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), a strain of coronavirus. The first cases were seen in Wuhan, China, in December 2019 before spreading globally, with more than 20 million cases now confirmed. 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 proven treatment or vaccine exists currently, although dexamethasone, a steroid agent, has been shown to markedly improve outcomes in ventilated/oxygen-dependent patients.

The official name of the illness is COVID-19 (a shortening of COronaVIrus Disease-19) 15 and it is caused by the "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 letter 'o' in the viral name, which is in lowercase 16,22,41

The official virus name is similar to SARS-CoV-1, the virus strain that caused epidemic severe acute respiratory syndrome (SARS) in 2002-2004, potentially causing confusion 38. The World Health Organization (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.

As of August 2020, the number of cases of confirmed COVID-19 globally is over 20 million affecting virtually every territory, other than isolated South Pacific island states and Antarctica 156, according to an online virus tracker created by the medical journal, The Lancet, and hosted by Johns Hopkins University 5. The United States has over five million cases, and both Brazil and India have had more than two million cases each 5

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 August 2020 the number of deaths from COVID-19 exceeds 735,000 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.

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.

NB: Surveillance methods and capacity vary dramatically between countries. The epidemiological parameters of any new disease are likely to change as larger cohorts of COVID-19 positive cases 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 people will be simultaneously changing their behaviors to alter transmission or prevalence patterns). 

COVID-19 typically presents with systemic and/or respiratory manifestations 93,170. Some also experience mild gastrointestinal or cardiovascular symptoms, although these are less common 18,50. Others may present solely with a gastroenteritis-like illness, which may not initially be recognized to be COVID-19 171.

A significant minority of individuals infected with SARS-CoV-2 remain asymptomatic throughout the course of their illness acting as carriers 70,113,164

The full spectrum of clinical manifestations of COVID-19 is broad 1,13. Symptoms and signs are non-specific 68:

Common

  • fever (85-90%)
  • cough (65-70%)
  • anosmia (and other taste and/or smell disturbances) (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
  • diarrhea (3-34%) 171

Rare

  • nausea, vomiting, abdominal pain, GI bleeding 93,171
  • nasal congestion (<10%) 93
  • palpitations, chest tightness 50
  • hemoptysis (<5%) 134
  • confusion 137, seizures, paresthesia, altered consciousness 121
  • stroke 149-151 (most commonly cryptogenic 150,151)

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 isolated conjunctivitis as the only visible manifestation in some COVID-19 patients 141.

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.

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.

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 (~4 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.

The place of antibody tests in the investigation of present and previous cases of COVID-19 remains unclear and contentious. It may have a complementary role in diagnosis, especially when the RT-PCR test is negative in those whom remain suspected to have COVID-19 160.

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

The most common ancillary laboratory findings in patients, including a study of 61,742, were the following 13,89:

Other commonly identified abnormalities include:

  • mild elevated inflammatory markers (CRP 89 and ESR)
  • elevated D-dimer
  • mildly elevated serum amylase: 17% patients (study of 52 cases) 145
  • mildly deranged liver function tests are common, primarily elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 145,146
    • bilirubin rise is generally mild 146
    • alkaline phosphatase (AKP) and gamma‐glutamyl transferase (GGT) levels remain normal 146

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:

In a small subgroup of severe ICU cases:

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

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 rare fatalities have been reported 126,127

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-1), 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 other coronaviruses are known to cause human disease. Two are zoonoses: the severe acute respiratory syndrome coronavirus (SARS-CoV-1) and Middle East respiratory syndrome coronavirus (MERS-CoV), both of which may sometimes be fatal. The remaining four viruses all cause the common cold

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 (ACE2) 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 ACE2 receptor, which is also commonly expressed on the cells of the cardiovascular system 50.

Although originating from animals, COVID-19 is now considered to be an indirect zoonosis, as its transmission is now primarily human-to-human. It was initially thought to be 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.

It is now thought that aerosol transmission of SARS-CoV-2, i.e. airborne transmission, also occurs 58,161,162,172. In the early stages of the pandemic aerosol risk was thought to be limited to so-called aerosol-generating procedures (AGPs) in healthcare facilities. However there is an increasing evidence base to show that aerosols are also produced by talking, singing, coughing and expiration 162.

Fomite transmission is also seen, explaining the emphasis on regular handwashing and regular cleaning of surfaces that might have been exposed to droplets/aerosols containing virion particles 58,162,172-174. The SARS-CoV-2 has a short half-life on some non-porous surfaces, including copper and latex, but is more persistent on other materials such as glass, plastics, stainless steel and porous fabrics 174

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.

Sexual transmission has not been seen in the field but remains possible, not least because the SARS-CoV-2 virus has been found in all bodily secretions including seminal and vaginal fluids 143.

It remains unclear if COVID-19 could be transmitted through a blood transfusion although no cases have yet be seen. Nevertheless, many national bodies have instituted controls to reduce the chance of this happening including advising that potential donors do not give blood until 28 days after recovering from COVID-19 142.

Cohort studies have been unable to rule out the possibility of vertical transmission, but it seems to be a rare event if it does occur 21,82,94,152. A large prospective cohort study of 427 pregnant women from all 194 birth units across the UK found that 5% of 265 live births were confirmed as COVID-19 on RT-PCR 152.

Presymptomatic carriers are likely present in many communities and presymptomatic transmission has been documented 163

Asymptomatic carriage and transmission are also thought to occur 163,164.

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 meta-analysis, in April 2020, 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

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 (August 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). A study of 420 clinical staff found that personal protective equipment (PPE) protected the development of SARS-CoV-2 infection 39,155.

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 102,165, although departmental protocols will vary significantly.

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

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. This decision has been criticized for its uncompromising approach, especially when the underlying evidence is far from being clear-cut, with a suggestion that for many the risk-benefit calculation is in favor in performing the joint injection 181.

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.

The primary findings of COVID-19 on chest radiograph and CT are those of atypical pneumonia 40,175 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 the vast majority of 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.

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/mild disease. In those COVID-19 cases 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.

    Although cardiac manifestations of COVID-19 are well-recognized, there is no published evidence of cardiac disease on chest radiographs 175.

    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 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<0.00151:

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

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

    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 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

    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.

    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
      • representing 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 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

    FDG uptake is increased in ground-glass opacities in those with presumed/confirmed COVID-19 42,75,167. It has been hypothesized that those with higher SUVs in lung lesions take longer to heal 77

    The British Society of Thoracic Imaging (BSTI) have published a reporting proforma for the plain chest radiographic appearances of potential COVID-19 cases 168

    • classic/probable COVID-19
      • lower lobe and peripheral predominant multiple opacities that are bilateral (>> unilateral)
    • indeterminate for COVID-19
      • does not fit classic or non-COVID-19 descriptors
    • non-COVID-19
      • pneumothorax / lobar pneumonia / pleural effusion(s) / pulmonary edema / other
    • normal
      • COVID-19 not excluded

    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
      • peripheral, bilateral, GGO +/- consolidation or visible intralobular lines (“crazy paving” pattern)
      • multifocal GGO of rounded morphology +/- consolidation or visible intralobular lines (“crazy paving” pattern)
      • reverse halo sign or other findings of organizing pneumonia
    • indeterminate appearance
      • 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
      • 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

    A study evaluating the RSNA chest CT classification system for COVID-19 against RT-PCR results found moderate interobserver agreement. Using a cohort of 96 patients, it reported that 76.9-96.6% of "typical" scans, 51.2-64.1% of "indeterminate" scans, 2.8-5.3% "atypical" scans and 20-25% of "negative" scans returned a RT-PCR confirming COVID-19 99,147.

    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-RADS124. Another study found that CO-RADS is sensitive and specific for diagnosing COVID-19, using RT-PCR as the gold standard 184. CO-RADS-AI, a system using deep machine learning has been validated for diagnosing COVID-19 on CT chest 183.

    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.

    No specific treatment or vaccine exists for COVID-19 (August 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 11:

    • meticulous hand-washing
    • wearing of face masks
    • social distancing
    • avoidance of large crowds/crowded environments
    • self-isolation

    There is now increasing concern that aerosol transmission has a more significant role in viral spread than initially thought and this means that additional public health measures will need to be introduced, these will include 161,162:

    • better ventilation, especially in indoor public spaces, workplaces, educational establishments, healthcare facilities, and community residential centers for the elderly, in many cases this will be as simple as opening windows
    • specific aerosol infection control systems, such as:
      • high throughput and effective air filtration
      • virucidal UV (ultraviolet) lighting

    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.

    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

    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. A preliminary trial in May 2020 showed a small decrease in time to recovery, from 15 to 11 days, in those treated with remdesivir 153. However there are concerns about this evidence, and remdesivir has not been shown to decrease mortality nor reduce length of hospital stay 169. Other antivirals in phase III trials include oseltamivir, ASC09F (HIV protease inhibitor), lopinavir, ritonavir, darunavir, and cobicistat 80.

    Dexamethasone, was demonstrated in the large RECOVERY (Randomized Evaluation of COVid-19 thERapY) randomized controlled trial, in June 2020 to decrease deaths by a third in those on mechanical ventilation (p=0.0003), and by a fifth those non-ventilated patients requiring oxygen (p=0.0021). No benefit was seen in those not needing respiratory support 148.

    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.

    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.

    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. Human vaccines for coronaviruses have been under development since the SARS outbreak, but none are yet available 11,26. Over 125 vaccine candidates are now in preclinical trials 154.

    In early 2020 there were concerns raised about the safety of non-steroidal anti-inflammatory drugs (NSAIDs) in those with COVID-19. This was based upon anecdotal reports and expert opinion rather than published scientific evidence 61,166. There remains no evidence that the use of NSAIDs increases the risk of developing COVID-19 or worsens established disease. Several international and national medical regulatory agencies now state that there are no associated risks with using NSAIDs in those with, or at risk of developing, COVID-19 166.

    In Italy a document detailing 6801 patients who died from COVID-19 discovered that the median time from the first symptoms to hospital admission was five days, and nine days from symptom onset to death 178.

    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.

    In a study of 101 patients with COVID-19 who were referred for palliative care, breathlessness, delirium, drowsiness and agitation were the most frequently found symptoms 180.

    In general, pregnant women do not have worse outcomes than non-pregnant women with COVID-19 152. In a cohort of 427 women in the UK, 10% required a admission to critical care for respiratory support and 1% succumbed to the disease 152.

    "Long covid" has been used to refer to the condition whereby those who have recovered from COVID-19 still experience persistent manifestations or those with COVID-19 suffer symptoms for a longer time than normal 177

    As of July 2020 there is a dearth of published evidence of the long term effects following COVID-19 infection. An Italian study of 143 patients who had been discharged from hospital following a recovery from COVID-19 reveals that almost 90% people were still complaining of at least one symptom 60 days after the illness had begun 176. Common symptoms included lethargy, breathlessness, arthralgia and chest discomfort 176.

    The first cases were seen in Wuhan, China, in early 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 on 3 April 2020, two million on 15 April, five million on 21 May, 10 million on 28 June, 15 million on 23 July and 20 million on 11 August 5. The number of global deaths surpassed 100,000 on 10 April, 200,000 on 26 April and 500,000 on 28 June 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

    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 might raise suspicion for pulmonary embolism which is not an imaging differential in many cases 134.

    These lists are in alphabetical order:

    Article information

    rID: 73913
    System: Chest
    Section: Approach
    Synonyms or Alternate Spellings:
    • CO-RADS-AI
    • Long COVID
    • Novel coronavirus infected pneumonia (NCIP)
    • CO-RADS
    • COVID-19 Reporting and Data System
    • COVID-19 induced cytokine syndrome
    • COVID-19 pneumonia
    • Novel COVID-19-infected pneumonia (NCIP)
    • Wuhan virus
    • HCoV-19
    • Human coronavirus 2019 (HCoV-19)
    • COVID 19 virus
    • COVID-19 virus
    • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
    • SARS coronavirus 2
    • SARS CoV2
    • SARS-CoV2
    • SARS-CoV-2
    • Coronavirus disease-19
    • Severe acute respiratory syndrome coronavirus 2
    • Coronavirus disease 19
    • COVID 19
    • COVID19
    • Wuhan coronavirus infection
    • Novel coronavirus pneumonia
    • 2019 nCoV
    • 2019 novel coronavirus
    • Novel coronavirus-infected pneumonia (NCIP)
    • 2019-nCoV

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    Cases and figures

  • 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 5
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  • Case 6
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  • Case 12
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  • Case 13
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  • Case 14
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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 consolidations
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  • Case 20
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  • Case 21: exclusive gastrointestinal symptoms
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  • Case 22
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  • Case 23
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  • Case 24
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  • Case 25
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  • Case 26: on CT abdomen
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  • Case 27
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  • Case 39
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  • Case 40
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  • Case 41: post-intubation pneumomediastinum and pneumothorax with COVID-19 pneumonia
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  • Case 42: rapidly progressive ARDS
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  • Case 43
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  • Case 44
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  • Case 45
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  • Case 46: mild
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  • Case 50: mild
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  • Case 55
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  • Case 56: rapidly progressive
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  • Case 57: mild
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  • Case 58: incidental finding in asymptomatic patient
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  • Case 62
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  • Case 63
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  • Case 64: early stage
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  • Case 65: with superadded bacterial infection
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  • Case 71
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  • Case 72: early stage
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  • Case 74
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  • Case 75: early stage
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  • Case 93
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  • Case 94
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  • Case 95: with radiological resolution
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  • Case 96: COVID pneumonia and recovery
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