How does the coronavirus differ from seasonal flu?

The coronavirus and the influenza virus have similarities and differences. In order to comprehensively compare them, their genome sequencing data were examined by principal component analysis. Variations in coronavirus were smaller than those in a subclass of the influenza virus. In addition, differences among coronaviruses in a variety of hosts were small. These characteristics may have facilitated the infection of different hosts. Although many of the coronaviruses were more conservative, those repeatedly found among humans showed annual changes. If SARS-CoV-2 changes its genome like the Influenza H type, it will repeatedly spread every few years. In addition, the coronavirus family has many other candidates for subsequent pandemics. One Sentence Summary The genome data of coronavirus were compared to influenza virus, to investigate its spreading mechanism and future status. Coronavirus would repeatedly spread every few years. In addition, the coronavirus family has many other candidates for subsequent pandemics.

Coronavirus, as a source of pandemic pathogens

We have recently described the discovery of a novel coronavirus, coronavirus HKU1 (CoV-HKU1), associated with community-acquired pneumonia. However, the clinical spectrum of disease and the epidemiology of CoV-HKU1 infections in relation to infections with other respiratory viruses are unknown. In this 12-month prospective study, 4,181 nasopharyngeal aspirates from patients with acute respiratory tract infections were subjected to reverse transcription-PCRs specific for CoV-HKU1 and human coronaviruses NL63 (HCoV-NL63), OC43 (HCoV-OC43), and 229E (HCoV-229E). Coronaviruses were detected in 87 (2.1%) patients, with 13 (0.3%) positive for CoV-HKU1, 17 (0.4%) positive for HCoV-NL63, 53 (1.3%) positive for HCoV-OC43, and 4 (0.1%) positive for HCoV-229E. Of the 13 patients with CoV-HKU1 infections, 11 were children and 8 had underlying diseases. Similar to the case for other coronaviruses, upper respiratory infection was the most common presentation of CoV-HKU1 infections, although pneumonia, acute bronchiolitis, and asthmatic exacerbation also occurred. Despite a shorter duration of fever (mean, 1.7 days) and no difference in maximum temperature in children with CoV-HKU1 infections compared to patients with most other respiratory virus infections, a high incidence of febrile seizures (50%) was noted, which was significantly higher than those for HCoV-OC43 (14%), adenovirus (9%), human parainfluenza virus 1 (0%), and respiratory syncytial virus (8%) infections. CoV-HKU1 and HCoV-OC43 infections peaked in winter, although cases of the former also occurred in spring to early summer. This is in contrast to HCoV-NL63 infections, which mainly occurred in early summer and autumn but were absent in winter. Two genotypes of CoV-HKU1 cocirculated during the study period. Continuous studies over a longer period are warranted to ascertain the seasonal variation and relative importance of the different coronaviruses. Similar studies in other countries are required to better determine the epidemiology and genetic diversity of CoV-HKU1.

Coronavirus HKU1 and other coronavirus infections in Hong Kong.

There is currently debate about human coronavirus (HCoV) seasonality and pathogenicity, as epidemiological data are scarce. Here, we provide epidemiological and clinical features of HCoV patients with acute respiratory infection (ARI) examined in primary care general practice. We also describe HCoV seasonality over six influenza surveillance seasons (week 40 to 15 of each season) from the period 2014/2015 to 2019/2020 in Corsica (France). A sample of patients of all ages presenting for consultation for influenza-like illness (ILI) or ARI was included by physicians of the French Sentinelles Network during this period. Nasopharyngeal samples were tested for the presence of 21 respiratory pathogens by real-time RT-PCR. Among the 1389 ILI/ARI patients, 105 were positive for at least one HCoV (7.5%). On an annual basis, HCoVs circulated from week 48 (November) to weeks 14-15 (May) and peaked in week 6 (February). Overall, among the HCoV-positive patients detected in this study, HCoV-OC43 was the most commonly detected virus, followed by HCoV-NL63, HCoV-HKU1, and HCoV-229E. The HCoV detection rates varied significantly with age (p = 0.00005), with the age group 0-14 years accounting for 28.6% (n = 30) of HCoV-positive patients. Fever and malaise were less frequent in HCoV patients than in influenza patients, while sore throat, dyspnoea, rhinorrhoea, and conjunctivitis were more associated with HCoV positivity. In conclusion, this study demonstrates that HCoV subtypes appear in ARI/ILI patients seen in general practice, with characteristic outbreak patterns primarily in winter. This study also identified symptoms associated with HCoVs in patients with ARI/ILI. Further studies with representative samples should be conducted to provide additional insights into the epidemiology and clinical features of HCoVs.

Epidemiology and Clinical Symptoms Related to Seasonal Coronavirus Identified in Patients with Acute Respiratory Infections Consulting in Primary Care over Six Influenza Seasons (2014-2020) in France.

Epidemiology and Clinical Symptoms Related to Seasonal Coronavirus Identified in Patients with Acute Respiratory Infections Consulting in Primary Care over Six Influenza Seasons (2014-2020) in France

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to sweep the world, causing infection of millions and death of hundreds of thousands. The respiratory disease that it caused, COVID-19 (stands for coronavirus disease in 2019), has similar clinical symptoms with other two CoV diseases, severe acute respiratory syndrome and Middle East respiratory syndrome (SARS and MERS), of which causative viruses are SARS-CoV and MERS-CoV, respectively. These three CoVs resulting diseases also share many clinical symptoms with other respiratory diseases caused by influenza A viruses (IAVs). Since both CoVs and IAVs are general pathogens responsible for seasonal cold, in the next few months, during the changing of seasons, clinicians and public heath may have to distinguish COVID-19 pneumonia from other kinds of viral pneumonia. This is a discussion and comparison of the virus structures, transmission characteristics, clinical symptoms, diagnosis, pathological changes, treatment and prevention of the two kinds of viruses, CoVs and IAVs. It hopes to provide information for practitioners in the medical field during the epidemic season.

Comparative review of respiratory diseases caused by coronaviruses and influenza A viruses during epidemic season

Comparative seasonalities of influenza A, B and ‘common cold’ coronaviruses – setting the scene for SARSCoV-2 infections and possible unexpected host immune interactions

Four human coronaviruses (HCoV-229E, HCoV-HKU1, HCoV-NL63, and HCoV-OC43) are associated with a range of respiratory outcomes, including bronchiolitis and pneumonia. Their epidemiologies and clinical characteristics are poorly described and are often reliant on case reports. To address these problems, we conducted a large-scale comprehensive screening for all four coronaviruses by analysis of 11,661 diagnostic respiratory samples collected in Edinburgh, United Kingdom, over 3 years between July 2006 and June 2009 using a novel four-way multiplex real-time reverse transcription-PCR (RT-PCR) assay. Coronaviruses were detected in 0.3 to 0.85% of samples in all age groups. Generally, coronaviruses displayed marked winter seasonality between the months of December and April and were not detected in summer months, which is comparable to the pattern seen with influenza viruses. HCoV-229E was the exception; detection was confined to the winter of 2008 and was sporadic in the following year. There were additional longer-term differences in detection frequencies between seasons, with HCoV-OC43 predominant in the first and third seasons and HCoV-HKU1 dominating in the second (see Results for definitions of seasons). A total of 11 to 41% of coronaviruses detected were in samples testing positive for other respiratory viruses, although clinical presentations of coronavirus monoinfections were comparable to those of viruses which have an established role in respiratory disease, such as respiratory syncytial virus, influenza virus, and parainfluenza viruses. The novel multiplex assay for real-time pan-coronavirus detection enhances respiratory virus diagnosis, overcomes potential diagnostic problems arising through seasonal variation in coronavirus frequency, and provides novel insights into the epidemiology and clinical implications of coronaviruses.

Epidemiology and clinical presentations of the four human coronaviruses 229E, HKU1, NL63, and OC43 detected over 3 years using a novel multiplex real-time PCR method.

Abstract Background Study of human coronavirus and other virus-associated respiratory illnesses is needed to describe their clinical effects on chronically ill, older adults. Methods A prospective study during 2009 to 2013 clinically assessed acute respiratory illnesses soon after onset and 3 to 4 weeks later in patients aged ≥60 years with chronic lung and heart diseases (group 1, 100 subjects) and healthy adults aged 18 to 40 years (group 2, 101 subjects). Respiratory secretions were tested for nucleic acids of a panel of respiratory viruses. An increase in antibody titer was assessed for 4 coronavirus strains. Results Virus-associated illnesses (29 [39.1%] of 74 illnesses in group 1 and 59 [48.7%] of 121 illnesses in group 2) occurred in all calendar quarters, most commonly in the first and fourth quarters. Coronaviruses (group 1: 14 [18.9%] illnesses; group 2: 26 [21.5%] illnesses) and enteroviruses/rhinoviruses (group 1: 14 [18.9%] illnesses; group 2: 37 [30.6%] illnesses) were most common. Virus co-infections occurred in 10 illnesses. Illnesses with 9 to 11 symptoms were more common in group 1 (17 [23.0%]) than in group 2 (15 [12.4%]) (P < .05). Compared with group 2, more group 1 subjects reported dyspnea, more severe disease of longer duration, and treatment for acute illness with prednisone and antibiotics. Coronavirus-associated illnesses (percent of illnesses, group 1 vs group 2) were characterized by myalgias (21% vs 68%, P < .01), chills (50% vs 52%), dyspnea (71% vs 24%, P < .01), headache (64% vs 72%), malaise (64% vs 84%), cough (86% vs 68%), sputum production (86% vs 60%), sore throat (64% vs 80%), and nasal congestion (93% vs 96%). Conclusions Respiratory illnesses were commonly associated with coronaviruses and enteroviruses/rhinoviruses affecting chronically ill, older patients more than healthy, young adults.

Coronavirus and Other Respiratory Illnesses Comparing Older with Young Adults

Coronaviruses of humans were first identified more than 60 years ago from individuals with respiratory infections, mainly mild. Two different viruses, 229E and OC43 were initially recognized. Because of difficulty in isolating them using standard techniques, many of the early studies of their occurrence were seroepidemiologic. They were confirmed to be worldwide in distribution, and, in the North Temperate Zone, mainly occurring in the winter season. With the development of the reverse transcriptase polymerase chain reaction (PCR) technique, two additional distinct viruses have been identified, HKU1 and NL63. The four viruses have now been recognized as important in the etiology of common respiratory infections, second only to the rhinoviruses. In 2002, a previously unrecognized betacoronavirus emerged from a zoonotic reservoir in Southern China and spread during the following year to several major cities of the world. The resulting illness was termed Severe Acute Respiratory Syndrome (SARS) because of its potential lethality. More than 8,000 probable cases were reported during 2003, mainly from Hong Kong and mainland China, producing social and economic disruption in those areas affected. A constant feature of the outbreak was the importance of nosocomial spread. In spite of an estimated basic reproductive number higher than influenza, the outbreak was ended, in large part because of control of in-hospital transmission. In 2012, another betacoronavirus has emerged in the Arabian peninsula which is producing a somewhat similar illness, termed Middle East Respiratory Syndrome (MERS), also marked by extensive nosocomial transmission. The outcome of this emergence is currently unknown.

Coronaviruses

Coronaviruses have recently caused world-wide severe outbreaks: SARS (Severe Acute Respiratory Syndrome) in 2002 and MERS (Middle-East Respiratory Syndrome) in 2012. At the end of 2019, a new coronavirus outbreak appeared in Wuhan (China) seafood market as first focus of infection, becoming a pandemics in 2020, spreading mainly into Europe and Asia. Although the virus family is well-known, this specific virus presents considerable differences, as higher transmission rates, being a challenge for diagnostic methods, treatments and vaccines. Coronavirus.pro is a C++ application which simulates Coronavirus replication cycle. This software has identified virus type in short times and provided FASTA files of virus proteins, a list of mRNA sequences and secondary structures. Furthermore, the software has identified a list of structural, non-structural and accessory proteins in 2019-nCoV virus genome more similar to SARS than to MERS, as several fusion proteins characteristics of this virus type. These results are useful as a first step in order to develop diagnostic methods, new vaccines or antiviral drugs, which could avoid virus replication in any stage: fusion inhibitors, RdRp inhibitors and PL2pro/3CLpro protease inhibitors.

Coronavirus SARS-CoV-2: Analysis of subgenomic mRNA transcription, 3CLpro and PL2pro protease cleavage sites and protein synthesis

Public health preparedness for coronavirus disease 2019 (COVID-19) is challenging in the absence of setting-specific epidemiological data. Here we describe the epidemiology of seasonal human coronaviruses (sCoVs) and other cocirculating viruses in the West of Scotland, UK. We analyzed routine diagnostic data for >70,000 episodes of respiratory illness tested molecularly for multiple respiratory viruses between 2005 and 2017. Statistical associations with patient age and sex differed between CoV-229E, CoV-OC43 and CoV-NL63. Furthermore, the timing and magnitude of sCoV outbreaks did not occur concurrently and coinfections were not reported. With respect to other cocirculating respiratory viruses, we found evidence of positive, rather than negative, interactions with sCoVs. These findings highlight the importance of considering cocirculating viruses in the differential diagnosis of COVID-19. Further work is needed to establish the occurrence/degree of cross-protective immunity conferred across sCoVs and with COVID-19, as well as the role of viral coinfection in COVID-19 disease severity.

Epidemiology of seasonal coronaviruses: Establishing the context for COVID-19 emergence

In February 2003, a severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in humans in Guangdong Province, China, and caused an epidemic that had severe impact on public health, travel, and economic trade. Coronaviruses are worldwide in distribution, highly infectious, and extremely difficult to control because they have extensive genetic diversity, a short generation time, and a high mutation rate. They can cause respiratory, enteric, and in some cases hepatic and neurological diseases in a wide variety of animals and humans. An enormous, previously unrecognized reservoir of coronaviruses exists among animals. Because coronaviruses have been shown, both experimentally and in nature, to undergo genetic mutations and recombination at a rate similar to that of influenza viruses, it is not surprising that zoonosis and host switching that leads to epidemic diseases have occurred among coronaviruses. Analysis of coronavirus genomic sequence data indicates that SARS-CoV emerged from an animal reservoir. Scientists examining coronavirus isolates from a variety of animals in and around Guangdong Province reported that SARS-CoV has similarities with many different coronaviruses including avian coronaviruses and SARS-CoV-like viruses from a variety of mammals found in live-animal markets. Although a SARS-like coronavirus isolated from a bat is thought to be the progenitor of SARS-CoV, a lack of genomic sequences for the animal coronaviruses has prevented elucidation of the true origin of SARS-CoV. Sequence analysis of SARS-CoV shows that the 5' polymerase gene has a mammalian ancestry; whereas the 3' end structural genes (excluding the spike glycoprotein) have an avian origin. Spike glycoprotein, the host cell attachment viral surface protein, was shown to be a mosaic of feline coronavirus and avian coronavirus sequences resulting from a recombination event. Based on phylogenetic analysis designed to elucidate evolutionary links among viruses, SARS-CoV is believed to have branched from the modern Group 2 coronaviruses, suggesting that it evolved relatively rapidly. This is significant because SARS-CoV is likely still circulating in an animal reservoir (or reservoirs) and has the potential to quickly emerge and cause a new epidemic.

The relationship of severe acute respiratory syndrome coronavirus with avian and other coronaviruses.

Public health preparedness for coronavirus disease 2019 (COVID-19) is challenging in the absence of setting-specific epidemiological data. Here we describe the epidemiology of seasonal coronaviruses (sCoVs) and other cocirculating viruses in the West of Scotland, UK. We analyzed routine diagnostic data for >70,000 episodes of respiratory illness tested molecularly for multiple respiratory viruses between 2005 and 2017. Statistical associations with patient age and sex differed between CoV-229E, CoV-OC43 and CoV-NL63. Furthermore, the timing and magnitude of sCoV outbreaks did not occur concurrently and coinfections were not reported. With respect to other cocirculating respiratory viruses, we found evidence of positive, rather than negative, interactions with sCoVs. These findings highlight the importance of considering cocirculating viruses in the differential diagnosis of COVID-19. Further work is needed to establish the occurrence/degree of cross-protective immunity conferred across sCoVs and with COVID-19, as well as the role of viral coinfection in COVID-19 disease severity.

Four coronaviruses (HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1) are endemic in humans and mainly associated with mild respiratory illnesses; whereas the other two coronaviruses [Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV)] present as emerging infections causing severe respiratory syndrome. Coronaviruses evolve by accumulation of point mutations and recombination of genomes among different strains or species. Mammalian coronaviruses including those infect humans are evolved from bat coronaviruses. While SARS-CoV and MERS-CoV are genetically closely related to bat coronaviruses, intermediate host(s) is (are) likely to be involved in the emergence and cross-species transmission of these novel human viruses. High prevalence of SARS-like coronaviruses have been found from masked palm civet cats and raccoon dogs collected from markets around the time of outbreaks in humans, but these animals are likely to be a transient accidental host rather than a persisting reservoir. More research is needed to elucidate the ecology of coronaviruses. Vigilance and surveillance should be maintained to promptly identify newly emerged coronaviruses.

Tracing the SARS-coronavirus.

Coronavirus, which can cause respiratory syndrome, to date has affected over seventeen thousand individuals, especially in China. Coronavirus is interspecies and can also be transmitted from man to man, with an incubation ranging from 1 to 14 days. Human coronavirus infections can induce not only mild to severe respiratory diseases, but also inflammation, high fever, cough, acute respiratory tract infection and dysfunction of internal organs that may lead to death. Coronavirus infection (regardless of the various types of corona virus) is primarily attacked by immune cells including mast cells (MCs), which are located in the submucosa of the respiratory tract and in the nasal cavity and represent a barrier of protection against microorganisms. Viral activate MCs release early inflammatory chemical compounds including histamine and protease; while late activation provokes the generation of pro-inflammatory IL-1 family members including IL-1, IL-6 and IL-33. Here, we propose for the first time that inflammation by coronavirus may be inhibited by anti-inflammatory cytokines belonging to the IL-1 family members.

Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy.

Rhinoviruses are picornaviruses that cause colds. They are naturally temperature sensitive and highly adapted to grow in respiratory epithelium. Coronaviruses are structurally quite different, being enveloped viruses but are also adapted to grow in respiratory epithelium and also cause colds.

Rhinoviruses and coronaviruses - virological aspects of their role in causing colds in man.

Public health preparedness for coronavirus (CoV) disease 2019 (COVID-19) is challenging in the absence of setting-specific epidemiological data. Here we describe the epidemiology of seasonal CoVs (sCoVs) and other cocirculating viruses in the West of Scotland, United Kingdom. We analyzed routine diagnostic data for >70 000 episodes of respiratory illness tested molecularly for multiple respiratory viruses between 2005 and 2017. Statistical associations with patient age and sex differed between CoV-229E, CoV-OC43, and CoV-NL63. Furthermore, the timing and magnitude of sCoV outbreaks did not occur concurrently, and coinfections were not reported. With respect to other cocirculating respiratory viruses, we found evidence of positive, rather than negative, interactions with sCoVs. These findings highlight the importance of considering cocirculating viruses in the differential diagnosis of COVID-19. Further work is needed to establish the occurrence/degree of cross-protective immunity conferred across sCoVs and with COVID-19, as well as the role of viral coinfection in COVID-19 disease severity.

Epidemiology of Seasonal Coronaviruses: Establishing the Context for the Emergence of Coronavirus Disease 2019

An overview of coronaviruses including the SARS-2 coronavirus - Molecular biology, epidemiology and clinical implications

Differences and similarities between Severe Acute Respiratory Syndrome (SARS)-CoronaVirus (CoV) and SARS-CoV-2. Would a rose by another name smell as sweet?

The emergence of 2019 novel coronavirus (2019-nCoV) is of global concern and might have emerged from RNA recombination among existing coronaviruses. CoV spike (S) protein which is crucial for receptor binding, membrane fusion via conformational changes, internalization of the virus, host tissue tropism and comprises crucial targets for vaccine development, remain largely uncharacterized. Therefore, the present study has been planned to determine the sequence variation, structural and antigenic divergence of S glycoprotein which may be helpful for the management of 2019-nCoV infection. The sequences of spike glycoprotein of 2019-nCoV and SARS coronavirus (SARS-CoV) were used for the comparison. The sequence variations were determined using EMBOSS Needle pairwise sequence alignment tools. The variation in glycosylation sites was predicted by NetNGlyc 1.0 and validated by N-GlyDE server. Antigenicity was predicted by NetCTL 1.2 and validated by IEDB Analysis Resource server. The structural divergence was determined by using SuperPose Version 1.0 based on cryo-EM structure of the SARS coronavirus spike glycoprotein. Our data suggests that 2019-nCoV is newly spilled coronavirus into humans in China is closely related to SARS-CoV, which has only 12.8% of difference with SARS-CoV in S protein and has 83.9% similarity in minimal receptor-binding domain with SARS-CoV. Addition of a novel glycosylation sites were observed in 2019-nCoV. In addition, antigenic analysis proposes that great antigenic differences exist between both the viral strains, but some of the epitopes were found to be similar between both the S proteins. In spite of the variation in S protein amino acid composition, we found no significant difference in their structures. Collectively, for the first time our results exhibit the emergence of human 2019-nCoV is closely related to predecessor SARS-CoV and provide the evidence that 2019-nCoV uses various novel glycosylation sites as SARS-CoV and may have a potential to become pandemic owing its antigenic discrepancy. Further, demonstration of novel Cytotoxic T lymphocyte epitopes may impart opportunities for the development of peptide based vaccine for the prevention of 2019-nCoV.

Structural, glycosylation and antigenic variation between 2019 novel coronavirus (2019-nCoV) and SARS coronavirus (SARS-CoV)

The respiratory syndrome caused by a new type of coronavirus has been emerging from China and caused more than 1000 death globally since December 2019. This new virus, called 2019 novel coronavirus (2019-nCoV) uses the same receptor called Angiotensinconverting enzyme 2 (ACE2) to attack humans as the coronavirus that caused the severe acute respiratory syndrome (SARS) seventeen years ago. Both viruses recognize ACE2 through the spike proteins (S-protein) on their surfaces. It was found that the S-protein from the SARS coronavirus (SARS-CoV) bind stronger to ACE2 than 2019-nCoV. However, function of a bio-system is often under kinetic, rather than thermodynamic, control. To address this issue, we constructed a structural model for complex formed between ACE2 and the S-protein from 2019-nCoV, so that the rate of their association can be estimated and compared with the binding of S-protein from SARS-CoV by a multiscale simulation method. Our simulation results suggest that the association of new virus to the receptor is slower than SARS, which is consistent with the experimental data obtained very recently. We further integrated this difference of association rate between virus and receptor into a mathematical model which describes the life cycle of virus in host cells and its interplay with the innate immune system. Interestingly, we found that the slower association between virus and receptor can result in longer incubation period, while still maintaining a relatively higher level of viral concentration in human body. Our computational study therefore provides, from the molecular level, one possible explanation that the new disease by far spread much faster than SARS.

A Multiscale and Comparative Model for Receptor Binding of 2019 Novel Coronavirus and the Implication of its Life Cycle in Host Cells

PURPOSE: Influenza A viruses, human coronaviruses (hCoV) and human bocavirus (hBoV) are emerging respiratory viruses. This study investigated the association between influenza A viruses co-infection with hBoV and hCoV and severity and the sensitivity of a real-time polymerase chain reaction (RT-PCR) assay for identification of 15 coronaviruses. METHODOLOGY: Published sequences for the 15 human coronaviruses were used to design a consensus PCR targeting the replicase open reading frame 1b. A previously published PCR targeting the NS1 Gene of all known human bocavirus strains was also utilized. A series of 217 samples from patients aged 37.7 (SD ± 30.4)] with seasonal influenza A viruses (SeasFluA) identified between 06/2011 and 06/2012 in NW England were tested for hCoV and hBoV using RT-PCR. Association between co-infection and disease outcome was assessed using logistic regression. RESULTS: The limit of detection of hCoV RT-PCR assay was 2 copies/µl of human coronavirus RNA template, a sensitivity comparable to a previously published SYBR green assay for human coronaviruses. A total of 12 hCoV and 17 hBoV were identified in the 217 influenza A positive samples. A higher proportion (61.5 %; 8/13) of SeasFluA/hBoV co-infections were identified in patients that were admitted either to a general ward or the intensive care unit compared to 44.3 % (66/149) of single SeasFlu A virus infections (OR 2.5 95 % CI 0.67–9.34, p = 0.17). In a stratified analysis, there was a trend towards higher association between FluA, hCoV and hBoV with increasing age (especially in patients aged 24–45 years and >65 year old). CONCLUSION: Our hCoV RT-PCR protocol appeared to be of adequate analytical sensitivity for diagnosis. More and larger studies are needed to confirm the role of hCoV, hBoV in causing severe disease when they co-infect with influenza A viruses.

Pan-human coronavirus and human bocavirus SYBR Green and TaqMan PCR assays; use in studying influenza A viruses co-infection and risk of hospitalization

Coronavirus can cause respiratory syndrome which to date has affected about twelve thousand individuals, especially in China. Coronavirus is interspecies and can also be transmitted from man to man, with an incubation ranging from 1 to 14 days. Human coronavirus infections can induce not only mild to severe respiratory diseases, but also inflammation, high fever, cough, acute respiratory tract infection and dysfunction of internal organs that may lead to death. Coronavirus infection (regardless of the various types of corona virus) is primarily attacked by immune cells including mast cells (MCs), which are located in the submucosa of the respiratory tract and in the nasal cavity and represent a barrier of protection against microorganisms. Viral activate MCs release early inflammatory chemical copounds including histamine and protease; while late activation provoke the generation of pro-inflammatory IL-1 family members including IL-1, IL-6 and IL-33. Here, we propose for the first time that inflammation by coronavirus maybe inhibited by anti-inflammatory cytokines belonging to the IL-1 family members.

Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy

After the outbreak of the severe acute respiratory syndrome (SARS) in the world in 2003, human coronaviruses (HCoVs) have been reported as pathogens that cause severe symptoms in respiratory tract infections. Recently, a new emerged HCoV isolated from the respiratory epithelium of unexplained pneumonia patients in the Wuhan seafood market caused a major disease outbreak and has been named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus causes acute lung symptoms, leading to a condition that has been named as "coronavirus disease 2019" (COVID-19). The emergence of SARS-CoV-2 and of SARS-CoV caused widespread fear and concern and has threatened global health security. There are some similarities and differences in the epidemiology and clinical features between these two viruses and diseases that are caused by these viruses. The goal of this work is to systematically review and compare between SARS-CoV and SARS-CoV-2 in the context of their virus incubation, originations, diagnosis and treatment methods, genomic and proteomic sequences, and pathogenic mechanisms.

Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV

After the outbreak of the severe acute respiratory syndrome (SARS) in the world in 2003, human coronaviruses (HCoVs) have been reported as pathogens that cause severe symptoms in respiratory tract infections. Recently, a new emerged HCoV isolated from the respiratory epithelium of unexplained pneumonia patients in the Wuhan seafood market caused a major disease outbreak and has been named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus causes acute lung symptoms, leading to a condition that has been named as “coronavirus disease 2019” (COVID-19). The emergence of SARS-CoV-2 and of SARS-CoV caused widespread fear and concern and has threatened global health security. There are some similarities and differences in the epidemiology and clinical features between these two viruses and diseases that are caused by these viruses. The goal of this work is to systematically review and compare between SARS-CoV and SARS-CoV-2 in the context of their virus incubation, originations, diagnosis and treatment methods, genomic and proteomic sequences, and pathogenic mechanisms.

Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats1-4. Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans5-7. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor-angiotensin converting enzyme II (ACE2)-as SARS-CoV.

A pneumonia outbreak associated with a new coronavirus of probable bat origin

In December 2019, a new pneumonia case emerged in the Wuhan, Hubei province of China which had an association with the novel Corona Virus (2019-nCoV). Most of the diagnosed cases had exposure to the Huanan seafood market. The present case is the successor of three earlier similar cases of Coronavirus known as SARS-Corona (Severe Acute Respiratory Syndrome) Virus and MERS-Corona Virus (Middle Eastern Respiratory Syndrome). The origin of the epidemic is still unknown and a lot of other uncertainties hinders the development of vaccines for the virus. As studies suggest that this virus is an evolution of SARS virus concerns are growing around the world as death toll has already surpassed that of SARS virus. This paper explores about the coronavirus, its relation to the similar SARS and MERS virus, its outreach and global impact according to the current scenario.

Corona virus: A novel outbreak

Summary The novel severe acute respiratory syndrome (SARS) coronavirus caused severe disease and heavy economic losses before apparently coming under complete control. Our understanding of the forces driving seasonal disappearance and recurrence of infectious diseases remains fragmentary, thus limiting any predictions about whether, or when, SARS will recur. It is true that most established respiratory pathogens of human beings recur in wintertime, but a new appreciation for the high burden of disease in tropical areas reinforces questions about explanations resting solely on cold air or low humidity. Seasonal variation in host physiology may also contribute. Newly emergent zoonotic diseases such as ebola or pandemic strains of influenza have recurred in unpredictable patterns. Most established coronaviruses exhibit winter seasonality, with a unique ability to establish persistent infections in a minority of infected animals. Because SARS coronavirus RNA can be detected in the stool of some individuals for at least 9 weeks, recurrence of SARS from persistently shedding human or animal reservoirs is biologically plausible.

Seasonality of infectious diseases and severe acute respiratory syndrome–what we don't know can hurt us

Comparative seasonalities of influenza A, B and 'common cold' coronaviruses - setting the scene for SARS-CoV-2 infections and possible unexpected host immune interactions

A newly identified betacoronavirus, human coronavirus EMC (HCoV-EMC), has been isolated from several patients with respiratory and renal disease in the Middle East. While only a few infected patients have been identified, the mortality of the infection is greater than 50%. Like its better-known cousin severe acute respiratory syndrome coronavirus (SARS-CoV), HCoV-EMC appears to have originated from bats. In a recent article in mBio, Müller et al. described several important differences between the two viruses [M. A. Müller et al., mBio 3(6):e00515-12, 2012, doi:10.1128/mBio.00515-12]. Unlike SARS-CoV, HCoV-EMC can directly infect bat cells. As important, HCoV-EMC does not enter cells using the SARS-CoV receptor, human angiotensin-converting receptor-2 (hACE2). These results provide a strong incentive for identifying the host cell receptor used by HCoV-EMC. Identification of the receptor will provide insight into the pathogenesis of pulmonary and renal disease and may also suggest novel therapeutic interventions.

Human Coronavirus EMC Is Not the Same as Severe Acute Respiratory Syndrome Coronavirus

Abstract Strains of human coronavirus (HCoV), namely HCoV-OC43, HCoV-229E, HCoV-NL63, and HCoV-HKU1, primarily infect the upper respiratory and gastrointestinal tracts and are the most common cause of non-rhinovirus-induced common cold in humans. Although the manifestations of coronavirus infection (i.e., rhinorrhea, sneezing, cough, nasal obstruction, and bronchitis) are generally self-limiting in healthy adults, certain strains such as HCoV-NL63 and HCoV-HKU1 can cause severe lower respiratory tract infection and febrile seizure, especially in infants, people of advanced age, and immunocompromised hosts. In 2003, a novel HCoV strain was identified as the causative agent of the severe acute respiratory syndrome (SARS) epidemic that began in Asia in 2002. The strain has hence been referred to as SARS-CoV. In addition, as recently as September 2012, another novel HCoV, human betacoronavirus 2c EMC2012, was identified as being the cause of fever, renal failure, pneumonia, and severe respiratory distress in two patients in the Middle East. Phylogenetic analysis has revealed highly conserved sequences of ORF1ab, spike, nucleocapsid, and envelope protein genes, but not membrane protein genes, between human betacoronavirus 2c EMC2012 and SARS-CoV. This review focuses on the differences in the genomes of certain HCoV strains, the pathogenesis of said strains, and recent developments in the establishment of therapeutic agents that might aid in the treatment of patients with such infections.

Human coronaviruses: Clinical features and phylogenetic analysis

1. Coronaviruses accounted for 1.6% (98/6272) of respiratory tract infections based on nasopharyngeal aspirate samples. 2. HCoV-OC43 was the most common coronavirus detected,followed by HCoV-NL63, CoVHKU1,and HCoV-229E. 3. Although CoV-HKU1 infections were most often associated with the upper respiratory tract, more severe illness (pneumonia,acute bronchiolitis, and asthmatic exacerbation) may occur, especially in those with underlying disease. In young children, CoV-HKU1 infection is associated with a high rate of febrile seizures (50%). 4. CoV-HKU1 and HCoV-OC43 infections peaked in winter, in contrast to HCoV-NL63, which mainly occurred in early summer and autumn, but was absent in winter. 5. Reverse transcriptase polymerase chain reaction is useful for the rapid diagnosis of coronavirus infections.

Epidemiology of coronavirus-associated respiratory tract infections and the role of rapid diagnostic tests: a prospective study.

Abstract Coronavirus infections have emerged as epidemic and pandemic threats in last two decades. After the H1N1 influenza pandemic in 2009, recently diagnosed novel betacoronavirus or severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has spread across 203 countries and territories in all 5 major continents. World Health Organization (WHO) declared this as a public health emergency of international concern on January 30, 2020. Subsequently on February 11, 2020 a new name was given to this disease i.e. COVID-19 by an expert group from WHO. As of April 12, 2020, 10:00 CET, GMT+2:00, 1,696,588 confirmed cases and 105,952 confirmed deaths have been reported to the WHO. (Coronavirus disease 2019, situation report 83). It possibly originated from a small animal market in Wuhan, China. A cluster of patients were admitted with unusual pneumonia not responding to treatment in various hospitals. Epidemiological, genomic analysis and correlation with other coronaviruses led to the isolation of new coronavirus, closely resembling the bat coronaviruses, from such patients in Wuhan. They were identified as the SARS-CoV-2. This virus infection presents as influenza like illness in the affected people. Fever, cough, respiratory distress with fatigue, diarrhea, nausea and vomiting are common symptoms seen in adults. This may progress on to respiratory distress, hypoxia, need for oxygen supplementation and ventilator support as seen in patients in the SARS-CoV-1 epidemic (2003) in Guangdong, China. The transmissibility of SARS-CoV-1 was less as compared to SARS-CoV-2 infection, and it was well controlled with good public health efforts. The present COVID-19 epidemic is still in the acceleration phase of 3 and 4 in various countries. Without any effective antiviral agents available at present, the need of the hour is early case detection, isolation of cases, use of good preventive care measures by the household contacts and in the hospital set up. The results of ongoing clinical trials on hydroxychloroquine, azithromycin alone or in combination and a new antiviral agent remdesivir may help to treat some of the infections. A need for effective vaccine is being seen an as good preventive strategy in this pandemic. However the results of clinical trials and incorporation of vaccines in public health programs is a long way to go.

An overview of coronaviruses including the SARS-2 coronavirus – Molecular biology, epidemiology and clinical implications

The seasonal cycle of respiratory viral diseases has been widely recognized for thousands of years, as annual epidemics of the common cold and influenza disease hit the human population like clockwork in the winter season in temperate regions. Moreover, epidemics caused by viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and the newly emerging SARS-CoV-2 occur during the winter months. The mechanisms underlying the seasonal nature of respiratory viral infections have been examined and debated for many years. The two major contributing factors are the changes in environmental parameters and human behavior. Studies have revealed the effect of temperature and humidity on respiratory virus stability and transmission rates. More recent research highlights the importance of the environmental factors, especially temperature and humidity, in modulating host intrinsic, innate, and adaptive immune responses to viral infections in the respiratory tract. Here we review evidence of how outdoor and indoor climates are linked to the seasonality of viral respiratory infections. We further discuss determinants of host response in the seasonality of respiratory viruses by highlighting recent studies in the field. Expected final online publication date for the Annual Review of Virology, Volume 7 is September 29, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Seasonality of Respiratory Viral Infections.

BACKGROUND We have described occurrence and clinical manifestations of human coronaviruses (HCoV) in hospitalized Norwegian children with respiratory tract infection (RTI) and compared them with a group of respiratory syncytial virus (RSV)-infected children. METHODS AND POPULATION We used in-house TaqMan multiplex real-time polymerase chain reaction to test nasopharyngeal samples from 536 RTI episodes in 452 children who were admitted during the 2006-2007 winter. Twenty-one viruses, including HCoV-OC43, HCoV-NL63, HCoV-229E, HCoV-HKU1, and RSV were tested. The amount of viral nucleic acid was recorded semiquantitatively based on the cycle threshold value. RESULTS A total of 665 positive polymerase chain reaction tests were recorded in 536 nasopharyngeal specimens. Coronavirus was found in 68 (12.7%): HCoV-OC43, n = 44 (8.2%), and HCoV-NL63, n = 24 (4.5%). Only RSV and rhinovirus were detected more frequently. Neither HCoV-229E nor HCoV-HKU1 was detected. Among children with HCoV-OC43, 73.0% tested positive for at least one other virus, compared with 41.2% with HCoV-NL63 and 40.3% with RSV (P = 0.03 and P < 0.01, respectively). Children with HCoV-OC43 and HCoV-NL63 were older than children with RSV (median age, 19 vs. 10 months, P = 0.01). Lower respiratory tract infection (LRTI) was half as common in children with HCoV-OC43 (48.6%) and HCoV-NL63 (47.1%) as in children with RSV (82.3%) (both P < 0.01). After adjusting for age, chronic disease, LRTI, and co-detection of other viruses in a multiple logistic regression analysis, HCoV was associated with a shorter fever period and shorter hospitalization time than RSV. CONCLUSIONS HCoV-OC43 and HCoV-NL63 are common among hospitalized Norwegian children with RTI. Children with HCoV-OC43 and HCoV-NL63 have LRTI less frequently and may need a shorter hospital stay than children with RSV.

Coronavirus causes lower respiratory tract infections less frequently than RSV in hospitalized Norwegian children.

Human coronaviruses (HCoVs) cause mild to severe respiratory diseases. Six types of HCoVs have been discovered, the most recent one termed the Middle East respiratory syndrome coronavirus (MERS-CoV). The aim of this study is to monitor the circulation of HCoV types in the population during 2015–2016 in Israel. HCoVs were detected by real-time PCR analysis in 1910 respiratory samples, collected from influenza-like illness (ILI) patients during the winter sentinel influenza survey across Israel. Moreover, 195 HCoV-positive samples from hospitalized patients were detected during one year at Soroka University Medical Center. While no MERS-CoV infections were detected, 10.36% of patients in the survey were infected with HCoV-OC43 (43.43%), HCoV-NL63 (44.95%), and HCoV-229E (11.62%) viruses. The HCoVs were shown to co-circulate with respiratory syncytial virus (RSV) and to appear prior to influenza virus infections. HCoV clinical symptoms were more severe than those of RSV infections but milder than influenza symptoms. Hospitalized patients had similar HCoV types percentages. However, while it was absent from the public winter survey, 22.6% of the patients were HCoV-HKU1 positives, mainly during the spring-summer period.

Human Coronavirus Infections in Israel: Epidemiology, Clinical Symptoms and Summer Seasonality of HCoV-HKU1

Abstract Human rhinovirus and influenza virus infections of the upper airway lead to colds and the flu and can trigger exacerbations of lower airway diseases including asthma and chronic obstructive pulmonary disease. Novel diagnostic and therapeutic targets are still needed to differentiate between the cold and the flu, since the clinical course of influenza can be severe while that of rhinovirus is usually more mild. In our investigation of influenza and rhinovirus infection of human respiratory epithelial cells, we used a systems approach to identify the temporally changing patterns of host gene expression from these viruses. After infection of human bronchial epithelial cells (BEAS-2B) with rhinovirus, influenza virus or co-infection with both viruses, we studied the time-course of host gene expression changes over three days. We modeled host responses to these viral infections with time and documented the qualitative and quantitative differences in innate immune activation and regulation.

A systems approach to understanding human rhinovirus and influenza virus infection

Coronaviruses (CoVs) belong to the family of Coronaviridae, the order Nidovirales, and the genus Coronavirus. They are the largest group of viruses causing respiratory and gastrointestinal infections. Morphologically, CoVs are enveloped viruses containing a non-segmented positive-sense, single-stranded ribonucleic acid (RNA) viruses. CoVs are categorized into four important genera that include Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus. A novel member of human CoV that has recently emerged in Wuhan, China, is now formally named as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). This is a unique strain of RNA viruses that have not been previously observed in humans. The virus has wide host adaptability and is capable of causing severe diseases in humans, masked palm civets, mice, dogs, cats, camels, pigs, chickens, and bats. The SARS-CoV-2 typically causes respiratory and gastrointestinal sickness in both humans and animals. It can be transmitted through aerosols and direct/indirect contact, as well as during medical cases and laboratory sample handling. Specific structural proteins, which might be found on the surface of the virus, play an important role in the pathogenesis and development of the complications. The disease is characterized by distinct medical signs and symptoms that include high fever, chills, cough, and shortness of breath or difficulty in breathing. The infected people may also present with other symptoms such as diarrhea, myalgia, fatigue, expectoration, and hemoptysis. It is important from the public health and economic point of view as it affects the growth of the country, which is majorly attributed to the restriction in the movement of the people and the cost associated with the control and prevention of the disease. Since there is no specific therapeutic intervention nor a vaccine available against the virus, supportive management and treatment with non-specific therapeutic agents (repurposed drugs) may provide relief to the patients. Some preventive strategies of the disease include blocking the routes of transmission of the infections, disinfection of instruments used during medical case handling, using personal protective equipment, proper and early diagnosis of the disease, avoiding contact with the sick patients, and quarantine of the infected/exposed people.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): An Update

It: Two Coronaviruses, HCoV-229E and HCoV-OC43, causing generally mild respiratory tract infections in humans, were described in the XX c Pandemic Coronaviruses were first discovered as late as in the XXI c : SARS-HCoV in 2002 – causing severe respiratory tract infections (SARS) in China;MERS-HCoV in 2012 – circulating mostly on the Arabian Peninsula The SARS epidemic ended in 2004 resulting in morbidity of >8000 and >770 deaths, while the MERS epidemic is still ongoing (>2000 ill, >700 deaths) although its intensity decreased Both viruses are zoonotic and require at least two “host jumps” for the transmission of the infection to humans: for HCoV-SARS – from bat to palm civet and then to human;for HCoV-MERS – from bats to camels and subsequently to humans Primary mode of transmission is droplet in close contact (<1 m), but both viruses remain active in aerosol (up to 24 h), so infection can be also spread by air (ventilation) The ability for human-to-human transmission is higher for HCoV-SARS than for HCoV-MERS (8 generations vs 4, respectively) Moreover, there are differences in genome structure and pathogenic mechanisms: different receptor, cell entry mechanism, different way of host response modulation (e g inhibition of IFNβ cascade), etc Probably, these differences influence the overall manifestation of the disease in humans Infection caused by HCoV-MERS might manifest itself as ARDS, a mild-mannered and asymptomatic disease HCoV-SARS infections seem to be associated with severe disease only In this paper, a comparison of the structure of these viruses, the mechanisms underlying their ability to cross the interspecies barrier and to multiply in the human body, including modulation of IFNβ cascade, as well as routes of infection transmission and symptoms caused, were presented

Pandemic Human Coronavirus – Characterization and Comparison of Selected Properties of Hcov-sars and Hcov-mers

Seasonality of Respiratory Viral Infections

Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats(1–4). Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans(5–7). Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.

Since the SARS outbreak 18 years ago, a large number of severe acute respiratory syndrome related coronaviruses (SARSr-CoV) have been discovered in their natural reservoir host, bats1-4. Previous studies indicated that some of those bat SARSr-CoVs have the potential to infect humans5-7. Here we report the identification and characterization of a novel coronavirus (nCoV-2019) which caused an epidemic of acute respiratory syndrome in humans, in Wuhan, China. The epidemic, started from December 12th, 2019, has caused 198 laboratory confirmed infections with three fatal cases by January 20th, 2020. Full-length genome sequences were obtained from five patients at the early stage of the outbreak. They are almost identical to each other and share 79.5% sequence identify to SARS-CoV. Furthermore, it was found that nCoV-2019 is 96% identical at the whole genome level to a bat coronavirus. The pairwise protein sequence analysis of seven conserved non-structural proteins show that this virus belongs to the species of SARSr-CoV. The nCoV-2019 virus was then isolated from the bronchoalveolar lavage fluid of a critically ill patient, which can be neutralized by sera from several patients. Importantly, we have confirmed that this novel CoV uses the same cell entry receptor, ACE2, as SARS-CoV.

Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin

Human coronaviruses (HCoV) OC43, 229E, NL63, and HKU1 are common respiratory viruses which cause various respiratory diseases, including pneumonia. There is a paucity of evidence on the epidemiology and clinical manifestations of these four HCoV strains worldwide. We collected 11,399 throat swabs from hospitalized children with acute respiratory tract infection from July 2009 to June 2016 in Guangzhou, China. These were tested for four strains of HCoV infection using real-time polymerase chain reaction (PCR). HCoV-positive patients were then tested for 11 other respiratory pathogens. 4.3% (489/11399) of patients were positive for HCoV, of which 3.0% were positive for OC43 (346/11399), 0.6% for 229E (65/11399), 0.5% for NL63 (60/11399), and 0.3% for HKU1 (38/11399). Patients aged 7–12 months had the highest prevalence of HCoV and OC43 when compared with other age groups (p < 0.001). The peak seasons of infection varied depending on the HCoV strain. Patients infected with a single strain of HCoV infection were less likely to present fever (≥ 38 °C) (p = 0.014) and more likely to present pulmonary rales (p = 0.043) than those co-infected with more than one HCoV strain or other respiratory pathogens. There were also significant differences in the prevalence of certain symptoms, including coughing (p = 0.032), pneumonia (p = 0.026), and abnormal pulmonary rales (p = 0.002) according to the strain of HCoV detected. This retrospective study of the prevalence of four HCoV strains and clinical signs among a large population of pediatric patients in a subtropical region of China provides further insight into the epidemiology and clinical features of HCoV.

Epidemiology and clinical characteristics of human coronaviruses OC43, 229E, NL63, and HKU1: a study of hospitalized children with acute respiratory tract infection in Guangzhou, China

BACKGROUND Multiplex molecular assays now make it possible for clinical laboratories to detect human coronaviruses (HCoVs). We investigated the clinical characteristics of HCoV-OC43 and HCoV-NL63 in patients <5 years of age during a recent coronavirus season. METHODS Respiratory viruses were detected using a multiplex molecular assay at St. Louis Children`s Hospital starting in November 2012. We analyzed demographic and clinical data from all patients <5 years of age with solo detection of HCoV-OC43 (n = 52) and HCoV-NL63 (n = 44) and for comparison, samples of children with respiratory syncytial virus, parainfluenza virus and picornaviruses. RESULTS During the study period, HCoV-OC43 (4%) was the 5th and HCoV-NL63 the 8th (2%) most common respiratory virus. Coinfections were detected in 35% and 38% of children with HCoV-OC43 and HCoV-NL63, respectively. Croup was more common with HCoV-NL63 (30%) than with HCoV-OC43 (2%). Lower respiratory tract infection occurred in 33% of children with HCoV-OC43 and 25% of children with HCoV-NL63. Severe illness was less common in HCoV-NL63, HCoV-OC43 and parainfluenza virus (14%, each) compared with respiratory syncytial virus (30%) and picornaviruses (26%; P = 0.055 for HCoVs combined compared with the other respiratory viruses) and occurred mainly in those with underlying medical conditions. CONCLUSIONS Infections caused by HCoV-OC43 and HCoV-NL63 are common and include some with lower respiratory tract involvement and severe disease, especially in children with underlying medical conditions. Overall, a substantial burden of disease associated with both HCoV-OC43 and HCoV-NL63 was observed for hospitalized children <5 years of age.

Characterization of human coronavirus OC43 and human coronavirus NL63 infections among hospitalized children <5 years of age.

The pandemic potential of the novel coronavirus (nCoV) that emerged in Wuhan, China, during December 2019 is strongly tied to the number and contagiousness of undocumented human infections. Here we present findings from a proactive longitudinal sampling study of acute viral respiratory infections that documents rates of asymptomatic infection and clinical care seeking for seasonal coronavirus. We find that the majority of infections are asymptomatic by most symptom definitions and that only 4% of individuals experiencing a seasonal coronavirus infection episode sought medical care for their symptoms. These numbers indicate that a very high percentage of seasonal coronavirus infections are undocumented and provide a reference for understanding the spread of the emergent nCoV.

Direct Measurement of Rates of Asymptomatic Infection and Clinical Care-Seeking for Seasonal Coronavirus

Since December, 2019, an outbreak of pneumonia caused by the new coronavirus (2019-nCoV) has hit the city of Wuhan in the Hubei Province. With the continuous development of the epidemic, it has become a national public health crisis and calls for urgent antiviral treatments or vaccines. The spike protein on the coronavirus envelope is critical for host cell infection and virus vitality. Previous studies showed that 2019-nCoV is highly homologous to human SARS-CoV and attaches host cells though the binding of the spike receptor binding domain (RBD) domain to the angiotensin-converting enzyme II (ACE2). However, the molecular mechanisms of 2019-nCoV binding to human ACE2 and evolution of 2019-nCoV remain unclear. In this study, we have extensively studied the RBD-ACE2 complex, spike protein, and free RBD systems of 2019-nCoV and SARS-CoV using protein-protein docking and molecular dynamics (MD) simulations. It was shown that the RBD-ACE2 binding free energy for 2019-nCoV is significantly lower than that for SARS-CoV, which is consistent with the fact that 2019-nCoV is much more infectious than SARS-CoV. In addition, the spike protein of 2019-nCoV shows a significantly lower free energy than that of SARS-CoV, suggesting that 2019-nCoV is more stable and able to survive a higher temperature than SARS-CoV. This may also provide insights into the evolution of 2019-nCoV because SARS-like coronaviruses are thought to have originated in bats that are known to have a higher body-temperature than humans. It was also revealed that the RBD of 2019-nCoV is much more flexible especially near the binding site and thus will have a higher entropy penalty upon binding ACE2, compared to the RBD of SARS-CoV. That means that 2019-nCoV will be much more temperature-sensitive in terms of human infection than SARS-CoV. With the rising temperature, 2019-nCoV is expected to decrease its infection ability much faster than SARS-CoV, and get controlled more easily. The present findings are expected to be helpful for the disease prevention and control as well as drug and vaccine development of 2019-nCoV.

Molecular mechanism of evolution and human infection with the novel coronavirus (2019-nCoV)

The human coronavirus (HCoV) contains HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV- HKU1, SARS-CoV and MERS-CoV. HCoV-229E, HCoV-NL63, HCoV-OC43 and HCoV-HKU1 are pathogens of common cold. During 2002-2003, a new coronavirus, the SARS-CoV, was found to be the cause of an acute, severe frequently fatal respiratory disease with prominent systemic symptoms (severe acute respiratory syndrome). The outbreak originated in south- ern China, probably following transmission from an animal in animal markets or bats to hu- mans. In 2012, some cases of novel coronavirus infection were reported in Arabian Peninsula with pneumonia and acute kidney injury. This novel coronavirus has been named Middle East respiratory syndrome coronavirus (MERS-CoV). The virus probably has come from camels and bats. I describe here about coronaviruses that have wide disease spectrum.from common colds to severe fatal illness as emerging infectious diseases.

SARS, MERS and coronavirus infections.

Severe acute respiratory syndrome (SARS) is caused by the SARS-associated coronavirus (SARS-CoV), which uses angiotensin-converting enzyme 2 (ACE2) as its receptor for cell entry. A group of SARS-like CoVs (SL-CoVs) has been identified in horseshoe bats. SL-CoVs and SARS-CoVs share identical genome organizations and high sequence identities, with the main exception of the N terminus of the spike protein (S), known to be responsible for receptor binding in CoVs. In this study, we investigated the receptor usage of the SL-CoV S by combining a human immunodeficiency virus-based pseudovirus system with cell lines expressing the ACE2 molecules of human, civet, or horseshoe bat. In addition to full-length S of SL-CoV and SARS-CoV, a series of S chimeras was constructed by inserting different sequences of the SARS-CoV S into the SL-CoV S backbone. Several important observations were made from this study. First, the SL-CoV S was unable to use any of the three ACE2 molecules as its receptor. Second, the SARS-CoV S failed to enter cells expressing the bat ACE2. Third, the chimeric S covering the previously defined receptor-binding domain gained its ability to enter cells via human ACE2, albeit with different efficiencies for different constructs. Fourth, a minimal insert region (amino acids 310 to 518) was found to be sufficient to convert the SL-CoV S from non-ACE2 binding to human ACE2 binding, indicating that the SL-CoV S is largely compatible with SARS-CoV S protein both in structure and in function. The significance of these findings in relation to virus origin, virus recombination, and host switching is discussed.

Difference in receptor usage between severe acute respiratory syndrome (SARS) coronavirus and SARS-like coronavirus of bat origin.

were identified beginning with the discovery of SARS-CoV in 2002. With the recent detection of SARS-CoV-2, there are now seven human coronaviruses. Those that cause mild diseases are the 229E, OC43, NL63 and HKU1, and the pathogenic species are SARS-CoV, MERS-CoV and SARS-CoV-2 Coronaviruses (order Nidovirales, family Coronaviridae, and subfamily Orthocoronavirinae) are spherical (125nm diameter), and enveloped with club-shaped spikes on the surface giving the appearance of a solar corona. Within the helically symmetrical nucleocapsid is the large positive sense, single stranded RNA. Of the four coronavirus genera (α,ß,Î³,Î´), human coronaviruses (HCoVs) are classified under α-CoV (HCoV-229E and NL63) and ß-CoV (MERS-CoV, SARS-CoV, HCoVOC43 and HCoV-HKU1). SARS-CoV-2 is a ß-CoV and shows fairly close relatedness with two bat-derived CoV-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. Even so, its genome is similar to that of the typical CoVs. SARS-CoV and MERS-CoV originated in bats, and it appears to be so for SARS-CoV-2 as well. The possibility of an intermediate host facilitating the emergence of the virus in humans has already been shown with civet cats acting as intermediate hosts for SARS-CoVs, and dromedary camels for MERS-CoV. Human-to-human transmission is primarily achieved through close contact of respiratory droplets, direct contact with the infected individuals, or by contact with contaminated objects and surfaces. The coronaviral genome contains four major structural proteins: the spike (S), membrane (M), envelope (E) and the nucleocapsid (N) protein, all of which are encoded within the 3' end of the genome. The S protein mediates attachment of the virus to the host cell surface receptors resulting in fusion and subsequent viral entry. The M protein is the most abundant protein and defines the shape of the viral envelope. The E protein is the smallest of the major structural proteins and participates in viral assembly and budding. The N protein is the only one that binds to the RNA genome and is also involved in viral assembly and budding. Replication of coronaviruses begin with attachment and entry. Attachment of the virus to the host cell is initiated by interactions between the S protein and its specific receptor. Following receptor binding, the virus enters host cell cytosol via cleavage of S protein by a protease enzyme, followed by fusion of the viral and cellular membranes. The next step is the translation of the replicase gene from the virion genomic RNA and then translation and assembly of the viral replicase complexes. Following replication and subgenomic RNA synthesis, encapsidation occurs resulting in the formation of the mature virus. Following assembly, virions are transported to the cell surface in vesicles and released by exocytosis.

Properties of Coronavirus and SARS-CoV-2

OBJECTIVE Human infections with zoonotic coronavirus contain emerging and reemerging pathogenic characteristics which have raised great public health concern. This study aimed at investigating the global prevalence, biological and clinical characteristics of novel coronavirus, Wuhan China (2019-nCoV), Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection outbreaks. MATERIALS AND METHODS The data on the global outbreak of "2019-nCoV, SARS-CoV, and MERS-CoV" were obtained from World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), concerned ministries and research institutes. We also recorded the information from research documents published in global scientific journals indexed in ISI Web of Science and research centers on the prevalence, biological and clinical characteristics of 2019-nCoV, SARS-CoV, and MERS-CoV. RESULTS Worldwide, SARS-CoV involved 32 countries, with 8422 confirmed cases and 916 (10.87%) casualties from November 2002 to August 2003. MERS-CoV spread over 27 states, causing 2496 cases and 868 (34.77%) fatalities during the period April 2012 to December 2019. However, the novel coronavirus 2019-nCoV spread swiftly the global borders of 27 countries. It infected 34799 people and resulted in 724 (2.08%) casualties during the period December 29, 2019 to February 7, 2020. The fatality rate of coronavirus MERS-CoV was (34.77%) higher than SARS-CoV (10.87%) and 2019-nCoV (2.08%); however, the 2019-nCoV transmitted rapidly in comparison to SARS-CoV and MERS-CoV. CONCLUSIONS The novel coronavirus 2019-nCoV has diverse epidemiological and biological characteristics, making it more contagious than SARS-CoV and MERS-CoV. It has affected more people in a short time period compared to SARS-CoV and MERS-CoV, although the fatality rate of MERS-CoV was higher than SARS-CoV and 2019-nCoV. The major clinical manifestations in coronavirus infections 2019-nCoV, MERS-CoV, and SARS CoV are fever, chills, cough, shortness of breath, generalized myalgia, malaise, drowsy, diarrhea, confusion, dyspnea, and pneumonia. Global health authorities should take immediate measures to prevent the outbreaks of such emerging and reemerging pathogens across the globe to minimize the disease burden locally and globally.

Novel coronavirus 2019-nCoV: prevalence, biological and clinical characteristics comparison with SARS-CoV and MERS-CoV.

Seasonal Influenza Vaccination and the Heightened Risk of Coronavirus and Other Pandemic Virus Infections: Fact or Fiction?

Detailed genomic and structure-based analysis of a new coronavirus, namely 2019-nCoV, showed that the new virus is a new type of bat coronavirus and is genetically fairly distant from the human SARS coronavirus. Structure analysis of the spike (S) protein of this new virus showed that its S protein only binds weakly to the ACE2 receptor on human cells whereas the human SARS coronavirus exhibits strongly affinity to the ACE receptor. These findings suggest that the new virus does not readily transmit between humans and should theoretically not able to cause very serious human infection. These data are important to guide design of infection control policy and inform the public on the nature of threat imposed by 2019-nCov when results of direct laboratory tests on this virus are not expected to be available in the near future.

Genomic and protein structure modelling analysis depicts the origin and infectivity of 2019-nCoV, a new coronavirus which caused a pneumonia outbreak in Wuhan, China

The positive-strand RNA viruses, severe acute respiratory syndrome coronavirus (SARS-CoV) and recently emerged COVID-19 epidemics, demonstrated the transmission capability of the coronaviruses by crossing the species barrier and emergence in humans. The source of coronavirus disease 2019 (COVID-19) is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), firstly reported in December 2019 at Wuhan, China. COVID-19 is a kind of viral pneumonia. The outbreak of SARS-CoV-2 (COVID-19) has been reported as the introduction of the third highly pathogenic coronavirus which crossed the species barrier and spread into the human population. Severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) were the first two epidemic viruses, respectively, in the twenty-first century. Introduction of the 2019 novel coronaviruses (2019-nCoV) in human population is a worldwide concern, and this might have generated via RNA recombination among the previous reported coronaviruses. The COVID-19 is spreading in an alarming rate, and till date no vaccine or specific medicines are available in the market. The newly emerged coronavirus COVID-19 is strongly related to SARS-CoV except little dissimilarity. In this chapter, we will discuss about the alterations and variations in antigenicity, structural changes, and RNA recombination which might be responsible for the COVID-19 emergence.

Emergence and Reemergence of Severe Acute Respiratory Syndrome (SARS) Coronaviruses

HCoV-NL63 and HCoV-229E are two of the four human coronaviruses that circulate worldwide. These two viruses are unique in their relationship towards each other. Phylogenetically, the viruses are more closely related to each other than to any other human coronavirus, yet they only share 65% sequence identity. Moreover, the viruses use different receptors to enter their target cell. HCoV-NL63 is associated with croup in children, whereas all signs suggest that the virus probably causes the common cold in healthy adults. HCoV-229E is a proven common cold virus in healthy adults, so it is probable that both viruses induce comparable symptoms in adults, even though their mode of infection differs. Here, we present an overview of the current knowledge on both human coronaviruses, focusing on similarities and differences.

Human Coronaviruses 229E and NL63: Close Yet Still So Far

Background. Human coronavirus NL63 (HCoV-NL63) is a recently discovered human coronavirus found to cause respiratory illness in children and adults that is distinct from the severe acute respiratory syndrome (SARS) coronavirus and human coronaviruses 229E (HCoV-229E) and OC43 (HCoV-OC43). Methods. We investigated the role that HCoV-NL63, HCoV-OC43, and HCoV-229E played in children hospitalized with fever and acute respiratory symptoms in Hong Kong during the period from August 2001 through August 2002. Results. Coronavirus infections were detected in 26 (4.4%) of 587 children studied; 15 (2.6%) were positive for HCoV-NL63, 9 (1.5%) were positive for HCoV-OC43, and 2 (0.3%) were positive for HCoV-229E. In addition to causing upper respiratory disease, we found that HCoV-NL63 can present as croup, asthma exacerbation, febrile seizures, and high fever. The mean age (± standard deviation [SD]) of the infected children was 30.7 ± 19.8 months (range, 6–57 months). The mean maximum temperature (±SD) for the 12 children who were febrile was 39.3°C ± 0.9°C, and the mean total duration of fever (±SD) for all children was 2.6 ± 1.2 days (range, 1–5 days). HCoV-NL63 infections were noted in the spring and summer months of 2002, whereas HCoV-OC43 infection mainly occurred in the fall and winter months of 2001. HCoV-NL63 viruses appeared to cluster into 2 evolutionary lineages, and viruses from both lineages cocirculated in the same season. Conclusions. HCoV-NL63 is a significant pathogen that contributes to the hospitalization of children, and it was estimated to have caused 224 hospital admissions per 100,000 population aged ⩽6 years each year in Hong Kong.

Human Coronavirus NL63 Infection and Other Coronavirus Infections in Children Hospitalized with Acute Respiratory Disease in Hong Kong, China

Coronaviruses (CoVs) are positive-strand RNA viruses with the largest genome among all RNA viruses. They are able to infect many host, such as mammals or birds. Whereas CoVs were identified 1930s, they became known again in 2003 as the agents of the Severe Acute Respiratory Syndrome (SARS). The spike protein is thought to be essential in the process of CoVs entry, because it is associated with the binding to the receptor on the host cell. It is also involved in cell tropism and pathogenesis. Receptor recognition is the crucial step in the infection. CoVs are able to bind a variety of receptors, although the selection of receptor remains unclear. Coronaviruses were initially believed to enter cells by fusion with the plasma membrane. Further studies demonstrated that many of them involve endocytosis through clathrin-dependent, caveolae-dependent, clathrin-independent, as well as caveolae-independent mechanisms. The aim of this review is to summarise current knowledge about coronaviruses, focussing especially on CoVs entry into the host cell. Advances in understanding coronaviruses replication strategy and the functioning of the replicative structures are also highlighted. The development of host-directed antiviral therapy seems to be a promising way to treat infections with SARS-CoV or other pathogenic coronaviruses. There is still much to be discovered in the inventory of pro- and anti-viral host factors relevant for CoVs replication. The latest pandemic danger, originating from China, has given our previously prepared work even more of topicality.

Coronaviruses fusion with the membrane and entry to the host cell.

After the outbreak of the middle east respiratory syndrome (MERS) worldwide in 2012. Currently, a novel human coronavirus has caused a major disease outbreak, and named corona virus disease 2019 (COVID-19). The emergency of MRES-COV and COVID-19 has caused global panic and threatened health security. Unfortunately, the similarities and differences between the two coronavirus diseases remain to be unknown. The aim of this study, therefore, is to perform a systematic review to compare epidemiological, clinical and laboratory features of COVID-19 and MERS-COV population. We searched PubMed, EMBASE and Cochrane Register of Controlled Trials database to identify potential studies reported COVID-19 or MERS-COV. Epidemiological, clinical and laboratory outcomes, the admission rate of intensive cure unit (ICU), discharge rate and fatality rate were evaluated using GraphPad Prism software. Thirty-two studies involving 3770 patients (COVID-19 = 1062, MERS-COV = 2708) were included in this study. The present study revealed that compared with COVID-19 population, MERS-COV population had a higher rate of ICU admission, discharge and fatality and longer incubation time. It pointed out that fever, cough and generalised weakness and myalgia were main clinical manifestations of both COVID-19 and MERS-COV, whereas ARDS was main complication. The most effective drug for MERS-COV is ribavirin and interferon.

Clinical Characteristics of Two Human to Human Transmitted Coronaviruses: Corona Virus Disease 2019 versus Middle East Respiratory Syndrome Coronavirus.

OBJECTIVE: Human infections with zoonotic coronavirus contain emerging and reemerging pathogenic characteristics which have raised great public health concern. This study aimed at investigating the global prevalence, biological and clinical characteristics of novel coronavirus, Wuhan China (2019-nCoV), Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection outbreaks. MATERIALS AND METHODS: The data on the global outbreak of "2019-nCoV, SARS-CoV, and MERS-CoV" were obtained from World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), concerned ministries and research institutes. We also recorded the information from research documents published in global scientific journals indexed in ISI Web of Science and research centers on the prevalence, biological and clinical characteristics of 2019-nCoV, SARS-CoV, and MERS-CoV. RESULTS: Worldwide, SARS-CoV involved 32 countries, with 8422 confirmed cases and 916 (10.87%) casualties from November 2002 to August 2003. MERS-CoV spread over 27 states, causing 2496 cases and 868 (34.77%) fatalities during the period April 2012 to December 2019. However, the novel coronavirus 2019-nCoV spread swiftly the global borders of 27 countries. It infected 34799 people and resulted in 724 (2.08%) casualties during the period December 29, 2019 to February 7, 2020. The fatality rate of coronavirus MERS-CoV was (34.77%) higher than SARS-CoV (10.87%) and 2019-nCoV (2.08%); however, the 2019-nCoV transmitted rapidly in comparison to SARS-CoV and MERS-CoV. CONCLUSIONS: The novel coronavirus 2019-nCoV has diverse epidemiological and biological characteristics, making it more contagious than SARS-CoV and MERS-CoV. It has affected more people in a short time period compared to SARS-CoV and MERS-CoV, although the fatality rate of MERS-CoV was higher than SARS-CoV and 2019-nCoV. The major clinical manifestations in coronavirus infections 2019-nCoV, MERS-CoV, and SARS CoV are fever, chills, cough, shortness of breath, generalized myalgia, malaise, drowsy, diarrhea, confusion, dyspnea, and pneumonia. Global health authorities should take immediate measures to prevent the outbreaks of such emerging and reemerging pathogens across the globe to minimize the disease burden locally and globally.

Novel coronavirus 2019-nCoV: prevalence, biological and clinical characteristics comparison with SARS-CoV and MERS-CoV

PURPOSE: To compare the frequency and the severity of influenza and respiratory syncytial viruses (RSV) infections among children < 24 months hospitalized with respiratory symptoms. METHODS: Data from a prospective study conducted during the peak of five influenza seasons in the Province of Quebec, Canada were used. RESULTS: We detected higher frequency of RSV compared to influenza viruses (55.3% vs. 16.3%). Radiologically confirmed pneumonia was significantly more frequent in children with RSV (39%) than those with influenza (18%) and the clinical course was more severe in RSV than influenza-infected children, especially among infants < 3 months. CONCLUSION: Even during peak weeks of influenza season, we found a higher burden and severity of RSV compared with influenza virus disease in hospitalized children < 24 months.

Respiratory syncytial virus contributes to more severe respiratory morbidity than influenza in children < 2 years during seasonal influenza peaks

Emerging of infectious diseases such as severe acute respiratory syndrome (SARS) which is a present major menace to public health, although intense research efforts, how, when, and where new diseases are appearing which still a source of considerable uncertainty is A serious respiratory disease was recently reported in Wuhan, Hubei province, china At least 1,975cases had been reported till 25 January 2020, since the patient was hospitalized on 12 December 2019 Epidemiology research has suggested that the beginning of the virus was associated with seafood contact in Wuhan Here we considered a single patient who was one of the workers in the market and was admitted to Central Hospital of Wuhan on 26 December of 2019 He was experiencing severe respiratory syndrome which is included with dizziness and cough After analysis, it was identified as a new RNA virus strain, from the family Coronaviridae, which is generally designated as WH-Human 1’ Corona virus is also referred to 2019 –nCoV The phylogenetic analysis started that this virus was mostly closely selected to a group of SARS and MERS like corona virus these are previously been found in bats in China

Corona virus-An upadated review

The novel coronavirus pneumonia (NCP) continues to spread throughout the country, and the prevention and control of the epidemic has entered a critical period. However, southern cities with severe outbreaks are about to enter the seasonal influenza season. We should strengthen the epidemiological investigation, optimize the laboratory testing strategy, take effective measures, strengthen the prevention and control of influenza epidemic, and minimize the interference to the new coronavirus epidemic.

[Be alert to superposed effect of seasonal influenza while fighting against novel coronavirus pneumonia].

Lower respiratory tract symptoms during seasonal coronavirus infections in children are associated with RSV co-detection and increased levels of Haemophilus and Fusobacterium species.

Symptomatology during seasonal coronavirus infections in children is associated with viral and bacterial co-detection

SUMMARYIn recent decades, several new diseases have emerged in different geographical areas, with pathogens including Ebola virus, Zika virus, Nipah virus, and coronaviruses (CoVs). Recently, a new type of viral infection emerged in Wuhan City, China, and initial genomic sequencing data of this virus do not match with previously sequenced CoVs, suggesting a novel CoV strain (2019-nCoV), which has now been termed severe acute respiratory syndrome CoV-2 (SARS-CoV-2). Although coronavirus disease 2019 (COVID-19) is suspected to originate from an animal host (zoonotic origin) followed by human-to-human transmission, the possibility of other routes should not be ruled out. Compared to diseases caused by previously known human CoVs, COVID-19 shows less severe pathogenesis but higher transmission competence, as is evident from the continuously increasing number of confirmed cases globally. Compared to other emerging viruses, such as Ebola virus, avian H7N9, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 has shown relatively low pathogenicity and moderate transmissibility. Codon usage studies suggest that this novel virus has been transferred from an animal source, such as bats. Early diagnosis by real-time PCR and next-generation sequencing has facilitated the identification of the pathogen at an early stage. Since no antiviral drug or vaccine exists to treat or prevent SARS-CoV-2, potential therapeutic strategies that are currently being evaluated predominantly stem from previous experience with treating SARS-CoV, MERS-CoV, and other emerging viral diseases. In this review, we address epidemiological, diagnostic, clinical, and therapeutic aspects, including perspectives of vaccines and preventive measures that have already been globally recommended to counter this pandemic virus.

Coronavirus Disease 2019-COVID-19.

Coronavirus is a large family of viruses that infect mammals and birds. Coronaviruses are known to cross barrier species and infect new ones. In the past twenty years, we witnessed the emergence of three different coronaviruses, the latest one being the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) responsible for the COVID-19 (covid disease 19) pandemic. Coronaviruses are enveloped virus with a long positive sense RNA genome. Like all viruses, they hijack the cellular machinery to replicate and produce new virions. There is no approved vaccine or specific antiviral molecule against coronaviruses but with the urgency to treat COVID-19, several candidate therapies are currently investigated.

[Coronavirus, emerging viruses].

Those downplaying the coronavirus ignore our lack of immunity and vaccines

This really is nothing like flu

Human coronaviruses (HCoVs) are responsible for respiratory tract infections ranging from common colds to severe acute respiratory syndrome. HCoV-NL63 and HCoV-229E are two of the four HCoVs that circulate worldwide and are close phylogenetic relatives. HCoV infections can lead to hospitalization of children, elderly individuals, and immunocompromised patients. Globally, approximately 5% of all upper and lower respiratory tract infections in hospitalized children are caused by HCoV-229E and HCoV-NL63. The latter virus has recently been associated with the childhood disease croup. Thus, differentiation between the two viruses is relevant for epidemiology studies. The aim of this study was to develop a double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) as a potential tool for identification and differentiation between HCoV-NL63 and HCoV-229E. The nucleocapsid (N) proteins of HCoV-NL63 and HCoV-229E were expressed in an Escherichia coli system and used to immunize mice in order to obtain monoclonal antibodies (MAbs) specific for each virus. Three specific MAbs to HCoV-NL63, one MAb specific to HCoV-229E, and four MAbs that recognized both viruses were obtained. After their characterization, three MAbs were selected in order to develop a differential DAS-ELISA. The described assay could detect up to 3 ng/ml of N protein and 50 50% tissue culture infective doses/ml of virus stock. No cross-reactivity with other human coronaviruses or closely related animal coronaviruses was found. The newly developed DAS-ELISA was species specific, and therefore, it could be considered a potential tool for detection and differentiation of HCoV-NL63 and HCoV-229E infections.

Differentiation between human coronaviruses NL63 and 229E using a novel double-antibody sandwich enzyme-linked immunosorbent assay based on specific monoclonal antibodies.

Coronaviruses (CoVs) are a large family of enveloped, positive-strand RNA viruses Four human CoVs (HCoVs), the non-severe acute respiratory syndrome (SARS)-like HCoVs (namely HCoV 229E, NL63, OC43, and HKU1), are globally endemic and account for a substantial fraction of upper respiratory tract infections Non-SARS-like CoV can occasionally produce severe diseases in frail subjects but do not cause any major (fatal) epidemics In contrast, SARS like CoVs (namely SARS-CoV and Middle-East respiratory syndrome coronavirus, MERS-CoV) can cause intense short-lived fatal outbreaks The current epidemic caused by the highly contagious SARS-CoV-2 and its rapid spread globally is of major concern There is scanty knowledge on the actual pandemic potential of this new SARS-like virus It might be speculated that SARS-CoV-2 epidemic is grossly underdiagnosed and that the infection is silently spreading across the globe with two consequences: (i) clusters of severe infections among frail subjects could haphazardly occur linked to unrecognized index cases;(ii) the current epidemic could naturally fall into a low-level endemic phase when a significant number of subjects will have developed immunity Understanding the role of paucisymptomatic subjects and stratifying patients according to the risk of developing severe clinical presentations is pivotal for implementing reasonable measures to contain the infection and to reduce its mortality Whilst the future evolution of this epidemic remains unpredictable, classic public health strategies must follow rational patterns The emergence of yet another global epidemic underscores the permanent challenges that infectious diseases pose and underscores the need for global cooperation and preparedness, even during inter-epidemic periods

Coronavirus infections: Epidemiological, clinical and immunological features and hypotheses

BACKGROUND: The prevalence, symptom course, and shedding in persons infected with the 4 most common human coronaviruses (HCoV)‐229E, HKU1, NL63, and OC43 are poorly described. OBJECTIVES: We estimate their prevalence and associated symptoms among college students identified via a social network study design. PATIENTS/METHODS: We collected 1‐3 samples (n = 250 specimens) from 176 participants between October 2012 and January 17, 2013: participants with acute respiratory infection (ARI; cough and body aches or chills or fever/feverishness) and their social contacts. Virus was detected using RT‐PCR. RESULTS: 30.4% (76/250) of specimens tested positive for any virus tested, and 4.8% (12/250) were positive for 2 or more viruses. Human coronaviruses (HCoVs [22.0%; 55/250]), rhinovirus (7.6%; 19/250), and influenza A (6.4%; 16/250) were most prevalent. Symptoms changed significantly over time among ARI participants with HCoV: the prevalence of cough and chills decreased over 6 days (P = .04, and P = .01, respectively), while runny nose increased over the same period (P = .02). HCoV‐NL63 was the most frequent virus detected 6 days following symptom onset (8.9%), followed by rhinovirus (6.7%). CONCLUSIONS: During a 3‐month period covering a single season, HCoVs were common, even among social contacts without respiratory symptoms; specific symptoms may change over the course of HCoV‐associated illness and were similar to symptoms from influenza and rhinovirus.

Human coronaviruses and other respiratory infections in young adults on a university campus: Prevalence, symptoms, and shedding

Coronavirus (CoV) infection of humans is usually not associated with severe disease. However, discovery of the severe acute respiratory syndrome (SARS) CoV revealed that highly pathogenic human CoVs (HCoVs) can evolve. The identification and characterization of new HCoVs is, therefore, an important task. Recently, a HCoV termed NL63 was discovered in patients with respiratory tract illness. Here, cell tropism and receptor usage of HCoV-NL63 were analyzed. The NL63 spike (S) protein mediated infection of different target cells compared with the closely related 229E-S protein but facilitated entry into cells known to be permissive to SARS-CoV-S-driven infection. An analysis of receptor engagement revealed that NL63-S binds angiotensin-converting enzyme (ACE) 2, the receptor for SARS-CoV, and HCoV-NL63 uses ACE2 as a receptor for infection of target cells. Potent neutralizing activity directed against NL63- but not 229E-S protein was detected in virtually all sera from patients 8 years of age or older, suggesting that HCoV-NL63 infection of humans is common and usually acquired during childhood. Here, we show that SARS-CoV shares its receptor ACE2 with HCoV-NL63. Because the two viruses differ dramatically in their ability to induce disease, analysis of HCoV-NL63 might unravel pathogenicity factors in SARS-CoV. The frequent HCoV-NL63 infection of humans suggests that highly pathogenic variants have ample opportunity to evolve, underlining the need for vaccines against HCoVs.

Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry.

Recently, Coronavirus has been given considerable attention from the biomedical community based on the emergence and isolation of a deadly coronavirus infecting human. To understand the behavior of the newly emerging MERS-CoV requires knowledge at different levels (epidemiologic, antigenic, and pathogenic), and this knowledge can be generated from the most related viruses. In this study, we aimed to compare between 3 species of Coronavirus, namely Middle East Respiratory Syndrome (MERS-CoV), Severe Acute Respiratory Syndrome (SARS-CoV), and NeoCoV regarding whole genomes and 6 similar proteins (E, M, N, S, ORF1a, and ORF1ab) using different bioinformatics tools to provide a better understanding of the relationship between the 3 viruses at the nucleotide and amino acids levels. All sequences have been retrieved from National Center for Biotechnology Information (NCBI). Regards to target genomes’ phylogenetic analysis showed that MERS and SARS-CoVs were closer to each other compared with NeoCoV, and the last has the longest relative time. We found that all phylogenetic methods in addition to all parameters (physical and chemical properties of amino acids such as the number of amino acid, molecular weight, atomic composition, theoretical pI, and structural formula) indicated that NeoCoV proteins were the most related to MERS-CoV one. All phylogenetic trees (by both maximum-likelihood and neighbor-joining methods) indicated that NeoCoV proteins have less evolutionary changes except for ORF1a by just maximum-likelihood method. Our results indicated high similarity between viral structural proteins which are responsible for viral infectivity; therefore, we expect that NeoCoV sooner may appear in human-related infection.

NeoCoV Is Closer to MERS-CoV than SARS-CoV

BACKGROUND: More than a decade after the outbreak of human coronaviruses (HCoVs) SARS in Guangdong province and Hong Kong SAR of China in 2002, there is still no reoccurrence, but the evolution and recombination of the coronaviruses in this region are still unknown. Therefore, surveillance on the prevalence and the virus variation of HCoVs circulation in this region is conducted. METHODS: A total of 3298 nasopharyngeal swabs samples were collected from cross-border children (<6 years, crossing border between Southern China and Hong Kong SAR) showing symptoms of respiratory tract infection, such as fever (body temperature > 37.5 °C), from 2014 May to 2015 Dec. Viral nucleic acids were analyzed and sequenced to study the prevalence and genetic diversity of the four human coronaviruses. The statistical significance of the data was evaluated with Fisher chi-square test. RESULTS: 78 (2.37%; 95%CI 1.8-2.8%) out of 3298 nasopharyngeal swabs specimens were found to be positive for OC43 (36;1.09%), HKU1 (34; 1.03%), NL63 (6; 0.18%) and 229E (2;0.01%). None of SARS or MERS was detected. The HCoVs predominant circulating season was in transition of winter to spring, especially January and February and NL63 detected only in summer and fall. Complex population with an abundant genetic diversity of coronaviruses was circulating and they shared homology with the published strains (99-100%). Besides, phylogenetic evolutionary analysis indicated that OC43 coronaviruses were clustered into three clades (B,D,E), HKU1 clustered into two clades(A,B) and NL63 clustered into two clades(A,B). Moreover, several novel mutations including nucleotides substitution and the insertion of spike of the glycoprotein on the viral surface were discovered. CONCLUSIONS: The detection rate and epidemic trend of coronaviruses were stable and no obvious fluctuations were found. The detected coronaviruses shared a conserved gene sequences in S and RdRp. However, mutants of the epidemic strains were detected, suggesting continuous monitoring of the human coronaviruses is in need among cross-border children, who are more likely to get infected and transmit the viruses across the border easily, in addition to the general public.

Prevalence and genetic diversity analysis of human coronaviruses among cross-border children

Coronaviruses (CoVs) cause a broad spectrum of diseases in domestic and wild animals, poultry, and rodents, ranging from mild to severe enteric, respiratory, and systemic disease, and also cause the common cold or pneumonia in humans. Seven coronavirus species are known to cause human infection, 4 of which, HCoV 229E, HCoV NL63, HCoV HKU1 and HCoV OC43, typically cause cold symptoms in immunocompetent individuals. The others namely SARS-CoV (severe acute respiratory syndrome coronavirus), MERS-CoV (Middle East respiratory syndrome coronavirus) were zoonotic in origin and cause severe respiratory illness and fatalities. On 31 December 2019, the existence of patients with pneumonia of an unknown aetiology was reported to WHO by the national authorities in China. This virus was officially identified by the coronavirus study group as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the present outbreak of a coronavirus-associated acute respiratory disease was labelled coronavirus disease 19 (COVID-19). COVID-19's first cases were seen in Turkey on March 10, 2020 and was number 47,029 cases and 1006 deaths after 1 month. Infections with SARS-CoV-2 are now widespread, and as of 10 April 2020, 1,727,602 cases have been confirmed in more than 210 countries, with 105,728 deaths.

Coronaviruses and SARS-COV-2

Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Replication of HCoV is regulated by a diversity of host factors and induces drastic alterations in cellular structure and physiology. Activation of critical signaling pathways during HCoV infection modulates the induction of antiviral immune response and contributes to the pathogenesis of HCoV. Recent studies have begun to reveal some fundamental aspects of the intricate HCoV-host interaction in mechanistic detail. In this review, we summarize the current knowledge of host factors co-opted and signaling pathways activated during HCoV infection, with an emphasis on HCoV-infection-induced stress response, autophagy, apoptosis, and innate immunity. The cross talk among these pathways, as well as the modulatory strategies utilized by HCoV are also discussed. Expected final online publication date for the Annual Review of Microbiology Volume 73 is September 9, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Human Coronavirus: Host-Pathogen Interaction.

Summary Background An outbreak of severe acute respiratory syndrome (SARS) has been reported in Hong Kong. We investigated the viral cause and clinical presentation among 50 patients. Methods We analysed case notes and microbiological findings for 50 patients with SARS, representing more than five separate epidemiologically linked transmission clusters. We defined the clinical presentation and risk factors associated with severe disease and investigated the causal agents by chest radiography and laboratory testing of nasopharyngeal aspirates and sera samples. We compared the laboratory findings with those submitted for microbiological investigation of other diseases from patients whose identity was masked. Findings Patients' age ranged from 23 to 74 years. Fever, chills, myalgia, and cough were the most frequent complaints. When compared with chest radiographic changes, respiratory symptoms and auscultatory findings were disproportionally mild. Patients who were household contacts of other infected people and had older age, lymphopenia, and liver dysfunction were associated with severe disease. A virus belonging to the family Coronaviridae was isolated from two patients. By use of serological and reverse-transcriptase PCR specific for this virus, 45 of 50 patients with SARS, but no controls, had evidence of infection with this virus. Interpretation A coronavirus was isolated from patients with SARS that might be the primary agent associated with this disease. Serological and molecular tests specific for the virus permitted a definitive laboratory diagnosis to be made and allowed further investigation to define whether other cofactors play a part in disease progression.

Coronavirus as a possible cause of severe acute respiratory syndrome

PURPOSE: During the late autumn to winter season (October to December) in the Republic of Korea, respiratory syncytial virus (RSV) is the most common pathogen causing lower respiratory tract infections (LRTIs). Interestingly, in 2014, human coronavirus (HCoV) caused not only upper respiratory infections but also LRTIs more commonly than in other years. Therefore, we sought to determine the epidemiology, clinical characteristics, outcomes, and severity of illnesses associated with HCoV infections at a single center in Korea. MATERIALS AND METHODS: We retrospectively identified patients with positive HCoV respiratory specimens between October 2014 and December 2014 who were admitted to Severance Children’s Hospital at Yonsei University Medical Center for LRTI. Charts of the patients with HCoV infection were reviewed and compared with RSV infection. RESULTS: During the study period, HCoV was the third most common respiratory virus and accounted for 13.7% of infections. Coinfection was detected in 43.8% of children with HCoV. Interestingly, one patient had both HCoV-OC43 and HCoV-NL63. Mild pneumonia was most common (60.4%) with HCoV, and when combined with RSV, resulted in bronchiolitis. Two patients required care in the intensive care unit. However, compared with that of RSV infection, the disease course HCoV was short. CONCLUSION: Infections caused by HCoVs are common, and can cause LRTIs. During an epidemic season, clinicians should be given special consideration thereto. When combined with other medical conditions, such as neurologic or cardiologic diseases, intensive care unit (ICU) care may be necessary.

Human Coronavirus in the 2014 Winter Season as a Cause of Lower Respiratory Tract Infection

BACKGROUND: Human coronaviruses (HCoVs) have been recognized as causative agents of respiratory tract infections.Our aim was to describe HCoV infections in hospitalized children in a prospective surveillance study for 14 years and compare them with other respiratory viruses. METHODS: As a part of an ongoing prospective study to identify the etiology of viral respiratory infections in Spain, we performed the analysis of HCoV infections in children hospitalized in a secondary hospital in Madrid, between October 2005 and June 2018. Clinical data of HCoV patients were compared with those infected by rhinovirus, respiratory syncytial virus and influenza. RESULTS: The study population consisted of 5131 hospitalizations for respiratory causes in children. A total of 3901 cases (75.9%) had a positive viral identification and 205 cases (4.1%) were positive for HCoV. Only 41 cases (20%) of HCoV infection were detected as single infections. Episodes of recurrent wheezing were the most common diagnosis, and 112 children (54%) had hypoxia. Clinical data in HCoV cases were similar to those associated with rhinovirus; however, patients with HCoV were younger. Other viruses were associated with hypoxia more frequently than cases with HCoV; high fever was more common in influenza infections and bronchiolitis in respiratory syncytial virus group. Although a slight peak of circulation appears mostly in winter, HCoV has been detected throughout the year as well. CONCLUSIONS: HCoV infections represent a small fraction of respiratory infections that require hospitalization in children and their characteristics do not differ greatly from other respiratory viral infections.

A 14-year Prospective Study of Human Coronavirus Infections in Hospitalized Children: Comparison With Other Respiratory Viruses

Acute respiratory viruses often result in significant morbidity and mortality. The potential impact of human respiratory coronavirus (CoV) infections was underestimated until the severe acute respiratory syndrome (SARS-CoV) outbreak in 2003, which showed that new, highly pathogenic coronaviruses could be introduced to humans, highlighting the importance of monitoring the circulating coronaviruses. The use of sensitive molecular methods has contributed to the differential diagnosis of viruses circulating in humans. Our study aim was to investigate the molecular epidemiology of human CoV strains circulating in Arkansas, their genetic variability and their association with reported influenza-like symptoms. We analyzed 200 nasal swab samples, collected by the Arkansas Department of Health in 2010, for influenza diagnosis. All samples were from patients showing acute respiratory symptoms while testing negative for influenza. Samples were pre-screened, using a quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) multiprobe for coronavirus, and subjected to confirmatory pancoronavirus and/or strain-specific reverse transcriptase (RT)-PCR followed by sequence analysis. Seventy-nine samples (39.5%) were positive by qRT-PCR and 35 samples (17.5%) were confirmed by conventional RT-PCR. Twenty-three of the confirmed samples (59%) were sequenced. The most frequent strain detected was HCoV-OC43-like followed by NL63-like; only one sample was positive for HCoV-229E and one for HCoV-HKU1. Feline-like CoV strains were detected in three samples, representing possible evidence of interspecies transmission or a new human strain. Seventeen percent of the coronavirus positive samples were also positive for other respiratory viruses, such as Respiratory Syncytial Virus (RSV), Parainfluenza 2 and 3, and Rhinovirus. Thus, HCoV-OC43, NL63, HKU1 and new feline-like strains were circulating in Arkansas in 2010. HCoV was the sole respiratory virus detected in 16% of the patients who showed acute respiratory symptoms with negative diagnoses for influenza virus.

Human Respiratory Coronaviruses Detected In Patients with Influenza-Like Illness in Arkansas, USA

were identified beginning with the discovery of SARS-CoV in 2002. With the recent detection of SARS-CoV-2, there are now seven human coronaviruses. Those that cause mild diseases are the 229E, OC43, NL63 and HKU1, and the pathogenic species are SARS-CoV, MERS-CoV and SARS-CoV-2 Coronaviruses (order Nidovirales, family Coronaviridae, and subfamily Orthocoronavirinae) are spherical (125nm diameter), and enveloped with club-shaped spikes on the surface giving the appearance of a solar corona. Within the helically symmetrical nucleocapsid is the large positive sense, single stranded RNA. Of the four coronavirus genera (α,β,γ,δ), human coronaviruses (HCoVs) are classified under α-CoV (HCoV-229E and NL63) and β-CoV (MERS-CoV, SARS-CoV, HCoVOC43 and HCoV-HKU1). SARS-CoV-2 is a β-CoV and shows fairly close relatedness with two bat-derived CoV-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. Even so, its genome is similar to that of the typical CoVs. SARS-CoV and MERS-CoV originated in bats, and it appears to be so for SARS-CoV-2 as well. The possibility of an intermediate host facilitating the emergence of the virus in humans has already been shown with civet cats acting as intermediate hosts for SARS-CoVs, and dromedary camels for MERS-CoV. Human-to-human transmission is primarily achieved through close contact of respiratory droplets, direct contact with the infected individuals, or by contact with contaminated objects and surfaces. The coronaviral genome contains four major structural proteins: the spike (S), membrane (M), envelope (E) and the nucleocapsid (N) protein, all of which are encoded within the 3' end of the genome. The S protein mediates attachment of the virus to the host cell surface receptors resulting in fusion and subsequent viral entry. The M protein is the most abundant protein and defines the shape of the viral envelope. The E protein is the smallest of the major structural proteins and participates in viral assembly and budding. The N protein is the only one that binds to the RNA genome and is also involved in viral assembly and budding. Replication of coronaviruses begin with attachment and entry. Attachment of the virus to the host cell is initiated by interactions between the S protein and its specific receptor. Following receptor binding, the virus enters host cell cytosol via cleavage of S protein by a protease enzyme, followed by fusion of the viral and cellular membranes. The next step is the translation of the replicase gene from the virion genomic RNA and then translation and assembly of the viral replicase complexes. Following replication and subgenomic RNA synthesis, encapsidation occurs resulting in the formation of the mature virus. Following assembly, virions are transported to the cell surface in vesicles and released by exocytosis.

Properties of Coronavirus and SARS-CoV-2.

As the result of prolonged (17 years) observations of patients with acute respiratory infections hospitalized in basic departments of clinics of the Research Institute of Influenza, coronavirus infection was found to be the cause of respiratory diseases, on the average, in 12% of cases (in some years in 6.8% to 28.6% of cases). The analysis of extensive morbidity rates among different age groups of the population showed that children were affected by coronavirus infection 5-7 times more often than adults. Three year cycles of this infection were established. The periods of coronaviruses activation were accompanied by their detection in patient material by electron-microscopy, a sharp increase of immune response of patients as well as in the number of nosocomial infections and the proportion of the monoinfection of the coronavirus nature. Coronaviruses played the leading role among other viruses in the etiology of hospital respiratory infections. Mucosal antibodies to coronaviruses in the secretions of the nasal cavity proved to be more important than serum antibodies not only in protection from infection, but also in the pattern of clinical manifestations of the disease.

[Seroepidemiological study of coronavirus infection in children and adults in St. Petersburg].

AIM Study the circulation of respiratory viruses in children with community-acquired pneumonia (CAP) during the period from October 2012 to May 2013. MATERIALS AND METHODS 136 children with CAP aged from 3 months to 16 years with ARI symptoms at the disease debut were studied. RNA/DNA of influenza A, B, parainfluenza (PI); adeno-, rhino-, RS-viruses, corona-, metapneumo- (MPV) and bocaviruses were detected in nasopharynx smears by PCR with hybridization-fluorescent detection in real time. Antibodies against influenza viruses A/H1N1/pdm09 California/07/09, epidemic reference strains of influenza viruses A/H1N1/Brisbane/59/07, A/ H3N2/Victoria/361/201 1, B/Wisconsin/1/10, against PI viruses type 1, 2, 3 were determined in paired sera by HAI. RESULTS In February-March 2013 the number of children protected by antibodies against influenza decreased, and circulation of influenza viruses A/H3N2 and A/H1N1/ pdm09 was detected. Rhinoviruses and PI viruses were determined throughout the epidemic season, bocavirus and adenoviruses--during the autumn-winter period, RS-virus and MPV--during winter-spring. Coronaviruses were not detected. The peak of virus detection was established in February when the threshold of influenza and ARI morbidity was exceeded. The main pathogens of children of the first 3 years of life are rhinoviruses, RS-virus, PI viruses and bocavirus. RS-virus infection at the debut of CAP in children younger than 3 years in 55.5% of cases is associated with the development of broncho-obstructive syndrome. Bocavirus infection in 50% of cases progresses with laryngo-tracheitis and bronchiolitis. CONCLUSION The fraction of viruses in etiologic structure ofARI in children varies depending on immune layer, season and age of children. Etiology of viral infection at the debut of CAP could only be proven using specialized laboratory studies.

[Monitoring of influenza and other respiratory diseases causative agents in children, hospitalized with community-acquired pneumonia in 2012-2013 epidemic season].

Coronaviruses (CoVs) cause a broad spectrum of diseases in domestic and wild animals, poultry, and rodents, ranging from mild to severe enteric, respiratory, and systemic disease, and also cause the common cold or pneumonia in humans. Seven coronavirus species are known to cause human infection, 4 of which, HCoV 229E, HCoV NL63, HCoV HKU1 and HCoV OC43, typically cause cold symptoms in immunocompetent individuals. The others namely SARS-CoV (severe acute respiratory syndrome coronavirus), MERS-CoV (Middle East respiratory syndrome coronavirus) were zoonotic in origin and cause severe respiratory illness and fatalities. On 31 December 2019, the existence of patients with pneumonia of an unknown aetiology was reported to WHO by the national authorities in China. This virus was officially identified by the coronavirus study group as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the present outbreak of a coronavirus-associated acute respiratory disease was labelled coronavirus disease 19 (COVID-19). COVID-19’s first cases were seen in Turkey on March 10, 2020 and was number 47,029 cases and 1006 deaths after 1 month. Infections with SARS-CoV-2 are now widespread, and as of 10 April 2020, 1,727,602 cases have been confirmed in more than 210 countries, with 105,728 deaths.

Coronaviruses and SARS-COV-2

Coronaviridae is a family of single-stranded positive enveloped RNA viruses. This article aimed to review the history of these viruses in the last 60 years since their discovery to understand what lessons can be learned from the past. A review of the PubMed database was carried out, describing taxonomy, classification, virology, genetic recombination, host adaptation, and main symptoms related to each type of virus. SARS-CoV-2 is responsible for the ongoing global pandemic, and SARS-CoV and MERS-CoV were responsible for causing severe respiratory illness and regional epidemics in the past while the four other strains of CoVs (229-E OC43, NL63, and HKU1) circulate worldwide and normally only cause mild upper respiratory tract infections. Given the enormous diversity of coronavirus viruses in wildlife and their continuous evolution and adaptation to humans, future outbreaks would undoubtedly occur. Restricting or banning all trade in wild animals in wet markets would be a necessary measure to reduce future zoonotic infections.

Coronaviridae-Old friends, new enemy!

A novel coronavirus (SARS-CoV-2) first detected in Wuhan, China, has spread rapidly since December 2019, causing more than 100,000 confirmed infections and 4000 fatalities (as of 10 March 2020). The outbreak has been declared a pandemic by the WHO on Mar 11, 2020. Here, we explore how seasonal variation in transmissibility could modulate a SARS-CoV-2 pandemic. Data from routine diagnostics show a strong and consistent seasonal variation of the four endemic coronaviruses (229E, HKU1, NL63, OC43) and we parameterise our model for SARS-CoV-2 using these data. The model allows for many subpopulations of different size with variable parameters. Simulations of different scenarios show that plausible parameters result in a small peak in early 2020 in temperate regions of the Northern Hemisphere and a larger peak in winter 2020/2021. Variation in transmission and migration rates can result in substantial variation in prevalence between regions. While the uncertainty in parameters is large, the scenarios we explore show that transient reductions in the incidence rate might be due to a combination of seasonal variation and infection control efforts but do not necessarily mean the epidemic is contained. Seasonal forcing on SARS-CoV-2 should thus be taken into account in the further monitoring of the global transmission. The likely aggregated effect of seasonal variation, infection control measures, and transmission rate variation is a prolonged pandemic wave with lower prevalence at any given time, thereby providing a window of opportunity for better preparation of health care systems.

Potential impact of seasonal forcing on a SARS-CoV-2 pandemic

Coronaviruses fusion with the membrane and entry to the host cell

Corona viruses belong to a group of not yet well known viruses isolated in patients with infections of the upper respiratory organs, especially in winter months. It is presumed that they provoke about 15% - 20% of all infections. However, in the last years more attention has been paid to the role of human corona viruses in the provocation of sickness in man and they are becoming a special field of interest in scientific studies.

[Coronaviruses].

Abstract Influenza A and B, and many unrelated viruses including rhinovirus, RSV, adenovirus, metapneumovirus and coronavirus share the same seasonality, since these viral acute respiratory tract infections (vARIs) are much more common in winter than summer. Unfortunately, early investigations that used recycled “pedigree” virus strains seem to have led microbiologists to dismiss the common folk belief that vARIs often follow chilling. Today, incontrovertible evidence shows that ambient temperature dips and host chilling increase the incidence and severity of vARIs. This review considers four possible mechanisms, M1 - 4, that can explain this link: (M1) increased crowding in winter may enhance viral transmission; (M2) lower temperatures may increase the stability of virions outside the body; (M3) chilling may increase host susceptibility; (M4) lower temperatures or host chilling may activate dormant virions. There is little evidence for M1 or M2, which are incompatible with tropical observations. Epidemiological anomalies such as the repeated simultaneous arrival of vARIs over wide geographical areas, the rapid cessation of influenza epidemics, and the low attack rate of influenza within families are compatible with M4, but not M3 (in its simple form). M4 seems to be the main driver of seasonality, but M3 may also play an important role.

Seasonality and selective trends in viral acute respiratory tract infections

The novel coronavirus pneumonia (NCP) continues to spread throughout the country, and the prevention and control of the epidemic has entered a critical period. However, southern cities with severe outbreaks are about to enter the seasonal influenza season. We should strengthen the epidemiological investigation, optimize the laboratory testing strategy, take effective measures, strengthen the prevention and control of influenza epidemic, and minimize the interference to the new coronavirus epidemic.

[Be alert to superposed effect of seasonal influenza while fighting against novel coronavirus pneumonia]

Potential impact of seasonal forcing on a SARS-CoV-2 pandemic.

A serologic surveillance of lower respiratory tract disease in 417 hospitalized children under 18 months of age revealed infection with coronaviruses (strains OC43 and/or 229E) in 34 (8.2%). During the same interval, one of 13 control infants was infected. There were two distinct periods lasting six and 14 weeks, respectively, during which the incidence rose to as high as 18.9% of patients with lower respiratory tract disease. The incidence of coronavirus infection in patients with pneumonia and bronchiolitis was higher than the incidences of adenoviruses, influenza, parainfluenza viruses types 1 and 2, and rhinoviruses, and lower only than the incidences of parainfluenza virus type 3 and respiratory syncytial virus. Coronaviruses serologically similar or identical to strain 229E were recovered from frozen nasal washes obtained during the acute phase of pneumonia in two children.

Coronavirus Infection in Acute Lower Respiratory Tract Disease of Infants

Many respiratory viral infections such as influenza and measles result in severe acute respiratory symptoms and epidemics. In the spring of 2003, an epidemic of coronavirus pneumonia spread from Guangzhou to Hong Kong and subsequently to the rest of the world. The WHO coined the acronym SARS (severe acute respiratory syndrome) and subsequently the causative virus as SARS-CoV. In the summer of 2012, epidemic of pneumonia occurred again in Saudi Arabia which was subsequently found to be caused by another novel coronavirus. WHO coined the term MERS (Middle East respiratory syndrome) to denote the Middle East origin of the novel virus (MERS-CoV). In the winter of 2019, another outbreak of pneumonia occurred in Wuhan, China which rapidly spread globally. Yet another novel coronavirus was identified as the culprit and has been named SARS-CoV-2 due to its similarities with SARS-CoV, and the disease as coronavirus disease-2019. This overview aims to compare and contrast the similarities and differences of these three major episodes of coronavirus outbreak, and conclude that they are essentially the same viral respiratory syndromes caused by similar strains of coronavirus with different names. Coronaviruses have caused major epidemics and outbreaks worldwide in the last two decades. From an epidemiological perspective, they are remarkably similar in the mode of spread by droplets. Special focus is placed on the pediatric aspects, which carry less morbidity and mortality in all three entities.

Overview: The history and pediatric perspectives of severe acute respiratory syndromes: Novel or just like SARS

Acute respiratory tract infection is a leading cause of hospital admission of children. This study used a broad capture, rapid and sensitive method (multiplex PCR assay) to detect 20 different respiratory pathogens including influenza A subtypes H1, H3, and H5; influenza B; parainfluenza types 1, 2, 3, and 4; respiratory syncytial virus (RSV) groups A and B; adenoviruses; human rhinoviruses; enteroviruses; human metapneumoviruses; human coronaviruses OC43, 229E, and SARS‐CoV; Chlamydophila pneumoniae; Legionella pneumophila; and Mycoplasma pneumoniae; from respiratory specimens of 475 children hospitalized over a 12‐month period for acute respiratory tract infections. The overall positive rate (47%) was about twice higher than previous reports based on conventional methods. Influenza A, parainfluenza and RSV accounted for 51%, and non‐cultivable viruses accounted for 30% of positive cases. Influenza A peaked at March and June. Influenza B was detected in January, February, and April. Parainfluenza was prevalent throughout the year except from April to June. Most RSV infections were found between February and September. Adenovirus had multiple peaks, whereas rhinovirus and coronavirus OC43 were detected mainly in winter and early spring. RSV infection was associated with bronchiolitis, and parainfluenza was associated with croup; otherwise the clinical manifestations were largely nonspecific. In general, children infected with influenza A, adenovirus and mixed viruses had higher temperatures. In view of the increasing concern about unexpected outbreaks of severe viral infections, a rapid multiplex PCR assay is a valuable tool to enhance the management of hospitalized patients, and for the surveillance for viral infections circulating in the community. J. Med. Virol. 81:153–159, 2009. © 2008 Wiley‐Liss, Inc.

Identification of viral and atypical bacterial pathogens in children hospitalized with acute respiratory infections in Hong Kong by multiplex PCR assays

In the winter–spring seasons 2003–2004 and 2004–2005, 47 (5.7%) patients with acute respiratory infection associated with human coronavirus (hCoV) 229E‐, NL63‐, and OC43‐like strains were identified among 823 (597 immunocompetent and 226 immunocompromised) patients admitted to hospital with acute respiratory syndromes. Viral infections were diagnosed by either immunological (monoclonal antibodies) or molecular (RT‐PCR) methods. Each of two sets of primer pairs developed for detection of all CoVs (panCoV) failed to detect 15 of the 53 (28.3%) hCoV strains identified. On the other hand, all hCoV strains could be detected by using type‐specific primers targeting genes 1ab and N. The HuH‐7 cell line was found to be susceptible to isolation and identification of OC43‐ and 229E‐like strains. Overall, hCoV infection was caused by OC43‐like, 229E‐like, and NL63‐like strains in 25 (53.2%), 10 (21.3%), and 9 (19.1%) patients, respectively. In addition, three patients (6.4%) were infected by untypeable hCoV strains. NL63‐like strains were not found to circulate in 2003–2004, and 229E‐like strains did not circulate in 2004–2005, while OC43‐like strains were detected in both seasons. The monthly distribution reached a peak during January through March. Lower predominated over upper respiratory tract infections in each age group. In addition, hCoV infections interested only immunocompetent infants and young children during the first year of life, while all adults were immunocompromised patients. Coinfections of hCoVs and other respiratory viruses (mostly interesting the first year of life) were observed in 14 of the 47 (29.8%) patients and were associated with severe respiratory syndromes more frequently than hCoV single infections (P = 0.002). In conclusion, the use of multiple primer sets targeting different genes is recommended for diagnosis of all types of hCoV infection. In addition, the detection of still untypeable hCoV strains suggests that the number of hCoVs involved in human pathology might further increase. Finally, hCoVs should be screened routinely for in both infants and immunocompromised patients with acute respiratory infection. J. Med. Virol. 78:938–949, 2006. © 2006 Wiley‐Liss, Inc.

Genetic variability of human coronavirus OC43‐, 229E‐, and NL63‐like strains and their association with lower respiratory tract infections of hospitalized infants and immunocompromised patients

The pathogenesis of severe acute respiratory syndrome (SARS) is poorly understood and cytokine dysregulation has been suggested as one relevant mechanism to be explored. We compared the cytokine profile in Caco2 cells after infection of SARS coronavirus (SARS‐CoV) with other respiratory viruses including respiratory syncytial virus (RSV), influenza A virus (FluAV), and human parainfluenza virus type 2 (hPIV2). Interferon (IFN) system (production and response) was not suppressed by SARS‐CoV infection. Therefore, SARS‐CoV replication was suppressed by pretreatment with IFN. SARS‐CoV and RSV induced high levels of IL‐6 and RANTES compared with FluAV and hPIV2. Induction level of suppressor of cytokine signaling‐3 (SOCS3) by SARS‐CoV was significantly lower than that by RSV in spite of the significant production of IL‐6. Toll‐like receptors 4 and 9, which correlate with the induction of inflammatory response, were upregulated by SARS‐CoV infection. Collectively, overinduction of inflammatory cytokine and dysregulation of cytokine signaling may contribute to the immunopathology associated with “severe” inflammation in SARS. J. Med. Virol. 78:417–424, 2006. © 2006 Wiley‐Liss, Inc.

Cytokine regulation in SARS coronavirus infection compared to other respiratory virus infections

BACKGROUND Human coronaviruses (HCoVs) have been recognized as causative agents of respiratory tract infections.Our aim was to describe HCoV infections in hospitalized children in a prospective surveillance study for 14 years and compare them with other respiratory viruses. METHODS As a part of an ongoing prospective study to identify the etiology of viral respiratory infections in Spain, we performed the analysis of HCoV infections in children hospitalized in a secondary hospital in Madrid, between October 2005 and June 2018. Clinical data of HCoV patients were compared with those infected by rhinovirus, respiratory syncytial virus and influenza. RESULTS The study population consisted of 5131 hospitalizations for respiratory causes in children. A total of 3901 cases (75.9%) had a positive viral identification and 205 cases (4.1%) were positive for HCoV. Only 41 cases (20%) of HCoV infection were detected as single infections. Episodes of recurrent wheezing were the most common diagnosis, and 112 children (54%) had hypoxia. Clinical data in HCoV cases were similar to those associated with rhinovirus; however, patients with HCoV were younger. Other viruses were associated with hypoxia more frequently than cases with HCoV; high fever was more common in influenza infections and bronchiolitis in respiratory syncytial virus group. Although a slight peak of circulation appears mostly in winter, HCoV has been detected throughout the year as well. CONCLUSIONS HCoV infections represent a small fraction of respiratory infections that require hospitalization in children and their characteristics do not differ greatly from other respiratory viral infections.

A 14-year Prospective Study of Human Coronavirus Infections in Hospitalized Children: Comparison With Other Respiratory Viruses.

BACKGROUND: Viral interaction in which outbreaks of influenza and other common respiratory viruses might affect each other has been postulated by several short studies. Regarding longer time periods, influenza epidemics occasionally occur very early in the season, as during the 2009 pandemic. Whether early occurrence of influenza epidemics impacts outbreaks of other common seasonal viruses is not clear. OBJECTIVES: We investigated whether early occurrence of influenza outbreaks coincides with shifts in the occurrence of other common viruses, including both respiratory and non‐respiratory viruses. METHODS: We investigated time trends of and the correlation between positive laboratory diagnoses of eight common viruses in the Netherlands over a 10‐year time period (2003–2012): influenza viruses types A and B, respiratory syncytial virus (RSV), rhinovirus, coronavirus, norovirus, enterovirus, and rotavirus. We compared trends in viruses between early and late influenza seasons. RESULTS: Between 2003 and 2012, influenza B, RSV, and coronavirus showed shifts in their occurrence when influenza A epidemics occurred earlier than usual (before week 1). Although shifts were not always consistently of the same type, when influenza type A hit early, RSV outbreaks tended to be delayed, coronavirus outbreaks tended to be intensified, and influenza virus type B tended not to occur at all. Occurrence of rhinovirus, norovirus, rotavirus, and enterovirus did not change. CONCLUSION: When influenza A epidemics occured early, timing of the epidemics of several respiratory winter viruses usually occurring close in time to influenza A was affected, while trends in rhinoviruses (occurring in autumn) and trends in enteral viruses were not.

Early occurrence of influenza A epidemics coincided with changes in occurrence of other respiratory virus infections

BACKGROUND: Influenza virus (IV) is a leading cause of morbidity and mortality worldwide; however, understanding the contribution of non-influenza viruses (NIV) to the annual burden of respiratory illnesses (RI) is evolving. Improvements in diagnostic techniques, including the increasing clinical use of respiratory viral PCR panels (vPCR), have markedly advanced our understanding of the contributions of NIV to the “influenza season.” METHODS: A retrospective analysis of all vPCR results from one hospital system, collected between October 1, 2016 and March 7, 2017, including inpatient and outpatient samples was performed. 2,047 vPCR tests were reviewed; after removing those with undetermined results and internal control samples, 1,924 were analyzed. Data points abstracted included detection and identification of virus, and date of detection. We compared the total and monthly rates of NIV with IV, throughout the study period. RESULTS: Of 1,924 vPCR results, 985 (51%) were positive for a respiratory virus. Of these, 302 (31%) were IV, and 683 (69%) were NIV. For every month studied, the ratio of NIV to IV exceeded 50%, including the height of the season. The most commonly detected viruses were Influenza A (30%), Rhino/Enterovirus (24%), RSV (19%), Coronavirus OC43 (7%) and Metapneumovirus (5%). The peak influenza incidence temporally coincided with the national peak months of January and February. The NIV incidence paralleled the trend in IV incidence, dominated by Rhino/Enterovirus and RSV, but without a specific virus driving the trend. CONCLUSION: Non-influenza respiratory viruses cause substantial viral RI during the winter months. Many viral syndromes during the height of influenza season have traditionally been attributed to IV, including influenza-like-illness (ILI); however, these can now be better characterized using patient-specific vPCR panels, leading to improved understanding of NIV epidemiology. Even during the period of highest IV incidence, NIV infections were more common than IV. Understanding the high prevalence of NIV infections may improve the judicious use of both antibiotics and antivirals. There may also be a role for refinement of ILI, including best practices for diagnosis and treatment. DISCLOSURES: All Authors: No reported disclosures.

2518. The Role of Non-Influenza Viruses in the Seasonal Viral Respiratory Illness: A Epidemiologic Study From October 2016–March 2017

Rhinoviruses and coronaviruses cause the majority of common colds and play a part in more serious respiratory illnesses that lead to increased morbidity and mortality. Patients who are infants or elderly, have asthma or chronic obstructive pulmonary disease (COPD), or are immunosuppressed have increased frequency of rhinovirus-related respiratory complications. Newer diagnostic tests such as reverse transcriptase polymerase chain reaction (RT-PCR) have greatly expanded our understanding of the importance of these respiratory viruses. Although there are no currently approved antiviral agents for clinical use, our increased understanding of the virus-host interaction should lead to new intervention strategies.

Rhinovirus and coronavirus infections.

This manuscript explores the question of the seasonality of severe acute respiratory syndrome coronavirus 2 by reviewing 4 lines of evidence related to viral viability, transmission, ecological patterns, and observed epidemiology of coronavirus disease 2019 in the Southern Hemispheres' summer and early fall.

Will Coronavirus Disease 2019 Become Seasonal?

Coronaviridae is a family of single‐stranded positive enveloped RNA viruses. This article aimed to review the history of these viruses in the last 60 years since their discovery to understand what lessons can be learned from the past. A review of the PubMed database was carried out, describing taxonomy, classification, virology, genetic recombination, host adaptation, and main symptoms related to each type of virus. SARS‐CoV‐2 is responsible for the ongoing global pandemic, SARS‐CoV and MERS‐CoV were responsible for causing severe respiratory illness and regional epidemics in the past while the four other strains of CoVs (229‐E OC43, NL63, and HKU1) circulate worldwide and normally only cause mild upper respiratory tract infections. Given the enormous diversity of coronavirus viruses in wildlife and their continuous evolution and adaptation to humans, future outbreaks would undoubtedly occur. Restricting or banning all trade in wild animals in wet markets would be a necessary measure to reduce future zoonotic infections.

Coronaviridae ‐ old friends, new enemy!

Viruses require specific cellular receptors to infect their target cells. Angiotensin-converting enzyme 2 (ACE2) is a cellular receptor for two divergent coronaviruses, SARS coronavirus (SARS-CoV) and human coronavirus NL63 (HCoV-NL63). In addition to hostcell receptors, lysosomal cysteine proteases are required for productive infection by some viruses. Here we show that SARS-CoV, but not HCoV-NL63, utilizes the enzymatic activity of the cysteine protease cathepsin L to infect ACE2-expressing cells. Inhibitors of cathepsin L blocked infection by SARS-CoV and by a retrovirus pseudotyped with the SARS-CoV spike (S) protein but not infection by HCoV-NL63 or a retrovirus pseudotyped with the HCoV-NL63 S protein. Expression of exogenous cathepsin L substantially enhanced infection mediated by the SARS-CoV S protein and by filovirus GP proteins but not by the HCoV-NL63 S protein or the vesicular stomatitis virus G protein. Finally, an inhibitor of endosomal acidification had substantially less effect on infection mediated by the HCoV-NL63 S protein than on that mediated by the SARS-CoV S protein. Our data indicate that two coronaviruses that utilize a common receptor nonetheless enter cells through distinct mechanisms.

SARS coronavirus, but not human coronavirus NL63, utilizes cathepsin L to infect ACE2-expressing cells.