#13 – SARS-CoV-1: the Outbreak That Almost Became a Pandemic
Show notes
Before SARS-CoV-2, there was SARS-CoV-1 - a closely related coronavirus that caused a serious outbreak in 2002–2003 with a case fatality rate of around 10%. Unlike its successor, SARS-CoV-1 only became transmissible after symptoms appeared, which made it possible to identify and isolate infected people even without PCR tests. The virus spread from China to Hong Kong, Canada, Singapore, and Vietnam via superspreader events before a global effort managed to contain it by June 2003. The likely origin: horseshoe bats at wet markets in Guangdong, with palm civets and raccoon dogs as intermediate hosts.
Review about the origins of SARS-CoV: https://pmc.ncbi.nlm.nih.gov/articles/PMC7120088/pdf/978-3-540-70962-6Chapter13.pdf
SARS outbreak at the Amoy Gardens residential towers: https://www.nejm.org/doi/full/10.1056/NEJMoa032867
Science article about superspreaders and the Metropole hotel in Hong Kong [unfortunately behind a paywall]: https://www.science.org/doi/10.1126/science.339.6125.1272
+++++
You can support the podcast via our German Steady page: https://steady.page/virologisch/
Questions, feedback or topic suggestions? Feel free to contact us at: virological@podcastwerkstatt.com
+++++
Krammer laboratory information
Krammer Laboratory at the Icahn School of Medicine at Mount Sinai https://labs.icahn.mssm.edu/krammerlab/
Ludwig Boltzmann Institute for Science Outreach and Pandemic Preparedness https://soap.lbg.ac.at/
Ignaz Semmelweis Institute https://semmelweisinstitute.ac.at/
+++++
Conflict of interest statement
The Icahn School of Medicine at Mount Sinai has filed patent applications relating to influenza virus vaccines and therapeutics, SARS-CoV-2 serological assays and NDV-based SARS-CoV-2 vaccines which name me as inventor. Mount Sinai has spun out a company, CastleVax, to commercialize NDV-based SARS-CoV-2 vaccines and I am named as co-founder and scientific advisory board member of that company.
I have previously consulted for Curevac, Merck, Gritstone, Sanofi, Seqirus, GSK and Pfizer and I am currently consulting for 3rd Rock Ventures (US) and Avimex (Mexico).
My laboratory has been collaborating in the past with Pfizer on animal models of SARS-CoV-2 and with GlaxoSmithKline and VIR on the development of influenza virus vaccines and therapeutics and we are currently collaborating with Dynavax, Inspirevax and Inimmune on development of influenza virus vaccines.
My work in the on immunity and infectious diseases in the US is supported by the National Institutes of Health, but also by FluLab and Tito’s Handmade Vodka. In the past I have also received funding from the Bill and Melinda Gates Foundation, PATH and the US Department of Defense.
My work in Austria is supported by the Ludwig Boltzmann Gesellschaft and by the Ignaz Semmelweis Institute through the Medical University of Vienna.
Show transcript
00:00:06: China basically didn't communicate this quickly, which is different to what happened during SARS-CoV-II.
00:00:12: During that outbreak they actually reported it relatively quickly but back in the day for SARS-COV-I They basically reported this very late and was of course not very helpful because the virus could spread without people knowing about it.
00:00:52: Hello and welcome to this week's episode of Virological!
00:00:55: This episode recorded on March third of twenty-twenty six in Austria and Western Syria.
00:01:02: And today we're going to talk about a coronavirus, actually a coronavirus that caused SARS epidemic as our outbreak before.
00:01:13: SARS CoV two is actually the reason why SARS Cov two is called SARS Co V Two.
00:01:19: there was similar virus Before and that virus was named SARS Co v initially.
00:01:25: Now a lot of people refer to it as SARS-CoV-one.
00:01:29: And so when this outbreak happened initially, It wasn't clear what was causing it and the first name for the disease in that case is Severe Acute Respiratory Syndrome.
00:01:40: So SARS!
00:01:42: Once it became clear that it was caused by coronavirus, The virus was named SARS Coronavirus or SARS-Cov-E.
00:01:50: A little bit about coronaviruses.
00:01:52: Coronaviruse have positive polarized RNA genome, single-stranded and it's about thirty thousand base pairs long which is pretty large for an RNA virus.
00:02:05: These viruses are called coronaviruses because when you look at them under electron microscope they look a little bit like a crown and that where the name corona comes from.
00:02:17: SARS coronavirus specifically part of the beta coronoviruses And within the beta coronaviruses, it's part of the subpecovirus group.
00:02:28: Subpecovirus basically brings together SARS and then beta corona so subpecho.
00:02:38: And SARS-Coronavirus II is also a part of these becoviruses.
00:02:42: So SARS-CoV-I and SARS-Cov-II are pretty closely related.
00:02:48: But there's a lot of other subcoviruses that circulate in animals specifically in bats.
00:02:54: And we'll get to that later.
00:02:56: How does the virus look like?
00:02:57: Basically, We have the genome on the inside.
00:03:00: The genome is protected by nuclear protein.
00:03:04: Then you have a lipid envelope and then this lipid envelopes both matrix-brotein and an envelope-brotin.
00:03:10: and the spike-broten Is also anchored into this lipida envelope.
00:03:15: And the spike protein is a major surface glycoprotein of the virus that the virus uses for binding to our cells.
00:03:22: The spike protein of SARS-Coronavirus I looks very, very similar to this spike protein in SARS-coronavirus II and it actually also binds with the same receptor NGiotensin converting enzyme II or ACEII.
00:03:35: so both viruses use the same receptors to get into ourselves.
00:03:40: A little bit about disease...the incubation time somewhere between one and fourteen days.
00:03:46: Typically it's four to six days, but they can be as long as fourteen days an as short is one day.
00:03:52: the symptoms are flu-like.
00:03:54: basically.
00:03:55: typically people get a fever muscle pain They become lethargic tired A cough often develops a sore throat Shortness of breath And then pneumonia.
00:04:12: A lot of cases.
00:04:13: this is a severe disease as the name says, Severe Acute Respiratory Syndrome.
00:04:18: The mortality rate or case fidelity rate back during that in the day-during that outbreak was about ten eleven percent.
00:04:26: How's the virus transmitted?
00:04:28: Or how was this virus transmitted?
00:04:30: via the respiratory tract mostly partially via respiratory droplets partially also by aerosols and could also be transmitted via fomites or via basically contaminated objects and in some cases it was also transmitted by a difficult oral route.
00:04:49: In general they are not so.
00:04:51: the reproductive number between two and four, one person infected with two to three other people And that's in line with what SARS-CoV-II did at first.
00:05:03: So there is no difference but there were two things that were different.
00:05:08: The first one is in many cases we had what you call super spreaders, so basically one person infecting a huge amount of other people –that's what they called as Super Spreader– and it was much more pronounced during SARS-CoV-I than it SARS-CoV-I only started to transmit once people became symptomatic.
00:05:39: And that's an important distinction, because when people are symptomatic and they have a fever... ...they're easier to identify.
00:05:46: then you can fish them out or isolate it.
00:05:48: You can quarantine in there.
00:05:50: doing this will stop the outbreak.
00:05:54: For SARS-COV-II that is much more difficult Because A we have a lot of asymptomatic infected individuals but they still transmit the virus.
00:06:05: And we didn't have a lot of asymptomatic cases for SARS-CoV-I, that did not seem to be much of a thing.
00:06:12: and for SARS CoV-II you can also already infect other people before you become symptomatic.
00:06:20: so it's really hard to stop a virus because... You gave the virus to others before even knowing that you were infected or sick.
00:06:31: That was different from SARS-Cov-I where most infections were caused by people who had symptoms and so it was easier to fish them out.
00:06:41: So what happened back in the day with this outbreak?
00:06:43: The outbreak started in November of two thousand two, in Foshan which is a city in Guangdong And It took quite awhile until China reported this outbreak through the WHO.
00:06:57: They reported on February eleventh of two-thousand three.
00:07:02: At that point, they already had three hundred five cases.
00:07:05: A hundred-five of them were healthcare workers and that's not a good sign.
00:07:09: So basically people got infected then went to the hospital And started infecting people there.
00:07:16: China didn't communicate this quickly Which is different from what happened during SARS-CoV-II.
00:07:22: During their outbreak They actually reported it relatively quickly But back in day for SARS-Cov-I They basically reported this very late was of course not very helpful because the virus could spread without people knowing about it outside China.
00:07:38: And in fact, the virus did spread outside of China relatively quickly.
00:07:44: It's actually super interesting Because this was investigated and infection chains were investigated.
00:07:53: The first outbreak that started outside of china in Hong Kong Could be traced back to an infection chain in the Sun Yat-sen Memorial Hospital, in Guangzhou.
00:08:06: That's the capital of Guangdong.
00:08:10: So I believe a fishmonger went to that hospital on January thirty first of two thousand three because he was sick and In that hospital infected about thirty healthcare workers.
00:08:23: One of these health care workers was Liu Zhang Lun who then went to Hong Kong on February twenty-first of two thousand three to visit relatives and he checked into the major ball hotel in Hong Kong.
00:08:40: He had a room under ninth floor, Room nine eleven.
00:08:44: you can imagine how many conspiracy theories came out that just because it was number nine eleven And yeah...he checked this hotel then started visiting family in Hongkong And at the hotel alone he infected twenty-three other guests.
00:09:00: Of course, you also infected family members that he visited and unfortunately He died on March fourth of two thousand three.
00:09:08: Approximately eighty percent of all cases All SARS-CoV.
00:09:12: one case in Hong Kong can be traced back to Liuzhan Lone.
00:09:18: This is what I mean with super spreaders right?
00:09:21: So he really infected a lot different people And from Hong Kong, the virus traveled on.
00:09:27: Another person who got infected in Hong Kong Johnny Chen went to Vietnam fell sick and then was admitted to the French hospital in Hanoi... ...and died there on March thirteenth.
00:09:41: but he already had infected health care workers there including Kalu Urbani Epidemiologist who worked for the WHO and unfortunately Kalu urbani also died on march twenty-ninth from the infection.
00:09:57: One of their main SARS-CoV-one strains that is used in researches, it's actually the Urbani strain which was isolated from him.
00:10:06: The virus didn't stay in Southeast Asia It also made to the Americas.
00:10:12: Quanzuichu Was also a guest at the metropole hotel because infected there and afterwards went back to Canada to Toronto.
00:10:22: She got sick there.
00:10:23: I was admitted to the Scarborough Grace Hospital in Toronto and unfortunately died on March fifth, but also infected healthcare workers there.
00:10:34: Infected patients.
00:10:36: that led to the first wave of SARS-CoV-I in Canada And then there was a second wave associated with the North York hospital.
00:10:46: Also in Toronto We'll get into numbers in a minute But Canada had quite few cases of SARS Cov-I infections.
00:10:55: Another interesting case is what happened at Amoy Gardens.
00:10:58: This is a complex of high-rise residential towers in Hong Kong, and one of the visitors was infected with SARS-CoV-I.
00:11:13: And I mentioned earlier that sometimes you have thickly oral infection route associated with SARS Cov-I and SARS-CoV-one also quite frequently caused diarrhea symptoms.
00:11:28: And so this person had diarrhea, induced a restroom in one of these apartments flushed the toilet... ...and there was something wrong with the plumbing system!
00:11:39: So the toilet produced lots of aerosol that actually left the building and spread into this complex made it to some other high-rise towers and that led to about three hundred infected individuals, unfortunately approximately forty deaths.
00:12:00: And the interesting part here is really this was a building-to-building spread by aerosol that came from defective plumbing system.
00:12:09: somebody used who had diarrhea which was infected with SARS-CoV-one.
00:12:14: That's actually very nice paper that describes this incident and they looked at wind direction, wind speed and so on.
00:12:22: And figured out why some of the towers had cases... ...and other towers didn't have cases?
00:12:28: They had to do with the wind direction….
00:12:31: …how that aerosol was spread.
00:12:33: It's a very nice paper and it is nicely worked-out.
00:12:37: The peak of this epidemic was in May of two thousand three.
00:12:42: A lot of counter measures were put into place.
00:12:46: People were quarantined when they had a fever.
00:12:49: The airport started to measure temperature of travelers by infrared cameras.
00:12:55: if you have elevated temperatures, then you got fished out and quarantined And as I mentioned earlier only people who were symptomatic were transmitting the virus.
00:13:04: so this helped.
00:13:06: They were actually able to control these outbreaks just by quarantining people and isolating them And their outbreak officially ended in June.
00:13:17: of two thousand three.
00:13:18: the countries that were most affected where China and Hong Kong.
00:13:23: And then Taiwan had a lot of cases, Canada had two hundred forty one cases and fourty-three deaths.
00:13:30: so canada had a load of cases.
00:13:31: it was amazing they could stop with.
00:13:34: Singapore also have alot of cases.
00:13:36: Vietnam has alot of case.
00:13:39: US had twenty seven cases no death.
00:13:42: I guess the US was lucky in that sense, there were no bigger outbreaks like Canada.
00:13:49: Globally about eight thousand cases associated with this outbreak and about eight hundred deaths.
00:13:56: So case for deload rate of ten percent.
00:13:58: it's a little bit higher maybe eleven percent if you look at all their numbers.
00:14:04: Globarly they are totaled by eight thousand.
00:14:12: The amazing thing about this outbreak is we all still remember SARS-CoV-II, right?
00:14:18: For SARS-Cov-II from the beginning.
00:14:20: We had ways of detecting the virus and testing people if they were infected with all these PCR tests.
00:14:29: but that was absolutely not the case for SARS-COV-I.
00:14:32: It took until April of two thousand three to figure out what actually caused this outbreak.
00:14:39: At that point the virus was identified, genome was sequenced.
00:14:43: This first shift in Canada at British Columbia Cancer Agency and the virus then isolated in Hong Kong by Malik Byris I believe And at Erasmus Medical Center In The Netherlands.
00:14:58: they infected macaques with this virus and could reproduce the disease.
00:15:03: So there really an international effort to decode it To figure out what's going on identified a causative agent.
00:15:12: But again, this wasn't clear until April of two thousand three.
00:15:16: so for most of the outbreak there were no PCRs.
00:15:18: that was not testing specifically for the virus.
00:15:21: infected people are identified by just you know looking at symptoms and then isolating them And that's how their outbreak was controlled.
00:15:29: as I mentioned The outbreak was declared over in June of two hundred three.
00:15:33: There were infections afterwards.
00:15:35: they were laboratory associated In Singapore, a person got infected in a lab in August of two thousand three.
00:15:43: And Taipei and Taiwan in December of two-thousand three.
00:15:47: so these are single cases.
00:15:49: then in April of two hundred four one person got affected in the laboratory in Beijing and passed the virus on to six more individuals.
00:15:58: but this cluster could be stopped.
00:16:01: So since then This virus has not been circulating in humans But it's certainly out there at the animal reservoir.
00:16:09: And of course, there were a lot of investigations after the outbreak because people wanted to figure out where this virus came from.
00:16:16: It became clear quite quickly that all kinds of animals at wet markets in China and Guangdong were infected with these viruses.
00:16:26: This included palm civets, raccoon dogs, ferret batches but also domestic cats.
00:16:33: And in two thousand five it was found that rhinolophous bats also carried the virus or a virus that was very closely related.
00:16:40: So these are horseshoe bats, they're relatively common all over Asia.
00:16:46: some of them even exist in Europe and actually SARS-like viruses have been found in rhino-lophose bats in Europe as well I think in Bulgaria.
00:16:55: but The idea in the end is this bats are sometimes found on wet markets sometimes sold on this market.
00:17:04: The idea was that these bats carried the virus and then basically at wet markets, holding pens infected the civets, infected the raccoon dogs, infected other animals... And then the virus jumped from these animals that were sold to customers into humans!
00:17:23: That seems how this outbreak developed.
00:17:28: Later on…the potential source of the virus in terms of the bats was also identified.
00:17:38: It seems that you can trace back the virus to a bat cave, in the Yunnan province.
00:17:45: so this virus is probably still out there but again hasn't caused any issues since two thousand and three And slightly circulating in beds But not not in humans anymore.
00:17:57: Of course after they outbreak people started to look into counter measures.
00:18:02: vaccines were developed.
00:18:04: two vaccines made it into clinical trials.
00:18:06: In early stage phase one trials, one DNA vaccine that NIH developed in the US and then one inactivated virus vaccine that was developed in China and also made it to a Phase One trial.
00:18:21: And this is actually a vaccine very similar to SARS-CoV-II inactivate vaccine which was also developped in China in year of twenty and used by many different countries.
00:18:32: Of course there were many other vaccine approaches that were developed to pre-clinically, so in animal models but never made it into clinical testing.
00:18:40: And even the two vaccines that made them into clinical tests was stopped after phase one because they had no need right?
00:18:48: The virus was eradicated from humans and wasn't circulating anymore... ...and there's not a need for further clinically developing these vaccines.
00:18:59: I think what is also interesting to mention With our exposure now to SARS-CoV-II through infections, vaccination and so on.
00:19:09: We actually do have neutralizing antibody titers against SARS-COV-I.
00:19:14: So if you take blood from random people in the human population right now And you run neutralization asses against SARS CoV- II Of course a lot of people are very high neutralizing antibodies.
00:19:26: But if you run neutralization as is against SARS-CoV-I, You also find some neutralizing antibodies.
00:19:32: Much much lower titers and concentration.
00:19:35: but people now have neutralized antibodies against this virus And so in my opinion it's very unlikely that SARS-Cov-I currently would be pandemic threat or an issue because of causing another outbreak.
00:19:49: Because we all these antibodies are in the population there probably a lot resistance.
00:19:54: In my opinion, this is unlikely that these virus would make it in the human population and could cause a large outbreak.
00:20:03: On the other side viruses are often unpredictable so maybe I shouldn't even say that but again there's some immunity to the populations against this virus.
00:20:11: now Alright!
00:20:12: That's it for today.
00:20:14: Super interesting outbreak back in two thousand three.
00:20:19: It actually amazing.
00:20:21: It could be stopped.
00:20:22: This would have easily been another pandemic, but it was able through global efforts to stop this outbreak and basically end in June of two thousand three.
00:20:35: as always if you any comments questions suggestions concerns please write an email to Virological at podcast.com And If You like the podcast you can support on steady.
00:20:48: thanks for listening until next week.
00:20:54: If you're enjoying the podcast and would like to support our work, visit us on Steady.
00:20:59: You'll find a link in the show notes And don't forget to follow & leave a review of your favorite podcast app Podcastwerkstatt.
New comment