Can you explain COVID-19 in lay terms?<\/strong><\/span><\/h3>\nChristopher Mason<\/strong>:<\/span>\u00a0COVID-19 is the name of the disease that is caused by\u00a0severe acute respiratory syndrome coronavirus 2<\/a>, or SARS-CoV-2. That name doesn\u2019t roll off the tongue, so it is shortened as COVID-19 because the disease was found at the end of 2019. There are seven types of coronaviruses. It\u2019s called a coronavirus because it has these little spikes on the outside. If you look at the virus under a microscope, it looks like it\u2019s wearing a crown \u2014 \u201ccorona\u201d is Latin for crown. Those little spike proteins can actually adhere to human epithelial cells, like in your lungs. Once the coronavirus gets into your cells, it hijacks the cells\u2019 machinery. To get started, it converts its RNA into proteins, which provide the raw materials to start the job of replicating itself. It uses the human cells\u2019 machinery that normally modifies and controls human proteins to make new virus \u201cpackages\u201d \u2014 which contain new copies of the virus RNA and other proteins \u2014 and leave the cell as a\u00a0\u201cvirion,\u201d<\/a>\u00a0which can then infect other cells. It basically convinces the human cell to make a copy of something bad.<\/p>\nHow does COVID-19 compare with the flu?<\/strong><\/span><\/h3>\nIt is about two times more infectious than the flu, based on what\u2019s called an R naught [R0] statistic of how many people one person will infect. At the same time, it is about ten to 30 times more deadly than the flu, keeping in mind that the fatality rate of the flu is about 0.1 percent.\u00a0The flu infects millions of people every year<\/a>\u00a0\u2014 32 million in the U.S., on average \u2014 and tens of thousands die every year. However, one of the reasons people are more worried about COVID-19 is that we don\u2019t want to have a \u201cflu part two\u201d that\u2019s always roaming between the hemispheres and infecting people annually \u2014 and is more deadly. It\u2019s too late for the flu, but hopefully it\u2019s not too late for COVID-19.<\/p>\nIs Weill Cornell seeing a lot of COVID-19 patients?<\/strong><\/span><\/h3>\nYes. Of those coming in and getting tested, it started out that about 10 to 15 percent of people were showing the SARS-CoV-2 virus. Then it was 25 percent. Recently, more than half of the people coming in who think they have COVID actually do. Finally, it has started to flatten out and come down.<\/p>\n
What role does your lab play?<\/strong><\/span><\/h3>\nWhen patients are tested, their samples go to pathology to get a yes or a no answer to: is the virus there? Then, most of those samples [positive or negative] come to our lab. We have four people processing hundreds of samples a day doing RNA sequencing. We then look at all of the RNA species: human, viral, bacterial, fungal, and anything else. If there are other viruses present, we can see them. For example, in some of our patients we\u2019ve identified influenza as well as coronavirus. Some people are getting an unfortunate double-dose of a virus; we can see that in the data.<\/p>\n
We\u2019re also developing a new test that has the potential to detect the virus in a fast and easy way. Instead of the traditional way of getting a sample using a\u00a0nasopharyngeal swab<\/a>\u00a0\u2014 which is inserted through the nasal cavity to the back of your throat and is the equivalent of a cranial colonoscopy \u2014 our test works with just a buccal swab of your mouth or saliva. When our assay is fully rolled out, we could have results in as soon as 20 to 30 minutes.<\/p>\nWhy do traditional testing methods take so long?<\/strong><\/span><\/h3>\nThe current way you diagnose someone is to use a molecular biology technique called a qRT-PCR, or\u00a0quantitative reverse-transcription polymerase chain reaction<\/a>, to detect and amplify the virus\u2019s RNA. First you have to extract the RNA from the patient\u2019s cells, which you have to do in an automated way in the pathology laboratory. Next, the PCR machine, which amplifies the RNA through a series of thermal cycles, takes time. After you get the results back, you\u2019ll want to perform quality control (\u201cQC them\u201d), to make sure your positives are positive and your negatives are negative. All in, PCR tests could take anywhere between two and eight hours.<\/p>\nWhat\u2019s cool about our new experimental test is that it uses a single-tube reaction called LAMP, which stands for\u00a0loop-mediated isothermal amplification<\/a>. LAMP works really fast because we use what is called the strand displacement polymerase \u2014 once the primer finds the virus, it\u2019ll keep making many, many copies continuously. [A primer is a short strand of nucleic acid used to start DNA synthesis.] Whereas with RT-PCR you have to heat up the reaction, essentially make it so the molecules disassociate, and then cool it back down again and then watch if the reaction happens a second time, with LAMP you keep everything at the same temperature. You run it at 65 degrees Celsius, and you\u2019ll know essentially whether the virus is there within minutes. We put a chemistry into the tube that is like a pH meter, which goes from pink to yellow. So, if the virus is there, you could know in as fast as 15 to 20 minutes; if it\u2019s a less-abundant virus it could be 30 minutes. That\u2019s the goal we are working toward.<\/p>\n\n![\"\"](\"https:\/\/www.worldquant.com\/wp-content\/uploads\/2022\/04\/Mason-Pic-BW-scaled.jpg\")
<\/div>\nSince the virus mutates as it moves through the world, you can predict the likely origin of a mutation based on the country in which it was first seen.<\/p><\/blockquote>\n
<\/div>\nAnd how did you come up with the idea for the test?<\/strong><\/span><\/h3>\nThe chemistry behind the idea is actually old. The first paper on LAMP was published 20 years ago; it was a kind of proof of principle. In 2014,\u00a0New England Biolabs<\/a>\u00a0(NEB) commercialized the method to make it more reliable, flexible and automated. I\u2019ve advised the company for a while and know many of their scientists and methods, so I asked, \u201cWhat is the fastest way to track the virus?\u201d They said, \u201cWe collaborated with one group in China that got LAMP to work on seven samples.\u201d The Chinese data were intriguing, but we all knew more data was needed. So, I said, \u201cWell, we\u2019ve got samples starting to come in here. Let\u2019s try it. Let\u2019s optimize it, then let\u2019s make it mobile.\u201d Since March, we have been working very closely with NEB\u2019s scientists to get LAMP working across the U.S. and internationally, and we are openly publishing our protocol updates as we go along.<\/p>\nHow does your LAMP test compare with the rapid COVID-19 test developed by Abbott Labs?<\/strong><\/span><\/h3>\nThe\u00a0Abbott Labs<\/a>\u00a0test can give results in about 15 minutes, and is built around some of the same ideas of \u201cisothermal amplification.\u201d However, technicians can test only one patient at a time, whereas LAMP and even PCR is scalable. We are setting up our reagents and protocols to all be open-source so people can build from them.<\/p>\nDid the strain of COVID-19 that hit New York come from Europe?<\/strong><\/span><\/h3>\nWe think so, and we know this from several types of data. As samples started coming into Weill Cornell Medicine, we used a technology method called\u00a0\u201ctotal RNA sequencing\u201d<\/a>\u00a0to examine the genetic code of the virus for the patients infected with SARS-CoV-2, as well as any other viruses present, and also to track the response of the infected human cells. This let us look at all the mutations present in the virus, and we could immediately compare this to other strains deposited online using a database called\u00a0GISAID<\/a>. Since the virus mutates as it moves through the world, you can predict the likely origin of a mutation based on the country in which it was first seen. We found a case in Belgium that seems to be one of the first sources of the New York strain. Our data was confirmed by work by other groups at\u00a0NYU Langone<\/a>\u00a0and\u00a0Mount Sinai<\/a>, which shows that the majority of cases in NYC likely came from Europe.<\/p>\nAs a geneticist, can you talk about the evolution of COVID-19?<\/strong><\/span><\/h3>\nWe have seen different types of the virus, or strains, emerge as it has moved throughout the world. Once a virus comes into a region (like from Belgium), it can spread with different speeds. In China, scientists saw a mutation that defined a possible new strain called the \u201cL strain,\u201d and this was found in over 70 percent of the country\u2019s cases. They postulated that this might be what made the virus so severe in Wuhan, and it was also seen in other places in Europe, but more data were needed. Strikingly, we identified a clear predominance of the L strain (94 percent) in NYC, which supports this idea. However, we don\u2019t yet know how significant this is in terms of the biology of the virus and what it does to patient cells and if it leads to worse outcomes for those who get it \u2014 we are looking at this clinical data right now as a next step.<\/p>\n
Is there a demonstrable difference between the strains of COVID-19 that came from China and from Europe, and how will that affect efforts to come up with a vaccine?<\/strong><\/span><\/h3>\nYes, indeed, we are seeing varying strain distributions, like the L strain, but we also have found unique mutations and subgroups of viruses specific to New York City. The deletion we found in the virus for some NYC patients removed a piece of the SARS-CoV-2 virus that had evolved to be different from SARS-CoV-1, which means that some patients had a virus has somewhat \u201cregressed back\u201d to the previously known sequence of SARS. The deletion is in a conserved portion of a gene called NSP1, which has been linked to how humans respond to the virus and could potentially explain why the cases were so severe. All of our sequence data has been deposited into the GISAID and CDC databases, so other scientists and clinicians can develop better tests for tracking the virus and developing vaccines. Although the world has never been more interconnected \u2014 and thus at risk of a pandemic \u2014 we also have never been more scientifically and medically integrated to be able to rapidly track, sequence and respond to a viral threat as soon as it emerges. It gives me hope.<\/p>\n
Is there anything that can be done in the future to prevent a similar pandemic?<\/strong><\/span><\/h3>\n
How does COVID-19 compare with the flu?<\/strong><\/span><\/h3>\nIt is about two times more infectious than the flu, based on what\u2019s called an R naught [R0] statistic of how many people one person will infect. At the same time, it is about ten to 30 times more deadly than the flu, keeping in mind that the fatality rate of the flu is about 0.1 percent.\u00a0The flu infects millions of people every year<\/a>\u00a0\u2014 32 million in the U.S., on average \u2014 and tens of thousands die every year. However, one of the reasons people are more worried about COVID-19 is that we don\u2019t want to have a \u201cflu part two\u201d that\u2019s always roaming between the hemispheres and infecting people annually \u2014 and is more deadly. It\u2019s too late for the flu, but hopefully it\u2019s not too late for COVID-19.<\/p>\nIs Weill Cornell seeing a lot of COVID-19 patients?<\/strong><\/span><\/h3>\nYes. Of those coming in and getting tested, it started out that about 10 to 15 percent of people were showing the SARS-CoV-2 virus. Then it was 25 percent. Recently, more than half of the people coming in who think they have COVID actually do. Finally, it has started to flatten out and come down.<\/p>\n
What role does your lab play?<\/strong><\/span><\/h3>\nWhen patients are tested, their samples go to pathology to get a yes or a no answer to: is the virus there? Then, most of those samples [positive or negative] come to our lab. We have four people processing hundreds of samples a day doing RNA sequencing. We then look at all of the RNA species: human, viral, bacterial, fungal, and anything else. If there are other viruses present, we can see them. For example, in some of our patients we\u2019ve identified influenza as well as coronavirus. Some people are getting an unfortunate double-dose of a virus; we can see that in the data.<\/p>\n
We\u2019re also developing a new test that has the potential to detect the virus in a fast and easy way. Instead of the traditional way of getting a sample using a\u00a0nasopharyngeal swab<\/a>\u00a0\u2014 which is inserted through the nasal cavity to the back of your throat and is the equivalent of a cranial colonoscopy \u2014 our test works with just a buccal swab of your mouth or saliva. When our assay is fully rolled out, we could have results in as soon as 20 to 30 minutes.<\/p>\nWhy do traditional testing methods take so long?<\/strong><\/span><\/h3>\nThe current way you diagnose someone is to use a molecular biology technique called a qRT-PCR, or\u00a0quantitative reverse-transcription polymerase chain reaction<\/a>, to detect and amplify the virus\u2019s RNA. First you have to extract the RNA from the patient\u2019s cells, which you have to do in an automated way in the pathology laboratory. Next, the PCR machine, which amplifies the RNA through a series of thermal cycles, takes time. After you get the results back, you\u2019ll want to perform quality control (\u201cQC them\u201d), to make sure your positives are positive and your negatives are negative. All in, PCR tests could take anywhere between two and eight hours.<\/p>\nWhat\u2019s cool about our new experimental test is that it uses a single-tube reaction called LAMP, which stands for\u00a0loop-mediated isothermal amplification<\/a>. LAMP works really fast because we use what is called the strand displacement polymerase \u2014 once the primer finds the virus, it\u2019ll keep making many, many copies continuously. [A primer is a short strand of nucleic acid used to start DNA synthesis.] Whereas with RT-PCR you have to heat up the reaction, essentially make it so the molecules disassociate, and then cool it back down again and then watch if the reaction happens a second time, with LAMP you keep everything at the same temperature. You run it at 65 degrees Celsius, and you\u2019ll know essentially whether the virus is there within minutes. We put a chemistry into the tube that is like a pH meter, which goes from pink to yellow. So, if the virus is there, you could know in as fast as 15 to 20 minutes; if it\u2019s a less-abundant virus it could be 30 minutes. That\u2019s the goal we are working toward.<\/p>\n\n<\/div>\nSince the virus mutates as it moves through the world, you can predict the likely origin of a mutation based on the country in which it was first seen.<\/p><\/blockquote>\n
<\/div>\nAnd how did you come up with the idea for the test?<\/strong><\/span><\/h3>\nThe chemistry behind the idea is actually old. The first paper on LAMP was published 20 years ago; it was a kind of proof of principle. In 2014,\u00a0New England Biolabs<\/a>\u00a0(NEB) commercialized the method to make it more reliable, flexible and automated. I\u2019ve advised the company for a while and know many of their scientists and methods, so I asked, \u201cWhat is the fastest way to track the virus?\u201d They said, \u201cWe collaborated with one group in China that got LAMP to work on seven samples.\u201d The Chinese data were intriguing, but we all knew more data was needed. So, I said, \u201cWell, we\u2019ve got samples starting to come in here. Let\u2019s try it. Let\u2019s optimize it, then let\u2019s make it mobile.\u201d Since March, we have been working very closely with NEB\u2019s scientists to get LAMP working across the U.S. and internationally, and we are openly publishing our protocol updates as we go along.<\/p>\nHow does your LAMP test compare with the rapid COVID-19 test developed by Abbott Labs?<\/strong><\/span><\/h3>\nThe\u00a0Abbott Labs<\/a>\u00a0test can give results in about 15 minutes, and is built around some of the same ideas of \u201cisothermal amplification.\u201d However, technicians can test only one patient at a time, whereas LAMP and even PCR is scalable. We are setting up our reagents and protocols to all be open-source so people can build from them.<\/p>\nDid the strain of COVID-19 that hit New York come from Europe?<\/strong><\/span><\/h3>\nWe think so, and we know this from several types of data. As samples started coming into Weill Cornell Medicine, we used a technology method called\u00a0\u201ctotal RNA sequencing\u201d<\/a>\u00a0to examine the genetic code of the virus for the patients infected with SARS-CoV-2, as well as any other viruses present, and also to track the response of the infected human cells. This let us look at all the mutations present in the virus, and we could immediately compare this to other strains deposited online using a database called\u00a0GISAID<\/a>. Since the virus mutates as it moves through the world, you can predict the likely origin of a mutation based on the country in which it was first seen. We found a case in Belgium that seems to be one of the first sources of the New York strain. Our data was confirmed by work by other groups at\u00a0NYU Langone<\/a>\u00a0and\u00a0Mount Sinai<\/a>, which shows that the majority of cases in NYC likely came from Europe.<\/p>\nAs a geneticist, can you talk about the evolution of COVID-19?<\/strong><\/span><\/h3>\nWe have seen different types of the virus, or strains, emerge as it has moved throughout the world. Once a virus comes into a region (like from Belgium), it can spread with different speeds. In China, scientists saw a mutation that defined a possible new strain called the \u201cL strain,\u201d and this was found in over 70 percent of the country\u2019s cases. They postulated that this might be what made the virus so severe in Wuhan, and it was also seen in other places in Europe, but more data were needed. Strikingly, we identified a clear predominance of the L strain (94 percent) in NYC, which supports this idea. However, we don\u2019t yet know how significant this is in terms of the biology of the virus and what it does to patient cells and if it leads to worse outcomes for those who get it \u2014 we are looking at this clinical data right now as a next step.<\/p>\n
Is there a demonstrable difference between the strains of COVID-19 that came from China and from Europe, and how will that affect efforts to come up with a vaccine?<\/strong><\/span><\/h3>\nYes, indeed, we are seeing varying strain distributions, like the L strain, but we also have found unique mutations and subgroups of viruses specific to New York City. The deletion we found in the virus for some NYC patients removed a piece of the SARS-CoV-2 virus that had evolved to be different from SARS-CoV-1, which means that some patients had a virus has somewhat \u201cregressed back\u201d to the previously known sequence of SARS. The deletion is in a conserved portion of a gene called NSP1, which has been linked to how humans respond to the virus and could potentially explain why the cases were so severe. All of our sequence data has been deposited into the GISAID and CDC databases, so other scientists and clinicians can develop better tests for tracking the virus and developing vaccines. Although the world has never been more interconnected \u2014 and thus at risk of a pandemic \u2014 we also have never been more scientifically and medically integrated to be able to rapidly track, sequence and respond to a viral threat as soon as it emerges. It gives me hope.<\/p>\n
Is there anything that can be done in the future to prevent a similar pandemic?<\/strong><\/span><\/h3>\n
Is Weill Cornell seeing a lot of COVID-19 patients?<\/strong><\/span><\/h3>\nYes. Of those coming in and getting tested, it started out that about 10 to 15 percent of people were showing the SARS-CoV-2 virus. Then it was 25 percent. Recently, more than half of the people coming in who think they have COVID actually do. Finally, it has started to flatten out and come down.<\/p>\n
What role does your lab play?<\/strong><\/span><\/h3>\nWhen patients are tested, their samples go to pathology to get a yes or a no answer to: is the virus there? Then, most of those samples [positive or negative] come to our lab. We have four people processing hundreds of samples a day doing RNA sequencing. We then look at all of the RNA species: human, viral, bacterial, fungal, and anything else. If there are other viruses present, we can see them. For example, in some of our patients we\u2019ve identified influenza as well as coronavirus. Some people are getting an unfortunate double-dose of a virus; we can see that in the data.<\/p>\n
We\u2019re also developing a new test that has the potential to detect the virus in a fast and easy way. Instead of the traditional way of getting a sample using a\u00a0nasopharyngeal swab<\/a>\u00a0\u2014 which is inserted through the nasal cavity to the back of your throat and is the equivalent of a cranial colonoscopy \u2014 our test works with just a buccal swab of your mouth or saliva. When our assay is fully rolled out, we could have results in as soon as 20 to 30 minutes.<\/p>\nWhy do traditional testing methods take so long?<\/strong><\/span><\/h3>\nThe current way you diagnose someone is to use a molecular biology technique called a qRT-PCR, or\u00a0quantitative reverse-transcription polymerase chain reaction<\/a>, to detect and amplify the virus\u2019s RNA. First you have to extract the RNA from the patient\u2019s cells, which you have to do in an automated way in the pathology laboratory. Next, the PCR machine, which amplifies the RNA through a series of thermal cycles, takes time. After you get the results back, you\u2019ll want to perform quality control (\u201cQC them\u201d), to make sure your positives are positive and your negatives are negative. All in, PCR tests could take anywhere between two and eight hours.<\/p>\nWhat\u2019s cool about our new experimental test is that it uses a single-tube reaction called LAMP, which stands for\u00a0loop-mediated isothermal amplification<\/a>. LAMP works really fast because we use what is called the strand displacement polymerase \u2014 once the primer finds the virus, it\u2019ll keep making many, many copies continuously. [A primer is a short strand of nucleic acid used to start DNA synthesis.] Whereas with RT-PCR you have to heat up the reaction, essentially make it so the molecules disassociate, and then cool it back down again and then watch if the reaction happens a second time, with LAMP you keep everything at the same temperature. You run it at 65 degrees Celsius, and you\u2019ll know essentially whether the virus is there within minutes. We put a chemistry into the tube that is like a pH meter, which goes from pink to yellow. So, if the virus is there, you could know in as fast as 15 to 20 minutes; if it\u2019s a less-abundant virus it could be 30 minutes. That\u2019s the goal we are working toward.<\/p>\n\n<\/div>\nSince the virus mutates as it moves through the world, you can predict the likely origin of a mutation based on the country in which it was first seen.<\/p><\/blockquote>\n
<\/div>\nAnd how did you come up with the idea for the test?<\/strong><\/span><\/h3>\nThe chemistry behind the idea is actually old. The first paper on LAMP was published 20 years ago; it was a kind of proof of principle. In 2014,\u00a0New England Biolabs<\/a>\u00a0(NEB) commercialized the method to make it more reliable, flexible and automated. I\u2019ve advised the company for a while and know many of their scientists and methods, so I asked, \u201cWhat is the fastest way to track the virus?\u201d They said, \u201cWe collaborated with one group in China that got LAMP to work on seven samples.\u201d The Chinese data were intriguing, but we all knew more data was needed. So, I said, \u201cWell, we\u2019ve got samples starting to come in here. Let\u2019s try it. Let\u2019s optimize it, then let\u2019s make it mobile.\u201d Since March, we have been working very closely with NEB\u2019s scientists to get LAMP working across the U.S. and internationally, and we are openly publishing our protocol updates as we go along.<\/p>\nHow does your LAMP test compare with the rapid COVID-19 test developed by Abbott Labs?<\/strong><\/span><\/h3>\nThe\u00a0Abbott Labs<\/a>\u00a0test can give results in about 15 minutes, and is built around some of the same ideas of \u201cisothermal amplification.\u201d However, technicians can test only one patient at a time, whereas LAMP and even PCR is scalable. We are setting up our reagents and protocols to all be open-source so people can build from them.<\/p>\nDid the strain of COVID-19 that hit New York come from Europe?<\/strong><\/span><\/h3>\nWe think so, and we know this from several types of data. As samples started coming into Weill Cornell Medicine, we used a technology method called\u00a0\u201ctotal RNA sequencing\u201d<\/a>\u00a0to examine the genetic code of the virus for the patients infected with SARS-CoV-2, as well as any other viruses present, and also to track the response of the infected human cells. This let us look at all the mutations present in the virus, and we could immediately compare this to other strains deposited online using a database called\u00a0GISAID<\/a>. Since the virus mutates as it moves through the world, you can predict the likely origin of a mutation based on the country in which it was first seen. We found a case in Belgium that seems to be one of the first sources of the New York strain. Our data was confirmed by work by other groups at\u00a0NYU Langone<\/a>\u00a0and\u00a0Mount Sinai<\/a>, which shows that the majority of cases in NYC likely came from Europe.<\/p>\nAs a geneticist, can you talk about the evolution of COVID-19?<\/strong><\/span><\/h3>\nWe have seen different types of the virus, or strains, emerge as it has moved throughout the world. Once a virus comes into a region (like from Belgium), it can spread with different speeds. In China, scientists saw a mutation that defined a possible new strain called the \u201cL strain,\u201d and this was found in over 70 percent of the country\u2019s cases. They postulated that this might be what made the virus so severe in Wuhan, and it was also seen in other places in Europe, but more data were needed. Strikingly, we identified a clear predominance of the L strain (94 percent) in NYC, which supports this idea. However, we don\u2019t yet know how significant this is in terms of the biology of the virus and what it does to patient cells and if it leads to worse outcomes for those who get it \u2014 we are looking at this clinical data right now as a next step.<\/p>\n
Is there a demonstrable difference between the strains of COVID-19 that came from China and from Europe, and how will that affect efforts to come up with a vaccine?<\/strong><\/span><\/h3>\nYes, indeed, we are seeing varying strain distributions, like the L strain, but we also have found unique mutations and subgroups of viruses specific to New York City. The deletion we found in the virus for some NYC patients removed a piece of the SARS-CoV-2 virus that had evolved to be different from SARS-CoV-1, which means that some patients had a virus has somewhat \u201cregressed back\u201d to the previously known sequence of SARS. The deletion is in a conserved portion of a gene called NSP1, which has been linked to how humans respond to the virus and could potentially explain why the cases were so severe. All of our sequence data has been deposited into the GISAID and CDC databases, so other scientists and clinicians can develop better tests for tracking the virus and developing vaccines. Although the world has never been more interconnected \u2014 and thus at risk of a pandemic \u2014 we also have never been more scientifically and medically integrated to be able to rapidly track, sequence and respond to a viral threat as soon as it emerges. It gives me hope.<\/p>\n
Is there anything that can be done in the future to prevent a similar pandemic?<\/strong><\/span><\/h3>\n
When patients are tested, their samples go to pathology to get a yes or a no answer to: is the virus there? Then, most of those samples [positive or negative] come to our lab. We have four people processing hundreds of samples a day doing RNA sequencing. We then look at all of the RNA species: human, viral, bacterial, fungal, and anything else. If there are other viruses present, we can see them. For example, in some of our patients we\u2019ve identified influenza as well as coronavirus. Some people are getting an unfortunate double-dose of a virus; we can see that in the data.<\/p>\n
We\u2019re also developing a new test that has the potential to detect the virus in a fast and easy way. Instead of the traditional way of getting a sample using a\u00a0nasopharyngeal swab<\/a>\u00a0\u2014 which is inserted through the nasal cavity to the back of your throat and is the equivalent of a cranial colonoscopy \u2014 our test works with just a buccal swab of your mouth or saliva. When our assay is fully rolled out, we could have results in as soon as 20 to 30 minutes.<\/p>\n The current way you diagnose someone is to use a molecular biology technique called a qRT-PCR, or\u00a0quantitative reverse-transcription polymerase chain reaction<\/a>, to detect and amplify the virus\u2019s RNA. First you have to extract the RNA from the patient\u2019s cells, which you have to do in an automated way in the pathology laboratory. Next, the PCR machine, which amplifies the RNA through a series of thermal cycles, takes time. After you get the results back, you\u2019ll want to perform quality control (\u201cQC them\u201d), to make sure your positives are positive and your negatives are negative. All in, PCR tests could take anywhere between two and eight hours.<\/p>\n What\u2019s cool about our new experimental test is that it uses a single-tube reaction called LAMP, which stands for\u00a0loop-mediated isothermal amplification<\/a>. LAMP works really fast because we use what is called the strand displacement polymerase \u2014 once the primer finds the virus, it\u2019ll keep making many, many copies continuously. [A primer is a short strand of nucleic acid used to start DNA synthesis.] Whereas with RT-PCR you have to heat up the reaction, essentially make it so the molecules disassociate, and then cool it back down again and then watch if the reaction happens a second time, with LAMP you keep everything at the same temperature. You run it at 65 degrees Celsius, and you\u2019ll know essentially whether the virus is there within minutes. We put a chemistry into the tube that is like a pH meter, which goes from pink to yellow. So, if the virus is there, you could know in as fast as 15 to 20 minutes; if it\u2019s a less-abundant virus it could be 30 minutes. That\u2019s the goal we are working toward.<\/p>\n Since the virus mutates as it moves through the world, you can predict the likely origin of a mutation based on the country in which it was first seen.<\/p><\/blockquote>\n The chemistry behind the idea is actually old. The first paper on LAMP was published 20 years ago; it was a kind of proof of principle. In 2014,\u00a0New England Biolabs<\/a>\u00a0(NEB) commercialized the method to make it more reliable, flexible and automated. I\u2019ve advised the company for a while and know many of their scientists and methods, so I asked, \u201cWhat is the fastest way to track the virus?\u201d They said, \u201cWe collaborated with one group in China that got LAMP to work on seven samples.\u201d The Chinese data were intriguing, but we all knew more data was needed. So, I said, \u201cWell, we\u2019ve got samples starting to come in here. Let\u2019s try it. Let\u2019s optimize it, then let\u2019s make it mobile.\u201d Since March, we have been working very closely with NEB\u2019s scientists to get LAMP working across the U.S. and internationally, and we are openly publishing our protocol updates as we go along.<\/p>\n The\u00a0Abbott Labs<\/a>\u00a0test can give results in about 15 minutes, and is built around some of the same ideas of \u201cisothermal amplification.\u201d However, technicians can test only one patient at a time, whereas LAMP and even PCR is scalable. We are setting up our reagents and protocols to all be open-source so people can build from them.<\/p>\n We think so, and we know this from several types of data. As samples started coming into Weill Cornell Medicine, we used a technology method called\u00a0\u201ctotal RNA sequencing\u201d<\/a>\u00a0to examine the genetic code of the virus for the patients infected with SARS-CoV-2, as well as any other viruses present, and also to track the response of the infected human cells. This let us look at all the mutations present in the virus, and we could immediately compare this to other strains deposited online using a database called\u00a0GISAID<\/a>. Since the virus mutates as it moves through the world, you can predict the likely origin of a mutation based on the country in which it was first seen. We found a case in Belgium that seems to be one of the first sources of the New York strain. Our data was confirmed by work by other groups at\u00a0NYU Langone<\/a>\u00a0and\u00a0Mount Sinai<\/a>, which shows that the majority of cases in NYC likely came from Europe.<\/p>\n We have seen different types of the virus, or strains, emerge as it has moved throughout the world. Once a virus comes into a region (like from Belgium), it can spread with different speeds. In China, scientists saw a mutation that defined a possible new strain called the \u201cL strain,\u201d and this was found in over 70 percent of the country\u2019s cases. They postulated that this might be what made the virus so severe in Wuhan, and it was also seen in other places in Europe, but more data were needed. Strikingly, we identified a clear predominance of the L strain (94 percent) in NYC, which supports this idea. However, we don\u2019t yet know how significant this is in terms of the biology of the virus and what it does to patient cells and if it leads to worse outcomes for those who get it \u2014 we are looking at this clinical data right now as a next step.<\/p>\n Yes, indeed, we are seeing varying strain distributions, like the L strain, but we also have found unique mutations and subgroups of viruses specific to New York City. The deletion we found in the virus for some NYC patients removed a piece of the SARS-CoV-2 virus that had evolved to be different from SARS-CoV-1, which means that some patients had a virus has somewhat \u201cregressed back\u201d to the previously known sequence of SARS. The deletion is in a conserved portion of a gene called NSP1, which has been linked to how humans respond to the virus and could potentially explain why the cases were so severe. All of our sequence data has been deposited into the GISAID and CDC databases, so other scientists and clinicians can develop better tests for tracking the virus and developing vaccines. Although the world has never been more interconnected \u2014 and thus at risk of a pandemic \u2014 we also have never been more scientifically and medically integrated to be able to rapidly track, sequence and respond to a viral threat as soon as it emerges. It gives me hope.<\/p>\nWhy do traditional testing methods take so long?<\/strong><\/span><\/h3>\n
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<\/div>\nAnd how did you come up with the idea for the test?<\/strong><\/span><\/h3>\n
How does your LAMP test compare with the rapid COVID-19 test developed by Abbott Labs?<\/strong><\/span><\/h3>\n
Did the strain of COVID-19 that hit New York come from Europe?<\/strong><\/span><\/h3>\n
As a geneticist, can you talk about the evolution of COVID-19?<\/strong><\/span><\/h3>\n
Is there a demonstrable difference between the strains of COVID-19 that came from China and from Europe, and how will that affect efforts to come up with a vaccine?<\/strong><\/span><\/h3>\n
Is there anything that can be done in the future to prevent a similar pandemic?<\/strong><\/span><\/h3>\n