Severe acute respiratory syndrome--associated coronavirus in lung tissue.Efforts to contain severe acute respiratory syndrome Severe Acute Respiratory Syndrome (SARS) Definition Severe acute respiratory syndrome (SARS) is the first emergent and highly transmissible viral disease to appear during the twenty-first century. (SARS) have been limited by the lack of a standardized, sensitive, and specific test for SARS-associated coronavirus coronavirus /co·ro·na·vi·rus/ (ko-ro´nah-vi?rus) any virus belonging to the family Coronaviridae. Coronavirus /Co·ro·na·vi·rus/ (ko-ro´nah-vi?rus (CoV). We used a standardized reverse transcription-polymerase chain reaction assay to detect SARS-CoV in lung samples obtained from well-characterized patients who died of SARS and from those who died of other reasons. SARS-CoV was detected in all 22 postmortem postmortem /post·mor·tem/ (post-mort´im) performed or occurring after death. post·mor·tem adj. Relating to or occurring during the period after death. n. See autopsy. lung tissues (to [10.sup.9] viral copies/g) from 11 patients with probable SARS but was not detected in any of the 23 lung control samples (sample analysis was blinded). The sensitivity and specificity (95% confidence interval confidence interval, n a statistical device used to determine the range within which an acceptable datum would fall. Confidence intervals are usually expressed in percentages, typically 95% or 99%. ) were 100% (84.6% to 100%) and 100% (85.1% to 100%), respectively. Viral loads were significantly associated with a shorter course of illness but not with the use of ribavirin ribavirin /ri·ba·vi·rin/ (ri?bah-vi´rin) a broad-spectrum antiviral used in the treatment of severe viral pneumonia caused by respiratory syncytial virus, particularly in high-risk infants; also used in conjunction with interferon or steroids. CoV was consistently identified in the lungs of all patients who died of SARS but not in control patients, supporting a primary role for CoV in deaths. ********** From its origins in November 2002 in Guangdong Province, China, severe acute respiratory syndrome (SARS) has become an emerging infectious disease An emerging infectious disease (EID) is an infectious disease whose incidence has increased in the past 20 years and threatens to increase in the near future. EIDs include diseases caused by a newly identified microorganism or newly identified strain of a known microorganism (e.g. that has spread to areas throughout the world, including Hong Kong, Vietnam, Singapore, Taiwan, and Canada (1). Although controversy remains over the etiology of SARS, the World Health Organization has declared a newly described virus known as the SARS-associated coronavirus (SARS-CoV) as the cause (2). This announcement has led to a rapid proliferation of different in-house laboratory tests aimed at detecting either SARS-CoV-specific antibodies or SARS-CoV nucleic acid nucleic acid, any of a group of organic substances found in the chromosomes of living cells and viruses that play a central role in the storage and replication of hereditary information and in the expression of this information through protein synthesis. in clinical specimens. The Centers for Disease Control and Prevention Centers for Disease Control and Prevention (CDC), agency of the U.S. Public Health Service since 1973, with headquarters in Atlanta; it was established in 1946 as the Communicable Disease Center. definition for a confirmed case of SARS includes the results of these laboratory tests (3). However, because different assays are being used, comparing results from different centers has been difficult. In addition, the inability of these nonstandardized tests to detect SARS-CoV in all cases has led to speculation that other agents may be associated with SARS. Some researchers have suggested that illnesses that progress to respiratory failure Respiratory Failure Definition Respiratory failure is nearly any condition that affects breathing function or the lungs themselves and can result in failure of the lungs to function properly. and death may not be caused by uncontrolled viral replication but rather are the result of an immunopathologic process (4). In a recent report of six fatal cases of SARS, SARS-CoV was detected by reverse transcriptase-polymerase chain reaction (RT-PCR RT-PCR reverse transcriptase-polymerase chain reaction. See PCR1. ) in postmortem lung tissue in only four patients (5). The purpose of this study was to use a standardized, commercially available, RT-PCR assay to test for the presence of SARS-CoV RNA RNA: see nucleic acid. RNA in full ribonucleic acid One of the two main types of nucleic acid (the other being DNA), which functions in cellular protein synthesis in all living cells and replaces DNA as the carrier of genetic . Lung tissue obtained at autopsy from well-characterized patients with SARS who died during the outbreak in Canada were compared to lung samples obtained at autopsy from patients without SARS who died during the outbreak and lung samples from patients who died before the outbreak. Methods Patients All patients who met the current World Health Organization case definition of probable SARS and who underwent a postmortem examination postmortem examination n. See autopsy. in Canada during the March-April 2003 outbreak were included in this study. Clinical details were extracted retrospectively from hospital records. Clinical descriptions of some of these cases have been published separately (6,7). As of May 14, 2003, a total of 24 patients died of SARS in Canada; all died in Toronto. Of the 24 patients, autopsies were performed on 11 patients. Results of ante- and postmortem examination for routine bacterial and viral respiratory pathogens from these 11 patients, as described elsewhere, were negative (6). Lung Tissue Samples A total of 22 discrete postmortem lung samples collected from these 11 patients were included in this analysis. An additional 13 postmortem lung samples from 7 patients who died during the SARS outbreak but whose deaths were attributed to other causes were also included. The attributed cause of death in these patients was as follows: a 46-year-old woman died of invasive group A streptococcal infection The group A streptococcus bacterium (Streptococcus pyogenes, or GAS) is a form of Streptococcus bacteria responsible for most cases of streptococcal illness. Other types (B, C, D, and G) may also cause infection. ; a 93-year-old man died of congestive heart failure congestive heart failure, inability of the heart to expel sufficient blood to keep pace with the metabolic demands of the body. In the healthy individual the heart can tolerate large increases of workload for a considerable length of time. ; a 37-year-old man died of sudden death cardiovascular disease Cardiovascular disease Disease that affects the heart and blood vessels. Mentioned in: Lipoproteins Test cardiovascular disease ; a 74-year-old man died of amiodarone pulmonary toxicity; a 78-year-old woman died of dementia and aspiration pneumonia aspiration pneumonia n. Bronchopneumonia resulting from the entrance of foreign material, usually food particles or vomit, into the bronchi. aspiration pneumonia ; a 47-year-old woman died of diabetes and congestive heart failure; and an 81-year-old man died of bladder cancer bladder cancer Malignant tumour of the bladder. The most significant risk factor associated with bladder cancer is smoking. Exposure to chemicals called arylamines, which are used in the leather, rubber, printing, and textiles industries, is another risk factor. and aspiration pneumonia. In addition, 10 lung samples collected in 1998 from 10 patients (4 women and 6 men; age range 54 75 years) with lung cancer lung cancer, cancer that originates in the tissues of the lungs. Lung cancer is the leading cause of cancer death in the United States in both men and women. Like other cancers, lung cancer occurs after repeated insults to the genetic material of the cell. were also included as negative controls. All samples collected at the time of autopsy were snap frozen in a mixture of absolute ethanol and dry ice and subsequently stored at -70[degrees]C until tested. The samples were coded and then processed, subjected to RT-PCR analysis, and interpreted before the identity of the samples was divulged. This study was approved by the research ethics boards at Mount Sinai Hospital Mount Sinai Hospital can refer to:
RT-PCR Lung tissue samples were thawed and immediately homogenized ho·mog·e·nize v. ho·mog·e·nized, ho·mog·e·niz·ing, ho·mog·e·niz·es v.tr. 1. To make homogeneous. 2. a. To reduce to particles and disperse throughout a fluid. b. in lysis buffer (QIAGEN, Mississauga, Canada) with disposable tissue grinders (Kendall Precision, Mansfield, MA). The homogenate homogenate /ho·mog·e·nate/ (ho-moj´in-at) material obtained by homogenization. homogenate material obtained by homogenization. was passed through QIAshredder columns (QIAGEN) before RNA isolation by using the RNeasy Mini Kit (QIAGEN). The sample was eluted in 30 [micro]L of RNAse free water. The RTPCR RTPCR Reverse Transcriptase Polymerase Chain Reaction was carried out by using the RealArt HPA-Coronavirus LightCycler RT Reagents Assay (Artus GmbH, Hamburg, Germany) with a LightCycler real-time platform (Roche Diagnostics, Laval, Canada). The HPA-Coronavirus Master Mix contains reagents and enzymes for the specific amplification of an 80-bp region of the SARS-CoV polymerase gene from 5 [micro]L of RNA with the primer pairs published by the Bernhard-Nocht Institute (Hamburg, Germany) as posted on the World Health Organization Web site (available from: URL URL in full Uniform Resource Locator Address of a resource on the Internet. The resource can be any type of file stored on a server, such as a Web page, a text file, a graphics file, or an application program. : http://www.who.int/csr/sars/primers/en/). Viral load was calculated from a standard curve based on four external positive controls (quantification standards) included in the RealArt HPA-Coronavirus LightCycler RT Reagents Assay kit (Figure A and B). The standards were treated as previously purified samples, and the same 5-mL volume was added per capillary. A standard preparation of SARS-CoV isolated from cell culture supernatants of VeroE6 cells was used as a calibrator calibrator an instrument for dilating a tubular structure or for determining the caliber of such a structure. in each run. In addition, the kit contains a second heterologous heterologous /het·er·ol·o·gous/ (het?er-ol´ah-gus) 1. made up of tissue not normal to the part. 2. xenogeneic. het·er·ol·o·gous adj. 1. amplification system amplification system Physiology A generic term for any group of proteins that function in coordinated sequences, forming positive feedback loops for expanding the response to a low intensity signal Amplification systems
PCR abbr. polymerase chain reaction Polymerase chain reaction (PCR) inhibition exclusively, if added to the extracted RNA, or RNA isolation quality as well as PCR inhibition, if added during the RNA isolation procedure (Figure C). Although the assay insert states that the primers and probes used in the assay were checked for possible similarity to other pathogens by means of sequence comparison, 25 randomly chosen amplicons from our sample pool were independently sequenced to confirm SARS-CoV-specific amplification and detection. Univariate analysis comparing potential predictors of viral load (e.g., duration of illness, the use of ribavirin, the use of steroids) was completed by using Fisher exact test. Two-sided p values [less than or equal to] 0.05 were considered significant. [FIGURE OMITTED] Results The clinical description and RT-PCR results for the 11 patients with probable SARS from whom postmortem lung tissue samples were examined are summarized in Table 1. The mean age of the 11 patients was 70 years (range 43-99). Six of the 11 patients were men. All but 1 of the 11 patients had underlying coexisting conditions, the most common of which was diabetes mellitus diabetes mellitus Disorder of insufficient production of or reduced sensitivity to insulin. Insulin, synthesized in the islets of Langerhans (see Langerhans, islets of), is necessary to metabolize glucose. In diabetes, blood sugar levels increase (hyperglycemia). in 6 patients. The mean duration of illness was 20 days (range 8-32). Seven patients had been intubated and mechanically ventilated ven·ti·late tr.v. ven·ti·lat·ed, ven·ti·lat·ing, ven·ti·lates 1. To admit fresh air into (a mine, for example) to replace stale or noxious air. 2. before death. Three patients had requested not to be intubated (information on ventilation was not available for one patient). Ten of the 11 patients were treated with ribavirin; 6 of the 11 patients were treated with steroids. SARS-CoV was detected in all 22 postmortem lung tissue samples collected from all 11 patients who died with a diagnosis of probable SARS. All 13 postmortem lung samples from the seven non-SARS fatalities that occurred during the SARS outbreak were negative for SARS-CoV, as were all 10 lung-tissue samples collected from patients with lung cancer 5 years before the outbreak (Table 2). The corresponding sensitivity and specificity of the RealArt HPA-Coronavirus LightCycler RT Reagent assay are both 100% (95% confidence interval [CI] for sensitivity 84.6% to 100%; 95% CI for specificity 85.1% to 100%) for the detection of SARS-CoV. The SARS-CoV viral load in postmortem lung tissue ranged from 2.7 x [10.sup.4] copies/g tissue to 3.8 x [10.sup.9] copies/g tissue. Higher viral loads ([greater than or equal to] [10.sup.6] copies/g tissue) were associated with patients who had a shorter duration of illness ([less than or equal to] 21 days) (p=0.002, Fisher exact test). The use of ribavirin or steroids was not significantly associated with viral load levels (Table 2). Twenty-five randomly selected amplicons from the sample pool were sequenced to assess specificity and possible cross-reactivity to other pathogens. A BLAST (available from: URL: http://www.ncbi.nlm.nih.gov/BLAST/) search performed against the SARS-CoV genomes in GenBank, European Molecular Biology Laboratory The European Molecular Biology Laboratory (EMBL) is a molecular biology research institution supported by 19 countries comprising nearly all of western Europe and Israel. , DNA DNA: see nucleic acid. DNA or deoxyribonucleic acid One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes. Data Bank of Japan, and Protein Data Bank on the National Center for Biotechnology Information The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health. The NCBI is located in Bethesda, Maryland and was founded in 1988. Web site (available from: URL: http://www.ncbi.nlm.nih.gov/), indicated that all amplicon samples contained SARS-CoV polymerase gene sequence. Discussion By using a standardized RT-PCR assay, SARS-CoV has been unequivocally identified in the lung tissue of all patients who died with probable SARS but not in any of the controls. These observations support a primary role for this virus in patients with SARS who have fatal outcomes and provide additional, strong evidence to fulfill Koch's postulates Koch's postulates pl.n. The series of conditions that must be met in order to establish a microorganism as the causative agent of a disease, namely: it must be present in all cases of the disease; inoculations of its pure cultures must produce the regarding SARS-CoV as the cause of SARS (8). SARS-CoV was found in different lung samples from the same patient, suggesting that the virus is widely disseminated throughout the lung at the time of death. Previous studies suggested that progression of disease to respiratory failure may be primarily mediated by host immune response immune response n. An integrated bodily response to an antigen, especially one mediated by lymphocytes and involving recognition of antigens by specific antibodies or previously sensitized lymphocytes. rather than viral replication (4). Although viral RNA in lung tissue does not necessarily indicate replicating virus, virus in multiple lung lobes, often in high copy number, at the time of death suggests that SARS-CoV may also be contributing to disease progression. The fact that higher viral loads were significantly associated with patients with a shorter duration from onset of illness to death supports the role of viral replication as a contributor to death. Ten of the 11 patients had received therapy with ribavirin, and 6 patients were treated with steroids. The failure to eradicate SARS-CoV despite ribavirin therapy and the lack of association between the use of ribavirin and SARS-CoV viral load are consistent with in vitro in vitro /in vi·tro/ (in ve´tro) [L.] within a glass; observable in a test tube; in an artificial environment. in vi·tro adj. In an artificial environment outside a living organism. data showing that ribavirin has no activity against this agent (9). Global efforts to contain SARS have been severely impeded by the lack of a standardized, sensitive, and specific diagnostic test for SARS-CoV. Different diagnostic strategies, including culture, serologic se·rol·o·gy n. pl. se·rol·o·gies 1. The science that deals with the properties and reactions of serums, especially blood serum. 2. assays, and molecular detection methods, have been described, but each of these tests has limitations. In-house RT-PCR assays have been associated with sensitivities as low as 50% in patients with SARS (10), which raises uncertainty about the role of CoV versus co-pathogens in mediating severe or fatal SARS. By contrast, the sensitivity and specificity of the RealArt HPA-Coronavirus RT-PCR assay for detecting CoV in lung tissue samples appear to be excellent. In addition, with the real-time LightCycler system, the assay generates quantitative results within 1 hour, which is much shorter than traditional PCR reactions. The type of specimen tested, the timing of sample collection, (i.e., acute versus convalescent con·va·les·cent adj. Relating to convalescence. n. A person who is recovering from an illness, an injury, or a surgical operation. convalescent 1. pertaining to or characterized by convalescence. 2. phase) the method of specimen collection, as well as the method of sample preservation may have substantial impact on the results obtained from a diagnostic test. The lower sensitivity of SARS-CoV detection reported by Peiris et al. (10) may be a consequence of these cofounding factors. Our study design of examining lung biopsies from clearly defined patient populations overcame confounding confounding when the effects of two, or more, processes on results cannot be separated, the results are said to be confounded, a cause of bias in disease studies. confounding factor issues, such as sampling technique, nonspecific nonspecific /non·spe·cif·ic/ (non?spi-sif´ik) 1. not due to any single known cause. 2. not directed against a particular agent, but rather having a general effect. nonspecific 1. case definitions, and possible undocumented exposure to SARS. Given the predominance of respiratory symptoms in patients with SARS, lung samples have perhaps the highest viral titers of all specimen types; yet in nonfatal cases, obtaining routine lung biopsies is not practical. Other respiratory tract respiratory tract n. The air passages from the nose to the pulmonary alveoli, including the pharynx, larynx, trachea, and bronchi. Respiratory tract specimens may be satisfactory substitutes for biopsies, but further studies examining the prevalence of SARS-CoV in these other specimen types and in a larger population are needed. With the use of standardized commercially available assays, comparison of results from different centers may be facilitated.
Table 1. Clinical description and SARS-CoV RT-PCR results
for 11 patients who died with probable SARS (a)
Illness and treatment
duration (days)
Sex/age Coexisting conditions Illness Ventilation
M/43 Type II DM, HTN 15 4
M/76 Type II DM, CAD, 11 4
HTN
F/78 Type II DM, CAD, 8 5
hypercholesterolemia,
chronic obstructive
pulmonary disease
M/62 Rectal cancer, HTN, 8 N/A
hypercholesterolemia
F/73 HTN, 28 DNI
hypercholesterolemia
F/99 Osteoarthritis 26 DNI
M/63 Hypercholesterolemia, 20 12
cerebral vascular
disease
F/78 Type II DM, HTN, 24 18
hypercholesterolemia
M/44 29 18
M/77 Type II DM, HTN, [greater than [greater than
hypercholesterolemia or equal to] 18 or equal to] 1
F/79 Type II DM, HTN, 32 DNI
hypercholesterolemia
Illness and treatment
duration (days)
Sex/age Coexisting conditions Ribavirin Steroids
M/43 Type II DM, HTN 0 0
M/76 Type II DM, CAD, 6 (started on day 0
HTN 6 of illness)
F/78 Type II DM, CAD, [greater than 0
hypercholesterolemia, or equal to]
chronic obstructive 5 (started on
pulmonary disease day 4 of illness)
M/62 Rectal cancer, HTN, [greater than 0
hypercholesterolemia or equal to]
5 (started on
day 4 of illness)
F/73 HTN, 14 (started on 12 (stated
hypercholesterolemia day 5 of illness) on day
14 of illness)
F/99 Osteoarthritis 13 (started on 0
day 1 of illness)
M/63 Hypercholesterolemia, 16 (started on 16 (started
cerebral vascular day 4 of illness) on day
disease 6 of illness)
F/78 Type II DM, HTN, 10 (started on 18 (started
hypercholesterolemia day 3 of illness) on day
5 of illness)
M/44 18 (started on 17 (started
day 8 of illness) on day
12 of illness)
M/77 Type II DM, HTN, [greater than [greater than
hypercholesterolemia or equal to] or equal to]
1 (started on 7 (started on
day 10 of illness) day 10 of
illness)
F/79 Type II DM, HTN, 11 (started on [greater than
hypercholesterolemia day 2 of illness) or equal to]
4 (started on
day 12 of
illness)
Postmortem
lung tissue
Sex/age Coexisting conditions description
M/43 Type II DM, HTN RUL
RML (#1)
RML (#2)
RML (#3)
RML (#4)
M/76 Type II DM, CAD, Lung
HTN
F/78 Type II DM, CAD, RT lung
hypercholesterolemia, LUL
chronic obstructive
pulmonary disease
M/62 Rectal cancer, HTN, LT lung
hypercholesterolemia
F/73 HTN, LT lung
hypercholesterolemia RT lung
F/99 Osteoarthritis Lung
M/63 Hypercholesterolemia, RUL lung
cerebral vascular LLL
disease
F/78 Type II DM, HTN, LT lung
hypercholesterolemia RUL
M/44 RT lung
LT lung
M/77 Type II DM, HTN, LLL
hypercholesterolemia LUL
F/79 Type II DM, HTN, LT lung
hypercholesterolemia Lung
RealArt HPA Coronavirus
RT-PCR (b)
Copies of
Sex/age Coexisting conditions Results CoV/g tissue
M/43 Type II DM, HTN Positive 1.5 x [10.sup.8]
Positive 5.4 x [10.sup.7]
Positive 2.8 x [10.sup.7]
Positive 7.4 x [10.sup.6]
Positive 6.4 x [10.sup.8]
M/76 Type II DM, CAD, Positive 3.8 x [10.sup.9]
HTN
F/78 Type II DM, CAD, Positive 1.0 x [10.sup.9]
hypercholesterolemia, Positive 9.4 x [10.sup.7]
chronic obstructive
pulmonary disease
M/62 Rectal cancer, HTN, Positive 5.3 x [10.sup.7]
hypercholesterolemia
F/73 HTN, Positive 3.0 x [10.sup.4]
hypercholesterolemia Positive 3.6 x [10.sup.5]
F/99 Osteoarthritis Positive 5.0 x [10.sup.4]
M/63 Hypercholesterolemia, Positive 3.2 x [10.sup.6]
cerebral vascular Positive 2.5 x [10.sup.7]
disease
F/78 Type II DM, HTN, Positive 4.1 x [10.sup.5]
hypercholesterolemia Positive 4.9 x [10.sup.5]
M/44 Positive 7.6 x [10.sup.4]
Positive 4.1 x [10.sup.4]
M/77 Type II DM, HTN, Positive 5.6 x [10.sup.5]
hypercholesterolemia Positive 5.7 x [10.sup.5]
F/79 Type II DM, HTN, Positive 2.7 x [10.sup.4]
hypercholesterolemia Positive 2.1 x [10.sup.5]
(a) SARS, severe acute respiratory syndrome; CoV, coronavirus;
RT-PCR, reverse transcription polymerase chain reaction;
F, female; M, male; DM, diabetes mellitus; HTN, hypertension;
RUL, right upper lobe; RML, right middle lobe; CAD, coronary
artery disease; RT, right; LT, left; LUL, left upper lobe;
LLL, left lower lobe; N/A, not available; DNI, "Do not
intubate" order written.
(b) RealArt HPA Coronavirus RT-PCR (Artus GmbH, Hamburg, Germany).
Table 2. Univariate analysis of predictors of high viral
loads in postmortem lung tissue
Viral load
[greater than Viral load
or equal to] < [10.sup.6] Fisher
[10.sup.6] copies/g copies/g exact
Predictor lung tissue lung tissue test
Short duration of 5/5 0/6 p=0.002
illness ([less than
or equal to] 21 d)
Use of ribavirin 4/5 6/6 p=0.45
Use of steroids 1/5 5/6 p=0.08
Acknowledgments We thank Allison McGeer, Karen Green, Poolak Akhavan, Sylvia Pong-Porter, Peter Faure, Wayne Gold, the Ontario Coroner's Office; Brendan Mullen for generously providing 10 control lung samples; H.W. Doerr and M. Niedrig for generously providing supernatants of VeroE6 cells; and all of the clinicians who were involved in courageously caring for the patients described in this paper who lost their lives to severe acute respiratory syndrome. This study is supported by a grant from the Canadian Institute of Health Research (MT-13721 to K.C.K). K.C.K. is supported by a Career Scientist Award from the Ontario Ministry of Health and a Canada Research Chair Canada Research Chairs (CRCs) are Canadian university research professorships created through the Canada Research Chairs Program. Program goals The program, established in 2000, is an integral part of a Government of Canada plan to drive Canadian research and development . Artus GmbH provided assays for this study, but neither they nor the sponsors of the study had any role in the study design, data collection, data analysis, data interpretation, or writing of the report. None of the authors has a conflict of interest in relationship to this study. References (1.) Update: outbreak of severe acute respiratory syndrome--worldwide, 2003. MMWR MMWR Morbidity & Mortality Weekly Report Epidemiology A news bulletin published by the CDC, which provides epidemiologic data–eg, statistics on the incidence of AIDS, rabies, rubella, STDs and other communicable diseases, causes of mortality–eg, Morb Mortal Wkly Rep 2003;52:241-6. (2.) World Health Organization. Coronavirus never before seen in humans is the cause of SARS--update 31. Geneva Geneva, canton and city, Switzerland Geneva (jənē`və), Fr. Genève, canton (1990 pop. 373,019), 109 sq mi (282 sq km), SW Switzerland, surrounding the southwest tip of the Lake of Geneva. : The Organization; 2003. (3.) Updated interim surveillance case definition for severe acute respiratory syndrome (SARS)--United States, April 29, 2003. MMWR Morb Mortal Wkly Rep 2003;52:391-3. (4.) Peiris JSM JSM Journal of Sexual Medicine JSM Just Shoot Me (sitcom) JSM Journal of Sport Management JSM Journal of Software Maintenance JSM Jabber Session Manager JSM John Sidney McCain JSM JEOL Scanning Microscope , Chu CM, Cheng VCC An electronics designation that refers to voltage from a power supply connected to the "collector" terminal of a bipolar transistor. In an NPN bipolar (BJT) transistor, it would be +Vcc, while in a PNP transistor, it would be -Vcc. , Chart KS, Hung IFN IFN abbr. interferon IFN interferon. IFN Interferon, see there , Poon poon n. Any of several trees of the genus Calophyllum, of southern Asia, having light hard wood used for masts and spars. [Sinhalese p LLM LLM abbr. Latin Legum Magister (Master of Laws) LLM Master of Laws [Latin Legum Magister] Noun 1. , et al. Clinical progression and viral load in a community outbreak of corunavirus-associated SARS pneumonia: a prospective study. Lancet 2003;361:1767-72. (5.) Nicholls JM, Poon LLM, Lee KC, Ng WF, Lai ST, Leung CY, et al. Lung pathology of fatal severe acute respiratory syndrome. Lancet 2003;361:1773-8. (6.) Poutanen SM, Low DE, Henry B, Finkelstein S, Rose D, Green K, et al. Identification of severe acute respiratory syndrome in Canada. N Engl J Med 2003;348:1995-2005. (7.) Booth CM, Matukas LM, Tomlinson GA, Rachlis AR, Rose DB, Dwosh HA, et al. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area The Greater Toronto Area (widely abbreviated as the GTA) is the most populous metropolitan area in Canada. The GTA is a provincial planning area with a population of 5,555,912 at the 2006 Canadian Census. . JAMA JAMA abbr. Journal of the American Medical Association 2003;289:14. (8.) Fouchier RA, Kuiken T, Schutten M, van Amerongen G, Van Doornum GJ, van den Hoogen BG, et al. Aetiology aetiology see etiology. : Koch's postulates fulfilled for SARS virus. Nature 2003;423:240. (9.) Severe acute respiratory syndrome (SARS) and coronavirus testing--United States, 2003. MMWR Morb Mortal Wkly Rep 2003;52:297-302. (10.) Peiris JS, Lai ST, Poon LL, Guan guan: see curassow. Y, Yam LY, Lira W, et al. Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet 2003;361:1319-25. Dr. Mazzulli is deputy chief microbiologist at Toronto Medical Labaratories/Mount Sinai Hospital Department of Microbiology, Toronto Canada. He is also associate professor in the Department of Pathology and Laboratory Medicine, University of Toronto Research at the University of Toronto has been responsible for the world's first electronic heart pacemaker, artificial larynx, single-lung transplant, nerve transplant, artificial pancreas, chemical laser, G-suit, the first practical electron microscope, the first cloning of T-cells, . Address for correspondence: Kevin Kain, Tropical Disease Unit, Eaton South 9-414, Toronto General Hospital The Toronto General Hospital (TGH), part of the University Health Network, is a major teaching hospital in downtown Toronto, Canada. It is located in the Discovery District, directly north of the Hospital for Sick Children, across Gerrard Street West, and east of Princess , 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada; fax: 416-595-5826; email: kevin.kain @uhn.on.ca Tony Mazzulli, * ([dagger]) ([double dagger]) Gabriella A. Farcas, ([double dagger]) ([section]) Susan M. Poutanen, * ([dagger]) ([double dagger]) Barbara M. Willey, * ([dagger]) Donald E. Low, * ([dagger]) ([double dagger]) Jagdish Butany, ([dagger]) ([double dagger]) ([paragraph]) Sylvia L. Asa, ([dagger]) ([double dagger]) ([section]) and Kevin C. Kain ([double dagger]) ([section]) (1) * Mount Sinai Hospital, Toronto, Ontario, Canada; ([dagger]) Toronto Medical Laboratories, Toronto Ontario, Canada; ([double dagger]) University of Toronto, Toronto, Ontario, Canada; ([section]) Toronto General Hospital, Toronto, Ontario, Canada; and ([paragraph]) University Health Network, Toronto, Ontario, Canada (1) Drs. Mazzulli and Farcas contributed equally to the manuscript. All authors jointly conceived and designed the study and wrote the report. Gabriella A. Farcas performed the majority of the reverse transcription-polymerase chain reaction assays. |
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