2164 CHAPTER 342  PRE-2019 Coronaviruses

342
PRE-2019 CORONAVIRUSES
SUSAN I. GERBER AND JOHN T. WATSON

DEFINITION
Human coronaviruses were, until 2003, recognized as a frequent cause of
common cold symptoms, occasionally a cause of lower respiratory tract disease,
but rarely if ever a cause of serious disease. In 2003 a novel coronavirus was
recognized in humans as the etiologic agent of the outbreak of severe acute
respiratory syndrome (SARS).1,2 The SARS outbreak demonstrated that
coronaviruses can be serious human pathogens and led to discovery of other
novel human coronaviruses as well as multiple novel coronaviruses in bats,
the likely reservoir for SARS coronavirus. In 2012 the Middle East respira-
tory syndrome (MERS) coronavirus emerged and provided another example
of coronavirus’s ability to cause severe human disease.3,4 Then in 2019, the
SARS coronavirus 2 (SARS-CoV-2) emerged and caused coronavirus disease
2019 (COVID-19), which has led to the largest global pandemic for at least
a century (Chapter 342A).

The Pathogens
Coronaviruses are members of the family Coronaviridae, which includes two
subfamilies, Coronavirinae and Torovirinae. Coronaviruses are single-stranded
positive-sense RNA viruses with a genome of approximately 30 kb, the largest
genome among RNA viruses. These viruses were named coronaviruses because
by electron microscopy they have club-shaped surface projections that give
them a crown-like appearance. The genome encodes four or five structural
proteins (a spike protein [S], a small envelope protein [E], a membrane protein
[M], a nucleocapsid protein [N], and sometimes a hemagglutinin-esterase
protein [HE]), a varying number of open reading frames scattered among
the structural genes, and a polyprotein that is processed into multiple (usually
16) nonstructural proteins. These nonstructural proteins participate in virus
replication but are not incorporated into the virion. Coronaviruses have also

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 CHAPTER 342  PRE-2019 Coronaviruses 2164.e3

ABSTRACT KEYWORDS
Human coronaviruses were, until 2003, recognized frequently as a cause of coronavirus
common cold symptoms, occasionally as a cause of lower respiratory tract severe acute respiratory syndrome (SARS)
disease, but rarely if ever as a cause of serious disease. In 2003, however, a Middle East respiratory syndrome (MERS)
novel coronavirus was recognized as the cause of the severe acute respiratory human-animal interface
syndrome (SARS). The SARS outbreak demonstrated that coronaviruses can
be serious human pathogens and led to discovery of other novel human coro-
naviruses as well as multiple novel coronaviruses in bats, the likely reservoir
for SARS coronavirus. In 2012 the Middle East respiratory syndrome (MERS)
coronavirus provided another example of coronavirus’s ability to cause severe
human disease, but the emergence of SARS coronavirus 2 (SARS-CoV-2)
and coronavirus disease 2019 (COVID-19) has resulted in the most serious
human infectious disease pandemic in at least a century.

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 CHAPTER 342  PRE-2019 Coronaviruses
been isolated from a variety of animals and birds and, in their respective
species, cause a wide range of respiratory, gastrointestinal (GI), neurologic,
and systemic illnesses. The coronaviruses are divided into four genera: alpha,
beta, gamma, and delta. The 229E and NL63 viruses are alphacoronaviruses,
whereas OC43 and HKU1 are betacoronaviruses. SARS coronavirus, MERS
coronavirus, and SARS-CoV-2 are betacoronaviruses but belong to different
lineages. Detection and characterization of novel coronaviruses in bats has
greatly expanded our understanding of diversity among coronaviruses and
will likely continue to do so.  enzyme 2 (ACE2), respectively. The receptors for OC43 and HKU1 corona-
Pre-2019 Coronaviruses
EPIDEMIOLOGY
The common human coronaviruses—229E, OC43, NL63, and HKU1—appear
to be transmitted through close contact that probably includes contamination
of hands from person-to-person contact or from fomites, followed by autoin-
oculation to the mucosal surfaces of the mouth, nose, or eyes or inhalation of
infectious droplets and possibly aerosols. Infections are seasonal, with U.S.
cases peaking in December through March.4b Recent data suggest that about
25% of cases are from an infected household contact.4c
Symptoms occur 2 to 4 days after infection. These coronaviruses are detected
in patients with acute respiratory illnesses, most often a mild upper respiratory
tract illness (i.e., common cold) but also in patients with more serious respiratory
illnesses, including pneumonia, bronchiolitis, and croup. Coronavirus infections
are detected early in childhood, and repeated infections can occur throughout
life. About 50% of children have antibodies against OC43 by 3 years of age, and
about 70% of adults have such antibodies. Up to 75% of children have antibodies
against NL63 and 229E by 3 to 4 years of age. Studies looking for 229E- and
OC43-like infections suggest that coronaviruses are associated with about 15%
of cases of the common cold and with up to 10% of cases of acute respiratory
illnesses in children and adults. Individually, 229E, OC43, HKU1, and NL63
are detected in less than 1 to 4% of cases, and their individual contributions
will vary by location and year. Serious illness has been reported in outbreaks
among elderly patients in nursing homes. In one outbreak associated with OC43
infection, for example, 23 residents and 24 staff reported influenza-like illness,
and three residents died. However, some reports have found rates of detection
of coronaviruses among hospitalized children with acute respiratory illness
and/or fever to be similar to the rates of asymptomatic controls, thereby raising
questions about the virus’s role in more severe disease and hospitalization. The
229E, OC43, NL63, and HKU1 coronaviruses can be detected throughout the
year, but peak detection is often during fall and winter months in temperate
climates. A second respiratory viral pathogen can be detected in 20 to 60% of
specimens positive for one of these coronaviruses.
Most documented SARS coronavirus infections in humans occurred in
persons ill with a SARS-like illness during the 2002–2003 global outbreak.
It is likely that wild animal markets in Guangdong Province, China, played
a key role in amplifying and introducing the virus into humans, but the
original source of the outbreak virus was likely bats. Detection of multiple
SARS-like and other coronaviruses in bats suggests that they are a rich
source of coronaviruses. A coronavirus recently isolated from bats has 95%
nucleotide sequence identity to the SARS viruses and can infect humans
via the ACE2 receptor. Although animals were the original source of human
infections, global spread of SARS coronavirus occurred through human-to-
human transmission and involved droplet, fomite transmission, and, in some
instances, probably small-particle aerosol transmission. Most transmission
occurred within households, hospitals, or other health care facilities; little
transmission occurred in the community.
MERS coronavirus was first recognized in the Arabian Peninsula in 2012.
Coronaviruses similar to the MERS coronavirus have been detected in bats,
suggesting that bats may be a source of this virus. Dromedary camels, however,
appear to act as a reservoir for the virus and a vehicle for human transmission.
Dromedary camels in the Middle East and Africa may harbor live MERS
coronavirus, and young camels in these areas nearly universally have anti-
body titers detected by the age of 2 years. Furthermore, in humans without
known preillness exposure to other human MERS cases, direct exposure to
dromedary camels during the prior 2 weeks is independently associated with
developing MERS.5 Person-to-person spread occurs within health care settings
and is associated with the majority of reported transmission. For example, an
outbreak of 186 cases in the Republic of Korea in 2015 resulted from a single
infected traveler who returned from the Arabian peninsula.6 Transmission
among household family members also has been reported, but so far there
has been no evidence of sustained community transmission. The incubation
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2165
period is estimated at just over 5 days (range, 2 to 14 days), and sporadic human
cases and clusters of MERS coronavirus infections continue to be reported. 
PATHOBIOLOGY
The human coronaviruses characterized to date infect humans through the
respiratory tract. The sites where the virus then replicates is determined at least
in part by which cells express the respective receptors. The receptors for 229E
and NL63 coronaviruses are aminopeptidase N and angiotensin-converting
viruses have not yet been determined, but OC43 may use several cell surface
molecules as receptors, including 9-O-acetylated neuraminic acid. The primary
receptor for SARS coronavirus is ACE2, but the virus also binds to two C-type
lectins expressed on dendritic cells, DC-SIGN and L-SIGN. Aminopeptidase
N is expressed in various cells, including respiratory, GI, kidney epithelial,
and myeloid cells, but 229E is known to infect only respiratory epithelial
cells. ACE2 is found in various tissues, including the lung, GI tract, heart,
and kidneys. The SARS coronavirus has consistently been detected in pneu-
mocytes in the lung and enterocytes in the GI tract and is occasionally found
in other cells, including distal tubular cells in the kidney and macrophages
in various tissues. Autopsy studies suggest that infection in the lung leads
initially to diffuse alveolar damage and later may lead to a repair process that
includes fibrosis in the alveolar walls. It is not known whether NL63, which
also uses ACE2 as its receptor, infects sites other than the respiratory tract.
The MERS coronavirus receptor is the exopeptidase dipeptidyl peptidase 4
(DPP4), also known as CD26. DPP4 is found on many different cell types
including nonciliated bronchial epithelial cells, bronchiolar epithelial cells,
alveolar epithelial cells, endothelial cells, and lung ex vivo organ cultures. In
addition, DPP4 is expressed on the epithelial cells in kidney, small intestine,
liver, and prostate as well as in activated leukocytes.
It is likely that the illness associated with coronavirus infections results from
both the cytopathic effect of the virus and the host immune and inflamma-
tory response to the viral infection. How this interplay contributes to disease,
however, is not understood. The biphasic course of SARS in some patients, with
the onset of severe disease in the second week of illness and the decrease in
lymphocyte numbers, suggests a role for the host response and virus-induced
immune suppression in the disease process. Similarly, it appears that the host
response and virus-induced immune suppression may also contribute to MERS
coronavirus disease. 
CLINICAL MANIFESTATIONS
229E, OC43, NL63, and HKU1 coronavirus infections are commonly associ-
ated with acute respiratory illnesses that are usually mild and consistent with
the common cold (Chapter 337) but can also result in the full range of acute
respiratory illnesses, including pneumonia (Chapter 91),6b croup (Chapter 401),
bronchiolitis, and bronchitis (Chapter 90). Endemic common human coronavi-
ruses account for about 5% of hospitalized adults with acute respiratory illnesses.6c
The best studied of these coronaviruses, human coronaviruses 229E
and OC43, cause respiratory symptoms (e.g., rhinorrhea, nasal conges-
tion, sore throat, cough) as well as systemic symptoms (e.g., fever, head-
ache, malaise) when they are inoculated intranasally into adult volunteers.
Symptoms develop 2 to 4 days after inoculation, but about 30% of vol-
unteers who excrete virus have no associated illness. Symptoms usually
persist for about 1 week but sometimes for as long as 3 weeks. Previous
infection does not induce high levels of protective immunity. Humans can
be reinfected with respiratory coronaviruses throughout life, and human
volunteers can be symptomatically reinfected with the same strain of coro-
navirus 1 year after the first infection. As with other infections, the severity
of disease varies among individual patients during the same outbreak and
among groups of patients during different outbreaks in the same community.
In contrast to the mild illness associated with 229E and OC43, SARS
coronavirus infection nearly always results in a serious illness that requires
hospitalization, often in an intensive care unit (ICU), and a high fatality rate.
Radiologic evidence of pneumonia was seen in nearly all SARS coronavi-
rus–infected persons, and acute respiratory distress syndrome (Chapter 96)
requiring admission to an ICU and mechanical ventilation developed in 20%
or more of patients. The initial clinical manifestation of SARS was often sys-
temic symptoms of fever, malaise, and myalgias from 2 to 10 days (rarely
>10 days) after exposure. Several days after the onset of systemic symptoms,
lower respiratory tract symptoms of nonproductive cough and shortness of
breath were noted. Unlike patients with other respiratory virus infections,
the majority of patients never experience upper respiratory tract symptoms
such as rhinorrhea, sore throat, or nasal congestion (Table 342-1). During the
2166 CHAPTER 342  PRE-2019 Coronaviruses
TABLE 342-1 PERCENTAGE OF HOSPITALIZED SARS
AND MERS CORONAVIRUS–INFECTED
PATIENTS WITH SELECTED CLINICAL AND
LABORATORY FEATURES OF SARS AND MERS
CORONAVIRUS INFECTIONS
SARS MERS
CLINICAL OR AT HOSPITAL AT
LABORATORY FINDING ADMISSION PRESENTATION
Fever 90-100% ≈90-100%
Cough or shortness of breath 40-75% 83%
Diarrhea 20-30% 26%
Chest radiograph abnormalities 65-90% 100%
Lymphopenia* 50-90% 34%
+ +
*Both CD4 and CD8 lymphocyte counts are decreased.
MERS = Middle East respiratory syndrome; SARS = severe acute respiratory syndrome.
From Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, et al. Epidemiological, demographic, and clinical
characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi
Arabia: a descriptive study. Lancet Infect Dis. 2013;13:752-761.
course of their illness, most SARS coronavirus–infected patients had elevated
liver enzyme levels and lymphopenia, including a substantial drop in numbers
of both CD4+ and CD8+ T cells. In general, children had less severe illness
than adults.
The clinical spectrum of MERS coronavirus illness ranges from asympto-
matic infection to severe illness.7 Symptoms include cough, fever, malaise,
chills, arthralgias, rigors, and dyspnea. Approximately 25% of patients have
GI symptoms that include diarrhea, vomiting, and abdominal pain. Patients
who are severely ill have pneumonia that sometimes progresses to acute res-
piratory distress syndrome.
Laboratory findings include leukopenia and lymphopenia, and some patients
have thrombocytopenia and abnormal liver enzymes. Chest radiographic find-
ings have included patchy infiltrates, lobar opacities, and similar to the SARS
coronavirus, a ground-glass appearance. 
DIAGNOSIS
Because illness is usually mild and there is no effective treatment, the
diagnosis of 229E, OC43, NL63, and HKU1 coronavirus infections has
not been important to the management of patients. The accurate diagno-
sis of SARS and MERS coronavirus infections is, however, critical for the
management of individual patients and to mount an appropriate public
health response.
229E, OC43, HKU1, and NL63 Coronavirus Infections
Coronavirus polymerase chain reaction (PCR) assays are the assays of choice
for diagnosis of infection. Most coronavirus PCR assays are type specific—that
is, specific to MERS coronavirus, SARS coronavirus, 229E, OC43, HKU1,
or NL63 RNA. Coronavirus diagnostic assays are becoming more generally
available and are sometimes part of a PCR panel designed to detect respiratory
viruses. Presence of the virus can also be inferred by electron microscopy and
confirmed by in situ or immunohistologic assays of affected tissues. Positive
immunohistologic and in situ hybridization studies document the site of
infection and help support a link between the virus and the disease process.
A variety of enzyme or fluorescent immunoassays for antibodies have been
used successfully to detect infection. Most assays detect immunoglobulin G
(IgG) antibodies, but virus neutralization antibody assays are more specific.
Serologic tests to detect a diagnostic rise in antibodies between acute and
convalescent serum specimens for 229E, OC43, HKU1, and NL63 coronavirus
infections are not helpful for managing an acute illness but can be helpful for
epidemiologic studies. 
SARS
Three features of SARS cases help guide approach to its diagnosis. First, SARS
has been documented only in persons who have some potential exposure—that
is, to patients with SARS, to a location with SARS transmission, to a laboratory
working on SARS coronavirus, or to a setting where SARS-infected animals
might be located (e.g., southern China). Second, nearly 100% of infected
patients develop chest radiographic abnormalities by day 10 of their illness.
Finally, SARS nearly always develops within 10 days of exposure. Thus a sus-
picion of SARS and a diagnostic evaluation can be limited to patients who
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have a severe lower respiratory tract illness and some potential exposure to
SARS within 10 days before the onset of illness.
Laboratory confirmation of SARS coronavirus infection early in the illness
proved to be difficult even with sensitive real-time PCR assays. Unlike in most
respiratory viral infections, the highest titer of virus or viral RNA was found
in clinical specimens from the beginning of the second week of illness. During
the first week of illness, the best way to detect infection is by a sensitive PCR
assay or a sensitive enzyme immunoassay for N protein antigen applied to
respiratory and serum specimens. During the second week of illness, respiratory
and stool specimens are most likely to be positive for viral RNA. Antibodies
were sometimes detected early in the second week of illness but at times
were not detected until 4 weeks into the illness. Because antibodies to SARS
coronavirus were rarely present before the 2003 outbreak, a single positive
antibody test result from an ill person could be considered diagnostic of an
acute SARS coronavirus infection. However, because the reemergence of SARS
coronavirus will have substantial public health, social, and economic impact,
and because of occasional cross-reacting antibodies induced by other corona-
viruses, a neutralization antibody test and confirmatory testing by a reference
laboratory are required to confirm the diagnosis. Public health departments
should be consulted for questions about SARS diagnostic tests. 
MERS
A diagnosis of MERS coronavirus infection should be considered in patients
with severe acute respiratory infection of unknown cause and a possible expo-
sure or epidemiologic link to the Arabian Peninsula.8,8b PCR assays have been
used to detect RNA in upper respiratory tract specimens (nasopharyngeal,
oropharyngeal) and preferably in lower respiratory tract specimens (sputum,
tracheal aspirate, and bronchoalveolar lavage fluid have the highest viral loads),
as well as in serum, stool, and urine. A confirmed case of MERS coronavirus
infection requires a positive PCR on at least two specific gene targets or a
single positive target with sequencing on a second.
A number of serologic assays can detect antibodies to the nucleocapsid and
spike proteins. The sensitivity and specificity of these assays for diagnosing
current or past MERS coronavirus infection have not yet been determined.
Public health departments should be consulted for questions about MERS
diagnostic tests.
TREATMENT
There is no virus-specific treatment for 229E, OC43, HKU1, and NL63 corona-
virus infections, but the illnesses are mild and usually resolve in a few days to a
week. Patients require symptomatic therapy or, uncommonly, management of
complications of infection.
Treatment of SARS and MERS coronavirus infections is more complex. For
MERS, a combination of recombinant inteferon beta-1b and lopinavir–ritonavir,
when administered within seven days of onset, was shown in one study to
lower mortality from 44% to 28% among hospitalized patients with laboratory-
confirmed disease.A1b Currently, however, there is no consensus recommendation
for the treatment of MERS, and no antiviral drug has proved to be effective for
SARS. With the high death rate associated with both of these viruses, supportive
measures, including mechanical ventilation and oxygenation regimens (Chapter
96), are key. In the SARS coronavirus outbreak, in vitro data showed little if any
antiviral effect with ribavirin and suggested that interferon alfa, SARS convales-
cent phase immune globulin, and lopinavir plus ritonavir might have been useful.
Although many people were treated during the outbreak, lack of control groups
makes it impossible to determine which if any therapies were beneficial. For MERS
coronavirus, in vitro data and animal models demonstrate inhibitory effects for
a number of antiviral agents, including interferons, ribavirin, and lopinavir/rito-
navir. Immunotherapeutic options undergoing evaluation include convalescent
plasma and monoclonal and polyclonal antibodies. However, no consensus is
currently available regarding their efficacy for treating human infection.
 
PREVENTION
Handwashing and other infection-control measures probably decrease the
spread of coronaviruses in the home, health care facilities, and other settings.
These strategies focus on reinforcing the need for patients with respiratory
illnesses to cover the nose and mouth when coughing or sneezing, to use
tissues to contain respiratory secretions, and to wash the hands after contact
with respiratory secretions. Staff should use good infection-control practices.
Within 4 months of the initiation of the 2003 SARS outbreak, the out-
break was contained and human-to-human transmission stopped without a
vaccine or effective antiviral therapy but thorough implementation of the
classic public health tools of early case detection, isolation, and contact tracing
and management, including quarantine of contacts. For MERS, the effective-
ness of these measures in interrupting transmission also has been repeatedly
demonstrated, most notably for outbreaks associated with health care facilities.
The cases of laboratory-acquired SARS coronavirus infection and the
subsequent transmission of disease to others after one such case reinforces
the importance of strict attention to safe laboratory practices. Because the
reemergence of SARS could lead to global spread, the local, national, and
global public health and health care communities must be alerted quickly and
updated regularly about new cases and the status of transmission.
Strict attention to standard contact and airborne precautions is recom-
mended for SARS and MERS coronavirus–infected patients within hospital
settings. MERS coronavirus infections continue to occur in the Middle East,
and local, national, and global public health and health care communities
should be immediately notified of a case. Vaccine development is underway
for both SARS and MERS coronaviruses. 

PROGNOSIS
Patients with typical community-acquired coronavirus infections typically
recover completely. However, patients with compromised cardiac, pulmonary,
or immune systems are at increased risk of more serious lower respiratory tract
illness, and outbreaks of human coronavirus infections in elderly patients in
chronic care facilities can cause severe lower respiratory illnesses and deaths.
In the SARS outbreak, nearly 10% of patients died. The death rate was espe-
cially high, approaching 50%, in elderly patients and patients with underlying
illnesses. Although most survivors of SARS coronavirus infection appeared
to achieve full recovery, as many as 25% had abnormal pulmonary findings
such as ground-glass opacities on chest radiograph or abnormal pulmonary
function test results (e.g., decreased diffusing capacity) 6 months or more
after their illness. The MERS fatality rate initially was reported to be about
40%, but is now lower as less severe cases and seropositive persons without
obvious infection have been identified.9 
SARS Coronavirus 2 (SARS-CoV-2) and COVID-19
See Chapter 342A.

Grade A References

A1b.  Arabi YM, Asiri AY, Assiri AM, et al. Interferon beta-1b and lopinavir-ritonavir for Middle East
respiratory syndrome. N Engl J Med. 2020;383:1645-1656.

GENERAL REFERENCES
For the General References and other additional features, please visit Expert Consult
at https://expertconsult.inkling.com.

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 CHAPTER 342  PRE-2019 Coronaviruses 2167.e1

GENERAL REFERENCES  
1. U.S. Department of Health & Human Services. Centers for Disease Control and Prevention. Severe
acute respiratory syndrome (SARS). http://www.cdc.gov/sars. Accessed June 8, 2019.  
2. World Health Organization. Severe acute respiratory syndrome (SARS). www.who.int/csr/sars/en/.
Accessed June 8, 2019.
3. U.S. Department of Health & Human Services. Centers for Disease Control and Prevention. Middle
East respiratory syndrome (MERS). http://www.cdc.gov/coronavirus/mers. Accessed June 8,
2019.
4. World Health Organization. Middle East respiratory syndrome coronavirus (MERS-CoV). http://
www.who.int/csr/disease/coronavirus_infections/en/. Accessed June 8, 2019.
  4b.  Killerby ME, Biggs HM, Haynes A, et  al. Human coronavirus circulation in the United States  
2014-2017. J Clin Virol. 2018;101:52-56.
  4c.  Monto AS, DeJonge PM, Callear AP, et al. Coronavirus occurrence and transmission over 8 years
in the HIVE cohort of households in Michigan. J Infect Dis. 2020;222:9-16.
5. Alraddadi BM, Watson JT, Almarashi A, et  al. Risk factors for primary Middle East respiratory
syndrome coronavirus illness in humans, Saudi Arabia, 2014. Emerg Infect Dis. 2016;22:49-55.
6. Kim SW, Park JW, Jung HD, et al. Risk factors for transmission of Middle East respiratory syndrome
coronavirus infection during the 2015 outbreak in South Korea. Clin Infect Dis. 2017;64:551-557.
6b.  da Veiga ABG, Martins LG, Riediger I, et al. More than just a common cold: Endemic coronaviruses
OC43, HKU1, NL63, and 229E associated with severe acute respiratory infection and fatality cases
among healthy adults. J Med Virol. 2021;93:1002-1007.
6c.  Gilca R, Carazo S, Amini R, et al. Relative severity of common human coronaviruses and influenza
in patients hospitalized with acute respiratory infection: results from 8-year hospital-based surveil-
lance in Quebec, Canada. J Infect Dis. 2021;223:1078-1087.
7. Arabi YM, Balkhy HH, Hayden FG, et  al. Middle East respiratory syndrome. N Engl J Med.
2017;376:584-594.
8. Ahmed AE, Al-Jahdali H, Alshukairi AN, et  al. Early identification of pneumonia patients at
increased risk of Middle East respiratory syndrome coronavirus infection in Saudi Arabia. Int J
Infect Dis. 2018;70:51-56.
8b.  Memish ZA, Perlman S, Van Kerkhove MD, et  al. Middle East respiratory syndrome. Lancet.
2020;395:1063-1077.
9. Sikkema RS, Farag E, Himatt S, et al. Risk factors for primary Middle East respiratory syndrome
coronavirus infection in camel workers in Qatar during 2013-2014: a case-control study. J Infect Dis.
2017;215:1702-1705.

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2167.e2 CHAPTER 342  PRE-2019 Coronaviruses
REVIEW QUESTIONS 2. What statement is most true about common human coronaviruses (OC43,
229E, NL63, and HKU1)?
1. Middle East respiratory syndrome (MERS) coronavirus has been detected
in which patient specimens? A . W henever a common human coronavirus is detected, there are associ-
ated severe clinical symptoms.
A . Respiratory tract specimen B. Common human coronaviruses are detected in individuals with mild
B. Serum or no clinical symptoms.
C. Stool C. All common colds are associated with common human coronaviruses.
D. Urine D. Common human coronaviruses have never been associated with croup
E. All of the above or pneumonia.
Answer: E  Virus has been demonstrated to be detectable in all of these patient Answer: B  Human coronaviruses may be detected from clinical specimens
specimens. Although respiratory tract specimens are most important for diag- from mildly ill or asymptomatic individuals. Human coronaviruses are only
nosis, specimens from additional sites may aid in the diagnosis of patients. one cause of the common cold, and these viruses also have been associated
with croup and pneumonia.

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