Coronas are not (just) beers.

Severe acute respiratory syndrome (SARS), as its name suggests, is a respiratory illness Coronaviridaewhich largely targets the upper respiratory tract, with its defining symptom being a fever with a temperature of 38°C (100.4°F) or higher. Other symptoms include flu-like symptoms such as chills, muscle aches, headaches, fatigue and sore throat. As the illness progresses, patients may then develop a dry cough and/or shortness of breath, followed by pneumonia, respiratory failure, and acute respiratory distress, potentially leading to death. The incubation period of the virus is about 2-13 days, with a mean of 5 days.

SARS is caused by the virus SARS-coronavirus (SARS-CoV). This virus was responsible for the SARS epidemic of November 2002 to July 2003. At the end of epidemic, there were a total of 8273 cases, and 775 deaths. The case fatality rate – that is, the number of deaths as a ratio of the number of cases – has been stated as being somewhere between 9.6%-11%, depending on the definition of case fatality rate used. Although the case fatality rate was somewhat high (the case fatality rate for the recent 2009 influenza pandemic was about 0.03%), the number of deaths was likely mitigated by the fact that many of the people infected by SARS-CoV had access to very good supportive/palliative healthcare, helping their immune systems to fight off the virus.

An electron micrograph of a SARS-CoV virion. Image by CDC/ C. D. Humphrey and T. G. Ksiazek.

An electron micrograph of a SARS-CoV virion. Note the distinctive “corona”, which gives the family Coronaviridae its name. Image by CDC/ C. D. Humphrey and T. G. Ksiazek.

SARS-CoV is a coronavirus, so named for the protein spikes that surround this spherical virus, which looks like a corona. Although SARS-CoV was initially suspected to have originated in masked palm civets – which were commonly sold in markets in China, where some of the first cases of SARS was reported – it was finally traced back via phylogenetics to the Chinese horseshoe bat. Both the human and civet cat SARS-CoV were found to have descended from bat coronaviruses.

Although there are no cures or vaccines currently available for SARS-CoV, there is a vaccine in development by MassBiologics, cooperating with researchers at NIH and the CDC. The 2002-2003 epidemic was successfully controlled by quarantining those infected, and suspected to be infected by the virus, and is a viable alternative solution in countries where such measures can be effectively implemented. The determination of the incubation period of the virus was a vital part of this counter-measure, as it enabled health officials to determine how long had to elapse before people who had come into contact with SARS patients could be declared free from SARS.

A similar coronavirus surfaced in Saudi Arabia in April 2012. Known as Middle East respiratory syndrome coronavirus (MERS-CoV), there have been 94 confirmed cases, 16 probable cases and 47 dead, with a case fatality rate of approximately 50%, as of August 2013. Like SARS, this is a viral respiratory illness; its symptoms include fever, cough and shortness of breath, which may be followed by kidney failure and respiratory distress, potentially leading to death. People who have weaker immune systems are more likely to die from Middle East respiratory syndrome (MERS). Thus far, all cases have been linked to the Middle Eastern area.

A negatively-stained electron micrograph of MERS-CoV,  revealing its ultrastructural morphology. Image by CDC/ Cynthia Goldsmith; Azaibi Tamin, Ph.D.

A negatively-stained electron micrograph of MERS-CoV, revealing its ultrastructural morphology. Image by CDC/ Cynthia Goldsmith; Azaibi Tamin, Ph.D.

MERS-CoV can be transmitted from person to person if there has been close contact without protective equipment e.g. gloves and masks, but in general, it appears that there has not been a sustained spread of MERS in people. There are three main epidemiological patterns to the transmission of MERS-CoV – 1) sporadic cases, probably after coming into contact with an animal carrying MERS-CoV. 2) Family clusters and 3) healthcare workers are similar, as they are both sets of people who would have come into close contact with an infected person while the person is contagious. The incubation period of MERS-CoV seems to be from 2-14 days; thus, isolation protocols similar to those as carried out in the SARS 2002-2003 epidemic can be applied to people who are suspected to be infected with MERS-CoV. There is also no known cure or vaccine for MERS-CoV. The only treatment available is supportive/palliative care, ensuring that the patient manages to live while their immune system fights off the virus.

Not much is known about MERS-CoV; it seems to be a genetic match to a coronavirus found in Egyptian tomb bats, but recently there has been a report that camels may be the actual animal reservoir for this strain of coronavirus. It also appears that a large amount of virus is actually needed to cause an infection, as only about 20% of our respiratory epithelial cells – that is to say, about 20% of our lungs and airways – are carrying the protein receptor DPP4, which allows MERS-CoV to enter, and hence infect, them.

On an slightly more unsettling note, it seems that there has been at least one case of asymptomatic MERS – that is to say, a person was infected, and then produced anti-MERS-CoV antibodies, without ever showing signs of MERS. If asymptomatic MERS can be confirmed, and people with asymptomatic MERS can transmit the virus to other people, this could potentially explain the sporadic cases of MERS that seem to pop up out of nowhere. Of course, this would also lower the case fatality rate of MERS-CoV. There are also further concerns about the potential for a serious epidemic as there will be an increase in the number of people going to Mecca in Saudi Arabia for the Muslim Haj. While a vaccine could potentially be developed, it might be that the MERS epidemic would burn itself out the same way the SARS epidemic did, thus rendering the development of the vaccine unnecessary and unprofitable.

 

References:

Summary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003

Tracking SARS back to its source

S. K. P. Lau, P. C. Y. Woo, K. S. M. Li, Y. Huang, H-W. Tsoi, B. H. L Wong, S. S. Y. Wong, S-Y. Leung, K-H. Chan and K-Y. Yuen. Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats PNAS Vol. 102 No. 39 14040–14045, doi: 10.1073/pnas.0506735102

Special Online Edition: The SARS Epidemic

CDC | MERS

A. Rambaut MERS-Coronavirus Molecular Epidemiology and Genetic Analysis – Origin and Evolution

C. BEM Reusken, B. L. Haagmans, M. A. Müller, C. Gutierrez, G-J. Godeke, B. Meyer, D. Muth, V. S. Raj, L. Smits-De Vries, V. M. Corman, J-F. Drexler, S. L. Smits, Y. E. El Tahir, R. De Sousa, J. van Beek, N. Nowotny, K. van Maanen, E. Hidalgo-Hermoso, B-J. Bosch, P. Rottier, A. Osterhaus, C. Gortázar-Schmidt, C. Drosten, M. PG Koopmans Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study The Lancet Infectious Diseases, Volume 13, Issue 10, 859 – 866 doi:10.1016/S1473-3099(13)70164-6

R. Roos Saudis, WHO Report 8 Silent MERS Cases

D. Butler Receptor for new coronavirus found


Virology 100x: Let’s start from the very beginning

Tobacco Mosaic Virus

The tobacco mosaic virus; the first virus discovered and studied.

Let me get one thing straight first – viruses are NOT the same thing as bacteria. They’re just not. Okay? Great.

What are viruses, then? Well, I could tell you that they’re nucleoprotein complexes that make use of cells to replicate; I could tell you that they are obligate intracellular parasites – that is to say, they’re obliged to be parasites inside our cells; I could even tell you that they do not undergo cell division. But I won’t.

Oh. I already did.

Never mind then.

The point is, viruses are all that and more. One of the most interesting things in the world, we still can’t decide if viruses are living organisms or not. They carry genetic material, and are able to replicate themselves (but only after they’ve infected a host cell). However, outside of cells, they become metabolically inert – they can’t make their own proteins or copy their own DNA (or in the cases of some cells, their own RNA). Yet they can ‘die’ – if they’re outside of their host cell for long enough, or are otherwise exposed to adverse conditions, they can no longer successfully infect cells. This straddling of the line between life and non-life is very likely to be a clue to how life originated; most viral genes are so unlike the genes of the rest of the planet that they may well have come from a common ancestor before cell-based life existed.

The core of any virus is its genetic material – either DNA or RNA; this may be wrapped up with viral proteins to form a nucleoprotein complex (from combining “nucle”ic acid + “protein”). Viral proteins are also incorporated into the protective coat surrounding the nucleoprotein complex to give rise to the basic viral particle (or the virion). Some viruses, particularly those that infect mammals, may also have an additional lipid envelope over its protective coat.

You may think that all viruses are harmful to us, but this is not true. Because of the proteins embedded in their protein coat (or lipid envelope), viruses are very specific about which species they will infect, much like how only one specific key can open one specific lock. In fact, there are viruses, known as bacteriophages, which are beneficial to us because they are able to infect, and thus cause the death of bacteria that are harmful to us. It has been suspected that some “healing waters” may have been effective due to the presence of viruses that infect pathogenic bacteria. Viruses also infect amoeba, fungi, plants, and of course, other animals. In fact, every species on Earth has a whole host of viruses that is specifically only able to infect that species.

lock and key

In this case, the pink object refers to a viral surface protein, while the orange object refers to a host cell surface protein/glycoprotein. Only when viral protein keys are able to fit into host protein/glycoprotein locks can the infection of a cell start to happen, so viruses are VERY specific about who they are able to infect.

The gold standard for determining a new virus is by cultivating and isolating the virus, and viewing it under an electron microscope. Unfortunately, this species specificity means that it is very difficult to cultivate human viruses in order to study them, because they won’t infect non-human cells. The best way to go about studying human viruses would of course be by infecting humans, but this is ethically problematic, to say the least. One partial solution would be to culture human cells in a dish, and throw some human viruses on top to infect the human cells. This helps with studying how viruses infect cells in the first place, and what effects they have on cells in isolation. However, viruses are very finicky, and it first takes a lot of trial and error, and later, precision and time, to properly grow them. This still doesn’t answer how viruses act in the whole body, though – especially in the presence of our immune system, which has been implicated in a large amount of the cellular damage it causes as it tries to rip the virus from our bodies. Scientists thus have to use genetically near-identical species such as monkeys, or modify mice and other model organisms such that they carry human proteins, and are then able to be infected by our human viruses.

Because viruses are basically protein coats around genetic material, they are therefore also ideal as a mechanism for transferring genes to our own genomes. These engineered viruses are known as viral vectors, and have been modified such that they no longer cause disease. Viral vectors have a wide range of applications, including gene therapy, cancer treatmentvaccine development, and even in basic neuroscience research. Virus-like particles, which are viruses emptied of their genetic material, are also being investigated for use in nanotechnology applications like drug delivery and diagnosis.