Coronaviruses - UpToDate https://www.uptodate.

com/contents/coronaviruses/print

Official reprint from UpToDate®

www.uptodate.com ©2020 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

The content on the UpToDate website is not intended nor recommended as a substitute for
medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other
qualified health care professional regarding any medical questions or conditions. The use of
UpToDate content is governed by the UpToDate Terms of Use. ©2020 UpToDate, Inc. All rights
reserved.

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: Feb 2020. | This topic last updated: Feb 18, 2020.

INTRODUCTION

Coronaviruses are important human and animal pathogens. During epidemics, they 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 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, epidemiology, clinical manifestations, diagnosis, treatment, and prevention of

community-acquired coronaviruses will be discussed here. Severe acute respiratory syndrome
coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and
coronavirus disease 2019 (COVID-19) are reviewed separately. (See "Severe acute respiratory
syndrome (SARS)" and "Middle East respiratory syndrome coronavirus: Virology, pathogenesis,
and epidemiology" and "Coronavirus disease 2019 (COVID-19)".)

1 of 21 3/23/2020, 9:17 PM
Coronaviruses - UpToDate https://www.uptodate.com/contents/coronaviruses/print

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 elsewhere, 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]. COVID-19 is discussed in detail elsewhere. (See
"Coronavirus disease 2019 (COVID-19)".)

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], and the
severe acute respiratory syndrome coronavirus [SARS-CoV]) (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 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

2 of 21 3/23/2020, 9:17 PM
Coronaviruses - UpToDate https://www.uptodate.com/contents/coronaviruses/print

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 (figure 1) [2,3]. There are five non-SARS coronavirus serotypes that have been associated
with disease in humans: HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, and a novel
coronavirus (MERS-CoV) that emerged in 2012.

● 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 the SARS-CoV (a betacoronavirus), 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.

● 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], and SARS-
CoV, although the last two are genetically somewhat distant from HCoV-OC43 and HCoV-

3 of 21 3/23/2020, 9:17 PM
Coronaviruses - UpToDate https://www.uptodate.com/contents/coronaviruses/print

HKU1 (figure 1).

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 1900 [20].

● The gammacoronavirus genus contains primarily avian coronaviruses, the most prominent of
which is infectious bronchitis virus of chickens. This is 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 community-acquired 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

Seasonality — Community-acquired coronaviruses are ubiquitous; wherever investigators have

looked, they have been detected. 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]. 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 [33]. In other surveys, HCoV-OC43,
HCoV-NL63, HCoV-229E, and HCoV-HKU1 predominate unpredictably in certain years and in

4 of 21 3/23/2020, 9:17 PM
Coronaviruses - UpToDate https://www.uptodate.com/contents/coronaviruses/print

certain parts of the world [26,32-34]. In almost all such 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.

A large polymerase chain reaction (PCR)-based study of viruses in adults and children with acute
respiratory illness was performed in Scotland, with sampling in over 44,000 episodes over nine
years and gives some idea of the incidence and seasonality of community-acquired HCoV
infections in relation to other respiratory viruses in a temperate climate [35]. HCoV infections were
most common in the winter, were distributed across all age groups, and were less common than
those caused by rhinovirus, influenza, or respiratory syncytial virus but more common than other
respiratory viruses; coinfections were relatively common, particularly in young children.

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 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 [34]. HCoV-associated
lower respiratory tract infection hospitalization rates for the population under five years were
calculated at 1.5 per 1000 children per year.

Routes of transmission — Respiratory coronaviruses probably spread in a fashion similar to that

of rhinoviruses, via direct contact with infected secretions or large aerosol droplets. 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 [36]. 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].

Middle East respiratory syndrome and severe acute respiratory syndrome are both zoonoses.
Animals implicated in these infections are discussed in detail separately. (See "Middle East
respiratory syndrome coronavirus: Virology, pathogenesis, and epidemiology", section on 'Possible
sources and modes of transmission' and "Severe acute respiratory syndrome (SARS)", section on
'Intermediate host and reservoir'.)

CLINICAL MANIFESTATIONS

The clinical manifestations of infections caused by community-acquired human coronaviruses

(HCoVs) are described here; coronavirus disease 2019 (COVID-19), Middle East respiratory
syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus (SARS-

5 of 21 3/23/2020, 9:17 PM
Coronaviruses - UpToDate https://www.uptodate.com/contents/coronaviruses/print

CoV) are discussed separately. (See "Coronavirus disease 2019 (COVID-19)" and "Middle East
respiratory syndrome coronavirus: Clinical manifestations and diagnosis", section on 'Clinical
manifestations' and "Severe acute respiratory syndrome (SARS)", 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 upper
respiratory tract symptoms such as nasal congestion and rhinorrhea [23,39]. 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.

Human 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, coronaviruses can be detected in middle ear
effusions and have been implicated as important viral causes of acute otitis media in children [40].
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 [34,41]. 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 HCoV RNA
concentration (cycle threshold <28) and both respiratory tract disease (compared with
asymptomatic controls) and lack of coinfection [34]. (See "Epidemiology, clinical manifestations,
and pathogenesis of rhinovirus infections" and "Acute otitis media in children: Epidemiology,
microbiology, and complications", section on 'Viral pathogens'.)

Coronavirus infections have also been linked to more severe respiratory diseases. In adults with
community-acquired pneumonia, 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,
coronaviruses were detected more frequently in those with pneumonia (13 percent) than in healthy
controls (4 percent), although coronaviruses were also detected in a substantial proportion of
patients with nonpneumonic lower respiratory tract infection (10 percent) [42]. 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

6 of 21 3/23/2020, 9:17 PM
Coronaviruses - UpToDate https://www.uptodate.com/contents/coronaviruses/print

without evidence of pneumonia) were sampled [43]. HCoV was the third most common virus
detected (after rhinovirus and influenza virus) and was found significantly more often than in
matched healthy controls. In another study, the numbers were small and the difference in detection
of coronaviruses in adults with community-acquired pneumonia compared with asymptomatic
individuals was not significant [44].

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 [45]. Further information on the role of
coronaviruses in acute respiratory illness in adults comes from a four-year cohort study comparing
HCoV-229E with HCoV-OC43 [46].

Among older adult patients, there is increasing evidence that 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 [47-50]. Several outbreaks of HCoV-OC43 respiratory disease in older adults living in
long-term care facilities have been described [51,52], 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 [53].

In children hospitalized in New York City with HCoV 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 [54].

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) [55]. They have been temporally linked to
acute asthma attacks in both children and adults [56-58]. 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 [24,59,60]. They are also an important cause of nosocomial
infections in neonatal intensive care units [61]. One of the more recently discovered human
coronaviruses, HCoV-NL63, has been associated with croup in children [54,62,63].

Coronaviruses also probably cause pneumonia in immunocompromised hosts, including adults

7 of 21 3/23/2020, 9:17 PM
Coronaviruses - UpToDate https://www.uptodate.com/contents/coronaviruses/print

with HIV infection [64-67]. 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 [68]. 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 [69]. (See "Parainfluenza viruses in adults" and
"Parainfluenza viruses in children" and "Viral infections following lung transplantation", section on
'Rejection'.)

The clinical manifestations of COVID-19, MERS-CoV, and SARS-CoV are discussed separately.
(See "Coronavirus disease 2019 (COVID-19)", section on 'Clinical features' and "Severe acute
respiratory syndrome (SARS)", section on 'Clinical manifestations' and "Middle East respiratory
syndrome coronavirus: Clinical manifestations and diagnosis", section on 'Clinical manifestations'.)

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 [70] or
necrotizing enterocolitis in newborns [71]. In several studies, CVLPs have been purified that
appear to be antigenically related to HCoV-OC43 [70].

All four HCoV 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) [31,72]. 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 [72,73]. In a study that used RT-PCR to investigate the frequency of 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 [74].

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) [75]. Viruses were sought
from respiratory and stool samples and bacteria from stool samples only. Gastrointestinal

8 of 21 3/23/2020, 9:17 PM
Coronaviruses - UpToDate https://www.uptodate.com/contents/coronaviruses/print

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. Community-acquired human coronaviruses (HCoVs) can infect neural cells in vitro
[76], and three-week-old mice develop generalized encephalitis after intracerebral inoculation with
HCoV-OC43 [77]. HCoV-OC43 RNA sequences have been detected in the cerebrospinal fluid of a
15-year-old boy with acute demyelinating encephalomyelitis (ADEM) [78]. 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 [79].

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) [80], investigators
have sought to link 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 [81]. 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 [82].

Despite these findings, an etiologic connection between coronaviruses and MS or other

demyelinating diseases remains tentative and unproven. (See "Manifestations of multiple sclerosis
in adults".)

Kawasaki disease — An association of coronavirus infection with Kawasaki disease was reported
by one group of investigators and stimulated a flurry of investigation worldwide [83]. Others failed
to confirm this finding, and, at the present time, it is assumed that known coronaviruses have no
role in this disease [84,85]. (See "Kawasaki disease: Epidemiology and etiology", section on
'Infectious etiology'.)

9 of 21 3/23/2020, 9:17 PM
Coronaviruses - UpToDate https://www.uptodate.com/contents/coronaviruses/print

DIAGNOSIS

Since there is no effective treatment for coronavirus infections, establishing the diagnosis is of
limited utility in patients suspected of having community-acquired coronavirus infections. In
contrast, diagnosing coronavirus disease 2019 (COVID-19), Middle East respiratory syndrome
coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus (SARS-CoV) is
critically important for understanding outbreak epidemiology and limiting transmission of infection.
(See "Coronavirus disease 2019 (COVID-19)", section on 'Evaluation and diagnosis' and "Middle
East respiratory syndrome coronavirus: Clinical manifestations and diagnosis", section on
'Diagnosis' and "Severe acute respiratory syndrome (SARS)", section on 'Diagnosis'.)

Until recently, no sensitive, rapid method existed to detect all of the known human coronavirus
strains. Rapid techniques that can be used to detect coronaviruses from nasopharyngeal samples
include reverse-transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence
antigen detection assays [86-88].

Because of its utility for detecting all four of the known human coronavirus strains to cause
community-acquired infections, 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 [86,89]. The sensitivity may be further
improved by using real-time RT-PCR [32]. (See "Severe acute respiratory syndrome (SARS)",
section on 'Diagnosis'.)

Community-acquired coronaviruses are difficult to replicate in tissue culture.

TREATMENT AND PREVENTION

There is currently no treatment recommended for coronavirus infections except for supportive care
as needed. Several antivirals and other agents were used during the severe acute respiratory
syndrome coronavirus (SARS-CoV) outbreak, but the efficacy of these drugs has not been
established. (See "Severe acute respiratory syndrome (SARS)", section on 'Treatment'.)

Chloroquine, which has potent antiviral activity against the SARS-CoV [90], has been shown to
have similar activity against HCoV-229E in cultured cells [91] and against HCoV-OC43 both in
cultured cells and in a mouse model [92]. However, there have been no studies of efficacy in
humans.

Preventive measures are the same as for rhinovirus infections, which consist of handwashing and

10 of 21 3/23/2020, 9:17 PM
Coronaviruses - UpToDate https://www.uptodate.com/contents/coronaviruses/print

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 [93]. More detailed
information on prevention of coronavirus disease 2019 (COVID-19), Middle East respiratory
syndrome coronavirus (MERS-CoV), and SARS-CoV is discussed separately. (See "Coronavirus
disease 2019 (COVID-19)", 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 [94]. 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 [95-97].
Likewise, hexachlorophene [98], 2% glutaraldehyde [95] and 1% povidone-iodine [95,97] 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 [96,97]. Coronaviruses were not killed by
benzalkonium chloride or chlorhexidine unless 70% ethanol was added [95].

There has been little interest in developing vaccines for the non-SARS community-acquired
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 [36]. 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 [99]. There has been interest in the
development of a SARS-CoV vaccine and a MERS-CoV vaccine. (See "Severe acute respiratory
syndrome (SARS)", section on 'Vaccine development' and "Middle East respiratory syndrome
coronavirus: Treatment and prevention", section on 'Vaccine development'.)

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: Coronavirus disease 2019
(COVID-19)" and "Society guideline links: Middle East respiratory syndrome coronavirus".)

11 of 21 3/23/2020, 9:17 PM
Coronaviruses - UpToDate https://www.uptodate.com/contents/coronaviruses/print

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics."
The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading
level, and they answer the four or five key questions a patient might have about a given condition.
These articles are best for patients who want a general overview and who prefer short, easy-to-
read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and
more detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or
e-mail these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on "patient info" and the keyword(s) of interest.)

● Basics topic (see "Patient education: Coronavirus disease 2019 (COVID-19) (The Basics)")

SUMMARY AND RECOMMENDATIONS

● 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 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.)

● Community-acquired coronaviruses are ubiquitous; wherever investigators have looked, they

have been detected. 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. (See 'Epidemiology' above.)

● Most community-acquired coronavirus infections are diagnosed clinically, although reverse-

transcriptase polymerase chain reaction applied to respiratory secretions is the diagnostic test
of choice. (See 'Diagnosis' above and "Middle East respiratory syndrome coronavirus: Clinical
manifestations and diagnosis", section on 'Diagnosis'.)

12 of 21 3/23/2020, 9:17 PM
Coronaviruses - UpToDate https://www.uptodate.com/contents/coronaviruses/print

● There is currently no treatment recommended for coronavirus infections except for supportive
care as needed. (See 'Treatment and prevention' above and "Middle East respiratory
syndrome coronavirus: Treatment and prevention", section on 'Treatment'.)

● Severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome
coronavirus are discussed in detail separately. (See "Severe acute respiratory syndrome
(SARS)" and "Middle East respiratory syndrome coronavirus: Virology, pathogenesis, and
epidemiology".)

● 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 "Coronavirus
disease 2019 (COVID-19)".)

REFERENCES

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

n 11 February 2020. https://www.who.int/dg/speeches/detail/who-director-general-s-remarks-
at-the-media-briefing-on-2019-ncov-on-11-february-2020 (Accessed on February 12, 2020).

2. Chan JF, Lau SK, To KK, et al. Middle East respiratory syndrome coronavirus: another
zoonotic betacoronavirus causing SARS-like disease. Clin Microbiol Rev 2015; 28:465.

3. International Committee on Taxonomy of Viruses. http://ictvonline.org/virusTaxonomy.asp (Ac

cessed on May 21, 2015).

4. 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 U S A 1967; 57:933.

5. Masters PS, Perlman S. Coronaviridae. In: Fields Virology, 6th ed, Knipe DM, Howley PM, C
ohen JI, et al (Eds), Lippincott Williams & Wilkins, a Wolters Kluwer business, Philadelphia 2
013. Vol 2, p.825.

6. McIntosh K, Peiris JSM. Coronaviruses. In: Clinical Virology, 3rd ed, Richman DD, Whitley R
J, Hayden FG (Eds), ASM Press, Washington, DC 2009. p.1155.

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

13 of 21 3/23/2020, 9:17 PM
Coronaviruses - UpToDate https://www.uptodate.com/contents/coronaviruses/print

induced diseases. A review. Adv Exp Med Biol 1995; 380:197.

8. Masters PS, Kuo L, Ye R, et al. Genetic and molecular biological analysis of protein-protein
interactions in coronavirus assembly. Adv Exp Med Biol 2006; 581:163.

9. Kuo L, Masters PS. Genetic evidence for a structural interaction between the carboxy termini
of the membrane and nucleocapsid proteins of mouse hepatitis virus. J Virol 2002; 76:4987.

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

immunological aspects. Adv Exp Med Biol 1998; 440:503.

11. Luytjes W, Bredenbeek PJ, Noten AF, et al. Sequence of mouse hepatitis virus A59 mRNA 2:
indications for RNA recombination between coronaviruses and influenza C virus. Virology
1988; 166:415.

12. Siu YL, Teoh KT, Lo J, et al. The M, E, and N structural proteins of the severe acute
respiratory syndrome coronavirus are required for efficient assembly, trafficking, and release
of virus-like particles. J Virol 2008; 82:11318.

13. Anthony SJ, Johnson CK, Greig DJ, et al. Global patterns in coronavirus diversity. Virus Evol
2017; 3:vex012.

14. Yeager CL, Ashmun RA, Williams RK, et al. Human aminopeptidase N is a receptor for
human coronavirus 229E. Nature 1992; 357:420.

15. Hofmann H, Pyrc K, van der Hoek L, et al. Human coronavirus NL63 employs the severe
acute respiratory syndrome coronavirus receptor for cellular entry. Proc Natl Acad Sci U S A
2005; 102:7988.

16. Vlasak R, Luytjes W, Spaan W, Palese P. Human and bovine coronaviruses recognize sialic
acid-containing receptors similar to those of influenza C viruses. Proc Natl Acad Sci U S A
1988; 85:4526.

17. Zaki AM, van Boheemen S, Bestebroer TM, et al. Isolation of a novel coronavirus from a man
with pneumonia in Saudi Arabia. N Engl J Med 2012; 367:1814.

18. Centers for Disease Control and Prevention (CDC). Severe respiratory illness associated
with a novel coronavirus--Saudi Arabia and Qatar, 2012. MMWR Morb Mortal Wkly Rep
2012; 61:820.

19. Carstens EB. Ratification vote on taxonomic proposals to the International Committee on

14 of 21 3/23/2020, 9:17 PM
Coronaviruses - UpToDate https://www.uptodate.com/contents/coronaviruses/print

Taxonomy of Viruses (2009). Arch Virol 2010; 155:133.

20. Vijgen L, Keyaerts E, Moës E, et al. Complete genomic sequence of human coronavirus
OC43: molecular clock analysis suggests a relatively recent zoonotic coronavirus
transmission event. J Virol 2005; 79:1595.

21. Hamre D, Procknow JJ. A new virus isolated from the human respiratory tract. Proc Soc Exp
Biol Med 1966; 121:190.

22. Bradburne AF. Antigenic relationships amongst coronaviruses. Arch Gesamte Virusforsch
1970; 31:352.

23. Bradburne AF, Bynoe ML, Tyrrell DA. Effects of a "new" human respiratory virus in
volunteers. Br Med J 1967; 3:767.

24. McIntosh K, Chao RK, Krause HE, et al. Coronavirus infection in acute lower respiratory tract
disease of infants. J Infect Dis 1974; 130:502.

25. McIntosh K, Kapikian AZ, Turner HC, et al. Seroepidemiologic studies of coronavirus
infection in adults and children. Am J Epidemiol 1970; 91:585.

26. Monto AS. Medical reviews. Coronaviruses. Yale J Biol Med 1974; 47:234.

27. Esper F, Weibel C, Ferguson D, et al. Evidence of a novel human coronavirus that is
associated with respiratory tract disease in infants and young children. J Infect Dis 2005;
191:492.

28. Fouchier RA, Hartwig NG, Bestebroer TM, et al. A previously undescribed coronavirus
associated with respiratory disease in humans. Proc Natl Acad Sci U S A 2004; 101:6212.

29. van der Hoek L, Pyrc K, Jebbink MF, et al. Identification of a new human coronavirus. Nat
Med 2004; 10:368.

30. Woo PC, Lau SK, Chu CM, et al. Characterization and complete genome sequence of a
novel coronavirus, coronavirus HKU1, from patients with pneumonia. J Virol 2005; 79:884.

31. Vabret A, Dina J, Gouarin S, et al. Human (non-severe acute respiratory syndrome)
coronavirus infections in hospitalised children in France. J Paediatr Child Health 2008;
44:176.

32. Gaunt ER, Hardie A, Claas EC, et al. Epidemiology and clinical presentations of the four

15 of 21 3/23/2020, 9:17 PM
Coronaviruses - UpToDate https://www.uptodate.com/contents/coronaviruses/print

human coronaviruses 229E, HKU1, NL63, and OC43 detected over 3 years using a novel
multiplex real-time PCR method. J Clin Microbiol 2010; 48:2940.

33. Zeng ZQ, Chen DH, Tan WP, et al. 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. Eur J Clin Microbiol Infect Dis 2018; 37:363.

34. Heimdal I, Moe N, Krokstad S, et al. Human Coronavirus in Hospitalized Children With
Respiratory Tract Infections: A 9-Year Population-Based Study From Norway. J Infect Dis
2019; 219:1198.

35. Nickbakhsh S, Thorburn F, VON Wissmann B, et al. Extensive multiplex PCR diagnostics
reveal new insights into the epidemiology of viral respiratory infections. Epidemiol Infect
2016; 144:2064.

36. Reed SE. The behaviour of recent isolates of human respiratory coronavirus in vitro and in
volunteers: evidence of heterogeneity among 229E-related strains. J Med Virol 1984; 13:179.

37. Gagneur A, Vallet S, Talbot PJ, et al. Outbreaks of human coronavirus in a pediatric and
neonatal intensive care unit. Eur J Pediatr 2008; 167:1427.

38. Falsey AR, Dallal GE, Formica MA, et al. Long-term care facilities: a cornucopia of viral
pathogens. J Am Geriatr Soc 2008; 56:1281.

39. Bradburne AF, Somerset BA. Coronative antibody tires in sera of healthy adults and
experimentally infected volunteers. J Hyg (Lond) 1972; 70:235.

40. Chonmaitree T, Revai K, Grady JJ, et al. Viral upper respiratory tract infection and otitis
media complication in young children. Clin Infect Dis 2008; 46:815.

41. Prill MM, Iwane MK, Edwards KM, et al. Human coronavirus in young children hospitalized
for acute respiratory illness and asymptomatic controls. Pediatr Infect Dis J 2012; 31:235.

42. Lieberman D, Shimoni A, Shemer-Avni Y, et al. Respiratory viruses in adults with community-
acquired pneumonia. Chest 2010; 138:811.

43. Ieven M, Coenen S, Loens K, et al. Aetiology of lower respiratory tract infection in adults in
primary care: a prospective study in 11 European countries. Clin Microbiol Infect 2018;
24:1158.

44. Self WH, Williams DJ, Zhu Y, et al. Respiratory Viral Detection in Children and Adults:

16 of 21 3/23/2020, 9:17 PM
Coronaviruses - UpToDate https://www.uptodate.com/contents/coronaviruses/print

Comparing Asymptomatic Controls and Patients With Community-Acquired Pneumonia. J

Infect Dis 2016; 213:584.

45. Wansaula Z, Olsen SJ, Casal MG, et al. Surveillance for severe acute respiratory infections
in Southern Arizona, 2010-2014. Influenza Other Respir Viruses 2016; 10:161.

46. Walsh EE, Shin JH, Falsey AR. Clinical impact of human coronaviruses 229E and OC43
infection in diverse adult populations. J Infect Dis 2013; 208:1634.

47. Falsey AR, McCann RM, Hall WJ, et al. The "common cold" in frail older persons: impact of
rhinovirus and coronavirus in a senior daycare center. J Am Geriatr Soc 1997; 45:706.

48. Graat JM, Schouten EG, Heijnen ML, et al. A prospective, community-based study on
virologic assessment among elderly people with and without symptoms of acute respiratory
infection. J Clin Epidemiol 2003; 56:1218.

49. Nicholson KG, Kent J, Hammersley V, Cancio E. Acute viral infections of upper respiratory
tract in elderly people living in the community: comparative, prospective, population based
study of disease burden. BMJ 1997; 315:1060.

50. Kherad O, Kaiser L, Bridevaux PO, et al. Upper-respiratory viral infection, biomarkers, and
COPD exacerbations. Chest 2010; 138:896.

51. Birch CJ, Clothier HJ, Seccull A, et al. Human coronavirus OC43 causes influenza-like illness
in residents and staff of aged-care facilities in Melbourne, Australia. Epidemiol Infect 2005;
133:273.

52. Patrick DM, Petric M, Skowronski DM, et al. An Outbreak of Human Coronavirus OC43
Infection and Serological Cross-reactivity with SARS Coronavirus. Can J Infect Dis Med
Microbiol 2006; 17:330.

53. Galante O, Avni YS, Fuchs L, et al. Coronavirus NL63-induced Adult Respiratory Distress
Syndrome. Am J Respir Crit Care Med 2016; 193:100.

54. Varghese L, Zachariah P, Vargas C, et al. Epidemiology and Clinical Features of Human
Coronaviruses in the Pediatric Population. J Pediatric Infect Dis Soc 2018; 7:151.

55. Zwaans WA, Mallia P, van Winden ME, Rohde GG. The relevance of respiratory viral
infections in the exacerbations of chronic obstructive pulmonary disease—a systematic
review. J Clin Virol 2014; 61:181.

17 of 21 3/23/2020, 9:17 PM
Coronaviruses - UpToDate https://www.uptodate.com/contents/coronaviruses/print

56. McIntosh K, Ellis EF, Hoffman LS, et al. The association of viral and bacterial respiratory
infections with exacerbations of wheezing in young asthmatic children. J Pediatr 1973;
82:578.

57. Nicholson KG, Kent J, Ireland DC. Respiratory viruses and exacerbations of asthma in
adults. BMJ 1993; 307:982.

58. Kwak HJ, Park DW, Kim JE, et al. Prevalence and Risk Factors of Respiratory Viral
Infections in Exacerbations of Chronic Obstructive Pulmonary Disease. Tohoku J Exp Med
2016; 240:131.

59. Kuypers J, Martin ET, Heugel J, et al. Clinical disease in children associated with newly
described coronavirus subtypes. Pediatrics 2007; 119:e70.

60. Talbot HK, Shepherd BE, Crowe JE Jr, et al. The pediatric burden of human coronaviruses
evaluated for twenty years. Pediatr Infect Dis J 2009; 28:682.

61. Sizun J, Soupre D, Legrand MC, et al. Neonatal nosocomial respiratory infection with
coronavirus: a prospective study in a neonatal intensive care unit. Acta Paediatr 1995;
84:617.

62. van der Hoek L, Sure K, Ihorst G, et al. Croup is associated with the novel coronavirus NL63.
PLoS Med 2005; 2:e240.

63. Sung JY, Lee HJ, Eun BW, et al. Role of human coronavirus NL63 in hospitalized children
with croup. Pediatr Infect Dis J 2010; 29:822.

64. Garbino J, Inoubli S, Mossdorf E, et al. Respiratory viruses in HIV-infected patients with
suspected respiratory opportunistic infection. AIDS 2008; 22:701.

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

immunocompromised patients. Clin Infect Dis 2003; 37:929.

66. Simon A, Völz S, Fleischhack G, et al. Human coronavirus OC43 pneumonia in a pediatric
cancer patient with down syndrome and acute lymphoblastic leukemia. J Pediatr Hematol
Oncol 2007; 29:432.

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

distress syndrome due to coronavirus infection in a child with severe combined
immunodeficiency. Influenza Other Respir Viruses 2013; 7:634.

18 of 21 3/23/2020, 9:17 PM
Coronaviruses - UpToDate https://www.uptodate.com/contents/coronaviruses/print

68. Ogimi C, Waghmare AA, Kuypers JM, et al. Clinical Significance of Human Coronavirus in
Bronchoalveolar Lavage Samples From Hematopoietic Cell Transplant Recipients and
Patients With Hematologic Malignancies. Clin Infect Dis 2017; 64:1532.

69. Kumar D, Husain S, Chen MH, et al. A prospective molecular surveillance study evaluating
the clinical impact of community-acquired respiratory viruses in lung transplant recipients.
Transplantation 2010; 89:1028.

70. Gerna G, Passarani N, Battaglia M, Rondanelli EG. Human enteric coronaviruses: antigenic
relatedness to human coronavirus OC43 and possible etiologic role in viral gastroenteritis. J
Infect Dis 1985; 151:796.

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

neonatal necrotizing enterocolitis. Pediatrics 1982; 69:209.

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

collected stool samples and nasopharyngeal swabs from hospitalized children with acute
gastroenteritis. Virol J 2013; 10:46.

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

children with acute gastroenteritis. J Clin Virol 2010; 48:27.

74. Esper F, Ou Z, Huang YT. Human coronaviruses are uncommon in patients with
gastrointestinal illness. J Clin Virol 2010; 48:131.

75. Minodier L, Masse S, Capai L, et al. Clinical and virological factors associated with
gastrointestinal symptoms in patients with acute respiratory infection: a two-year prospective
study in general practice medicine. BMC Infect Dis 2017; 17:729.

76. Arbour N, Ekandé S, Côté G, et al. Persistent infection of human oligodendrocytic and
neuroglial cell lines by human coronavirus 229E. J Virol 1999; 73:3326.

77. Jacomy H, Talbot PJ. Vacuolating encephalitis in mice infected by human coronavirus OC43.
Virology 2003; 315:20.

78. Yeh EA, Collins A, Cohen ME, et al. Detection of coronavirus in the central nervous system
of a child with acute disseminated encephalomyelitis. Pediatrics 2004; 113:e73.

79. Morfopoulou S, Brown JR, Davies EG, et al. Human Coronavirus OC43 Associated with Fatal
Encephalitis. N Engl J Med 2016; 375:497.

19 of 21 3/23/2020, 9:17 PM
Coronaviruses - UpToDate https://www.uptodate.com/contents/coronaviruses/print

80. Houtman JJ, Fleming JO. Pathogenesis of mouse hepatitis virus-induced demyelination. J
Neurovirol 1996; 2:361.

81. Boucher A, Desforges M, Duquette P, Talbot PJ. Long-term human coronavirus-myelin cross-
reactive T-cell clones derived from multiple sclerosis patients. Clin Immunol 2007; 123:258.

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

coronaviruses. J Virol 2000; 74:8913.

83. Esper F, Shapiro ED, Weibel C, et al. Association between a novel human coronavirus and
Kawasaki disease. J Infect Dis 2005; 191:499.

84. Chang LY, Chiang BL, Kao CL, et al. Lack of association between infection with a novel
human coronavirus (HCoV), HCoV-NH, and Kawasaki disease in Taiwan. J Infect Dis 2006;
193:283.

85. Dominguez SR, Anderson MS, Glodé MP, et al. Blinded case-control study of the relationship
between human coronavirus NL63 and Kawasaki syndrome. J Infect Dis 2006; 194:1697.

86. Gerna G, Campanini G, Rovida F, et al. 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. J Med Virol 2006; 78:938.

87. Gerna G, Percivalle E, Sarasini A, et al. Human respiratory coronavirus HKU1 versus other
coronavirus infections in Italian hospitalised patients. J Clin Virol 2007; 38:244.

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

antibodies and RT-PCR for the detection of human coronaviruses 229E and OC43 in cell
culture. J Virol Methods 1998; 72:145.

89. Zlateva KT, Coenjaerts FE, Crusio KM, et al. No novel coronaviruses identified in a large
collection of human nasopharyngeal specimens using family-wide CODEHOP-based
primers. Arch Virol 2013; 158:251.

90. Keyaerts E, Vijgen L, Maes P, et al. In vitro inhibition of severe acute respiratory syndrome
coronavirus by chloroquine. Biochem Biophys Res Commun 2004; 323:264.

91. Kono M, Tatsumi K, Imai AM, et al. Inhibition of human coronavirus 229E infection in human
epithelial lung cells (L132) by chloroquine: involvement of p38 MAPK and ERK. Antiviral Res
2008; 77:150.

20 of 21 3/23/2020, 9:17 PM
Coronaviruses - UpToDate https://www.uptodate.com/contents/coronaviruses/print

92. Keyaerts E, Li S, Vijgen L, et al. Antiviral activity of chloroquine against human coronavirus
OC43 infection in newborn mice. Antimicrob Agents Chemother 2009; 53:3416.

93. Otter JA, Donskey C, Yezli S, et al. Transmission of SARS and MERS coronaviruses and
influenza virus in healthcare settings: the possible role of dry surface contamination. J Hosp
Infect 2016; 92:235.

94. Geller C, Varbanov M, Duval RE. Human coronaviruses: insights into environmental
resistance and its influence on the development of new antiseptic strategies. Viruses 2012;
4:3044.

95. Sattar SA, Springthorpe VS, Karim Y, Loro P. Chemical disinfection of non-porous inanimate
surfaces experimentally contaminated with four human pathogenic viruses. Epidemiol Infect
1989; 102:493.

96. Hulkower RL, Casanova LM, Rutala WA, et al. Inactivation of surrogate coronaviruses on
hard surfaces by health care germicides. Am J Infect Control 2011; 39:401.

97. Dellanno C, Vega Q, Boesenberg D. The antiviral action of common household disinfectants
and antiseptics against murine hepatitis virus, a potential surrogate for SARS coronavirus.
Am J Infect Control 2009; 37:649.

98. Cao J, Forrest JC, Zhang X. A screen of the NIH Clinical Collection small molecule library
identifies potential anti-coronavirus drugs. Antiviral Res 2015; 114:1.

99. Vennema H, de Groot RJ, Harbour DA, et al. Early death after feline infectious peritonitis
virus challenge due to recombinant vaccinia virus immunization. J Virol 1990; 64:1407.

Topic 8298 Version 51.0

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

21 of 21 3/23/2020, 9:17 PM