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The symptoms of 2019-nCoV infection were nonspecific. The most common symptoms were onset of fever, generalized weakness and dry cough. Some patients had headache and/or myalgia, but upper respiratory symptoms such as runny nose were rare. Diarrhea was often identified, which had been reported 10.6% in SARS and up to 30% in MERS. More than half of patients developed shortness of breath, the median duration from disease onset to dyspnea was 8 days. Patients infected with 2019-nCoV might develop acute respiratory distress syndrome (ARDS), followed by septic shock, refractory metabolic acidosis and coagulation dysfunction, if the disease could not be controlled.
Notably, some patients were afebrile or confirmed biologically to have an asymptomatic infection. These cryptic cases of walking pneumonia might serve as a possible source to propagate the outbreak. Further studies on the epidemiological significance of these asymptomatic cases are warranted.
According to the “Diagnosis & Treatment Scheme for Novel Coronavirus Pneumonia (Trial) 6th Edition” enacted by the National Health Commission of the People’s Republic of China on 19 February 2020, the incubation time after exposure is about 1–14 days. Fever, fatigue, and a dry cough are the main manifestations. Nasal obstruction, runny nose, and other upper respiratory symptoms are rare. About half of the patients developed dyspnea one week later, and severe cases developed rapidly into acute respiratory distress syndrome, septic shock, hard-to-correct metabolic acidosis, and coagulation dysfunction. Severe and critical patients may present moderate to low fever, or even no obvious fever. Some patients have mild onset symptoms, no fever, and mostly recovered after one week. Most patients have a favorable prognosis, although some patients are left in a critical condition, or do not survive. The aged patients and the patients with basic diseases have worse prognosis. Children cases are relatively mild.
The unconfirmed cases met the criteria of the suspected cases and are identified positive with SARS-CoV-2 RNA, by real-time RT-PCR or gene sequencing, from the sputum, throat swab, lower respiratory tract secretion, or other samples collected from patients.
An outbreak of novel coronavirus pneumonia is ongoing, called 2019-nCoV, was first identified in Wuhan, Hubei province, China at the end of 2019 [1, 2]. As of February 10th, 2020, at least 40,261 cases confirmed, 23,589 cases suspected, 909 cases death and 3444 cases were cured in China (Fig. 1). 24 countries (Fig. 2) such as Japan, Singapore, Thailand, Korea, and the United States have 383 cases being diagnosed, with 1 case death so far. Although Chinese authorities improved surveillance network, made the laboratory be able to recognize the outbreak within a few weeks and announced the virus genome that provide efficient epidemiological control, World Health Organization (WHO) assessed the risk as ‘very high’ in China and ‘high’ in global level in the coming weeks, and declared the public health emergency of international concern (PHEIC) over the global outbreak of 2019-nCoV in January 31, 2020.
Based on the current epidemiological survey and data, more comprehensive information is required to understand 2019-nCoV feature, epidemiology of the outbreak including the source, transmission, extent of infection, and the clinical picture. Further strategies are required to determine according to the current status.
Coronavirus 2019-nCoV infection commonly presents with signs and symptoms of pneumonia or as a nonspecific lower respiratory illness, with coughing or difficulty breathing accompanied by fever.5,19,20 Fever and cough constitute the most common presentations. However, patients may have other respiratory symptoms, sore throat, nasal congestion, malaise, myalgia, and headache. Bilateral infiltrates may be seen on chest X-ray. Severe cases may present with sepsis and even shock. Conversely, some patients may present as only mildly ill or asymptomatic altogether.21 To date, patients with underlying medical conditions and the elderly are more likely to become severely ill, require hospitalization, and ultimately die.22 Early predictions for incubation time are between 2 and 14 days, based on data from similar coronaviruses. The 14-day criterion for epidemiological risk assumes the longest estimated incubation time.23 In addition, the World Health Organization (WHO) has created its own interim case definition.24
The complete clinical manifestation is not clear yet, as the reported symptoms range from mild to severe, with some cases even resulting in death. The most commonly reported symptoms are fever, cough, myalgia or fatigue, pneumonia, and complicated dyspnea, whereas less common reported symptoms include headache, diarrhea, hemoptysis, runny nose, and phlegm-producing cough [3, 16]. Patients with mild symptoms were reported to recover after 1 week while severe cases were reported to experience progressive respiratory failure due to alveolar damage from the virus, which may lead to death. Cases resulting in death were primarily middle-aged and elderly patients with pre-existing diseases (tumor surgery, cirrhosis, hypertension, coronary heart disease, diabetes, and Parkinson’s disease). Case definition guidelines mention the following symptoms: fever, decrease in lymphocytes and white blood cells, new pulmonary infiltrates on chest radiography, and no improvement in symptoms after 3 days of antibiotics treatment.
For patients with suspected infection, the following procedures have been suggested for diagnosis: performing real-time fluorescence (RT-PCR) to detect the positive nucleic acid of SARS-CoV-2 in sputum, throat swabs, and secretions of the lower respiratory tract samples [13, 14, 43].
Human coronaviruses (HCoV) were first described in the mid-1960s. HCoV is an enveloped RNA virus with a single chain and positive polarity. The name “corona” comes from the crown-like spikes on the surface of the virus. Four major subgroups are known as follows: alpha, beta, gamma and delta. Subtypes of coronaviruses circulating in humans (HCoV-229E, HCoV-OC43, HCoV-NL63 and HKU1-CoV) are mostly viruses that cause colds. Coronaviruses are zoonotic viruses that infect many mammals and birds. There are many coronaviruses that have not been transmitted to humans yet but are detected in animals. Before the virus (most likely a bat virus) gained the ability to infect humans, it jumps an intermediate host as occurred in previous outbreaks. It has been revealed that for emerge of SARS-CoV (Severe acute respiratory syndrome), civet cats played an imported role for transmission of disease to humans, whereas one-humped camels played an intermediate host for MERS-CoV (Middle East Respiratory Syndrome). SARS-CoV was first defined in February 2003 in Asia (Guandong, China) and has spread to more than two dozen countries in North and South America, Europe and Asia. In about eight months, 8098 people are infected, and 774 people died. Since 2004, to our knowledge, there have been no new cases reported in the world. MERS- CoV also causes a severe respiratory disease with symptoms of fever, cough and shortness of breath. The disease was seen for the first time in September 2012 in Saudi Arabia, and all the patients with MERS- CoV had a history of travel or residence in the Arabian Peninsula and nearby countries. Outside the Arabian Peninsula, the disease was seen in the Republic of Korea in 2015. Again, the outbreak was associated with a traveler returning from the Arabian Peninsula. To date, 2494 people have been infected, and there 858 related deaths were reported related to MERS [2, 3].
The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus two (SARS-CoV 2), is a member of Betacoronaviruses, like the former human coronaviruses SARS coronavirus (SARS-Cov) and the Middle East respiratory syndrome (MERS). Human coronaviruses are positive-sense, long (30,000 base pairs) single-stranded RNA viruses. COVID-19 was first detected in humans towards the end of 2019 and the first cases were traced back to Wuhan city (Hubei province) in China. The virus appears to spread via human to human transmission in a similar fashion to influenza and several viruses causing upper respiratory infections, i.e., through contact with secretions from infected individuals. There is also concern regarding airborne transmission as well as oro-fecal transmission. The virus predominantly replicates in the respiratory system during the prodromal period, which further contributes to the transmission of the disease as patients may still be harboring the infection in the absence of symptoms. After the initial reports of infection, in the following several weeks, COVID-19 outbreaks were reported in South Korea, Iran, and Italy. This was quickly followed by several other European, Asian, and North and South American countries reporting cases. COVID-19 was declared a pandemic by the World Health Organization (WHO) on March 11, 2020.
Compared to adults, there have been significantly less reported cases of COVID-19 in the pediatric population. As of February 2020, 2.4% of the 75,465 cases (confirmed and suspected) in China were reported in the pediatric population. This article looks to review specific epidemiological factors, symptomatology, laboratory, and imaging workup and other relevant metrics derived from the limited published literature that are specific to the pediatric population to provide a review for the pediatric practitioner and guide in part towards the creation of an interim algorithm for the management of COVID-19 in the pediatric population.
A retrospective review was conducted of the clinical, lab tests, and radiologic findings for nine children and their families admitted to the Jinan Infectious Diseases Hospital identified to be nucleic acid-positive for SARS-CoV-2 from 24 January 2020 to 24 February 2020. Sample collection and pathogen identification after admission to the hospital, respiratory tract samples including sputum and nasopharyngeal swabs were collected from the patients, which were tested for influenza, avian influenza, respiratory syncytial virus, adenovirus, parainfluenza virus, Mycoplasma pneumoniae and chlamydia, along with routine bacterial, fungal, and pathogenic microorganism tests. Real-time PCR used the SARS-CoV-2 (ORF1ab/N) nucleic acid detection kit (Bio-germ, Shanghai, China) and performed refer to previous literature. All the patients were recorded with basic information and epidemiological histories including (1) History of travel or residence in Wuhan and surrounding areas or other reported cases within 14 days of onset; (2) History of contact with new coronavirus infection (nucleic acid-positive) 14 days before onset; (3) history of contact with patients with fever or respiratory symptoms from Wuhan and surrounding areas, or from communities with case reports within 14 days before onset; (4) Cluster onset, along with disease condition changes.
A 35-year-old man presented with fever for 3 days and cough for 2 days and was admitted to the emergency department of Jiangxi Provincial People's Hospital. The patient had a history of good physical health with no underlying diseases but had returned to Nanchang, Jiangxi Province, from Wuhan 1 week before. Physical examination showed fever, with a body temperature of 38.7℃, and the laboratory examination results showed a normal leukocyte count (5520/µL), increased neutrophils (76.2%), decreased lymphocytes (16.1%), elevated glucose (7.4 mmol/L), and elevated C-reactive protein (14.00 mg/L). The patient tested negative for eight common respiratory pathogens, which were respiratory syncytial virus, adenovirus, influenza A virus, Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila, parainfluenza virus, and influenza B virus, and the influenza A antigen screening was also negative. Finally, he was diagnosed with 2019-nCoV based on the real-time reverse-transcriptase-polymerase chain reaction (rRT-PCR) amplification of the viral DNA from a sputum sample.
CT showed multiple regions of patchy consolidation and ground-glass opacities with indistinct border in both lungs. The lesions were distributed along the bronchial bundles or within the subpleural lung regions (Fig. 1). Neither pleural effusion nor lymphadenopathy was found.
Coronaviruses belong to the Coronaviridae family in the Nidovirales order. Corona represents crown-like spikes on the outer surface of the virus; thus, it was named as a coronavirus. Coronaviruses are minute in size (65–125 nm in diameter) and contain a single-stranded RNA as a nucleic material, size ranging from 26 to 32kbs in length (Fig. 1). The subgroups of coronaviruses family are alpha (α), beta (β), gamma (γ) and delta (δ) coronavirus. The severe acute respiratory syndrome coronavirus (SARS-CoV), H5N1 influenza A, H1N1 2009 and Middle East respiratory syndrome coronavirus (MERS-CoV) cause acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) which leads to pulmonary failure and result in fatality. These viruses were thought to infect only animals until the world witnessed a severe acute respiratory syndrome (SARS) outbreak caused by SARS-CoV, 2002 in Guangdong, China. Only a decade later, another pathogenic coronavirus, known as Middle East respiratory syndrome coronavirus (MERS-CoV) caused an endemic in Middle Eastern countries.
Recently at the end of 2019, Wuhan an emerging business hub of China experienced an outbreak of a novel coronavirus that killed more than eighteen hundred and infected over seventy thousand individuals within the first fifty days of the epidemic. This virus was reported to be a member of the β group of coronaviruses. The novel virus was named as Wuhan coronavirus or 2019 novel coronavirus (2019-nCov) by the Chinese researchers. The International Committee on Taxonomy of Viruses (ICTV) named the virus as SARS-CoV-2 and the disease as COVID-19,,. In the history, SRAS-CoV (2003) infected 8098 individuals with mortality rate of 9%, across 26 contries in the world, on the other hand, novel corona virus (2019) infected 120,000 induviduals with mortality rate of 2.9%, across 109 countries, till date of this writing. It shows that the transmission rate of SARS-CoV-2 is higher than SRAS-CoV and the reason could be genetic recombination event at S protein in the RBD region of SARS-CoV-2 may have enhanced its transmission ability. In this review article, we discuss the origination of human coronaviruses briefly. We further discuss the associated infectiousness and biological features of SARS and MERS with a special focus on COVID-19.
Since the first pneumonia patient was identified around December 2019, in Wuhan, China, multiple human cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. The 2019 novel coronavirus disease (COVID-19) has now swept through the continents and poses a global threat to public health. Up till 12th March 2020, at least 80,980 cases in China and 43,538 cases beyond China were confirmed, covering 118 countries, areas or territories.
Many infections amongst medical staff have been reported, of whom three ophthalmologists from Wuhan Central Hospital died of COVID-19 due to occupational exposure, and Dr. Guangfa Wang, a pneumonia expert, was infected by SARS-CoV-2 through unprotected eye exposure. These events raise an alarm on the route of SARS-CoV-2 transmission. Faced with the possibility of ocular transmission, ophthalmologists are very likely to contract the infection. Drawing on the rich experience during the previous SARS outbreak, the Chinese government has promptly released various protection measures for ophthalmology, and recommended protection for the eyes, as well as mouth and nose, when caring for patients potentially infected with SARS-CoV-2. The American Academy of Ophthalmology recently published a similar recommendation for ophthalmologists from the Centers for Disease Control and Prevention (CDC). Based on the latest published literatures, guidelines and clinical practice experience in domestic hospitals, we have summarized the Chinese experience through the lens of ophthalmology, hoping to make a contribution to protecting ophthalmologists and patients around the world, and praying that the pandemic will be contained as soon as possible.
Laboratory test results were compiled, including standard blood counts, blood biochemistry, C-reactive protein (CRP), procalcitonin (PCT), erythrocyte sedimentation rate(ESR), Interleukin-6 (IL-6) and myocardial enzyme spectrum. Additional data collected included medical imaging, treatment regimens, and prognosis (any severe complications, including death), and recover or discharge date (Table 1).
Since December 2019, a succession of cases of pneumonia with unknown causes has appeared in Wuhan, Hubei Province, China. On January 7, 2020, the 2019 novel coronavirus (2019-nCoV or officially named by the World Health Organization as COVID-19) was identified as the causative agent based on virus typing (12). By January 27, 2020, 2823 cases were confirmed, with 81 deaths. To date, there have been a few reports of chest computed tomography (CT) findings in patients infected by 2019-nCoV. Here, we report chest CT findings in two patients confirmed with 2019-nCoV pneumonia at Jiangxi Provincial People's Hospital. This report was approved by Jiangxi Provincial People's Hospital Institutional Review Board, and the requirement for informed consent was waived.
In December 2019, a cluster of pneumonia cases, caused by a newly identified β-coronavirus, occurred in Wuhan, China. This coronavirus, was initially named as the 2019-novel coronavirus (2019-nCoV) on 12 January 2020 by World Health Organization (WHO). WHO officially named the disease as coronavirus disease 2019 (COVID-19) and Coronavirus Study Group (CSG) of the International Committee proposed to name the new coronavirus as SARS-CoV-2, both issued on 11 February 2020. The Chinese scientists rapidly isolated a SARS-CoV-2 from a patient within a short time on 7 January 2020 and came out to genome sequencing of the SARS-CoV-2. As of 1 March 2020, a total of 79,968 cases of COVID-19 have been confirmed in mainland China including 2873 deaths. Studies estimated the basic reproduction number (R0) of SARS-CoV-2 to be around 2.2, or even more (range from 1.4 to 6.5), and familial clusters of pneumonia outbreaks add to evidence of the epidemic COVID-19 steadily growing by human-to-human transmission.
Since the identification of the first coronavirus – infectious bronchitis virus (IBV) isolated from birds – many coronaviruses have been discovered from such animals as bats, camels, cats, dogs, pigs, and whales. They may cause respiratory, enteric, hepatic, or neurologic diseases with different levels of severity in a variety of hosts, including humans. Coronaviruses have positive-sense single-stranded RNAs, their genomic size are 26 to 32 kilobases, the largest for an RNA virus. And the viruses themselves appear crown-shaped under electron microscopy. Coronaviruses belong to the subfamily Coronavirinae in the family Coronaviridae in the order Nidovirales. Coronavirinae is further divided into four genera, Alpha-, Beta-, Gamma-, and Deltacoronavirus, based on their phylogenetic relationships and genomic structures.
Coronaviruses occasionally jump across host barriers, often with lethal consequences. The alpha- and betacoronaviruses only infect mammals and usually cause respiratory illness in humans and gastroenteritis in animals. Gamma- and deltacoronaviruses mainly infect birds, and no human infection has been reported. Six coronaviruses known to infect humans are 229E, NL63 (genus Alpha-), OC43, HKU1, SARS-CoV, and MERS-CoV (Beta-), whereas only SARS- and MERS-CoV have caused large worldwide outbreaks with fatality, others usually cause mild upper-respiratory tract illnesses. A novel coronavirus was identified in a pneumonia patient in Wuhan on January 9 of this year represents the seventh human-infecting coronaviruses.
Severe acute respiratory syndrome (SARS, induced by SARS-CoV) first emerged in Guangdong province, China in 2002 and quickly spread around the world, with more than 8000 people infected and nearly 800 died. The MERS-CoV is a new member of Betacoronavirus and caused the first confirmed case of Middle East Respiratory Syndrome (MERS) in Saudi Arabia in 2012. Over 2000 MERS-related infections have been reported as of 2019 with a ∼34% fatality rate (https://www.who.int/).
Until the very end of 2019, there were six coronaviruses known to cause disease in humans. Four of these result in little more than a common cold and are endemic around the world. The viruses known as human coronavirus (hCoV)-229E, hCoV-HKU1, hCoV-NL63, and hCoV-OC43 are of little concern at a global public health level. The other two, however, have caused more widespread concern. In 2002, severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in the human population. In a matter of months, this virus from a bat that transmitted via a palm civet to infect a human in the Guangdong province of China infected over 8,000 people, killing roughly 10% (1). In 2003, SARS-CoV infections stopped, and the virus has not been seen since. A second epidemic coronavirus, known as Middle East respiratory syndrome coronavirus (MERS-CoV), emerged in 2012. Like the SARS-CoV outbreak, MERS-CoV started with a patient suffering pneumonia and came from a zoonotic event (this time from a bat via a camel to a human) (1). However, MERS-CoV has shown far more limited human-to-human transmission than SARS-CoV. Since 2012, there have been roughly 2,500 cases of MERS-CoV, mostly confined to regions of the Middle East. While case numbers are low for MERS-CoV, there is a high case fatality ratio (CFR) of approximately 35%, making this virus one of the deadliest human pathogens. Coronaviruses that infect humans all appear to have respiratory transmission, making them pathogens of pandemic potential. The end of 2019 saw the emergence of a novel human coronavirus that is rapidly spreading around the global and has a higher degree of lethality than the endemic coronaviruses, though not to the level of SARS-CoV or MERS-CoV. The virus was initially named 2019-nCoV but is now termed SARS-CoV-2 and causes the disease COVID-19 (coronavirus disease 2019). At the time of writing, there have been over 115,000 cases and over 4,000 deaths.
The first case of COVID-19 was reported to the WHO by Chinese authorities on 31 December 2019 as a result of a patient suffering pneumonia in Wuhan City, Hubei Province, China. Over the following days, more patients were suspected to be suffering the same disease, and by 9 January, a novel coronavirus had been detected and the sequence was published online shortly thereafter (2). The 2 months since emergence of SARS-CoV-2 have demonstrated the rapid pace at which a virus can spread and which science can develop. After an initial lag phase, cases of COVID-19 followed a closely exponential curve. The vast majority of cases are, at the time of writing, still from mainland China. However, over 100 other countries have reported cases. Most cases outside China have been associated with travel to that country, but more clusters of cases are now being detected without travel history. In this article, we will discuss what has already been learned about the virus and will then outline 10 key questions and directions of study for this novel coronavirus.
Early identification of infected patients and timely medical intervention are key to preventing rapid spread of the virus. We attempt to adopt a strategy of screening patients for 2019-nCoV early after the admission. Currently, diagnosis is based on epidemiological associations, clinical manifestations, laboratory findings, and radiological characteristics.4 Both WHO and The National Health Commission have issued definitions of suspected cases.4,11(i) Patients must meet any one of the four epidemiological criteria:(a) A history of travel or residency in Wuhan, Hubei Province, China or other epidemic areas, since December 2019;(b) Close contact with a person who has traveled to Wuhan or other epidemic areas since December 2019 or presented with respiratory symptoms in the 14 days before the onset of signs and symptoms, or close contact with a patient confirmed to have the 2019-nCoV virus;(c) A health worker without enough protection but took care of patients who have the earlier-mentioned conditions;(d) An individual case in a cluster outbreak of the infection.(ii) Patients must present with the following clinical manifestations within 10 days of likely exposure:(a) A history of fever or a high temperature;(b) A dry cough or sore throat;(c) Malaise;(d) Shortness of breath.
Patients who meet any of these epidemiological criteria and who present with some of the above clinical manifestations should be quickly referred to designated hospitals for further examination.
To the editor: We read with interest the recent article by Reusken et al. about laboratory readiness for molecular testing of the novel coronavirus 2019, recently named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in expert laboratories in 30 European countries. At the time of the Middle East respiratory syndrome (MERS)-coronavirus epidemic in 2012, we had highlighted the absence of diagnosis of this virus among travellers returning from the Hajj pilgrimage, which contrasted with the considerable anxiety relating to this emerging infection and its risk of importation and spread in mainland France. Instead of MERS-CoV, influenza A and B viruses had been detected. This illustrated the major disconnect between the fear of a hypothetical spread in France of a virus emerging in the Middle East and the reality of the absence of diagnosed cases, while concomitantly the very real and high incidence of respiratory viruses common worldwide and in our country and their associated mortality appeared largely neglected. Seven years later, the emergence of SARS-CoV-2 in December 2019 reproduced this pattern of disproportionate fear of importation and spread of infections in mainland France while the cases reported worldwide remain almost only localised in China as only 34 people died of this disease (Covid-19) outside China as at 25 February 2020.
In our reference institute for infectious diseases, we have been implementing since the end of January 2020 PCR detection of SARS-CoV-2 RNA using several systems, including those released at the European level. In total, we have tested to date (as at 19 February 2020) 4,084 respiratory samples by PCR and all the tests have been negative for SARS-CoV-2. These tests were carried out on the samples of 32 suspected SARS-CoV-2 cases, 337 people repatriated at the beginning of February 2020 from China tested twice, 164 patients who died in public hospitals in Marseille between 2014 and 2019 of whom at least one respiratory sample had been sent to our laboratory, and they also included 3,214 respiratory samples sent since January 2020 to our laboratory to search for a viral aetiology. In striking contrast, we have tested 5,080 respiratory samples for various suspected respiratory viral infections since 1 January 2020 and identified in 3,380 cases respiratory viruses. In decreasing order of frequency, they were: influenza A virus (n = 794), influenza B virus (n = 588), rhinovirus (n = 567), respiratory syncytial virus (n = 361), adenovirus (n = 226), metapneumovirus (n = 192), enterovirus (n = 171), bocavirus (n = 83), parainfluenza virus (n = 24), and parechovirus (n = 8). Among the diagnosed viruses, there were also 373 common human coronaviruses (HCoV), including 205 HCoV-HKU1, 94 HCoV-NL63, 46 HCoV-OC43, and 28 HCoV-229E. Furthermore, analysis of the mortality associated with these viruses has been able to show that since 1 January 2020, one patient died after being diagnosed with HCoV-HKU1, and respiratory viruses were found in 13 other patients who died, which included influenza A virus (3 cases), respiratory syncytial virus (3 cases), rhinovirus (5 cases), adenovirus (1 case) and metapneumovirus (1 case). Retrospectively, analysis of deaths in patients who have had a respiratory sample has shown that at least nine patients have died between 2017 and 2019 after being diagnosed with one of the four coronaviruses commonly circulating in humans.
Thus, it is surprising to see that all the attention focused on a virus whose mortality ultimately appears to be of the same order of magnitude as that of common coronaviruses or other respiratory viruses such as influenza or respiratory syncytial virus, while the four common HCoV diagnosed go unnoticed although their incidence is high. In fact, the four common HCoV are often not even identified in routine diagnosis in most laboratories, although they are genetically very different from each other and associated with distinct symptomatology.
As more cases of COVID-19 occur, it is becoming established that the most severe cases and mortality are associated with underlying health conditions. The most common associated comorbidities are pulmonary disease, diabetes, and old age (10). Interesting questions as to how these comorbidities impact viral pathogenesis are open for investigation. More severe SARS cases were also associated with age, and work in mice has demonstrated this (12–14). Severe MERS is associated with diabetes and other underlying health conditions (15, 16), and again, work in mice has shown that diabetes can impact the immune response to infection, leading to increased pathogenesis (17). It will be interesting to see whether SARS-CoV-2 infection is similarly impacted.
In December 2019, several patients with pneumonia of unknown cause were identified in Wuhan, China.1 The results of genome sequencing, released on 10 January 2020, showed that the pneumonia outbreak was related to a new coronavirus, named 2019 novel coronavirus (2019-nCoV), whose genetic sequence is homologous to that of the coronavirus causing severe acute respiratory syndrome (SARS).2 Coronaviruses are enveloped with a positive-sense, single-stranded RNA genome and with a nucleocapsid.3 Although the 2019-nCoV is a new coronavirus, it has characteristics common to other coronaviruses, such as sensitivity to heat (it can be inactivated after 30 minutes at 56 °C), diethyl ether, 75% ethanol, chlorine-containing disinfectants, peracetic acid, and chloroform.4
Further genetic and amino acid sequencing of the S-protein of 2019-nCoV established that the receptor-binding domain of the S-protein binds to recipient cells and interacts strongly with human angiotensin-converting enzyme 2 (ACE2) receptor molecules.2 This finding shows that the underlying pathogenesis of the virus is to infect the human respiratory epithelium through the S-protein-ACE2 binding pathway. The sequencing from isolated 2019-nCoV became available to the World Health Organization (WHO) on 12 January 2020,5 and the genomic sequence substantially facilitated the development of real-time reverse transcription-PCR (RT-PCR) assays to detect the virus.
By 29 January 2020, the virus had infected more than 7000 people in China and had caused 170 deaths.6 At the same time, the disease is gradually being spread to several other countries as the virus can be transmitted through air and contact.4 Fortunately, at least 124 patients have been cured, according to a recent report of the National Health Commission of the People’s Republic of China.6
According to the research that examined the infectious patients in Wuhan Jinyintan Hospital,7 typical clinical features included fever (98%, 40 of 41), cough (76%, 31 of 41), malaise (44%, 18 of 41), sputum production (28%, 11 of 39), and other less-common symptoms (headache, haemoptysis, diarrhoea, etc.). The median age of the infected patients was 47 years (interquartile range [IQR], 41.0–58.0), and the median time from onset to admission was 7 days (IQR, 4.0–8.0). Severely ill patients may have acute respiratory distress syndrome (ARDS), acute cardiac injury, secondary infection, septic shock, and acute kidney injury. Laboratory findings include lymphopenia, leucopenia, elevated concentrations of procalcitonin, serum amyloid A, D-dimer, and hypersensitive troponin and longer prothrombin times.7
The 2019-nCoV epidemic is suspected to be highly similar to other highly threatening coronavirus diseases such as SARS and Middle Eastern respiratory syndrome (MERS), both intensely infectious diseases related to animals.2,3 Like with other epidemics, health systems need to respond quickly and accurately to control the spread of the virus. Here, we describe our understanding of the 2019-nCoV epidemic and our experience with other coronavirus-related diseases in West China Hospital. Based on this, we aim to establish a precision medicine approach to managing Wuhan coronavirus pneumonia, starting from accurate and rapid recognition of individuals infected by 2019-nCoV. It will facilitate decision-making by health care workers with necessary clinical information, laboratory detection, and imaging findings. The approach consists of the following four parts: screening, diagnosis, preventive control, and treatment of 2019-CoV pneumonia (Fig. 1). Given our clinical experience in preventing and treating various viral pneumonia, including those caused by coronaviruses, we believe that such an approach would help in preventing further the spreading of 2019-nCoV.
On January 9 2020, the World Health Organization (WHO) declared the identification, by Chinese Health authorities, of a novel coronavirus, further classified as SARS-CoV-2. This new virus, initially emerged in the Chinese city of Wuhan in December 2019, led to a sharply spreading outbreak of human respiratory disease (COVID-2019), both within People’s Republic of China and in several other countries worldwide. On March 9 2020, WHO declared COVID-19 a global pandemic. Currently, Italy is the second most affected country by COVID-19 infection after China. The first autochthonous infection case was confirmed in Italy on February 21 2020 and up to now (March 12), 12462 cases with 827 deaths have been registered in Italy. Considering the recent evolution of Italian epidemiologic picture, many health-care facilities will be likely in charge of managing patients affected by COVID-19 in the next days. The “L. Spallanzani” National Institute for the Infectious Diseases, IRCCS has been the first Italian hospital to admit patients affected by COVID-19. Therefore, it will be useful to share the protocol for the clinical management of COVID-19 confirmed cases, applied within our Institute, in order to support other facilities that may have a limited experience in treating COVID-19 patients.
Procedures described in the present document are applied in agreement with the “Regional Network for the Infectious Diseases”, the “Regional Hospital and Medical Specialties Network” and with the active cooperation of the “Regional Agency for the Health Emergencies – ARES 118”. This latter is in charge for the response to the territorial health emergencies and for the transport of patients within the hospital network. Recommendations described within this document are based on very limited clinical evidences. Consequently, they should be considered as expert opinions, which may be modified according to newly produced literature data.
Based on the current information, most patients had a good prognosis, while a few patients were in critical condition, especially the elderly and those with chronic underlying diseases. As of 1 March 2020, a total of 79,968 confirmed cases, including 14,475 (18.1%) with severe illness, and 2873 deaths (3.5%) in mainland China had been reported by WHO. Complications included acute respiratory distress syndrome (ARDS), arrhythmia, shock, acute kidney injury, acute cardiac injury, liver dysfunction and secondary infection. The poor clinical outcome was related to disease severity. The disease tends to progress faster in elderly people, with the median number of days from the occurrence of the first symptoms to death shorter among people aged 65 years or more [56, 57]. Similar to H7N9 patients, the elderly male with comorbidities and ARDS showed a higher death risk. Additionally, more than 100 children were infected, with the youngest being 30 h after birth. Neonates and the elderly need more attention and care due to their immature or weak immune system.
We searched MEDLINE, ScienceDirect, Embase, the Cochrane Library, WanFang Database, VIP Database, SinoMed, China National Knowledge Infrastructure (CNKI), the CDC for COVID-19 website (https://www.cdc.gov/coronavirus/2019-ncov/publications.htm), Chinese Scientific Research Academic Exchange Platform for COVID-19 (http://medjournals.cn/2019NCP/index.do), and relevant references for papers related to "ophthalmology and SARS-CoV-2/COVID-19"; published till 12th March 2020. The search strategy was as follows: (SARS-CoV-2 or 2019-nCov or COVID-19 or NCP or coronavirus or "severe acute respiratory syndrome coronavirus 2" [Supplementary Concept] or "COVID-19" [Supplementary Concept]) and (ocular or eye or ophthalm* or ophthalmologist or tear or conjunctiv* or "Conjunctivitis"[Mesh] or "Conjunctivitis, Viral"[Mesh]).
We identified 33 articles in total published by Chinese scholars directly relevant to ophthalmology and SARS-CoV-2/COVID-19. Twenty-seven articles are published in Chinese journals, most articles are reviews, almost all regarding ophthalmic precautions and ocular surface transmission of SARS-CoV-2 infection (Table 1).
In late 2019, a novel corona virus (first: 2019-nCov, then: SARS-CoV-2) was identified as the cause of a cluster of pneumonia cases, which infected a lot of people in Wuhan, a city in the Hubei province of China (1). SARS-CoV-2 rapidly spread and led to an outbreak in China and then became a global health emergency. Although control measures and isolations have been applied for prevention, the infection has increased and caused a pandemic (2). Although this virus belongs to a relatively well-known viral family, Coronaviridae, and is similar to viruses that caused severe acute respiratory syndrome (SARS), which had an outbreak in 2002, and Middle East respiratory syndrome (MERS), which had an outbreak in 2012, in some characteristics, there are a lot of uncertainties and unknown specifications about this virus such as its origin and source of infection, its emergence, and its mechanism of action and transmission (3, 4).
Since the number of COVID-2019 cases is rising around the world and it has been associated with a large number of mortality and morbidity, it has led to a new global phobia called Coro phobia (5). Based on recent reports, the novel Corona virus can be identified through various symptoms (Fever, Cough, Dyspnea, Myalgia, and Fatigue) (6-8).
Similar to other viral respiratory infections, SARS-CoV-2 or COVID-19 can be transmitted through the respiratory tract. It mainly causes respiratory tract infections and develops severe pneumonia in infected patients who may require intensive care. Severe disease may result in death due to progressive respiratory failure (9, 10).
Everyone is susceptible to this virus, but the elderly and those with underlying diseases are more at risk of adverse outcomes. Current knowledge has shown that death rate is high in people with chronic underlying diseases (11). Therefore, special attention should be paid to the elderly and immunocompromised patients. Infections might progress rapidly in these groups and timely clinical decisions are needed (12). Currently, information on the prevalence of predominant chronic diseases is rare. Moreover, knowing the underlying diseases in COVID-19 infected patients is important for healthcare workers. In the current study, a systematic review and meta-analysis was conducted on the prevalence of underlying diseases in confirmed hospitalized COVID-19 cases.