A rotavirus

A virus is a biological agent that reproduces inside the cells of living hosts. When infected by a virus, a host cell is forced to produce thousands of identical copies of the original virus at an extraordinary rate. Unlike most living things, viruses do not have cells that divide; new viruses are assembled in the infected host cell. But unlike still simpler infectious agents, viruses contain genes, which gives them the ability to mutate and evolve. Over 5,000 species of viruses have been discovered.^[1]

The origins of viruses are unclear: some may have evolved from plasmids—pieces of DNA that can move between cells—while others may have evolved from bacteria. A virus consists of two or three parts: genes, made from either DNA or RNA, long molecules that carry genetic information; a protein coat that protects the genes; and in some viruses, an envelope of fat that surrounds the protein coat and is used, in combination with specific receptors, to enter a new host cell. Viruses vary in shape from the simple helical and icosahedral to more complex structures. Viruses range in size from 20 to 300 nanometres; it would take 33,000 to 500,000 of them, side by side, to stretch to 1 centimetre (0.39 in).

Viruses spread in many ways. Just as many viruses are very specific as to which host species or tissue they attack, each species of virus relies on a particular method for propagation. Plant viruses are often spread from plant to plant by insects and other organisms, known as vectors. Some viruses of animals, including humans, are spread by exposure to infected bodily fluids. Viruses such as influenza are spread through the air by droplets of moisture when people cough or sneeze. Viruses such as norovirus are transmitted by the faecal–oral route, which involves the contamination of hands, food and water. Rotavirus is often spread by direct contact with infected children. The human immunodeficiency virus, HIV, is transmitted by bodily fluids transferred during sex. Others, such as the Dengue virus, are spread by blood-sucking insects.

Viral infections can cause disease in humans, animals and even plants. However, they are usually eliminated by the immune system, conferring lifetime immunity to the host for that virus. Antibiotics have no effect on viruses, but antiviral drugs have been developed to treat life-threatening infections. Vaccines that produce lifelong immunity can prevent some viral infections.

Discovery

Scanning electron micrograph of HIV-1 viruses, coloured green, budding from a lymphocyte

In 1884 the French microbiologist Charles Chamberland invented a filter, known today as the Chamberland filter or Chamberland–Pasteur filter, that has pores smaller than bacteria. Thus he could pass a solution containing bacteria through the filter and completely remove them from the solution.^[2] In the early 1890s the Russian biologist Dmitri Ivanovsky used this filter to study what became known as the tobacco mosaic virus. His experiments showed that extracts from the crushed leaves of infected tobacco plants remain infectious after filtration.

At the same time several other scientists proved that, although these agents (later called viruses) were different from bacteria, they could still cause disease, and they were about one hundredth the size of bacteria. In 1899 the Dutch microbiologist Martinus Beijerinck observed that the agent multiplied only in dividing cells. Having failed to demonstrate its particulate nature, he called it a “contagium vivum fluidum“, a “soluble living germ”.^[3] In the early 20th century the English bacteriologist Frederick Twort discovered viruses that infect bacteria,^[4] and the French-Canadian microbiologist Félix d’Herelle described viruses that, when added to bacteria growing on agar, would lead to the formation of whole areas of dead bacteria. Counting these dead areas allowed him to calculate the number of viruses in the suspension.^[5]

With the invention of the electron microscope in 1931 by the German engineers Ernst Ruska and Max Knoll came the first images of viruses.^[6] In 1935 American biochemist and virologist Wendell Meredith Stanley examined the tobacco mosaic virus and found it to be mostly made from protein.^[7] A short time later, this virus was separated into protein and RNA parts.^[8] A problem for early scientists was that they did not know how to grow viruses without using live animals. The breakthrough came in 1931, when the American pathologist Ernest William Goodpasture and Alice Miles Woodruff grew influenza and several other viruses in fertilised chickens’ eggs.^[9] Some viruses could not be grown in chickens’ eggs, but this problem was solved in 1949 when John Franklin Enders, Thomas Huckle Weller and Frederick Chapman Robbins grew polio virus in cultures of living animal cells.^[10] Over 5,000 species of virus have been discovered.^[11]

Origins

Viruses co-exist with life wherever it occurs. They have probably existed since living cells first evolved. The origin of viruses remains unclear because they do not form fossils, so molecular techniques have been the most useful means of hypothesising how they arose. However, these techniques rely on the availability of ancient viral DNA or RNA but most of the viruses that have been preserved and stored in laboratories are less than 90 years old.^[12]^[13] Molecular methods have only been successful in tracing the ancestry of viruses that evolved in the 20th century.^[14] New groups of viruses might have repeatedly emerged at all stages of the evolution of life.^[15] Three main theories speculate on the origins of viruses:^[15]^[16]

Regressive theory: Viruses may have once been small cells that parasitised larger cells. Over time, genes not required by their parasitism were lost. The bacteria rickettsia and chlamydia are living cells that, like viruses, can reproduce only inside host cells. They lend credence to this theory, as their dependence on parasitism is likely to have caused the loss of genes that enabled them to survive outside a cell.^[17]

Cellular origin theory: Some viruses may have evolved from bits of DNA or RNA that “escaped” from the genes of a larger organism. The escaped DNA could have come from plasmids—pieces of DNA that can move between cells—while others may have evolved from bacteria.^[18]

Coevolution theory: Viruses may have evolved from complex molecules of protein and DNA at the same time as cells first appeared on earth and would have depended on cellular life for many millions of years.^[19]

There are problems with all of these hypotheses: the regressive hypothesis does not explain why even the smallest of cellular parasites do not resemble viruses in any way. The escape hypothesis does not explain the structures of virus particles. The coevolution, or virus-first hypothesis, contravenes the definition of viruses, in that they are dependent on host cells.^[19] But viruses are recognised as ancient and to have origins that pre-date the divergence of life into the three domains.^[20] This discovery has led modern virologists to reconsider and re-evaluate these three classical hypotheses.^[20]^[15]

Structure

A simplified diagram of the structure of a virus

A virus particle, also known as a virion, consists of genes made from DNA or RNA which are surrounded by a protective coat of protein called a capsid.^[21] The capsid is made of many smaller, identical protein molecules which are called capsomers. The arrangement of the capsomers can either be icosahedral (20-sided), helical or more complex. There is an inner shell around the DNA or RNA called the nucleocapsid, which is formed by proteins. Some viruses are surrounded by a bubble of lipid (fat) called an envelope.

Size

Viruses are among the smallest infectious agents, and most of them can only be seen by electron microscopy. Most viruses cannot be seen by light microscopy (in other words, they are sub-microscopic); their sizes range from 20 to 300 nm. They are so small that it would take 30,000 to 750,000 of them, side by side, to stretch to one cm.^[21] By contrast bacterial sizes are typically around 1 micrometre (1000 nm) in diameter, and the cells of higher organisms a few tens of micrometres. Some viruses such as megaviruses and pandoraviruses are relatively large. At around 1 micrometer, these viruses, which infect amoebae, were discovered in 2003 and 2013. They are around a thousand times larger than influenza viruses and the discovery of these “giant” viruses astonished scientists.^[22]

Genes

Genes are made from DNA (deoxyribonucleic acid) and, in many viruses, RNA (ribonucleic acid). The biological information contained in an organism is encoded in its DNA or RNA. Most organisms use DNA, but many viruses have RNA as their genetic material. The DNA or RNA of viruses consists of either a single strand or a double helix.^[23]

Viruses reproduce rapidly because they have only a few genes compared to humans who have 20,000–25,000.^[24] For example, influenza virus has only eight genes and rotavirus has eleven. These genes encode structural proteins that form the virus particle, or non-structural proteins, that are only found in cells infected by the virus.^[25]

All cells, and many viruses, produce proteins that are enzymes called DNA polymerase and RNA polymerase which make new copies of DNA and RNA. A virus’s polymerase enzymes are often much more efficient at making DNA and RNA than the host cell’s.^[26] However, RNA polymerase enzymes often make mistakes, and this is one of the reasons why RNA viruses often mutate to form new strains.^[27]

In some species of RNA virus, the genes are not on a continuous molecule of RNA, but are separated. The influenza virus, for example, has eight separate genes made of RNA. When two different strains of influenza virus infect the same cell, these genes can mix and produce new strains of the virus in a process called reassortment.^[28]

Protein synthesis

Diagram of a typical eukaryotic cell, showing subcellular components. Organelles: (1) nucleolus (2) nucleus (3) ribosome (4) vesicle (5) rough endoplasmic reticulum (ER) (6) Golgi apparatus (7) cytoskeleton (8) smooth ER (9) mitochondria (10) vacuole (11) cytoplasm (12) lysosome (13) centrioles within centrosome (14) virus particle shown to approximate scale

Proteins are essential to life. Cells produce new protein molecules from amino acid building blocks based on information coded in DNA. Each type of protein is a specialist that usually only performs one function, so if a cell needs to do something new, it must make a new protein. Viruses force the cell to make new proteins that the cell does not need, but are needed for the virus to reproduce. Protein synthesis consists of two major steps: transcription and translation.

Transcription is the process where information in DNA, called the genetic code, is used to produce RNA copies called messenger RNA (mRNA). These migrate through the cell and carry the code to ribosomes where it is used to make proteins. This is called translation because the protein’s amino acid structure is determined by the mRNA’s code. Information is hence translated from the language of nucleic acids to the language of amino acids.

Some nucleic acids of RNA viruses function directly as mRNA without further modification. For this reason, these viruses are called positive-sense RNA viruses.^[29] In other RNA viruses, the RNA is a complementary copy of mRNA and these viruses rely on the cell’s or their own enzyme to make mRNA. These are called negative-sense RNA viruses. In viruses made from DNA, the method of mRNA production is similar to that of the cell. The species of viruses called retroviruses behave completely differently: they have RNA, but inside the host cell a DNA copy of their RNA is made with the help of the enzyme reverse transcriptase. This DNA is then incorporated into the host’s own DNA, and copied into mRNA by the cell’s normal pathways.^[30]

Life-cycle

Life-cycle of a typical virus (left to right); following infection of a cell by a single virus, hundreds of offspring are released.

When a virus infects a cell, the virus forces it to make thousands more viruses. It does this by making the cell copy the virus’s DNA or RNA, making viral proteins, which all assemble to form new virus particles.^[31]

There are six basic, overlapping stages in the life cycle of viruses in living cells:^[32]

Attachment is the binding of the virus to specific molecules on the surface of the cell. This specificity restricts the virus to a very limited type of cell. For example, the human immunodeficiency virus (HIV) infects only human T cells, because its surface protein, gp120, can only react with CD4 and other molecules on the T cell’s surface. Plant viruses can only attach to plant cells and cannot infect animals. This mechanism has evolved to favour those viruses that only infect cells in which they are capable of reproducing.
Penetration follows attachment; viruses penetrate the host cell by endocytosis or by fusion with the cell.
Uncoating happens inside the cell when the viral capsid is removed and destroyed by viral enzymes or host enzymes, thereby exposing the viral nucleic acid.
Replication of virus particles is the stage where a cell uses viral messenger RNA in its protein synthesis systems to produce viral proteins. The RNA or DNA synthesis abilities of the cell produce the virus’s DNA or RNA.
Assembly takes place in the cell when the newly created viral proteins and nucleic acid combine to form hundreds of new virus particles.
Release occurs when the new viruses escape or are released from the cell. Most viruses achieve this by making the cells burst, a process called lysis. Other viruses such as HIV are released more gently by a process called budding.

Effects on the host cell[

The range of structural and biochemical effects that viruses have on the host cell is extensive.^[33] These are called cytopathic effects.^[34] Most virus infections eventually result in the death of the host cell. The causes of death include cell lysis (bursting), alterations to the cell’s surface membrane and apoptosis (cell “suicide”).^[35] Often cell death is caused by cessation of its normal activity due to proteins produced by the virus, not all of which are components of the virus particle.^[36]

Some viruses cause no apparent changes to the infected cell. Cells in which the virus is latent and inactive show few signs of infection and often function normally.^[37] This causes persistent infections and the virus is often dormant for many months or years. This is often the case with herpes viruses.^[38]^[39]

Some viruses, such as Epstein-Barr virus, often cause cells to proliferate without causing malignancy;^[40] but some other viruses, such as papillomavirus, are an established cause of cancer.^[41] When a cell’s DNA is damaged by a virus, and if the cell cannot repair itself, this often triggers apoptosis. One of the results of apoptosis is destruction of the damaged DNA by the cell itself. Some viruses have mechanisms to limit apoptosis so that the host cell does not die before progeny viruses have been produced; HIV, for example, does this.^[35]

Viruses and diseases

Norovirus. Ten Norovirus particles; this RNA virus causes winter vomiting disease. It is often in the news as a cause of gastro-enteritis on cruise ships and in hospitals.

Common human diseases caused by viruses include the common cold, the flu, chickenpox and cold sores. Serious diseases such as Ebola and AIDS are also caused by viruses. Many viruses cause little or no disease and are said to be “benign”. The more harmful viruses are described as virulent. Viruses cause different diseases depending on the types of cell that they infect. Some viruses can cause lifelong or chronic infections where the viruses continue to reproduce in the body despite the host’s defence mechanisms.^[42] This is common in hepatitis B virus and hepatitis C virus infections. People chronically infected with a virus are known as carriers. They serve as important reservoirs of the virus. If there is a high proportion of carriers in a given population, a disease is said to be endemic.^[43]

There are many ways in which viruses spread from host to host but each species of virus uses only one or two. Many viruses that infect plants are carried by organisms; such organisms are called vectors. Some viruses that infect animals, including humans, are also spread by vectors, usually blood-sucking insects. However, direct transmission is more common. Some virus infections, such as norovirus and rotavirus, are spread by contaminated food and water, hands and communal objects and by intimate contact with another infected person, while others are airborne (influenza virus). Viruses such as HIV, hepatitis B and hepatitis C are often transmitted by unprotected sex or contaminated hypodermic needles. It is important to know how each different kind of virus is spread to prevent infections and epidemics.^[44]

Diseases of plants

Peppers infected by mild mottle virus

There are many types of plant virus, but often they only cause a loss of yield, and it is not economically viable to try to control them. Plant viruses are often spread from plant to plant by organisms (vectors). These are normally insects, but some fungi, nematode worms and single-celled organisms have been shown to be vectors. When control of plant virus infections is considered economical (perennial fruits, for example) efforts are concentrated on killing the vectors and removing alternate hosts such as weeds.^[45] Plant viruses are harmless to humans and other animals because they can only reproduce in living plant cells.^[46]

Bacteriophages

The structure of a typical bacteriophage

Bacteriophages are viruses that infect bacteria and archaea. The International Committee on Taxonomy of Viruses officially recognises 28 genera of bacteriophages that belong to 11 families.^[47] They are important in marine ecology: as the infected bacteria burst, carbon compounds are released back into the environment, which stimulates fresh organic growth. Bacteriophages are useful in scientific research because they are harmless to humans and can be studied easily. These viruses can be a problem in industries that produce food and drugs by fermentation and depend on healthy bacteria. Some bacterial infections are becoming difficult to control with antibiotics, so there is a growing interest in the use of bacteriophages to treat infections in humans.^[48]

Host resistance

Innate immunity of animals

Animals, including humans, have many natural defences against viruses. Some are non-specific and protect against many viruses regardless of the type. This innate immunity is not improved by repeated exposure to viruses and does not retain a “memory” of the infection. The skin of animals, particularly its surface, which is made from dead cells, prevents many types of viruses from infecting the host. The acidity of the contents of the stomach destroys many viruses that have been swallowed. When a virus overcomes these barriers and enters the host, other innate defences prevent the spread of infection in the body. A special hormone called interferon is produced by the body when viruses are present, and this stops the viruses from reproducing by killing the infected cell and its close neighbours. Inside cells, there are enzymes that destroy the RNA of viruses. This is called RNA interference. Some blood cells engulf and destroy other virus infected cells.^[49]

Adaptive immunity of animals

Two rotavirus particles: the one on the right is coated with antibodies which stop its attaching to cells and infecting them

Specific immunity to viruses develops over time and white blood cells called lymphocytes play a central role. Lymphocytes retain a “memory” of virus infections and produce many special molecules called antibodies. These antibodies attach to viruses and stop the virus from infecting cells. Antibodies are highly selective and attack only one type of virus. The body makes many different antibodies, especially during the initial infection; however, after the infection subsides, some antibodies remain and continue to be produced, often giving the host lifelong immunity to the virus.^[50]

Plant resistance

Plants have elaborate and effective defence mechanisms against viruses. One of the most effective is the presence of so-called resistance (R) genes. Each R gene confers resistance to a particular virus by triggering localised areas of cell death around the infected cell, which can often be seen with the unaided eye as large spots. This stops the infection from spreading.^[51] RNA interference is also an effective defence in plants.^[52] When they are infected, plants often produce natural disinfectants which destroy viruses, such as salicylic acid, nitric oxide and reactive oxygen molecules.^[53]

Resistance to bacteriophages

The major way bacteria defend themselves from bacteriophages is by producing enzymes which destroy foreign DNA. These enzymes, called restriction endonucleases, cut up the viral DNA that bacteriophages inject into bacterial cells.

Prevention and treatment of viral disease in humans and other animals[edit]

Vaccines

The structure of DNA showing the position of the nucleosides and the phosphorus atoms that form the “backbone” of the molecule

Vaccination is a way of preventing diseases caused by viruses. Vaccines simulate a natural infection and its associated immune response, but do not cause the disease. Their use has resulted in the eradication of smallpox and a dramatic decline in illness and death caused by infections such as polio, measles, mumps and rubella.^[54] Vaccines are available to prevent over fourteen viral infections of humans^[55] and more are used to prevent viral infections of animals.^[56] Vaccines may consist of either live or killed viruses.^[57] Live vaccines contain weakened forms of the virus, but these vaccines can be dangerous when given to people with weak immunity. In these people, the weakened virus can cause the original disease.^[58] Biotechnology and genetic engineering techniques are used to produce “designer” vaccines that only have the capsid proteins of the virus. Hepatitis B vaccine is an example of this type of vaccine.^[59] These vaccines are safer because they can never cause the disease.^[57]

Antiviral drugs

Since the mid 1980s, the development of antiviral drugs has increased rapidly, mainly driven by the AIDS pandemic. Antiviral drugs are often nucleoside analogues, which are molecules very similar, but not identical to DNA building blocks. When the replication of virus DNA begins, some of these fake building blocks are incorporated. As soon as that happens, replication stops prematurely—the fake building blocks lack the essential features that allow the addition of further building blocks. Thus, DNA production is halted, and the virus can no longer reproduce.^[60] Examples of nucleoside analogues are aciclovir for herpes virus infections and lamivudine for HIV and hepatitis B virus infections. Aciclovir is one of the oldest and most frequently prescribed antiviral drugs.^[61]

The structure of the DNA base guanosine and the antiviral drug aciclovir

Other antiviral drugs target different stages of the viral life cycle. HIV is dependent on an enzyme called the HIV-1 protease for the virus to become infectious. There is a class of drugs called protease inhibitors, which bind to this enzyme and stop it from functioning.^[62]

Hepatitis C is caused by an RNA virus. In 80% of people infected, the disease becomes chronic, and they remain infectious for the rest of their lives unless they are treated. There is an effective treatment that uses the nucleoside analogue drug ribavirin combined with interferon.^[63] Treatments for chronic carriers of the hepatitis B virus by a similar strategy using lamivudine and other anti-viral drugs have been developed.^[64] In both diseases, the drugs stop the virus from reproducing and the interferon kills any remaining infected cells.

HIV infections are usually treated with a combination of antiviral drugs, each targeting a different stage in the virus’s life-cycle. There are drugs that prevent the virus from attaching to cells, others that are nucleoside analogues and some poison the virus’s enzymes that it needs to reproduce.^[62] The success of these drugs is proof of the importance of knowing how viruses reproduce.

Role in ecology

Viruses are the most abundant biological entity in aquatic environments^[65]—there are about one million of them in a teaspoon of seawater^[66]—and they are essential to the regulation of saltwater and freshwater ecosystems.^[67] Most of these viruses are bacteriophages, which are harmless to plants and animals. They infect and destroy the bacteria in aquatic microbial communities and this is the most important mechanism of recycling carbon in the marine environment. The organic molecules released from the bacterial cells by the viruses stimulate fresh bacterial and algal growth.^[68]

Microorganisms constitute more than 90% of the biomass in the sea. It is estimated that viruses kill approximately 20% of this biomass each day and that there are fifteen times as many viruses in the oceans as there are bacteria and archaea. Viruses are mainly responsible for the rapid destruction of harmful algal blooms,^[69] which often kill other marine life.^[70] The number of viruses in the oceans decreases further offshore and deeper into the water, where there are fewer host organisms.^[71]

Their effects are far-reaching; by increasing the amount of respiration in the oceans, viruses are indirectly responsible for reducing the amount of carbon dioxide in the atmosphere by approximately 3 gigatonnes of carbon per year.^[71]

Marine mammals are also susceptible to viral infections. In 1988 and 2002, thousands of harbour seals were killed in Europe by phocine distemper virus.^[72] Many other viruses, including caliciviruses, herpesviruses, adenoviruses and parvoviruses, circulate in marine mammal populations.^[71]

References …

Bibliography

Collier, Leslie; Balows, Albert; Sussman Max (1998) Topley and Wilson’s Microbiology and Microbial Infections ninth edition, Volume 1, Virology, volume editors: Mahy, Brian and Collier, Leslie. Arnold. ISBN 0-340-66316-2
Shors, Teri (2017). Understanding Viruses. Jones and Bartlett Publishers. ISBN 978-1284025927

External links

Virus Pathogen Resource – Genomic and other research data about human pathogenic viruses
Influenza Research Database – Genomic and other research data about influenza viruses

https://en.wikipedia.org/wiki/Introduction_to_viruses

2019–20 Wuhan coronavirus outbreak

Genomic information
NCBI genome ID	MN908947
Genome size	30473 bp
Year of completion	2020

2019–20 outbreak of novel coronavirus
	Location of Wuhan, the epicentre of the outbreak, in China.
Date	12 December 2019 – present
Location	Origin: Wuhan, Hubei, China
Casualties

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An outbreak of the novel coronavirus 2019-nCoV was initially identified during mid-December 2019 in the city of Wuhan in central China, as an emerging cluster of people with pneumonia with no clear cause, which was linked primarily to stallholders who worked at the Huanan Seafood Market, which also sold live animals. Chinese scientists subsequently isolated a new strain of the coronavirus – given the initial designation of 2019-nCoV – which has been found to be at least 70 percent similar in genome sequence to SARS-CoV. With the development of a specific diagnostic PCR test for detecting the infection, a number of cases were confirmed in people directly linked to the market and in those who were not directly associated with it. Whether this virus is of the same severity or lethality as SARS is unclear.^[13]^[14]^[15]^[16]

On 20 January 2020, Chinese premier Li Keqiang urged decisive and effective efforts to prevent and control the pneumonia epidemic caused by a novel coronavirus.^[17] As of 23 January 2020, 18 deaths have occurred, all in China, and there is evidence of human-to-human transmission. Extensive testing has revealed over 600 confirmed cases, some of whom are healthcare workers.^[18]^[19]^[20] Confirmed cases have also been reported in Thailand, South Korea, Japan, Taiwan, Macau, Hong Kong, the United States,^[19] Singapore,^[9] and Vietnam.^[7]

On 23 January 2020, the WHO decided against declaring the outbreak a public health emergency of international concern.^[21] The WHO had previously warned that a wider outbreak was possible,^[22] and there were concerns of further transmission during China’s peak travel season around the Chinese New Year.^[15]^[23] The sudden increase in occurrences of the disease has raised questions relating to wildlife trade, uncertainties surrounding the virus’s ability to spread and cause harm,^[24] whether the virus has been circulating for longer than previously thought, its origin and the possibility of the outbreak being a super-spreader event.^[16]^[25]^[23]^[26]^[27]

The first suspected cases were reported on 31 December 2019,^[28] with the first instances of symptomatic illness appearing just over three weeks earlier on 8 December 2019.^[29] The market was closed off on 1 January 2020, and people who showed signs and symptoms of the coronavirus infection were isolated.^[28] Over 700 people, including more than 400 healthcare workers who came into close contact with possibly infected individuals, were initially monitored.^[30] After the development of a specific diagnostic PCR test for detecting the infection, the presence of 2019-nCoV was subsequently confirmed in 41 people in the original Wuhan cluster,^[13]^[31] of which two were later reported to be a married couple, one of whom had not been present in the marketplace, and another three who were members of the same family that worked at the marketplace’s seafood stalls.^[32]^[33] The first confirmed death from the coronavirus infection occurred on 9 January 2020.^[34]

On 23 January 2020, Wuhan was placed under quarantine, in which all public transport in and out of Wuhan have been suspended.^[35] The cities of Huanggang, Ezhou, Chibi and Zhijiang, adjacent to Wuhan, will also be placed under a similar quarantine from 24 January 2020 onwards.^[36]^[37]

Context[edit]

Replication cycle of a coronavirus

As the inaugural cluster of cases with “pneumonia of unknown cause” was linked to a wholesale animal and fish market, which had a thousand stalls selling chickens, pheasants, bats, marmots, venomous snakes, spotted deer and the organs of rabbits and other wild animals (Ye wei), i.e. bushmeat, the immediate hypothesis was that this was a novel coronavirus from an animal source.^[14]^[38]^[39]^[40]

Coronaviruses mainly circulate among animals, but have been known to evolve and infect humans, as has been seen with SARS, MERS and four other coronaviruses found in humans which cause mild respiratory symptoms like in the common cold. All six can spread from human to human.^[41]^[42] In 2002, with an origin in civet horseshoe bats from live animal markets, an outbreak of SARS started in mainland China, and with the help of a few super-spreaders and international air travel, reached as far as Canada and the United States, resulting in over 700 deaths worldwide. The last case occurred in 2004.^[41]^[43]^[44] At the time, China was criticised by the WHO for its handling of the epidemic.^[45] Ten years after the onset of SARS, the dromedary-camel-related coronavirus, MERS, resulted in 750 deaths in over 27 countries.^[41] The Wuhan outbreak’s association with a large seafood and animal market, has led to the presumption of the illness having an animal source.^[42] This has resulted in the fear that it would be similar to the previous SARS outbreak,^[43]^[46] a concern exacerbated by the expectation of a high numbers of travelers for Chinese New Year, which begins on 25 January 2020.^[47]

Wuhan is the capital of Hubei province and is the seventh-largest city in China, with a population of more than 11 million people. It is a major transportation hub of the country, long known in China as “Nine Provinces’ Thoroughfare” (九省通衢). It is approximately 700 miles (1,100 km) south of Beijing,^[48] 500 miles (800 km) west of Shanghai, and 600 miles (970 km) north of Hong Kong.^[49] It is considered today as the political, economic, financial, commercial, cultural and educational center of Central China. Direct flights from Wuhan also connect with Europe: six flights weekly to Paris, three weekly to London, and five weekly to Rome.^[50]

Since 2000, the World Health Organization has coordinated international reactions against several new diseases such as MERS, SARS (2003–2004), 2009 swine flu and others.

Phylogenetics[edit]

Sequences of Wuhan betacoronavirus show similarities to betacoronaviruses found in bats; however, the virus is genetically distinct from other coronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS) and Middle East respiratory syndrome-related coronavirus (MERS).^[51] Like SARS-CoV, it is a member of Beta-CoV lineage B.^[52]

Five genomes of the novel coronavirus have been isolated and reported including BetaCoV/Wuhan/IVDC-HB-01/2019, BetaCoV/Wuhan/IVDC-HB-04/2020, BetaCoV/Wuhan/IVDC-HB-05/2019, BetaCoV/Wuhan/WIV04/2019, and BetaCoV/Wuhan/IPBCAMS-WH-01/2019 from the China CDC National Institute for Viral Disease Control and Prevention, Institute of Pathogen Biology, and Wuhan Jinyintan Hospital.^[51]^[53]^[54] Its RNA sequence is approximately 30 kbp in length.^[51]

On 22 January 2020, scientists from Peking University, Guangxi Traditional Chinese Medical University, Ningbo University and Wuhan Biology Engineering College published an article, concluded that snakes were the most likely natural reservoir for the 2019-nCoV.^[55]^[56] This is disputed by some other scientists, who argue that the wildlife reservoir must be bird or mammal.^[56]

Epidemiology[edit]

Confirmed cases outside of mainland China include three women and one man in Thailand, one man in Japan, one woman in South Korea, one woman in Taiwan, two men in Hong Kong, two men in Vietnam, one nurse in Saudi Arabia, one man in Singapore, one man in Macau and one man in the United States.^[10]^[57]^[58]^[59]^[25] The figures are supported by experts including Michael Osterholm.^[60]

On 17 January, an Imperial College group in the UK published an estimate that there had been 1,723 cases (95% confidence interval, 427–4,471) with onset of symptoms by 12 January 2020. This was based on the pattern of the initial spread to Thailand and Japan. They also concluded that “self-sustaining human-to-human transmission should not be ruled out”.^[61]^[62] As further cases came to light, they later recalculated that “4,000 cases of 2019-nCoV in Wuhan City… had onset of symptoms by 18th January 2020”.^[18]^[20] A Hong Kong University group has reached a similar conclusion as the earlier study, with additional detail on transport within China.^[63]

On 20 January, China reported a sharp rise in cases with nearly 140 new patients, including two people in Beijing and one in Shenzhen.^[64] As of 23 January, the number of laboratory-confirmed cases stands at 650, including 633 in Mainland China, 4 in Thailand, 3 in Hong Kong, 2 in Macau, 2 in Vietnam, one in Japan, one in South Korea, one in Taiwan, one in Saudi Arabia, one in Singapore and one in the United States.^[12]^[65]^[66]^[67]^[68]^[69]

Chronology[edit]

The fourth shut-down city[edit]

Chinese government announced at 23:00 (UTC+8) 23 January to shut down Chibi City effective at 00:00 on 24 January, preceded by the prefecture-level cities of Huanggang, Ezhou, and Wuhan.^[70]

Reportedly, Wuhan City government has demanded a state-owned enterprise (中建三局集团) to re-construct an accommodation in Wuhan into a Virus Therapy Center at the fastest speed comparable to that during the SARS outbreak in 2003.^[71]

An epidemiologist and SARS virologist with teams consisting of medical specialists who just flew back to Hong Kong after their one-day inspection in Wuhan told correspondants that the Wuhan Outbreak is at least 10 times larger than that of SARS, calling people to stay away from Wuhan as soon as possible.^[72]^[73]^[74]^[75]

Some posts on Weibo showed that hospital in Wuhan has already overloaded with thousands of people with fever and were highly critical of the reliability of the figures from the Chinese government although such posts are now deleted due to unknown reasons.^[76]

Global: reported cases and responses[edit]

Number of cases in Greater China

Map of the 2019-nCoV outbreak (as of 23 January 2020):

Country of origin (Mainland China)

Confirmed cases reported

(The Saudi Arabia case is uncertain.)

Suspected cases reported

Since 31 December 2019, some regions and countries near China tightened their screening of selected travellers.^[16] The US Centers for Disease Control and Prevention (CDC) later issued a Level 1 travel watch.^[38]^[77] Guidances and risk assessments were shortly posted by others including the European Centre for Disease Prevention and Control and Public Health England.^[78] In China, airports, railway stations and coach stations installed infrared thermometers. People with fevers are subsequently taken to medical institutions after being registered and given masks.^[65]

Top 20 flight routes from Wuhan with data on the Infectious Disease Vulnerability Index for each country

An analysis of air travel patterns was used to map out and predict patterns of spread, and was published in the Journal of Travel Medicine in mid-January 2020. Based on information from the International Air Transport Association (2018), Bangkok, Hong Kong, Tokyo, and Taipei had the largest volume of travellers from Wuhan. Dubai in the United Arab Emirates and Sydney and Melbourne in Australia were also reported as popular destinations for people traveling from Wuhan. Using the validated tool, the Infectious Disease Vulnerability Index (IDVI), to assess ability of managing a disease threat, Bali was reported as least able in preparedness, while cities in Australia were most able.^[29]^[79]

Confirmed cases[edit]

Hong Kong[edit]

Reported suspected cases of novel coronavirus in Hong Kong

Hong Kong’s Centre for Health Protection (CHP) added the term “unidentified pneumonia” to their list of notifiable diseases to expand their authority on quarantine. The Hong Kong government also shortened hospital visits and made it a requirement for visitors to wear face masks. Screening was tightened at airports and train stations with connections to Wuhan.^[44] In the first week of 2020, 30 unwell travelers from Wuhan were tested. Most were found to be positive for other respiratory viruses.^[77]^[80] On 22 January 2020, a mainlander man, age 39, who traveled from Shenzhen developed symptoms of pneumonia. The man had been to Wuhan in the previous month. He tested positive for 2019-nCoV and was hospitalised in the Queen Elizabeth Hospital in Kowloon. A 56-year old man from Ma On Shan, who had visited Wuhan, had also tested positive for 2019-nCoV, raising the number of confirmed cases to two.^[5]^[81]

The Hong Kong government designated the Lady MacLehose Holiday Village in Sai Kung as a quarantine centre. On 23 January 2020, three people who had come into close contact with the two aforementioned cases were quarantined, including two medical workers and a visitor from Australia.^[82]

Japan[edit]

A 30-year-old Chinese national who had previously travelled to Wuhan developed a fever on 3 January 2020 and subsequently returned to Japan on 6 January. He tested positive for 2019-nCoV during a hospital admission between 10 and 15 January 2020. He had not visited the Huanan Seafood Market, but possibly had close contact with an affected person in Wuhan.^[58]^[83]

Macau[edit]

As of 22 January 2020, Macau has confirmed two cases of 2019-nCoV, that of a 52-year-old woman, and a 66-year-old man, both from Wuhan.^[6]

Singapore[edit]

Singapore’s Ministry of Health (MOH) issued a health advisory on the pneumonia outbreak on 2 January 2020, and implemented temperature checks for passengers arriving in Changi Airport from Wuhan the following day.^[84] On 20 January 2020, temperature screening at Changi Airport was extended to all travellers coming from China. In addition, individuals with pneumonia who had travelled to Wuhan within 14 days before the onset of symptoms will be isolated in hospital. MOH also issued a reminder to hospitals and general practitioners to be vigilant for cases with pneumonia who have recently traveled to Wuhan.^[85]^[86] On 22 January, quarantine measures were extended to travelers who arrived from China and display symptoms.^[87] Three more suspected cases were detected on 22 January 2020. At the same time, the MOH began to form a multi-ministry taskforce to tackle the virus. The MOH also advised against non-essential trips to Wuhan^[88] and later expanded the travel advisory to the whole of Hubei.^[89]

The first case was confirmed on 23 January 2020 involving a 66-year-old China national from Wuhan who flew from Guangzhou via China Southern Airlines flight CZ351 with 9 companions and stayed at Shangri-La’s Rasa Sentosa Resort and Spa. Contact tracing of the hotel staff and flight passengers has begun.^[90] Preliminary tests also showing positive results for a 53-year-old. Another 28 suspected cases were detected as a result of enhanced testing. Border control measures were enhanced and extended to land and sea checkpoints from 24 January 2020.^[9]

South Korea[edit]

A suspected case was reported in South Korea on 8 January 2020, with the person isolated as a result.^[91] There have been four suspected cases since then, and a confirmed case on 20 January 2020.

Taiwan[edit]

On 21 January 2020, the first case in Taiwan was confirmed in a 50-year-old woman who just returned to Taoyuan International Airport from her teaching job in Wuhan.^[11] She reported her signs to the patrols on her own initiative and was then sent hospitalised upon arrival without formal domestic entry and is being treated in quarantine.^[11]

Among the 4 suspected cases reported, 3 have been tested negative in the initial screenings.^[38]^[77]^[92]

Thailand[edit]

In Thailand, screening passengers arriving from Wuhan at four different airports began on 3 January 2020, and a number of suspected cases have been found to have other common respiratory conditions.^[59]^[93]

On 13 January 2020, Thailand witnessed the first confirmed case of 2019-nCoV outside China. The affected individual was a 61-year-old Chinese woman who is a resident of Wuhan; she had not visited the Huanan Seafood Market, but was noted to have been to other markets. She developed a sore throat, fever, chills and a headache on 5 January, flew directly with her family and a tour group from Wuhan to Suvarnabhumi airport in Bangkok on 8 January, where she was detected using thermal surveillance and was hospitalised that same day. Four days later, using RT-PCR, she tested positive for the new coronavirus.^[29]^[94]^[95]^[94]

Thailand’s second case occurred in a 74-year-old woman who arrived in Bangkok on a flight from Wuhan on 17 January.^[57]

On 21 January 2020, an 18-year-old male patient suspected who arrived in Chiang Mai from Wuhan was hospitalized with a high fever. Blood samples were sent to Bangkok for further analysis.^[96]^[97]

On 22 January 2020, the Thai Ministry of Public Health announced a report for two additional confirmed cases of infection found in Thailand. The third was a 68-year-old man, a Chinese tourist like previous cases. The fourth was a 73-year-old Thai woman, who had returned from Wuhan, the first case for Thai citizen.^[98]^[99]

United States[edit]

The first confirmed case of the new coronavirus in the United States, a man in his 30s from Snohomish County, Washington, was announced by the CDC on 21 January 2020.^[100] The man had traveled from Wuhan to Seattle–Tacoma International Airport on 15 January and reported four days later to the Providence Regional Medical Center in Everett, Washington, after feeling ill with symptoms of pneumonia.^[12]^[101]^[102]

Between 60,000 and 65,000 people travel from Wuhan to the United States every year, with January being a peak.^[103] At San Francisco International Airport, Los Angeles International Airport, and John F. Kennedy International Airport in New York City, arriving passengers began to be screened for symptoms of the virus ahead of the Chinese New Year peak travel season. As the number of cases started to increase, O’Hare International Airport in Chicago and Hartsfield–Jackson Atlanta International Airport have also started screening arriving passengers.^[104]^[105]

Vietnam[edit]

Two suspected cases of pneumonia were detected on 14 January 2020 after two Chinese tourists arrived in Vietnam through Da Nang International Airport with a fever. The tourists were quarantined, and later released after having tested negative for the virus.^[106]

Prime Minister of Vietnam Nguyễn Xuân Phúc has ordered relevant ministries, including Health, Transport, Foreign Affairs, Public Security, Defence, Information and Communications, Culture, Sports and Tourism, Labour, Invalids and Social Affairs, Agriculture and Rural Development, to deploy measures to prevent and counter the spread of the disease into Vietnam, as well as to warn Vietnamese citizens not to visit the epidemic areas.^[107] Deputy minister Đỗ Xuân Tuyên said that Vietnam is considering to close border with China as a necessary countermeasure.^[108] Saigon Tourist announced that it has cancelled all tours to or transit in Wuhan.^[109]

The first two cases of confirmed infected were hospitalized on 22 January and treated at Cho Ray Hospital, Ho Chi Minh City. One case is a Chinese man travelling from Wuhan to Hanoi to visit his son living in Vietnam. The second is the man’s son who is believed to have contracted the disease from his father.^[110]

Suspected cases[edit]

As of 22 January, Nepal, Hong Kong and Taiwan were monitoring suspected cases, per the ECDC.

Brazil[edit]

The Health Secretary of the state of Minas Gerais reported on 22 January a suspected case from a 35 year old Brazilian woman who arrived in Belo Horizonte on 18 January from Shanghai, who self-reportedly did not visit Wuhan. Medical tests are underway to confirm the case.^[111]^[112]

Canada[edit]

The Canada Border Services Agency (CBSA) has implemented signage in Toronto, Vancouver and Montreal airports to raise awareness of the virus and has added a health screening question to the electronic kiosks for passengers arriving from central China; however, there are no direct flights from Wuhan to Canada.^[113]^[114]

As of 22 January, six people were put under observation in Quebec after showing signs of a respiratory virus since recently returning from China.^[115] On the following day, the Minister of Health Patty Hajdu said that five or six people were being monitored for signs of coronavirus, including at least one person in Quebec and another in Vancouver.^[116]

Malaysia[edit]

One patient, a tourist from China, has been placed in isolation ward at Queen Elizabeth Hospital in Sabah for suspected infection of the virus.^[117]^[118]

Nepal[edit]

A suspected case was reported in Nepal on 16 January 2020. The Nepali national had returned from Wuhan and was quarantined in Kathmandu.^[119]

Philippines[edit]

One suspected case involved a five-year old child from Wuhan who had arrived in Cebu City on 12 January 2020. Samples from the child were sent to the Research Institute for Tropical Medicine in Muntinlupa for testing. The case tested positive for a “non-specific pancorona virus”, although it has yet to be determined if the pathogen is the 2019-nCoV.^[120]

Samples from the child had been sent to a laboratory in Australia for further testing and the authorities are awaiting the results. Three other travellers from China were checked by authorities at another airport, but they did not show symptoms that corresponded with the warning issued by the World Health Organization about the virus from Wuhan.^[121] Another two suspected cases tested negative for the virus, and were allowed to return home.^[122]

The outbreak has prompted urging from at least a member of the House of Representatives. Muntinlupa representative Ruffy Biazon sent a letter dated on 22 January 2020 to the Civil Aviation Authority of the Philippines (CAAP) to suspend flights from Wuhan to any part of the Philippines. Royal Air Charter Service operates direct flights from Wuhan to Kalibo in Aklan.^[123]

Russia[edit]

On 22 January 2020, a 23 year old Russian man arriving in Pulkovo Airport, St. Petersburg, from Shanghai was hospitalised.^[124]

United Kingdom[edit]

Four suspected cases underwent testing in Scotland on 23 January: three in Edinburgh and one in Glasgow. All had recently been to Wuhan.^[125] Heathrow Airport has tightened surveillance of the three direct flights that it receives from Wuhan every week. Each of these flights will be met by a Port Health team, comprising principal port medical inspector, port health doctor, administrative support, and team leader. In addition, all airports in the UK will have written guidance available for unwell travellers.^[78]

United States

Local health officials in Brazos County Texas are investigating a suspected case of 2019-nCoV. The patient is a Texas A&M student who had recently travelled from Wuhan, China, where the coronavirus originated. The patient is currently in isolation at his home, while the precautionary testing is being done. Results of the testing are expected to be completed by 24 January.^[126]

On 22 January an American Airlines passenger arriving at Los Angeles International Airport from Mexico City received medical attention upon arrival, American spokesman Curtis Blessing said. He was transported to a medical center for disease control for precautionary reasons. ^[127]

Prevention in other countries

Bangladesh

Enhanced screening measures have been set up at Shahjalal International Airport in Bangladesh.^[128]

Cambodia

The Cambodian Ministry of Health has taken preventive measures by installing thermal scanners at Phnom Penh International Airport, Siem Reap International Airport and Sihanouk International Airport to prevent the entry of the novel coronavirus (2019-nCoV). The thermal scanners are operated by the quarantine service personnel sent by the Ministry of Health. Currently, no case has been detected yet.^[129]

India

The Government of India issued a travel advisory to its citizens, particularly for Wuhan, where about 500 Indian medical students study.^[130]

It was announced that passengers arriving at Chhatrapati Shivaji International Airport from China would undergo thermal screening.^[131] Later, the procedures were extended to six other major international airports.^[132]

Malaysia

The director general of the Ministry of Health, Noor Hisham Abdullah, said thermal scanners were being used to screen travellers at border points, and that the Malaysian health authorities were placed on high alert following the global outbreaks.^[133]

Netherlands

Airlines and the main international airport Schiphol are, as of 22 January, not taking extra measures yet against the spread of the virus, stating the lack of direct flights from or to Wuhan.^[134]

North Korea

As a precaution against the virus, North Korea is to temporarily ban foreign tourists until the government feels that the virus is well under control.^[135]

Panama

The Panamanian government has enhanced its sanitary control measures at all ports of entry, in preparation for the arrival of the virus.^[136]

Sri Lanka

The Ministry of Health in Sri Lanka informed the Quarantine Unit at Bandaranaike International Airport to screen passengers for symptoms. Additionally, the ministry warned that infants, children, pregnant mothers, elderly and people who suffer from chronic diseases among other issues should avoid visiting crowded places when possible.^[137]

Turkey

The Ministry of Health announced that Turkey has arranged quarantine rooms, inspection centres and thermal cameras for screening at the airports as added precautions, even though the World Health Organization does not consider them necessary for the country.^[138]

United Arab Emirates

On 23 January 2020, Dubai Airport announced that travelers arriving directly from China would have their temperatures screened.^[139]

Symptoms at Clinical presentation

Reported symptoms have included fever in 90% of cases,^[13] fatigue and a dry cough in 80%,^[13]^[140] and shortness of breath in 20%, with respiratory distress in 15%.^[38]^[77]^[140] Chest x-rays have revealed signs in both lungs.^[38]^[77] Vital signs were generally stable at the time of admission of those hospitalised.^[140] Blood tests have commonly shown low white blood cell counts (leucopenia and lymphopenia).^[13]

Testing

On 15 January 2020, the WHO published a protocol on diagnostic testing for 2019-nCoV, developed by a virology team from Charité Hospital in Germany.^[141]

Prevention and manageme

Airport screening

2019-nCoV does not currently have an effective medicine treatment or vaccine, though efforts to develop some are underway.^[142]^[143] Its symptoms include, among others, fever, breathing difficulties and coughing,^[144] which have been described as “flu-like“.^[145] To prevent infection, the WHO recommends “regular hand washing, covering mouth and nose when coughing and sneezing… [and] avoid[ing] close contact with anyone showing symptoms of respiratory illness (such as coughing and sneezing).”^[51] Though there are no specific treatments for general human coronaviruses, the U.S. CDC provides generic advice that an infected person can relieve their symptoms by taking regular flu medications, drinking fluids and resting.^[146] Some countries require people to report flu-like symptoms to their doctor, especially if they have visited mainland China.^[147]

The situation in Wuhan is being monitored with respect to the forthcoming third round of the 2020 AFC Women’s Olympic Qualifying Tournament, some of which is due to be played there over the course of the tournament’s span from 3 February 2020 to 9 February 2020.^[148] On 22 January 2020, the AFC announced that it would be moving the Group A matches previously scheduled to be played in Wuhan—which included the respective squads from Australia, China PR, Taiwan and Thailand—to Nanjing instead due to the coronavirus outbreak.^[149]

An effective quarantine on travel in and out of Wuhan was imposed from 23 January 2020, 10:00 onwards. Flights and trains in and out of Wuhan, public buses, the metro system and long-distances coaches were suspended until further notice. The move is an effort to stop the spread of the virus out of Wuhan, and to ensure the health and safety of the people, according to China’s Xinhua News Agency. Large-scale gatherings and group tours were also required to be suspended.^[150] Various logistic issues have occurred after the quarantine, including rising food prices^[151] and difficulty for medical staff commuting to the hospital.^[152]

References …

External links

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