Features, Evaluation and Treatment Coronavirus (COVID-19)
According to the World Health Organization (WHO), viral diseases continue to emerge and represent a serious issue to public health. In the last twenty years, several viral epidemics such as the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 to 2003, and H1N1 influenza in 2009, have been recorded. Most recently, the Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia in 2012.
In a timeline that reaches the present day, an epidemic of cases with unexplained low respiratory infections detected in Wuhan, the largest metropolitan area in China's Hubei province, was first reported to the WHO Country Office in China, on December 31, 2019. Published literature can trace the beginning of symptomatic individuals back to the beginning of December 2019. As they were unable to identify the causative agent, these first cases were classified as "pneumonia of unknown etiology." The Chinese Center for Disease Control and Prevention (CDC) and local CDCs organized an intensive outbreak investigation program. The etiology of this illness is now attributed to a novel virus belonging to the coronavirus (CoV) family, COVID-19.
On February 11, 2020, the WHO Director-General, Dr. Tedros Adhanom Ghebreyesus, announced that the disease caused by this new CoV was a "COVID-19," which is the acronym of "coronavirus disease 2019". In the past twenty years, two additional coronavirus epidemics have occurred. SARS-CoV provoked a large-scale epidemic beginning in China and involving two dozen countries with approximately 8000 cases and 800 deaths, and the MERS-CoV that began in Saudi Arabia and has approximately 2,500 cases and 800 deaths and still causes as sporadic cases.
This new virus seems to be very contagious and has quickly spread globally. In a meeting on January 30, 2020, per the International Health Regulations (IHR, 2005), the outbreak was declared by the WHO a Public Health Emergency of International Concern (PHEIC) as it had spread to 18 countries with four countries reporting human-to-human transmission. An additional landmark occurred on February 26, 2020, as the first case of the disease, not imported from China, was recorded in the United States.
Initially, the new virus was called 2019-nCoV. Subsequently, the task of experts of the International Committee on Taxonomy of Viruses (ICTV) termed it the SARS-CoV-2 virus as it is very similar to the one that caused the SARS outbreak (SARS-CoVs).
The CoVs have become the major pathogens of emerging respiratory disease outbreaks. They are a large family of single-stranded RNA viruses (+ssRNA) that can be isolated in different animal species.[1] For reasons yet to be explained, these viruses can cross species barriers and can cause, in humans, illness ranging from the common cold to more severe diseases such as MERS and SARS. Interestingly, these latter viruses have probably originated from bats and then moving into other mammalian hosts — the Himalayan palm civet for SARS-CoV, and the dromedary camel for MERS-CoV — before jumping to humans. The dynamics of SARS-Cov-2 are currently unknown, but there is speculation that it also has an animal origin.
The potential for these viruses to grow to become a pandemic worldwide seems to be a serious public health risk. Concerning COVID-19, the WHO raised the threat to the CoV epidemic to the "very high" level, on February 28, 2020. Probably, the effects of the epidemic caused by the new CoV has yet to emerge as the situation is quickly evolving. World governments are at work to establish countermeasures to stem possible devastating effects. Health organizations coordinate information flows and issues directives and guidelines to best mitigate the impact of the threat. At the same time, scientists around the world work tirelessly, and information about the transmission mechanisms, the clinical spectrum of disease, new diagnostics, and prevention and therapeutic strategies are rapidly developing. Many uncertainties remain with regard to both the virus-host interaction and the evolution of the epidemic, with specific reference to the times when the epidemic will reach its peak.
At the moment, the therapeutic strategies to deal with the infection are only supportive, and prevention aimed at reducing transmission in the community is our best weapon. Aggressive isolation measures in China have led to a progressive reduction of cases in the last few days. In Italy, in geographic regions of the north of the peninsula, political and health authorities are making incredible efforts to contain a shock wave that is severely testing the health system.
In the midst of the crisis, the authors have chosen to use the "Statpearls" platform because, within the PubMed scenario, it represents a unique tool that may allow them to make updates in real-time. The aim, therefore, is to collect information and scientific evidence and to provide an overview of the topic that will be continuously updated.
In a timeline that reaches the present day, an epidemic of cases with unexplained low respiratory infections detected in Wuhan, the largest metropolitan area in China's Hubei province, was first reported to the WHO Country Office in China, on December 31, 2019. Published literature can trace the beginning of symptomatic individuals back to the beginning of December 2019. As they were unable to identify the causative agent, these first cases were classified as "pneumonia of unknown etiology." The Chinese Center for Disease Control and Prevention (CDC) and local CDCs organized an intensive outbreak investigation program. The etiology of this illness is now attributed to a novel virus belonging to the coronavirus (CoV) family, COVID-19.
On February 11, 2020, the WHO Director-General, Dr. Tedros Adhanom Ghebreyesus, announced that the disease caused by this new CoV was a "COVID-19," which is the acronym of "coronavirus disease 2019". In the past twenty years, two additional coronavirus epidemics have occurred. SARS-CoV provoked a large-scale epidemic beginning in China and involving two dozen countries with approximately 8000 cases and 800 deaths, and the MERS-CoV that began in Saudi Arabia and has approximately 2,500 cases and 800 deaths and still causes as sporadic cases.
This new virus seems to be very contagious and has quickly spread globally. In a meeting on January 30, 2020, per the International Health Regulations (IHR, 2005), the outbreak was declared by the WHO a Public Health Emergency of International Concern (PHEIC) as it had spread to 18 countries with four countries reporting human-to-human transmission. An additional landmark occurred on February 26, 2020, as the first case of the disease, not imported from China, was recorded in the United States.
Initially, the new virus was called 2019-nCoV. Subsequently, the task of experts of the International Committee on Taxonomy of Viruses (ICTV) termed it the SARS-CoV-2 virus as it is very similar to the one that caused the SARS outbreak (SARS-CoVs).
The CoVs have become the major pathogens of emerging respiratory disease outbreaks. They are a large family of single-stranded RNA viruses (+ssRNA) that can be isolated in different animal species.[1] For reasons yet to be explained, these viruses can cross species barriers and can cause, in humans, illness ranging from the common cold to more severe diseases such as MERS and SARS. Interestingly, these latter viruses have probably originated from bats and then moving into other mammalian hosts — the Himalayan palm civet for SARS-CoV, and the dromedary camel for MERS-CoV — before jumping to humans. The dynamics of SARS-Cov-2 are currently unknown, but there is speculation that it also has an animal origin.
The potential for these viruses to grow to become a pandemic worldwide seems to be a serious public health risk. Concerning COVID-19, the WHO raised the threat to the CoV epidemic to the "very high" level, on February 28, 2020. Probably, the effects of the epidemic caused by the new CoV has yet to emerge as the situation is quickly evolving. World governments are at work to establish countermeasures to stem possible devastating effects. Health organizations coordinate information flows and issues directives and guidelines to best mitigate the impact of the threat. At the same time, scientists around the world work tirelessly, and information about the transmission mechanisms, the clinical spectrum of disease, new diagnostics, and prevention and therapeutic strategies are rapidly developing. Many uncertainties remain with regard to both the virus-host interaction and the evolution of the epidemic, with specific reference to the times when the epidemic will reach its peak.
At the moment, the therapeutic strategies to deal with the infection are only supportive, and prevention aimed at reducing transmission in the community is our best weapon. Aggressive isolation measures in China have led to a progressive reduction of cases in the last few days. In Italy, in geographic regions of the north of the peninsula, political and health authorities are making incredible efforts to contain a shock wave that is severely testing the health system.
In the midst of the crisis, the authors have chosen to use the "Statpearls" platform because, within the PubMed scenario, it represents a unique tool that may allow them to make updates in real-time. The aim, therefore, is to collect information and scientific evidence and to provide an overview of the topic that will be continuously updated.
EtiologyCoVs are positive-stranded RNA viruses with a crown-like appearance under an electron microscope (coronam is the Latin term for crown) due to the presence of spike glycoproteins on the envelope. The subfamily Orthocoronavirinae of the Coronaviridae family (order Nidovirales) classifies into four genera of CoVs: Alphacoronavirus (alphaCoV), Betacoronavirus (betaCoV), Deltacoronavirus (deltaCoV), and Gammacoronavirus (gammaCoV). Furthermore, the betaCoV genus divides into five sub-genera or lineages.[2] Genomic characterization has shown that probably bats and rodents are the gene sources of alphaCoVs and betaCoVs. On the contrary, avian species seem to represent the gene sources of deltaCoVs and gammaCoVs.
Members of this large family of viruses can cause respiratory, enteric, hepatic, and neurological diseases in different animal species, including camels, cattle, cats, and bats. To date, seven human CoVs (HCoVs) — capable of infecting humans — have been identified. Some of HCoVs were identified in the mid-1960s, while others were only detected in the new millennium.
In general, estimates suggest that 2% of the population are healthy carriers of a CoV and that these viruses are responsible for about 5% to 10% of acute respiratory infections.[3]
Common human CoVs: HCoV-OC43, and HCoV-HKU1 (betaCoVs of the A lineage); HCoV-229E, and HCoV-NL63 (alphaCoVs). They can cause common colds and self-limiting upper respiratory infections in immunocompetent individuals. In immunocompromised subjects and the elderly, lower respiratory tract infections can occur.
Other human CoVs: SARS-CoV, SARS-CoV-2, and MERS-CoV (betaCoVs of the B and C lineage, respectively). These cause epidemics with variable clinical severity featuring respiratory and extra-respiratory manifestations. Concerning SARS-CoV, MERS-CoV, the mortality rates are up to 10% and 35%, respectively.
Thus, SARS-CoV-2 belongs to the betaCoVs category. It has round or elliptic and often pleomorphic form, and a diameter of approximately 60–140 nm. Like other CoVs, it is sensitive to ultraviolet rays and heat. Furthermore, these viruses can be effectively inactivated by lipid solvents including ether (75%), ethanol, chlorine-containing disinfectant, peroxyacetic acid and chloroform except for chlorhexidine.
In genetic terms, Chan et al. have proven that the genome of the new HCoV, isolated from a cluster-patient with atypical pneumonia after visiting Wuhan, had 89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV[4]. For this reason, the new virus was called SARS-CoV-2. Its single-stranded RNA genome contains 29891 nucleotides, encoding for 9860 amino acids. Although its origins are not entirely understood, these genomic analyses suggest that SARS-CoV-2 probably evolved from a strain found in bats. The potential amplifying mammalian host, intermediate between bats and humans, is, however, not known. Since the mutation in the original strain could have directly triggered virulence towards humans, it is not certain that this intermediary exists.
Members of this large family of viruses can cause respiratory, enteric, hepatic, and neurological diseases in different animal species, including camels, cattle, cats, and bats. To date, seven human CoVs (HCoVs) — capable of infecting humans — have been identified. Some of HCoVs were identified in the mid-1960s, while others were only detected in the new millennium.
In general, estimates suggest that 2% of the population are healthy carriers of a CoV and that these viruses are responsible for about 5% to 10% of acute respiratory infections.[3]
Common human CoVs: HCoV-OC43, and HCoV-HKU1 (betaCoVs of the A lineage); HCoV-229E, and HCoV-NL63 (alphaCoVs). They can cause common colds and self-limiting upper respiratory infections in immunocompetent individuals. In immunocompromised subjects and the elderly, lower respiratory tract infections can occur.
Other human CoVs: SARS-CoV, SARS-CoV-2, and MERS-CoV (betaCoVs of the B and C lineage, respectively). These cause epidemics with variable clinical severity featuring respiratory and extra-respiratory manifestations. Concerning SARS-CoV, MERS-CoV, the mortality rates are up to 10% and 35%, respectively.
Thus, SARS-CoV-2 belongs to the betaCoVs category. It has round or elliptic and often pleomorphic form, and a diameter of approximately 60–140 nm. Like other CoVs, it is sensitive to ultraviolet rays and heat. Furthermore, these viruses can be effectively inactivated by lipid solvents including ether (75%), ethanol, chlorine-containing disinfectant, peroxyacetic acid and chloroform except for chlorhexidine.
In genetic terms, Chan et al. have proven that the genome of the new HCoV, isolated from a cluster-patient with atypical pneumonia after visiting Wuhan, had 89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV[4]. For this reason, the new virus was called SARS-CoV-2. Its single-stranded RNA genome contains 29891 nucleotides, encoding for 9860 amino acids. Although its origins are not entirely understood, these genomic analyses suggest that SARS-CoV-2 probably evolved from a strain found in bats. The potential amplifying mammalian host, intermediate between bats and humans, is, however, not known. Since the mutation in the original strain could have directly triggered virulence towards humans, it is not certain that this intermediary exists.
Transmission
Because the first cases of the CoVID-19 disease were linked to direct exposure to the Huanan Seafood Wholesale Market of Wuhan, the animal-to-human transmission was presumed as the main mechanism. Nevertheless, subsequent cases were not associated with this exposure mechanism. Therefore, it was concluded that the virus could also be transmitted from human-to-human, and symptomatic people are the most frequent source of COVID-19 spread. The possibility of transmission before symptoms develop seems to be infrequent, although it cannot be excluded. Moreover, there are suggestions that individuals who remain asymptomatic could transmit the virus. This data suggests that the use of isolation is the best way to contain this epidemic.
As with other respiratory pathogens, including flu and rhinovirus, the transmission is believed to occur through respiratory droplets from coughing and sneezing. Aerosol transmission is also possible in case of protracted exposure to elevated aerosol concentrations in closed spaces. Analysis of data related to the spread of SARS-CoV-2 in China seems to indicate that close contact between individuals is necessary. The spread, in fact, is primarily limited to family members, healthcare professionals, and other close contacts.
Based on data from the first cases in Wuhan and investigations conducted by the China CDC and local CDCs, the incubation time could be generally within 3 to 7 days and up to 2 weeks as the longest time from infection to symptoms was 12.5 days (95% CI, 9.2 to 18).[5] This data also showed that this novel epidemic doubled about every seven days, whereas the basic reproduction number (R0 - R naught) is 2.2. In other words, on average, each patient transmits the infection to an additional 2.2 individuals. Of note, estimations of the R0 of the SARS-CoV epidemic in 2002-2003 were approximately 3.[6]
It must be emphasized that this information is the result of the first reports. Thus, further studies are needed to understand the mechanisms of transmission, the incubation times and the clinical course, and the duration of infectivity.
Because the first cases of the CoVID-19 disease were linked to direct exposure to the Huanan Seafood Wholesale Market of Wuhan, the animal-to-human transmission was presumed as the main mechanism. Nevertheless, subsequent cases were not associated with this exposure mechanism. Therefore, it was concluded that the virus could also be transmitted from human-to-human, and symptomatic people are the most frequent source of COVID-19 spread. The possibility of transmission before symptoms develop seems to be infrequent, although it cannot be excluded. Moreover, there are suggestions that individuals who remain asymptomatic could transmit the virus. This data suggests that the use of isolation is the best way to contain this epidemic.
As with other respiratory pathogens, including flu and rhinovirus, the transmission is believed to occur through respiratory droplets from coughing and sneezing. Aerosol transmission is also possible in case of protracted exposure to elevated aerosol concentrations in closed spaces. Analysis of data related to the spread of SARS-CoV-2 in China seems to indicate that close contact between individuals is necessary. The spread, in fact, is primarily limited to family members, healthcare professionals, and other close contacts.
Based on data from the first cases in Wuhan and investigations conducted by the China CDC and local CDCs, the incubation time could be generally within 3 to 7 days and up to 2 weeks as the longest time from infection to symptoms was 12.5 days (95% CI, 9.2 to 18).[5] This data also showed that this novel epidemic doubled about every seven days, whereas the basic reproduction number (R0 - R naught) is 2.2. In other words, on average, each patient transmits the infection to an additional 2.2 individuals. Of note, estimations of the R0 of the SARS-CoV epidemic in 2002-2003 were approximately 3.[6]
It must be emphasized that this information is the result of the first reports. Thus, further studies are needed to understand the mechanisms of transmission, the incubation times and the clinical course, and the duration of infectivity.
Epidemiology
Data provided by the WHO Health Emergency Dashboard (March 03, 10.00 am CET) report 87,137 confirmed cases worldwide since the beginning of the epidemic. Of these, 2977 (3.42%) have been fatal. About 92% (79,968) of the confirmed cases were recorded in China, where almost all the deaths were also recorded (2,873, 96.5%). Of note, the "confirmed" cases reported between February 13, 2020, and February 19, 2020, include both laboratory-confirmed and clinically diagnosed patients from the Hubei province.
Outside China, there are 7169 confirmed cases in 59 countries including the Republic of Korea (3736 cases), Italy (1128), international conveyance (Diamond Princess, 705 cases), the Islamic Republic of Iran (593), Japan (239), Singapore (102), France (100), United States of America (62), Germany (57), Kuwait (45), Spain (45), Thailand (42), Bahrain (40), Australia (25), Malaysia (24), United Kingdom (23), Canada (19), United Arab Emirates (19), Switzerland (18), Viet Nam (16), Norway (15), Iraq (13), Sweden (13), Austria (10), Croatia (7), Israel (7), Netherlands (7), Oman (6), Pakistan (4), Azerbaijan (3), Denmark (3), Georgia (3), Greece (3), India (3), Philippines (3), Romania (3). Moreover, two cases were recorded respectively in Brazil, Finland, Lebanon, Mexico, the Russian Federation, and a single case each in Afghanistan, Algeria, Belarus, Belgium, Cambodia, Ecuador, Egypt, Estonia, Ireland, Lithuania, Monaco, Nepal, New Zealand, Nigeria, North Macedonia, Qatar, San Marino, and Sri Lanka.
The most up-to-date source for the epidemiology of this emerging pandemic can be found at the following sources:
The WHO Novel Coronavirus (COVID-19) Situation Board
The Johns Hopkins Center for Systems Science and Engineering site for Coronavirus Global Cases COVID-19, which uses openly public sources to track the spread of the epidemic
Data provided by the WHO Health Emergency Dashboard (March 03, 10.00 am CET) report 87,137 confirmed cases worldwide since the beginning of the epidemic. Of these, 2977 (3.42%) have been fatal. About 92% (79,968) of the confirmed cases were recorded in China, where almost all the deaths were also recorded (2,873, 96.5%). Of note, the "confirmed" cases reported between February 13, 2020, and February 19, 2020, include both laboratory-confirmed and clinically diagnosed patients from the Hubei province.
Outside China, there are 7169 confirmed cases in 59 countries including the Republic of Korea (3736 cases), Italy (1128), international conveyance (Diamond Princess, 705 cases), the Islamic Republic of Iran (593), Japan (239), Singapore (102), France (100), United States of America (62), Germany (57), Kuwait (45), Spain (45), Thailand (42), Bahrain (40), Australia (25), Malaysia (24), United Kingdom (23), Canada (19), United Arab Emirates (19), Switzerland (18), Viet Nam (16), Norway (15), Iraq (13), Sweden (13), Austria (10), Croatia (7), Israel (7), Netherlands (7), Oman (6), Pakistan (4), Azerbaijan (3), Denmark (3), Georgia (3), Greece (3), India (3), Philippines (3), Romania (3). Moreover, two cases were recorded respectively in Brazil, Finland, Lebanon, Mexico, the Russian Federation, and a single case each in Afghanistan, Algeria, Belarus, Belgium, Cambodia, Ecuador, Egypt, Estonia, Ireland, Lithuania, Monaco, Nepal, New Zealand, Nigeria, North Macedonia, Qatar, San Marino, and Sri Lanka.
The most up-to-date source for the epidemiology of this emerging pandemic can be found at the following sources:
The WHO Novel Coronavirus (COVID-19) Situation Board
The Johns Hopkins Center for Systems Science and Engineering site for Coronavirus Global Cases COVID-19, which uses openly public sources to track the spread of the epidemic
Treatment / Management
There is no specific antiviral treatment recommended for COVID-19, and no vaccine is currently available. The treatment is symptomatic, and oxygen therapy represents the major treatment intervention for patients with severe infection. Mechanical ventilation may be necessary in cases of respiratory failure refractory to oxygen therapy, whereas hemodynamic support is essential for managing septic shock.
On January 28, 2020, the WHO released a document summarizing WHO guidelines and scientific evidence derived from the treatment of previous epidemics from HCoVs. This document addresses measures for recognizing and sorting patients with severe acute respiratory disease; strategies for infection prevention and control; early supportive therapy and monitoring; a guideline for laboratory diagnosis; management of respiratory failure and ARDS; management of septic shock; prevention of complications; treatments; and considerations for pregnant patients.
Among these recommendations, we report the strategies for addressing respiratory failure, including protective mechanical ventilation and high-flow nasal oxygen (HFNO) or non-invasive ventilation (NIV).
Intubation and protective mechanical ventilation
Special precautions are necessary during intubation. The procedure should be executed by an expert operator who uses personal protective equipment (PPE) such as FFP3 or N95 mask, protective goggles, disposable gown long sleeve raincoat, disposable double socks, and gloves. If possible, rapid sequence intubation (RSI) should be performed. Preoxygenation (100% O2 for 5 minutes) should be performed via the continuous positive airway pressure (CPAP) method. Heat and moisture exchanger (HME) must be positioned between the mask and the circuit of the fan or between the mask and the ventilation balloon.
Mechanical ventilation should be with lower tidal volumes (4 to 6 ml/kg predicted body weight, PBW) and lower inspiratory pressures, reaching a plateau pressure (Pplat) < 28 to 30 cm H2O. PEEP must be as high as possible to maintain the driving pressure (Pplat-PEEP) as low as possible (< 14 cmH2O). Moreover, disconnections from the ventilator must be avoided for preventing loss of PEEP and atelectasis. Finally, the use of paralytics is not recommended unless PaO2/FiO2 < 150 mmHg. The prone ventilation for > 12 hours per day, and the use of a conservative fluid management strategy for ARDS patients without tissue hypoperfusion (strong recommendation) are emphasized.
Non-invasive ventilation
Concerning HFNO or non-invasive ventilation (NIV), the experts' panel, points out that these approaches performed by systems with good interface fitting do not create widespread dispersion of exhaled air, and their use can be considered at low risk of airborne transmission.[17] Practically, non-invasive techniques can be used in non-severe forms of respiratory failure. However, if the scenario does not improve or even worsen within a short period of time (1–2 hours) the mechanical ventilation must be preferred.
Other therapies
Among other therapeutic strategies, systemic corticosteroids for the treatment of viral pneumonia or acute respiratory distress syndrome (ARDS) are not recommended. Moreover, unselective or inappropriate administration of antibiotics should be avoided. Although no antiviral treatments have been approved, alpha-interferon (e.g., 5 million units by aerosol inhalation twice per day), and lopinavir/ritonavir have been suggested. Preclinical studies suggested that remdesivir (GS5734) — an inhibitor of RNA polymerase with in vitro activity against multiple RNA viruses, including Ebola — could be effective for both prophylaxis and therapy of HCoVs infections.[18] This drug was positively tested in a rhesus macaque model of MERS-CoV infection.[19]
When the disease results in complex clinical pictures of MOD, organ function support in addition to respiratory support, is mandatory. Extracorporeal membrane oxygenation (ECMO) for patients with refractory hypoxemia despite lung-protective ventilation should merit consideration after a case-by-case analysis. It can be suggested for those with poor results to prone position ventilation.
There is no specific antiviral treatment recommended for COVID-19, and no vaccine is currently available. The treatment is symptomatic, and oxygen therapy represents the major treatment intervention for patients with severe infection. Mechanical ventilation may be necessary in cases of respiratory failure refractory to oxygen therapy, whereas hemodynamic support is essential for managing septic shock.
On January 28, 2020, the WHO released a document summarizing WHO guidelines and scientific evidence derived from the treatment of previous epidemics from HCoVs. This document addresses measures for recognizing and sorting patients with severe acute respiratory disease; strategies for infection prevention and control; early supportive therapy and monitoring; a guideline for laboratory diagnosis; management of respiratory failure and ARDS; management of septic shock; prevention of complications; treatments; and considerations for pregnant patients.
Among these recommendations, we report the strategies for addressing respiratory failure, including protective mechanical ventilation and high-flow nasal oxygen (HFNO) or non-invasive ventilation (NIV).
Intubation and protective mechanical ventilation
Special precautions are necessary during intubation. The procedure should be executed by an expert operator who uses personal protective equipment (PPE) such as FFP3 or N95 mask, protective goggles, disposable gown long sleeve raincoat, disposable double socks, and gloves. If possible, rapid sequence intubation (RSI) should be performed. Preoxygenation (100% O2 for 5 minutes) should be performed via the continuous positive airway pressure (CPAP) method. Heat and moisture exchanger (HME) must be positioned between the mask and the circuit of the fan or between the mask and the ventilation balloon.
Mechanical ventilation should be with lower tidal volumes (4 to 6 ml/kg predicted body weight, PBW) and lower inspiratory pressures, reaching a plateau pressure (Pplat) < 28 to 30 cm H2O. PEEP must be as high as possible to maintain the driving pressure (Pplat-PEEP) as low as possible (< 14 cmH2O). Moreover, disconnections from the ventilator must be avoided for preventing loss of PEEP and atelectasis. Finally, the use of paralytics is not recommended unless PaO2/FiO2 < 150 mmHg. The prone ventilation for > 12 hours per day, and the use of a conservative fluid management strategy for ARDS patients without tissue hypoperfusion (strong recommendation) are emphasized.
Non-invasive ventilation
Concerning HFNO or non-invasive ventilation (NIV), the experts' panel, points out that these approaches performed by systems with good interface fitting do not create widespread dispersion of exhaled air, and their use can be considered at low risk of airborne transmission.[17] Practically, non-invasive techniques can be used in non-severe forms of respiratory failure. However, if the scenario does not improve or even worsen within a short period of time (1–2 hours) the mechanical ventilation must be preferred.
Other therapies
Among other therapeutic strategies, systemic corticosteroids for the treatment of viral pneumonia or acute respiratory distress syndrome (ARDS) are not recommended. Moreover, unselective or inappropriate administration of antibiotics should be avoided. Although no antiviral treatments have been approved, alpha-interferon (e.g., 5 million units by aerosol inhalation twice per day), and lopinavir/ritonavir have been suggested. Preclinical studies suggested that remdesivir (GS5734) — an inhibitor of RNA polymerase with in vitro activity against multiple RNA viruses, including Ebola — could be effective for both prophylaxis and therapy of HCoVs infections.[18] This drug was positively tested in a rhesus macaque model of MERS-CoV infection.[19]
When the disease results in complex clinical pictures of MOD, organ function support in addition to respiratory support, is mandatory. Extracorporeal membrane oxygenation (ECMO) for patients with refractory hypoxemia despite lung-protective ventilation should merit consideration after a case-by-case analysis. It can be suggested for those with poor results to prone position ventilation.
Prevention
Preventive measures are the current strategy to limit the spread of cases. Because an epidemic will increase as long as R0 is greater than 1 (COVID-19 is 2.2), control measures must focus on reducing the value to less than 1.
Preventive strategies are focused on the isolation of patients and careful infection control, including appropriate measures to be adopted during the diagnosis and the provision of clinical care to an infected patient. For instance, droplet, contact, and airborne precautions should be adopted during specimen collection, and sputum induction should be avoided.
The WHO and other organizations have issued the following general recommendations:
Avoid close contact with subjects suffering from acute respiratory infections.
Wash your hands frequently, especially after contact with infected people or their environment.
Avoid unprotected contact with farm or wild animals.
People with symptoms of acute airway infection should keep their distance, cover coughs or sneezes with disposable tissues or clothes and wash their hands.
Strengthen, in particular, in emergency medicine departments, the application of strict hygiene measures for the prevention and control of infections.
Individuals that are immunocompromised should avoid public gatherings.
The most important strategy for the populous to undertake is to frequently wash their hands and use portable hand sanitizer and avoid contact with their face and mouth after interacting with a possibly contaminated environment.
Healthcare workers caring for infected individuals should utilize contact and airborne precautions to include PPE such as N95 or FFP3 masks, eye protection, gowns, and gloves to prevent transmission of the pathogen.
Meanwhile, scientific research is growing to develop a coronavirus vaccine. In recent days, China has announced the first animal tests, and researchers from the University of Queensland in Australia have also announced that, after completing the three-week in vitro study, they are moving on to animal testing. Furthermore, in the U.S., the National Institute for Allergy and Infectious Diseases (NIAID) has announced that a phase 1 trial has begun for a novel coronavirus immunization in Washington state.
Preventive measures are the current strategy to limit the spread of cases. Because an epidemic will increase as long as R0 is greater than 1 (COVID-19 is 2.2), control measures must focus on reducing the value to less than 1.
Preventive strategies are focused on the isolation of patients and careful infection control, including appropriate measures to be adopted during the diagnosis and the provision of clinical care to an infected patient. For instance, droplet, contact, and airborne precautions should be adopted during specimen collection, and sputum induction should be avoided.
The WHO and other organizations have issued the following general recommendations:
Avoid close contact with subjects suffering from acute respiratory infections.
Wash your hands frequently, especially after contact with infected people or their environment.
Avoid unprotected contact with farm or wild animals.
People with symptoms of acute airway infection should keep their distance, cover coughs or sneezes with disposable tissues or clothes and wash their hands.
Strengthen, in particular, in emergency medicine departments, the application of strict hygiene measures for the prevention and control of infections.
Individuals that are immunocompromised should avoid public gatherings.
The most important strategy for the populous to undertake is to frequently wash their hands and use portable hand sanitizer and avoid contact with their face and mouth after interacting with a possibly contaminated environment.
Healthcare workers caring for infected individuals should utilize contact and airborne precautions to include PPE such as N95 or FFP3 masks, eye protection, gowns, and gloves to prevent transmission of the pathogen.
Meanwhile, scientific research is growing to develop a coronavirus vaccine. In recent days, China has announced the first animal tests, and researchers from the University of Queensland in Australia have also announced that, after completing the three-week in vitro study, they are moving on to animal testing. Furthermore, in the U.S., the National Institute for Allergy and Infectious Diseases (NIAID) has announced that a phase 1 trial has begun for a novel coronavirus immunization in Washington state.
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