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Coronaviruses
Author: Kenneth McIntosh, MD
Section Editor: Martin S Hirsch, MD
Deputy Editor: Allyson Bloom, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Aug 2021. | This topic last updated: Jun 11, 2020.
INTRODUCTION
Coronaviruses are important human and animal pathogens.
During epidemics, common cold coronaviruses are the cause of up to one-third of

community-acquired upper respiratory tract infections in adults and probably also play a role
in severe respiratory infections in both children and adults. In addition, it is possible that
certain common cold coronaviruses cause diarrhea in infants and children. Their role in
central nervous system diseases, except for a single case report of encephalitis in a severely
immunocompromised infant, has been suggested but not proven. (See 'Neurologic disease'
below.)
The microbiology of coronaviruses and the epidemiology, clinical manifestations, diagnosis,

treatment, and prevention of common cold coronaviruses will be discussed here.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus

disease 2019 (COVID-19), is discussed in detail separately. (See "COVID-19: Questions and
answers".)
Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory
syndrome coronavirus (MERS-CoV) are also reviewed separately. (See "Severe acute
respiratory syndrome (SARS)" and "Middle East respiratory syndrome coronavirus: Virology,
pathogenesis, and epidemiology".)
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CORONAVIRUS DISEASE 2019 (COVID-19) PANDEMIC
A novel coronavirus, previously designated 2019-nCoV, was identified as the cause of a

cluster of pneumonia cases in Wuhan, a city in the Hubei Province of China, at the end of
2019. It subsequently spread throughout China and then worldwide, becoming a global
health emergency. In February 2020, the World Health Organization (WHO) designated the
disease COVID-19, which stands for coronavirus disease 2019 [1]. Severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2) is the cause of COVID-19, which is discussed in detail
elsewhere. (See "COVID-19: Questions and answers".)
VIROLOGY
Coronaviruses are classified as a family within the Nidovirales order, viruses that replicate
using a nested set of mRNAs ("nido-" for "nest"). The coronavirus subfamily is further
classified into four genera: alpha, beta, gamma, and delta coronaviruses. The human
coronaviruses (HCoVs) are in two of these genera: alpha coronaviruses (HCoV-229E and
HCoV-NL63) and beta coronaviruses (HCoV-HKU1, HCoV-OC43, Middle East respiratory
syndrome coronavirus [MERS-CoV], the severe acute respiratory syndrome coronavirus
[SARS-CoV]), and SARS-CoV-2 ( figure 1) [2,3].
Viral composition — Coronaviruses are medium-sized enveloped positive-stranded RNA

viruses whose name derives from their characteristic crown-like appearance in electron
micrographs ( picture 1) [4,5]. These viruses have the largest known viral RNA genomes,
with a length of 27 to 32 kb. The host-derived membrane is studded with glycoprotein spikes
and surrounds the genome, which is encased in a nucleocapsid that is helical in its relaxed
form but assumes a roughly spherical shape in the virus particle ( figure 2). Replication of
viral RNA occurs in the host cytoplasm by a unique mechanism in which RNA polymerase
binds to a leader sequence and then detaches and reattaches at multiple locations, allowing
for the production of a nested set of mRNA molecules with common 3' ends ( figure 3).
The genome encodes four or five structural proteins, S, M, N, HE, and E. HCoV-229E, HCoV-
NL63, and the SARS coronavirus possess four genes that encode the S, M, N, and E proteins,
respectively, whereas HCoV-OC43 and HCoV-HKU1 also contain a fifth gene that encodes the
HE protein [6].
● The spike (S) protein projects through the viral envelope and forms the characteristic
spikes in the coronavirus "crown." It is heavily glycosylated, probably forms a
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homotrimer, and mediates receptor binding and fusion with the host cell membrane.
The major antigens that stimulate neutralizing antibody, as well as important targets of
cytotoxic lymphocytes, are on the S protein [7]. Receptor usage is discussed below. (See
'Viral serotypes' below.)
● The membrane (M) protein has a short N-terminal domain that projects on the external
surface of the envelope and spans the envelope three times, leaving a long C terminus
inside the envelope. The M protein plays an important role in viral assembly [8].
● The nucleocapsid protein (N) associates with the RNA genome to form the nucleocapsid.
It may be involved in the regulation of viral RNA synthesis and may interact with M
protein during virus budding [8,9]. Cytotoxic T lymphocytes recognizing portions of the
N protein have been identified [10].
● The hemagglutinin-esterase glycoprotein (HE) is found only in the betacoronaviruses,

HCoV-OC43 and HKU1 (see 'Viral serotypes' below). The hemagglutinin moiety binds to
neuraminic acid on the host cell surface, possibly permitting initial adsorption of the
virus to the membrane. The esterase cleaves acetyl groups from neuraminic acid. The HE
genes of coronaviruses have sequence homology with influenza C HE glycoprotein and
may reflect an early recombination between the two viruses [11].
● The small envelope (E) protein leaves its C terminus inside the envelope and then either
spans the envelope or bends around and projects its N terminus internally. Its function is
not known, although, in the SARS-CoV, the E protein along with M and N are required for
proper assembly and release of the virus [12].
Viral serotypes — Coronaviruses are widespread among birds and mammals, with bats
being host to the largest variety of genotypes [13]. Animal and human coronaviruses fall into
four distinct genera [2,3]. Seven coronavirus serotypes have been associated with disease in
humans: HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, SARS-CoV, SARS-CoV-2, and
MERS-CoV.
● The alphacoronavirus genus includes two human virus species, HCoV-229E and HCoV-
NL63. HCoV-229E, like several animal alphacoronaviruses, utilizes aminopeptidase N
(APN) as its major receptor [14]. In contrast, HCoV-NL63, like SARS-CoV and SARS-CoV-2
(betacoronaviruses), uses angiotensin-converting enzyme-2 (ACE-2) [15]. Important
animal alphacoronaviruses are transmissible gastroenteritis virus of pigs and feline
infectious peritonitis virus. There are also several related bat coronaviruses among the
alphacoronaviruses.
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● Two of the non-SARS human species of the betacoronavirus genus, HCoV-OC43 and
HCoV-HKU1, have hemagglutinin-esterase activity and probably utilize sialic acid
residues as receptors [16]. This genus also contains several bat viruses, MERS-CoV
[17,18], SARS-CoV, and SARS-CoV-2, although the last three are genetically somewhat
distant from HCoV-OC43 and HCoV-HKU1.
Important animal betacoronaviruses are mouse hepatitis virus, a laboratory model for
both viral hepatitis and demyelinating central nervous system disease, and bovine
coronavirus, a diarrhea-causing virus of cattle. Bovine coronavirus is so similar to HCoV-
OC43 that the two viruses have been merged into a single species termed
betacoronavirus 1 [19]. HCoV-OC43 is thought to have jumped from one animal host to
the other as recently as 1890 [20].
● The gammacoronavirus genus contains primarily avian coronaviruses, the most

prominent of which is avian infectious bronchitis virus (AIBV), an important veterinary
pathogen causing respiratory and reproductive tract disease in chickens.
● The deltacoronavirus genus contains recently discovered avian coronaviruses found in

several species of songbirds.
None of the common cold human coronaviruses (HCoV-OC43, HCoV-NE63, HCoV-HKU1, and
HCoV-229E) replicate easily in tissue culture, and, until recently, this impeded progress in
their study. Both HCoV-229E and HCoV-OC43 were discovered in the 1960s and were shown
in volunteer experiments to produce common colds in adults [4,21-23]. Studies in the 1970s
and 1980s linked them to as much as one-third of upper respiratory tract infections during
winter outbreaks, 5 to 10 percent of overall colds in adults, and some proportion of lower
respiratory illness in children [24-26].
Little further information developed after this until the emergence of SARS in 2002 and the
development of molecular diagnostic methods. Then HCoV-NL63 and HCoV-HKU1 were
quickly discovered and found to have worldwide distribution [27-30]. The polymerase chain
reaction may be used for the diagnosis of each of the four human coronaviruses, and this
technique has allowed substantial investigation into their epidemiology and pathogenicity.
(See 'Diagnosis' below.)
EPIDEMIOLOGY
This section discusses the epidemiology of common cold coronaviruses.
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The epidemiology of coronavirus disease 2019 (COVID-19), severe acute respiratory

syndrome (SARS), and Middle East respiratory syndrome (MERS) is discussed separately:
● (See "COVID-19: Epidemiology, virology, and prevention", section on 'Epidemiology'.)

● (See "Severe acute respiratory syndrome (SARS)", section on 'Epidemiology'.)
● (See "Middle East respiratory syndrome coronavirus: Virology, pathogenesis, and
epidemiology", section on 'Epidemiology'.)
Seasonality — Common cold coronaviruses are ubiquitous; wherever investigators have

looked, they have been detected. Their seasonality depends, in part, on the climate:
● Temperate regions – In temperate climates, coronavirus respiratory infections occur

primarily in the winter, although smaller peaks are sometimes seen in the fall or spring,
and infections can occur at any time of the year [25,31,32]. The winter seasonality was
confirmed in an eight-year study in Michigan in the United States, in which common cold
coronavirus infections were identified between December and May, with a peak in
January and February; only 2.5 percent of infections were identified between June and
September [33].
A large study from Scotland, in which molecular testing for respiratory viruses was
performed in over 74,000 acute respiratory illnesses among adults and children from
2005 to 2017, gives some idea of the age incidence and seasonality of common cold
coronavirus infections (OC43, 229E, and NL63) in relation to other respiratory viruses in a
temperate climate [34]. The samples were obtained in general practitioner offices and
hospital in- or out-patient facilities. Common cold coronavirus infections were most
common in the winter during influenza season (accounting for approximately 7 percent
of all respiratory viral detections), were distributed across all age groups, and were less
common than those caused by rhinovirus (15 to 46 percent), influenza (13 to 34 percent),
or respiratory syncytial virus (10 to 22 percent). Coinfections were relatively common,
particularly in young children. The three species differed in their age incidence patterns:
OC43 (the most common overall) was found most often in infants, young (one to five
years old) children, and the elderly; 229E was most common in adults (>17 years old) of
all ages; NL63 was found most often in infants under a year of age, with a gradual
decrease in frequency throughout child- and adulthood.
A nine-year survey of all children under 16 years of age admitted for acute respiratory
illness at the only hospital in Sør-Trøndelag County, Norway, a region with approximately
59,000 children, found that both HCoV-OC43 and HCoV-NL63 were detected most
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frequently and were epidemic every other winter, that HCoV-HKU-1 usually prevailed
every other winter during the years when HCoV-OC43 and HCoV-NL63 did not, and that
detection of 229E was unusual [35]. HCoV-associated lower respiratory tract infection
hospitalization rates for the population under five years were calculated at 1.5 per 1000
children per year.
● Subtropical regions – A seven-year study of hospitalized children in Guangzhou, China,

described the seasonality in a subtropical region, with outbreaks at almost any time of
year but predominantly in the spring and fall [36]. In other surveys, HCoV-OC43, HCoV-
NL63, HCoV-229E, and HCoV-HKU1 predominate unpredictably in certain years and in
certain parts of the world [26,32,35,36].
In almost all these surveys, HCoV-OC43 is the most common of the four strains, followed by
HCoV-NL63, but the prevalence of the various strains in any particular year is often
unpredictable.
Routes and risk of transmission — Common cold coronaviruses probably spread in a

fashion similar to that of rhinoviruses, via direct contact with infected secretions or large
aerosol droplets. Thus, they can spread easily through a household. In one study, the
secondary infection rate among household members was 7 to 12 percent, depending on the
serotype, with an average serial interval of 3.2 to 3.6 days between the index and secondary
infection [33].
In hospital settings, spread among pediatric patients probably occurs through shedding by
their infected caretakers [37]. Outbreaks are common in long-term care facilities for older
adults [38].
Immunity and reinfection — Immunity develops soon after infection but wanes gradually
over time. Reinfection is common, presumably because of waning immunity, but possibly
because of antigenic variation within species [39].
CLINICAL MANIFESTATIONS
The clinical manifestations of infections caused by common cold human coronaviruses

(HCoVs) are described here.
Clinical features of coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome
(SARS), and Middle East respiratory syndrome (MERS) are discussed separately:
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● (See "COVID-19: Diagnosis" and "COVID-19: Clinical features".)

● (See "Severe acute respiratory syndrome (SARS)", section on 'Clinical manifestations'.)
● (See "Middle East respiratory syndrome coronavirus: Clinical manifestations and
diagnosis", section on 'Clinical manifestations'.)
Respiratory — HCoV-229E and HCoV-OC43 have been proven to have pathogenicity in

humans in volunteer studies where they, along with other less well-characterized coronavirus
strains, reproducibly induced colds very similar to those induced by rhinoviruses,
characterized by an incubation period of three days followed by upper respiratory tract
symptoms such as nasal congestion and rhinorrhea [23,40]. It is assumed that HCoV-NL63
and HCoV-HKU1 have similar pathogenicity, but proof of this is lacking. Moreover, when
tested by polymerase chain reaction (PCR), asymptomatic individuals of all ages periodically
carry coronaviruses.
Common cold coronaviruses probably account for 5 to 10 percent of all acute upper
respiratory tract infections in adults [26], with outbreaks during which 25 to 35 percent of
respiratory infections can be attributed to a single species. Like rhinoviruses, common cold
coronaviruses can be detected in middle ear effusions and have been implicated as
important viral causes of acute otitis media in children [41]. Respiratory tract infection
surveys that include asymptomatic babies and children indicate that coronaviruses, like
rhinoviruses, are often coinfections with other respiratory viruses and are also often found in
the absence of respiratory symptoms, suggesting that, although common, their
pathogenicity in healthy infants and children may be low [35,42]. In one large study, when
the concentration of viral RNA found in nasopharyngeal aspirates was measured (using the
PCR cycle threshold value), multivariate analysis showed a significant association between a
high common cold coronavirus RNA concentration (cycle threshold <28) and both respiratory
tract disease (compared with asymptomatic controls) and lack of coinfection [35]. (See
"Epidemiology, clinical manifestations, and pathogenesis of rhinovirus infections" and "Acute
otitis media in children: Epidemiology, microbiology, and complications", section on 'Viral
pathogens'.)
Common cold coronavirus infections have also been linked to more severe respiratory
diseases. In adults with community-acquired pneumonia, common cold coronaviruses are
detected by PCR at frequencies similar to or somewhat lower than those of other respiratory
viruses such as influenza virus, rhinovirus, and respiratory syncytial virus. Their etiologic role
is not clear, in part because copathogens are often found. In three studies, simultaneous
sampling of healthy adults was carried out. In one study, common cold coronaviruses were
detected more frequently in those with pneumonia (13 percent) than in healthy controls (4
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percent), although coronaviruses were also detected in a substantial proportion of patients

with nonpneumonic lower respiratory tract infection (10 percent) [43]. In a third study, which
included 3104 adults in Europe spanning two and a half years, patients with lower respiratory
tract infection (which included community-acquired pneumonia as well as cough without
evidence of pneumonia) were sampled [44]. Common cold coronaviruses were the third most
common viruses detected (after rhinoviruses and influenza viruses) and were found
significantly more often than in matched healthy controls. In another study, the numbers
were small and the difference in detection of common cold coronaviruses in adults with
community-acquired pneumonia compared with asymptomatic individuals was not
significant [45].
The ratio of HCoV-OC43 outpatient infections to inpatient infections was threefold lower than
that for HCoV-229E, suggesting that HCoV-OC43 may have greater clinical impact. Another
survey of severe acute respiratory infections from 2010 to 2014 in Arizona in the United
States found influenza virus most frequently (50 cases), followed by human
metapneumovirus (25 cases), parainfluenza viruses (20 cases), coronaviruses (16 cases), and
respiratory syncytial virus (11 cases); among coronaviruses, HCoV-OC43 predominated [46].
Further information on the role of common cold coronaviruses in acute respiratory illness in
adults comes from a four-year cohort study comparing HCoV-229E with HCoV-OC43 [47].
Among older adult patients, there is increasing evidence that common cold coronaviruses
are important causes of influenza-like illness, acute exacerbations of chronic bronchitis, and
pneumonia, where their frequency is below those of influenza and respiratory syncytial virus
but similar to that of rhinoviruses [48-51]. Several outbreaks of HCoV-OC43 respiratory
disease in older adults living in long-term care facilities have been described [52,53], with
case-fatality rates of 8 percent. A fatal case of acute respiratory distress syndrome in a 76-
year-old woman with no underlying diseases and mono-infection with HCoV-NL63 has also
been reported [54].
In children hospitalized in New York City with common cold coronavirus infection and
respiratory disease, a majority were under five years of age and had some underlying
condition such as heart disease, chronic lung disease, or congenital abnormalities [55].
Common cold coronaviruses have been found in 4 to 6 percent of adults with exacerbations
of chronic obstructive pulmonary disease (less frequent than rhinoviruses and respiratory
syncytial virus; equally frequent or somewhat less frequent than influenza; and more
frequent than parainfluenza viruses, human metapneumovirus, and adenoviruses) [56]. They
have been temporally linked to acute asthma attacks in both children and adults [57-59].
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They have been found in variable proportions, ranging from 2 to 8 percent, of neonates,
infants, and young children hospitalized with community-acquired pneumonia, and have
been identified even more frequently in lower respiratory tract disease in outpatients
[24,60,61]. They are also an important cause of nosocomial infections in neonatal intensive
care units [62]. One of the more recently discovered common cold coronaviruses, HCoV-
NL63, has been associated with croup in children [55,63,64].
Common cold coronaviruses also probably cause pneumonia in immunocompromised hosts,

including adults with HIV infection [65-68]. Twenty-eight HCoV-infected hematopoietic cell
transplant (HCT) recipients were compared with published series of similar HCT patients with
influenza virus, RSV, and parainfluenza virus infections from the same center [69]. All viruses
were detected in bronchoalveolar lavage specimens. In multivariable models, no differences
in survival were seen between the HCoV-infected patients and those infected with the other
respiratory viruses. There is also some evidence of an association between coronavirus
infection and acute rejection and bronchiolitis obliterans syndrome in lung transplant
recipients, although the association is less clear than for other respiratory viruses [70]. (See
"Parainfluenza viruses in adults" and "Parainfluenza viruses in children" and "Viral infections
following lung transplantation", section on 'Rejection'.)
Enteric — The idea that coronaviruses produce diarrhea in humans is intriguing because of

their clear intestinal pathogenicity in animals. Early human studies depended on finding
"coronavirus-like particles" (CVLPs) by electron microscopy in stool samples. The most
convincing studies showed a strong association between the presence of CVLPs and diarrhea
in infants [71] or necrotizing enterocolitis in newborns [72]. In several studies, CVLPs have
been purified that appear to be antigenically related to HCoV-OC43 [71].
All four common cold human coronavirus species have been found by reverse-transcriptase
polymerase chain reaction (RT-PCR) in the stools of a small proportion of infants and children
hospitalized with diarrhea (often with respiratory symptoms as well) [31,73]. Three surveys of
diarrhea used molecular methods to screen for all four HCoV species known to cause
community-acquired infections. In one study, all four species were found in stools from 2.5
percent of 878 children with diarrhea and 1.8 percent of 112 asymptomatic children by RT-
PCR; however, in this and other surveys, most diarrhea-associated coronavirus-positive stools
also contained other known pathogens, such as rotavirus or norovirus [73,74]. In a study that
used RT-PCR to investigate the frequency of common cold coronaviruses in stool samples
from children and adults with gastrointestinal illness, CoV-HKU1 was found in 4 of 479
patients (0.8 percent), and no other HCoV species were found [75].
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A study assessed the association between gastrointestinal manifestations (diarrhea,

vomiting, nausea, and abdominal pain) in adults reporting to general practitioners with
respiratory symptoms plus systemic symptoms or signs (fever, chills, headache, or myalgia)
[76]. Viruses were sought from respiratory and stool samples and bacteria from stool
samples only. Gastrointestinal symptoms, which occurred in 57 percent of patients, were
more likely to occur in those with fever >39°C (102.2°F), headache, a gastrointestinal
pathogen, or HCoV respiratory infection. Although a few HCoVs were found in stool samples,
the authors thought that these were likely swallowed viruses. The pathogenetic mechanism
of these gastrointestinal manifestations remains unclear.
POSSIBLE DISEASE ASSOCIATIONS
Neurologic disease — The clear involvement of several animal coronaviruses in acute and

chronic neurologic disease has stimulated a search for similar pathogenicity of human
coronaviruses. Common cold human coronaviruses (HCoVs) can infect neural cells in vitro
[77], and three-week-old mice develop generalized encephalitis after intracerebral
inoculation with HCoV-OC43 [78]. HCoV-OC43 RNA sequences have been detected in the
cerebrospinal fluid of a 15-year-old boy with acute demyelinating encephalomyelitis (ADEM)
[79]. In another report, full-length HCoV-OC43 RNA was recovered from the brain, with
widespread cerebral immunohistochemical staining at autopsy, in an 11-month-old boy with
severe combined immunodeficiency and acute encephalitis following umbilical cord blood
transplantation [80].
With the observation that rats and mice infected with certain strains of mouse hepatitis virus
(MHV) developed a severe demyelinating encephalitis similar to multiple sclerosis (MS) [81],
investigators have sought to link common cold coronaviruses with MS. Currently available
evidence is inconclusive. T cell clones from patients with MS have been shown to react both
with HCoV-229E antigens and myelin basic protein, suggesting molecular mimicry as a basis
of pathogenesis [82]. Some, but not all, investigators have detected RNA of the human
coronaviruses, HCoV-OC43 and HCoV-229E, more frequently in brain tissue from MS patients
by reverse-transcriptase polymerase chain reaction than in healthy individuals [83].
Despite these findings, an etiologic connection between common cold coronaviruses and MS
or other demyelinating diseases remains tentative and unproven. (See "Manifestations of
multiple sclerosis in adults".)
Kawasaki disease — An association of common cold coronavirus infection with Kawasaki
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disease was reported by one group of investigators and stimulated a flurry of investigation
worldwide [84]. Others failed to confirm this finding, and, at the present time, it is assumed
that common cold coronaviruses have no role in this disease [85,86]. (See "Kawasaki disease:
Epidemiology and etiology", section on 'Infectious etiology'.)
There have been reports of a multisystem inflammatory syndrome in children associated

with coronavirus disease 2019 (COVID-19) that has clinical features similar to those of
Kawasaki disease and/or toxic shock syndrome. This is discussed in detail elsewhere. (See
"COVID-19: Multisystem inflammatory syndrome in children (MIS-C) clinical features,
evaluation, and diagnosis".)
DIAGNOSIS
Since there is no effective treatment for common cold coronavirus infections, establishing
the diagnosis is of limited utility in patients suspected of having these infections. In contrast,
diagnosing coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome (SARS),
and Middle East respiratory syndrome (MERS) is critically important for understanding
outbreak epidemiology and limiting transmission of infection. These issues are discussed
elsewhere. (See "Middle East respiratory syndrome coronavirus: Clinical manifestations and
diagnosis", section on 'Diagnosis' and "Severe acute respiratory syndrome (SARS)", section on
'Diagnosis' and "COVID-19: Diagnosis", section on 'Diagnostic approach'.)
Rapid techniques that can be used to detect common cold coronaviruses from
nasopharyngeal samples include reverse-transcription polymerase chain reaction (RT-PCR)
and immunofluorescence antigen detection assays [87-89].
Because of its utility for detecting all four of the known common cold human coronavirus
strains, RT-PCR has supplanted other diagnostic methods. Although broadly reacting pan-
coronavirus primers have been developed, they are less sensitive than primers designed for
each of the four human strains [87,90]. The sensitivity may be further improved by using
real-time RT-PCR [32]. All four common cold strains are included in many respiratory nucleic
acid amplification diagnostic panels.
Common cold coronaviruses are difficult to replicate in tissue culture.
TREATMENT AND PREVENTION
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There is currently no treatment recommended for common cold coronavirus infections

except for supportive care as needed.
Chloroquine, which has potent antiviral activity against SARS-CoV [91], has been shown to
have similar activity against HCoV-229E in cultured cells [92] and against HCoV-OC43 both in
cultured cells and in a mouse model [93]. However, there have been no studies of efficacy in
humans.
Preventive measures are the same as for rhinovirus infections, which consist of handwashing
and the careful disposal of materials infected with nasal secretions. The use of surface
disinfectants is also an important issue in infection control, since coronaviruses appear to
survive for one or more days after drying on surfaces such as stainless steel, plastic, or cloth
[94]. More detailed information on prevention of coronavirus disease 2019 (COVID-19), SARS,
and Middle East respiratory syndrome (MERS) is discussed separately. (See "COVID-19:
Epidemiology, virology, and prevention", section on 'Prevention' and "Severe acute
respiratory syndrome (SARS)", section on 'Prevention' and "Middle East respiratory syndrome
coronavirus: Treatment and prevention", section on 'Prevention'.)
The efficacy of various disinfectants was examined both on viruses in liquid suspension and
on viruses dried on surfaces [95]. Human coronaviruses, including CoV-229E and SARS-CoV,
as well as several animal coronaviruses (eg, mouse hepatitis virus and transmissible
gastroenteritis virus of pigs), were studied. These viruses (both in suspension and dried on
surfaces) were very susceptible to 70% ethanol, with reduction of viability by greater than 3
log within seconds [96-98]. Likewise, hexachlorophene [99], 2% glutaraldehyde [96] and 1%
povidone-iodine [96,98] each produced satisfactory killing. It appears that susceptibility of
coronaviruses to 6% sodium hypochlorite (the active agent in bleach) solutions has been
variable, but satisfactory killing was achieved with concentrations of 1:40 or higher [97,98].
Coronaviruses were not killed by benzalkonium chloride or chlorhexidine unless 70% ethanol
was added [96].
There has been little interest in developing vaccines for the common cold coronaviruses for
several reasons. First, four separate species have been described and there is evidence
within at least one of these species of clinically significant antigenic variation [39]. In
addition, vaccine enhancement of disease has been shown for one animal coronavirus, feline
coronavirus; hypersensitivity was induced in some animals by prior exposure to a vaccine
containing the S protein, with the production of an immunologically mediated severe
disease, feline infectious peritonitis, upon reinfection with a coronavirus [100].
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Development of vaccines to prevent COVID-19, SARS, and MERS is discussed elsewhere. (See
"COVID-19: Epidemiology, virology, and prevention", section on 'Vaccines' and "Severe acute
respiratory syndrome (SARS)", section on 'Vaccine development' and "Middle East respiratory
syndrome coronavirus: Treatment and prevention", section on 'Vaccine development' and
"COVID-19: Vaccines to prevent SARS-CoV-2 infection".)
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: COVID-19 – Index of
guideline topics" and "Society guideline links: Middle East respiratory syndrome
coronavirus".)
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Here are the patient education articles that are relevant to this topic. We encourage you to
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education: COVID-19 vaccines (The Basics)")
SUMMARY AND RECOMMENDATIONS
● Common cold coronaviruses are the cause of 5 to 10 percent of community-acquired

upper respiratory tract infections in adults, occurring sporadically or in outbreaks of
variable size, and probably also play a role in severe respiratory infections in both
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children and adults, particularly adults with underlying pulmonary disease and older
adults. (See 'Introduction' above and 'Clinical manifestations' above.)
● Coronaviruses are medium-sized enveloped positive-stranded RNA viruses whose name

derives from their characteristic crown-like appearance in electron micrographs (
picture 1). (See 'Viral composition' above.)
● Common cold coronaviruses are ubiquitous; wherever investigators have looked, they
have been detected. In temperate climates, common cold coronavirus respiratory
infections occur primarily in the winter, although smaller peaks are sometimes seen in
the fall or spring, and infections can occur at any time of the year. (See 'Epidemiology'
above.)
● Most common cold coronavirus infections are diagnosed clinically, although reverse-
transcription polymerase chain reaction applied to respiratory secretions is the
diagnostic test of choice. (See 'Diagnosis' above.)
● There is currently no treatment recommended for common cold coronavirus infections

except for supportive care as needed. (See 'Treatment and prevention' above.)
● In late 2019, a novel coronavirus was identified as the cause of a cluster of pneumonia
cases in Wuhan, a city in China. It subsequently spread throughout China and elsewhere,
becoming a global health emergency. In February 2020, the World Health Organization
designated the disease COVID-19, which stands for coronavirus disease 2019. Previously,
this virus was referred to as 2019-nCoV. COVID-19 is discussed in detail elsewhere. (See
"COVID-19: Questions and answers".)
● Severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome
coronavirus are also discussed in detail separately. (See "Severe acute respiratory
syndrome (SARS)" and "Middle East respiratory syndrome coronavirus: Virology,
pathogenesis, and epidemiology".)
Use of UpToDate is subject to the Subscription and License Agreement.
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Topic 8298 Version 61.0
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GRAPHICS
Phylogenetic tree of coronaviruses [1]
Phylogenetic tree of coronaviruses (content in bold/italic red font is the latest addition of newly emerged SARS-CoV-2). The phylogenetic tre
of SARS-CoV-2 (denoted as dashed red line) to selected coronavirus is based on nucleotide sequences of the complete genome. The viruse
genera (prototype shown): Alphacoronavirus (gray), betacoronavirus (light orange), gammacoronavirus (yellow), and deltacoronavirus (ligh
are labeled as 1a and 1b for the alphacoronavirus and 2a, 2b, 2c, and 2d for the betacoronavirus. This tree is based on the published trees
reconstructed with sequences of the complete RNA-dependent RNA polymerase-coding region of the representative novel coronaviruses.
SARS-CoV: severe acute respiratory syndrome coronavirus; SARS-CoV-2: SARS coronavirus 2; MERS-CoV: Middle East respiratory syndrome coronavir
diarrhea virus; PHEV: porcine hemagglutinating encephalomyelitis virus; PRCV: porcine respiratory coronavirus; MHV: mouse hepatitis virus; TGEV: t
virus.
Reference:
1. Shereen MA, Khan S, Kazmi A, et al. COVID-19 Infection: Origin, Transmission, and Characteristics of Human Coronaviruses. J Adv Res 2020; 24:91.
Reproduced with permission from: Muhammad Adnan Shereen, Suliman Khan, Abeer Kazmi, et al. Copyright © 2020 Shareen MA, Khan S, Kazmi A, et al. All r
Graphic 128365 Version 1.0
23 de 27 09/09/2021 07:57 p. m.
Coronavirus electron micrograph
Group of coronavirus particles, negatively stained with phosphotungstic acid (PTA).

Some variation in size is seen, but shape is relatively uniform. Magnification 144,000x.
Reproduced with permission from: McIntosh K, Dees JH, Becker WB, et al. Recovery in tracheal
organ cultures of novel viruses from patients with respiratory disease. Proc Natl Acad Sci USA.
1967; 57:933. Copyright © 1967 Kenneth McIntosh, MD.
24 de 27 09/09/2021 07:57 p. m.
Model of coronavirus structure: A schematic diagram of virion

structure
Schematic showing the major structural proteins of the coronavirus virion.
S: spike protein; M: membrane protein; E: envelope protein; N: nucleocapsid protein.
Reproduced with permission from: Masters PS, Perlman S. Coronaviridae. In: Fields Virology, 6th
edition, Knipe DM, Howley PM (Eds), Lippincott Williams & Wilkins, Philadelphia, 2013. Copyright ©
2013 Lippincott Williams & Wilkins. www.lww.com.
25 de 27 09/09/2021 07:57 p. m.
Coronavirus replication
Steps in coronavirus replication that are potential targets for antiviral drugs and vaccines. The spike glycoprotein S
is a good candidate for vaccines because neutralizing antibodies are directed against S. Blockade of the specific
virus receptor on the surface of the host cell by monoclonal antibodies or other ligands can prevent virus entry.
Receptor-induced conformational changes in the S protein can be blocked by peptides that inhibit membrane
fusion and virus entry. The polyprotein of the replicase protein is cleaved into functional units by virus-encoded
proteinases. Protease inhibitors may block replication. The polymerase functions in a unique membrane-bound
complex in the cytoplasm, and the assembly and functions of this complex are potential drug targets. Viral mRNAs
made by discontinuous transcription are shown in the cytoplasm with the protein that each encodes indicated at
the right. The common 70 base long leader sequence on the 5' end of each mRNA is shown in red. Budding and
exocytosis are processes essential to virus replication that may be targets for development of antiviral drugs.
M: membrane protein required for virus budding; S: viral spike glycoprotein that has receptor binding and membrane
fusion activities; E: small membrane protein that plays a role in coronavirus assembly; N: nucleocapsid phosphoprotein
associated with viral RNA inside the virion.
Reproduced with permission from: Holmes KV. SARS coronavirus: a new challenge for prevention and therapy. J Clin Invest 2003;
111:1605. Copyright © 2003 American Society for Clinical Investigation.
26 de 27 09/09/2021 07:57 p. m.
Contributor Disclosures
Kenneth McIntosh, MD Nothing to disclose Martin S Hirsch, MD Nothing to disclose Allyson
Bloom, MD Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.
Conflict of interest policy
27 de 27 09/09/2021 07:57 p. m.

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Coronaviruses are important human and animal pathogens.

During epidemics, common cold coronaviruses are the cause of up to one-third of

The microbiology of coronaviruses and the epidemiology, clinical manifestations, diagnosis,

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus

CORONAVIRUS DISEASE 2019 (COVID-19) PANDEMIC

A novel coronavirus, previously designated 2019-nCoV, was identified as the cause of a

Viral composition — Coronaviruses are medium-sized enveloped positive-stranded RNA

● The hemagglutinin-esterase glycoprotein (HE) is found only in the betacoronaviruses,

● The gammacoronavirus genus contains primarily avian coronaviruses, the most

● The deltacoronavirus genus contains recently discovered avian coronaviruses found in

This section discusses the epidemiology of common cold coronaviruses.

The epidemiology of coronavirus disease 2019 (COVID-19), severe acute respiratory

● (See "COVID-19: Epidemiology, virology, and prevention", section on 'Epidemiology'.)

Seasonality — Common cold coronaviruses are ubiquitous; wherever investigators have

● Temperate regions – In temperate climates, coronavirus respiratory infections occur

● Subtropical regions – A seven-year study of hospitalized children in Guangzhou, China,

Routes and risk of transmission — Common cold coronaviruses probably spread in a

The clinical manifestations of infections caused by common cold human coronaviruses

● (See "COVID-19: Diagnosis" and "COVID-19: Clinical features".)

Respiratory — HCoV-229E and HCoV-OC43 have been proven to have pathogenicity in

percent), although coronaviruses were also detected in a substantial proportion of patients

Common cold coronaviruses also probably cause pneumonia in immunocompromised hosts,

Enteric — The idea that coronaviruses produce diarrhea in humans is intriguing because of

A study assessed the association between gastrointestinal manifestations (diarrhea,

POSSIBLE DISEASE ASSOCIATIONS

Neurologic disease — The clear involvement of several animal coronaviruses in acute and

Kawasaki disease — An association of common cold coronavirus infection with Kawasaki

There have been reports of a multisystem inflammatory syndrome in children associated

Common cold coronaviruses are difficult to replicate in tissue culture.

TREATMENT AND PREVENTION

There is currently no treatment recommended for common cold coronavirus infections

SOCIETY GUIDELINE LINKS

INFORMATION FOR PATIENTS

SUMMARY AND RECOMMENDATIONS

● Common cold coronaviruses are the cause of 5 to 10 percent of community-acquired

● Coronaviruses are medium-sized enveloped positive-stranded RNA viruses whose name

● There is currently no treatment recommended for common cold coronavirus infections

Use of UpToDate is subject to the Subscription and License Agreement.

1. World Health Organization. Director-General's remarks at the media briefing on 2019-nC

3. International Committee on Taxonomy of Viruses. http://ictvonline.org/virusTaxonomy.a

7. Enjuanes L, Smerdou C, Castilla J, et al. Development of protection against coronavirus

10. Perlman S. Pathogenesis of coronavirus-induced infections. Review of pathological and

22. Bradburne AF. Antigenic relationships amongst coronaviruses. Arch Gesamte

34. Nickbakhsh S, Ho A, Marques DFP, et al. Epidemiology of Seasonal Coronaviruses:

43. Lieberman D, Shimoni A, Shemer-Avni Y, et al. Respiratory viruses in adults with

66. Pene F, Merlat A, Vabret A, et al. Coronavirus 229E-related pneumonia in

68. Szczawinska-Poplonyk A, Jonczyk-Potoczna K, Breborowicz A, et al. Fatal respiratory

immunodeficiency. Influenza Other Respir Viruses 2013; 7:634.

71. Gerna G, Passarani N, Battaglia M, Rondanelli EG. Human enteric coronaviruses:

72. Chany C, Moscovici O, Lebon P, Rousset S. Association of coronavirus infection with

73. Jevšnik M, Steyer A, Zrim T, et al. Detection of human coronaviruses in simultaneously

74. Risku M, Lappalainen S, Räsänen S, Vesikari T. Detection of human coronaviruses in

82. Boucher A, Desforges M, Duquette P, Talbot PJ. Long-term human coronavirus-myelin

83. Arbour N, Day R, Newcombe J, Talbot PJ. Neuroinvasion by human respiratory

89. Sizun J, Arbour N, Talbot PJ. Comparison of immunofluorescence with monoclonal

93. Keyaerts E, Li S, Vijgen L, et al. Antiviral activity of chloroquine against human

98. Dellanno C, Vega Q, Boesenberg D. The antiviral action of common household

Phylogenetic tree of coronaviruses [1]

Graphic 128365 Version 1.0

Coronavirus electron micrograph

Group of coronavirus particles, negatively stained with phosphotungstic acid (PTA).

Graphic 62033 Version 4.0