Coronavirus

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The disease COVID-19, caused by the virus commonly known as coronavirus, is zoonotic: it came from animals and jumped into humans. But when, and from what animal? How old is the virus, and why are there huge discrepancies in the scientific findings?

Origin

Coronavirus, was thought to originate from the Huanan Seafood Market in Wuhan, China, where wild animals, including marmots, birds, rabbits, bats and snakes, are traded illegally. However, recent work has demonstrated that the market is only one possible origin of the disease, and patient zero – the first human to contract coronavirus – may well have come earlier and elsewhere.

Although a group of stallholders came down with the disease, other cases of COVID-19 have been uncovered amongst people with apparently no link to the market, suggesting it may already have mutated into a zoonotic virus that could jump to humans.

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Rowena Fletcher-Wood
The human strand of coronavirus is most similar to a strand found in bats. Image credit: Rowena Fletcher-Wood
The source of the infection has not been identified, but many animals are contenders. The human strand is most similar to a strand found in bats (96% identical DNA), followed closely by that found in pangolins (88.5-92.4%). Scientists are sceptical of the theory that it jumped more than once from animals to people, mostly because there is no evidence that repeated contact with animals has led to any further infections.

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Studies of the COVID-19 and coronavirus spread have concluded that there was no one single patient zero in the UK: over 1,356 strains entered the country and replicated, as demonstrated by 20,000 viral samples, which assembled a family tree for the virus, showing ~34% of cases from Spain, 29% from France, 14% from Italy and <0.1% from China. In collaboration with international travel data, researchers have concluded that infection rate peaked around 15th March, prompting criticism over decisions to keep international travel open in February and March.

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Age

Under the current pandemic, advanced genome sequencing techniques have been used to probe the coronavirus and its cousin diseases[1].

These viruses are common and most diverse in bats and birds[2][3][4], and as such have been tied to the coevolution and divergence of these species in the carboniferous period, over 300 million years ago. Indeed, one genetically-related alphacoronavirus has been found in different mouse-eared bats on different continents which are non migratory.

However, until recently, molecular clock dating analyses aged them at just 10,000 years old – mere evolutionary babies. The strains found in the mouse-eared bats are thought to be just 200-4,400 years ago…[2][4] A clearly incompatible finding!

As such, researchers have been updating standard nucleotide models to try to account for this discrepancy, and think that strong “purifying” selection may have led to a massive underestimate[1]. A new method that models varying strength of natural selection over time was tried out in coronaviruses, and dates them to at least tens of millions of years ago – when their natural hosts (bats and birds) started diversifying[2][3][4]. This would give the coronavirus a history similar to that of filoviruses like Ebola[5][6], or herpesviruses[7][8], amongst others. The finding has important implications for the fight against coronavirus, as it’s possible that if bats and birds coevolved alongside coronaviruses, they developed metabolic and immunological tolerances that we might identify and use to support disease treatment and eradication[1][9][10].

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© Sylvain Haye (CC BY-SA 3.0) via Wikimedia Commons
Coronavirus is thought to have coevolved with bats and birds when these species diversified. Image credit: © Sylvain Haye (CC BY-SA 3.0) via Wikimedia Commons 

An unequal illness

How long does coronavirus last? For most, it’s about two weeks, but some have had the illness for 60, 70, or 80 days, and counting. They suffer symptoms including fatigue, loss of concentration, coughs, fevers, and difficulty breathing. Hallucinations, delirium, and short-term memory loss have also been reported. The symptoms may improve or worsen, and the only thing that’s constant is that the ill-effects are ever-changing. After months of suffering, some have borne out the illness, but for others it has shown no signs of abating – and we’ve no idea how long it might last.

Friends, family, and even doctors have suggested ongoing symptoms are in the sufferer’s head – because they’re unable to process a prolonged condition. These dismissals disproportionately affect women. To make this worse, long-haul sufferers test negative for the virus – it’s gone. Scientists have suggested that the lingering effects are not a direct consequence of the virus, but likely due to the host’s immune system in overdrive – but they don’t know. Long-haulers might still carry the virus (or inactive genetic fragments) in a “reservoir organ”. Supporting the immune system hypothesis is the finding that people taking tamsulosin for urinary retention have better odds against coronavirus, which works by blocking inflammatory cytokines in the body.

The journey through long-haul coronavirus has been well-documented by Paul Garner, professor of infectious diseases at Liverpool School of Tropical Medicine.

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© Ross Berteig (CC BY 2.0) via Flickr
Image credit: © Ross Berteig (CC BY 2.0) via Flickr 

The variability of coronavirus symptoms is confusing, and suggests it may be more to do with the host than the virus. Some think the virus directly attacks organs, whilst others think it is solely due to immune system overstimulation. The Chinese detection of the protein “D-dimer” may be indicative of those at highest risk from coronavirus: the protein has been found at concentrations four times higher than usual in hosts who later die[11]. Tests have been developed to identify elevated concentrations.

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Luca Florio via Flickr Creative Commons with Attribution
Image credit: Luca Florio via Flickr Creative Commons with Attribution 

We don’t know how many people who get the virus die – somewhere between 0.1 and 15% – but even more mysterious is who, and why. Estimates of coronavirus mortalities suggest that black deaths are 3.57 times higher than white deaths. In Switzerland, French speakers are 1.6 times more likely to die than German speakers, and Italian speakers are 2.4 times more likely to die.

There have always been racial disparities in epidemics[12], and this alone tells us that biologic or behavioural differences cannot explain the trend. Sociologists speculate that this is likely due to a host of other factors, including socioeconomic status, food security, housing conditions, access to healthcare, previous health status, family size, and whether you live in a city or the countryside. The Harvard Public Health Disparities Geocoding Project is now attempting to unravel, these factors by paralleling coronavirus data with Census data.

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Aftermath

What does an antibody test for coronavirus tell us? At the moment, we don’t know. False positives are sufficiently common that if enough people test who haven’t had the disease, even a test that is correct over 90% of the time can identify more people incorrectly than correctly. The challenge of measuring the trail left by coronavirus continues.

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The aftermath of coronavirus – just like so many other viruses – is poorly understood, and long-lasting symptoms are rarely mentioned: but they do exist. Survivors may be left with disabilities, including scarring in the lungs[13], or ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome).

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This article was written by the Things We Don’t Know editorial team, with contributions from Rowena Fletcher-Wood.

This article was first published on and was last updated on 2020-06-29.

References
why don’t all references have links?

[1] Wertheim, Joel O., et al. A case for the ancient origin of coronaviruses. Journal of Virology 87.12 (2013): 7039-7045. doi: 10.1128/JVI.03273-12
[2] Woo, Patrick CY, et al. Discovery of seven novel Mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus. Journal of virology 86.7 (2012): 3995-4008. doi:10.1128/JVI.06540-11
[3] Chu, Daniel KW, et al. Avian coronavirus in wild aquatic birds. Journal of virology 85.23 (2011): 12815-12820. doi:10.1128/JVI.05838-11
[4] Vijaykrishna, D., et al. Evolutionary insights into the ecology of coronaviruses. Journal of virology 81.8 (2007): 4012-4020. doi:10.1128/JVI.02605-06
[5] Belyi, Vladimir A., Arnold J. Levine, and Anna Marie Skalka. Unexpected inheritance: multiple integrations of ancient bornavirus and ebolavirus/marburgvirus sequences in vertebrate genomes. PLoS pathogens 6.7 (2010). doi: 10.1371/journal.ppat.1001030
[6] Taylor, Derek J., Robert W. Leach, and Jeremy Bruenn. Filoviruses are ancient and integrated into mammalian genomes. BMC evolutionary biology 10.1 (2010): 193. doi: 10.1186/1471-2148-10-193
[7] McGeoch, Duncan J., and Simon Cook. Molecular phylogeny of the alphaherpesvirinae subfamily and a proposed evolutionary timescale. Journal of molecular biology 238.1 (1994): 9-22. doi: 10.1006/jmbi.1994.1264
[8] McGeoch, Duncan J., et al. Molecular phylogeny and evolutionary timescale for the family of mammalian herpesviruses. Journal of molecular biology 247.3 (1995): 443-458. doi: 10.1006/jmbi.1995.0152
[9] Wang, Lin-Fa, Peter J. Walker, and Leo LM Poon. Mass extinctions, biodiversity and mitochondrial function: are bats ‘special’as reservoirs for emerging viruses? Current opinion in virology 1.6 (2011): 649-657. doi: 10.1016/j.coviro.2011.10.013
[10] Zhang, Guojie, et al. Comparative analysis of bat genomes provides insight into the evolution of flight and immunity. Science 339.6118 (2013): 456-460. doi: 10.1126/science.1230835
[11] Zhang, Litao, et al. "D‐dimer levels on admission to predict in‐hospital mortality in patients with Covid‐19." Journal of Thrombosis and Haemostasis 18.6 (2020): 1324-1329. doi: 10.1111/jth.14859. [12] Chowkwanyun, Merlin, and Adolph L. Reed Jr. Racial health disparities and Covid-19—caution and context. New England Journal of Medicine (2020). doi: 10.1056/NEJMp2012910.
[13] Wang, Yuhui, et al. Temporal changes of CT findings in 90 patients with COVID-19 pneumonia: a longitudinal study. Radiology (2020): 200843. doi: 10.1148/radiol.2020200843

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