Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Severe Acute Respiratory Syndrome (SARS)

  • Author: Faustine Ong, MD; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM  more...
 
Updated: Jun 23, 2016
 

Practice Essentials

Severe acute respiratory syndrome (SARS) is a serious, potentially life-threatening viral infection caused by a previously unrecognized virus from the Coronaviridae family, the SARS-associated coronavirus (SARS-CoV). Since the 2002-2003 outbreak of SARS, which apparently began in southern China but eventually involved more than 8000 persons worldwide (see the image below), global efforts have virtually eradicated SARS as a threat.

World map of severe acute respiratory syndrome (SA World map of severe acute respiratory syndrome (SARS) distribution from the 2002-2003 outbreak infection. The greatest number of past and new cases of SARS are in mainland China, Hong Kong, Taiwan, and Singapore (red). Canada, more specifically Toronto, Ontario (yellow), is the fifth-ranked area, although community transmission of SARS now appears to be contained, according to the US Centers for Disease Control and Prevention. Green represents the other countries reporting SARS cases.

Signs and symptoms

The clinical course of SARS generally follows a typical pattern. Stage 1 is a flulike prodrome that begins 2-7 days after incubation, lasts 3-7 days, and is characterized by the following:

  • Fever (>100.4°F [38°C])
  • Fatigue
  • Headaches
  • Chills
  • Myalgias
  • Malaise
  • Anorexia

Less common features include the following[1, 2, 3] :

  • Sputum production
  • Sore throat
  • Coryza
  • Nausea and vomiting
  • Dizziness
  • Diarrhea

Stage 2 is the lower respiratory tract phase and is characterized by the following:

  • Dry cough
  • Dyspnea
  • Progressive hypoxemia in many cases
  • Respiratory failure that requires mechanical ventilation in some cases

See Clinical Presentation for more detail.

Diagnosis

Initial tests in patients suspected of having SARS include the following:

  • Pulse oximetry
  • Blood cultures
  • Sputum Gram stain and culture
  • Viral respiratory pathogen tests, notably influenza A and B viruses and respiratory syncytial virus
  • Legionella and pneumococcal urinary antigen testing should also be considered

Data from the 2002-2003 outbreak indicate that SARS may be associated with the following laboratory findings[1, 2, 3, 4] :

  • Modest lymphopenia, leukopenia, and thrombocytopenia: Series have shown white blood cell (WBC) counts of less than 3.5 x 10 9/L and lymphopenia of less than approximately 1 x 10 9/L
  • Mild hyponatremia and hypokalemia
  • Elevated levels of lactate dehydrogenase, alanine aminotransferase, and hepatic transaminase
  • Elevated creatine kinase level

According to guidelines from the Centers for Disease Control and Prevention (CDC), the laboratory diagnosis of SARS-CoV infection is established on the basis of detection of any of the following with a validated test, with confirmation in a reference laboratory[5, 6] :

  • Serum antibodies to SARS-CoV in a single serum specimen
  • A 4-fold or greater increase in SARS-CoV antibody titer between acute- and convalescent-phase serum specimens tested in parallel
  • Negative SARS-CoV antibody test result on acute-phase serum and positive SARS-CoV antibody test result on convalescent-phase serum tested in parallel
  • Isolation in cell culture of SARS-CoV from a clinical specimen, with confirmation using a test validated by the CDC
  • Detection of SARS-CoV RNA via reverse transcriptase polymerase chain reaction (RT-PCR) assay validated by the CDC, with confirmation in a reference laboratory, from (1) two clinical specimens from different sources or (2) two clinical specimens collected from the same source on 2 different days [7]

Chest radiography results in SARS are as follows:

  • In one study, abnormalities were found on initial studies in approximately 60% of patients and were observed in serial examinations in nearly all patients by 10-14 days after symptom onset [8, 9]
  • Interstitial infiltrates can be observed early in the disease course
  • As the disease progresses, widespread opacification affects large areas, generally starting in the lower lung fields

High-resolution computed tomography (HRCT) scanning is controversial in the evaluation of SARS but may be considered when SARS is a strong clinical possibility despite normal chest radiographs.[9, 10] HRCT findings consistent with SARS include the following:

  • In early-stage SARS, an infiltrate in the retrocardiac region
  • Ground-glass opacification, with or without thickening of the intralobular or interlobular interstitium
  • Frank consolidation

See Workup for more detail.

Management

No definitive medication protocol specific to SARS has been developed, although various treatment regimens have been tried without proven success.[11, 12] The CDC recommends that patients suspected of or confirmed as having SARS receive the same treatment that would be administered if they had any serious, community-acquired pneumonia.

The following measures may be used:

  • Isolate confirmed or suspected patients and provide aggressive treatment in a hospital setting
  • Mechanical ventilation and critical care treatment may be necessary during the illness. [13, 12]
  • An infectious disease specialist, a pulmonary specialist, and/or a critical care specialist should direct the medical care team
  • Communication with local and state health agencies, the CDC, and World Health Organization is critical

See Treatment and Medication for more detail.

Next

Pathophysiology

The lungs and gastrointestinal tract have been demonstrated to be the only major organ systems that support SARS-CoV replication.[14, 15]

After establishment of infection, SARS-CoV causes tissue damage by (1) direct lytic effects on host cells and (2) indirect consequences resulting from the host immune response. Autopsies demonstrated changes that were confined mostly to pulmonary tissue, where diffuse alveolar damage was the most prominent feature. (See the image below.)

Pathologic slide of pulmonary tissue infected with Pathologic slide of pulmonary tissue infected with severe acute respiratory syndrome–associated coronavirus. Diffuse alveolar damage is seen along with a multinucleated giant cell with no conspicuous viral inclusions. Courtesy of the US Centers for Disease Control and Prevention.

Multinucleated syncytial giant cells were thought to be characteristic of SARS but were rarely seen. Angiotensin-converting enzyme-2 (ACE-2), being a negative regulator of the local rennin-angiotensin system, was thought to be a major contributor to the development of this damage.[16]

The other mechanism was thought to be the induction of apoptosis. The SARS-CoV–3a and –7a proteins have been demonstrated to be inducers of apoptosis in various cell lines.[17]

Immunologically, SARS is characterized by a phase of cytokine storm, with various chemokines and cytokines being elevated.[15, 18]

Previous
Next

Etiology

Sources

Coronaviruses (CoVs) are found in a wide range of animal species, including in cats, dogs, pigs, rabbits, cattle, mice, rats, chickens, pheasants, turkeys, and whales, as well as in humans.[19] They cause numerous veterinary diseases (eg, feline infectious peritonitis, avian infectious bronchitis); they can also cause upper and, more commonly, lower respiratory tract illness in humans (group 1 [human CoV 229E] and group 2 [human CoV OC43]).

The near absence of SARS-CoV antibodies in persons who did not have SARS demonstrated that SARS-CoV had not circulated to any significant extent in humans before 2003 and was introduced into humans from animals.[20] Preliminary data after the outbreak started suggested that animals in the markets of Guangdong province in China may have been the source of human infection. However SARS-CoV ̶ like viruses were not found in animals prior to arrival in the markets.

A wide range of other coronaviruses in bats has been found,[21, 22] suggesting that bats are the most likely animal reservoir for the SARS outbreak. SARS infection in animals before arrival in the markets was uncommon, and these animals were probably not the original reservoir of the outbreak, although they may have acted as amplifying hosts. The proximity in which humans and livestock live in rural southern China may have led to the transmission of the virus to humans.[21]

Cellular binding

Single-stranded ribonucleic acid (RNA) viruses such as the SARS-CoV have no inherent proofreading mechanism during replication. Accordingly, mutations in the RNA sequence replication of coronaviruses are relatively common. Such mutations can cause the resulting new virus to be either less or more virulent.[23]

The surface envelop S protein of SARS-CoV is thought to be a major determinant in establishing infection and cell and tissue tropism.[24] This protein, after binding to its receptor—which is thought to be angiotensin-converting enzyme 2 (ACE-2) and is expressed in a variety of tissues, including pulmonary, intestinal, and renal—undergoes conformational change and cathepsin L–mediated proteolysis within the endosome.[25, 26]

The binding of SARS-CoV to DC-SIGN (dendritic cell–specific intercellular adhesion molecule–grabbing nonintegrin), which recognizes a variety of microorganisms, does not lead to entry of the virus into dendritic cells. It instead facilitates the transfer and dissemination within the infected host.[27]

Immune response

The type I interferon (IFN-alfa/beta) system represents a powerful part of the innate immune system and has potent antiviral activity. However, SARS-CoV discourages attack by the IFN system. Replication of the virus occurs in cytoplasmic compartments surrounded by a double membrane layer. Such concealment within cells probably causes a spatial separation of the viral pathogen-associated molecular patterns (PAMPs) and the cellular cytoplasmic pattern recognition receptors (PRRs).[28, 29, 30, 31]

In addition, the activation of IFN regulatory factor–3 (IRF-3) is actively inhibited by SARS-CoV, with IRF-3 being targeted by 5 known SARS-CoV proteins in order to prevent IFN-system activation. IFN induction can also be affected by unspecific degradation of host messenger RNA (mRNA).[31]

These defensive measures prevent tissue cells from mounting an antiviral IFN attack following SARS-CoV infection. Ultimately, however, an IFN immune response can occur. Plasmacytoid dendritic cells (pDCs) use Toll-like receptors (TLRs) to recognize pathogen structures and use IRF-7 to induce IFN transcription. Large amounts of IFN are thus produced by the pDCs following infection with SARS-CoV.[32, 31]

In a study that examined 40 clinically well-defined human SARS cases, high levels of IFN were found in the infection’s early stages, except in more severe cases, and early production of IFN correlated with a beneficial outcome for the infected individuals.[31, 33]

Nuclear factor

SARS-CoV membrane protein, most likely by interacting directly with IkappaB kinase (IKK), also suppresses nuclear factor-kappaB (NF-kappaB) activity and reduces cyclooxygenase-2 (COX-2) expression. These disturbances may aid SARS pathogenesis.[23, 34]

Middle East respiratory syndrome coronavirus (MERS-CoV)

Middle East respiratory syndrome coronavirus (MERS-CoV; formerly referred to as novel coronavirus [NCoV]), a new virus from the same family as the common cold virus and SARS-CoV, emerged in the Middle East in 2012, with some recent recorded cases in Britain and France among travelers to the Middle East.[35, 36] Although only distantly related to SARS-CoV, MERS-CoV is also apparently of zoonotic origin and causes severe respiratory illness, fever, coughing, and breathing difficulties. Interferons have been shown to efficiently reduce MERS-CoV replication in human airway epithelial cell cultures, suggesting a possible mode of treatment in the event of a large-scale outbreak.

According to the WHO, it is possible for MERS-CoV to be passed between humans, but only after prolonged contact.[37] So far, however, there is no evidence that the virus is able to sustain generalized transmission in communities, a scenario that would raise the specter of a pandemic. Although no specific vaccine or medication is currently available for MERS-CoV, patients have been responding to treatment.

Previous
Next

Background

Severe acute respiratory syndrome (SARS) is a serious, potentially life-threatening viral infection caused by a previously unrecognized virus from the Coronaviridae family.[38] This virus has been named the SARS-associated coronavirus (SARS-CoV). Previously, Coronaviridae was best known as the second-most-frequent cause of the common cold. (See the images below.)

Thin-section electron micrograph of the severe acu Thin-section electron micrograph of the severe acute respiratory syndrome–associated coronavirus isolated in FRhK-4 cells. Courtesy of the Government Virus Unit, Department of Health, Hong Kong SAR, China.
Chest radiograph of a 52-year-old symptomatic woma Chest radiograph of a 52-year-old symptomatic woman with severe acute respiratory syndrome (March 20, 2003) taken 5 days after presentation. Moderately severe-to-severe ground-glass and consolidative bilateral changes are noted in the lung fields and are somewhat worse on the left side. Courtesy of Michael E. Katz, MD.

The SARS-CoV strain is believed to have originated in Guangdong province in southern China prior to its spread to Hong Kong, neighboring countries in Asia, and Canada and the United States during the 2002-2003 outbreak.[1, 2, 3, 39, 40] In early 2004, several new cases of SARS were investigated in Beijing and in the Anhui province of China. The most recent outbreak was believed to have been successfully contained without spread into the general population. There have subsequently been three instances of laboratory-acquired infection, and one reintroduction from animals in Guangdong Province, China. (See Epidemiology.)[41, 42]

Despite concerns that new cases of SARS would emerge in the region, no new human-to-human transmission has been reported. The reasons for this maybe (1) a very high prevalence of serious illness, making identification of cases and transmission easier and (2) a low risk of transmission before the development of severe illness.

The World Health Organization’s (WHO’s) timely updates on where SARS cases were occurring, the clinical and epidemiologic features of infection, laboratory methods, strategies to control the disease’s spread, and the intensive collaborative global response to SARS were also responsible for the effective prevention of a global pandemic. (See Epidemiology, Workup, and Treatment.)[43, 44]

Global efforts to acknowledge and research the CoV have virtually eradicated SARS as a threat. Although much has already been learned about the virus, ongoing efforts are being made to better understand it in hopes of developing medications and vaccinations to maintain its suppression. Global organizations, including WHO, the Centers for Disease Control and Prevention (CDC), and the National Institutes of Health (NIH) are still facilitating research on the virus and its family. (See Etiology, Workup and Treatment.)

Previous
Next

Epidemiology

In November 2002, an unusual epidemic of severe pneumonia of unknown origin in Guangdong Province in southern China was noted. There was a high rate of transmission to health care workers (HCWs).[1, 2] Some of these patients were positive for SARS-CoV in the nasopharyngeal aspirates(NPA), whereas 87% patients had positive antibodies to SARS-CoV in their convalescent sera. Genetic analysis showed that the SARS-CoV isolates from Guangzhou had the same origin as those in other countries, with a phylogenetic pathway that matched the spread of SARS to other parts of the world.

The 2002-2003 SARS outbreak predominantly affected mainland China, Hong Kong, Singapore, and Taiwan. In Canada, a significant outbreak occurred in the area around Toronto, Ontario. In the United States, 8 individuals contracted laboratory-confirmed SARS. All patients had traveled to areas where active SARS-CoV transmission had been documented.[1, 2, 3, 44]

SARS is thought to be transmitted primarily via close person-to-person contact, through droplet transmission.[45] Most cases have involved persons who lived with or cared for a person with SARS or who had exposure to contaminated secretions from a patient with SARS. Some affected patients may have acquired SARS-CoV infection after their skin, respiratory system, or mucous membranes came into contact with infectious droplets propelled into the air by a coughing or sneezing patient with SARS.

Leaky, backed-up sewage pipes; fans; and a faulty ventilation system were likely responsible for a severe outbreak of SARS in the Amoy Gardens residential complex in Hong Kong. Transmission may have occurred within the complex via airborne, virus-laden aerosols.[46]

The worldwide number of SARS cases from the original outbreak (November 2002 through July 31, 2003) reached more than 8000 persons, including 1706 healthcare workers. Of those cases, 774 resulted in death, with a case fatality ratio of 9.6% deaths, and 7295 recoveries. The majority of these cases occurred in mainland China (5327 cases, 349 deaths), Hong Kong (1755 cases, 299 deaths), with Taiwan (346 cases, 37 deaths), and Singapore (238 cases, 33 deaths).

In North America, there were 251 cases, with 43 resulting in death (all in Canada).[43] The map below shows the worldwide distribution of SARS cases during the 2002-03 outbreak.

World map of severe acute respiratory syndrome (SA World map of severe acute respiratory syndrome (SARS) distribution from the 2002-2003 outbreak infection. The greatest number of past and new cases of SARS are in mainland China, Hong Kong, Taiwan, and Singapore (red). Canada, more specifically Toronto, Ontario (yellow), is the fifth-ranked area, although community transmission of SARS now appears to be contained, according to the US Centers for Disease Control and Prevention. Green represents the other countries reporting SARS cases.
Previous
Next

Prognosis

WHO data indicate that mortality from SARS is highly variable. The mortality rate has been found to range from less than 1% in patients below age 24 years to more than 50% in patients aged 65 and older. Certain risk factors, including the following, have been associated with a poorer prognosis[47, 48] :

  • Older age
  • Chronic hepatitis B infection
  • Laboratory features - Including marked lymphopenia and leukocytosis, elevated lactate dehydrogenase level, hepatitis, high SARS-CoV viral load, and comorbidities such as diabetes mellitus

Elevated levels of interferon-inducible protein 10 (IP-10), monokine induced by IFN-gamma (MIG), and interleukin 8 (IL-8) during the first week, as well as an increase of MIG during the second week, have also been associated with a poor prognosis.[49]

A study of SARS survivors found that most of these had significant improvement clinically, radiographically, and in their pulmonary function studies. However, 27.8% of patients still exhibited abnormal radiographs at 12 months. Significant reductions in the diffusing capacity of carbon monoxide and in exercise ability (6-min walking distance) were also documented at 12 months.[50] Polyneuropathy and myopathy associated with critical illness, avascular necrosis (possibly steroid induced), steroid toxicity, and psychosis were some of the other long-term sequel observed in the SARS survivors.[13]

Morbidity and mortality

SARS can result in significant illness and medical complications that require hospitalization, intensive care treatment, and mechanical ventilation.[51]

Morbidity and mortality rates were observed to be greater in elderly patients. The overall mortality rate of SARS has been approximately 10%. According to the CDC and WHO, the death rate among individuals older than age 65 years exceeds 50%.

Previous
 
 
Contributor Information and Disclosures
Author

Faustine Ong, MD Resident Physician, Department of Internal Medicine, Einstein Medical Center

Faustine Ong, MD is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Coauthor(s)

Sarah Perloff, DO, FACP Director, Antibiotic Stewardship Program, Associate Program Director, Internal Medicine Residency, Program Director, Infectious Diseases Fellowship, Einstein Medical Center

Sarah Perloff, DO, FACP is a member of the following medical societies: American College of Physicians, American Osteopathic Association, Infectious Diseases Society of America, HIV Medicine Association

Disclosure: Nothing to disclose.

Chief Editor

Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM Professor of Critical Care Medicine, Bioengineering, Cardiovascular Disease, Clinical and Translational Science and Anesthesiology, Vice-Chair of Academic Affairs, Department of Critical Care Medicine, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine

Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM is a member of the following medical societies: American College of Chest Physicians, Association of University Anesthetists, European Society of Intensive Care Medicine, American College of Critical Care Medicine, American Heart Association, American Thoracic Society, Shock Society, Society of Critical Care Medicine

Disclosure: Received income in an amount equal to or greater than $250 from: Masimo<br/>Received honoraria from LiDCO Ltd for consulting; Received intellectual property rights from iNTELOMED for board membership; Received honoraria from Edwards Lifesciences for consulting; Received honoraria from Masimo, Inc for board membership.

Additional Contributors

Prashant Malhotra, MBBS, FACP, FIDSA Assistant Professor of Medicine, Division of Infectious Diseases, Department of Medicine, LIJ School of Medicine at Hofstra University; Attending Physician, Division of Infectious Diseases, Department of Internal Medicine, North Shore-Long Island Jewish Health System

Prashant Malhotra, MBBS, FACP, FIDSA is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Manish N Trivedi, MD Fellow in Infectious Diseases, North Shore-Long Island Jewish Hospital

Disclosure: Nothing to disclose.

Acknowledgements

Burke A Cunha, MD Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Asim A Jani, MD, MPH, FACP Clinician-Educator and Epidemiologist, Consultant and Senior Physician, Florida Department of Health; Diplomate, Infectious Diseases, Internal Medicine and Preventive Medicine

Asim A Jani, MD, MPH, FACP is a member of the following medical societies: American Association of Public Health Physicians, American College of Physicians, American College of Preventive Medicine, American Medical Association, American Public Health Association, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Richard Oehler, MD Associate Professor, Department of Internal Medicine, Division of Infectious Diseases and International Medicine, University of South Florida College of Medicine; Director of Clinical Education, Division of Infectious Diseases, Tampa Veterans Affairs Medical Center

Richard Oehler, MD is a member of the following medical societies: American College of Physicians, American Medical Association, Infectious Diseases Society of America, and Society for Healthcare Epidemiology of America

Disclosure: Nothing to disclose.

Charles V Sanders, MD Edgar Hull Professor and Chairman, Department of Internal Medicine, Professor of Microbiology, Immunology and Parasitology, Louisiana State University School of Medicine at New Orleans; Medical Director, Medicine Hospital Center, Charity Hospital and Medical Center of Louisiana at New Orleans; Consulting Staff, Ochsner Medical Center

Charles V Sanders, MD is a member of the following medical societies: Alliance for the Prudent Use of Antibiotics, Alpha Omega Alpha, American Association for the Advancement of Science, American Association of University Professors, American Clinical and Climatological Association, American College of Physician Executives, American College of Physicians, American Federation for Medical Research, American Foundation for AIDS Research, American GeriatricsSociety, American Lung Association, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Association for Professionals in Infection Control and Epidemiology, Association of American Medical Colleges, Association of American Physicians, Association of Professors of Medicine, Infectious Disease Society for Obstetrics and Gynecology, Infectious Diseases Societyof America, Louisiana State Medical Society, Orleans Parish Medical Society, Royal Society of Medicine, Sigma Xi, Society of General Internal Medicine, Southeastern Clinical Club, Southern Medical Association, Southern Society for Clinical Investigation, and Southwestern Association of Clinical Microbiology

Disclosure: Nothing to disclose.

Sat Sharma, MD, FRCPC Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St Boniface General Hospital

Sat Sharma, MD, FRCPC is a member of the following medical societies: American Academy of Sleep Medicine, American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, American Thoracic Society, Canadian Medical Association, Royal College of Physicians and Surgeons of Canada, Royal Society of Medicine, Society of Critical Care Medicine, and World Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

References
  1. Lee N, Hui D, Wu A, Chan P, Cameron P, Joynt GM, et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med. 2003 May 15. 348(20):1986-94. [Medline].

  2. Tsang KW, Ho PL, Ooi GC, Yee WK, Wang T, Chan-Yeung M, et al. A cluster of cases of severe acute respiratory syndrome in Hong Kong. N Engl J Med. 2003 May 15. 348(20):1977-85. [Medline].

  3. Centers for Disease Control and Prevention. 2003. Severe Acute Respiratory Syndrome. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/ncidod/sars/. Accessed: November 07, 2011.

  4. Armed Forces Institute of Pathology. Severe Acute Respiratory Syndrome (SARS). Armed Forces Institute of Pathology.;

  5. Centers for Disease Control and Prevention. Clinical Guidance on the Identification and Evaluation of Possible SARS-CoV Disease among Persons Presenting with Community-Acquired Illness, Version 2. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/ncidod/sars/clinicalguidance.htm.

  6. Vijay R, Hua X, Meyerholz DK, Miki Y, Yamamoto K, Gelb M, et al. Critical role of phospholipase A2 group IID in age-related susceptibility to severe acute respiratory syndrome-CoV infection. J Exp Med. 2015 Sep 21. [Medline].

  7. Sui J, Li W, Murakami A, Tamin A, Matthews LJ, Wong SK, et al. Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association. Proc Natl Acad Sci U S A. 2004 Feb 24. 101(8):2536-41. [Medline]. [Full Text].

  8. Hsu LY, Lee CC, Green JA, Ang B, Paton NI, Lee L, et al. Severe acute respiratory syndrome (SARS) in Singapore: clinical features of index patient and initial contacts. Emerg Infect Dis. 2003 Jun. 9(6):713-7. [Medline]. [Full Text].

  9. Nicolaou S, Al-Nakshabandi NA, Müller NL. SARS: imaging of severe acute respiratory syndrome. AJR Am J Roentgenol. 2003 May. 180(5):1247-9. [Medline].

  10. Kotani T, Tanabe H, Yusa H, Saito S, Yamazaki K, Ozaki M. Electrical impedance tomography-guided prone positioning in a patient with acute cor pulmonale associated with severe acute respiratory distress syndrome. J Anesth. 2015 Oct 7. [Medline].

  11. Ho W. Guideline on management of severe acute respiratory syndrome (SARS). Lancet. 2003 Apr 19. 361(9366):1313-5. [Medline].

  12. Lapinsky SE, Hawryluck L. ICU management of severe acute respiratory syndrome. Intensive Care Med. 2003 Jun. 29(6):870-5. [Medline].

  13. Tsai LK, Hsieh ST, Chao CC, Chen YC, Lin YH, Chang SC, et al. Neuromuscular disorders in severe acute respiratory syndrome. Arch Neurol. 2004 Nov. 61(11):1669-73. [Medline].

  14. Hui DS, Chan PK. Clinical features, pathogenesis and immunobiology of severe acute respiratory syndrome. Curr Opin Pulm Med. 2008 May. 14(3):241-7. [Medline].

  15. Lo AW, Tang NL, To KF. How the SARS coronavirus causes disease: host or organism?. J Pathol. 2006 Jan. 208(2):142-51. [Medline].

  16. Hui DS, Chan PK. Severe acute respiratory syndrome and coronavirus. Infect Dis Clin North Am. 2010 Sep. 24(3):619-38. [Medline].

  17. Tan YJ, Fielding BC, Goh PY, Shen S, Tan TH, Lim SG, et al. Overexpression of 7a, a protein specifically encoded by the severe acute respiratory syndrome coronavirus, induces apoptosis via a caspase-dependent pathway. J Virol. 2004 Dec. 78(24):14043-7. [Medline]. [Full Text].

  18. Jiang Y, Xu J, Zhou C, Wu Z, Zhong S, Liu J, et al. Characterization of cytokine/chemokine profiles of severe acute respiratory syndrome. Am J Respir Crit Care Med. 2005 Apr 15. 171(8):850-7. [Medline].

  19. Peiris JS, Lai ST, Poon LL, Guan Y, Yam LY, Lim W, et al. Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet. 2003 Apr 19. 361(9366):1319-25. [Medline].

  20. Hui DS, Sung JJ. Severe acute respiratory syndrome. Chest. 2003 Jul. 124(1):12-5. [Medline].

  21. Wong GW, Hui DS. Severe acute respiratory syndrome (SARS): epidemiology, diagnosis and management. Thorax. 2003 Jul. 58(7):558-60. [Medline]. [Full Text].

  22. Wang LF, Shi Z, Zhang S, Field H, Daszak P, Eaton BT. Review of bats and SARS. Emerg Infect Dis. 2006 Dec. 12(12):1834-40. [Medline].

  23. Rota PA, Oberste MS, Monroe SS, Nix WA, Campagnoli R, Icenogle JP, et al. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science. 2003 May 30. 300(5624):1394-9. [Medline].

  24. Tripet B, Howard MW, Jobling M, Holmes RK, Holmes KV, Hodges RS. Structural characterization of the SARS-coronavirus spike S fusion protein core. J Biol Chem. 2004 May 14. 279(20):20836-49. [Medline].

  25. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003 Nov 27. 426(6965):450-4. [Medline].

  26. Frieman M, Baric R. Mechanisms of severe acute respiratory syndrome pathogenesis and innate immunomodulation. Microbiol Mol Biol Rev. 2008 Dec. 72(4):672-85, Table of Contents. [Medline]. [Full Text].

  27. Yang ZY, Huang Y, Ganesh L, Leung K, Kong WP, Schwartz O, et al. pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN. J Virol. 2004 Jun. 78(11):5642-50. [Medline]. [Full Text].

  28. Samuel CE. Antiviral actions of interferons. Clin Microbiol Rev. 2001 Oct. 14(4):778-809, table of contents. [Medline]. [Full Text].

  29. Stertz S, Reichelt M, Spiegel M, Kuri T, Martínez-Sobrido L, García-Sastre A, et al. The intracellular sites of early replication and budding of SARS-coronavirus. Virology. 2007 May 10. 361(2):304-15. [Medline].

  30. Versteeg GA, Bredenbeek PJ, van den Worm SH, Spaan WJ. Group 2 coronaviruses prevent immediate early interferon induction by protection of viral RNA from host cell recognition. Virology. 2007 Apr 25. 361(1):18-26. [Medline].

  31. Kuri T, Weber F. Interferon interplay helps tissue cells to cope with SARS-coronavirus infection. Virulence. 2010 Jul-Aug. 1(4):273-5. [Medline].

  32. Cervantes-Barragan L, Züst R, Weber F, Spiegel M, Lang KS, Akira S, et al. Control of coronavirus infection through plasmacytoid dendritic-cell-derived type I interferon. Blood. 2007 Feb 1. 109(3):1131-7. [Medline].

  33. Cameron MJ, Ran L, Xu L, Danesh A, Bermejo-Martin JF, Cameron CM, et al. Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome. J Virol. 2007 Aug. 81(16):8692-706. [Medline]. [Full Text].

  34. Fang X, Gao J, Zheng H, Li B, Kong L, Zhang Y, et al. The membrane protein of SARS-CoV suppresses NF-kappaB activation. J Med Virol. 2007 Oct. 79(10):1431-9. [Medline].

  35. Kelland K. Deadly New Virus Well-Adapted to Infect Humans. Medscape Medical News. February 19, 2013. Available at http://www.medscape.com/viewarticle/779538. Accessed: February 27, 2013.

  36. Kindler E, Jónsdóttir HR, Muth D, Hamming OJ, et al. Efficient Replication of the Novel Human Betacoronavirus EMC on Primary Human Epithelium Highlights Its Zoonotic Potential. MBio. 2013 Feb 19. 4(1):[Medline]. [Full Text].

  37. New SARS-like virus can probably pass person-to-person. Medscape Medical News. May 13, 2013. [Full Text].

  38. Fouchier RA, Kuiken T, Schutten M, van Amerongen G, van Doornum GJ, van den Hoogen BG, et al. Aetiology: Koch's postulates fulfilled for SARS virus. Nature. 2003 May 15. 423(6937):240. [Medline].

  39. 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. JAMA. 2003 Jun 4. 289(21):2801-9. [Medline].

  40. Severe acute respiratory syndrome (SARS) and coronavirus testing--United States, 2003. MMWR Morb Mortal Wkly Rep. 2003 Apr 11. 52(14):297-302. [Medline].

  41. Lim PL, Kurup A, Gopalakrishna G, Chan KP, Wong CW, Ng LC, et al. Laboratory-acquired severe acute respiratory syndrome. N Engl J Med. 2004 Apr 22. 350(17):1740-5. [Medline].

  42. Liang G, Chen Q, Xu J, Liu Y, Lim W, Peiris JS, et al. Laboratory diagnosis of four recent sporadic cases of community-acquired SARS, Guangdong Province, China. Emerg Infect Dis. 2004 Oct. 10(10):1774-81. [Medline].

  43. World Health Organization. Severe acute respiratory syndrome (SARS): Status of the outbreak and lessons for the immediate future. World Health Organization. Available at http://www.who.int/csr/media/sars_wha.pdf. Accessed: October 2007.

  44. Liang WN, Liu M, Chen Q, Liu ZJ, He X, Pan Y, et al. Assessment of impacts of public health interventions on the SARS epidemic in Beijing in terms of the intervals between its symptom onset, hospital admission, and notification. Biomed Environ Sci. 2005 Jun. 18(3):153-8. [Medline].

  45. Yu IT, Li Y, Wong TW, Tam W, Chan AT, Lee JH, et al. Evidence of airborne transmission of the severe acute respiratory syndrome virus. N Engl J Med. 2004 Apr 22. 350(17):1731-9. [Medline].

  46. Cyranoski D, Abbott A. Apartment complex holds clues to pandemic potential of SARS. Nature. 2003 May 1. 423(6935):3-4. [Medline].

  47. Chan JW, Ng CK, Chan YH, Mok TY, Lee S, Chu SY, et al. Short term outcome and risk factors for adverse clinical outcomes in adults with severe acute respiratory syndrome (SARS). Thorax. 2003 Aug. 58(8):686-9. [Medline]. [Full Text].

  48. Tansey CM, Louie M, Loeb M, Gold WL, Muller MP, de Jager J, et al. One-year outcomes and health care utilization in survivors of severe acute respiratory syndrome. Arch Intern Med. 2007 Jun 25. 167(12):1312-20. [Medline].

  49. Tang NL, Chan PK, Wong CK, To KF, Wu AK, Sung YM, et al. Early enhanced expression of interferon-inducible protein-10 (CXCL-10) and other chemokines predicts adverse outcome in severe acute respiratory syndrome. Clin Chem. 2005 Dec. 51(12):2333-40. [Medline].

  50. Hui DS, Wong KT, Ko FW, Tam LS, Chan DP, Woo J, et al. The 1-year impact of severe acute respiratory syndrome on pulmonary function, exercise capacity, and quality of life in a cohort of survivors. Chest. 2005 Oct. 128(4):2247-61. [Medline].

  51. Tsui PT, Kwok ML, Yuen H, Lai ST. Severe acute respiratory syndrome: clinical outcome and prognostic correlates. Emerg Infect Dis. 2003 Sep. 9(9):1064-9. [Medline]. [Full Text].

  52. Centers for Disease Control and Prevention. Updated Interim U.S. Case Definition for Severe Acute Respiratory Syndrome (SARS). Centers for Disease Control and Prevention. Available at http://www.cdc.gov/ncidod/sars/casedefinition.htm. Accessed: Oct 26 2011.

  53. World Health Organization. WHO recommended measures for persons undertaking international travel from areas affected by severe acute respiratory syndrome (SARS). Wkly Epidemiol Rec. 2003 Apr 4. 78(14):97-9. [Medline].

  54. Ng LF, Wong M, Koh S, Ooi EE, Tang KF, Leong HN, et al. Detection of severe acute respiratory syndrome coronavirus in blood of infected patients. J Clin Microbiol. 2004 Jan. 42(1):347-50. [Medline]. [Full Text].

  55. Chen X, Zhou B, Li M, Liang X, Wang H, Yang G, et al. Serology of severe acute respiratory syndrome: implications for surveillance and outcome. J Infect Dis. 2004 Apr 1. 189(7):1158-63. [Medline].

  56. Reuters. FDA Grants Emergency Approval for Test to Detect MERS. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/807916. Accessed: July 22, 2013.

  57. Taccone P, Pesenti A, Latini R, Polli F, Vagginelli F, Mietto C, et al. Prone positioning in patients with moderate and severe acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2009 Nov 11. 302(18):1977-84. [Medline].

  58. Lee N, Allen Chan KC, Hui DS, Ng EK, Wu A, Chiu RW, et al. Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients. J Clin Virol. 2004 Dec. 31(4):304-9. [Medline].

  59. Sung JJ, Wu A, Joynt GM, Yuen KY, Lee N, Chan PK, et al. Severe acute respiratory syndrome: report of treatment and outcome after a major outbreak. Thorax. 2004 May. 59(5):414-20. [Medline]. [Full Text].

  60. Ho JC, Ooi GC, Mok TY, Chan JW, Hung I, Lam B, et al. High-dose pulse versus nonpulse corticosteroid regimens in severe acute respiratory syndrome. Am J Respir Crit Care Med. 2003 Dec 15. 168(12):1449-56. [Medline].

  61. Tan EL, Ooi EE, Lin CY, Tan HC, Ling AE, Lim B, et al. Inhibition of SARS coronavirus infection in vitro with clinically approved antiviral drugs. Emerg Infect Dis. 2004 Apr. 10(4):581-6. [Medline].

  62. Chu CM, Cheng VC, Hung IF, Wong MM, Chan KH, Chan KS, et al. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax. 2004 Mar. 59(3):252-6. [Medline]. [Full Text].

  63. Chan KS, Lai ST, Chu CM, Tsui E, Tam CY, Wong MM, et al. Treatment of severe acute respiratory syndrome with lopinavir/ritonavir: a multicentre retrospective matched cohort study. Hong Kong Med J. 2003 Dec. 9(6):399-406. [Medline].

  64. Ströher U, DiCaro A, Li Y, Strong JE, Aoki F, Plummer F, et al. Severe acute respiratory syndrome-related coronavirus is inhibited by interferon- alpha. J Infect Dis. 2004 Apr 1. 189(7):1164-7. [Medline].

  65. Haagmans BL, Kuiken T, Martina BE, Fouchier RA, Rimmelzwaan GF, van Amerongen G, et al. Pegylated interferon-alpha protects type 1 pneumocytes against SARS coronavirus infection in macaques. Nat Med. 2004 Mar. 10(3):290-3. [Medline].

  66. Loutfy MR, Blatt LM, Siminovitch KA, Ward S, Wolff B, Lho H, et al. Interferon alfacon-1 plus corticosteroids in severe acute respiratory syndrome: a preliminary study. JAMA. 2003 Dec 24. 290(24):3222-8. [Medline].

  67. Das D, Kammila S, Suresh MR. Development, characterization, and application of monoclonal antibodies against severe acute respiratory syndrome coronavirus nucleocapsid protein. Clin Vaccine Immunol. 2010 Dec. 17(12):2033-6. [Medline]. [Full Text].

  68. ter Meulen J, Bakker AB, van den Brink EN, Weverling GJ, Martina BE, Haagmans BL, et al. Human monoclonal antibody as prophylaxis for SARS coronavirus infection in ferrets. Lancet. 2004 Jun 26. 363(9427):2139-41. [Medline].

  69. Lew TW, Kwek TK, Tai D, Earnest A, Loo S, Singh K, et al. Acute respiratory distress syndrome in critically ill patients with severe acute respiratory syndrome. JAMA. 2003 Jul 16. 290(3):374-80. [Medline].

  70. Cheng Y, Wong R, Soo YO, Wong WS, Lee CK, Ng MH, et al. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis. 2005 Jan. 24(1):44-6. [Medline].

  71. Chen L, Liu P, Gao H, Sun B, Chao D, Wang F, et al. Inhalation of nitric oxide in the treatment of severe acute respiratory syndrome: a rescue trial in Beijing. Clin Infect Dis. 2004 Nov 15. 39(10):1531-5. [Medline].

  72. Cinatl J, Morgenstern B, Bauer G, Chandra P, Rabenau H, Doerr HW. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet. 2003 Jun 14. 361(9374):2045-6. [Medline].

  73. Chen Z, Zhang L, Qin C, Ba L, Yi CE, Zhang F, et al. Recombinant modified vaccinia virus Ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies primarily targeting the receptor binding region. J Virol. 2005 Mar. 79 (5):2678-88. [Medline]. [Full Text].

  74. Zhou Z, Post P, Chubet R, Holtz K, McPherson C, Petric M, et al. A recombinant baculovirus-expressed S glycoprotein vaccine elicits high titers of SARS-associated coronavirus (SARS-CoV) neutralizing antibodies in mice. Vaccine. 2006 Apr 24. 24 (17):3624-31. [Medline].

  75. Bolles M, Deming D, Long K, Agnihothram S, Whitmore A, Ferris M, et al. A double-inactivated severe acute respiratory syndrome coronavirus vaccine provides incomplete protection in mice and induces increased eosinophilic proinflammatory pulmonary response upon challenge. J Virol. 2011 Dec. 85 (23):12201-15. [Medline]. [Full Text].

  76. Tseng CT, Sbrana E, Iwata-Yoshikawa N, Newman PC, Garron T, Atmar RL, et al. Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. PLoS One. 2012. 7 (4):e35421. [Medline]. [Full Text].

  77. Honda-Okubo Y, Barnard D, Ong CH, Peng BH, Tseng CT, Petrovsky N. Severe acute respiratory syndrome-associated coronavirus vaccines formulated with delta inulin adjuvants provide enhanced protection while ameliorating lung eosinophilic immunopathology. J Virol. 2015 Mar. 89 (6):2995-3007. [Medline].

  78. Martin JE, Louder MK, Holman LA, Gordon IJ, Enama ME, Larkin BD, et al. A SARS DNA vaccine induces neutralizing antibody and cellular immune responses in healthy adults in a Phase I clinical trial. Vaccine. 2008 Nov 25. 26 (50):6338-43. [Medline].

  79. Mandavilli A. SARS epidemic unmasks age-old quarantine conundrum. Nat Med. 2003 May. 9 (5):487. [Medline].

  80. Yang W. Severe acute respiratory syndrome (SARS): infection control. Lancet. 2003 Apr 19. 361 (9366):1386-7. [Medline].

 
Previous
Next
 
Thin-section electron micrograph of the severe acute respiratory syndrome–associated coronavirus isolated in FRhK-4 cells. Courtesy of the Government Virus Unit, Department of Health, Hong Kong SAR, China.
World map of severe acute respiratory syndrome (SARS) distribution from the 2002-2003 outbreak infection. The greatest number of past and new cases of SARS are in mainland China, Hong Kong, Taiwan, and Singapore (red). Canada, more specifically Toronto, Ontario (yellow), is the fifth-ranked area, although community transmission of SARS now appears to be contained, according to the US Centers for Disease Control and Prevention. Green represents the other countries reporting SARS cases.
Pathologic slide of pulmonary tissue infected with severe acute respiratory syndrome–associated coronavirus. Diffuse alveolar damage is seen along with a multinucleated giant cell with no conspicuous viral inclusions. Courtesy of the US Centers for Disease Control and Prevention.
Severe acute respiratory syndrome case definition put forth by the US Centers for Disease Control and Prevention (CDC) on April 29, 2003. Courtesy of the CDC.
Clinical and laboratory criteria for severe acute respiratory syndrome cases and infection per the US Centers for Disease Control and Prevention (CDC) on April 29, 2003. Courtesy of the CDC.
Chest radiograph of a 52-year-old symptomatic woman with severe acute respiratory syndrome (March 20, 2003) taken 5 days after presentation. Moderately severe-to-severe ground-glass and consolidative bilateral changes are noted in the lung fields and are somewhat worse on the left side. Courtesy of Michael E. Katz, MD.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.