Commentary
COMMENTARY
COMMENTARY
Novel coronavirus and severe acute respiratory syndrome
Published online April 8, 2003
RNA, and none of 200 serum samples from blood
http://image.thelancet.com/extras/03cmt87web.pdf
donors had serum antibody to this new coronavirus.
These findings significantly strengthen the tentative
aetiological association reported by other investigators
“The terror of the unknown is seldom better displayed
from the Centers for Disease Control and Prevention
than by the response of a population to the appearance
(CDCP) in Atlanta and from Toronto, who have also
of an epidemic, particularly when the epidemic strikes
isolated a novel coronavirus from patients with SARS.2,3
without apparent cause”.1 This quote from 1977 by
As other pathogens, such as human metapneumovirus
Edward Kass, describing the fears surrounding the
and Chlamydia spp, are identified in SARS patients, it
newly recognised legionnaires’ disease, aptly describes
will be important to use control groups to determine
the public response to the recent appearance of an
their role in causality or as cofactors for severe disease.2,4
unexplained atypical pneumonia referred to as severe
The clinical features associated with SARS are rapidly
acute respiratory syndrome (SARS).
becoming available through Peiris’ and other reports.2,5
In today’s Lancet, Joseph Peiris and colleagues
The Hong Kong investigators identified five clusters of
provide strong evidence that SARS is associated with a
patients by using a modified WHO case definition for
novel coronavirus that has not been previously identified
SARS, and describe the clinical manifestations of this
in human beings or animals, and begin the process of
serious disease. It is notable that nearly 40% of the
eliminating the many unknowns from this new
patients developed respiratory failure that required
syndrome (figure). The investigators used classic viral
assisted ventilation. Clinical descriptions will be
culture and serological techniques, as well as modern
important in modifying the case definition of this
molecular genetic methods, to characterise and to
syndrome should it spread, as is likely, beyond the
determine the cause of the disease in 50 patients with
tightly linked clusters that have characterised the
SARS in Hong Kong. One of the strengths of their
epidemiology of SARS thus far. Unfortunately, the early
report, and an important means of establishing
clinical appearance may not allow ready distinction from
causality, is their analysis of specimens from control
other common winter-time respiratory viral infections.6,7
patients. None of 40 respiratory secretions from patients
However, certain characteristics of SARS are
with other respiratory diseases contained coronavirus
noteworthy. The constellation of absence of upper
respiratory symptoms, the presence of
dry cough, and minimal auscultatory
findings with consolidation on chest
radiographs may alert the clinician to
the possible diagnosis of SARS. The
presence of lymphopenia, leucopenia,
thrombocytopenia, and elevated liver
enzymes and creatinine kinase may
also raise suspicion.
Clinical diagnosis will become
particularly problematic once the
association with travel or case contact
is lost. Thus, rapid and accurate
diagnostic tools will be critical in the
management of this epidemic. Given
the experience with other respiratory
viruses, it is likely that culture and
direct antigen-detection from
respiratory secretions will not suffice
in view of the lethality and contagious
nature of this new agent. Rapid
diagnosis of SARS, which is
Figure 2 from Peiris and colleagues’ report on coronavirus as cause of SARS
important for infection-control
Thin-section electron micrograph of lung-biopsy sample from patient with SARS and of human
pneumonia-associated infected cells.
measures and potential treatment,
1
THE LANCET • Published online April 8, 2003 • http://image.thelancet.com/extras/03cmt87web.pdf
For personal use. Only reproduce with permission from The Lancet Publishing Group.
COMMENTARY
will require very sensitive and specific methods. Real-
*Ann R Falsey, Edward E Walsh
time RT-PCR, currently in use for other respiratory
Rochester General Hospital, University of Rochester School of
viruses primarily in research settings, may be required as
Medicine and Dentistry, Rochester, NY 1462, USA
a routine test in clinical diagnostic microbiological
(e-mail: Ann.Falsey@viahealth.org)
laboratories.8,9
1
Kass EH. Legionnaires’ disease. N Engl J Med 1977; 297: 1229–30.
Peiris and colleagues suggest that early therapy with
2
Poutanen SM, Low DE, Henry B, et al. Identification of severe
intravenous ribavirin and high-dose glucocorticosteroids
respiratory syndrome in Canada. N Engl J Med March 31, 2003:
may be beneficial. However, the lack of untreated
http://content.nejm.org/cgi/content/abstract/NEJMoa030634v2
(accessed April 7, 2003).
control patients precludes a firm conclusion about
3
Centers for Disease Control and Prevention. CDC lab analysis
benefit. Clinicians often find it difficult to withhold
suggests new coronavirus may cause SARS. March 24, 2003:
potentially beneficial, yet unproven, therapy in life-
http://www.cdc.gov/od/oc/media/pressrel/r030324.htm (accessed
threatening situations. Controlled studies may be
April 7, 2003).
difficult to do and there are obviously no historical
4
Centers for Disease Control and Prevention. CDC telebriefing
transcript: CDC update on severe acute respiratory distress syndrome
controls for the treatment of SARS. Therefore it will be
(SARS). April 4, 2003: http://www.cdc.gov/od/oc/media/transcripts/
important for treating physicians to carefully document
t030404.htm (accessed April 7, 2003).
the dose, timing, and types of therapies used, and the
5 Tsang KW, Ho PL, Ooi GC, et al. A cluster of severe acute
clinical and viral status of patients, so that experiences
respiratory syndrome in Hong Kong. N Engl J Med March 31, 2003:
can be pooled and information productively analysed.
http://content.nejm.org/cgi/content/abstract/NEJMoa030666v2
(accessed April 7, 2003).
It is truly remarkable and unprecedented that the
6
Falsey AR, Cunningham CK, Barker WH, et al. Respiratory syncytial
progress reported by Peiris and colleagues, and
virus and Influenza A infections in the hospitalized elderly.
elsewhere, on the aetiology and clinical and
J Infect Dis 1995; 172: 389–94.
epidemiological characteristics of SARS has been
7
Peret TC, Boivin G, Li Y, et al. Characterization of human
achieved in less than 2 months. It is fortuitous that this
metapneumoviruses isolated from patients in North America.
J Infect Dis 2002; 185: 1660–63.
outbreak occurred at a time when viral surveillance-
8
Zambon MC, Stockton JD, Clewley JP, Fleming DM. Contribution
systems headed by WHO in collaboration with CDCP
of influenza and respiratory syncytial virus to community cases of
are in place throughout the world. The work of
influenza-like illness: an observational study. Lancet 2001; 358:
individual laboratories, such as the ones in Hong Kong,
1410–16.
Toronto, and CDCP, and cooperation between health
9
Nicholson KG, Kent J, Hammersley V, Cancio E. Acute viral
infections of upper respiratory tract in elderly people living in the
authorities in many countries provides protection from
community; comparative, prospective, population based study of
the inevitable threat of new epidemic diseases.
disease burden. BMJ 1997; 315: 1060–64.
THE LANCET • Published online April 8, 2003 • http://image.thelancet.com/extras/03cmt87web.pdf
2
For personal use. Only reproduce with permission from The Lancet Publishing Group.
