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Pastimes : SARS - what next? -- Ignore unavailable to you. Want to Upgrade?

To: Maurice Winn who wrote (812)	12/27/2003 9:09:33 PM
From: Henry Niman	Respond to of 1070

The Guangzhou patient is sero-converting as we speak and he has been PCR positive at least once. At least one media report has indicated that his girlfriend has a fever, so things are definitely heating up in Guangzhou.

To: Maurice Winn who wrote (812)	12/29/2003 10:38:34 AM
From: Henry Niman	Respond to of 1070

The report in today's WSJ that the current Guangzhou case was a suspect SARS case in March, points to the importance of reliable data from the first outbreak, which unfortunately has been subject to significant manipulation (like the 36 deaths in Taiwan who were SARS CoV positive but were removed from the Taiwan SARS total because they were said to have had underlying disease - which was not fully supported by Taiwan's own web site, yet have been removed from the WHO totals). However, science can overcome these manipulations with sequence data. The sequences out of Guangzhou were from some early (late Jan/ early Feb cases) and this data can shed some light on the origin of the current infection. If it matches the earlier sequences (heavily mutated with 29 nt deletion), then the chance that the virus persisted at a low level in this patient is increased. The reported rising antibody titer would indicate that the current infection is recent.

To: Maurice Winn who wrote (812)	12/31/2003 6:44:47 AM
From: Henry Niman	Respond to of 1070

Reading between the lines, it is quite clear that the Guangzhou patient is positive for SARS CoV (many times in many tests), but without an epi-link, WHO is working overtime on ways to discount the confirming lab data. The in-between the lines are in the comments below "Researchers had yet to draw a clear contact link for the man in Guangdong, but the WHO's representative in China, Henk Bekedam, told Reuters if there was one, the case for SARS would be stronger. "If he would be a lab worker, then for sure a lot of red flags would be there," he said. "But the lab results on their own are inconclusive." Appearing on Hong Kong Cable Television, Zhong Nanshan, one of China's top respiratory experts, said some tests showed the patient was infected with SARS. "Yesterday, in Beijing, we conducted a comprehensive test... The comprehensive test, which included tests on the patient's serum and antibodies, showed the patient was infected with the SARS virus," he said. "There is not a very obvious origin of infection. If there is a case in the community, we need to be very careful in confirming it. That's a main reason why up to now the case has still not been confirmed." 31 Dec 2003 09:59:34 GMT WRAPUP 2-China to send samples abroad for more SARS tests -------------------------------------------------------------------------------- (Adds WHO quotes) By John Ruwitch BEIJING, Dec 31 (Reuters) - China will send samples from a suspected SARS patient abroad for tests after researchers were unable to confirm whether the man has the deadly virus, the World Health Organisation said on Wednesday. The decision was likely to delay a final diagnosis -- if any is possible -- on the 32-year-old television producer in hospital in the southern province of Guangdong with symptoms of Severe Acute Respiratory Syndrome. The Health Ministry said in a statement the case could not be confirmed as of 10 a.m. (0200 GMT) on Wednesday.

To: Maurice Winn who wrote (812)	1/1/2004 8:40:32 AM
From: Henry Niman	Respond to of 1070

SCRS in Guangzhou? Hopefully Beijing will not try to be "creative" with its definitions and use the prior illness in March to obscure the fact that the patient has evidence of SARS CoV infection. Taiwan's manipulations are still at their SARS website for all to see. cdc.gov.tw The started with 73 patients who died, had been classified as probable SARS because they had tested positive for SARS CoV. 36 of them were reclassified as non-SARS due to underlying conditions. However, the page linked above shows that of the 73, 22 had a coesiting medical disorder. Even if all 22 were reclassified, there would still be 14 patients who had died, were SARS CoV positive, had no documented co-existing condition, yet were removed from the probable SARS fatality list. The classification acrobatics created some rather glaring problems. Those cases that were SARS CoV positive had a case fatality rate of 21.2%, while those that were SARS CoV negative had a case fatality rate of 33.8%. Thus the manipulated data managed to show that SARS CoV infection saved lives by lowering the case fatality rate from 33.8% to 21.1% (the web site the gets creative on the statistics side by dividing up the SARS CoV positive group into SARS and "SARS-related" groups which cuts the numerator in half, but conveniently leaves the denominator alone, thereby lowering the SARS case fatality rate to "10.7%" and the SARS-related rate to (10.4%). Surprisingly, WHO allowed this manipulation to carry over to its web-site, which now shows just 37 fatalities in Taiwan. This creative classification could be expanded elsewhere. The Amoy Gardens index case initially was positive for Influenza A. Thus, using Taiwan's creative approach, his pneumonia could be reclassified as the flu and the associated SARS CoV could be called a marker for the flu. The SARS CoV from the Amoy Gardens index case (CUHK-AG1) had a unique mutation profile, which was found in a high percentage of Amoy Gardens cases as well as Taiwan cases. Hopefully, Beijing won't use these tricks to call the Guangzhou case a non-SARS case because of the prior March illness. I noticed in the latest AP story, WHO mentions the word acute: "She said antibody tests indicated "a likely viral infection but not necessarily...an acute SARS infection." I thought it was odd that a 32 year old free-lance journalist would have pneumonia or a pneumonia-like disease twice in a 9 month period (several reports indicate he was a SARS suspect case in March) Are the antibody data suggesting the patient has a Severe Chronic Respiratory Syndrome (SCRS)?

To: Maurice Winn who wrote (812)	1/1/2004 11:34:20 PM
From: Henry Niman	Respond to of 1070

Reading between the line of the NY Times article, I think that Guangzhou is sounding more and more like Severe Chronic Respiratory Syndrome. One sample has tested positive by three different labs and I suspect that by now there is some sequence data and it is an exact match for SARS CoV in Guangzhou last March Thus, the two simplest explanations were a re-activation of an old SARS CoV infection, or contamination. However, the antibody data would discount contamination, but WHO is considering a scenario similar to the one in Surrey. BC. However, there are several important differences. The antibody in Surrey was only found in new tests that used M or N gene products as targets and the assay generated some cross reactivity with OC43. The Surrey samples had OC43 antibodies because the patients had symptoms of a cold (and an OC43 infection). Moreover, the more traditional antibody tests did not detect cross reacting antibodies and registered the Surrey samples as negatives. In view of those results, I doubt that the Guangzhou and Beijing labs are using antibody tests that cross react with coronaviruses that cause colds (OC43 or 299E). Moreover the patient did not have cold symptoms, he had classical SARS symptoms, including pneumonia. Thus, I think that the lab data has met the criteria for confirmed SARS many times over, but the sequence data has raised the possibility of contamination. I suspect that instead of contamination, the samples are positive for SARS CoV RNA and antibody because the patient has had a reactivation of the SARS CoV infection he had last March. Re-activation of SARS CoV has many medical as well as social and economic implications, which could loom large if this is re-activation and is not an isolated case (and I think that it is far too early in SARS season to classify this case as atypical.

To: Maurice Winn who wrote (812)	1/3/2004 7:13:22 PM
From: Henry Niman	Read Replies (1) \| Respond to of 1070

I guess someone's always trying to build a better mousetrap: " The centre also said that before the patient fell ill, he had used chopsticks to try to catch a rat. Tests on rats caught in the man's apartment in the Panyu Lijiang Garden showed they had coronavirus. Hong Kong medical experts say the Sars virus is close in form to the coronavirus found in rats." Prior to the SARS outbreak, rat coronaviruses had been isolated and sequenced and these isolates were quite unlike the SARS CoV. The rat sequences were most like mouse hepatitis virus, another class II coronavirus. SARS CoVs have very limited homology to the previously sequenced rat coronaviruses and the sequence from the Guangzhou patient is approximately 99% homologous to SARS CoV (at least in the S, M, and N genes, which are the three described in the recent press release). The comment that the patient's sequence is close to the coronavirus sequence found in rats in the patient's apartment raises several new issues. The first brings back the potential for contamination. The patient's sequence is quite distinct from all SARS CoVs at GenBank, but a similar sequence in rat material from the apartment raises the possibility of that material contaminating the patient's sample. If sequence data was obtained from the patient before rat samples entered the lab, then of course such contamination would not be possible. The sequence from the patient is clearly novel. The entire S gene has been sequenced and it is 98.8% to 99.4% homologous with SARS CoV sequences at GenBank. That means there are 22 nucleotide differences between the Guangzhou sequence and the closest sequence at GenBank and difference among all of the SARS CoV sequences is only an additional 22 nucleotides, so the recent sequence clearly is distinct from all of the other sequences. The sequence itself will provide more data, because some of the changes in the SARS CoV are related to the time of isolation last season while others are linked to geographical location. The sequence homology with Guangzhou rat isolates also may relate to the 99% homology in the N gene. If the patients N gene really has 10-11 nucleotide changes, then linkage to SARS CoVs from an animal reservoir other than masked palm civets is likely. Most of the SARS CoVs have exact matches with the N gene from the masked palm civets, and 10-11 changes would again set the Guangzhou isolate(s) apart from the SARS CoVs at GenBank. In any event, the novel SARS CoV described in yesterday's press release is clearly a virus that will undergo considerable scrutiny and a more extensive screening of Guangzhou rats should be a high priority. straitstimes.asia1.com.sg Is it Sars or not? By Mary Kwang CONFUSION over whether a suspected Sars patient in Guangzhou has the disease deepened yesterday when tests suggested he might have been infected by a new strain of the virus, the Chinese media reported. Xinhua news agency, quoting a Chinese medical expert, Professor Zhong Nanshan, director of the Guangzhou Institute of Respiratory Diseases, said that test results showed a possibility that the Sars coronavirus had taken a new form.