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A Hypothesis of Transmission Patterns
of the SARS Epidemic
---An Epidemiologist’s Point of View
Ruey-Shiung Lin, MD, Dr. PH
Institute of Preventive Medicine
National Taiwan University
An epidemiologist is to observe the
outbreak of a disease and its
distribution pattern in a defined
population. Through logical deduction
and rational interpretation can a
conclusion then be formed for such a
phenomenon.
From the spread of SARS (Severe
Acute Respiratory Syndrome) in
Guangdong, Hong Kong, Taiwan, Hanoi,
Singapore, and Toronto, during the past
3-4 months, we can conclude that the
route of transmission is limited to faceto-face droplet infection and direct
individual contact.
Such a conclusion is reached by the
fact that the infected cases were mainly
medical and nursing personnel in the
hospital, as well as those visiting
relatives and friends who had close
contact with the infected hospital
inmates.
This disease appeared in the vicinity of
Guangzhou as early as this past
November or December. It reached a
peak around January or February this
year. The confirmed cases might have
reached 700-800. If SARS was
infectious in the early stage (e.g.
presence of fever, respiratory symptoms,
or cough) when the patient does not
require hospitalization, it would certainly
lead to an epidemic in the community.
However a “supra-giant experiment” of
negative findings of community spread
of SARS for last 4 months in such a
large population of Taiwan, Hongkong,
and Guangzhou, has revealed the
following facts. First, SARS in the early
stage is not easily infectious. Second,
the only time that SARS would become
infectious is when acute respiratory
symptoms appear, prompting the need
for treatment in the hospital.
The conclusion is based on the
speculation that infectiousness may
occur in the later stage of SARS when
there are changes within the virus or it
is combined with secretions produced at
the time of respiratory distress or
hypoxia.
My hypothesis : Non-community spread
of SARS is due to lack of infectivity of
this virus before the stage of respiratory
distress;while the infectiousness of
SARS is dependent on substances
present in respiratory secretion at the
time of respiratory distress (ARDS) .
Trypsin-like enzymes are one of the
possible candidates given that their
concentration increases profoundly in
this stage to dissolve the mucus
produced in severe inflammatory
reactions in the lung. The trypsin-like
enzymes may also change the coat
protein antigenicity of this culprit virus.
Schematic Model of Transmission Patterns of SARS Epidemic
Patients
Respiratory
(Fever)
Infected
April 7, 2003
onset
distress
Cough
R
Antibody
Trypsin
Recovery
L1
H4
A
Replication ------------------------------H1
H5
A
H2
Sexual transmission
A
H6
L2 (flora in vagina)
H3
H7
urine, stool
A
L3 (flora in sewage)
: novel coronavirus with infectivity
Hi : Individual specific coat protein (antigenicity)
H8
Amoy Gardens Estate outbreaks
H9
(A+Hi) : novel coronavirus with individual specific antigenicity will not infect other people(except persons with
the same HLA type, e.g. the first-degree relatives)
L1
L2
L3
trypsin-like enzymes which can washout Hi antigenecity
Dead
This model can explain the
epidemiologic findings of why there is
no community spread of SARS (0%)
due to the strong xenogenicity of SARS
virus, and then after the action of trypsin,
the virus dramatically shifts to 100%
infectivity to hospital staff.
It is possible that there are some trypsin-like
enzymes (L2, L3) produced by the flora in the
sewage and in the vagina which can also
digest the protein coat of virus and wash out
the virus individual-specific antigenicity. Thus,
contamination from the sewage system may
induce the outbreak among residents of
Amoy Gardens Estate. The viral particles
have been found at high levels in the stool,
urine, and possibly also in the vaginal
secretions of SARS patients even before the
onset of the disease.
In addition, my hypothesis can also
explain why COPD patients and
immunocompromised patients such as
diabetic or chronic renal disease
patients if contract SARS, then they
easily transmit SARS to other people in
the very early stage due to a high level
of trypsin in their lungs.
The “white (0%) to black (100%)”
extraordinary transmission pattern is a
unique epidemiological characteristic of
SARS which is totally against the
traditional epidemiological concept of a
“normal curve distribution” of infectious
diseases with multiple risk factors and /
or dosage involved in the causation of
disease.
The findings of a family cluster of SARS can
be explained by the assumption that the
SARS virus may be attached to parts of HLA
antigen (epitopes) of the host that allow the
SARS virus to propagate in the body through
the receptors (key-lock) of cell membranes.
This would then allow the SARS virus to be
transmitted airborne to people with the same
HLA type, i.e.. first-degree relatives (branch
line of line 1 in the model)
From this schematic model, we can
make the following conclusions:
The xenogenicity of SARS virus (novel
coronavirus) limits the infectivity of the
virus to other people (no community
spread). The propogation of SARS virus
in the body is dependent on attachment
to host HLA antigens (epitopes) to pass
through receptors of cell membranes
(key-lock mechanism).
First-degree relatives with the same
HLA type will be infected (through
airborne(?)) by SARS virus even with a
strong xenogenicity. It will be very
interesting to find the mechanism of the
SARS virus RNA chain and how it
connects with host HLA antigen.
It is speculated that the coat protein or
spike proteins of xenogenicity will be
dissolved after the action of trypsin, and
the “naked” SARS virus will be changed
to a “formless” state that will only
survive in aqueous solution. If
desiccated, the “naked” SARS virus will
lose its viability which is suitable to the
epidemiologic pattern of limited infection
to close contact with droplets.
The aqueous form of “naked” SARS
virus without xenogenicity and host HLA
antigens is easily passed through
channels of cell membranes (mucous
membranes). Through this channel,
small water molecules and the “naked”
SARS virus pieces (single strain RNA
chain is easily cut by RNA enzymes in
mucous membranes) pass the bilayer
lipoprotein membranes.
The “formless” aqueous stage of “naked”
SARS virus possesses the ability to
invade anybody and all mucous
membranes including respiratory tract,
conjunctiva, oral cavity, and urogenital
tract. This is documented in 100%
infectivity to hospital staff and anybody
with close contact with the SARS
patient in the acute respiratory distress
stage which induces trypsin secretion.
My hypothesis can be proved by the
following epidemiological studies:
1. To compare the HLA type between the infected
first–degree relatives and non-infected first-degree
relatives who have been exposed to the index
patient.
2. To compare the onset time of SARS in the sexual
partner of index patients to find out whether they are
infected before the index patient progresses to the
respiratory distress stage.
3. To compare the onset time of affected first-degree
relatives to find out whether they are infected before
the index patient progresses to respiratory distress .
Although, my hypothesis is plausible
based on current epidemiologic findings,
it still needs further confirmation from
the laboratory. However, the limited
infectivity of this virus before the
development of respiratory distress
should allow relaxation of international
traveling restrictions and also relieve
hysteria among people in affected
countries.
My hypothesis of non-community
spread of SARS also implies the
following 4 conditions:
1.A healthy ( non-immunocompromised)
person if contracted SARS will not infect
other people in the early stage of disease
when they are still in the community.
2.No subclinical infection SARS cases
3.No recovery healthy carriers
4.No animal in community will play as a SARS
host or vector.
If the above stated hypothesis be
proved right, then we can predict that if
all SARS patients are isolated and
cured, then there will be no more SARS
outbreak in the world in this coming
winter or next years.