1. NELSON C. AGAPAY JR. MD,DPAFP

2. Coronaviruses large, enveloped RNA viruses. human coronaviruses cause common colds have been implicated in gastroenteritis in infants cause of a worldwide outbreak of a severe acute respiratory syndrome (SARS) in 2003. Animal coronaviruses cause diseases of economic importance in domestic animals. The human viruses are difficult to culture and therefore are poorly characterized.

3. Structure & Composition Coronaviruses are enveloped 120- to 160-nm particles that contain an unsegmented genome of single-stranded positive-sense RNA (27–32 kb) the largest genome among RNA viruses. Isolated genomic RNA is infectious. Helical nucleocapsid is 9–11 nm in diameter. There are 20-nm-long club- or petal-shaped projections that are widely spaced on the outer surface of the envelope, suggestive of a solar corona

4. The viral structural proteins include : a 50–60 kDa phosphorylated nucleocapsid (N) protein a 20–35 kDa membrane (M) glycoprotein that serves as a matrix protein embedded in the envelope lipid bilayer and interacting with the nucleocapsid the spike (S; 180–220 kDa) glycoprotein that makes up the petal-shaped peplomers. Some viruses, including human coronavirus OC43, contain a third glycoprotein (HE; 65 kDa) that causes hemagglutination.

5. Classification Characteristics used to classify Coronaviridae include : particle morphology unique RNA replication strategy genome organization nucleotide sequence homology. There are two genera in the Coronaviridae family: Coronavirus Torovirus- are widespread in ungulates and appear to be associated with diarrheas.

6. Two serogroups of human coronaviruses: strains 229E strains OC43. There is a third distinct antigenic group which contains the avian infectious bronchitis virus of chickens. Cross-reactions occur between some human and some animal strains. Some strains have hemagglutinins. The novel coronavirus recovered in 2003 from patients with severe acute respiratory syndrome (SARS) appears to represent a new (fourth) group of viruses.

7. Coronavirus Replication Human coronaviruses do not grow well in cell culture. details of viral replication have come from studies with mouse hepatitis virus, which is closely related to human strain OC43 Replication cycle takes place in the cytoplasm of cells. Exhibit a high frequency of mutation during each round of replication including the generation of a high incidence of deletion mutations. undergo a high frequency of recombination during replication this is unusual for an RNA virus with a nonsegmented genome and may contribute to the evolution of new virus strains.

9. Summary of Replicative Cycle The virus adsorbs to cells via its surface spikes (hemagglutinin) after which it enters the cytoplasm, where it is uncoated. The positive-strand genome is translated into two large polypeptides, which are self-cleaved by the virus-encoded protease. Two of these peptides aggregate to form the RNA polymerase (transcriptase) that replicates the genome. In addition, mRNAs are synthesized, and then translated into the structural proteins. The virus is assembled and obtains its envelope from the endoplasmic reticulum, not from the plasma membrane. Replication occurs in the cytoplasm.

10. Transmission & Epidemiology Coronaviruses are transmitted by the respiratory aerosol. Infection occurs worldwide and occurs early in life, as evidenced by finding antibody in more than half of children. Outbreaks occur primarily in the winter on a 2- to 3-year cycle. SARS originated in China in November 2002 and spread rapidly to other countries. There have been 8300 cases and 785 deaths—a fatality rate of approximately 9%. Human-to-human transmission occurs, and some patients with SARS are thought to be "super-spreaders," but this remains to be confirmed.

11. Many hospital personnel were affected, but respiratory infection control procedures have greatly reduced the spread within hospitals. There are many animal coronaviruses, and they are suspected of being the source of the CoV-SARS. The horseshoe bat appears to be the natural reservoir for CoV-SARS, with the civet cat serving as an intermediate host.

12. Pathogenesis & Immunity Coronavirus infection is typically limited to the mucosal cells of the respiratory tract. Approximately 50% of infections are asymptomatic, and it is unclear what role they play in the spread of infection. Immunity following infection appears to be brief and reinfection can occur. Pneumonia caused by SARS coronavirus is characterized by diffuse edema resulting in hypoxia. The binding of the virus to angiotensin-converting enzyme-2 on the surface of respiratory tract epithelium may contribute to the dysregulation of fluid balance that causes the edema in the alveolar space.

13. Clinical Findings The human coronaviruses produce "colds," usually afebrile, in adults. Symptoms are similar to those produced by rhinoviruses, typified by nasal discharge and malaise. Incubation period is from 2 days to 5 days, and symptoms usually last about 1 week. The lower respiratory tract is seldom involved, although pneumonia in military recruits has been attributed to coronavirus infection. Asthmatic children may suffer wheezing attacks, and chronic pulmonary disease in adults may exacerbate respiratory symptoms.

14. The newly recognized SARS coronavirus causes severe respiratory disease. The incubation period averages about 6 days. Early symptoms include fever, malaise, chills, headache, dizziness, cough, and sore throat, followed a few days later by shortness of breath. Many patients have abnormal chest radiographs. Some cases progress rapidly to acute respiratory distress, requiring ventilatory support. Death from progressive respiratory failure occurs in almost 10% of cases, with the death rate highest among the elderly. Clinical features of coronavirus-associated enteritis have not been clearly described. They appear to be similar to those of rotavirus infections.

15. Laboratory Diagnosis The diagnosis of the "common cold" is primarily a clinical one. If SARS is suspected, antibody-based and PCR-based tests can be used. Antigen and Nucleic Acid Detection Coronavirus antigens in cells in respiratory secretions may be detected using the ELISA test if a high-quality antiserum is available. Enteric coronaviruses can be detected by examination of stool samples by electron microscopy. Polymerase chain reaction assays will be useful to detect coronavirus nucleic acid in respiratory secretions and in stool samples.

16. Isolation and Identification of Virus Isolation of human coronaviruses in cell culture has been difficult. However, the SARS virus was recovered from oropharyngeal specimens using Vero monkey kidney cells. Serology Because of the difficulty of virus isolation, serodiagnosis using acute and convalescent sera is the practical means of confirming coronavirus infections. ELISA and hemagglutination tests may be used. Serologic diagnosis of infections with strain 229E is possible using a passive hemagglutination test in which red cells coated with coronavirus antigen are agglutinated by antibody-containing sera.

17. Treatment, Prevention, & Control There is no antiviral therapy or vaccine available. A combination of ribavirin and steroids has been tried in the treatment of life-threatening cases of SARS, but their efficacy is uncertain. Control measures that were effective in stopping the spread of SARS included: isolation of patients quarantine of those who had been exposed travel restrictions use of gloves, gowns, goggles, and respirators by health care workers.

19. Diseases causes rubella (German measles) and congenital rubella syndrome. Congenital rubella syndrome - congenital malformations. Important Properties member of the togavirus family one piece of single-stranded RNA icosahedral nucleocapsid lipoprotein envelope. positive-strand RNA surface spikes contain hemagglutinin. has a single antigenic type. Antibody against hemagglutinin neutralizes infectivity. Humans are the natural host.

23. Summary of Replicative Cycle After penetration of the cell and uncoating plus-strand RNA genome is translated into several nonstructural and structural proteins. translates its RNA into a single large polyprotein, which is subsequently cleaved. One of the nonstructural rubella proteins is an RNA- dependent RNA polymerase, which replicates the genome first by making a minus-strand template and then, from that, plus-strand progeny. Both replication and assembly occur in the cytoplasm envelope is acquired from the outer membrane as the virion exits the cell.

24. Transmission & Epidemiology transmitted via respiratory droplets from mother to fetus transplacentally. The disease occurs worldwide. In 2005, the Centers for Disease Control and Prevention (CDC) declared rubella eliminated from the United States. The few cases that occurred in the United States were acquired outside. Elimination was made possible by the widespread use of the vaccine. As a result, cytomegalovirus is a much more common cause of congenital malformations in the United States than is rubella virus.

25. Pathogenesis & Immunity Initial replication of the virus occurs in the nasopharynx and local lymph nodes. From there it spreads via the blood to the internal organs and skin. The origin of the rash is unclear; it may be due to antigen/antibody–mediated vasculitis. Natural infection leads to lifelong immunity. Second cases of rubella do not occur. Antibody crosses the placenta and protects the newborn.

26. Clinical Findings Rubella milder, shorter disease than measles. incubation period of 14 to 21 days prodromal period with fever and malaise is followed by a maculopapular rash starts on the face and progresses downward to involve the extremities. Posterior auricular lymphadenopathy is characteristic. The rash typically lasts 3 days. When rubella occurs in adults, especially women, polyarthritis caused by immune complexes often occurs.

28. Congenital Rubella Syndrome Teratogen nonimmune pregnant woman is infected during the first trimester, significant congenital malformations can occur as a result of maternal viremia and fetal infection. attributed to the very sensitive organ development that occurs at that time. malformations are widespread and involve primarily the heart (e.g., patent ductus arteriosus), the eyes (e.g., cataracts), and the brain (e.g., deafness and mental retardation).

30. Laboratory Diagnosis can be grown in cell culture produces little cytopathic effect (CPE). usually identified by its ability to interfere with echovirus CPE. diagnosis can also be made by observing a fourfold or greater rise in antibody titer between acute-phase and convalescent-phase sera in the hemagglutination inhibition test or ELISA or by observing the presence of IgM antibody in a single acute-phase serum sample. In a pregnant woman exposed to rubella virus, the presence of IgM antibody indicates recent infection 1:8 or greater titer of IgG antibody indicates immunity and consequent protection of the fetus.

31. Treatment There is no antiviral therapy. Prevention Prevention involves immunization with the live, attenuated vaccine. The vaccine is effective and long-lasting (at least 10 years) causes few side effects, except for transient arthralgias in some women. It is given subcutaneously to children at 15 months of age (usually in combination with measles and mumps vaccine). unimmunized young adult women if they are not pregnant and will use contraception for the next 3 months. Because it is a live vaccine, it should not be given to immunocompromised patients or to pregnant women.

32. Prevention The vaccine has caused a significant reduction in the incidence of both rubella and congenital rubella syndrome. It induces some respiratory IgA, thereby interrupting the spread of virulent virus by nasal carriage. Immune serum globulins (IG) can be given to pregnant women in the first trimester, who have been exposed to a known case of rubella. To protect pregnant women from exposure to rubella virus, many hospitals require their personnel to demonstrate immunity, either by serologic testing or by proof of immunization.