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Severe Acute Respiratory Syndrome (SARS), Pediatric

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Severe Acute Respiratory Syndrome (SARS), Pediatric

Basics

Description

The virus attaches to human receptor cells and initiates a nonspecific acute lung injury response leading to diffuse, severe alveolar damage. ‚

  • WHO clinical criteria (2003):Suspect severe acute respiratory syndrome (SARS) case:A person presenting after November 1, 2002, with high fever (>38 ‚ °C), andCough or difficulty breathing, andClose contact with SARS patient or travel criteria to SARS area (see "History " ť)Probable SARS case:A suspect case with radiographic pneumonia or respiratory distress syndromeA suspect case with confirmatory laboratory studies (see "Lab ")A suspect case with autopsy findings
  • CDC clinical criteria (2003):Early illness2 or more constitutional symptoms " ”fever, chills, rigors, myalgia, headache, diarrhea, sore throat, or rhinorrheaMild to moderate illnessTemperature >100.4 ‚ °F (>38 ‚ °C)1 or more lower respiratory findings " ”cough, shortness of breath, or difficulty breathingSevere illnessClinical criteria of mild to moderate illness, and1 or more of the following " ”radiographic evidence, acute respiratory distress syndrome, or autopsy findings
  • Clinical criteria for SARS must be interpreted in the context of the prevailing epidemiologic laboratory criteria as published by the WHO and the CDC.
  • Suspect severe acute respiratory syndrome (SARS) case:A person presenting after November 1, 2002, with high fever (>38 ‚ °C), andCough or difficulty breathing, andClose contact with SARS patient or travel criteria to SARS area (see "History " ť)
  • Probable SARS case:A suspect case with radiographic pneumonia or respiratory distress syndromeA suspect case with confirmatory laboratory studies (see "Lab ")A suspect case with autopsy findings
  • A person presenting after November 1, 2002, with high fever (>38 ‚ °C), and
  • Cough or difficulty breathing, and
  • Close contact with SARS patient or travel criteria to SARS area (see "History " ť)
  • A suspect case with radiographic pneumonia or respiratory distress syndrome
  • A suspect case with confirmatory laboratory studies (see "Lab ")
  • A suspect case with autopsy findings
  • Early illness2 or more constitutional symptoms " ”fever, chills, rigors, myalgia, headache, diarrhea, sore throat, or rhinorrhea
  • Mild to moderate illnessTemperature >100.4 ‚ °F (>38 ‚ °C)1 or more lower respiratory findings " ”cough, shortness of breath, or difficulty breathing
  • Severe illnessClinical criteria of mild to moderate illness, and1 or more of the following " ”radiographic evidence, acute respiratory distress syndrome, or autopsy findings
  • 2 or more constitutional symptoms " ”fever, chills, rigors, myalgia, headache, diarrhea, sore throat, or rhinorrhea
  • Temperature >100.4 ‚ °F (>38 ‚ °C)
  • 1 or more lower respiratory findings " ”cough, shortness of breath, or difficulty breathing
  • Clinical criteria of mild to moderate illness, and
  • 1 or more of the following " ”radiographic evidence, acute respiratory distress syndrome, or autopsy findings

Epidemiology

  • SARS time lineNovember 2002: A series of severe idiopathic respiratory illnesses begin occurring in Southeast Asian countries (China, Hong Kong, Vietnam, and Singapore).February 2003The Chinese Ministry of Health notifies the WHO that 305 cases of acute respiratory syndrome of unknown etiology have occurred in Guangdong province in southern China.SARS outbreak in TorontoMarch 2003CDC activates emergency operations center with first confirmed death of SARS patient.CDC implicates a coronavirus as the causative SARS agent.May 2003: Deaths dramatically rise " ”7,761 cases, 623 deaths, 31 countriesJune 2003: Reported cases slow " ”over 8,000 cases, >770 deaths, 32 countriesJuly 2003: WHO declares the SARS epidemic over.Since July 2003, no further epidemics, but brief reemergence from accidental laboratory exposures in Singapore, Taiwan, and Beijing and from recurrent animal-to-human transmissions in Guangzhou in late 2003 and early 2004
  • First emergence of an important human pathogen in the 21st century
  • Final statistics of epidemics:Worldwide: >8,000 cases, nearly 800 deaths, >30 countries affectedUnited States: 134 suspected cases, 19 probable cases, 8 confirmed cases, no deaths, 17 states affected
  • November 2002: A series of severe idiopathic respiratory illnesses begin occurring in Southeast Asian countries (China, Hong Kong, Vietnam, and Singapore).
  • February 2003The Chinese Ministry of Health notifies the WHO that 305 cases of acute respiratory syndrome of unknown etiology have occurred in Guangdong province in southern China.SARS outbreak in Toronto
  • March 2003CDC activates emergency operations center with first confirmed death of SARS patient.CDC implicates a coronavirus as the causative SARS agent.
  • May 2003: Deaths dramatically rise " ”7,761 cases, 623 deaths, 31 countries
  • June 2003: Reported cases slow " ”over 8,000 cases, >770 deaths, 32 countries
  • July 2003: WHO declares the SARS epidemic over.
  • Since July 2003, no further epidemics, but brief reemergence from accidental laboratory exposures in Singapore, Taiwan, and Beijing and from recurrent animal-to-human transmissions in Guangzhou in late 2003 and early 2004
  • The Chinese Ministry of Health notifies the WHO that 305 cases of acute respiratory syndrome of unknown etiology have occurred in Guangdong province in southern China.
  • SARS outbreak in Toronto
  • CDC activates emergency operations center with first confirmed death of SARS patient.
  • CDC implicates a coronavirus as the causative SARS agent.
  • Worldwide: >8,000 cases, nearly 800 deaths, >30 countries affected
  • United States: 134 suspected cases, 19 probable cases, 8 confirmed cases, no deaths, 17 states affected

Risk Factors

  • TransmissionDirect or indirect contact of mucous membranes with infectious respiratory droplets or fomites, thus simple masks and good hand hygiene are important.Period of infectivity: most likely during period with active symptoms (fever, cough)Incubation period 2 " “14 days but may be as long as 21 days; mean 6 daysAll cases can be traced to contact with individuals from Asian countries or community, spread from an individual whose illness could be traced to Asia.There have been no suspected SARS cases among casual contacts of the U.S. cases.Many health care workers were infected after providing care to SARS patients.No evidence that SARS is transmitted from asymptomatic individualsHowever, health care workers who developed SARS may have been a source of transmission within health care facilities during early phases of illness, when symptoms were mild and not recognized as SARS.There is no evidence that SARS can be spread after recovery from the disease.Pediatric populationChildren pose a lower risk of transmission than do adults; only 1 reported case of transmission of SARS from pediatric patient.Vertical transmission of SARS coronavirus (SARS-CoV) from infected mothers to their newborns has not been observed.None of the newborns had clinical, laboratory, or radiologic evidence suggestive of SARS-CoV infection.
  • Direct or indirect contact of mucous membranes with infectious respiratory droplets or fomites, thus simple masks and good hand hygiene are important.
  • Period of infectivity: most likely during period with active symptoms (fever, cough)
  • Incubation period 2 " “14 days but may be as long as 21 days; mean 6 days
  • All cases can be traced to contact with individuals from Asian countries or community, spread from an individual whose illness could be traced to Asia.
  • There have been no suspected SARS cases among casual contacts of the U.S. cases.
  • Many health care workers were infected after providing care to SARS patients.
  • No evidence that SARS is transmitted from asymptomatic individuals
  • However, health care workers who developed SARS may have been a source of transmission within health care facilities during early phases of illness, when symptoms were mild and not recognized as SARS.
  • There is no evidence that SARS can be spread after recovery from the disease.
  • Pediatric populationChildren pose a lower risk of transmission than do adults; only 1 reported case of transmission of SARS from pediatric patient.Vertical transmission of SARS coronavirus (SARS-CoV) from infected mothers to their newborns has not been observed.None of the newborns had clinical, laboratory, or radiologic evidence suggestive of SARS-CoV infection.
  • Children pose a lower risk of transmission than do adults; only 1 reported case of transmission of SARS from pediatric patient.
  • Vertical transmission of SARS coronavirus (SARS-CoV) from infected mothers to their newborns has not been observed.
  • None of the newborns had clinical, laboratory, or radiologic evidence suggestive of SARS-CoV infection.

General Prevention

  • As there is no specific treatment, public health and infection control measures including contact tracing and quarantine of close contacts are paramount.
  • Hospital infection control precautions:Hospitalized patients meeting SARS case definition should be placed in a negative-pressure, single examination room.Protective equipment appropriate for standard, contact, and airborne precautions (e.g., hand hygiene, gown, gloves, and N95 respirator) in addition to eye protection are recommended for health care workers to prevent transmission of SARS in health care settings.
  • Pediatric patients with potential SARS exposure:Children who have been exposed to an ill individual who is suspected of having SARS, or children who have traveled to an area where SARS is occurring, should be evaluated based on the following:If well, parents should self-monitor the child 's condition for fever or respiratory tract illness. Attendance at child care or school is not restricted.If the child is not well, parents should contact their physician and the child should be isolated at home.If the child is not well and is experiencing breathing difficulty, he or she should be hospitalized. Health care workers should be informed before the admission so SARS precautions can be initiated.Children who have been exposed to individuals who are not ill but have traveled to areas where SARS is occurring do not require isolation.
  • VaccineNo effective human vaccine has been developed.Safety concerns exist for vaccine production workers.
  • Hospitalized patients meeting SARS case definition should be placed in a negative-pressure, single examination room.
  • Protective equipment appropriate for standard, contact, and airborne precautions (e.g., hand hygiene, gown, gloves, and N95 respirator) in addition to eye protection are recommended for health care workers to prevent transmission of SARS in health care settings.
  • Children who have been exposed to an ill individual who is suspected of having SARS, or children who have traveled to an area where SARS is occurring, should be evaluated based on the following:If well, parents should self-monitor the child 's condition for fever or respiratory tract illness. Attendance at child care or school is not restricted.If the child is not well, parents should contact their physician and the child should be isolated at home.If the child is not well and is experiencing breathing difficulty, he or she should be hospitalized. Health care workers should be informed before the admission so SARS precautions can be initiated.
  • Children who have been exposed to individuals who are not ill but have traveled to areas where SARS is occurring do not require isolation.
  • If well, parents should self-monitor the child 's condition for fever or respiratory tract illness. Attendance at child care or school is not restricted.
  • If the child is not well, parents should contact their physician and the child should be isolated at home.
  • If the child is not well and is experiencing breathing difficulty, he or she should be hospitalized. Health care workers should be informed before the admission so SARS precautions can be initiated.
  • No effective human vaccine has been developed.
  • Safety concerns exist for vaccine production workers.

Pathophysiology

Etiology

  • SARS-CoV, a previously unrecognized single-stranded RNA coronavirus
  • Coronaviruses are a common cause of mild to moderate upper respiratory infections in humans and have occasionally been linked to pneumonia.
  • Many believe that the virus originated in an animal species in China, then mutated in such a way that it was able to attach itself to human receptor cells.

Diagnosis

History

  • Recent travelTravel (including transit in an airport) within 10 days of onset of symptoms to an area with recently documented or suspected transmission of SARS is an important epidemiologic criterion for diagnosis.At the height of the SARS epidemic, these areas included China, Hong Kong, Singapore, Taiwan, Toronto, and Hanoi.
  • Recent contact with a SARS patientClose contact within 10 days of onset of symptoms with a person known or suspected to have SARS infection is another important epidemiologic criterion.
  • The clinical presentation of SARS in children >12 years of age is similar to that of adults.
  • Constitutional symptoms, such as fever, chills, rigors, headache, malaise, myalgias, and diarrhea, are common in older patients.
  • A meta-analysis (Stockman et al.) of 6 pediatric series of 135 SARS cases noted the following symptom prevalence: fever (98%), cough (60%), and nausea or vomiting (41%).
  • Respiratory symptomsAt the onset of illness, most cases have mild respiratory symptoms.After 3 " “7 days, a dry, nonproductive cough begins, often with dyspnea.
  • Travel (including transit in an airport) within 10 days of onset of symptoms to an area with recently documented or suspected transmission of SARS is an important epidemiologic criterion for diagnosis.
  • At the height of the SARS epidemic, these areas included China, Hong Kong, Singapore, Taiwan, Toronto, and Hanoi.
  • Close contact within 10 days of onset of symptoms with a person known or suspected to have SARS infection is another important epidemiologic criterion.
  • At the onset of illness, most cases have mild respiratory symptoms.
  • After 3 " “7 days, a dry, nonproductive cough begins, often with dyspnea.

Physical Exam

  • Fever generally heralds the start of the illness.
  • Tachypnea, increased work of breathing, or rales are common in adults.
  • Adult patients generally present with some evidence of respiratory distress or hypoxemia.
  • Importantly, however, although some children present with cough or difficulty breathing, many have remarkably normal examinations.

Diagnostic Tests & Interpretation

  • Detection of SARS coronavirus: confirmatory laboratory criteria for the diagnosis of SARS:Antibody by enzyme-linked immunosorbent assay (ELISA) or indirect fluorescent-antibody assay (IFA)RNA by reverse transcriptase-polymerase chain reaction (RT-PCR) assaysViral culture
  • SARS virus may be detected in blood, throat, nasopharyngeal aspirates, and stool samples.
  • CBC: Hematologic abnormalities are common in children with SARS.Leukopenia (lymphopenia or neutropenia)Thrombocytopenia
  • Liver enzymes: Elevated transaminases seen.
  • Raised serum lactate dehydrogenase is also seen.
  • Antibody by enzyme-linked immunosorbent assay (ELISA) or indirect fluorescent-antibody assay (IFA)
  • RNA by reverse transcriptase-polymerase chain reaction (RT-PCR) assays
  • Viral culture
  • Leukopenia (lymphopenia or neutropenia)
  • Thrombocytopenia
  • The characteristic feature of pulmonary SARS-CoV infection is patchy airspace consolidation predominantly located at the periphery of the lungs and in the lower lobes.
  • Normal chest radiographs also possible.

Differential Diagnosis

  • Bacterial infectionsPneumococcusStaphylococcusLegionellaMycoplasmaChlamydophila pneumoniae
  • Viral infectionsMiddle East respiratory syndrome (MERS)Avian influenza A(H7N9) infection (bird flu)Influenza A and BRespiratory syncytial virusEbola viral infection
  • Pneumococcus
  • Staphylococcus
  • Legionella
  • Mycoplasma
  • Chlamydophila pneumoniae
  • Middle East respiratory syndrome (MERS)
  • Avian influenza A(H7N9) infection (bird flu)
  • Influenza A and B
  • Respiratory syncytial virus
  • Ebola viral infection
  • Even during an epidemic of SARS, other diseases should still be considered.
  • Microbiologic studies should still be performed to confirm or rule out other infectious diseases.

Treatment

Inpatient Considerations

  • There is no proven effective treatment.
  • CDC currently recommends that patients with SARS receive the same treatment and supportive care that would be used for any patient with serious community-acquired atypical pneumonia of unknown cause.
  • Steroids, interferon, convalescent plasma, ribavirin, oseltamivir, and other antivirals have been used without consistent success.

Ongoing Care

Prognosis

  • Patients 12 years of age and youngerMilder diseaseFewer ICU admitsDecreased need for supplemental oxygenNo reported pediatric deaths
  • Overall fatality rate: 9.5% (all adults)Highest: 27% (Taiwan)Lowest: 0 (United States)
  • Milder disease
  • Fewer ICU admits
  • Decreased need for supplemental oxygen
  • No reported pediatric deaths
  • Highest: 27% (Taiwan)
  • Lowest: 0 (United States)

Complications

  • Overall, in 10 " “20% of cases, the respiratory illness was severe enough to require mechanical ventilation.
  • In children, only 5% required admission to an ICU, and <1% required mechanical ventilation.

Additional Reading

  • Braden ‚ CR, Dowell ‚ SF, Jernigan ‚ DB, et al. Progress in global surveillance and response capacity 10 years after severe acute respiratory syndrome. Emerg Infect Dis. 2013;19(6):864 " “869. ‚ [View Abstract]
  • Cheng ‚ VC, Chan ‚ JF, To ‚ KK, et al. Clinical management and infection control of SARS: lessons learned. Antiviral Res. 2013;100(2):407 " “419. ‚ [View Abstract]
  • Li ‚ AM, Ng ‚ PC. Severe acute respiratory syndrome (SARS) in neonates and children. Arch Dis Child Fetal Neonatal Ed. 2005;90(6):F461 " “F465. ‚ [View Abstract]
  • Momattin ‚ H, Mohammed ‚ K, Zumla ‚ A, et al. Therapeutic options for Middle East respiratory syndrome coronavirus (MERS-CoV) " ”possible lessons from a systematic review of SARS-CoV therapy. Int J Infect Dis. 2013;17(10):e792 " “e798. ‚ [View Abstract]
  • Stockman ‚ L, Massoudi ‚ MS, Helfand ‚ R, et al. Severe acute respiratory syndrome in children. Pediatr Infect Dis J. 2007;26(1):68 " “74. ‚ [View Abstract]

Codes

ICD09

  • 480.3 Pneumonia due to SARS-associated coronavirus
  • 079.82 SARS-associated coronavirus

ICD10

  • J12.81 Pneumonia due to SARS-associated coronavirus
  • B97.21 SARS-associated coronavirus causing diseases classd elswhr

SNOMED

  • 398447004 Severe acute respiratory syndrome (disorder)
  • 441590008 Pneumonia due to Severe acute respiratory syndrome coronavirus (disorder)

FAQ

  • Q: Is the clinical presentation and course different in children?
  • A: Fortunately, younger children tend to have a shorter and milder course, consisting mainly of low-grade fever, cough, and rhinorrhea. Adolescents, conversely, follow a more severe course, similar to that of adults.
  • Q: What constitutes close contact with a SARS patient?
  • A: Close contact includes having cared for or lived with a person known to have SARS or having a high likelihood of direct contact with respiratory secretions and/or body fluids of a patient known to have SARS.