CORONAVIRUSES

Genus Coronavirus CoV & Genus Torovirus

Coronaviridae

CORONAVIRUSES
The genome - SS linear non segmented +ve sense RNA - the largest among RNA viruses.

The family coronaviridae is composed of two genera:

Genus Coronaviruses
Genus Torovirus:
widespread in horses & cattle associated with gastroenteritis.

Genus Coronavirus
First isolated in chicken in 1937
First human corona virus was isolated in 1965 They cause prevalent disease in humans and domestic animals (cats, dogs, birds)

Structure:
Coronaviruses are large enveloped virions 80 to 160 nm,
Helical nucleocapsids.

A Crown-like Appearance when viewed by EM

On the surface of the envelop are club shaped projections that resemble a solar corona

Genus Coronaviruses
Genus Coronaviruses are difficult to isolate in cell culture So infections with this virus are rarely diagnosed in clinical practice

Tropism To Epithelial Cells

Respiratory tract

GI in infants

Relationship to human infections

- Based on serologic studies, coronaviruses cause respiratory tract infections and pneumonia in humans.
- Electron microscopy links coronaviruses to gastroenteritis in infants children and adults ( tropism to epithelial cells)

Genetic variation & evolution of new strains

a high frequency of:
deletion mutations high frequency of recombination during replication which is unusual for an RNA virus with unsegmented genome

The three major antigenic groups of CoV

Group I contains canine, feline, porcine coronaviruses and a human corona virus HCoV 229E the prototype of the group
Group II contains bovine, porcine, rat and mouse CoV and the other human strain which is OC43 Group III no human strains only Turkey and Avian CoV

Evolution of SARS 2002

A novel human corona virus named SARS associated corona virus represents a new fourth antigenic group intermediate between groups I & III

A NOVEL FOURTH ANTIGENIC GROUP SARS Evolution of SARS

gp I (229E)

gp III
SARS CoV NO HUMAN strains

gp II (OC43)

Clinical picture & epidemiology

Upper respiratory infections, similar to colds caused by rhinoviruses, but with a longer incubation period (average three days).
15-30% of respiratory illness in adults during winter months but lower respiratory infections were rare.
Antibodies appear early in childhood and are found in 90% in adults

CLINICAL PICTURE & EPIDEMIOLOGY

CORONAVIRUSES may be associated with gastroenteritis which occurs year-round. Confirmation of the etiology of this relationship is needed.

Laboratory Diagnosis
Direct Detection

Isolation

Serology

Laboratory Diagnosis of 1. coronaviruses

DIRECT DETECTION: Antigen detection in cells of respiratory secretions by IF or ELISA NA detection in respiratory secretions by RT-PCR ISOLATION: CoV are difficult to grow in CC.

Reliable isolation of the virus is accomplished using human embryonic tracheal organ cultures.
These methods are not routinely available.

Detection of Corona virus by Immunofluorescent Technique

Serology:
Serologic tests are not routinely available. Practical means to confirm coronavirus infection using paired sera to detect rising or stationary high antibody level by: - PASSIVE HAEMAGGLUTINATION

- ELISA

TEST

Laboratory diagnosis of Gastroenteritis caused by toroviruses

BASED ON DIRECT DETECTION ONLY:

Ag detection
NA detection

SARS

SEVERE ACUTE RESPIRATORY SYNDROME

SARS

Mystery pneumonia late 2002 in southern China Resulting in progressive respiratory failure

SEVERE ACUTE RESPIRATORY SYNDROME

Animal strain from a cat like mammal in Southern China Person to person spread by close contact through respiratory droplets

STRUCTURE & CHARACTERISTICS

Similar to coronaviruses EXCEPT: Grown easily on tissue culture cells resulting in cytopathic effect
Has tropism to LRT

SARS
First coronavirus that causes severe LRT disease in humans

Clinical picture
IP: 6 days
First epidemic 10% MR from progressive respiratory failure

Laboratory Diagnosis
Direct Detection: NA detection
Isolation of the virus using Vero monkey cells resulting in CPE. Confirmation by RT-PCR

Serology: 4 fold or greater rise in antibody response by ELISA or IF

Treatment
No successful treatment
No vaccine

YET STOPPING THE SPREAD OF INFECTION WAS POSSIBLE THROUGH EFFECTIVE CONTROL MEASURES

Control Measures
1. Isolation of patients 2. Quarantine of those exposed 3. Use of barrier Precautions:
1. 2. 3. gloves gowns & respirators by health workers

4. Hand Hygiene

Co- evolution & pathogenicity

Majority of corona viruses cause asymptomatic infection in their natural hosts reflecting

CO- EVOLUTION

HOST AND PATHOGEN

of

WHY SARS INFCTION IN HUMANS IS Fulminant

This is attributed to SARS jumped from animals to human i.e. A non natural host is infected

OTHER CAUSES OF FULMINANT INFECTION

The natural host is infected by an unusual route The infection is caused by a more virulent virus variant

EVIDENCE OF THE EFFECT OF CO-EVOLUTION

Milder cases of SARS Coronavirus infections in South China SARS coronavirus cause milder infections in populations previously affected by outbreaks

NOTE!!! Co-evolution takes years to develop

Always remember

CHANGE IN PATHOGENICITY IS ATTRIBUTED TO

A non natural host is infected

The natural host is infected by an unusual route The infection is caused by a more virulent virus variant

4 families of 1ry Respiratory

1.NA Name
2.Envelope 3.Structur e

DNA

RNA viruses

Adeno
Not
Enveloped 70-90 nm ds-DNA non segmented icosahedral six groups (A to F) 49 types

Rhino
Not
Enveloped

Orthomyxo
Enveloped
80-120 nm

Corona
Enveloped 80 to 160 nm ss+ve RNA non segmented
Helical symmetry

, 20-30nm

Ss +vesense Non segmented Icosahedral symmetry <100 serotypes

ss ve Sense

segmented RNA Helical symmetry

4. Antigenic structure

A,B,C 15 H, 9N

4 groups

5.Tropism

Adenoviruses infect and replicate in the epithelial cells

Cells URT

Respiratory mm

RT GI Do Not Spread

6.Spread

Spread To Regional Lymph Nodes EXCEPT in the immunocompromised

Do Not Spread

Do Not Spread

4 families of 1ry Respiratory viruses

DNA

RNA viruses

Adeno
7. Isolation
Human cells are required

Rhino
Cells of primate origin, Human diploid fibroblast cells

Orthomyxo
Primary tissue culture MK

Corona
human embryonic tracheal organ cultures SARS Vero monkey cells

8.Treatment

No antiviral drug

No antiviral

Treatment

No successful treatment

9. Important feature

Latency oncogenic potential in animals

< 50% of URTI

Mutability & high frequency of genetic reassortment

high frequency of: deletion mutations high frequency of recombination during replication

10. VACCINE

Available -

4 families of 1ry Respiratory viruses DNA RNA viruses Adeno

11. THREAT

Rhino
No Threat

Orthomyx o
Epidemic & potential pandemics

Corona
Potential repetition of infections similar to SARS

LATENCY
A. Respiratory diseases 5%: B. Eye infections: C. Gastrointestinal disease: D. OTHER DISEASES: - Acute haemorrhagic cystitis

12. Infections

Immuno-compromised patients manifestations are: -Pneumonia -hepatitis -gastroenteritis

50% Seasonal & of URT epidemic

URT 15% to 30% Diarreaha

influenza SARS