Public Health Guidance for Community-Level Preparedness and Response to
Severe Acute Respiratory Syndrome (SARS) Version 2

Core Document

Appendix 1

Clinical, Epidemiologic, and Virologic Features of SARS-CoV

## 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 2003).
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.

## References

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Wong RS, Wu A, To KF, Lee N, et al. Haematological manifestations in
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Br Med J 2003;326:1358-62.

For more information, visit
[www.cdc.gov/ncidod/sars](http://www.cdc.gov/ncidod/sars/) or call the
CDC public response hotline\
at (888) 246-2675 (English), (888) 246-2857 (Español), or (866) 874-2646
(TTY)