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 face- to-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 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.

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.