COVID-19

Changed by Bálint Botz, 19 Mar 2020
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COVID-19 is a zoonotic illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus was previously known as 2019 novel coronavirus. The first cases were seen in the city of Wuhan, China in December 2019, and have been linked to the Huanan Seafood Wholesale Market 1,2,10. The current outbreak is officially a pandemic 44.

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

Terminology

The WHO originally called this emerging zoonotic infectious 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), which was announced in a tweet 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 lower case 16,22,41. 

The WHO has expressed reservations about the official virus name in view of its closeness to the name SARS. It has publicly stated it will not be using it, instead using "COVID-19 virus" or the "virus that causes COVID-19". A group of Chinese virologists also stated in a letter published in The Lancet that the new name was likely to confuse the public due to its similarity to the disease SARS, and they suggested "human coronavirus 2019 (HCoV-19)" 38.

However, the scientific community is already using SARS-CoV-2 and it is likely that this will be gradually accepted by the wider world 22. The WHO has also publicly stated that although they will not be using the term SARS-CoV-2 in their public communications, it remains the official name of the virus 45.

Some publications have chosen to use a separate term "novel COVID-19-infected pneumonia (NCIP)" for the pneumonia secondary to COVID-19 40.

Epidemiology

As of 19 March 2020, over 218,500 cases of COVID-19 have been confirmed worldwide, with China now accounting for only 40% of all confirmed cases; this is according to an online virus tracker created by the medical journal, The Lancet, and hosted by Johns Hopkins University 5. Although the percentage of confirmed cases outside China is steadily increasing, the epidemic in China has plateaued 5. 

Seven other countries have over 5,000 confirmed cases 5:

  • Italy: 35,713
  • Iran: 17,361
  • Spain: 13,716
  • Germany: 10,999
  • United States of America: 9,415
  • France: 9,134
  • South Korea: 8,565

with a further eight countries between 1,000-5,000 cases 5:

  • Switzerland: 3,067
  • United Kingdom: 2,644
  • Netherlands: 2,056
  • Austria: 1,646
  • Norway: 1,591
  • Belgium: 1,486
  • Sweden: 1,301
  • Denmark: 1,117

In addition, 717 cases were confirmed on two cruise ships, the Diamond Princess, moored off Japan with 696 cases, and 21 cases on the Grand Princess moored off the Californian coast in the United States 5.

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 disease has now been diagnosed in over 155 territories, in six continents 5,13. 

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 mortality rate is about 2-3% 5 with currently 8,811 confirmed deaths (19 March 2020) 5. This includes confirmed deaths in 55 territories including 5:

  • 3,130 in China
  • 2,978 in Italy
  • 1,135 in Iran
  • 638 in Spain
  • 148 in France

In the largest study to date, a paper published by the Chinese Center for Disease Control and Prevention (CCDC) analysed all the cases diagnosed up to 11 February 2020, which came to 44,672 cases. Of these 1.2% were asymptomatic and 80.9% were classed as "mild". The overall mortality rate was found to be 2.3% 25. 

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. In this early cohort, there were no children under 15 years old. Using this dataset, the group estimated that the R0 (basic reproduction number) of the novel coronavirus was 2.2, that is each infected individual - on average - causes 2.2 new cases of the disease. The incubation period in this group has been calculated to be 5.2 days on average 12.

A more recent study, for which researchers reviewed 12 studies of COVID-19, calculated the average R0 to be higher at 3.28, with the authors estimating the likely R0 to lie between 2 and 3 33.

Interestingly children seem to be relatively unaffected by this virus, or indeed other closely-related coronaviruses 47. A Chinese study reviewing the first 31,211 cases in mainland China found that only nine children under one year of age were confirmed with COVID-19. All nine cases were admitted to hospital, and symptoms were mild or absent. None required intensive care or developed severe sequelae 31,47. A later study of the epidemiology by a case series of over 2,143 Chinese children showed there have been critically ill children, and although the numbers are fewer than in the elderly population, infants under 12 months were more likely to have become critically ill than other pediatric age groups 59.  In children, male gender does not seem to be a risk factor 59.

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, when symptomatic, tends to present with respiratory manifestations. However, it is now clear that some individuals, especially young children, remain asymptomatic, whilst others have mild upper respiratory tract symptoms only. Some also experience mild GI or cardiovascular symptoms 18,50. However, its full spectrum of clinical effects remains to be determined 1,13. Symptoms and signs are non-specific:

Diagnosis

The definitive test for SARS-CoV-2, the virus causing COVID-19, 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.

Therefore, in many cases, CT findings have been used as a surrogate diagnostic test 2,32. Indeed recent work supports the notion that CT is a more sensitive test for the virus than is the confirmatory RT-PCR test. In a cohort of 1,014 patients, with a positive PCR as the diagnostic test, the sensitivity of CT in reaching the same conclusion was 97%. In those patients in whom RT-PCR was negative - yet the CT chest was positive - clinical records were comprehensively re-reviewed and 48% of these cases were deemed to be "highly likely" to be COVID-19, with a further 33% as "probable" 34. On 16 March 2020, an American-Singaporean panel published that CT findings were not part of the diagnostic criteria for COVID-19 56. 

The WHO has published official case definitions for COVID-19 surveillance. These definitions remain under constant review.

Laboratory tests

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

Mild elevations of inflammatory markers (CRP 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 were:

In a small subgroup of severe ICU cases:

Pathology

Aetiology

The WHO confirmed that SARS-CoV-2 was the cause of COVID-19 on 9 January 2020 (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. 

The natural animal host of SARS-CoV-2 remains undetermined, although 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. 

Pathogenesis

The SARS-CoV-2 virus, like the closely-related, MERS and SARS coronaviruses, effects cellular entry via attachment of its virion spike 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

COVID-19 is primarily transmitted person-to-person, in a similar way to the common cold, via droplets (not aerosols), by close contact with infected individuals' upper respiratory tract secretions, e.g. from sneezing or coughing 19.  There is still uncertainty around as to if the virus can be transmitted through surface contamination. A recent Bayesian regression model has found that that aerosol and fomite transmission is 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.

Vertical transmission

A recent retrospective study of nine pregnant patients infected by SARS-CoV-2 did not show any evidence of intrauterine infection 21.

Considerations for medical imaging departments

Infection precautions

Given staff in the medical imaging department are some of the first parties to be in contract 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.

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

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. 

Radiographic features

The primary findings of COVID-19 on chest radiograph and CT are those of pneumonia 3,6,13,17,27,28,32. A chest radiograph is an insensitive test, and many cases demonstrate normal chest x-rays when mild/early in the disease course. 75% of cases have presented with bilateral pneumonia 6.

CT

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

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

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 a specificity of 100% for two radiologists, however, the American specialists viewed a much smaller dataset than their Chinese colleagues.

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

  • peripheral distribution
  • ground-glass opacity
  • vascular thickening
Atypical CT findings

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

Temporal CT changes

In one study, 18 of 21 patients (86%) with non-complicated COVID-19 pneumonia, in whom the temporal progression of the CT appearances in COVID-19 were studied, the severity of lung abnormalities peaked at 10 days post symptom onset, with a gradual tail-off after this time 17. In another study of 36 patients, HRCT showed rapid changes over time with "fibrous stripes" appearing upon improvement in the disease course 24. 

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.

Ultrasound

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

  • 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
    • may be associated with a discrete, localized pleural effusion
    • relatively avascular with color 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
    • reappearance of bilateral A lines
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.

Treatment and prognosis

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. 

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 suggestsuggested similar efficacy in the treatment of COVID-19 23. However, more a recent randomized, controlled trial failed to demonstrate and 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 being tested in humans 30.

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.

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 an 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 risk of developing COVID-19 or worsen established disease.Also at least one report shows antiviral activity by indometacin (a 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.

Studies have shown an increased risk of ARDS and death in men over the age of 60 years old 62.

In the earliest studies, the mortality rate was estimated at 3%, although later data, suggests it as being slightly closer to 2% 5. In a study of the first 44,672 diagnosed cases in mainland China, the fatality rate was found to be 2.3% 25. 

In a Chinese study looking at 138 hospitalised patients only, in-hospital mortality was higher at 4.3% 13.

Early reports show that in some patients the RT-PCR test remains positive despite the 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 WHO, was published in the Journal of Medical Virology on 16 January 2020 53.

Resources

Please keep these lists in alphabetical order.

  • -<li>relatively avascular with <a title="Color flow Doppler (ultrasound)" href="/articles/color-flow-doppler-ultrasound">color flow Doppler</a> interrogation</li>
  • +<li>relatively avascular with <a href="/articles/color-flow-doppler-ultrasound">color flow Doppler</a> interrogation</li>
  • -<li>tissue-like appearance with dynamic and static <a title="Air bronchograms" href="/articles/air-bronchogram">air bronchograms</a>
  • +<li>tissue-like appearance with dynamic and static <a href="/articles/air-bronchogram">air bronchograms</a>
  • -</ul><h5>Nuclear medicine</h5><h6>PET-CT</h6><p>An initial small case series published on 22 February 2020 demonstrated that <a href="/articles/f-18-fluorodeoxyglucose">FDG</a> uptake is increased in ground-glass opacities in those with presumed COVID-19 <sup>42</sup>.</p><h4>Treatment and prognosis</h4><p>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 <sup>11</sup>.</p><p>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 <a href="/articles/extracorporeal-membrane-oxygenation">extracorporeal membrane oxygenation (ECMO)</a> have also been used where clinically necessary. </p><p>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 <sup>20</sup>, and early reports suggest similar efficacy in the treatment of COVID-19 <sup>23</sup>. Remdesivir, a drug originally developed to treat <a href="/articles/ebola-virus-disease-1">Ebola virus</a> and shown to be effective against MERS-CoV and SARS-CoV, showed promising in vitro results against SARS-CoV-2 <sup>29</sup> and is being tested in humans <sup>30</sup>.</p><p>Vaccines for the coronaviruses have been under development since the SARS outbreak, but none are yet available for humans <sup>11,26</sup>. A phase I trial in humans of a potential vaccine against MERS-CoV has already been performed in the UK <sup>26</sup>.</p><p>Emerging expert opinion is that <a href="/articles/non-steroidal-anti-inflammatory-drugs">non-steroidal anti-inflammatory drugs (NSAIDs)</a> are relatively contraindicated in those with COVID-19. This is based upon several strands of "evidence" <sup>61</sup>:</p><ul>
  • +</ul><h5>Nuclear medicine</h5><h6>PET-CT</h6><p>An initial small case series published on 22 February 2020 demonstrated that <a href="/articles/f-18-fluorodeoxyglucose">FDG</a> uptake is increased in ground-glass opacities in those with presumed COVID-19 <sup>42</sup>.</p><h4>Treatment and prognosis</h4><p>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 <sup>11</sup>.</p><p>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 <a href="/articles/extracorporeal-membrane-oxygenation">extracorporeal membrane oxygenation (ECMO)</a> have also been used where clinically necessary. </p><p>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 <sup>20</sup>, and early reports suggested similar efficacy in the treatment of COVID-19 <sup>23</sup>. However, more a recent randomized, controlled trial failed to demonstrate and added benefit of lopinavir-ritonavir combination therapy <sup>66</sup>. </p><p>Remdesivir, a drug originally developed to treat <a href="/articles/ebola-virus-disease-1">Ebola virus</a> and shown to be effective against MERS-CoV and SARS-CoV, showed promising in vitro results against SARS-CoV-2 <sup>29</sup> and is being tested in humans <sup>30</sup>.</p><p>Vaccines for the coronaviruses have been under development since the SARS outbreak, but none are yet available for humans <sup>11,26</sup>. A phase I trial in humans of a potential vaccine against MERS-CoV has already been performed in the UK <sup>26</sup>.</p><p>Emerging expert opinion is that <a href="/articles/non-steroidal-anti-inflammatory-drugs">non-steroidal anti-inflammatory drugs (NSAIDs)</a> are relatively contraindicated in those with COVID-19. This is based upon several strands of "evidence" <sup>61</sup>:</p><ul>

References changed:

  • 66. Bin Cao, Yeming Wang, Danning Wen et-al. A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19. (2020) New England Journal of Medicine. <a href="https://doi.org/10.1056/NEJMoa2001282">doi:10.1056/NEJMoa2001282</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/32187464">Pubmed</a> <span class="ref_v4"></span>

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