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
Antibiotics are ineffective, as SARS is a viral disease. Treatment of SARS is largely supportive with antipyretics, supplemental oxygen and mechanical ventilation as needed.
People with SARS must be isolated, preferably in negative pressure rooms, with complete barrier nursing precautions taken for any necessary contact with these patients.
Some of the more serious damage caused by SARS may be due to the body's own immune system reacting in what is known as cytokine storm.
As of 2017, there is no cure or protective vaccine for SARS that has been shown to be both safe and effective in humans. The identification and development of novel vaccines and medicines to treat SARS is a priority for governments and public health agencies around the world. MassBiologics, a non-profit organization engaged in the discovery, development and manufacturing of biologic therapies, is cooperating with researchers at NIH and the CDC developed a monoclonal antibody therapy that demonstrated efficacy in animal models.
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.
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.
Neither the combination of antivirals and interferons (ribavirin + interferon alfa-2a or interferon alfa-2b) nor corticosteroids improved outcomes.
When rhesus macaques were given interferon-α2b and ribavirin and exposed to MERS, they developed less pneumonia than control animals. Five critically ill people with MERS in Saudi Arabia with ARDS and on ventilators were given interferon-α2b and ribavirin but all ended up dying of the disease. The treatment was started late in their disease (a mean of 19 days after hospital admission) and they had already failed trials of steroids so it remains to be seen whether it may have benefit earlier in the course of disease. Another proposed therapy is inhibition of viral protease or kinase enzymes. Researchers are investigating a number of ways to combat the outbreak of Middle East respiratory syndrome coronavirus, including using interferon, chloroquine, chlorpromazine, loperamide, and lopinavir, as well as other agents such as mycophenolic acid and camostat.
Main article: COVID-19 drug repurposing research
At least 29 phase II–IV efficacy trials in COVID-19 were concluded in March 2020 or scheduled to provide results in April from hospitals in China. There are more than 300 active clinical trials underway as of April 2020. Seven trials were evaluating already approved treatments for malaria, including four studies on hydroxychloroquine or chloroquine. Repurposed antiviral drugs make up most of the Chinese research, with nine phase III trials on remdesivir across several countries due to report by the end of April. Other potential candidates in trials include vasodilators, corticosteroids, immune therapies, lipoic acid, bevacizumab, and recombinant angiotensin-converting enzyme 2.
The COVID-19 Clinical Research Coalition has goals to 1) facilitate rapid reviews of clinical trial proposals by ethics committees and national regulatory agencies, 2) fast-track approvals for the candidate therapeutic compounds, 3) ensure standardised and rapid analysis of emerging efficacy and safety data and 4) facilitate sharing of clinical trial outcomes before publication. A dynamic review of clinical development for COVID-19 vaccine and drug candidates was in place, as of April 2020.
Several existing antiviral medications are being evaluated for treatment of COVID-19, including remdesivir, chloroquine and hydroxychloroquine, lopinavir/ritonavir and lopinavir/ritonavir combined with interferon beta. There is tentative evidence for efficacy by remdesivir, as of March 2020. Clinical improvement was observed in patients treated with compassionate-use remdesivir. Remdesivir inhibits SARS-CoV-2 in vitro. Phase III clinical trials are being conducted in the US, China and Italy.
Chloroquine, previously used to treat malaria, was studied in China in February 2020, with preliminary results. However, there are calls for peer review of the research. The Guangdong Provincial Department of Science and Technology and the Guangdong Provincial Health and Health Commission issued a report stating that chloroquine phosphate "improves the success rate of treatment and shortens the length of person's hospital stay" and recommended it for people diagnosed with mild, moderate and severe cases of novel coronavirus pneumonia.
On 17 March, the Italian Pharmaceutical Agency included chloroquine and hydroxychloroquine in the list of drugs with positive preliminary results for treatment of COVID-19. Korean and Chinese Health Authorities recommend the use of chloroquine. However, the Wuhan Institute of Virology, while recommending a daily dose of one gram, notes that twice that dose is highly dangerous and could be lethal. On 28 March 2020, the FDA issued an emergency use authorisation for hydroxychloroquine and chloroquine at the discretion of physicians treating people with COVID-19.
The Chinese 7th edition guidelines also include interferon, ribavirin or umifenovir for use against COVID-19. Preliminary data indicate that high doses of ribavirin are necessary to inhibit SARS-CoV-2 in vitro. Since studies have been inconsistent with respect to ribavirin's efficacy against other novel coronaviruses (e.g., SARS, MERS) and its significant toxicity, this suggests its role in treating COVID-19 is limited and its best chance of being effective is being a part of combination therapy.
In 2020, a trial found that lopinavir/ritonavir was ineffective in the treatment of severe illness. Nitazoxanide has been recommended for further in vivo study after demonstrating low concentration inhibition of SARS-CoV-2.
Studies have demonstrated that initial spike protein priming by transmembrane protease serine 2 (TMPRSS2) is essential for entry of SARS-CoV-2 via interaction with the ACE2 receptor. These findings suggest the TMPRSS2 inhibitor camostat approved for use in Japan for inhibiting fibrosis in liver and kidney disease might constitute an effective off-label treatment.
In February 2020, favipiravir was being studied in China for experimental treatment of the emergent COVID-19 disease.
In April 2020 ivermectin is being studied in Australia for a possible treatment for COVID-19 and has been shown to stop viral growth within 48 hours in vitro.
There are mixed results as of 3 April 2020 as to the effectiveness of hydroxychloroquine as a treatment for COVID-19, with some studies showing little or no improvement. The studies of chloroquine and hydroxychloroquine with or without azithromycin have major limitations that have prevented the medical community from embracing these therapies without further study.
Oseltamivir does not inhibit SARS-CoV-2 in vitro and has no known role in COVID-19 treatment.
As of April 2020, there is no specific treatment for COVID-19. Research is, however, ongoing. For symptoms, some medical professionals recommend paracetamol (acetaminophen) over ibuprofen for first-line use. The WHO does not oppose the use of non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen for symptoms, and the FDA says currently there is no evidence that NSAIDs worsen COVID-19 symptoms.
While theoretical concerns have been raised about ACE inhibitors and angiotensin receptor blockers, as of 19 March 2020, these are not sufficient to justify stopping these medications. Steroids, such as methylprednisolone, are not recommended unless the disease is complicated by acute respiratory distress syndrome.
Medications to prevent blood clotting have been suggested for treatment, and anticoagulant therapy with low molecular weight heparin appears to be associated with better outcomes in severe COVID‐19 showing signs of coagulopathy (elevated D-dimer).
While the mechanism of spread of MERS-CoV is currently not known, based on experience with prior coronaviruses, such as SARS, the WHO currently recommends that all individuals coming into contact with MERS suspects should (in addition to standard precautions):
- Wear a medical mask
- Wear eye protection (i.e. goggles or a face shield)
- Wear a clean, non sterile, long sleeved gown; and gloves (some procedures may require sterile gloves)
- Perform hand hygiene before and after contact with the person and his or her surroundings and immediately after removal of personal protective equipment (PPE)
For procedures which carry a risk of aerosolization, such as intubation, the WHO recommends that care providers also:
- Wear a particulate respirator and, when putting on a disposable particulate respirator, always check the seal
- Wear eye protection (i.e. goggles or a face shield)
- Wear a clean, non-sterile, long-sleeved gown and gloves (some of these procedures require sterile gloves)
- Wear an impermeable apron for some procedures with expected high fluid volumes that might penetrate the gown
- Perform procedures in an adequately ventilated room; i.e. minimum of 6 to 12 air changes per hour in facilities with a mechanically ventilated room and at least 60 liters/second/patient in facilities with natural ventilation
- Limit the number of persons present in the room to the absolute minimum required for the person’s care and support
- Perform hand hygiene before and after contact with the person and his or her surroundings and after PPE removal.
The duration of infectivity is also unknown so it is unclear how long people must be isolated, but current recommendations are for 24 hours after resolution of symptoms. In the SARS outbreak the virus was not cultured from people after the resolution of their symptoms.
It is believed that the existing SARS research may provide a useful template for developing vaccines and therapeutics against a MERS-CoV infection. Vaccine candidates are currently awaiting clinical trials.
The best prevention against viral pneumonia is vaccination against influenza, adenovirus, chickenpox, herpes zoster, measles, and rubella.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus strain that causes coronavirus disease 2019 (COVID-19), a respiratory illness. It is colloquially known as the coronavirus, and was previously referred to by its provisional name 2019 novel coronavirus (2019-nCoV). SARS-CoV-2 is a positive-sense single-stranded RNA virus. It is contagious in humans, and the World Health Organization (WHO) has designated the ongoing pandemic of COVID-19 a Public Health Emergency of International Concern. Because the strain was first discovered in Wuhan, China, it is sometimes referred to as "Wuhan virus" or "Wuhan coronavirus". Since the WHO discourages the use of names based on locations such as MERS, and to avoid confusion with the disease SARS, it sometimes refers to SARS-CoV-2 as "the COVID-19 virus" in public health communications. The general public frequently calls both SARS-CoV-2 and the disease it causes "coronavirus", but scientists typically use more precise terminology.
Taxonomically, SARS-CoV-2 is a strain of Severe acute respiratory syndrome-related coronavirus (SARSr-CoV). It is believed to have zoonotic origins and has close genetic similarity to bat coronaviruses, suggesting it emerged from a bat-borne virus. An intermediate animal reservoir such as a pangolin is also thought to be involved in its introduction to humans. The virus shows little genetic diversity, indicating that the spillover event introducing SARS-CoV-2 to humans is likely to have occurred in late 2019.
Epidemiological studies estimate each infection results in 1.4 to 3.9 new ones when no members of the community are immune and no preventive measures taken. The virus is primarily spread between people through close contact and via respiratory droplets produced from coughs or sneezes. It mainly enters human cells by binding to the receptor angiotensin converting enzyme 2 (ACE2).
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.
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.
Neuraminidase inhibitors may be used to treat viral pneumonia caused by influenza viruses (influenza A and influenza B). No specific antiviral medications are recommended for other types of community acquired viral pneumonias including SARS coronavirus, adenovirus, hantavirus, and parainfluenza virus. Influenza A may be treated with rimantadine or amantadine, while influenza A or B may be treated with oseltamivir, zanamivir or peramivir. These are of most benefit if they are started within 48 hours of the onset of symptoms. Many strains of H5N1 influenza A, also known as avian influenza or "bird flu", have shown resistance to rimantadine and amantadine. The use of antibiotics in viral pneumonia is recommended by some experts, as it is impossible to rule out a complicating bacterial infection. The British Thoracic Society recommends that antibiotics be withheld in those with mild disease. The use of corticosteroids is controversial.
Antibiotics improve outcomes in those with bacterial pneumonia. Antibiotic choice depends initially on the characteristics of the person affected, such as age, underlying health, and the location the infection was acquired. In the UK, treatment before culture results with amoxicillin is recommended as the first line for community-acquired pneumonia, with doxycycline or clarithromycin as alternatives. In North America, where the "atypical" forms of community-acquired pneumonia are more common, macrolides (such as azithromycin or erythromycin), and doxycycline have displaced amoxicillin as first-line outpatient treatment in adults. In children with mild or moderate symptoms, amoxicillin remains the first line. The use of fluoroquinolones in uncomplicated cases is discouraged due to concerns about side-effects and generating resistance in light of there being no greater clinical benefit.
For those who require hospitalization and caught their pneumonia in the community the use of a β-lactam such as cephazolin plus macrolide such as azithromycin or a fluoroquinolones is recommended. The addition of corticosteroids also appears to improve outcomes.
The duration of treatment has traditionally been seven to ten days, but increasing evidence suggests that shorter courses (three to five days) are similarly effective. Recommendations for hospital-acquired pneumonia include third- and fourth-generation cephalosporins, carbapenems, fluoroquinolones, aminoglycosides, and vancomycin. These antibiotics are often given intravenously and used in combination. In those treated in hospital, more than 90% improve with the initial antibiotics.
Treatment of CAP in children depends on the child's age and the severity of illness. Children under five are not usually treated for atypical bacteria. If hospitalization is not required, a seven-day course of amoxicillin is often prescribed, with co-trimaxazole an alternative when there is allergy to penicillins. Further studies are needed to confirm the efficacy of newer antibiotics. With the increase in drug-resistant Streptococcus pneumoniae, antibiotics such as cefpodoxime may become more popular. Hospitalized children receive intravenous ampicillin, ceftriaxone or cefotaxime, and a recent study found that a three-day course of antibiotics seems sufficient for most mild-to-moderate CAP in children.
Most newborn infants with CAP are hospitalized, receiving IV ampicillin and gentamicin for at least ten days to treat the common causative agents "streptococcus agalactiae", "listeria monocytogenes" and "escherichia coli". To treat the herpes simplex virus, IV acyclovir is administered for 21 days.
Vaccination helps prevent bronchopneumonia, mostly against influenza viruses, adenoviruses, measles, rubella, streptococcus pneumoniae, haemophilus influenzae, diphtheria, bacillus anthracis, chickenpox, and bordetella pertussis.
François Madec, a French author, has written many recommendations on how reduce PMWS symptoms. They are mostly measures for disinfection, management, and hygiene, referred to as the "20 Madec Points" [Madec & Waddilove, 2002].
These measures have recently been expanded upon by Dr. David Barcellos, a professor at the Veterinary College in the Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil. He presented these points at "1st Universidade Federal do Rio Grande do Sul Symposium about swine management, reproduction, and hygiene".
He divided his points by pig growth stage, and they can be loosely summarized as:
- keep the gutters clean
- increase feeder space
- use pens or small cages with solid dividers
- avoid mixing pigs from different origins
- improve the quality of air
- decrease maximum capacity, giving each pig more room
- separate sick animals as soon as possible, and treat them in a hospital pen. If they do not respond to antibiotics in three days, they should be culled
- control access of people and other animals
- reduce invironmental stress factors such as gases and air currents
- use immunizations and preventive medications for secondary agents commonly associated with PMWS
Methicillin-resistant Staphylococcus aureus (MRSA) evolved from Methicillin-susceptible Staphylococcus aureus (MSSA) otherwise known as common "S. aureus". Many people are natural carriers of "S. aureus", without being affected in any way. MSSA was treatable with the antibiotic methicillin until it acquired the gene for antibiotic resistance. Though genetic mapping of various strains of MRSA, scientists have found that MSSA acquired the mecA gene in the 1960s, which accounts for its pathogenicity, before this it had a predominantly commensal relationship with humans. It is theorized that when this "S. aureus" strain that had acquired the mecA gene was introduced into hospitals, it came into contact with other hospital bacteria that had already been exposed to high levels of antibiotics. When exposed to such high levels of antibiotics, the hospital bacteria suddenly found themselves in an environment that had a high level of selection for antibiotic resistance, and thus resistance to multiple antibiotics formed within these hospital populations. When "S. aureus" came into contact with these populations, the multiple genes that code for antibiotic resistance to different drugs were then acquired by MRSA, making it nearly impossible to control. It is thought that MSSA acquired the resistance gene through the horizontal gene transfer, a method in which genetic information can be passed within a generation, and spread rapidly through its own population as was illustrated in multiple studies. Horizontal gene transfer speeds the process of genetic transfer since there is no need to wait an entire generation time for gene to be passed on. Since most antibiotics do not work on MRSA, physicians have to turn to alternative methods based in Darwinian medicine. However prevention is the most preferred method of avoiding antibiotic resistance. By reducing unnecessary antibiotic use in human and animal populations, antibiotics resistance can be slowed.
Unfortunately a vaccine for malignant catarrhal fever (MCF) has not yet been developed. Developing a vaccine has been difficult because the virus will not grow in cell culture and until recently it was not known why. Researchers at the Agricultural Research Service (ARS) found that the virus undergoes changes within the animal's body, a process known as "cell tropism switching". In cell tropism switching, the virus targets different cells at different points in its life cycle. This phenomenon explains why it has been impossible to grow the virus on any one particular cell culture.
Because the virus is transmitted from sheep to bison and cattle, researchers are first focusing on the viral life cycle in sheep. The viral life cycle is outlined in three stages: entry, maintenance, and shedding. Entry occurs through the sheep's nasal cavity and enters into the lungs where it replicates. The virus undergoes a tropic change and infects lymphocytes, also known as white blood cells, which play a role in the sheep's immune system. In the maintenance stage the virus remains on the sheep's lymphocytes and circulates the body. Finally, during the shedding stage, the virus undergoes another change and shifts its target cells from lymphocytes to nasal cavity cells, where it is then shed through nasal secretions. This discovery undoubtedly puts scientists on the right track for developing a vaccine – starting with the correct cell culture for each stage of the virus lifecycle – but ARS researchers are also looking into alternative methods to develop a vaccine. Researchers are experimenting with the MCF virus that infects topi (an African antelope) because it will grow in cell culture and does not infect cattle. Researchers hope that inserting genes from the sheep MCF virus into the topi MCF virus will ultimately be an effective MCF vaccine for cattle and bison. While there is much ground left to cover, scientists are getting closer and closer to developing a vaccine.
Bovine malignant catarrhal fever (BMCF) is a fatal lymphoproliferative disease caused by a group of ruminant gamma herpes viruses including Alcelaphine gammaherpesvirus 1 (AlHV-1) and Ovine gammaherpesvirus 2 (OvHV-2) These viruses cause unapparent infection in their reservoir hosts (sheep with OvHV-2 and wildebeest with AlHV-1), but are usually fatal in cattle and other ungulates such as deer, antelope, and buffalo.
BMCF is an important disease where reservoir and susceptible animals mix. There is a particular problem with Bali cattle in Indonesia, bison in the US and in pastoralist herds in Eastern and Southern Africa.
Disease outbreaks in cattle are usually sporadic although infection of up to 40% of a herd has been reported. The reasons for this are unknown. Some species appear to be particularly susceptible, for example Pére Davids deer, Bali cattle and bison, with many deer dying within 48 hours of the appearance of the first symptoms and bison within three days. In contrast, post infection cattle will usually survive a week or more.
A number of topical antivirals are effective for herpes labialis, including acyclovir, penciclovir, and docosanol.
Several antiviral drugs are effective for treating herpes, including acyclovir, valaciclovir (valacyclovir), famciclovir, and penciclovir. Acyclovir was the first discovered and is now available in generic. Valacyclovir is also available as a generic and is slightly more effective than aciclovir for reducing lesion healing time.
Evidence supports the use of acyclovir and valacyclovir in the treatment of herpes labialis as well as herpes infections in people with cancer. The evidence to support the use of acyclovir in primary herpetic gingivostomatitis is weaker.
Porcine circoviral disease (PCVD) and Porcine circovirus associated disease (PCVAD), is a disease seen in domestic pigs. This disease causes illness in piglets, with clinical signs including progressive loss of body condition, visibly enlarged lymph nodes, difficulty in breathing, and sometimes diarrhea, pale skin, and jaundice. PCVD is very damaging to the pig-producing industry and has been reported worldwide. PCVD is caused by porcine circovirus type 2 (PCV-2).
The North American industry endorses "PCVAD" and European use "PCVD" to describe this 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.
There is some evidence that there may be a relationship between BoDV-1 infection and psychiatric disease.
In 1990, Janice E. Clements and colleagues reported in the journal "Science" that antibodies to a protein encoded by the BoDV-1 genome are found in the blood of patients with behavioral disorders. In the early 1990s, researchers in Germany, America, and Japan conducted an investigation of 5000 patients with psychiatric disorders and 1000 controls, in which a significantly higher percentage of patients than controls were positive for BoDV-1 antibodies. Subsequent studies have also presented evidence for an association between BoDV-1 and human psychiatric disorders. However, not all researchers consider the link between BoDV-1 and human psychiatric disease to be conclusively proven. A recent study found no BoDV-1 antibodies in 62 patients with the deficit form of schizophrenia.
Additional evidence for a role of BoDV-1 in psychiatric disorders comes from reports that the drug amantadine, which is used to treat influenza infections, has had some success in treating depression and clearing BoDV-1 infection. Counter-claims state that Borna virus infections are not cleared by amantadine. The issue is further complicated by the fact that amantadine is also used in the treatment of Parkinson's disease and may have direct effects on the nervous system.