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COVID-19
Dr Daniel J Bell◉ et al.

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 the 2019 novel coronavirus (2019-nCoV), a strain
of coronavirus. The first cases were seen in Wuhan, China, in late December 2019 before spreading globally.
The current outbreak was officially recognized as a pandemic by the World Health Organization (WHO) on 11
March 2020.

Definitive diagnosis of COVID-19 requires a positive RT-PCR test. Current best practice advises that CT chest
is not used to diagnose COVID-19, but maybe helpful in assessing for complications. The non-specific imaging
findings are most commonly of atypical or organizing pneumonia, often with a bilateral, peripheral, and basal
predominant distribution. No effective treatment or vaccine exists currently.

Terminology
The World Health Organization originally called this illness "novel coronavirus-infected pneumonia (NCIP)", and
the virus itself had been provisionally 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 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 capitalized, except for the 'o'
in the viral name, which is in lowercase 16,22,41.

The official virus name is similar to SARS-CoV, the virus strain that caused epidemic severe acute respiratory
syndrome (SARS) in 2002-2004, 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 when communicating with
the public 45.

Epidemiology
As of 31 May 2020, the number of cases of confirmed COVID-19 globally is over 6 million affecting virtually
every territory, other than isolated South Pacific island states and Antarctica, according to an online virus
tracker created by the medical journal, The Lancet, and hosted by Johns Hopkins University 5. As of June 2020,
the United States had more than 1.5 million cases, with more than ten other countries with >100,000 cases 5.

NB: Surveillance methods and capacity vary dramatically between countries. Presymptomatic carriers may be
present in many communities and presymptomatic transmission has been documented; asymptomatic carriers
have been uncommonly reported and no asymptomatic transmission has been documented (May 2020) 113.

The R0 (basic reproduction number) of SARS-CoV-2 has been estimated between 2.2 and 3.28 in a non-
lockdown population, that is each infected individual, on average, causes between 2-3 new infections 12,33.

The incubation period for COVID-19 was initially calculated to be about five days, which was based on 10
patients only 12. An American group performed an epidemiological analysis of 181 cases, for which days of
exposure and symptom onset could be estimated accurately. They calculated a median incubation period of 5.1
days, that 97.5% became symptomatic within 11.5 days (CI 8.2 to 15.6 days) of being infected, and that
extending the cohort to the 99th percentile results in almost all cases developing symptoms in 14 days after
exposure to SARS-CoV-2 92.

As of June 2020 the number of deaths from COVID-19 is in excess of 350,000 globally 5. The case fatality
rate is ~2-3% 5,93. It is speculated that the true case fatality rate is lower than this because many
mild/asymptomatic cases are not being tested, which thus skews the apparent death rate upwards 93.

A paper published by the Chinese Center for Disease Control and Prevention (CCDC) analyzed all 44,672
cases diagnosed up to 11 February 2020. Of these, ~1% were asymptomatic, and ~80% were classed as
"mild" 25.

Another study looked at clinical characteristics in COVID-19 positively tested close contacts of COVID-19
patients 81. Approximately 30% of those COVID-19 positive close contacts never developed any symptoms or
changes on chest CT scans. The remainder showed changes in CT, but ~20% reportedly 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 the Chinese population, 55-60%% of COVID-19 patients were male; the median age has been reported
between 47 and 59 years 12,93.

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 behaviors to alter transmission or prevalence patterns).

Pediatric
Children seem to be relatively unaffected by this virus, or indeed other closely-related coronaviruses 31,47,90 with
large cohort studies reporting that 1-2% of COVID-19 patients are children 59,90,91. However, there have been
cases of critically-ill children with infants under 12 months likely to be more seriously affected 59. A very low
number of pediatric deaths has been reported 90,91. In children, male gender does not seem to be a risk factor 59.
The incubation period has been reported to be shorter than in adults, at about two days 90.

Clinical presentation
COVID-19 typically presents with systemic and/or respiratory manifestations 93. 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.

The full spectrum of clinical manifestation of COVID-19 remains to be determined . Symptoms and signs
1,13

are non-specific 68:

 Common

 fever (85-90%)
 cough (65-70%)
 disturbed taste and smell (40-50%)
 fatigue (35-40%)
 sputum production (30-35%)
 shortness of breath (15-20%)
Less common

 myalgia/arthralgia (10-15%)
 headaches (10-36%) 121
 sore throat (10-15%)
 chills (10-12%)
 pleuritic pain
Rare

 nausea, vomiting, nasal congestion (<10%), diarrhea (<5%) 93

 palpitations, chest tightness 50
 hemoptysis (<5%) 134
 seizures, paraesthesia, altered consciousness 121
COVID-19 sufferers have reported high rates of disturbances of smell and taste, including anosmia,
hyposmia, ageusia, and dysgeusia. The numbers of patients affected vary and current evidence points more
towards a neurological than a conductive cause of the olfactory dysfunction 79,98,105-107,139.

Various reports suggest patients with the disease may have symptoms of conjunctivitis, and those
affected, may have positive viral PCR in their conjunctival fluid 103,104. However a meta-analysis of over 1,100
patients found that conjunctivitis was only present in 1.1% cases 140. A small case series found conjunctivitis to
be the only clinical manifestation in some patients with COVID-19 141.

A recent report suggests that cutaneous lesions may also be seen, similar to many other viral infections. In a
cohort of 88 patients, 20% developed skin disease, most commonly an erythematous rash. Most of the skin
abnormalities were self-limited, resolving in a few days 100.

Pediatric
In the main, the clinical presentation in children with COVID-19 is milder 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 diarrhea, 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. It is believed to be highly specific, but with sensitivity reported as low as 60-70% 32 and as high as 95-
97% 56. Meta-analysis has reported the pooled sensitivity of RT-PCR to be 89% 116. 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.
 Its sensitivity is predicated on time since exposure to SARS-CoV-2, with a false negative rate of 100% on the
first day after exposure, dropping to 67% on the fourth day. On the day of symptom onset (~ days after
exposure) the false negative rate remains at 38%, and it reaches its nadir of 20% three days after symptoms
begin (8 days post exposure). From this point on, the false negative rate starts to climb again reaching 66% on
day 21 after exposure 138.

CT as diagnostic test
Multiple radiological organizations and learned societies have stated that CT should not be relied upon as a
diagnostic/screening tool for COVID-19 52,57,87,88,116. 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
controversially as a surrogate diagnostic test by some 2,32,89.

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

 lymphopenia
 increased prothrombin time (PT)
 increased lactate dehydrogenase
Mild elevations of inflammatory markers (CRP 89 and ESR) and D-dimer are also seen.

Complications
In one of the largest studies of hospitalized patients, reviewing 1,099 individuals across China, the admission
rate to the intensive care unit (ICU) was 5% 93. In this same study, 6% of all patients required ventilation,
whether invasive or non-invasive.

ICU patients tend to be older with more comorbidities .

13,93

Commonly reported sequelae are:

 acute respiratory distress syndrome (ARDS): ~22.5% (range 17-29%) 89

 acute thromboembolic disease 130
o pulmonary embolism 114,117,131-133
o deep vein thrombosis (DVT) 123
 acute cardiac injury: elevated troponin levels
o myocardial ischemia
o cardiac arrest
o myocarditis 120
 CNS
o viral encephalitis 121
 secondary infections, e.g. bacterial pneumonia
 sepsis
 acute kidney injury (AKI)
 multiorgan failure 66
In a small subgroup of severe ICU cases:

 secondary hemophagocytic lymphohistiocytosis (a cytokine storm syndrome) 49

 Risk factors for pulmonary embolism
In a multivariate analysis, an elevated risk of developing PE was associated with :
133

 obesity
 elevated D-dimer
 elevated CRP
 rising D-dimer over time

Pediatric complications
In April 2020, reports started to appear of critically-ill children presenting with a multisystem inflammatory state
which bore some resemblance to Kawasaki disease and toxic shock syndrome. Typically abdominal pain and
other GI symptoms were present and often evidence of a myocarditis. The presentations necessitated ICU
admission and fatalities have been reported 126,127.

Pathology
Etiology
On 9 January 2020, the World Health Organization (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 one of the two strains of the SARS-CoV
species known to cause human disease, the other being the original severe acute respiratory syndrome
coronavirus (SARS-CoV), the cause of SARS. 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, 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.

Six coronaviruses are known to cause human disease. 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 all cause the common cold.

Pathophysiology
The SARS-CoV-2 virus, like the closely-related MERS and SARS coronaviruses, effects 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 now considered to be an indirect zoonosis, as
its transmission is now primarily human-to-human. It is predominantly 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 are plausible 58.
 Orofecal 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 recently published cohort study (26 March 2020) could not rule out the possibility of vertical transmission with
9% of neonates (n=3/33) developing an early onset SARS-CoV-2 infection despite strict infection control
measures during delivery 94. However, a 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

Imaging indications
The threshold for the imaging of patients with potential/confirmed COVID-19 demonstrates a degree of
variation globally due to local resources, the published guidelines of individual learned bodies and sociocultural
approaches to imaging.

The use of CT as a primary screening tool is discouraged, not least because these studies tended to suffer
from selection bias 52,57,87,88,115, with a recent (April 2020) meta-analysis reporting a pooled sensitivity of 94% and
specificity 37% 116. In low prevalence (<10%) countries, the positive predictive value of RT-PCR was ten-fold
that of CT chest 116.

According to a Fleischner Society consensus statement published on 7 April 2020 101:

 imaging is not indicated in patients with suspected COVID-19 and mild clinical features unless they are at risk for
disease progression
 imaging is indicated in a patient with COVID-19 and worsening respiratory status
 in a resource-constrained environment, imaging is indicated for medical triage of patients with suspected COVID-
19 who present with moderate-severe clinical features and a high pretest probability of disease
Moreover performing CT routinely for large cohorts of patients carries additional risks :
115

 depletion of finite resources, especially PPE due to excessive usage

 increased risk of viral transmission (to staff, patients and carers) as COVID-19 positive and negative patients come
into close proximity in the radiology department
 additional ionizing radiation exposures

Infection precautions
Given that the staff in a medical imaging department are often in the frontline when dealing 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. The causative organism, SARS-CoV-2,
can survive 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.
 There are case studies of portable chest x-rays performed through the glass window of the patient's room to
decrease both staff exposure and amount of personal protective equipment 102, although departmental protocols
will vary significantly.

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

Non-urgent care
Both the American College of Radiology (ACR) and the Centers for Disease Control and Prevention (CDC) in
the United States advise that non-urgent outpatient appointments should be rescheduled 83,84. 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 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
medium is indicated, for example a CT pulmonary angiogram (CTPA), a non-contrast scan should be
considered prior to contrast administration, as contrast may impact the interpretation of ground-glass
opacification (GGO) patterns 89.

Radiographic features
The primary findings of COVID-19 on chest radiograph and CT are those of atypical pneumonia 40 or organizing
pneumonia 32,34.

However imaging has limited sensitivity for COVID-19, as up to 18% demonstrate normal chest radiographs or
CT when mild or early in the disease course, but this decreases to 3% in severe disease 89,93. Bilateral and/or
multilobar involvement is common 6,78.

The current recommendation of many learned societies and professional radiological associations is that
imaging should not be employed as a screening/diagnostic tool for COVID-19, but reserved for the evaluation
of complications 115.

Plain radiograph
Although less sensitive than chest CT, chest radiography is typically the first-line imaging modality used for
patients with suspected COVID-19 97. For ease of decontamination, use of portable radiography units is
preferred 52.

Chest radiographs may be normal in early or mild disease. Of patients with COVID-19 requiring hospitalization,
69% had an abnormal chest radiograph at the initial time of admission, and 80% had radiographic
abnormalities sometime during hospitalization 97. Findings are most extensive about 10-12 days after symptom
onset 97.

The most frequent findings are airspace opacities, whether described as consolidation or, less
commonly, GGO 89,97. The distribution is most often bilateral, peripheral, and lower zone predominant 89.97. In
contrast to parenchymal abnormalities, pleural effusion is rare (3%) 97.

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

 ground-glass opacities (GGO): bilateral, subpleural, peripheral

 crazy paving appearance (GGOs and inter-/intra-lobular septal thickening)
 air space consolidation
 bronchovascular thickening in the lesion
 traction bronchiectasis
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.

The following chest CT findings have been reported to have 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:

 mediastinal lymphadenopathy 17
 pleural effusions: may occur as a complication of COVID-19
 multiple tiny pulmonary nodules (unlike many other types of viral pneumonia)
 tree-in-bud
 pneumothorax
 cavitation

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

o up to half of patients have normal CT scans within two 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 one month and beyond

Pediatric 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% of 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
o ranging from focal to diffuse with spared areas 64
o representing thickened subpleural interlobular septa
 may also manifest as a light beam sign, an evanescent, broad-based vertical reverberation artifact arising
from a regular pleural line 128
 irregular, thickened pleural line with scattered discontinuities 63
 subpleural consolidations
o can be associated with a discrete, localized pleural effusion
o relatively avascular with color flow Doppler interrogation
o pneumonic consolidation typically associated with preservation of flow or hyperemia 65

 alveolar consolidation
o tissue-like appearance with dynamic and static air bronchograms
o associated with severe, progressive disease
 restitution of aeration during recovery
o 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. 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.

Radiology report
The Radiological Society of North America (RSNA) has released a consensus statement endorsed by
the Society of Thoracic Radiology and the American College of Radiology (ACR) that classifies the CT
appearance of COVID-19 into four categories for standardized reporting language 99:

 typical appearance
o peripheral, bilateral, GGO +/- consolidation or visible intralobular lines (“crazy paving” pattern)
o multifocal GGO of rounded morphology +/- consolidation or visible intralobular lines (“crazy paving” pattern)
o reverse halo sign or other findings of organizing pneumonia
 indeterminate appearance
o absence of typical CT findings and the presence of
 multifocal, diffuse, perihilar, or unilateral GGO +/- consolidation lacking a specific distribution and are non-
rounded or non-peripheral
 few very small GGO with a non-rounded and non-peripheral distribution
 atypical appearance
o absence of typical or indeterminate features and the presence of
  isolated lobar or segmental consolidation without GGO
 discrete small nodules (e.g. centrilobular, tree-in-bud)
 lung cavitation
 smoother interlobular septal thickening with pleural effusion
 negative for pneumonia: no CT features to suggest pneumonia, in particular, absent GGO and consolidation

CO-RADS
In March 2020, the "COVID-19 standardized reporting working group" of the Dutch Association for Radiology
(NVvR) proposed a CT scoring system for COVID-19. They called it CO-RADS (COVID-19 Reporting and Data
System) to ensure CT reporting is uniform and replicable. This assigns a score of CO-RADS 1 to 5, dependent
on the CT findings. In some cases a score of 0 or 6 may need to be assigned as an alternative. If the CT is
uninterpretable then it is CO-RADS 0, and if there is a confirmed positive RT-PCR test then it is CO-RADS
6. 109,124.

The first study investigating the use of CO-RADS found a reasonable level of interobserver variation, with a
Fleiss' kappa score of 0.47 (cf. 0.24 for PI-RADS and 0.67 for Lung-RADS) 124.

COVID-RADS
In April 2020, American radiologists based at the University of Southern California proposed the COVID-19
imaging reporting and data system (COVID-RADS), which has a confusingly similar name to CO-RADS (see
above) 125.

Treatment and prognosis

Treatment
No specific treatment or vaccine exists for COVID-19 (May 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, social distancing,
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, both invasive and non-invasive, and extracorporeal membrane oxygenation
(ECMO) have also been used where clinically necessary.

Proning
Historical studies have demonstrated a net benefit for patients with moderate to severe ARDS being turned
prone 118. Many health care facilities have adopted the practice of turning the sicker COVID-19 patients into a
prone position, so-called "proning" to improve their lung oxygenation 119.

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.

In early 2020, published reports showed that two antimalarial drugs, chloroquine, and its close chemical
derivative, hydroxychloroquine, had strong anti-SARS-2-CoV activity in vitro. An initial open-label, randomized
clinical trial, 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. However this trial was later strongly criticized for methodological flaws and
questionable conclusions. Later studies have failed to replicate beneficial effects of these agents and also
highlight potential side-effects 135.

Passive immunity
Treatment with convalescent plasma (plasma from patients who have recovered from COVID-19 which
therefore contains anti-SARS-CoV-2 antibodies) or hyperimmune immunoglobulin (purified antibodies prepared
from convalescent plasma) has shown some success in some critically ill patients. Reports are still preliminary
and about a small number of patients 110-112,136. A Cochrane review in May 2020 failed to find convincing evidence
that convalescent plasma was an effective treatment, but this will be kept under active review 136.

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.

Risk factors for severe illness or poor outcome

 general 68,95
 o old age
o people in a long-term care facility or nursing home
o male gender
 comorbidities 68,95
o cardiovascular disease
o diabetes mellitus
o hypertension
o chronic respiratory disease, e.g. COPD
o cancer
o chronic liver disease
o chronic renal disease
o immunosuppression
 patient condition and laboratory values at hospital admission 96
o high sequential organ failure assessment (SOFA) score on admission
o D-dimer levels greater than 1µg/mL on hospital admission
o elevated levels of IL-6, troponin I, lactate dehydrogenase
o lymphopenia

History and etymology

The first cases were seen in Wuhan, China, in late December 2019 before spreading globally .
1,2,10

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 neighboring 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. On 9 January 2020, the
World Health Organization confirmed that SARS-CoV-2 was the cause of the new disease 14,37.

The first scientific article about the new disease, initially termed 2019‐new coronavirus (2019‐nCoV) by the
World Health Organization (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.

On 27 March 2020, the USA surpassed China as the country with the most confirmed cases 5. The number of
confirmed cases globally exceeded one million for the first time on 3 April 2020, two million on 15 April, five
million on 21 May 5. The number of global deaths surpassed 100,000 on 10 April and 200,000 on 26 April
2020 5.

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 WHO officially renamed the
clinical condition COVID-19 (a shortening of COronaVIrus Disease-19) 15. On the same day, the Coronavirus
Study Group 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
 viral pneumonia including 71,72:
o influenza pneumonia A and B
 distribution more along the bronchovascular bundles
 bronchial wall thickening
o paramyxovirus pneumonia
o cytomegalovirus (CMV) pneumonia
o adenovirus pneumonia 71,72
o SARS-CoV pneumonia
o MERS coronavirus
o HSV pneumonia
 in immunocompromised patients
 often shows pleural effusions
o respiratory syncytial virus (RSV) pneumonia
 atypical bacterial pneumonia
o mycoplasma pneumonia
 mainly children and adolescents
 bronchial wall thickening
 centrilobular nodules
o chlamydia pneumonia
 pulmonary edema 71

 interstitial lung disease 73

o cryptogenic organizing pneumonia
o chronic eosinophilic pneumonia (CEP)
o acute fibrinous organizing pneumonia
o rheumatoid arthritis-associated pneumonia 71
 certain drug-induced pneumonitides
o immune checkpoint inhibitor therapy-related pneumonitis
 for a "crazy paving" predominant manifestation also consider conditions such as
o pulmonary alveolar proteinosis

Clinical differential diagnoses

The clinical differential diagnosis is very similar to the imaging differential when patients present with typical
symptoms, e.g. cough and fever. However some divergence might be seen if there are less typical
presentations, e.g. acute breathlessness, which would raise suspicion for pulmonary embolism which is clearly
not an imaging differential most of the time 134.

Resources
These lists are in alphabetical order:

 general information
 o COVID-19 global cases by Johns Hopkins
o World Health Organization information page
 research publications and datasets
o ARRS - AJR Open Access COVID-19 Collection
o British Medical Journal COVID-19 collection
o European Radiology COVID-19 - latest articles
o New England Journal of Medicine COVID-19 resources
o RSNA COVID-19 research
o The Lancet COVID-19 resource center
o World Health Organization Database of publications on COVID-19
o COVID-19 Open Research Dataset (CORD-19)
 government information
o Australia (Department of Health)
o Australia (Smartraveller)
o Canada (Infection Prevention and Control Canada)
o Canada (Government of Canada)
o Europe (European Center for Disease Prevention and Control)
o Israel (Ministry of Health)
o Italy (Dipartimento della Protezione Civile)
o Mexico (Secretaría de Salud)
o New Zealand (Ministry of Health)
o Singapore (Ministry of Health)
o United Kingdom (National Health Service UK)
o United States of America (Centers for Disease Control and Prevention)

See also
 acute respiratory distress syndrome (ARDS)
 human coronaviruses
 Middle East respiratory syndrome coronavirus (MERS-CoV)
 secondary hemophagocytic lymphohistiocytosis
 severe acute respiratory syndrome coronavirus (SARS-CoV)
 World Health Organization (WHO)
Quiz questions
References

Related Radiopaedia articles

Viral infections
 coronavirus
o COVID-19 (summary)
 o Middle East respiratory syndrome coronavirus (MERS-CoV)
o severe acute respiratory syndrome (SARS)
 Ebola
 human immunodeficiency virus (HIV)
 human papilloma virus (HPV)
 influenza[+]
 Zika

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Cases and figures

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Figure 1: photo - SARS-CoV-2

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Case 1
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Case 2: pediatric
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Case 3
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Case 4: longitudinal imaging over a month

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Case 15: at day 13

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 Case 16: radiological evolution over 2 weeks
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Case 17
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Case 18: with unilateral air space consolidation

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Case 19: bilateral and peripheral alveolar consol…

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Case 20
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Case 21: exclusive gastrointestinal symptoms

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Case 26: on CT abdomen

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Case 41: post-intubation pneumomediastinum an…

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Case 42: rapidly progressive ARDS

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Case 46: mild

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Case 50: mild

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Case 56: rapidly progressive

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Case 57: mild

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Case 64: early stage

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Case 65: with superadded bacterial …

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Case 72: early stage

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Case 75: early stage

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Case 94
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 Case 95: with radiological resolution

Imaging differential diagnosis

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Influenza A pneumonia
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Cryptogenic organizing pneumonia

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Cytomegalovirus pneumonia
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Atypical pneumonia - mycoplasma

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Pulmonary alveolar proteinosis

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Pneumocystis jirovecii pneumonia