Article for Alive magazine by David Crowe Suggested Title: SARS: Steroid And Ribavirin Scandal? Wordcount: 600 Deadline: June 13, 2003 ========================================= Bio (50 words): David Crowe is a Calgary based environmentalist and analyst of the scientific justification for modern medicine. He has an HBSc in Biology and Mathematics. He can be reached at ========================================= SARS has been portrayed by the media as a titanic battle with public health officials, infectious disease doctors and virologists on the white team facing billions of nasty, constantly mutating coronaviruses with near-magical infectious capabilities on the black team. Criticisms, when voiced, are usually accusations of “too little, too late”. But, it may be a case of “too much, too soon”. It was accepted from the beginning, without proof, that SARS was caused by a virus, because of a report that 45 of 50 early SARS patients, but no healthy controls, had tested positive for a novel coronavirusi. Later, however, Dr. Frank Plummer, scientific director of the Canadian Microbiology Laboratory stated that the fraction of SARS victims testing positive had declined from 70% early on, to only 40% laterii,iii. Even then it was only detected in minute quantities by ultra-sensitive tests and 20% of 250 people without SARS tested positive. According to Plummer the coronavirus connection is “actually very weak”iv. In May, Dr. Salter of WHO noted a significantly higher death rate in countries with more advanced forms of health carev – 15-19% in Canada, 11-17% in Hong Kong and Singapore but only 5-13% in Chinavi. The story of a Toronto nurse published in several Southam papersvii illustrates that aggressive treatment may help explain these anomalies. Susan Sorrenti, after exposure to a SARS patient, quarantined herself at home. A few days later her temperature rose one degree above normal, giving her the second of three characteristics required for a suspect case (the third being “a cough or breathing difficulty” viii). As soon as she checked into hospital she was prescribed intense drug therapy, including steroids and, eventually, the antiviral drug ribavirin. Only after starting drugs did she start to get sick. So sick that she almost died, and still suffered debilitating weakness even after recovering enough to be removed from the drugs. Many different drugs, including potent antibiotics, have been prescribed, but two stand out – Steroids and Ribavirinix,x. An early paper on ten Hong Kong patients noted that all received this treatment and claimed that it coincided with clinical improvementix, although later reports were less enthusiasticxi. A report on the ten early Canadian cases reported mixed results, with several patients becoming sicker after hospitalization and initiation of therapyx. Doctors from Singapore noted no obvious benefit from antibiotics, steroids or ribavirin. In fact, they found that “several patients deteriorated ins spite of its [ribavirin] use” and others recovered without it.xii Others have called this therapy “controversial”, “possibly ineffective” and “potentially hazardous”xiii The long term consequences of this therapy are slowly emerging – continuing shortness of breathxiv, brain and nerve damage (in about 50% of people)xv and recurrences of illnessv. As a nucleoside analogue, Ribavirin interferes with RNA and DNA synthesis in cells, and in the energy regulating mitochondria found in every living cell. It can cause anemia, bone marrow suppression, heart troubles, fetal abnormalities and, ironically, respiratory difficulties.xiv Several papers described this choice of drugs as “empirical” rather than scientificix,,x. Its use may be based on the belief that standard therapy would be ineffective against a potent new pneumonia virus. The use of ribavirin for pneumonia is a new phenomenonxiv. It has previously been used with modest (or perhaps exaggeratedxvi) benefits only for some relatively rare conditions. An alternative view of the SARS epidemic is that the fear of a virulent viral pneumonia pandemic emerging from China late in 2002 led to a ‘buzz’ in favour of early, aggressive therapy with antibiotic-steroid-ribavirin ‘cocktails’. This may have turned fear of disease into an iatrogenic reality. References

i Peiris JSM et al. Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet. 2003 Apr 5; 361(9364). ii Walgate R. Cause of SARS disputed. The Scientist. 2003 Apr 11. iii Altman LK. Virus Proves Baffling, Turning Up in Only 40% of a Lab's Test Cases. NY Times. 2003 Apr 24. iv Doubts thrown on the cause of SARS. The Independent. 2003 Apr 24. p5. v Bradsher K, Altman LK. 12 SARS Patients Report Relapses. New York Times. 2003 May 1. vi SARS Fatality Ratio Varies Greatly. Doctor’s Guide. 2003 May 8. vii Nuttall-Smith C. SARS survivor fought for every breath. Calgary Herald. 2003 May 2; A3. viii Severe Acute Respiratory Syndrome (SARS) case definitions. Health Canada. 2003 Jun 9. ix Tsang KW et al. A Cluster of Cases of Severe Acute Respiratory Syndrome in Hong Kong. N Engl J Med. 2003 Apr 1. x Poutanen SM et al. Identification of Severe Acute Respiratory Syndrome in Canada. N Engl J Med. 2003 Mar 31. xi Lyn TE, Lee C. SARS virus in Hong Kong seen mutating rapidly. Reuters. 2003 May 2. xii Hsu L-Y et al. Severe acute respiratory syndrome (SARS) in Singapore: clinical features of index patient and initial contacts. Emerg Infect Dis. 2003 Jun; 9(6). xiii Oba Y et al. The use of corticosteroids in SARS [letter and response]. N Engl J Med. 2003 May 15; 348(20): 2034-5. xiv Koren G et al. Ribavirin in the treatment of SARS: A new trick for an old drug? CMAJ. 2003 May 13; 168(10): 1289-92. xv Luck A. SARS patients ‘suffer brain damage’ from steroid cocktail. Daily Telegraph. 2003 Jun 1. xvi Waldholz M et al. Claims that side effects of ICN drug weren’t reported are focus of 2 probes. WSJ. 1987 Feb 20.



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