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

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 III SARS CoV gp II (OC43) gp I (229E) NO HUMAN strains

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 TEST - ELISA

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.gloves 2.gowns & 3.respirators by health workers 4.Hand Hygiene

Co- evolution & pathogenicity

Majority of corona viruses cause asymptomatic infection in their natural hosts reflecting CO- EVOLUTION of HOST AND PATHOGEN

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 DNARNA viruses AdenoRhino Orthomyxo Corona 2.Envelope Not Enveloped Enveloped 3.Structur e nm ds-DNA non segmented icosahedral, 20-30nm Ss +vesense Non segmented Icosahedral symmetry nm ss –ve Sense segmented RNA Helical symmetry 80 to 160 nm ss+ve RNA non segmented Helical symmetry 4. Antigenic structure six groups (A to F) 49 types <100 serotypesA,B,C 15 H, 9N 4 groups 5.Tropism Adenoviruses infect and replicate in the epithelial cells Cells URTRespiratory mmRT GI 6.Spread Spread To Regional Lymph Nodes EXCEPT in the immunocompromised Do Not Spread

4 families of 1ry Respiratory viruses DNARNA viruses AdenoRhino Orthomyxo Corona 7. Isolation Human cells are required Cells of primate origin, Human diploid fibroblast cells Primary tissue culture MK human embryonic tracheal organ cultures SARS Vero monkey cells 8.Treatment No antiviral drug No antiviralTreatmentNo 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 DNARNA viruses AdenoRhino Orthomyx o Corona 11. THREAT LATENCY No Threat Epidemic & potential pandemics Potential repetition of infections similar to SARS 12. Infections A. Respiratory diseases 5%: B. Eye infections: C. Gastrointestinal disease: D. OTHER DISEASES: - Acute haemorrhagic cystitis Immuno-compromised patients manifestations are: -Pneumonia -hepatitis -gastroenteritis 50% of URT Seasonal & epidemic influenza URT 15% to 30% Diarreaha SARS