Knowns and Unknowns of the Coronavirus

The Princess Diamond cruise ship may become the source of the major contagion outside of China (AFP)

 

The world is witnessing the coronavirus SARS-CoV-2 outbreak in real time: how dangerous and contagious is it? There are many certainties but scientists are still asking questions.


 

What we know for sure


Common initial symptoms are fever and cough.

Some infected people have little or no symptoms, others become seriously ill or even die from the consequences of Covid 19 pneumonia. The most common symptoms are fever, cough and shortness of breath. But muscle and headache can also occur, diarrhea seems to be rare (The Lancet: Chen et al., 2020). Doctors who use computer tomography to examine patients in the hospital see signs of bilateral pneumonia in many cases. In a study that has not yet been reviewed by experts, it was found that pneumonia sufferers had to be treated more often in an intensive care unit than other corona patients, they also needed artificial ventilation and their risk of dying was higher.

 

The new virus is related to SARS and MERS.

The new pathogen had the provisional name 2019-nCoV for weeks, meanwhile scientists and researchers have officially named it. Because it resembles the causative agent of SARS' severe acute respiratory syndrome, the virus is now called SARS-CoV-2. CoV stands for Coronavirus, the name of the virus family. Such pathogens can infect humans and various animals. In humans, they sometimes trigger harmless colds and even fatal illnesses. Sometimes there are no symptoms despite infection. In addition to SARS, coronaviruses can also cause MERS, which stands for Middle East Respiratory Syndrome, a respiratory disease that first appeared on the Arabian Peninsula. During the largest SARS epidemic to date in 2002 and 2003, 774 people died worldwide. More than 800 people have died of MERS since 2012.
The new pathogen can also cause severe pneumonia in humans. The WHO has given the disease caused by SARS-CoV-2 the name Covid-19. That stands for Coronavirus Disease 2019.


The first major outbreak occurred in Wuhan.

 

Where did the new corona virus come from?

The most often repeated history of a new type of Coronavirus 2019-nCoV concerns food market in Wuhan. According to that version, the virus first appeared in December 2019 on a fish and wildlife market in central China's Wuhan. But this is only one of the hypotheses which recently has been contested even by the Chinese doctors and scientist.

The lung disease Covid-19 was first detected in the central Chinese city of Wuhan (The Lancet: Huang et al. 2020). From there, the virus has spread further. A fish and wild animal market, where many different live and dead animals were offered, apparently played a central role in the spread of SARS-CoV-2: Of 99 patients who were treated for infection at the beginning of the outbreak in Wuhan, 49 were associated with the market (The Lancet: Chen et al., 2020). Most of them had worked there, for example as sales staff or managers.
The authors of the same article in Lancet observed that at least one person who had not any links to the exotic food market in Wuhan also died due to the coronavirus in December 2019.

Several tens of thousands of cases of infection are now known, the majority of them in China. In recent days more than 25 other countries have now reported infections with the new corona virus. At the beginning of February, the first death outside of China occurred in the Philippines. The World Health Organisation regularly publishes the latest outbreak figures on its website. But the credibility of that data has recently been challenged by the analysts.

 

It is conceivable that there was an intermediate host in the infection chain.


 

What is almost certain?

 

The period between infection and the first symptoms is roughly known.

The incubation period is the time between the infection and the appearance of the first symptoms. According to current data, it averages around five days (The New England Journal of Medicine: Li et al., 2020). In this study, however, it was 12.5 days in five percent of the cases. In Germany, contacts of people with confirmed infection must be quarantined for 14 days. Thus, according to the RKI, "a wave of diseases in Germany is to be delayed and its dynamics weakened".

The RKI has also developed criteria for when a sick person can be released from the hospital. The earliest is ten days after the onset of symptoms, provided he has been free from fever for at least 48 hours and has had no other symptoms of the lung disease Covid-19 for at least 24 hours. In addition, two DNA tests that can detect the coronavirus in the genome must have been negative. Christian Drosten, head of the Institute of Virology at the Charité in Berlin, points out, however, that this PCR test (polymerase chain reaction) is hypersensitive and detects the virus even when the patient is actually no longer infectious. If more people in Germany become infected with the corona virus over time, Drosten will have to reconsider the hitherto strict discharge criteria.

 

It is conceivable that there was an intermediate host in the infection chain.



 

The virus is transmitted like a flu

Like other corona viruses or the influenza virus, the flu, the new pathogen is probably primarily transmitted via the air (Journal of Hospital Infection: Kampf et al, 2020). When an infected person exhales, sneezes or coughs, they spread microscopic droplets in the air that may contain the virus. A smear infection is also possible: if someone sneezes in the hands and then touches a door handle, for example, a person can become infected, who then takes the same handle in his hand and then touches his mouth with his hand. However, the main transmission pathway is assumed to be droplet infection, says the virologist Schmidt-Chanasit.

 

The virus can also multiply in the throat

Previous data indicate that the virus spreads more easily than the SARS pathogen. This should also be due to the fact that SARS-CoV-2 can obviously reproduce quite well in the throat - the SARS pathogen, however, only affects the deep airways. At first, researchers assumed that this was also the case with SARS-CoV-2, because the virus uses the same binding site (the ACE2 receptor) to slip into the cells of its host. However, researchers have found structures on the surface of the pathogen that also carry influenza viruses and that could allow the new virus to multiply effectively in the throat, said Charité virologist Christian Drosten. "A virus that jumps from lung to lung has a long way from person to person. But one that jumps from neck to neck is transmitted on the subway."

 

Children are not immune to the coronavirus infection

The research team does not assume that children are immune to SARS-CoV-2. Babies are likely to have less contact with potential carriers or develop symptoms that are so mild that an illness with Covid-19 remains undetected. "Children can pass on the pathogen, but in many cases do not appear immediately to be ill themselves," said Drosten. This is a big difference to influenza and other respiratory diseases, which often affect children at first. Why this seems to be different with SARS-CoV-2 is still unclear.

According to current knowledge, newborn children also do not necessarily become infected through their mother if she has been infected with the corona virus in late pregnancy. This is the case, for example, with the Zika virus, which became known through an outbreak in 2016 and can lead to brain malformations in unborn children. A research team from China and the United States examined nine women who had late pregnancy Covid-19 and their children (The Lancet: Chen et al. 2020). In six of the patients the amniotic fluid, umbilical cord blood and breast milk as well as a throat swab of their newborns were tested on SARS-CoV-2. None of the samples contained the virus.

 

Bats were originally home to the virus

"It is very certain that the virus was originally circulated in bats," says the virologist Jonas Schmidt-Chanasit from the Bernhard Nocht Institute for Tropical Medicine in Hamburg. This can be seen in the genome of the new corona virus, which has many genetic similarities with SARS-like viruses that originally occur in bats (The Lancet: Lu et al., 2020; Nature: Wu et al. 2020; Nature: Zhou et al. 2020). However, it did not necessarily means the bats passed the virus on to humans. It is conceivable that there was an intermediate host in the infection chain.

A man and woman wearing the protective masks in the centre of Shanghai on Feb 17, 2020. (AFP)

 

The scientists have not found answers to the most important questions which are fundamental for effective containment of the epidemic.


 

What is still unknown?

 

Nobody can say yet how many people got infected.

Even if more infected people are reported every day and included in the WHO statistics: Nobody knows how many people have actually contracted the new corona virus. The question of how the authorities define and record an infection plays an important role. The Chinese authorities have changed their counting method several times. According to the virologist Drosten, there is a "completely wrong assessment of the numbers in China". Many people with mild symptoms do not even go to a doctor or hospital. Obviously, they do not appear in any statistics. Experts like Drosten therefore assume that significantly more people are infected than previously known, that the virus can no longer be contained in China and that a pandemic is therefore becoming more likely every day.

As early as the end of January, a team from the University of Hong Kong had predicted that outbreaks could occur in major cities around the world by the transmission from Chinese tourists without their infection being noticed (The Lancet: Wu et al., 2020). "It will be crucial to correctly estimate the number of infected people with no or only very mild symptoms," said Harvard epidemiologist Pablo Salazar. In order to understand how the outbreak can develop, the epidemiologist advises to look at places that are well prepared for an outbreak and have close links with China - such as Singapore. Such countries have a well-functioning reporting system and can provide reliable figures. According to a study by Salazar and his colleagues that has not yet been assessed, other countries have far poorer skills in detecting infections and tracing chains of infection: especially in countries with low detection capacity but close links to the epicenter of the outbreak, such as Indonesia or in some countries in Africa Undetected cases of Covid-19 lung disease likely.


 

It is unknown in which phases infected people are contagious


To date, there has been insufficient research into the extent to which people who only experience mild cold-like symptoms are already contagious. In some cases, people who have had no specific symptoms may have contracted those affected. Based on the previous data, the WHO assumes that SARS-CoV-2 is mainly spread by infected people who also have symptoms.

Whether people can infect other people during the incubation period, even though they have no complaints themselves, could be decisive when it comes to how the outbreak will continue and where countermeasures need to be taken.

 

Researchers cannot assess how deadly is the coronavirus

To find out how high the mortality rate from infection with SARS-CoV-2 is, you have to know two things. First, how many people are infected? Second, how many does the virus kill? There is still no sure answer to both. Communist China has not allowed for an assessment of the situation by the independent experts. The WHO experts were not allowed the epicenter of the epidemic - Wuhan, and any other location in the Hubei province which is most infected with the coronavirus in China.

In this case one also cannot forget the statistics of deaths and the cases of sickness due to the coronavirus provided by the Communist China, and republished by WHO, are limited only to Hubei province. In other regions, Chinese Communist Parties instructed the doctors to call the sickness "a flu". This is why, according to the recent statistics the number of deaths decreased compared to the last week.

The proportion of deceased among the previously registered infected has so far been just over two percent, according to the statistics provided by Chinese Communist Party. For a respiratory infection, that would be quite a high proportion. However, experts expect that the more people tested, the two percent will decrease significantly in the course of the outbreak. Because among them there will surely be many with a mild course, which would otherwise not have been tested at all, and therefore would not have been recorded statistically. This was the case, for example, during the pandemic with the H1N1 influenza virus in 2009 and 2010. Initially, 59 fatalities in 850 suspected cases and thus an extremely high mortality rate of seven percent were assumed. As more data became available later, the death rate dropped to below 0.1 percent.

 

It is quite possible that patient zero was infected in November

The Chinese authorities reported the first cases of the novel lung disease to the World Health Organization (WHO) at the end of December 2019. However, Chinese scientists report that at least one patient should have had symptoms of the respiratory disease as early as December 1 (The Lancet: Huang et al. 2020). He could have been infected as early as November. The patient also had no contact with the Huanan Seafood Market, one of the starting points for the epidemic. So the market doesn't have to be the place where the first animal-to-human transmission happened. "It is possible, for example, that an animal was slaughtered and parts of it were sold on the market, but other parts elsewhere," says the virologist Schmidt-Chanasit. So it would be possible that one person infected elsewhere and other people became infected on the market. On the other hand, it is not plausible that a person brought the virus onto the market and infected other people or even animals there.

 

A possible transmission by faeces has not yet been sufficiently researched

In addition to infection from droplets when sneezing or coughing, it would also be conceivable to become infected through other body fluids. At least in the excrement of some infected people, evidence of the genetic material of the pathogen was found, for example in stool samples (New England Journal of Medicine: Holshue et al., 2020). "A positive virus detection in stool or anal swab does not necessarily mean that the virus was still alive and could infect others as a result," says the virologist Schmidt-Chanasit. So far, it has not been possible to isolate viruses in cell cultures from stool samples, i.e. to definitely detect the living virus. It has therefore not yet been finally clarified whether Sars-CoV-2 can also spread via faeces.

 

It is unclear which animal, and whether it was an animal that has transmitted the virus to humans

According to the virologist Schmidt-Chanasit, the results of the genetic analysis so far at least do not speak against the fact that the virus could have jumped directly from bats to humans. However, there is no argument against the fact that there was an intermediate host (virologists cannot exclude that the host could have been an artificial /not an animal or human/). In the case of SARS and MERS, there was an intermediate host.(The Lancet: Lu et al., 2020) Scientists can not exclude a scenario that the virus was transmitted by other methods to or in vicinity of the market. In fact, some Chinese scientists challenged completely the hypothesis that the food market was the first source of the contagion.

Those scientists who are considering an animal a source of the virus are still unable to state which animal could have stood between bat and human. The Chinese news agency Xinhua, Chinese Communist Party fully controls the agency's employees, reported in early February that a team of researchers from South China Agricultural University had identified a pangolin as a possible intermediate host of the novel corona virus. So far, the researchers have not yet published a study describing how they came to this conclusion. It seems that it was an attempt to distract the researchers rather than contribute with authentic information to their research.

 

It is conceivable that there was an intermediate host in the infection chain.


 

The virus is transmitted like a flu

Like other corona viruses or the influenza virus, the flu, the new pathogen is probably primarily transmitted via the air (Journal of Hospital Infection: Kampf et al, 2020). When an infected person exhales, sneezes or coughs, they spread microscopic droplets in the air that may contain the virus. A smear infection is also possible: if someone sneezes in the hands and then touches a door handle, for example, a person can become infected, who then takes the same handle in his hand and then touches his mouth with his hand. However, the main transmission pathway is assumed to be droplet infection, says the virologist Schmidt-Chanasit.

 

The virus can also multiply in the throat

Previous data indicate that the virus spreads more easily than the SARS pathogen. This should also be due to the fact that SARS-CoV-2 can obviously reproduce quite well in the throat - the SARS pathogen, however, only affects the deep airways. At first, researchers assumed that this was also the case with SARS-CoV-2, because the virus uses the same binding site (the ACE2 receptor) to slip into the cells of its host. However, researchers have found structures on the surface of the pathogen that also carry influenza viruses and that could allow the new virus to multiply effectively in the throat, said Charité virologist Christian Drosten. "A virus that jumps from lung to lung has a long way from person to person. But one that jumps from neck to neck is transmitted on the subway."

 

Children are not immune to the coronavirus infection

The research team does not assume that children are immune to SARS-CoV-2. Babies are likely to have less contact with potential carriers or develop symptoms that are so mild that an illness with Covid-19 remains undetected. "Children can pass on the pathogen, but in many cases do not appear immediately to be ill themselves," said Drosten. This is a big difference to influenza and other respiratory diseases, which often affect children at first. Why this seems to be different with SARS-CoV-2 is still unclear.

According to current knowledge, newborn children also do not necessarily become infected through their mother if she has been infected with the corona virus in late pregnancy. This is the case, for example, with the Zika virus, which became known through an outbreak in 2016 and can lead to brain malformations in unborn children. A research team from China and the United States examined nine women who had late pregnancy Covid-19 and their children (The Lancet: Chen et al. 2020). In six of the patients the amniotic fluid, umbilical cord blood and breast milk as well as a throat swab of their newborns were tested on SARS-CoV-2. None of the samples contained the virus.

 

There was an intermediate host for the coronavirus before a man got sick

"It is very certain that the virus was originally circulated in bats," says the virologist Jonas Schmidt-Chanasit from the Bernhard Nocht Institute for Tropical Medicine in Hamburg. This can be seen in the genome of the new corona virus, which has many genetic similarities with SARS-like viruses that originally occur in bats (The Lancet: Lu et al., 2020; Nature: Wu et al. 2020; Nature: Zhou et al. 2020). However, it did not necessarily means the bats passed the virus on to humans. It is conceivable that there was an intermediate host in the infection chain.

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