Tuesday, 28 April 2020

How soap can kill viruses: 20 seconds, lather and warm water

Since the outbreak of coronavirus in the UK, the government has been encouraging people to wash their hands frequently with soap in order to stop spreading the virus. The government's promotion successfully made people do this for a full 20 seconds by asking them to mentally sing "Happy Birthday" twice while washing our hands. (Those who don't like that particular song can now find suggestions for many other 20-second "hand-washing songs" online.) While it is easy to understand the reason for washing hands long enough, we may also like to know how we can optimise our hand washing efficiency using soap. An article with interviews from two professors gives us the answer: bubbles and foam, and warm water.1

Before we go into what the two professors had said, we can have a brief understanding of the structure of an encapsulated virus (such as coronavirus) and how this kind of virus attaches to our hands. An encapsulated virus consists of three key components: genetic material made up of ribonucleic acid (RNA), proteins, and lipids (basically called fat). The virus replicates in the host and makes lots of these components which then self-assemble to form complete viruses. The proteins and lipids form the virus envelope (including a lipid bilayer and membrane proteins), giving protection and attachment ability to the virus when it is outside the host cell. When an airborne virus comes in contact with the skin, the envelope of the virus interacts with proteins and fatty acids in the dead cells on the skin's surface. However, the bondings that hold the three key components in the virus, and the bonding between the virus and the skin's dead cells, are not strong.*

Soap molecules have a special property that disrupts those weak bondings. Each soap molecule has two ends: a hydrophillic ("water-loving") head, and a hydrophobic ("water fearing") tail that is attracted to grease. When soap is applied, the hydrophobic tail of the soap molecule is drawn to the fatty outer layer of the virus, competing with the lipids in the membrane and thus prying it open. Once the virus splits open, its contents is spilled out into the soapy water and "dies", or, more correctly, becomes inactive.**

The combination of water and scrubbing with hands using soap creates more soap bubbles. You may wonder if these have an actual function. The foam or bubbles created can disrupt the chemical bonds that allow a virus to stick to the skin's surface. After 20 seconds of thorough scrubbing to get into every crack and crevice of your hands and fingers, all the viruses that have been damaged, or inactivated, by soap molecules are washed away when you rinse your hands. Therefore, according to Professor William Schaffner of the preventive medicine and infectious disease department at Vanderbilt University of Medicine in Nashville, the "bubbles and foam literally pick germs up and wash them down the drain." It is "an indication that the soap is ... trying to encapsulate the dirt and the bacteria and the viruses in them," said Dr. Bill Wuest, an associate professor at Emory University who studies disinfectants.1

Dr. Wuest said that warm water can make everything bubbly more easily than can cold water: "Cold water will work, but you have to make sure you work really vigorously to get a lather and get everything soapy and bubbly." We may need to sing the "Happy Birthday" song three times instead of two. "Warm water with soap gets a much better lather, more bubbles."1

Therefore next time you wash your hands with soap, please remember that besides 20 seconds, warm water and a lot of bubbles are also essential to destroy the viruses and wash them away from the skin effectively.



*The lipid bilayer membrane is assembled by noncovalent bonds, which are weak bonds that hold molecules. The proteins and lipid molecules in the virus membrane are held together by Van der Waals forces, which also hold together the hydrophobic tails of soap molecules, and hydrogen bonding, which also binds the hydrophilic heads of soap molecules with water. These weak bondings help to stabilize the lipid bilayer structure of the virus.
Washing off the virus with water alone, therefore, is not enough, as water cannot eliminate the interaction between the virus and the dead cells on the skin's surface. Coronavirus covered with a membrane of lipid bilayer, the "greasy" virus, thus cannot be simply separated from the dead cells of the skin by water. Soap and ethanol are the best tools to do that.
**Almost all sanitizer, which typically contains 60%-80% ethanol, "kills" viruses in a similar fashion as soap. Both dissolve the greasy coating of the enveloped virus.



Reference

1. "Why soap, sanitizer and warm water work against COVID-19 and other viruses" CNN Health, 24th March, 2020. https://edition.cnn.com/2020/03/24/health/soap-warm-water-hand-sanitizer-coronavirus-wellness-scn/index.html

Thursday, 23 April 2020

Coronavirus (9) Warning from WHO on using antibody tests

Besides the problems with sensitivity and reliability of antibody tests for COVID-19,1,2 scientists from WHO issued a warning on the use of these tests, as they thus far do not have enough evidence that a person could be risk free from reinfection even if a positive antibody test result for COVID-19 is correct. This was announced in a news conference at WHO's Geneva headquarters. Their concern is based on two factors, for which they do not yet have answers because the disease has just newly emerged and has been threatening humans for only a few months.3,4

One concern is what level of blood antibody is enough for COVID-19 immunity and protection from reinfection. As mentioned in my last blog, people with severe illness tend to have a quicker and stronger antibody response, while people with mild or no symptoms tend to develop the antibodies slowly and in lower quantities. However, even among the people who developed a strong antibody response and have over 90% chance to be detected by an antibody test, that level of antibodies "does not mean that somebody is immune" said Dr. Maria Van Kerkhove, head of WHO's emerging diseases and zoonosis unit. These tests can detect serological antibodies if they reach the sensitivity level of the test. However, "right now, we have no evidence that the use of a serological test can show that an individual is immune or protected from reinfection."3

The other concern is the duration of protection the antibodies can give to a person who has been infected with SARS-CoV-2. Dr. Mike Ryan, executive director of emergencies program of WHO, said that "nobody is sure whether someone with antibodies is fully protected against having the disease or being exposed again," after his saying that scientists are still determining the length of protection antibodies might give to a person with coronavirus infection history. "With regards to recovery and then reinfection, I believe we do not have the answers to that. That is an unknown."3

The level and the duration of the serological antibody which can protect a previously infected person during the second time of SARS-CoV-2 infection are crucial knowledge in protecting patients. It will take a long time to find out the answers from bigger studies amid the increased number of the cases. Therefore it is better if countries or peoples do not use antibody tests as an indication of immunity before clearer answers emerge. Moreover, even if your antibodies do protect you from becoming sick, you may still harbour the virus and pass it to others.



References

1. "Coronavirus (5) What is RNA test? Antigen test? Or antibody test?" https://yunwenincambridge.blogspot.com/2020/04/coronavirus-5-what-is-rna-test-antigen.html
2. "Coronavirus (7) Abandonment of home-based antibody tests" https://yunwenincambridge.blogspot.com/2020/04/coronavirus-7-abandonment-of-home-based.html
3. "WHO warning: No evidence that antibody tests can show coronavirus immunity" CNBC, 17th April, 2020. https://www.cnbc.com/2020/04/17/who-issues-warning-on-coronavirus-testing-theres-no-evidence-antibody-tests-show-immunity.html
4. "Coronavirus: Double warning over antibody tests" BBC news, 18th April, 2020. https://www.bbc.co.uk/news/uk-52335210

Tuesday, 21 April 2020

Coronavirus (8) Why is it difficult to have a high accuracy home-based antibody test?

In my last blog post, I mentioned about the technical problems that prevent the home-based antibody test from giving an accurate and sensitive result. Two of the reference articles I cited1,2 tell us additional reasons that make antibody tests for COVID-19 difficult to apply at this moment. This is precious knowledge that we cannot learn from textbooks but only from experienced experts. Let us have a closer look at what they said.

Thus far, it has been found that people infected with COVID-19 can develop different degrees of symptoms for the disease.3,4,5 Some can be seriously ill, while some can show little or no symptoms at all. Based on the patient samples analysed by research team of Dr. David Da-i Ho, a leading scientist at Columbia University in New York who invented cocktail therapy for HIV and is now leading a team to look for COVID-19 treatment, the patients with severe illness tend to develop a faster and stronger antibody response, while the ones with milder symptoms tend to develop the antibody response more slowly. This means that the one with severe illness will have a positive antibody test result at an earlier stage of the disease development compared with the one with milder symptoms, yet it is not possible to predict how long it's going to take for the body to develop enough antibodies to give a positive result in the antibody test. This highly variable immunity response across the population makes the development of a simple, reliable home-based antibody test considerably challenging. 1

Moreover, the level of antibody production for the asymptomatic or mildly symptomatic cases remains low even after two weeks of antibody response. This can result in only about half of the cases being detected. Additionally, it is still unclear whether the antibody level will increase if these people are tested one or two weeks later. Prof Marion Koopmans from the Erasmus University Medical Centre in Rotterdam did not think that the detection rate can reach the levels seen in severe cases. She said that the claiming of over 90% sensitivity by the home-based test is likely to be based on tests in patients recovering in hospital, who represent the most severe cases. Therefore, for the people with low or no symptoms, which accounts for about 80% of the cases, the sensitivity of the home-based antibody test will "end up around 50%-60%", which is highly unreliable.1

A shortage of blood samples from people recovered from COVID-19 is another reason that holds up the development of an antibody test. This convalescent blood is necessary for academia and industry to develop and validate the tests. The shortage is due to the administration in the UK making it difficult to get patient samples. "Access to patient samples has been a longstanding issue for the industry, and that is highlighted now when companies desperately need them" said Dr. Doris-Ann Williams, chief executive of the British In Vitro Diagnostic Association. The other reason for the shortage of convalescent blood is simply because the disease is newly emerged. "People can have two weeks of disease and then three weeks to mount this antibody reponse, but if you look back five weeks or so, there was hardly anyone in Britain with the disease" said Prof John Bell from Oxford University.2

From these experts in the field, we now understand that the big range in immune response for a disease seen across the population makes it difficult to develop a simple home-based test which is reliable over an entire population. The shortage of blood also hampers the development and validation of the antibody test. As the problem arising from a wide range of immune response can never be changed, and the shortage of blood for antibody development will not be solved in the near future, I would not recommend the use of antibody test to check the history of infection of a person. The false results could be disastrous.


References

1. "Coronavirus 'game changer' testing kits could be unreliable, UK scientists say" The Guardian news, 5th April, 2020. https://www.theguardian.com/world/2020/apr/05/coronavirus-testing-kits-could-be-unreliable-uk-scientists-say
2. "UK COVID-19 antibody tests not ready until May at earliest" The Guardian, 8th April, 2020. https://www.theguardian.com/society/2020/apr/08/uk-covid-19-antibody-tests-not-ready-until-may-at-earliest
3. Qian G, Yang N, Ma AHY, et al. A COVID-19 Transmission within a family cluster by presymptomatic infectors in China. Clin Infect Dis 2020. Epub March 23, 2020.
4. Du Z, Xu X, Wu Y, Wang L, Cowling BJ, Meyers LA. Serial interval of COVID-19 among publicly reported confirmed cases. Emerg Infect Dis 2020. Epub March 19, 2020.
5. Kimball A, Hatfield KM, Arons M, et al. Asymptomatic and presymptomatic SARS-CoV-2 infections in residents of a long-term care skilled nursing facility-King County, Washington, March 2020. MMWR Morb Mortal Wkly Rep 2020. Epub March 27, 2020.

Saturday, 11 April 2020

Coronavirus (7) Abandonment of home-based antibody tests

In late March, the UK government announced the ordering of millions of home-based antibody tests and their planning to roll out the quick test to the public, in cooperation with Boots and Amazon.1 Thereafter, I wrote a blog post on introducing different types of test for SARS-CoV-2, which also compared the sensitivity and accuracy of the tests. I specifically pointed out that antibody tests, particularly the quick home-based antibody test, would have a much lower sensitivity and accuracy. Immediately the next day after the publication of the post, UK scientists who were involved in validating home testing kits said that no antibody test on the market has yet been shown to be sufficiently reliable.2 And the news in subsequent days was that the home-based antibody test will not be available in the UK in the coming few weeks, with the health secretary, Matt Hancock, saying that the tests are not yet "good enough".3,4

According to the news report, none of the antibody tests on the market have met the standards agreed with the Medicines and Healthcare products Regulatory Agency (HMRA). The Oxford group, which is responsible for assessing the tests, has characterised six different antibody tests and found that most failed to detect antibodies half the time, and the best spotted the immune cells only 70% of the time. If used at scale, the tests could leave millions of people who have immunity convinced they are still vulnerable to the infection. For the test to pass, the accuracy would have to be nearer 95%.3

In the same report, Professor Martin Hibberd from the London School of Hygiene and Tropical Medicine described that the finger-prick antibody tests are "traditionally very poor in terms of sensitivity and specificity". As I mentioned in my blog post, the low sensitivity is due to a tiny amount of blood being used. A false negative result would happen if the circulating antibody in the test sample is in low level; the poor specificity is due to the cross-reactivity which increases the chance of a false positive result. The monoclonal antibody raised against the target antibody wrongly recognizes another molecule which has high similar structural regions as the target. Therefore, the accuracy of the antibody test is largely dependent on how well the manufacturer raises and selects the antibody against the target. Unfortunately, those antibody tests available in the market "look very similar and probably come from the same factory in China," said Sir John Bell, a Regius professor of medicine at Oxford University. Due to the complexity of the work, a working antibody test with improved sensitivity and accuracy seems to be months away, or it's even possible that we won't get an antibody test that meets the standard.

On the basis of the finding of the quality of the tests and his experience, Prof Hibberd suggested "a centralised pathology lab antibody test" and that the UK government should drop the idea of making the finger-prick antibody test available to the public. Actually, the lab-based antibody test at Oxford University can distinguish positive and negative samples of blood with almost 100% accuracy.* The disadvantages are that blood needs to be taken from people, the whole test process takes much longer and involves much technical expertise.3

While the UK government is still struggling in validating the home-based antibody tests, Germany and the US have started carrying out a nationwide lab-based antibody test.5 The test project in Germany will be carried out jointly by three different universities, while the one in the US will be carried out by the CDC. With the references from other countries, it seems applicable for the UK government implementing a nationwide lab-based test which is more reliable than the home-based test.



*An antibody test, whatever a lab-based or a home-based finger-prick one, is basically an enzyme-linked immunosorbent assay (ELISA). However, a lab-based test has the advantage of being able to use a higher volume of blood sample, thus increasing the sensitivity of the test. Moreover, in the lab-based ELISA, washing steps are usually performed after the incubation of the test sample with the detection platform, which is mounted with detection agents. These washing steps can eliminate non-specific binding, and remove excessive components that can interfere with the assay, thus increasing the specificity of the assay. On the other hand, no adjustment can be done to improve the sensitivity and specificity of the home-based antibody test, due to the restriction of the setting.



References

1. "Coronavirus tests: UK to make 15 mins at-home kits available within weeks" The Independent, 25th March, 2020. https://www.independent.co.uk/news/uk/home-news/coronavirus-test-uk-kit-home-nhs-cases-symptoms-public-health-england-a9424741.html
2. "Coronavirus 'game changer' testing kits could be unreliable, UK scientists say" The Guardian, 5th April, 2020. https://www.theguardian.com/world/2020/apr/05/coronavirus-testing-kits-could-be-unreliable-uk-scientists-say
3. "UK government urged to abandon "poor" finger-prick antibody tests" The Guardian, 9th April, 2020. https://www.theguardian.com/world/2020/apr/09/uk-government-urged-to-abandon-poor-finger-prick-antibody-tests-coronavirus
4. "UK COVID-19 antibody tests not ready until May at earliest" The Guardian, 8th April, 2020. https://www.theguardian.com/society/2020/apr/08/uk-covid-19-antibody-tests-not-ready-until-may-at-earliest
5. "Germany to run Europe's first large-scale antibody test programme" Financial Times, 9th April, 2020. https://www.ft.com/content/fe211ec7-0ed4-4d36-9d83-14b639efb3ad

Friday, 10 April 2020

Can the Covid-19 tracking app be trusted?

A research team at King's College London have been attempting to track UK and USA Covid19 cases via a self-reporting app, available for iOS and Android at https://covid.joinzoe.com/ and would like to encourage as many people as possible to download the app and self-report every day so we have a better data-set. Some 2 million people have already joined the programme, and results are already being published.

But the ultra-cautious among us might be asking: since the app's source code is not available, how can we be sure it's really doing what it says it is, and not for example spying on our phones?

The development of the app was outsourced to a commercial startup company, Zoe Global Ltd, who unfortunately have been unable to "open-source" the app, probably because, like many commercial companies, they are afraid that disclosing their source code will somehow harm their future business—although in fact there are many good examples of successful companies that do disclose their source code, such as the Android platform itself, and the Jitsi alternative to Zoom, but not everyone has yet fully grasped how to harness such "open-source" business models, and Zoe Global Ltd seems to be one of the companies that cannot do it yet. Nevertheless they were able to quickly produce the app in a crisis, and the research team felt that good positive press coverage by The Guardian, the BBC, King's College London and Professor Tim Spector should be enough assurance of the app's good behaviour without also having to disclose its source code.

Although we were unable to be given the source code when we asked for it, we were nevertheless able to perform a limited independent investigation into how the app works by downloading the Android APK file for the app (package name com.joinzoe.covid-zoe) from a third-party mirror site called APKFab, and looking inside it.

The download from APKFab is a file called "COVID Symptom Tracker_v0.9_apkfab.com.xapk" which can be unpacked using the "unzip" command on GNU/Linux. It contains a "manifest.json" file that gives it the following permissions:
  • Receive messages from the Android Cloud to Device Messaging (C2DM) service. This lets the research team send you messages (which they'll probably do only if they want to clarify an exceptional case).
  • Access the Internet. This is obviously required to send the results. The app also requests permission to read the state of the Internet and Wi-Fi connections, which could be used for example to check that the Internet connection is good before trying to use it.
     
  • Display a window over the top of another app. It's not clear why they want this permission: most likely the requst was left in the code by mistake. This permission (which is requested by 10% of apps on the Google Play store) can in theory be abused by "overlay malware" to pop up a fake login screen on another app, so you think you have to enter login details into the other app but you are actually giving them to the malware author.
     
  • Modify audio settings. This allows the app to change the volume, and to change from headphones to speaker or vice versa. Again, there is no clear reason why the Covid19 app should have this permission (unless they want to be able to shout at you in an emergency)—most likely it was left in by mistake.
     
  • Run a "service" and start automatically after the phone is restarted. This is used to give you a notification reminding you to report if you haven't done so for a while.
     
  • Prompt to install new packages (apps). This permission is usually requested if an app wants to bundle its own update mechanism. It won't be able to actually install other apps unless you say "yes" when asked.
     
  • Access the phone's storage, i.e. shared files. This is not strictly necessary unless the app wants to store its data in a place that will persist even after it has been uninstalled and reinstalled, or if it wants to use the external storage card. Apps that request this permission can read files you leave in the shared filespace, so we normally want the app to have a good reason to ask for it.
     
  • A permission called "bind get install referrer service" which is automatically added by Google Play Services unless the developer overrides it; it's believed to be harmless analytics on where the app came from.
Looking further into the app, the "config.*" files mostly contain graphics and messages in various languages, although the file "config.arm64_v8a.apk" also contains various library files, including one whose purpose is to detect faces in images. Hopefully this was left in by mistake, since there's no reason for this app to go looking through your album picking out faces (it doesn't have permission to use the camera, but apps with the Storage permission could in theory look at pictures you've already taken). Given that the company had to write the app so quickly, they probably copy/pasted a lot of code from another project and this app ended up with large chunks of unused code which is what we are seeing here; if they'd had more time to develop it properly they'd have hopefully taken this out.

The main part of the app is in a file called "com.joinzoe.covid_zoe.apk" which contains more face-detection resources (in the "assets/models" directory, hopefully left in by mistake), supporting files for Google Play Services and crash-analytics libraries (they want to know what happens if their app crashes), a Soundex library (for matching mis-spelled words), and 16 megabytes of compiled Kotlin code.

It's hard to analyse the code without source code, but there are some tools that can try to back-translate ("decompile") it into code that is partly readable by a developer. We used the "d2j-dex2jar" utility to back-translate the code, although it did fail on some of it, most notably on a couple of libraries from Facebook, one of which is responsible for managing Facebook advertisements. Again we hope this was left in the app by mistake and not actually used.

After "d2j-dex2jar" has done its work, the resulting "jar" files can be inspected using a tool called "jd-gui". We browsed through it and found various user-interface support libraries (not all of which are used), the Amplitude library for tracking what users do in the app, the Bumptech Glide image loading library, and libraries from both Facebook and Google that include advertising functions. The app also bundled a library called Expo that includes a barcode scanner, camera handler (although the app does not have permission to use this), SMS, speech and printing functions\u2014obviously much of this is unused and they didn't have time to take it out (that's how apps end up taking more space on your phone than they should). It also contains an open-source cryptography library which can help send data to their servers securely.

What we were really looking for, though, was the main part of the program—not all libraries are used, so it would be nice to start at the entry point and see which of them actually are used. In future it would help if unused libraries were completely removed, so we wouldn't need to have conversations like “yes we have code in our app that tracks faces and Facebook, but it's switched off and we forgot to take it out”, but obviously the developers had to rush and their method does seem to be “copy everything from another project and use just some of it”.

Unfortunately the all-important main-program classes under "com.joinzoe" do not seem to have been listed as such by the "dex2jar" utility, so finding them would require reading through the best part of a million lines of support code, which would take quite some time. (Perhaps some companies have a deliberate practice of dumping lots of extra unused code in their work just to confuse anyone who tries to analyse it.)

So all we can say at this stage is: we haven't confirmed the app won't contact Facebook, mess with your volume control, pop up misleading boxes over other apps, or look for faces in your photo album, but at least it can't use your camera or microphone, can't read your precise location and can't access the phone, contacts or messages. And the researchers who founded the startup do seem to have a track record of not being particularly devious, so let's apply Hanlon's Razor (“never attribute to malice what is sufficiently explained by stupidity”) and assume the suspect functions were left in by mistake and are most likely turned off. Moreover, we need this data, so do please use the app and self-report every day if you can.

One final note that may be of interest: The app requires at least version 5 of Android to run. Android 5 was released in 2014, and Google figures say 90% of Android users are on Android 5 or above (this is a global figure; they don't say how it's distributed by country). If you are in the 10% who are still using Android phones more than 6 years old, or if you have a non-Android non-iOS phone, then you cannot use the app, which may give the results a certain selection bias. The app asks for your age, so they could in principle correct for the over-representation of younger people (the elderly are less likely to be smartphone users), but it's harder to correct for differences in income: a low-income person stuck on a 7-year-old phone (and therefore excluded from the study) is more likely to have to catch a bus to work in a supermarket every day instead of staying safe at home doing office work. If this bus user with a very old phone is therefore more likely to encounter the virus, then the data is not completely representative if we're not counting them. But some low-income families do in fact have up-to-date smartphones because they've saved up for them and made it a priority, for example because they wanted to use religious or learning apps that required smartphones, and these will now be able to participate in the Covid19 study if they wish.

(written with help from Silas S. Brown)

Thursday, 9 April 2020

Coronavirus (6) Animals tested positive for SARS-CoV-2

Three days ago, there was a report saying a Malayan tiger at the Bronx Zoo in New York city has tested positive for the SARS-CoV-2.1 It is suggested she and the other big cats (two other tigers and three African lions) were infected by an asymptomatic zoo keeper. They started to show COVID-19 symptoms like dry cough and decrease of appetite since late March this year, but they are all expected to make a full recovery soon.

That was the first report of humans transmitting the disease to animals and causing sickness to the animals. Other than that, there had been a couple of instances of pet dogs testing positive for the coronavirus elsewhere in the world.2,3 It is believed that they were being transmitted by their owners, but none of the dogs got sick or transmitted the disease to other species.

In my first article about coronavirus, I had mentioned that there is a chance animals can be infected, as ACE2, the receptor for SARS-CoV-2, is also present in dogs and cats. This indicates the potential of animals contracting the disease. However, we can expect that the number of coronavirus transmissions from humans to animals is not high, as transfer of a virus to a new host species is not a simple random process. For a virus to replicate and spread, it must be able to 1) bind to a cell-surface molecule; 2) carry out membrane fusion; 3) deliver critical components into the cytoplasm of the host; 4) avoid triggering apoptosis and highly suppressive type I interferon response; 5) interact successfully with cellular cofactors to replicate its genome and structural proteins; and 6) carry out virion assembly and exit the cells.

The infected animals in the Zoo have so far developed very mild symptoms and they are expected to recover soon. It is believed that they are infected with only a "fairly low dose" of the virus as the animals "did not have continual close contact with the asymptomatic zoo keeper", according to Dr Sarah Caddy, Veterinarian and Clinical Research Fellow at the University of Cambridge. However, as I said in my article written earlier, the other reason for very mild to no symptoms developed in the infected animals is their innate defences to suppress the infection. Additionally, their adaptive responses may eliminate the illness even if the infection from the virus overcomes their innate defenses. Therefore, the most common result of the virus transmission from humans to animals is the complete absence of disease or very mild symptoms.*

Although there is no need to fear the transmission of the virus back to humans from the infected animals, there is a possibility that the virus can linger on cats' fur and be "transmitted through touch in the same way it can be picked up from surfaces like tables and doorknobs." Therefore, according to Daniella Dos Santos, president of the British Veterinary Association (BVA), "cats should be kept inside if they live in a household where someone is suffering with the new coronavirus".4 Accordingly, the same principle should also apply to all households with animal pets.



*Although the first dog tested positive died few days after being released from mandatory quarantine, it did not show clinical symptoms when it was tested, and it was 17 years old, quite old by the breed's standards. Moreover, it was suffering from other underlying illnesses even before its 'weak positive' test. "It is very unlikely the virus had any contribution to the death of the dog."5



References

1. "Coronavirus: Tiger at Bronx Zoo tests positive for Covid-19" BBC News, 6th April, 2020. https://www.bbc.co.uk/news/world-us-canada-52177586
2. "Coronavirus: pet dog belonging to Covid-19 patient infected, Hong Kong health authorities confirm" South China Morning Post, 4thMarch,2020. https://www.scmp.com/news/hong-kong/health-environment/article/3065016/coronavirus-pet-dog-belonging-covid-19-patient
3. "Second Dog in Hong Kong Tests Positive for Covid-19 Virus" Bloomberg, 19th March,2020. https://www.bloomberg.com/news/articles/2020-03-19/second-dog-in-hong-kong-tests-positive-for-covid-19-virus
4. "Cats should be kept inside if owners show coronavirus symptoms, veterinary scientists say" CNBC, 8th April, 2020. https://www.cnbc.com/2020/04/08/cats-should-stay-inside-if-owners-show-coronavirus-symptoms-vets-say.html
5. "Coronavirus: 'very unlikely' Hong Kong dog that tested positive died from Covid-19, source says, citing old age, underlying illnesses" South China Morning Post, 4thMarch, 2020. https://www.scmp.com/news/hong-kong/health-environment/article/3075770/coronavirus-very-unlikely-hong-kong-dog-tested