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 late December 2019 before spreading globally, with more than ten 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 effective treatment or vaccine exists currently, although dexamethasone, a steroid agent, has been shown to markedly improve outcomes in the sickest patients.
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-1, 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.
As of late June 2020, the number of cases of confirmed COVID-19 globally is over 10 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 two million cases, Russia more than one million, with five other countries with >250,000 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 late June 2020 the number of deaths from COVID-19 passed half a million 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).
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.
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 1,13. Symptoms and signs are non-specific 68:
- fever (85-90%)
- cough (65-70%)
- disturbed taste and smell (40-50%)
- fatigue (35-40%)
- sputum production (30-35%)
- shortness of breath (15-20%)
- myalgia/arthralgia (10-15%)
- headaches (10-36%) 121
- sore throat (10-15%)
- chills (10-12%)
- pleuritic pain
- nausea, vomiting, nasal congestion (<10%), diarrhea (<5%) 93
- palpitations, chest tightness 50
- hemoptysis (<5%) 134
- confusion 137, 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.
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.
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.
The most common ancillary laboratory findings in a study of 138 hospitalized patients 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
- frank acute pancreatitis has not been reported
- 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:
- acute respiratory distress syndrome (ARDS): ~22.5% (range 17-29%) 89
- acute thromboembolic disease 130
- acute cardiac injury: elevated troponin levels
- secondary infections, e.g. bacterial pneumonia
- acute kidney injury (AKI)
- coagulopathy 144
- multiorgan failure 66
In a small subgroup of severe ICU cases:
Risk factors for pulmonary embolism
In a multivariate analysis, an elevated risk of developing PE was associated with 133:
- 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 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), 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.
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.
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.
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.
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
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 (June 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).
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.
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.
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.
The primary findings on CT in adults have been reported as 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)
Temporal CT changes
Four stages on CT have been described 17,24,32,86:
- early/initial stage (0-4 days): normal CT or GGO only
- up to half of patients have normal CT scans within 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
- 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
- reappearance of bilateral A-lines
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.
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
- 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
- absence of typical CT findings and the presence of
- 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
- absence of typical or indeterminate features and the presence of
- 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.
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
No specific treatment or vaccine exists for COVID-19 (June 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.
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 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.
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.
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.
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
- old age
- people in a long-term care facility or nursing home
- male gender
- comorbidities 68,95
- patient condition and laboratory values at hospital admission 96
- high sequential organ failure assessment (SOFA) score on admission
- D-dimer levels greater than 1µg/mL on hospital admission
- elevated levels of IL-6, troponin I, lactate dehydrogenase
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 on 3 April 2020, two million on 15 April, five million on 21 May, and 10 million on 28 June 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.
viral pneumonia including 71,72:
influenza pneumonia A and B
- distribution more along the bronchovascular bundles
- bronchial wall thickening
- paramyxovirus pneumonia
- cytomegalovirus (CMV) pneumonia
- adenovirus pneumonia 71,72
- SARS-CoV pneumonia
- MERS coronavirus
- in immunocompromised patients
- often shows pleural effusions
- respiratory syncytial virus (RSV) pneumonia
- influenza pneumonia A and B
- atypical bacterial pneumonia
- pulmonary edema 71
- interstitial lung disease 73
- certain drug-induced pneumonitides
- neutropenic sepsis
- aspiration pneumonitis
- for a "crazy paving" predominant manifestation also consider conditions such as
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 might raise suspicion for pulmonary embolism which is not an imaging differential in many cases 134.
These lists are in alphabetical order:
- general information
- research publications and datasets
- ARRS - AJR Open Access COVID-19 Collection
- British Medical Journal COVID-19 collection
- European Radiology COVID-19 - latest articles
- New England Journal of Medicine COVID-19 resources
- RSNA COVID-19 research
- The Lancet COVID-19 resource center
- World Health Organization Database of publications on COVID-19
- COVID-19 Open Research Dataset (CORD-19)
- government information
- Australia (Department of Health)
- Australia (Smartraveller)
- Canada (Infection Prevention and Control Canada)
- Canada (Government of Canada)
- Europe (European Center for Disease Prevention and Control)
- Israel (Ministry of Health)
- Italy (Dipartimento della Protezione Civile)
- Mexico (Secretaría de Salud)
- New Zealand (Ministry of Health)
- Singapore (Ministry of Health)
- United Kingdom (National Health Service UK)
- United States of America (Centers for Disease Control and Prevention)
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