinations <sup>40</sup>. It is recommended that any imaging examinations have two radiographers in attendance using the 'one clean, one in contact with the patient' system to minimize cross-contamination <sup>89</sup>. SARS-CoV-2 can exist on surfaces for up to 72 hours, reinforcing the need for protection of equipment with barriers such as covers and thorough cleaning of equipment between patients <sup>58</sup>.</p><p>Please follow your departmental policies on <a href="/articles/personal-protective-equipment-ppe">personal protective equipment (PPE)</a>.</p><h5>Non-urgent care</h5><p>The American College of Radiology and Centres for Disease Central and Prevention (USA) recommend to "reschedule non-urgent outpatient visits" <sup>83,84</sup>. In addition, the British Society of Skeletal Radiologists has recommended: "Intra-articular steroid, soft tissue, and perineural injections should be avoided, whenever possible during the COVID-19 pandemic to reduce the risk of reduced immunity to viral exposure" <sup>85</sup>.</p><h5>CT protocol</h5><p>Patients requiring CT should receive a <a href="/articles/ct-chest-non-contrast">non-contrast chest CT</a> (unless <a href="/articles/iodinated-contrast-media-1">iodinated contrast medium</a> is indicated), with reconstructions of the volume at 0.625-mm to 1.5-mm slice thickness (gapless) <sup>57</sup>. If iodinated contrast is indicated (for example a <a href="/articles/ct-pulmonary-angiogram-ctpa">CT pulmonary angiogram</a>), a non-contrast scan should be considered prior to contrast administration, as contrast may impact the interpretation of GGO patterns <sup>89</sup>.</p><h4>Radiographic features</h4><p>The primary findings of COVID-19 on <a href="/articles/chest-radiograph">chest radiograph</a> and <a href="/articles/ct-chest-summary">CT</a> are those of <a href="/articles/atypical-pneumonia">atypical pneumonia</a> <sup>40</sup> or <a href="/articles/organising-pneumonia">organising pneumonia</a> <sup>32,34</sup>. Imaging has limited sensitivity for COVID-19, up to 18% demonstrate normal chest x-rays or CT when mild/early in the disease course but this decreases to 3% in severe disease <sup>89</sup>. Bilateral and/or multilobar involvement is common <sup>6,78</sup>.</p><h5>Plain radiograph</h5><ul><li>asymmetric patchy or diffuse airspace opacities <sup>89</sup>
  • +</li></ul><h4>Pathology</h4><h5>Aetiology</h5><p>On 9 January 2020, the World Health Organisation (WHO) confirmed that SARS-CoV-2 was the cause of COVID-19 (2019-nCoV was the name of the virus at that time) <sup>14,37</sup>. It is a member of the <em>Betacoronavirus</em> genus, one of the genera of the <em>Coronaviridae</em> family of viruses. <a href="/articles/human-coronavirus-1">Coronaviruses</a> are enveloped single-stranded RNA viruses, that are found in humans, many other mammals, and birds. These viruses are responsible for pulmonary, hepatic, CNS, and intestinal disease. </p><p>As with many human infections, SARS-CoV-2 is <a href="/articles/zoonosis">zoonotic</a>. The closest animal coronavirus by genetic sequence is a bat coronavirus, and this is the likely ultimate origin of the virus <sup>11,19,26</sup>. The disease can also be transmitted by snakes <sup>24</sup>.</p><p>Hitherto, six coronaviruses have been known to be responsible for human diseases. Two are zoonoses: the <a href="/articles/sars">severe acute respiratory syndrome coronavirus (SARS-CoV)</a> and <a href="/articles/middle-east-respiratory-syndrome-coronavirus-mers-cov-infection">Middle East respiratory syndrome coronavirus (MERS-CoV)</a>, both of which may sometimes be fatal. The remaining four viruses are widespread in human society, causing the <a href="/articles/common-cold">common cold</a>. </p><h5>Pathophysiology</h5><p>The SARS-CoV-2 virus, like the closely-related MERS and SARS coronaviruses, affects its cellular entry via attachment of its virion spike protein (a.k.a. S protein) to the angiotensin-converting enzyme 2 (ACE 2) receptor. This receptor is commonly found on alveolar cells of the lung epithelium, underlying the development of respiratory symptoms as the commonest presentation of COVID-19 <sup>50</sup>. It is thought that the mediation of the less common cardiovascular effects is also via the same ACE-2 receptor which is also commonly expressed on the cells of the cardiovascular system <sup>50</sup>.</p><h5>Transmission</h5><p>Although originating from animals, COVID-19 is not considered a direct zoonosis as its transmission is now primarily human-to-human. It is primarily transmitted in a similar way to the common cold, via contact with droplets of infected individuals' upper respiratory tract secretions, e.g. from sneezing or coughing <sup>19</sup>.</p><p>A recent Bayesian regression model has found that aerosol and fomite transmission are plausible <sup>58</sup>.</p><p>Orofaecal spread was seen with the <a href="/articles/severe-acute-respiratory-syndrome-1">SARS</a> epidemic, and although it remains unclear if SARS-CoV-2 can be transmitted in this way, there is some evidence for it <sup>19,43</sup>.</p><p>A recent retrospective study of nine pregnant patients infected by SARS-CoV-2 did not show any evidence of vertical/intrauterine infection <sup>21</sup>. More recent published (20 March 2020) guidance from a joint American-Chinese consensus panel stated that it remains unclear if vertical transmission can occur <sup>82</sup>.</p><h4>Considerations for medical imaging departments</h4><h5>Infection precautions</h5><p>Given that the staff in a medical imaging department are some of the first parties to be in contact with COVID-19 patients, clear infection control guidelines are imperative. At the time of writing (8 March 2020) droplet-type precautions are in place for COVID-19 patients, that is, medical mask, gown, gloves, and eye protection (aerosol-generating procedures require N95 masks and aprons) <sup>39</sup>.</p><p>Patients requiring general radiography should receive it portably (to limit transporting patients) or in dedicated auxiliary units. Patients that require transport to departments must wear a mask to and from the unit. Machines, including any ancillary equipment used during examinations, should be cleaned after examinations <sup>40</sup>. It is recommended that any imaging examinations have two radiographers in attendance using the 'one clean, one in contact with the patient' system to minimize cross-contamination <sup>89</sup>. SARS-CoV-2 can exist on surfaces for up to 72 hours, reinforcing the need for protection of equipment with barriers such as covers and thorough cleaning of equipment between patients <sup>58</sup>.</p><p>Please follow your departmental policies on <a href="/articles/personal-protective-equipment-ppe">personal protective equipment (PPE)</a>.</p><h5>Non-urgent care</h5><p>Both the <a href="/articles/american-college-of-radiology">American College of Radiology (ACR)</a> and the <a href="/articles/centers-for-disease-control-and-prevention-cdc">Centers for Disease Control and Prevention (CDC)</a> in the United States advise that non-urgent outpatient appointments should be rescheduled <sup>83,84</sup>. The British Society of Skeletal Radiologists has advised that intra-articular, soft tissue and perineural steroid injections may reduce viral immunity and therefore should not be performed, unless they are unavoidable <sup>85</sup>.</p><h5>CT protocol</h5><p>Patients requiring CT should receive a <a href="/articles/ct-chest-non-contrast">non-contrast chest CT</a> (unless <a href="/articles/iodinated-contrast-media-1">iodinated contrast medium</a> is indicated), with reconstructions of the volume at 0.625-mm to 1.5-mm slice thickness (gapless) <sup>57</sup>. If iodinated contrast is indicated (for example a <a href="/articles/ct-pulmonary-angiogram-ctpa">CT pulmonary angiogram</a>), a non-contrast scan should be considered prior to contrast administration, as contrast may impact the interpretation of GGO patterns <sup>89</sup>.</p><h4>Radiographic features</h4><p>The primary findings of COVID-19 on <a href="/articles/chest-radiograph">chest radiograph</a> and <a href="/articles/ct-chest-summary">CT</a> are those of <a href="/articles/atypical-pneumonia">atypical pneumonia</a> <sup>40</sup> or <a href="/articles/organising-pneumonia">organising pneumonia</a> <sup>32,34</sup>. Imaging has limited sensitivity for COVID-19, up to 18% demonstrate normal chest x-rays or CT when mild/early in the disease course but this decreases to 3% in severe disease <sup>89</sup>. Bilateral and/or multilobar involvement is common <sup>6,78</sup>.</p><h5>Plain radiograph</h5><ul><li>asymmetric patchy or diffuse airspace opacities <sup>89</sup>
  • -</ul><h5>Paediatric CT</h5><p>In a small study of five children that had been admitted to hospital with positive COVID-19 RT-PCR tests and who had CT chest performed, only three children had abnormalities. The main abnormality was bilateral patchy ground-glass opacities, similar to the appearances in adults, but less florid, and in all three cases the opacities resolved as they clinically recovered <sup>48</sup>.</p><h5>Ultrasound</h5><p>Initial work on patients in China suggests that <a href="/articles/bedside-lung-ultrasound-in-emergency-approach">lung ultrasound</a> may be useful in the evaluation of critically ill COVID-19 patients <sup>55</sup>. The following patterns have been observed, tending to have a bilateral and posterobasal predominance:</p><ul>
  • +</ul><h5>Paediatric CT</h5><p>In a small study of five children that had been admitted to hospital with positive COVID-19 RT-PCR tests and who had CT chest performed, only three children had abnormalities. The main abnormality was bilateral patchy ground-glass opacities, similar to the appearances in adults, but less florid, and in all three cases the opacities resolved as they clinically recovered <sup>48</sup>.</p><p>On 18 March 2020, the details of a much larger cohort of 171 children with confirmed COVID-19, and evaluated in a hospital setting was published as a letter in the New England Journal of Medicine. Ground-glass opacities were seen in one third of the total, whereas almost 16% children had no imaging features of pneumonia <sup>91</sup>.</p><h5>Ultrasound</h5><p>Initial work on patients in China suggests that <a href="/articles/bedside-lung-ultrasound-in-emergency-approach">lung ultrasound</a> may be useful in the evaluation of critically ill COVID-19 patients <sup>55</sup>. The following patterns have been observed, tending to have a bilateral and posterobasal predominance:</p><ul>

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