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Preliminary Clinical Description of Severe Acute Respiratory Syndrome
PROMED ^
| 03-26-03
Posted on 03/26/2003 5:39:19 PM PST by Mother Abigail
Today, 80 clinicians from 13 countries participated in an electronic "grand rounds" on clinical features and treatment for patients with Severe Acute Respiratory Syndrome, known as SARS. Their discussion, organized by the WHO network of clinicians focused on the disease's features at presentation, treatment, progression, prognostic indicators, and discharge criteria. No therapy demonstrated any particular effectiveness. Clinicians agreed that a subset of SARS patients, perhaps 10 percent, decline and need mechanical assistance to breathe. These people often have other illnesses that complicate their care. In this group, mortality is high.
Based on their experiences with patients, SARS clinicians are drawing the following conclusions:
Disease presentation:
All of the clinicians described presentations of SARS patients and the general consensus is that presentation is relatively consistent across all nations. Presentation is of a prodromal illness with a sudden onset of high fever. In a great number of cases this sudden, high fever is associated with myalgia, chills, rigors, and non-productive cough. At presentation (which is often 3 to 4 days after onset of symptoms), a large proportion of patients have characteristic changes on chest x-rays.
Disease progression:
Following presentation, chest x-rays continue to worsen and most patients demonstrate bilateral changes with interstitial infiltrations (fluid build-up between cells in the lungs). These infiltrations produce x-rays with a characteristic cloudy appearance. Patients then fall into one of 2 groups. The majority, 80 to 90 percent of patients at day 6 or 7, show improvement in signs and symptoms. A second smaller group, progress to a more severe form of SARS, many of whom develop acute respiratory distress syndrome and require mechanical ventilatory support. Though mortality associated with the more severe group is high, a number of patients have remained on ventilator support for prolonged periods of time. Mortality in the severe group appears to be linked to a patient's other illnesses (co-morbid factors).
Prognostic indicators:
Generally, patients over 40 with other illnesses are more likely to progress to the severe form of the disease.
Therapy:
Numerous antibiotic therapies have been tried to date with little clear effect. Ribavirin with or without use of steroids has been used in an increasing number of patients. But in the absence of clinical indicators, its effectiveness has not been proven. Currently the most appropriate management measures are general supportive therapy, insuring the person is hydrated and treated for subsequent infections.
What next:
Planning these grand rounds regularly. The clinicians involved in establishing management guidelines (treatment, management of patients and contacts, discharge).
The participants agreed to "meet" regularly using electronic communications and to rapidly develop international guidelines for the care of SARS patients.
TOPICS: Front Page News; News/Current Events
KEYWORDS: sars
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Preliminary Clinical Description of Severe Acute Respiratory Syndrome
Severe acute respiratory syndrome (SARS) is a condition of unknown etiology that has been described in patients in Asia, North America, and Europe. This report summarizes the clinical description of patients with SARS based on information collected since mid-February 2003 by the World Health Organization (WHO), Health Canada, and CDC in collaboration with health authorities and clinicians in Hong Kong, Taiwan, Bangkok, Singapore, the United Kingdom, Slovenia, Canada, and the United States. This information is preliminary and limited by the broad and necessarily nonspecific case definition. As of 21 Mar 2003, the majority of patients identified as having SARS have been adults aged 25--70 years who were previously healthy. Few suspected cases of SARS have been reported among children aged <15 years.
The incubation period for SARS is typically 2--7 days; however, isolated reports have suggested an incubation period as long as 10 days. The illness begins generally with a prodrome of fever (greater than 100.4 F [greater than 38.0 C]). Fever often is high, sometimes is associated with chills and rigors, and might be accompanied by other symptoms, including headache, malaise, and myalgia.
At the onset of illness, some persons have mild respiratory symptoms. Typically, rash and neurologic or gastrointestinal findings are absent; however, some patients have reported diarrhea during the febrile prodrome. After 3--7 days, a lower respiratory phase begins with the onset of a dry, nonproductive cough or dyspnea, which might be accompanied by or progress to hypoxemia. In 10--20 percent of cases, the respiratory illness is severe enough to require intubation and mechanical ventilation.
The case-fatality rate among persons with illness meeting the current WHO case definition of SARS is approximately 3 percent [based on today's data with the additional information from China, 49 deaths reported and 1323 cases the observed case fatality rate is now 3.7 percent - Mod.MPP]. Chest radiographs might be normal during the febrile prodrome and throughout the course of illness.
However, in a substantial proportion of patients, the respiratory phase is characterized by early focal interstitial infiltrates progressing to more generalized, patchy, interstitial infiltrates. Some chest radiographs from patients in the late stages of SARS also have shown areas of consolidation. Early in the course of disease, the absolute lymphocyte count is often decreased.
Overall white blood cell counts have generally been normal or decreased. At the peak of the respiratory illness, approximately 50 percent of patients have leukopenia and thrombocytopenia or low-normal platelet counts (50 000 - 150 000 / microL).
Early in the respiratory phase, elevated creatine phosphokinase levels (as high as 3000 IU/L) and hepatic transaminases (2 to 6 times the upper limits of normal) have been noted. In the majority of patients, renal function has remained normal. The severity of illness might be highly variable, ranging from mild illness to death. Although a few close contacts of patients with SARS have developed a similar illness, the majority have remained well.
Some close contacts have reported a mild, febrile illness without respiratory signs or symptoms, suggesting the illness might not always progress to the respiratory phase. Treatment regimens have included several antibiotics to presumptively treat known bacterial agents of atypical pneumonia. In several locations, therapy also has included antiviral agents such as oseltamivir or ribavirin. Steroids have also been administered orally or intravenously to patients in combination with ribavirin and other antimicrobials. At present, the most efficacious treatment regimen, if any, is unknown.
We are posting this for the benefit of clinician subscribers who might not have seen cases of SARS and would be interested in the current clinical description and discussions. As more information on the clinical presentation and treatment guidelines become available we shall post these as well.
To: Marie; cherry; united1000; keri; maestro; riri; Black Agnes; vetvetdoug; CathyRyan; per loin; ...
Good info
To: Mother Abigail
3
posted on
03/26/2003 5:46:31 PM PST
by
Diogenesis
(If you mess with one of us, you mess with all of us.)
To: Diogenesis
Thank you
To: Mother Abigail
A few days ago it was posted here that this disease was a coronavirus. In other words, the common cold - so what causes the common cold to assume such a lethal form? Is this a phenomenon that is familiar to the medical profession and this particular manifestation just hasn't been identified yet or is this out of the norm? Anyone out there who can enlighten us on this?
5
posted on
03/26/2003 5:55:03 PM PST
by
Sabatier
To: Mother Abigail
The Stones have cancelled their Hong Kong concert.
6
posted on
03/26/2003 6:12:16 PM PST
by
per loin
To: All
7
posted on
03/26/2003 6:12:41 PM PST
by
Bob J
To: Sabatier
A number of viruses have been found in SARS victims (3), the exact function of these bugs is yet to be determined.
If it is a Coronavirus, it is a new strain.
In all honesty no one knows at this time, but a lot of good people are working on this problem.
Stay tuned
To: per loin
I would think so..
To: All
Epidemiology:
This epidemic apparently started in Guongdong Province in Southern China. Several cases have occurred in travelers to this area. An "impressive" cluster has been linked to one hotel in Hong Kong. A physician from Guongdong visited Hong Kong for a wedding on 21 Feb 2003, and stayed one night at this hotel. 12 other cases have been linked to this hotel; 9 of the 12 stayed on the same floor.
These cases were then responsible for secondary clusters in Toronto, Hanoi, Singapore, and further cases at 3 Hong Kong hospitals. It is my understanding that this floor is a "smoking floor" of the hotel, which may be of interest with regard to transmission. At least 200 cases have occurred in Hong Kong, and transmission has been documented from patients to healthcare workers to healthcare worker's families, and most recently into the schools in that area. WHO is currently investigating 456 cases, including 17 deaths in 16 countries.
This total does not include any from China. In the United States, CDC is currently investigating 40 cases that meet the case definition in 18 states. The age range is 7 years to 78 years. 16 of these cases were hospitalized, and one patient was placed on mechanical ventilation but has since recovered. There have been no deaths attributed to SARS in the United States to date. At least 10 of the cases had documented pneumonia by chest
x-ray. 2 of the cases occurred in health care workers and 4 have been in family contacts.
To: All
Etiology
On Monday evening [24 Mar 2003], CDC has detected evidence for a coronavirus-like agent in 5 patients. Samples from a patient from Thailand, although initially negative by PCR, produced a cytopathic effect in Vero cell culture.
Supernatants from cell cultures were then tested by PCR, including a broadly reactive primer set against the polymerase region, and detected the presence of a virus from the coronavirus family. A more specific primer set is now being used to test other specimens.
Initially, this 400 base-pair amplicon suggests through a virus dendrogram analysis, [a virus] outside the 3 existing groups of coronaviruses known to infect humans. cDNA cloning is in progress. CDC has developed an IFA in-house and has used this to test supernatants from cell culture as well as paired sera from additional patients.
Please note that these "paired" sera were not obtained more than 2 weeks apart and in fact, are often separated by only several days. Nevertheless, IFA was initially negative in acute samples and positive in a second sample from 3 patients from widely varied geographic areas.
Furthermore, CPE was detected in Vero cell culture from autopsy materials from the Hong Kong index patient. Again, PCR was positive.
The sequence of this amplicon is pending, but it will be interesting to note whether it is the same as from the Thai patient noted above. In addition, BAL-cell pellets from the autopsy materials from this Hong Kong index case also revealed coronavirus-like particles on thin-section electron microscopy.
CDC has stressed that all specimens that they have tested are negative for human metapneumovirus; nevertheless, these agents have been detected in material in Canada and Hong Kong by PCR, and according to Donald Low, a human metapneumovirus was grown from lung tissue yesterday in Frank Plummer's laboratory in Toronto.
A great deal of discussion followed this information and the potential for a coronavirus to "jump" from animals to humans.
This has been detected rarely in the past, but there is some precedent. At least in my view, it is premature to assume that a coronavirus is the etiologic agent. CDC is consulting numerous experts and has shared PCR reagents with groups in Toronto and Hong Kong.
To: All
Very little information is available on treatment regimens and/or outcomes. Physicians in Hong Kong have reported "success" with ribavirin, with or without the addition of corticosteroids.
As there are no controls, these reports must be considered anecdotal at present. CDC has not yet made recommendations on the potential use of ribavirin, the route of administration (oral, intravenous, and/or aerosol), nor on the need for adjunctive corticosteroids. It is worth noting that ribavirin is active against mouse hepatitis, which is a coronavirus. Lacking other information on pathogenesis, there is no known role for interferon, leukotriene inhibitors, etc.
W. Michael Scheld, MD
IDSA President
This is an excellent overview of the situation as of the time of writing of this letter, covering the epidemiology, clinical features, treatment, and the status of the investigations on the etiologic agent of SARS. Of additional note is the mention that ribavirin has been shown to be active against mouse hepatitis, a coronavirus, suggesting that if the etiologic agent is confirmed to be a member of the coronavirus family, this may be a viable treatment modality.
Again, it is very premature to draw conclusions, and in turn to draw conclusions about clinical management other than supportive measures, which have been shown to assist in presumptive mortality reduction.
To: All
This is the first coherent account of experimentation designed to establish the identity of the etiologic agent of SARS. The experimental data described appear to be consistent with the presence of a novel coronavirus in clinical material from a small number of SARS patients. The molecular data are preliminary but sufficiently broad-based to be convincing, and as a consequence the coronavirus hypothesis is more credible than any of the competing claims.
Robust data on seroconversion are lacking, however, which are necessary to establish that the virus propagated in cultured cells is the pathogen and not a fortuitous passenger in the respiratory tract of SARS patients. If this agent isolated by the CDC group proves to be a novel coronavirus, the hypothesis that SARS occurs as a result of coinfection by two or more unrelated viruses becomes less probable.
Nonetheless the detection of human metapneumovirus (HMPV) by PCR in laboratories in Hong Kong and Canada, and the isolation of HMPV in cultured cells in Canada cannot be discounted at this stage. The discovery of HMPV in the Netherlands in 2001, a ubiquitous human virus that had escaped detection earlier, was partially dependent on the use of a particular cell substrate. It is possible that the Vero cell cultures employed by the CDC group might not have picked up HMPV. The pace of research is certainly accelerating and it is likely that very soon these matters will be resolved.
Coronaviruses infect birds and many mammals; in humans coronaviruses are the second most frequent cause of common colds.
Infection of humans and animals by coronaviruses is common and unrestricted by geography. No biological vectors are known. The respiratory tract, gastrointestinal organs and neurological tissues are the most common targets of coronaviruses.
Coronavirus replication also occurs in macrophages. Respiratory, fecal-oral and mechanical routes of transmission are common. In general coronaviruses have restricted host ranges, but instances of cross-species transmission have been described.
The genus _Coronavirus_ comprises three groups of viruses. Goup 1 includes canine, feline, porcine and human viruses, Group 2 includes bovine, human, murine, porcine and rodent viruses, and group 3 includes avian viruses. The coronaviruses take their name from the prominent "crown" of envelope spikes clearly visible by electron microscopy.
To: All
Country: Cumulative no. case(s)/ No. deaths/ Local transmission*
Canada: 19/ 3/ Yes
China, Guangdong Province+: 792/ 31/ Yes
China, Hong Kong SAR: 316/ 10**/ Yes
China, Taiwan: 6/ 0/ Yes
France: 1/ 0/ None
Germany: 4/ 0/ None
Italy: 3/ 0/ None
Republic of Ireland: 2/ 0/ None
Singapore: 74/ 1/ Yes
Switzerland: 2/ 0/ To be determined
Thailand: 3/ 0/ None
United Kingdom: 3/ 0/ None
United States: 40 §/ 0/ To be determined
Viet Nam: 58/ 4/ Yes
Total: 1323/ 49
To: All
State: suspected cases under
investigation*
California: 10
Connecticut: 1
Hawaii: 3
Illinois: 1
Kansas: 1
Maine: 2
Massachusetts: 1
Michigan: 2
Missouri: 2
Mississippi: 1
New Jersey: 1
New Mexico: 1
North Carolina: 2
New York: 4
Pennsylvania: 2
Rhode Island: 1
Texas: 3
Utah: 3
Virginia: 3
Wisconsin: 1
Total suspected cases under investigation 45 [representing 20 states]
To: Mother Abigail
Thanks for posting all of this information.
16
posted on
03/26/2003 7:54:46 PM PST
by
InShanghai
(I was born on the crest of a wave, and rocked in the cradle of the deep.)
To: InShanghai
You are quite welcome
To: Mother Abigail
To: Mother Abigail
BUMP.
To: Mother Abigail
It appears I have worked myself out of a job.
Many of you are now posting threads on SARS, and the information seems to be flowing in an accurate and timely manner.
So I will take this opportunity to thank all the posters for their hard work and diligence.
NOTE: I have tried to answer all the e-mails, except of course, the many that asked for personal information. Hope I was of some help
Stay Strong, Come and see me and - bring all your nice friends.......
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