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A Rare Case of Human Coronavirus 229E Associated with Acute Respiratory Distress Syndrome in a Healthy Adult


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Human coronavirus 229E (HCoV-229E) is one of the first coronavirus strains being described. It is linked to common cold symptoms in healthy adults. Younger children and the elderly are considered vulnerable to developing lower respiratory tract infections (LRTIs). In particular, immunocompromised patients have been reported with severe and life-threatening LRTIs attributed to HCoV-229E. We report for the first time a case of LRTI and acute respiratory distress syndrome developed in a healthy adult with no comorbidities and HCoV-229E strain identified as the only causative agent. A 45-year-old female with a clear medical history presented with fever, cough, and headache. Respiratory tract infection was diagnosed, and empirical antibiotics were started. Within two days, she developed bilateral pleural effusions, diffuse consolidations, and ground glass opacities involving all lung fields. She needed immediate oxygen supply, while ABGs deteriorated and chest imaging and PaO 2 /FiO 2 indicated ARDS. Early administration of systemic corticosteroids led to gradual clinical improvement. Multiplex PCR from nasal secretions was positive only for HCoV-229E and negative for multiple other pathogens. It remains to be elucidated how an immunocompetent adult developed a life-threatening LRTI caused by a “benign considered” coronavirus strain, the HCoV-229E.
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Case Report
A Rare Case of Human Coronavirus 229E Associated with Acute
Respiratory Distress Syndrome in a Healthy Adult
Foula Vassilara,
Aikaterini Spyridaki ,
George Pothitos,
Athanassia Deliveliotou,
and Antonios Papadopoulos
Hygeia Hospital, Athens, Greece
4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece
Correspondence should be addressed to Aikaterini Spyridaki;
Received 19 January 2018; Accepted 26 March 2018; Published 15 April 2018
Academic Editor: Sin´esio Talhari
Copyright ©2018 Foula Vassilara et al. is is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Human coronavirus 229E (HCoV-229E) is one of the first coronavirus strains being described. It is linked to common cold
symptoms in healthy adults. Younger children and the elderly are considered vulnerable to developing lower respiratory tract
infections (LRTIs). In particular, immunocompromised patients have been reported with severe and life-threatening LRTIs
attributed to HCoV-229E. We report for the first time a case of LRTI and acute respiratory distress syndrome developed in
a healthy adult with no comorbidities and HCoV-229E strain identified as the only causative agent. A 45-year-old female with
a clear medical history presented with fever, cough, and headache. Respiratory tract infection was diagnosed, and empirical
antibiotics were started. Within two days, she developed bilateral pleural effusions, diffuse consolidations, and ground glass
opacities involving all lung fields. She needed immediate oxygen supply, while ABGs deteriorated and chest imaging and
indicated ARDS. Early administration of systemic corticosteroids led to gradual clinical improvement. Multiplex PCR
from nasal secretions was positive only for HCoV-229E and negative for multiple other pathogens. It remains to be elucidated how an
immunocompetent adult developed a life-threatening LRTI caused by a “benign considered” coronavirus strain, the HCoV-229E.
1. Introduction
Coronaviruses (CoVs), a genus of the Coronaviridae family,
are positive-stranded RNA viruses. e first human corona-
virus (HCoV) appeared in reports in the mid-1960s and was
isolated from persons with common cold. Two species were
first detected: HCoV-229E and subsequently HCoV-OC43
[1, 2]. Since then, more species were described [35].
e HCoV-229E strain was associated with common cold
symptoms [6]. Younger children and the elderly were consid-
ered more vulnerable to lower respiratory tract infections. Severe
lower respiratory tract infection so far has only been described in
immunocompromised patients [7, 8]. To our knowledge, there
is no report describing life-threatening conditions in immu-
nocompetent adults attributed to HCoV-229E. We report a case
of acute respiratory distress syndrome developed in a healthy
adult with no comorbidities and HCoV-229E strain identified
as the only causative agent.
2. Case Presentation
A 45-year-old female patient presented to the emergency
department with dry cough, headache, and fever up to
39.5°C lasting a few hours. Her past medical history was
unremarkable, and she did not take any medication regu-
larly. She has never smoked, worked as a teacher at a local
high school, and has not recently travelled.
Clinical examination revealed rales at her left lower lung
fields. Chest X-ray showed diffuse opacities and consoli-
dation at this field. e arterial blood gases (ABGs) were
normal, and intravenous ceftriaxone and azithromycin were
empirically administered for lower respiratory tract in-
fection (LRTI). S. pneumoniae and L. pneumophila antigen
in the patient’s urine specimen was negative, and blood
cultures were sterile.
Over the next two days, the patient’s clinical condi-
tion rapidly deteriorated, with development of tachypnea
Case Reports in Infectious Diseases
Volume 2018, Article ID 6796839, 4 pages
(34 respirations/minute), dyspnea, and hypoxemia. ABGs
changed to PaO
of 55.3 mmHg, PCO
of 31.4 mmHg, and pH of
7.487. Lung auscultation revealed diffuse rhonchi symmetrically
all over her chest, bronchial breathing at her right and left lower
lobes, and diminished vesicular sounds. Chest CT scan displayed
bibasilar pleural effusions and diffuse consolidations plus ground
glass opacities involving all lung fields (Figure 1). Oxygen was
supplied at 5 L/min, and antimicrobial therapy was changed
to levofloxacin 500 mg/day. Systemic corticosteroids and
bronchodilators were added about 40 hours after her hos-
pitalization. Samples of the pleural fluid showed exudate with
260 cells/mm
, negative Gram stain, and sterile cultures.
Nasal secretions were collected, and multiplex PCR tech-
nology was applied targeting multiple pathogens (RespiFinder®
22, PathoFinder), including coronavirus 229E; coronavirus NL63,
HKU1, and OC43; influenza A, B, and H1N1; parainfluenza 1, 2,
3, and 4; Mycoplasma pneumoniae;Legionella pneumophila;
Bordetella pertussis; bocavirus; rhinovirus/Enterovirus; adeno-
virus; RSV A and B; and Chlamydophila pneumoniae. e
result was positive for HCoV-229E, while negative for the
other tested pathogens; PCR for SARS-CoV and MERS-
CoV was also negative.
Within the next few hours, the patient’s clinical con-
dition further worsened and she required increased oxygen
supply. New ABGs showed PaO
76 mmHg, PCO
33 mmHg,
and pH 7.45 at FiO
0.50 with PaO
152, indi-
cating ARDS. e patient was in severe respiratory distress
and remained febrile and tachypneic, and a new chest X-ray
showed multiple consolidations all over her lung fields
(Figure 2). Intravenous linezolid was added to her regimen
(a) (b)
(c) (d)
Figure 1: Chest CT scan and chest X-ray (semisitting position, posterior-anterior view) of the patient after clinical deterioration depicting
diffuse bilateral opacities.
Figure 2: e patient’s chest X-ray showing extensive bilateral
airspace disease consistent with ARDS.
2Case Reports in Infectious Diseases
empirically in order to treat a possible community-acquired
Staphylococcus aureus pneumonia.
A repeat one-step RT-PCR in a nasal sample (Taqman, in-
house protocol, Hellenic Pasteur Institute) confirmed the ex-
clusive presence of human coronavirus 229E (HuCoV-229E).
After the administration of systemic corticosteroids, the patient
started to display clinical improvement within the first 24
hours. Further laboratory analyses did not reveal any immune
defect. After a week, she was discharged from the hospital well
and remained healthy 23 months later (Figure 3).
3. Discussion
e initially described coronavirus strain 229E has been
previously identified as the second most frequent cause of
common cold after rhinoviruses in healthy adults. Pre-
dominant symptoms were acute rhinorrhea, nasal conges-
tion, and/or sore throat [9, 10]. Nasal discharge was the
hallmark of all symptoms after inoculation of HuCoV-229E
to healthy volunteers, and further observed symptoms were
malaise, headache, chills, and cough [6].
HCoV-229E has been associated with bronchitis, acute
exacerbations of COPD, and pneumonia in infants, children,
and elderly persons with underlying illnesses [11–13]. Life-
threatening infections have only been described in immu-
nocompromised patients [7, 8], but the correlation of
HCoV-229E with LRTI in healthy adult individuals is un-
certain [9]. An adult patient with pneumonia tested positive
for HCoV-229E has been described in a study conducted in
rural ailand, but it is not made clear if other comorbidities
were present [14]. Nine Italian patients hospitalized with
LRTI have also been tested positive for HCoV-229E; however,
their age is not specified [15]. Although numerous studies
have tentatively linked 229E infections to severe respiratory
tract illness over many years, no study controlling for age and
underlying illness has demonstrated an epidemiologic asso-
ciation between infection with HcoV-229E in healthy adults
and any illness other than the common cold. Furthermore,
no case of HCoV-229E-associated ARDS has been re-
ported in immunocompetent adults. Only a few cases of
pulmonary infection and ARDS have been described in
a 76-year-old woman infected with the closely related
alpha coronavirus HCoV-NL63 [16] and in a 39-year-old
woman with poorly controlled DM and infected with the
beta coronavirus HCoV-OC43.
e patient was a teacher and thus exposed to multiple
pathogens from her students. She was an immunocompetent
adult with no underlying disease. Her symptoms progressed
rapidly, despite the immediate administration of broad-
spectrum antibiotics, and clinical, laboratory, and radio-
logic findings were compatible with ARDS [17]. e patient
came very close to intubation and mechanical ventilation,
but early addition of corticosteroids in her therapeutic
regimen seems to have played a decisive role towards her
favorable outcome. Close monitoring and continuous re-
cording and assessment of her vital signs warranted the
borderline avoidance of her transfer to the ICU.
HCoV-229E was isolated twice from the patient’s nasal
secretions; she was not intubated, and thus, the BAL sample
was not taken. Extensive workup did not reveal any immune
defect; all microbiological and serological studies remained
negative for other pathogens. Rapid and reliable diagnosis of
human coronavirus infections is of pronounced clinical
importance. New RT-PCR methods [18] in sputum and
nasal aspirates successfully have diagnosed human coro-
navirus infections. Multiplex RT-PCR is used increasingly to
diagnose respiratory infections and has shown to be more
sensitive than viral culture and antigen detection and also
rapid and cost-effective [19], with greater sensitivity and
similar specificity compared to real-time RT-PCR [20].
4. Conclusion
To our knowledge, it is the first time that human coronavirus
HCoV-229E has been detected in severe lower respiratory
tract infection with ARDS of a healthy adult with no
comorbidities. Although it is considered as a “benign”
microorganism and linked to mild respiratory symptoms,
the presence of HCoV-229E should not be underestimated
and considered as a possible pathogen even in coinfections
with other microorganisms and in more serious LRTIs. e
reason why HuCoV-229E causes different clinical mani-
festations in diverse patient groups has not yet been an-
swered. e process through which HCoV-229E may evade
normal immune defense and cause life-threatening illness
remains to be elucidated.
Conflicts of Interest
e authors declare that they have no conflicts of interest.
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4Case Reports in Infectious Diseases
... Coronaviruses (CoVs), named for their shape similar to the crown-shaped spikes on their surface, belong to the large family Coronaviridae, are positive-strand RNA viruses (Vassilara et al., 2018), which cause various diseases, from the common cold to SARS (severe acute respiratory syndrome), whose recorded clinical signs and symptoms are mainly fever and, Human coronaviruses were first identified and described in the mid-1960s, after being detected in the nasal cavities of patients with the common cold. They are an extensive family of viruses that can cause mild illnesses such as the common cold or serious illnesses such as severe acute respiratory syndrome (SARS) or Middle East Respiratory Syndrome (MERS) as described. ...
... The first human coronavirus (HCoV) appeared in the mid-1960s and was isolated from people with the common cold. Initially, two species were detected: HCoV-229E and later HCoV-OC43, both being among the viruses responsible for the common cold (Vassilara et al., 2018). The predominant symptoms were acute rhinorrhea, nasal congestion and / or sore throat, acute exacerbations of chronic obstructive pulmonary disease (COPD), and pneumonia in infants, children, and the elderly with underlying diseases, with nasal discharge being the hallmark of all symptoms after of the inoculation of HCoV-229E to healthy volunteers. ...
... About HCoV-229E, children and the elderly were considered the most vulnerable to lower respiratory tract infections, other symptoms observed were malaise, headache, chills, and cough (Vassilara et al., 2018). HCoV-NL63, It is customary to diagnose coronavirus infections using reverse transcription polymerase chain reaction (RT-PCR) and other nucleic acid tests of nasopharyngeal samples (Kofi, 2014). ...
Certainly, the coronavirus pandemic occurs less severely in patients without comorbidities, but more severely in immunocompromised patients, and although it is true that it began in 2019 with a high incidence in people aged 50 years or older, it is also true that nowadays it also affects children under 50 years of age, including children. The present literature review in databases such as Latindex, SciELO and Scopus, focuses mainly on the seven strains of coronavirus implicated with respiratory diseases in humans. The main results indicate that seven coronavirus strains related to respiratory diseases in humans have been reported: SARS-CoV-2, MERS-CoV, SARS-CoV, SARS-CoV, HCoV-HKU1, MERS-CoV, HCoV-OC43, HCoV-NL63, HCoV-229E, concluding that SARS-CoV and MERS-CoV viruses are the most lethal members of this family for humans, due to their virulence and the impact of their outbreaks worldwide.
... However, nosocomial viral respiratory infections among high-risk infants are also linked with it (21). In a recent study, this virus has been detected in infection of lower respiratory tract in an adult individual having acute respiratory distress syndrome with no co-morbidities (22). It appears that HCoV-229E has different clinical manifestations in different patients and the reason for these different manifestations is still not clear. ...
... However, infections with the former CoVs can be fatal if patients have low haemoglobin concentration, serum albumin levels or other such issues (96). Similarly, infants, immune-compromised individuals, and people with co-morbidities or those in old age are at high risk of developing serious clinical manifestations if infected with the former four HCoVs (22,29). ...
Full-text available
Viruses are the most abundant biological entities on our planet. On the basis of parameters like capsid structure, morphology, genetic material, etc., they are classified into different families. The Coronaviridae family of viruses includes a diverse group of positive strand RNA viruses and a subset of these viruses infects humans. Though some of these human-infecting coronaviruses cause minor respiratory ailments in healthy adults but three of them are responsible for major pandemics of the 21st century. These pandemics claimed thousands to several hundred thousands of human lives and have plunged the regional economies and even the global economy into an abyss. This work highlights the current research on human coronaviruses involving their diversity, evolution, clinical, and zoonotic attributes. An economic impact analysis of major coronaviruses is also presented to point out how these pathogens have claimed billions of dollars.
... These avian coronaviruses have been found in nondomestic avian species like peafowl, pheasant, teal, turkey, penguins, pigeon, duck, and Amazon parrot [3]. Further, the coronavirus types causing minor infection in humans are 229E, NL63, OC43, and HKU1 [4]. Rarely these coronaviruses may precipitate pneumonia or bronchitis in the human host. ...
... It is thus suggested the application of protective measures, including N95 masks. In general, the Coronavirus spread can be prevented by [2,4]: ...
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The new respiratory disease frequently observed are zoonoses exhibiting positive-stranded RNA viruses called Coronaviruses (CoVs). These groups of the virus are having origin from non-human species such as bats, cows and birds. The transmission of the virus to humans is reported to cause severe acute respiratory infection from cough to pneumonia. The mortality rate is increased from its origin from severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) to newly developed COVID-19. The following review states that the SARS, MERS to newly developed COVID-19 are generally types of coronavirus. The mode of infection and symptoms exhibited by all the corona types are nearly the same but with the difference in its virulence.
... However if a person is immunocompromised or has underlying any kind of cardiopulmonary disease, than it can result in pneumonia or bronchitis and severity will be stronger. If the infection is not detected and treated early can lead to life-threatening respiratory failure and even death [12,13]. Apart from respiratory tract infections the presence of coronaviruses were also reported in tears and gastrointestinal tract. ...
... Human adenoviruses (HAdVs) are non-enveloped, doublestranded DNA viruses in the adenoviridae family (1). Since the first isolation of the adenovirus in 1953, seven species (A-G) have been recognized, including 113 known genotypes or serotypes of HAdV (2)(3)(4)(5)(6). More than 60 genotypes are known to cause human infection (7). ...
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Objective Human adenovirus (HAdV) coinfection with other respiratory viruses is common, but adenovirus infection combined with human coronavirus-229E (HCoV-229E) is very rare. Study design and setting Clinical manifestations, laboratory examinations, and disease severity were compared between three groups: one coinfected with HAdV-Ad7 and HCoV-229E, one infected only with adenovirus (mono-adenovirus), and one infected only with HCoV-229E (mono-HCoV-229E). Results From July to August 2019, there were 24 hospitalized children: two were coinfected with HAdV-Ad7 and HCoV-229E, and 21 were infected with a single adenovirus infection. Finally, one 14-year-old boy presented with a high fever, but tested negative for HAdV-Ad7 and HCoV-229E. Additionally, three adult asymptotic cases with HCoV-229E were screened. No significant difference in age was found in the coinfection and mono-adenovirus groups (11 vs. 8 years, p = 0.332). Both groups had the same incubation period (2.5 vs. 3 days, p = 0.8302), fever duration (2.5 vs. 2.9 days, p = 0.5062), and length of hospital stay (7 vs. 6.76 days, p = 0.640). No obvious differences were found in viral loads between the coinfection and mono-adenovirus groups (25.4 vs. 23.7, p = 0.570), or in the coinfection and mono-HCoV-229E groups (32.9 vs. 30.06, p = 0.067). All cases recovered and were discharged from the hospital. Conclusion HAdV-Ad7 and HCoV-229E coinfection in healthy children may not increase the clinical severity or prolong the clinical course. The specific interaction mechanism between the viruses requires further study.
... GM-CSF might be a mediator of the hyperactive inflammatory response associated with respiratory failure and death. Blocking GM-CSF could subdue the activation of granulocytes and reduces downstream cytokine production, including MCP-1, IL5, IL9, IL12P70, etc (Vassilara et al., 2018). They played the indispensable roles in the body's inflammatory response. ...
Background The novel coronavirus pneumonia (COVID-19) has spread rapidly around the world. As a member against the epidemic, Qingfei Paidu Decoction (QFPDD) has been approved for the treatment of COVID-19 in China. However, its antiviral mechanism was still largely unclear. Purpose An integrated strategy was used to explore the antiviral mechanisms of QFPDD in cold and damp environment, including pharmacokinetic (PK), network pharmacology, metabolomics and protein verification. Methods Firstly, the pharmacokinetic study (PK) of the prototype absorbed ingredients were analyzed by UHPLC-QqQ-MS. Secondly, the metabolomics analysis of the endogenous constituents was carried out. Based on the aforementioned results, an integrated network was constructed to identify the curative components, crucial endogenous differential metabolites and related pathways. Finally, the validation tests were implemented by molecular docking and western blotting (WB). Results According to the pharmacokinetic behaviors analysis of 31 components in vivo, the flavonoids presented much more longer residence time and higher exposure compared with the other compounds. The efficacy and antiviral mechanism of QFPDD were verified by the poly-pharmacology, metabolomics, molecular docking and WB. For the occurrence of metabolic disorder, the change of amino acid transporters should not be neglected. Afterward, 8 curative compounds, 6 key genes and corresponding metabolic pathways were filtered by compound-reaction-enzyme-gene network. The molecular docking verified that the active ingredients bound to the relevant targets well. Conclusion In the present study, an in vivo comprehensive pharmacokinetic behaviors of QFPDD was analyzed for the first time. The results illustrated that QFPDD could exhibit immune regulation, anti-infection, anti-inflammation and metabolic disorder to perform a corresponding therapeutic effect. Moreover, our findings highlighted the roles of amino acid transporters in the coronavirus infection situation.
... Coronavirus disease was first identified in 1931 when the first human coronavirus HCoV-229E was isolated from a patient in 1965 (Vassilara et al., 2018). Coronavirus disease 2019 (COVID-19) is a current pandemic infection caused by a positive-sense RNA coronavirus. ...
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Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is a positive-sense RNA enveloped virus. It is characterized by club-like spikes that form unusually large RNA genomes from their surface and are a unique replication strategy. SARS-CoV-2 causes several diseases and distress in human and potentially fatal respiratory infections. COVID-19 caused by SARS-CoV-2 is a pandemic disease which has led to a global health crisis resulting in millions of deaths worldwide. The following is a brief introduction to the SARS-CoV-2, particularly discussing its replication, pathogenicity, and neurological complications.
Significance: Acute infectious conjunctivitis poses significant challenges to eye care providers. It can be highly transmissible and as etiology is often presumed, correct treatment and management can be difficult. This study utilizes unbiased deep sequencing to identify causative pathogens of infectious conjunctivitis, potentially allowing for improved approaches to diagnosis and management. Purposes: To identified associated pathogens of acute infectious conjunctivitis in a single ambulatory eye care center.Case ReportsThis study included patients who presented to the University of California Berkeley eye center with signs and symptoms suggestive of infectious conjunctivitis. From December 2021 to July 2021, samples were collected from 7 subjects (ages ranging from 18 to 38 years old). Deep sequencing identified associated pathogens in 5 out of 7 samples, including human adenovirus D (HAdV), Haemophilus influenzae, Chlamydia trachomatis, and human coronavirus 229E (HCoV-229E). Conclusions: Unbiased deep sequencing identified some unexpected pathogens in subjects with acute infectious conjunctivitis. HAdV was recovered from only one patient in this series. While all samples were obtained during the COVID-19 pandemic, only one case of HCoV-229E and no SARS-CoV-2was identified.
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Human coronavirus 229E (HCoV-229E) and NL63 (HCoV-NL63) are endemic causes of upper respiratory infections such as the "common cold" but may occasionally cause severe lower respiratory tract disease in the elderly and immunocompromised patients. There are no approved antiviral drugs or vaccines for these common cold coronaviruses (CCCoV). The recent emergence of COVID-19 and the possible cross-reactive antibody and T cell responses between these CCCoV and SARS-CoV-2 emphasize the need to develop experimental animal models for CCCoV. Mice are an ideal experimental animal model for such studies, but are resistant to HCoV-229E and HCoV-NL63 infections. Here, we generated 229E and NL63 mouse models by exogenous delivery of their receptors, human hAPN and hACE2 using replication-deficient adenoviruses (Ad5-hAPN and Ad5-hACE2), respectively. Ad5-hAPN- and Ad5-hACE2-sensitized IFNAR-/- and STAT1-/- mice developed pneumonia characterized by inflammatory cell infiltration with virus clearance occurring 7 d post infection. Ad5-hAPN- and Ad5-hACE2-sensitized mice generated virus-specific T cells and neutralizing antibodies after 229E or NL63 infection, respectively. Remdesivir and a vaccine candidate targeting spike protein of 229E and NL63 accelerated viral clearance of virus in these mice. 229E- and NL63-infected mice were partially protected from SARS-CoV-2 infection, likely mediated by cross-reactive T cell responses. Ad5-hAPN- and Ad5-hACE2-transduced mice are useful for studying pathogenesis and immune responses induced by HCoV-229E and HCoV-NL63 infections and for validation of broadly protective vaccines, antibodies, and therapeutics against human respiratory coronaviruses including SARS-CoV-2.
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Background: The incidence and clinical impact of coronavirus (CoV) infection in elderly persons and those with underlying cardiopulmonary disease over a long duration is not well described. We determined the incidence and clinical impact of 229E and OC43 CoV in this population during 4 consecutive winters, and compared illnesses to influenza A, respiratory syncytial virus, and human metapneumovirus. Methods: CoV 229E and OC43 were detected by reverse transcription polymerase chain reaction and serology in 4 adult populations under surveillance for acute respiratory illness during the winters of 1999-2003. Cohorts included healthy young adults, healthy elderly adults, high-risk adults with underlying cardiopulmonary disease, and a hospitalized group. Results: Three hundred ninety-eight CoV infections were identified, with annual infection rates ranging from 2.8% to 26% in prospective cohorts, and prevalence ranging from 3.3% to 11.1% in the hospitalized cohort. The incidence of infections with each strain was similar, although asymptomatic infection and viral coinfection was significantly more common with 229E than OC43 infection. Although the incidence and clinical manifestations were similar for each strain, OC43-infected subjects tended to seek more medical care, as OC43 was twice as common as 229E among the hospitalized cohort. Conclusions: CoV infections in the elderly are frequent, likely causing substantial medical disease burden.
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A previously unknown coronavirus was isolated from the sputum of a 60-year-old man who presented with acute pneumonia and subsequent renal failure with a fatal outcome in Saudi Arabia. The virus (called HCoV-EMC) replicated readily in cell culture, producing cytopathic effects of rounding, detachment, and syncytium formation. The virus represents a novel betacoronavirus species. The closest known relatives are bat coronaviruses HKU4 and HKU5. Here, the clinical data, virus isolation, and molecular identification are presented. The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.
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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.
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Two hundred young adults with common colds were studied during a 10-month period. Virus culture, antigen detection, PCR, and serology with paired samples were used to identify the infection. Viral etiology was established for 138 of the 200 patients (69%). Rhinoviruses were detected in 105 patients, coronavirus OC43 or 229E infection was detected in 17, influenza A or B virus was detected in 12, and single infections with parainfluenza virus, respiratory syncytial virus, adenovirus, and enterovirus were found in 14 patients. Evidence for bacterial infection was found in seven patients. Four patients had a rise in antibodies against Chlamydia pneumoniae, one had a rise in antibodies against Haemophilus influenzae, one had a rise in antibodies against Streptococcus pneumoniae, and one had immunoglobulin M antibodies against Mycoplasma pneumoniae. The results show that although approximately 50% of episodes of the common cold were caused by rhinoviruses, the etiology can vary depending on the epidemiological situation with regard to circulating viruses. Bacterial infections were rare, supporting the concept that the common cold is almost exclusively a viral disease.
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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.
The acute respiratory distress syndrome (ARDS) was defined in 1994 by the American-European Consensus Conference (AECC); since then, issues regarding the reliability and validity of this definition have emerged. Using a consensus process, a panel of experts convened in 2011 (an initiative of the European Society of Intensive Care Medicine endorsed by the American Thoracic Society and the Society of Critical Care Medicine) developed the Berlin Definition, focusing on feasibility, reliability, validity, and objective evaluation of its performance. A draft definition proposed 3 mutually exclusive categories of ARDS based on degree of hypoxemia: mild (200 mm Hg < PaO2/FIO2 ≤ 300 mm Hg), moderate (100 mm Hg < PaO2/FIO2 ≤ 200 mm Hg), and severe (PaO2/FIO2 ≤ 100 mm Hg) and 4 ancillary variables for severe ARDS: radiographic severity, respiratory system compliance (≤40 mL/cm H2O), positive end-expiratory pressure (≥10 cm H2O), and corrected expired volume per minute (≥10 L/min). The draft Berlin Definition was empirically evaluated using patient-level meta-analysis of 4188 patients with ARDS from 4 multicenter clinical data sets and 269 patients with ARDS from 3 single-center data sets containing physiologic information. The 4 ancillary variables did not contribute to the predictive validity of severe ARDS for mortality and were removed from the definition. Using the Berlin Definition, stages of mild, moderate, and severe ARDS were associated with increased mortality (27%; 95% CI, 24%-30%; 32%; 95% CI, 29%-34%; and 45%; 95% CI, 42%-48%, respectively; P < .001) and increased median duration of mechanical ventilation in survivors (5 days; interquartile [IQR], 2-11; 7 days; IQR, 4-14; and 9 days; IQR, 5-17, respectively; P < .001). Compared with the AECC definition, the final Berlin Definition had better predictive validity for mortality, with an area under the receiver operating curve of 0.577 (95% CI, 0.561-0.593) vs 0.536 (95% CI, 0.520-0.553; P < .001). This updated and revised Berlin Definition for ARDS addresses a number of the limitations of the AECC definition. The approach of combining consensus discussions with empirical evaluation may serve as a model to create more accurate, evidence-based, critical illness syndrome definitions and to better inform clinical care, research, and health services planning.
A new ether sensitive RNA virus was isolated during surveillance of URI among medical students in the winter of 1962. This virus is antigenically unrelated to all known human myxoviruses.
Respiratory infections due to coronaviruses 229 E and OC 43 in insurance company employees occurred almost exclusively in the winter and spring. Four per cent of all colds and 8 per cent of winter and spring colds were serologically related to infection with one of the two viruses. Studies of a group of families of employees showed that the prevalence of antibodies to 229 E and OC 43 increased with age. The infection rate for both coronaviruses in employees observed for one year or longer was 14.5 infections per 100 persons per year, and approximately one·third were reinfections rather than primary infections. Reinfections were commonly associated with respira· tory symptoms. Colds associated with coronavirus 229 E were mild and nasal symptoms were pre· dominant. Infections due to OC 43 coronavirus were associated with cough and pharyngitis as well as coryzal symptoms.