Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
There is no vaccine for SARS to date. Isolation and quarantine remain the most effective means to prevent the spread of SARS. Other preventative measures include:
- Disinfection of surfaces for fomites
- Wearing a surgical mask
- Avoiding contact with bodily fluids
- Washing the personal items of someone with SARS in hot, soapy water (eating utensils, dishes, bedding, etc.)
- Keeping children with symptoms home from school
Many public health interventions were taken to help control the spread of the disease; which is mainly spread through respiratory droplets in the air. These interventions included earlier detection of the disease, isolation of people who are infected, droplet and contact precautions, and the use of personal protective equipment (PPE); including masks and isolation gowns. A screening process was also put in place at airports to monitor air travel to and from affected countries. Although no cases have been identified since 2004, the CDC is still working to make federal and local rapid response guidelines and recommendations in the event of a reappearance of the virus.
Several consequent reports from China on some recovered SARS patients showed severe long-time sequelae exist. The most typical diseases include, among other things, pulmonary fibrosis, osteoporosis, and femoral necrosis, which have led to the complete loss of working ability or even self-care ability of these cases. As a result of quarantine procedures, some of the post-SARS patients have been documented suffering from posttraumatic stress disorder (PTSD) and major depressive disorder.
MERS cases have been reported to have low white blood cell count, and in particular low lymphocytes.
For PCR testing, the WHO recommends obtaining samples from the lower respiratory tract via bronchoalveolar lavage (BAL), sputum sample or tracheal aspirate as these have the highest viral loads. There have also been studies utilizing upper respiratory sampling via nasopharyngeal swab.
Several highly sensitive, confirmatory real-time RT-PCR assays exist for rapid identification of MERS-CoV from patient-derived samples. These assays attempt to amplify upE (targets elements upstream of the E gene), open reading frame 1B (targets the ORF1b gene) and open reading frame 1A (targets the ORF1a gene). The WHO recommends the upE target for screening assays as it is highly sensitive. In addition, hemi-nested sequencing amplicons targeting RdRp (present in all coronaviruses) and nucleocapsid (N) gene (specific to MERS-CoV) fragments can be generated for confirmation via sequencing. Reports of potential polymorphisms in the N gene between isolates highlight the necessity for sequence-based characterization.
The WHO recommended testing algorithm is to start with an upE RT-PCR and if positive confirm with ORF 1A assay or RdRp or N gene sequence assay for confirmation. If both an upE and secondary assay are positive it is considered a confirmed case.
Protocols for biologically safe immunofluorescence assays (IFA) have also been developed; however, antibodies against betacoronaviruses are known to cross-react within the genus. This effectively limits their use to confirmatory applications. A more specific protein-microarray based assay has also been developed that did not show any cross-reactivity against population samples and serum known to be positive for other betacoronaviruses. Due to the limited validation done so far with serological assays, WHO guidance is that "cases where the testing laboratory has reported positive serological test results in the absence of PCR testing or sequencing, are considered probable cases of MERS-CoV infection, if they meet the other conditions of that case definition."
According to World Health Organization, the interim case definition is that a confirmed case is identified in a person with a positive lab test by "molecular diagnostics including either a positive PCR on at least two specific genomic targets or a single positive target with sequencing on a second."
The WHO has published several testing protocols for the disease. The standard method of testing is real-time reverse transcription polymerase chain reaction (rRT-PCR). The test is typically done on respiratory samples obtained by a nasopharyngeal swab; however, a nasal swab or sputum sample may also be used. Results are generally available within a few hours to two days. Blood tests can be used, but these require two blood samples taken two weeks apart and the results have little immediate value. Chinese scientists were able to isolate a strain of the coronavirus and publish the genetic sequence so laboratories across the world could independently develop polymerase chain reaction (PCR) tests to detect infection by the virus. As of 4 April 2020, antibody tests (which may detect active infections and whether a person had been infected in the past) were in development, but not yet widely used. The Chinese experience with testing has shown the accuracy is only 60 to 70%. The FDA in the United States approved the first point-of-care test on 21 March 2020 for use at the end of that month.
Diagnostic guidelines released by Zhongnan Hospital of Wuhan University suggested methods for detecting infections based upon clinical features and epidemiological risk. These involved identifying people who had at least two of the following symptoms in addition to a history of travel to Wuhan or contact with other infected people: fever, imaging features of pneumonia, normal or reduced white blood cell count or reduced lymphocyte count.
A study asked hospitalized COVID-19 patients to cough into a sterile container, thus producing a saliva sample, and detected virus in eleven of twelve patients using RT-PCR. This technique has the potential of being quicker than a swab and involving less risk to health care workers (collection at home or in the car).
Along with laboratory testing, chest CT scans may be helpful to diagnose COVID-19 in individuals with a high clinical suspicion of infection but is not recommended for routine screening. Bilateral multilobar ground-glass opacities with a peripheral, asymmetric and posterior distribution are common in early infection. Subpleural dominance, crazy paving (lobular septal thickening with variable alveolar filling), and consolidation may appear as the disease progresses.
Few data are available about microscopic lesions and the pathophysiology of COVID-19. The main pathological findings at autopsy are:
- Macroscopy: pleurisy, pericarditis, lung consolidation and pulmonary oedema
- Four types of severity of viral pneumonia can be observed:
- minor pneumonia: minor serous exudation, minor fibrin exudation
- mild pneumonia: pulmonary oedema, pneumocyte hyperplasia, large atypical pneumocytes, interstitial inflammation with lymphocytic infiltration and multinucleated giant cell formation
- severe pneumonia: diffuse alveolar damage (DAD) with diffuse alveolar exudates. DAD is the cause of acute respiratory distress syndrome (ARDS) and severe hypoxemia.
- healing pneumonia: organisation of exudates in alveolar cavities and pulmonary interstitial fibrosis
- plasmocytosis in BAL
- Blood: disseminated intravascular coagulation (DIC); leukoerythroblastic reaction
- Liver: microvesicular steatosis
The best prevention against viral pneumonia is vaccination against influenza, adenovirus, chickenpox, herpes zoster, measles, and rubella.
Based on the low variability exhibited among known SARS-CoV-2 genomic sequences, the strain is thought to have been detected by health authorities within weeks of its emergence among the human population in late 2019. The earliest case of infection currently known is thought to have been found on 17 November 2019. The virus subsequently spread to all provinces of China and to more than 150 other countries in Asia, Europe, North America, South America, Africa, and Oceania. Human-to-human transmission of the virus has been confirmed in all of these regions. On 30 January 2020, SARS-CoV-2 was designated a Public Health Emergency of International Concern by the WHO, and on 11 March 2020 the WHO declared it a pandemic.
The basic reproduction number (R0) of the virus has been estimated to be between 1.4 and 3.9. This means that each infection from the virus is expected to result in 1.4 to 3.9 new infections when no members of the community are immune and no preventive measures are taken. The reproduction number may be higher in densely populated conditions such as those found on cruise ships. Many forms of preventive efforts may be employed in specific circumstances in order to reduce the propagation of the virus.
There have been about 82,000 confirmed cases of infection in mainland China. While the proportion of infections that result in confirmed cases or progress to diagnosable disease remains unclear, one mathematical model estimated that on 25 January 2020 75,815 people were infected in Wuhan alone, at a time when the number of confirmed cases worldwide was only 2,015. Before 24 February 2020, over 95% of all deaths from COVID-19 worldwide had occurred in Hubei province, where Wuhan is located. As of 17 April 2020, the percentage had decreased to 2.1%.
As of 17 April 2020, there have been 2,234,109 total confirmed cases of SARS-CoV-2 infection in the ongoing pandemic. The total number of deaths attributed to the virus is 153,379. Many recoveries from confirmed infections go unreported, but at least 567,695 people have recovered from confirmed infections.
In cases of viral pneumonia where influenza A or B are thought to be causative agents, patients who are seen within 48 hours of symptom onset may benefit from treatment with oseltamivir or zanamivir. Respiratory syncytial virus (RSV) has no direct acting treatments, but ribavirin in indicated for severe cases. Herpes simplex virus and varicella-zoster virus infections are usually treated with aciclovir, whilst ganciclovir is used to treat cytomegalovirus. There is no known efficacious treatment for pneumonia caused by SARS coronavirus, MERS coronavirus, adenovirus, hantavirus, or parainfluenza. Care is largely supportive.
Vaccination helps prevent bronchopneumonia, mostly against influenza viruses, adenoviruses, measles, rubella, streptococcus pneumoniae, haemophilus influenzae, diphtheria, bacillus anthracis, chickenpox, and bordetella pertussis.
Antibiotics do not help the many lower respiratory infections which are caused by parasites or viruses. While acute bronchitis often does not require antibiotic therapy, antibiotics can be given to patients with acute exacerbations of chronic bronchitis. The indications for treatment are increased dyspnoea, and an increase in the volume or purulence of the sputum. The treatment of bacterial pneumonia is selected by considering the age of the patient, the severity of the illness and the presence of underlying disease. Amoxicillin and doxycycline are suitable for many of the lower respiratory tract infections seen in general practice.
Human-to-human transmission of SARS-CoV-2 has been confirmed during the 2019–20 coronavirus pandemic. Transmission occurs primarily via respiratory droplets from coughs and sneezes within a range of about 1.8 metres (6 ft). Indirect contact via contaminated surfaces is another possible cause of infection. Preliminary research indicates that the virus may remain viable on plastic and steel for up to three days, but does not survive on cardboard for more than one day or on copper for more than four hours; the virus is inactivated by soap, which destabilises its lipid bilayer. Viral RNA has also been found in stool samples from infected individuals.
The degree to which the virus is infectious during the incubation period is uncertain, but research has indicated that the pharynx reaches peak viral load approximately four days after infection. On 1 February 2020, the World Health Organization (WHO) indicated that "transmission from asymptomatic cases is likely not a major driver of transmission". However, an epidemiological model of the beginning of the outbreak in China suggested that "pre-symptomatic shedding may be typical among documented infections" and that subclinical infections may have been the source of a majority of infections.
There is some evidence of human-to-animal transmission of SARS-CoV-2, including examples in felids. Some institutions have advised those infected with SARS-CoV-2 to restrict contact with animals.
In patients managed in the community, determining the causative agent is not cost-effective and typically does not alter management. For people who do not respond to treatment, sputum culture should be considered, and culture for "Mycobacterium tuberculosis" should be carried out in persons with a chronic productive cough. Testing for other specific organisms may be recommended during outbreaks, for public health reasons. In those hospitalized for severe disease, both sputum and blood cultures are recommended, as well as testing the urine for antigens to "Legionella" and "Streptococcus". Viral infections can be confirmed via detection of either the virus or its antigens with culture or polymerase chain reaction (PCR), among other techniques. The causative agent is determined in only 15% of cases with routine microbiological tests.
Physical examination may sometimes reveal low blood pressure, high heart rate, or low oxygen saturation. The respiratory rate may be faster than normal, and this may occur a day or two before other signs. Examination of the chest may be normal, but it may show decreased chest expansion on the affected side. Harsh breath sounds from the larger airways that are transmitted through the inflamed lung are termed bronchial breathing and are heard on auscultation with a stethoscope. Crackles (rales) may be heard over the affected area during inspiration. Percussion may be dulled over the affected lung, and increased, rather than decreased, vocal resonance distinguishes pneumonia from a pleural effusion.
Chest radiographs (X-ray photographs) often show a pulmonary infection before physical signs of atypical pneumonia are observable at all.
This is occult pneumonia. In general, occult pneumonia is rather often present in patients with pneumonia and can also be caused by "Streptococcus pneumoniae", as the decrease of occult pneumonia after vaccination of children with a pneumococcal vaccine suggests.
Infiltration commonly begins in the perihilar region (where the bronchus begins) and spreads in a wedge- or fan-shaped fashion toward the periphery of the lung field. The process most often involves the lower lobe, but may affect any lobe or combination of lobes.
Mycoplasma is found more often in younger than in older people.
Older people are more often infected by Legionella.
CAP may be prevented by treating underlying illnesses increasing its risk, by smoking cessation and vaccination of children and adults. Vaccination against "haemophilus influenzae" and "streptococcus pneumoniae" in the first year of life has reduced their role in childhood CAP. A vaccine against "streptococcus pneumoniae", available for adults, is recommended for healthy individuals over 65 and all adults with COPD, heart failure, diabetes mellitus, cirrhosis, alcoholism, cerebrospinal fluid leaks or who have had a splenectomy. Re-vaccination may be required after five or ten years.
Patients who are vaccinated against "streptococcus pneumoniae", health professionals, nursing-home residents and pregnant women should be vaccinated annually against influenza. During an outbreak, drugs such as amantadine, rimantadine, zanamivir and oseltamivir have been demonstrated to prevent influenza.
Patients with symptoms of CAP require evaluation. Diagnosis of pneumonia is made clinically, rather than on the basis of a particular test. Evaluation begins with a physical examination by a health provider, which may reveal fever, an increased respiratory rate (tachypnea), low blood pressure (hypotension), a fast heart rate (tachycardia) and changes in the amount of oxygen in the blood. Palpating the chest as it expands and tapping the chest wall (percussion) to identify dull, non-resonant areas can identify stiffness and fluid, signs of CAP. Listening to the lungs with a stethoscope (auscultation) can also reveal signs associated with CAP. A lack of normal breath sounds or the presence of crackles can indicate fluid consolidation. Increased vibration of the chest when speaking, known as tactile fremitus, and increased volume of whispered speech during auscultation can also indicate fluid.
When signs of pneumonia are discovered during evaluation, chest X-rays, are performed to support a diagnosis of CAP, and examination of the blood and sputum for infectious microorganisms and blood tests may be used to support a diagnosis of CAP. Diagnostic tools depend on the severity of illness, local practices and concern about complications of the infection. All patients with CAP should have their blood oxygen monitored with pulse oximetry. In some cases, arterial blood gas analysis may be required to determine the amount of oxygen in the blood. A complete blood count (CBC) may reveal extra white blood cells, indicating infection.
Chest X-rays and X-ray computed tomography (CT) can reveal areas of opacity (seen as white), indicating consolidation. CAP does not always appear on x-rays, because the disease is in its initial stages or involves a part of the lung an x-ray does not see well. In some cases, chest CT can reveal pneumonia not seen on x-rays. However, congestive heart failure or other types of lung damage can mimic CAP on x-rays.
Several tests can identify the cause of CAP. Blood cultures can isolate bacteria or fungi in the bloodstream. Sputum Gram staining and culture can also reveal the causative microorganism. In severe cases, bronchoscopy can collect fluid for culture. Special tests can be performed if an uncommon microorganism is suspected, such as urinalysis for Legionella antigen in Legionnaires' disease.
An emerging infectious disease (EID) is an infectious disease whose incidence has increased in the past 20 years and could increase in the near future. Emerging infections account for at least 12% of all human pathogens. EIDs are caused by newly identified species or strains (e.g. Severe acute respiratory syndrome, HIV/AIDS) that may have evolved from a known infection (e.g. influenza) or spread to a new population (e.g. West Nile fever) or to an area undergoing ecologic transformation (e.g. Lyme disease), or be "reemerging" infections, like drug resistant tuberculosis. Nosocomial (hospital-acquired) infections, such as methicillin-resistant Staphylococcus aureus are emerging in hospitals, and extremely problematic in that they are resistant to many antibiotics. Of growing concern are adverse synergistic interactions between emerging diseases and other infectious and non-infectious conditions leading to the development of novel syndemics. Many emerging diseases are zoonotic - an animal reservoir incubates the organism, with only occasional transmission into human populations.