SARS could still affect the United Kingdom, health secretary warns
BMJ 2003; 326 doi: https://doi.org/10.1136/bmj.326.7396.948/b (Published 03 May 2003) Cite this as: BMJ 2003;326:948All rapid responses
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Editor - At the time of writing, there are more than 1600 cases of
severe acute respiratory syndrome (SARS) in Hong Kong since its recent
outbreak in early March1. Prince of Wales Hospital, Hong Kong, is one of
the hospitals in the region taking care of relatively large number of
patients with SARS2. Although the hospital has implemented various
infection control measures to keep staff from contracting SARS, we have
relatively little information on how should we protect the surgical team
and other OT personnel from infection when major surgical procedures are
to be done on patients with SARS. The issue of precautions to prevent
transmission of SARS in the operating rooms has not been clearly addressed
by the guidelines from WHO and the Centers for Disease Control and
Prevention (CDC)3.
On first of May, 2003, we performed an emergency laparotomy for one
of our SARS patients with perforated bowel of uncertain aetiology. This
was the first patient with confirmed SARS who needed emergency surgical
procedure in the hospital. We operated on the patient in one of the
operating rooms designated for confirmed or suspected SARS patients. The
surgical team together with the anaesthetic team, scrub nurses and other
workers in the operating room; were gowned up for “up-graded” universal
precautions. In addition to the universal precautions issued by the CDC
around 15 years ago4, we wore double gloves, N95 masks, protective
eyewears, water-resistant gowns and hoods with powered air purification
blower unit as protective precautions.
While handling biological fluid (mainly blood and gastrointestinal
contents for abdominal surgery) which were potentially infectious with
very high viral load5; we attempted to cause minimal spillage onto the
drapes and the floor during the procedure. The operating room was then
completely disinfected and all operating room personnel had shower after
the procedure.
Every team member working that day is still being monitored closely
for development of SARS symptoms and we have just passed the first week.
We hope the stringent measures we have implemented would prevent
transmission of SARS to operating room users. Also, we wish to raise the
awareness of the surgical community and all operating room users of the
potential problems with SARS with particular reference to special
precautions in the operating rooms. Perhaps it is also the opportunity
for WHO and CDC to consider drafting guidelines on this issue.
Reference:
(1) Chan-Yeung M, Yu WC. Outbreak of severe acute respiratory syndrome in
Hong Kong Special Administrative Region: case report. BMJ 2003; 326:850-
852.
(2) Lee N, Hui D, Wu A, Chan P, Cameron P, Joynt GM, et al. A major
outbreak of severe acute respiratory syndrome in Hong Kong N Engl J Med
2003; 7 Apr. www.nejm.org
(3) Centers for Disease Control and Prevention. Severe acute respiratory
syndrome (SARS): Updated interim domestic infection control guidance in
the health-care and community setting for patients with suspected SARS.
www.cdc.gov/ncidod/sars/infectioncontrol.htm (assessed 1 May 2003).
(4) Centers for Disease Control and Prevention. Update: Universal
precautions for prevention of transmission of human immunodeficiency
virus, hepatitis B virus, and other bloodborne pathogens in health-care
settings. MMWR 1988; 37:377-388.
(5) Peiris JS, Lai ST, Poon LL, Guan Y, Yam LY, Lim W, et al. Coronavirus
as a possible cause of severe acute respiratory syndrome. Lancet. 2003;
361:1319-25.
Competing interests:
None declared
Competing interests: No competing interests
While the world takes precautions to contain SARS, one should not
forget its propensity to mutate. While officials screen people with
respiratory symptoms a element of caution should be shown for patients who
present with atypical symptoms. The corona virus could be a cause of
unexplained gastroenteritis or conjunctivitis etc.
It is important however that the people don't get alarmed with this
outbreak since like most other viral outbreak it is predicted to wane
away.
Competing interests:
None declared
Competing interests: No competing interests
Epidemiological investigation of the Severe Acute Respiratory
Syndrome (SARS) outbreak at our hospital has revealed that all medical
students, doctors and nurses who had contact with the index patient were
affected (1). As a result, the Intensive Care Unit was overwhelmed, all
non-essential operations and clinical teaching were cancelled and staff
from other departments had to be drafted in to take the place of those
health care workers who continue to fall ill. Once the hospital capacity
was saturated, patients were diverted to three other hospitals. Despite
prior knowledge of SARS and the implementation of barrier nursing
(including use of disposable gloves, gowns, N95 masks), the pattern
repeated itself, with more staff becoming infected in these centres.
The
Public Health Laboratory Service (PHLS) has issued a number of sensible
guidelines on SARS but there are two areas in which further precautions
could be taken (2).
First, Peiris and others have found that the mean time
from onset of symptoms to worsening was 8.3 days (3); we have also seen
patients who continue to worsen 48 hours after their fever have subsided.
In one series 108/138 initial chest radiographs were normal (1). Therefore
we disagree with the recommendation from the PHLS that suspected cases
with mild symptoms do not require admission.
Second, hospitals should
designate a small team of trained staff, equipped with protective suits to
assess all febrile patients who have traveled from affected areas. Once
they have assessed individuals with suspected or confirmed SARS they
should be excused from other duties to reduce the likelihood of passing on
the infection. This is important as nearly 90% of cases in the first
hospital outbreak were other staff, visitors and patients who were in the
ward for other problems (1).
In light of similar experiences from
Singapore and Toronto, the principle lesson to be learnt from this
outbreak is that one infected patient can lead to the paralysis of a whole
hospital (1,4). A high index of suspicion is required to prevent SARS from
establishing in the UK.
References
1) Lee N, Hui D, Wu A et al. A major outbreak of severe acute respiratory
syndrome in Hong Kong. N Engl J Med 2003;348.
2) Guidance for hospitals on the prevention of spread of SARS. Public
Health Laboratory Service. Accessed 1st May 2003,
http://www.phls.org.uk/topics_az/SARS/hospital_guidance
3) Peiris JSM, Lai ST, Poon LLM et al Coronavirus as a possible cause of
severe acute respiratory syndrome. Lancet 2003; 361: 1319-25.
4) Poutanen SM, Low DE, Henry B. Identification of Severe Acute
Respiratory Syndrome in Canada. N Engl J Med 2003;348.
Competing interests:
None declared
Competing interests: No competing interests
SARS virus S2 glycoprotein tryptophan-rich membrane anchor
SARS virus S2 glycoprotein
tryptophan-rich membrane anchor
Sir--SARS has exploded on the international scene negating the
notion
that human coronavirus infections are always benign. A novel
Coronavirus is thought to be the cause of SARS.
Coronaviruses are large enveloped RNA viruses. Enveloped viruses enter
cells through virus membrane fusion with host cell membrane. Distinct
species and tissue specificity correlate with changes in the spike protein
(S protein). S proteins are virus membrane proteins with ectodomains,
transmembrane spans and a short cytoplasmic tail. S protein is made of
S1 and S2 fragments. The peripheral S1 associates through non-covalent
interactions with S2. S2 is the core machinery necessary for membrane
fusion. In a murine hepatitis coronavirus model the S1 region forms a
dimer that binds the receptor carcinoembryonic antigen-related cell
adhesion molecule. Binding depends upon the quarternary structure of
S1 spike and leads to change in conformation and perhaps to release of
energy enabling fusion of virus to host cell membrane.1 After binding,
subsequent events, such as steric changes in the S1 and S2 regions, are
not well understood. Exchanges between S1 and S2 portions of S
glycoprotein can change the virulence of coronaviruses2,3
We performed sequence analysis on the S2 subunit of S protein3 of
2 released SARS virus complete genomes (Figure 1) and found complete
conservation in SARS and nearly complete conservation in all other
coronaviruses of the KWPWYVWL sequence (termed concensus octamer),
which is at the extravirion side of the transmembrane region
KWPWYVWLGFIAGLIAIVMVTILL. This sequence appears to anchor the
large external S glycoprotein into virus membrane, and the conserved
tryptophans (W) with their bulky side chains may function to strongly
anchor in the membrane. Alignments of other proteins in the SARS
genomes with other coronavirus genomes did not show any other
sequences of 8 or more adjacent amino acid that are as completely
conserved.
Indolicidin (LPWKWPWWPWRRG), the membrane-active peptide
antibiotic with antiviral activity against HIV1 is highly similar to this
KWPWYVWL SARS coronavirus concensus octamer sequence:
LPWKWPWWPWRRG
KWPWYVWL
Thus indolicidin might be effective against SARS and other
coronavirus
infections through mechanisms such as displacing the
WPWYVWLGFIAGLIAIVMVTILL transmembrane anchor of S2 from the viral
membrane. The tryptophan side chains of indolicidin and other
tryptophan rich peptide antibiotics position themselves in membranes
near the membrane-water interface.4 Steric changes and hindrance
occurring in the 3D structure of S1 and S2 portions of the virus2 might
make the conserved site unavailable for action of indolicidin or a
vaccine. This highly conserved region could be essential for cell-entry of
a coronavirus, but since it is present in nonvirulent coronaviruses may
be unimportant for virulence.
The SARS S2 also has Leucine zipper-like heptad repeats combined
with embedded N-linked glycosylation sites NXS as shown in this
sequence from SARS S2 glycoprotein:
INXSXXXIXXXXXXLXXXXXXLNXSXXXL, a combination also found in other
coronaviruses. This leucine zipper region in other coronaviruses and
paramyxoviruses mediates fusion of viral and cellular membranes, and is
linked to virulence of other coronaviruses5 and might be important for
vaccines and antivirals.
Figure 1: Multiple sequence alignment of the of C-terminal of S2
subunit of the S glycoprotein done with MEGALIGN computer program of
LASERGENE from DNASTAR. Conserved Consensus Octamer is
highlighted in yellow
1) SARS coronavirus (NP_828851)
2) rat sialodacryoadenitis coronavirus (AAF97738)
3) murine hepatitis virus (AAB30950)
4) Porcine hemagglutinating encephalomyelitis virus (AAL80031)
5) Bovine coronavirus (AAF25499)
6) human coronavirus (S44241)
1)
NESLIDLQELGKYEQYIKWPWYVWLGFIAGLIAIVMVTILLCCMTSC.CSCLKGACSC
GSCCKFDEDDSEPVLKG.VKLHYT
2)
NESYINLKEIGTYEMYVKWPWYVWLLIGLAGVAVCVLLFFICCCTGCGSCCFK...KC
GNCCDEYGGRQAGIVIHNISSHED
3)
NESYINLKEVGTYEMYVKWPWYVWLLIGLAGVAVCVLLFFICCCTGCGSCCFR...K
CGSCCDEYGGHQDSIVIHNISAHED
4)
NQSYINLKDIGTYEYYVKWPWYVWLLIGLAGVAMLVLLFFICCCTGCGTSCFK...KC
GGCCDDYTGHQEFVIKT...SHDD
5)
NQSYINLKDIGTYEYYVKWPWYVWLLIGLAGVAMLVLLFFICCCTGCGTSCFK...KC
GGCCDDYTGHQELVIKT...SHDD
6)
NQSYINLKDIGTYEYYVKWPWYVWLLIGFAGVAMLVLLFFICCCTGCGTSCFK...KC
GGCCDDYTGHQELVIKT...SHEG
*Carl H. Lawyer, Matthew C. Lawyer, Satyanarayan Bhat, Salil
Gulati,
Stephen M. Milner
Southern Illinois University School of Medicine (e-mail
CHLawyer@earthlink.net )
References:
1) Lewicki DN, Gallagher TM. Quaternary structure of coronavirus
spikes
in complex with carcinoembryonic antigen-related cell adhesion
molecule cellular receptors. J Biol Chem 2002 May 31;277(22):19727-34
2) Matsuyama S, Taguchi F. Communication between S1N330 and a
region in S2 of murine coronavirus spike protein is important for virus
entry into cells expressing CEACAM1b receptor. Virology 2002 Mar
30;295(1):160-71
3) Binns MM, Boursnell ME, Cavanagh D, Pappin DJ, Brown TD. Cloning and sequencing of the gene encoding the spike protein of the
coronavirus IBV. J Gen Virol. 1985 Apr;66 ( Pt 4):719-26.
4) Schibli DJ, Epand RF, Vogel HJ, Epand RM. Tryptophan-rich
antimicrobial peptides: comparative properties and membrane
interactions. Biochem Cell Biol 2002;80(5):667-77
5) Luo Z, Matthews AM, Weiss SR. Amino acid substitutions within
the
leucine zipper domain of the murine coronavirus spike protein cause
defects in oligomerization and the ability to induce cell-to-cell fusion.
J
Virol. 1999 Oct;73(10):8152-9.
Competing interests:
None declared
Competing interests: No competing interests