CORONAVIRUS — WHAT IS IT ?

COVID-19

Coronaviruses were first isolated from chickens in 1937. After the discovery of Rhinoviruses in the 1950’s, ~50% of colds still could not be ascribed to known agents. In 1965, Tyrrell and Bynoe used cultures of human ciliated embryonal trachea to propagate the first human coronavirus (HCoV) in vitro. There are now approximately 15 species in this family, which infect not only man but cattle, pigs, rodents, cats, dogs and birds (some are serious veterinary pathogens, especially chickens).

Most human coronaviruses do not grow in cultured cells, therefore relatively little is known about them, but two strains (229E & OC43) grow in some cell lines & have been used as a model. Replication is slow compared to other enveloped influenza viruses.

These viruses infect a variety of mammals & birds. The exact number of human isolates are not known as many cannot be grown in culture. In humans, they cause:

  • Respiratory infections (common), including Severe Acute Respirator Syndrome (SARS)
  • Enteric infections (occasional — mostly in infants <12 months)
  • Neurological syndromes (rare)

They are transmitted by aerosols of respiratory secretions, by the faecal-oral route, and by mechanical transmission. Most virus growth occurs in epithelial cells. Occasionally the liver, kidneys, heart or eyes may be infected, as well as other cell types such as macrophages. In cold-type respiratory infections, growth appears to be localized to the epithelium of the upper respiratory tract, but there is no adequate animal model for the human respiratory coronaviruses. Clinically, most infections cause a mild, self-limited disease (classical ‘cold’ or upset stomach), but there may be rare neurological complications. SARS is a form of viral pneumonia where infection encompasses the lower respiratory tract.

Coronavirus infection is very common and occurs worldwide. The incidence of infection is strongly seasonal, with the greatest incidence in children in winter. Adult infections are less common. The number of coronavirus serotypes and the extent of antigenic variation is unknown. Re-infections appear to occur throughout life, implying multiple serotypes (at least four are known) and/or antigenic variation, hence the prospects for immunization appear bleak.

Coronaviruses — the cause of SARS

SARS is a type of viral pneumonia, with symptoms including fever, a dry cough, dyspnea (shortness of breath), headache, and hypoxaemia (low blood oxygen concentration). Typical laboratory findings include lymphopaenia (reduced lymphocyte numbers) and mildly elevated aminotransferase levels (indicating liver damage). Death may result from progressive respiratory failure due to alveolar damage. The typical clinical course of SARS involves an improvement in symptoms during the first week of infection, followed by a worsening during the second week. Studies indicate that this worsening may be related to patient’s immune responses rather than uncontrolled viral replication.

The outbreak is believed to have originated in February 2003 in the Guangdong province of China, where 300 people became ill, and at least five died. After initial reports that a paramyxovirus was responsible, the true cause appears to be a novel coronavirus with some unusual properties. For one thing, the SARS virus can be grown in Vero cells (a fibroblast cell line isolated in 1962 from a primate) — a novel property for HCoV’s, most of which cannot be cultivated. In these cells, virus infection results in a cytopathic effect, and budding of coronavirus-like particles from the endoplasmic reticulum within infected cells.

The SARS virus is believed to be spread by droplets produced by coughing and sneezing, but other routes of infection may also be involved, such as faecal contamination, so wash your hands!

There is currently no general agreement that antiviral drugs have been shown to be consistently successful in treating SARS or any coronavirus infection. An inactivated vaccine against SARS recently began clinical trials, but even if successful will not be widelay available for a number of years. New drugs targeted specifically against this virus are under development.

Diagnostic tests for coronavirus infection fall into two types:

  • Serological testing for anti-coronavirus antibodies consists of indirect fluorescent antibody testing and enzyme-linked immunosorbent assays (ELISA) which detect antibodies against the virus produced in response to infection. Although some patients have detectable coronavirus antibody within 14 days of illness onset, definitive interpretation of negative coronavirus antibody tests is possible only for specimens obtained >21 days after onset of fever.
  • Molecular testing consists of reverse transcriptase-polymerase chain reaction (RT-PCR) tests specific for the RNA from this novel coronavirus. This can detect infection within the first 10 days after the onset of fever in some SARS patients, but the duration of detectable viraemia and virus shedding is unknown, so RT-PCR tests performed too late could give negative results. Commercial diagnostic tests are now available.

Might SARS coronavirus recombine with other human coronaviruses to produce an even more deadly virus? Fortunately, the coronaviruses of which we are aware indicate that recombination has not occurred between viruses of different groups, only within a group, so recombination does not seem likely given the distance between the SARS virus and HCoV.

There is considerable experience of development of coronavirus vaccines for veterinary purposes — though not all of it is encouraging. On the whole, inactivated coronavirus vaccines induce poor protection. The spike protein alone can induce immunity, but the internal nucleoprotein has also been reported to induce protective immunity. The WHO has recommended that SARS vaccines be developed. The quickest and probably safest to develop would be an inactivated or subunit vaccine. Even if such a vaccine were not fully protective against SARS infection, it might still provide some protection against life-threatening SARS pneumonia.

For more information, contact WHO, CDC and HPA

WUHAN VIRUS

According to Wikipedia, there is a BSL-4 facilitiy in Wuhan:

Wuhan Instutute of Virology

There have been a lot of study on the Coronavirus after the SARS outbreak. In 2015 a big study, led by Fondation Mérieux; The LaCoRIS project took place.

The primary objectives of LaCoRIS project were to measure the incidence rates of acute respiratory diseases and to identify their etiologic pathogens in metropolitan Vientiane.

According an article in Nature.com , there was a collaboration between Wuhan Institute of Virology and Foundation Mérieux.

Many staff from the Wuhan lab have been training at a BSL-4 lab in Lyon, which some scientists find reassuring. And the facility has already carried out a test-run using a low-risk virus.

Project LaCoRIS

In short

The LaCoRIS project aims to determine the incidence as well as the pathogens responsible for respiratory diseases by the prospective study of a Laotian community cohort, that is to say nearly 1,000 households in 25 villages in capital Vientiane.
Goal

This involves measuring the incidence rate of acute respiratory illnesses in Vientiane province and identifying the pathogens responsible for acute respiratory illnesses in urban and peri-urban areas of Laos. The study included: analysis of microbiological data obtained from samples and estimates of the incidence by age and risk factors.

Co-infections and the grouping of pathogens as a function of time and of households are also studied.
activities

Medical surveys were conducted on 433 individuals with respiratory symptoms.
Results

Initial results indicate an incidence rate of 11.6%, with high positivity rates for Streptococcus pneumoniae, followed by Staphylococcus aureus, Influenza A virus, rhinovirus and coronavirus 43.
Partners

Financial:

Naval Medical Research Unit Two (NAMRU-2)

Scientists:

London School of Hygiene & Tropical Medicine, Bangkok (Thailand)
LOMWRU, Microbiology Laboratory of Mahosot Hospital (Laos)
Lao Christophe Mérieux Infectiology Center in Vientiane (Laos)
Laboratory of Emerging Pathogens of Lyon (France)

What happened in Wuhan or what type of Coronavirus this is , is unknown.

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