Emergence of SARS-CoV
SARS first
came to global attention on February 11, 2003, when Chinese officials
informed WHO of the occurrence of 305 cases of atypical pneumonia and
5 deaths in Guangdong Province since November 2002 (WHO 2003). On
February 21, a Chinese physician with SARS traveled from Guangdong
to Hong Kong and spent the night in a hotel there. During the next
two days, he developed increasingly severe respiratory symptoms and
was hospitalized in a Hong Kong hospital, where he died from his illness.
His one-night stay in a Hong Kong hotel led to infection by yet unexplained
mechanisms in several other guests, who subsequently traveled to and
seeded SARS outbreaks in Vietnam, Singapore, Hong Kong, and Canada
(CDC 2003a; Hsu 2003; WHO 2003). In these areas, local spread was
initiated and maintained in hospitals, where healthcare personnel,
patients, and visitors - unaware
of the emergence of a new disease - acquired SARS-CoV from persons with
unrecognized infection (Booth 2003; CDC 2003b; CDC 2003c; Lee 2003; Varia 2003). During March-May, the spread of the virus from Guangdong to other
parts of China established additional foci of infection, such as Beijing
and Taiwan (CDC 2003d).
Once SARS was recognized in these locations and widespread community
transmission was noted in several outbreak sites, the spread of SARS-CoV
was controlled by aggressive community infection control measures including
active case finding, contact tracing and monitoring, travel restrictions,
and quarantine and other containment strategies. These measures were
implemented in many geopolitical jurisdictions and involved intense,
sustained collaboration among institutions and persons beyond the traditional
public health infrastructure. Areas with high transmission rates experienced
severe economic consequences and social disruption rivaling that seen
in other global epidemics (e.g., plague) of centuries past.
On March 14, 2003, CDC launched an emergency public health response
and established national surveillance for SARS to identify case-patients
in the United States and discover if domestic transmission was occurring.
Through July 2003, a total of 159 suspect and 33 probable cases had been
reported in the United States. Of the 33 probable cases, only 8 had
laboratory evidence of SARS-CoV infection (CDC 2003e; CDC 2003f; CDC 2003g; CDC 2003h). All of the eight cases with documented SARS-CoV infection
occurred in persons who had traveled to SARS-affected areas. One of these
case-patients might have acquired infection either abroad or from her
spouse, who was one of the other seven SARS-CoV-positive cases. Except
for this one person with possible transmission from a household contact,
no evidence of SARS-CoV infection was detected by serologic testing of
household contacts of SARS cases or of healthcare workers who cared for
SARS patients.
During the
global epidemic, transmission of SARS-CoV in hospitals was a major
factor in the amplification of outbreaks and the initiation of spread
into the community (Booth 2003; CDC 2003b; CDC 2003c; CDC 2003d; Lee 2003). In areas characterized by extensive outbreaks, early SARS-CoV
transmission occurred predominantly among healthcare workers, patients,
and visitors; these groups accounted for 18% to 58% of all SARS cases
in the five countries with the largest outbreaks. The concentration
of illness in previously healthy hospital staff placed an enormous
strain on hospital facilities and staff. The apparent ease of nosocomial
transmission - added
to the far-reaching public health ramifications of SARS-CoV transmission
in single hospitals - posed great challenges for healthcare institutions
in maintaining high levels of vigilance and infection control.
Clinical Features
The median
incubation period for SARS appears to be approximately 4 to 6 days;
most patients become ill within 2 to 10 days after exposure (Booth 2003; CDC 2003b; Donnelly 2003; Varia 2003). The clinical presentation
of SARS-CoV infection has some but not enough distinctive features
to enable diagnosis by clinical signs and symptoms alone (Hsu 2003).
Respiratory symptoms typically do not begin until 2 to 7 days after
onset of systemic symptoms such as fever, headache, myalgias. Respiratory
complaints usually include a non-productive cough and dyspnea but not
upper respiratory symptoms such as rhinnorhea and sore throat (Booth 2003; Donnelly 2003; Drosten 2003a; Lee 2003; Peiris 2003a; Poutanen 2003; Rainer 2003; Tsang 2003). Almost all patients with laboratory
evidence of SARS-CoV infection evaluated thus far developed radiographic
evidence of pneumonia (Poutanen 2003; Rainer 2003), and most (70%
-90%) developed lymphopenia (Booth 2003; Lee 2003; Peiris 2003a; Poutanen 2003; Tsang 2003; Wong 2003). The overall case-fatality rate of approximately
10% can increase to >50%
in persons older than age 60 (Peiris 2003a). Transmission
Epidemiologic
features of SARS provide keys to its diagnosis and control. The pattern
of spread suggests that SARS-CoV is transmitted primarily through droplets
and close personal contact (Seto 2003; Varia 2003). Studies documenting
stability of the virus for days in the environment suggest the possibility
of fomite transmission. There is also suggestive evidence that, in
a few instances, SARS-CoV may have been transmitted by small-particle
aerosols. Epidemiologic data suggest that infected persons do not transmit
SARS-CoV before the onset of symptoms and that most transmission occurs
late in the course of illness when patients are likely to be hospitalized
(Peiris 2003a). The lack of transmission before symptom onset and
during early illness explains the infrequency of community transmission
and the preponderance of hospital-associated transmission. Although
evidence indicates that most patients do not transmit SARS-CoV efficiently
(Lipsitch 2003), documentation of "super-spreaders" and "super-spreading
events" shows that, in certain situations, viral transmission can be
highly efficient (CDC 2003b).
Control Strategies
The rapidity with which SARS spread globally and the severity of the
disease require a rapid and integrated global response to SARS. SARS
anywhere in the world can potentially affect all other global regions.
In response to the 2003 SARS epidemic, WHO orchestrated a rapid and intense
effort to control transmission, which ultimately was effective in stopping
all global spread by early July 2003. The classic public health control
measures of isolation, contact tracing and monitoring, infection control,
and quarantine were an important part of the global control of SARS and
will be the key to controlling SARS if it returns.
The Virus and Its Re-emergence
SARS is caused by the newly identified SARS-associated coronavirus (SARS-CoV)
(Drosten 2003b; Ksiazek 2003). As SARS-CoV is distantly related to all
previously described coronaviruses, it is likely that the virus or its
parent virus has been circulating in some location for a long period.
Antibodies to SARS-CoV were not found in human serum samples banked before
the SARS outbreak, suggesting that the virus is new to the human population.
Evidence suggests that it is a previously unknown coronavirus, probably
from an animal host, that crossed the species barrier and somehow acquired
the ability to infected humans. No one knows if SARS-CoV will reappear,
but the most likely potential sources for its reintroduction are: 1)
the original animal or a new animal reservoir; 2) undetected transmission
in humans; 3) persistent infection in humans; or 4) the laboratory (as
occurred recently in Singapore). Since most other respiratory viruses
are seasonal, with outbreaks in fall, winter, or spring that spontaneously
resolve, it is possible that SARS may also be seasonal and spread more
efficiently during the respiratory virus season. Recurrence of or concern
about SARS during respiratory virus season will likely challenge the
healthcare and public health communities with large numbers of SARS-like
illnesses.
Laboratory Diagnostics
Laboratory
diagnostics are essential for detecting and documenting a resurgence
of SARS, responding to and managing outbreaks of SARS, and addressing
concerns about SARS in patients with other respiratory illnesses.
Two assays are most often used to diagnose SARS CoV infection: PCR assays for viral RNA and serologic testing for virus-specific antibodies (Drosten
2003b; Ksiazek
2003; Peiris
2003b). Both assays can be very specific
and sensitive in detecting RNA and antibodies, respectively. However,
because of the low titer of virus in clinical specimens from most patients
and the time it takes persons to mount an antibody response to infection,
neither assay can reliably detect SARS-CoV infection early in illness
(Ksiazek
2003; Peiris 2003a). Interpretation of these assays needs to
account for the possibility of false-negative results, which are frequent
occurrences early in infection, and false-positive results, which are
especially important concerns for PCR assays.
Prophylaxis and Treatment
No vaccines have yet been developed for SARS and no anti-viral treatment
has been shown to be effective. CDC, the National Institutes of Health
(NIH), the Food and Drug Administration (FDA) and academicians are developing
protocols to assess antiviral drugs that show activity in vitro against
SARS-CoV. It is not yet clear whether persons who recover from SARS-CoV
infection develop long-lasting protective immunity or whether they are
susceptible to re-infection and disease, as is the case with other human
coronaviruses.
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