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Coronavirus SARS-CoV1 infection (SARS)

Essential Evidence


Authors:
M. Joyce Green, MD, Assistant Professor, Penn State Health Hershey Medical Center
Pete Yunyongying, MD, FACP, Associate Professor , Carle-Illinois College of Medicine, University of Illinois
Mark H. Ebell, MD, MS, Professor, College of Public Health, University of Georgia
Mindy A. Smith, MD, MS, Clinical Professor, Department of Family Medicine, Michigan State University

Editor:
Mark H. Ebell, MD, MS, Professor, College of Public Health, University of Georgia

Last updated: 2021-03-10 © 2021 John Wiley & Sons, Inc.

Overall Bottom Line

  • The most common presenting symptoms of the SARS-CoV1 in 2003 were fever, chills, myalgia, malaise, and cough.1 Test patients for SARS-CoV1 using PCR only if no other cause of pneumonia can be found 72 hours after starting a workup and if the patient has risk factors for SARS-CoV1. Consult public health authorities prior to testing. C
  • Supportive care is the mainstay of treatment. Although most patients were treated with corticosteroids and antivirals, there is little evidence that these interventions improved outcomes, and they are known to have ill effects. C2
  • The case fatality ratio in over 8000 cases reported by the WHO in 2003 was 9.6%. C
  • A separate chapter address infection with SARS-CoV2 and COVID-19.

Background

  • Severe acute respiratory syndrome (SARS-CoV1) in 2002-2003 is a viral lower respiratory illness caused by SARS-CoV1 that is frequently associated with rapid progression resulting in acute respiratory distress syndrome (ARDS).3
  • Within months after its emergence in Guangdong Province in mainland China, it had affected more than 8000 patients and caused 774 deaths in 26 countries on five continents.1
  • Most recently, COVID-19 (coronavirus disease 2019) is a different viral lower respiratory infection first reported in Wuhan City, China that has rapidly spread to become a pandemic. It is caused by novel coronavirus named 2019-nCoV and more recently SARS-CoV2.

Incidence

  • During one of the largest outbreak of the disease, over 8000 cases of SARS-CoV1 were identified across at least 29 countries from November 2002 to July 2003.
  • The last known outbreak of SARS-CoV1 involved laboratory workers in China and was contained by 2004 (WHO, n.d.).
  • Most cases occurred in mainland China, with other large-scale outbreaks in Hong Kong, Singapore, and Canada.

Other Impact

  • The case fatality ratio was 9.6% among the reported SAR-CoV1 cases in 2002-2003.

Causes of the Condition

  • The cause of SARS-CoV1 is the coronavirus SARS-CoV-1.4

Pathophysiology

  • The SARS-CoV1 virus is a single-stranded enveloped RNA virus that binds to the angiotensin-converting enzyme 2 receptor to gain entry to host cells.5
  • Himalayan palm civets, Chinese ferret badgers, and raccoon dogs have all been found to carry the SARS-CoV1, but it is currently believed that the host for SARS-CoV1 is most likely bats.6
  • The incubation period of SARS-CoV1 is between 2 and 14 days, and hospital admission typically occurs 3 to 5 days after the onset of symptoms.7
  • One of the hallmarks of the SARS-CoV1 is diffuse alveolar damage, which is noted on the histopathology of deceased individuals. This is probably responsible for the severe respiratory symptoms.4
  • About 20% to 30% of patients progress to respiratory failure and require mechanical ventilation.1
  • Overall, 80% of hospitalized patients with SARS-CoV1 will have persistent ground-glass opacities on chest radiographs 1 month following hospitalization, while 95% will show these changes on chest CT scans.1

Risk Factors

Risk Factor
Living in or traveling to an endemic area for SARS-CoV1

Screening and Prevention

Bottom Line

  • The CDC recommended the use of airborne, droplet, and standard precautions for all personnel who come in contact with a SARS-CoV1 patient. C
  • Healthcare workers are at higher risk, especially those involved in procedures that may generate droplets or those that provide direct patient care.1 Strict airborne isolation is recommended, including use of negative pressure rooms as well as N95 respirators for healthcare workers who are treating these patients. C
  • During the 2003 SARS-CoV1 outbreak in Taiwan, wearing surgical face masks on entering the hospital, on hospital wards and in out-patient clinics prevented nearly all cases of SARS-CoV1 among healthcare workers.52
  • Based in part on experience with SARS-CoV1, masks and physical distancing have been broadly mandated around the world during the 2020 COVID-19/ SARS-CoV2 pandemic. A Cochrane review of 29 studies has concluded that these measures are consistently effective in slowing the spread of an epidemic. It is most effective when implemented early and in conjunction with other measures like closing schools and restricting travel.53
  • Contacts of SARS-CoV1 exposed individuals were recommended to be placed in quarantine for 10 days and monitored daily for fever and other symptoms C
  • The most recent 2020 CDC recommendation for COVID-19/ SARS-CoV 2 are similar. They recommend that contacts of COVID-19 exposed individuals should quarantine for 14 days with daily monitoring for fever and other symptoms. Persons living alone should have daily virtual contact with someone who can obtain help in the event of worsening.

Diagnosis

Bottom Line

  • Suspect severe coronavirus infection in persons with fever, cough, and other respiratory symptoms during an outbreak or pandemic.C
  • RT-PCR of multiple specimens is the most appropriate diagnostic testing method. Testing should be carried out according to guidelines from and in consultation with public health authorities.8B

Differential Diagnosis

Diagnosis
Community-acquired pneumonia caused by strep, influenza, legionella, mycoplasma, or other viruses
COPD exacerbation
Acute pulmonary edema
Interstitial lung disease
Severe coronavirus infection due to SARS-CoV2
Hantavirus pulmonary syndrome
Opportunistic infections causing pneumonia-complicating HIV infection (pneumocystis carrnii, histoplasmosis, or disseminated varicella pneumonia)
Middle Eastern Respiratory Syndrome

Diagnostic Criteria

  • The Centers for Disease Control and Prevention provided criteria for diagnosis of SARS-CoV1. Epidemiologic criteria are based on close contacts of those with respiratory illness or confirmed cases of SARS-CoV1 or travel to an area with recent SARS-CoV1 coronavirus outbreak.
  • Laboratory diagnosis of SARS-CoV1 requires a positive RT-PCR (with confirmation in a second laboratory) of two specimens from different sources or collected from the same source on different days.
  • SARS-CoV1 can be classified as having the following stages: Early illness—presence of two or more of fever, chills, rigors, myalgia, headache, diarrhea, sore throat, or rhinorrhea. Mild to moderate respiratory illness (“respiratory phase”)—temperature of >38ºC and one or more clinical features (cough, shortness of breath, etc.) of lower respiratory illness. Severe illness—meets the criteria above and has one or more of the following: radiographic evidence of pneumonia, ARDS, or ARDS or pneumonia at autopsy with no cause.
  • In the most recent 2020 SARS-CoV2 pandemic, the WHO defines different clinical syndromes that includes: mild illness, non severe pneumonia, severe pneumonia, acute respiratory distress syndrome, sepsis. (see SARS CoV2 article).

Using the History and Physical

  • Consider SARS-CoV1 in the differential diagnosis of patients who provide a history consistent with possible exposure to the SARS-CoV1 virus, such as travel to an affected area, employment in a risky occupation, or being part of a cluster of unexplained cases of pneumonia.
  • The incubation period of SARS-CoV1 is typically from 2 to 14 days, with some cases described as having incubation periods as long as 21 days.7
  • The disease begins with typical viral symptoms such as fever (99%), cough (66%), malaise (59%), chills (52%), and myalgias (48%). This is based on data from the four largest outbreaks.1
  • The dry cough and dyspnea usually start within 2 to 7 days of the initial symptoms.2 Two-thirds of SARS-CoV1 patients progress to a more serious respiratory phase 8 to 12 days after the onset of symptoms.21
  • The respiratory phase appears to last 1 week and recovery begins 2 to 3 weeks after the initial symptoms.2
  • Watery diarrhea occurs in around 20% of patients, and the SARS-CoV1 virus is found in large quantities in the stool.1
  • High viral load is correlated with organ failure and death. Viral load peaks 10 days after symptom onset.7

Selecting Diagnostic Tests

  • First, establish the diagnosis of pneumonia using CXR or chest CT, and then if possible, rule out causes other than SARS (see Differential Diagnosis). Any testing for SARS should be performed in conjunction with public health authorities.
  • Conventional RT-PCR shows low detection rates in early illness, and serology can take up to 28 days to reach a sensitivity above 90%.
  • Quantitative serum RT-PCR has a 79% detection rate (sensitivity) within the first 3 days, superior to nasal or throat swab and similar to that of nasopharyngeal aspirate.9
  • Nasopharyngeal specimens are usually negative in the first week of illness, and positive in the second. Lower respiratory specimens are more likely to be positive than upper respiratory.13
  • Collect multiple specimens including samples from different body sites and from different times during the illness. This includes acute and convalescent (>28 days) serum, sputum, nasopharyngeal, and oropharyngeal swabs, as well as stool, which demonstrates a high viral load particularly in the second week of the disease.18

Approach to the Patient

  • Airborne isolation precautions and other standard infection prevention measures should be continued.
  • In the absence of known SARS outbreak, if the patient has answered yes to one of the surveillance questions in Table 1 and is hospitalized with radiographically-confirmed pneumonia, the patient should first be evaluated for common causes of community-acquired pneumonia. This includes sending sputum for routine gram stain and culture, sending urine antigens for Legionella and pneumococcus, and testing for respiratory viral pathogens.
  • If the patient is part of a cluster of pneumonia with no explained cause or at high risk for SARS with no alternative diagnosis, the patient should be tested for SARS-CoV1 and CoV2.
  • If there is known person-to-person transmission of SARS-CoV1 in the environment, the algorithm in Figure 1 from the CDC is recommended.
  • Clinicians should utilize telehealth consultations which was widely used during the COVID 19/ SARS-CoV2 pandemic.54

Treatment

Bottom Line

  • Respiratory failure is the major cause of mortality in SARS-Cov1 infection and occurs in around 25% of patients. C1
  • There is no randomized trial evidence regarding treatment. C17
  • If mechanical ventilation is required, ventilator settings should mimic those required for the treatment of ARDS. C1

Drug Therapy

  • Corticosteroids were used for the treatment of almost all cases of SARS-Cov1 and in a retrospective analysis were associated with lower overall mortality and hospital stay. There is no specific recommendation regarding dosing or regimen.7 However, in subsequent systematic reviews corticosteroids have not been found to be helpful in treatment of SARS-Cov1 or MERS, with potential harms including increased mortality, complications, and delayed clearance of viral RNA from the respiratory tract. They are not routinely recommended based on interim WHO guidance.21
  • For patients whose medical treatment regimen for SARS-Cov1 were known, about half were treated with ribavirin.7 However, a retrospective analysis found no obvious clinical benefit of ribavirin.7 In addition, testing of the SARS-Cov1 coronavirus in vitro shows that ribavirin has no activity against it. Ribavirin was also associated with an increased risk of anemia, which increases the risk of death in SARS-Cov1 patients.10
  • In an uncontrolled study, interferon was associated with improvement in oxygenation, but the same patients were also given high-dose corticosteroids.7
  • A case control study of 75 patients with SARS-Cov1 concluded that use of lopinavir-ritonavir in addition to standard therapy was associated with a decreased death rate.11
  • See chapter on SARS-CoV2 for information on treatment of COVID 19.

Other Treatment

  • A trial randomized 249 patients with SARS-Cov1 to ECMO or usual care, and found no statistically significant evidence of benefit. However, a high rate of crossovers makes the trial difficult to interpret.14

Prognosis

Bottom Line

  • Increasing age and the presence of comorbid conditions appear to be the most important prognostic factors for SARS-Cov1.12B
  • The case fatality ratio in over 8000 SARS-Cov1 cases reported by the WHO in 2003 was 9.6%. C
  • Anti–SARS-Cov1 coronavirus antibodies were not detected in patients 6 years after infection, but T-cell responses were still present, raising questions about the outcomes of re-infected patients. C5

References and Additional Resources

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Practice Guidelines

  1. Balboni A, Battilani M, Prosperi S. The SARS-like coronaviruses: the role of bats and evolutionary relationships with SARS coronaviruses. New Microbiol 2012 Jan;35(1):1-16.
  2. Centers for Disease Control. (n.d.) Appendix B1: Revised CSTE SARS Surveillance Case Definition. Retrieved from Severe Acute Respiratory Syndrome (SARS). https://www.cdc.gov/sars/guidance/b-surveillance/app1.html
  3. Centers for Disease Control. (n.d.) Appendix F4: Guidelines for Collecting Speciments from Potential SARS Patients. Retrieved from Severe Acute Respiratory Syndrome. https://www.cdc.gov/sars/guidance/f-lab/app4.html
  4. Centers for Disease Control. (n.d.) Clinical Guidance on the Identification and Evaluation of Possible SARS-CoV Disease among Persons Presenting with Community-Acquired Illness. Retrieved from Severe Acute Respiratory Syndrome: Clinical Evaluation and Diagnosis. https://www.cdc.gov/sars/clinical/fig2.html
  5. Centers for Disease Control. (2012, July 07) Clinicial Guidance on the Identification and Evaluation of Possible SARS-CoV. Retrieved from https://cdc.gov/sars/clinical/guidance.html
  6. Chan KS, Lai ST, Chu CM, Tsui E, Tam CY, Wong MM, Tse MW, Que TL, Peiris JS, Sung J, Wong VC, Yuen KY. (2003) 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.
  7. Chiou HE, Liu CL, Buttrey MJ, Kuo HP, Liu HW, Kuo HT, Lu YT. Adverse effects of ribavirin and outcome in severe acute respiratory syndrome: experience in two medical centers. Chest 2005 Jul;128(1):263-272.
  8. Christian MD, Poutanen SM, Loutfy MR, Muller MP, Low DE. Severe acute respiratory syndrome. Clin Infect Dis 2004;38(10):1420–1427
  9. Cowling BJ, Muller MP, Wong IO, Ho LM, Lo SV, Tsang T, Lam TH, Louie M, Leung GM. Clinical prognostic rules for severe acute respiratory syndrome in low- and high-resource settings. Arch Intern Med 2006;166(14):1505-1511.
  10. Grant PR, Garson JA, Tedder RS, Chan PK, Tam JS, Sung JJ. Detection of SARS coronavirus in plasma by real-time RT-PCR. N Engl J Med 2003;349(25):2468-2469.
  11. Hui DS, Chan MC, Wu AK, Ng PC. Severe acute respiratory syndrome (SARS): epidemiology and clinical features. Postgrad Med J 2004;80(945):373-381.
  12. Ksiazek TG, Erdman D, Goldsmith CS, Zaki SR, Peret T, Emery S, Tong S, Urbani C, Comer JA, Lim W, Rollin PE, Dowell SF, Ling AE, Humphrey CD, Shieh WJ, Guarner J, Paddock CD, Rota P, Fields B, DeRisi J, Yang JY, Cox N, Hughes JM, LeDuc JW, Bellini WJ, Anderson LJ; SARS Working Group. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med 2003;348(20):1953-1966.
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Coronavirus SARS-CoV1 infection (SARS)

Tools, Tables, and Images

Tools

Tables

Table 1: CDC Recommendations for Surveillance for SARS.

Patients who are hospitalized for pneumonia or acute respiratory distress syndrome without an identifiable cause AND have one of the following:
  • Travel to mainland China, Hong Kong or Taiwan, or close contact with an ill person with a history of recent travel to one of those areas
  • Employment in an occupation associated with a risk for SARS-CoV exposure
  • Part of a cluster of cases of atypical pneumonia without an alternative diagnosis