Severe Acute Respiratory Syndrome - SARS prevention and control; global and local epidemiology

2. Severe Acute Respiratory
Syndrome (SARS)
Dr. Saira Mansoor
Department of Community Medicine
Liaquat National Medical College & Hospital

3. Session Objectives
At the end of this session, the learners shall be able to:
• Describe the epidemiology of Severe Acute Respiratory Syndrome
• Global burden of disease
• Causative agent
• Mode of transmission
• Incubation period
• Pathogenesis
• Signs & symptoms, complications and prognosis
• Describe the clinical and lab diagnostic criteria for SARS’ case definition
• Explain the relevant prevention & (treatment) measures for SARS control
• Treatment options
• Surveillance (community & individual)
• Post-exposure prophylaxis
• Community & hospital infection control

4. Introduction
• Severe acute respiratory syndrome (SARS) is a viral respiratory illness that was
recognized as a global threat in March 2003, after first appearing in Southern
China in November 2002
• Severe acute respiratory syndrome (SARS)  came to global attention in
February 2003
• Caused by a novel infectious agent – SARS-CoV
• Officials in China informed the World Health Organization  ~305 cases
of atypical pneumonia  in Guangdong Province
https://www.cdc.gov/sars/surveillance/absence.html

5. Epidemiology of SARS-
CoV
https://www.creativebiolabs.net/blog/wp-content/uploads/2020/02/CoV-Fig.2.jpg

6. Global Burden of SARS
• When the new infectious disease was declared contained in July 2003,
globally reported
• > 8,000 cases
• 780 deaths
• Since then  Active global surveillance for SARS-associated coronavirus
(SARS-CoV) disease in humans has detected no laboratory-confirmed
person-to-person transmission of SARS-CoV
reported from 29 countries worldwide
https://www.cdc.gov/sars/surveillance/absence.html

7. Incubation Period
• The median incubation period for SARS-CoV:
• ~ 4 to 6 days
• Most patients become ill within 2 to 10 days post-exposure

9. • Figure 2:
• A) Model of SARS structure. SARS virions are round, moderately
pleomorphic enveloped particles, measuring 100–150 nm in diameter and
covered with a distinctive fringe of widely spaced, club-shaped surface
structures about 20 nm in length composed of the spike glycoprotein (S).
The membrane glycoprotein (M) interacts with the nucleocapsid. The viral
nucleocapsid consist of the 29.7 kb plus-stranded genomic RNA and the
capsid phosphoprotein (N).
• (B) Genomic organization of SARS. Overall organization of the 29.7 kb
genomic RNA. Predicted open reading frames (ORF) 1a and 1b encode the
RNA polymerase and nonstructural proteins, followed by S, E, M and N.
Numbers above line indicate the start position of the ORF, and number
beneath the line indicate the stop position of the ORF. The numbering is
based on the genome of SARS virus deposited in GenBank, accession
number NC_004718.
• (C) Phylogenic dendrogram of coronavirus spike glycoproteins. The length
of each branch depicts relative sequence homology between the proteins.
Shaded areas illustrate receptor clusters. Abbreviations are severe acute
respiratory syndrome virus (SARS), human coronavirus strain 229E (HCoV-
229E), porcine epidemic diarrhoea virus (PEDV), porcine respiratory
coronavirus (PRCoV), avian infectious bronchitis virus strain H52 (AIBV-
H52), mouse hepatitis virus strain JHM (MHV-JHM), rat sialodacryoadenitis
coronavirus (RSC), porcine haemagglutinating encephalomyelitis virus
(PHE), bovine coronavirus strain LY138 (BCV-LY138) and human coronavirus
strain OC43 (HCoV-OC43). The phylogenetic tree is based on a clustal x
1.81 alignments of the full amino acid sequence of all included spike
proteins and the graphic presentation were generated using treeview.

10. Mode of Transmission
• The primary mode of transmission appears to be through close person-to-person
contact of mucous membranes of eyes, nose, or mouth with respiratory droplets
or fomites, directly or indirectly
• The use of aerosol-generating procedures (endotracheal intubation,
bronchoscopy, nebulization treatments) in hospitals  may amplify the
transmission of the SARS corona-virus
• The virus is shed in stool  but the role of fecal-oral transmission is unknown
• The natural reservoir: appears to be the horseshoe bat (which eats and drops
fruits ingested by civets, earlier presumed reservoir + amplifying host
• The SARS virus can survive for hours on common surfaces outside the human
body, and up to four days in human waste
• The virus can survive at least for 24 hours on a plastic surface at room
temperature, and can live for extended periods in the cold

11. https://scotdir.com/health-and-fitness-2/treatments-for-severe-acute-respiratory-syndrome

13. Case Definition of SARS
https://www.cdc.gov/dotw/sars/index.html
https://www.cdc.gov/dotw/sars/index.html

14. Clinical Case Definition
• 1. A history of fever, or documented fever
AND
• One or more symptoms of lower respiratory tract illness
• Cough
• Difficulty in breathing
• Shortness of breath)
AND
• 3. Radiographic evidence of lung infiltrates consistent with:
• Pneumonia OR
• Acute respiratory distress syndrome (ARDS) OR
• Autopsy findings consistent with the pathology of pneumonia or ARDS without an identifiable cause
AND
• 4. No alternative diagnosis fully explaining the illness

15. Diagnostic Tests Required For Laboratory Confirmation of
SARS
• Conventional reverse transcriptase PCR {RT-PCR) and real-time reverse transcriptase PCR (real-time
RT-PCR) assay detecting viral RNA present in:
• At least 2 different clinical specimens (e.g. nasopharyngeal and stool specimens)
OR
• The same clinical specimen collected on 2 or more occasions during the course of the illness (e.g. sequential
nasopharyngeal aspirates)
OR
• A new extract from the original clinical sample tested positive by 2 different assays or repeat RT-PCR or real-time RT-PCR
on each occasion of testing
OR
• Virus culture from any clinical specimen.
• Enzyme-linked immunosorbent assay (ELISA) and immunofluorescent assay (IFA)
• Negative antibody test on serum collected during the acute phase of illness, followed by positive antibody test on
convalescent-phase serum, tested simultaneously
OR
• A 4-fold or greater rise in antibody titer against SARS-CoV between an acute-phase serum specimen and a convalescent-
phase serum specimen (paired sera), tested simultaneously.
In the absence of known SARS-CoV transmission to humans, the positive predictive value of a SARS-CoV diagnostic test is extremely low; therefore, the diagnosis should
be independently verified in one or more WHO international SARS reference and verification network laboratories. Every single case of SARS must be reported to WHO

16. Signs & Symptoms
• Early clinical features of SARS-CoV disease show similarity to other viral illnesses and are
not sufficiently distinct to enable diagnosis by signs and symptoms alone
• The illness usually begins with systemic symptoms such as:
• Fever - temperature > 100.40F / 38.00C
• Headache
• Myalgias
• Some people also have mild respiratory symptoms at the outset
• Diarrhea – 20% – 30% patients

17. Signs & Symptoms
• Respiratory complaints:
• Develop 2 to 7 days after illness onset
• Usually include a non-productive cough and dyspnea
• Upper respiratory symptoms: rhinorrhea and sore throat may occur (uncommon)
• Almost all patients with laboratory evidence of SARS-CoV disease:
• Developed radiographic evidence of pneumonia by day 7-10 of illness
• Most (70% -90%) developed lymphopenia
• The overall case-fatality rate (CFR) of ~10% can increase to >50% in persons older than
age 60

19. Complications of SARS
• As with any viral pneumonia, pulmonary decompensation is the most feared
problem
• ARDS occurs in about 16% patients
• About 20-30% of patients require intubation and mechanical ventilation
• Sequelae of intensive care include:
• Infection with nosocomial pathogens
• Tension pneumothorax from ventilation at high peak pressures
• On-cardiogenic pulmonary edema

20. Prognosis of SARS
• The overall mortality rate of identified cases is about 14%
• Mortality is age-related, ranging from less than 1 % in persons under 24 years of
age to greater than 50% in persons over 65 years of age
• Poor prognostic factors include:
• Advanced age
• Chronic hepatitis B infection treated with lamivudine
• High initial or high peak lactate dehydrogenase concentration
• High neutrophil count on presentation
• Diabetes mellitus
• Acute kidney disease
• Low counts of CD4 and CD8 on presentation
• Many subclinical cases probably go undiagnosed
• Seasonality, as with influenza, is not established

21. Surveillance & Early Case Detection
• Severe respiratory illness in the context of a documented exposure risk is the
key to diagnosing SARS-CoV disease
• Providers should therefore consider SARS-CoV disease in patients requiring
hospitalization for:
• Radiographically confirmed pneumonia or acute respiratory distress syndrome of
unknown etiology, AND
• One of the following risk factors in the 10 days before illness onset:
• Travel to mainland China, Hong Kong, or Taiwan, or close contact with an ill person with a history of recent
travel to one of these areas, OR
• Employment in an occupation associated with a risk for SARS-CoV exposure (e.g., healthcare worker with
direct patient contact; worker in a laboratory that contains live SARS-CoV), OR
• Part of a cluster of cases of atypical pneumonia without an alternative diagnosis
• Infection control practitioners and other healthcare personnel should be alert for
clusters of pneumonia among two or more healthcare workers who work in the
same facility

22. Treatment of SARS
• Severe cases require intensive support
• Although several different agents including:
• Ribavirin (400-600 mg/d and 4 g/d)
• Lopinavir/ritonavir (400 mg/100 mg)
• Interferon type 1
• Intravenous immunoglobulin
• Systemic cortioco-steroids
Were used to treat SARS patients during the 2003 epidemic the treatment efficacy of these therapeutic
agents remains inconclusive and further research is needed
• Subsequent studies with ribavirin show no activity against the virus in vitro, and a
retrospective analysis of the epidemic in Toronto suggests worse outcomes in
patients who receive the drug

23. Prevention of SARS
• As there is no vaccine against SARS, the preventive measures for SARS control are appropriate
detection and protective measures which include:
1. Prompt identification of persons with SARS, their movements and contacts
2. Effective isolation of SARS patients in hospitals
3. Appropriate protection of medical staff treating these patients
4. Comprehensive identification and isolation of suspected SARS cases
5. Simple hygienic measures such as hand-washing after touching patients, use of appropriate and
well-fitted masks, and introduction of infection control measures
6. Exit screening of international travelers
7. Timely and accurate reporting and sharing of information with other authorities and/or
governments

24. SARS Virus – Select Agent
• On October 5, 2012, the National Select Agent Registry Program published
a final rule declaring SARS coronavirus a select agent
• A select agent is a bacterium, virus or toxin that has the potential to pose a
severe threat to public health and safety
https://www.cdc.gov/sars/index.html

25. Figure 1:
Clinical Guidance on the
Identification and Evaluation
of Possible SARS-CoV
among Persons Presenting
with Community-Acquired
Illness

26. Figure 2:
Clinical
Guidance on the
Identification
and Evaluation
of Possible
SARS-CoV
Disease among
Persons
Presenting with
Community-
Acquired Illness

27. SARS & Isolation
• During the 2003 global SARS outbreak, patients were isolated until they were no
longer infectious
• This practice allowed patients to receive appropriate care, and it helped contain
the spread of the illness
• Seriously ill patients were cared for in hospitals
• Persons with mild illness were cared for at home
• Persons being cared for at home were asked:
• To avoid contact with other people
• To remain at home until 10 days after the resolution of fever, provided respiratory symptoms
were absent or improving

28. SARS & Quarantine
• In Pakistan, there were no known reported cases
• Individual quarantine was an integral part of the control measures used in
countries more severely affected by the 2003 SARS outbreak i.e., China, Hong
Kong, Singapore, Vietnam
• Quarantine of large groups was used only in selected settings where extensive
transmission was occurring
• In the United States, where there was limited transmission of SARS-CoV during
the 2003 SARS outbreak, neither individual nor population-based quarantine of
contacts was recommended
• CDC advised persons who were exposed but not symptomatic to monitor
themselves for symptoms and advised home isolation and medical evaluation if
symptoms appeared

30. Coronavirus
• The 3 infectious diseases caused by 3
different strains of the Coronavirus
family
• All 3 are highly infectious and cause fast
spread via person-to-person contact
• All 3 have the potential to cause deadly
pandemics  SARS-CoV2 is causing a
global pandemic currently

31. In Conclusion
• No one knows if, when, or where person-to-person transmission of SARS-CoV will recur
• However, the rapidity of spread of infection and the high levels of morbidity & mortality
associated with SARS-CoV  call for careful monitoring for the recurrence of transmission
and preparations for the rapid implementation of control measures
• The 2003 global outbreaks demonstrated the ease with which SARS-CoV can seed and
spread in human populations when cases remain undetected or when infected persons
are not cared for in controlled environments that reduce the risk of transmission to others
• The two laboratory-acquired infections and the recent cases in Southern China show that
SARS-CoV continues to be a threat
• Early detection of SARS cases and contacts, plus swift and decisive implementation of
containment measures  essential to prevent transmission