Qanoil + 116 QA March 28, 2020 (edited) Editorial in The New England Journal of Medicine. Lead author is Andrew Fauci. Article posted in full for those who refuse to click the link to a legitimate medical news site. EDITORIAL March 26, 2020 Covid-19 — Navigating the Uncharted List of authors. Anthony S. Fauci, M.D., H. Clifford Lane, M.D., and Robert R. Redfield, M.D. The latest threat to global health is the ongoing outbreak of the respiratory disease that was recently given the name Coronavirus Disease 2019 (Covid-19). Covid-19 was recognized in December 2019.1 It was rapidly shown to be caused by a novel coronavirus that is structurally related to the virus that causes severe acute respiratory syndrome (SARS). As in two preceding instances of emergence of coronavirus disease in the past 18 years2 — SARS (2002 and 2003) and Middle East respiratory syndrome (MERS) (2012 to the present) — the Covid-19 outbreak has posed critical challenges for the public health, research, and medical communities. In their Journal article, Li and colleagues3 provide a detailed clinical and epidemiologic description of the first 425 cases reported in the epicenter of the outbreak: the city of Wuhan in Hubei province, China. Although this information is critical in informing the appropriate response to this outbreak, as the authors point out, the study faces the limitation associated with reporting in real time the evolution of an emerging pathogen in its earliest stages. Nonetheless, a degree of clarity is emerging from this report. The median age of the patients was 59 years, with higher morbidity and mortality among the elderly and among those with coexisting conditions (similar to the situation with influenza); 56% of the patients were male. Of note, there were no cases in children younger than 15 years of age. Either children are less likely to become infected, which would have important epidemiologic implications, or their symptoms were so mild that their infection escaped detection, which has implications for the size of the denominator of total community infections. On the basis of a case definition requiring a diagnosis of pneumonia, the currently reported case fatality rate is approximately 2%.4 In another article in the Journal, Guan et al.5 report mortality of 1.4% among 1099 patients with laboratory-confirmed Covid-19; these patients had a wide spectrum of disease severity. If one assumes that the number of asymptomatic or minimally symptomatic cases is several times as high as the number of reported cases, the case fatality rate may be considerably less than 1%. This suggests that the overall clinical consequences of Covid-19 may ultimately be more akin to those of a severe seasonal influenza (which has a case fatality rate of approximately 0.1%) or a pandemic influenza (similar to those in 1957 and 1968) rather than a disease similar to SARS or MERS, which have had case fatality rates of 9 to 10% and 36%, respectively.2 The efficiency of transmission for any respiratory virus has important implications for containment and mitigation strategies. The current study indicates an estimated basic reproduction number (R0) of 2.2, which means that, on average, each infected person spreads the infection to an additional two persons. As the authors note, until this number falls below 1.0, it is likely that the outbreak will continue to spread. Recent reports of high titers of virus in the oropharynx early in the course of disease arouse concern about increased infectivity during the period of minimal symptoms.6,7 China, the United States, and several other countries have instituted temporary restrictions on travel with an eye toward slowing the spread of this new disease within China and throughout the rest of the world. The United States has seen a dramatic reduction in the number of travelers from China, especially from Hubei province. At least on a temporary basis, such restrictions may have helped slow the spread of the virus: whereas 78,191 laboratory-confirmed cases had been identified in China as of February 26, 2020, a total of 2918 cases had been confirmed in 37 other countries or territories.4 As of February 26, 2020, there had been 14 cases detected in the United States involving travel to China or close contacts with travelers, 3 cases among U.S. citizens repatriated from China, and 42 cases among U.S. passengers repatriated from a cruise ship where the infection had spread.8 However, given the efficiency of transmission as indicated in the current report, we should be prepared for Covid-19 to gain a foothold throughout the world, including in the United States. Community spread in the United States could require a shift from containment to mitigation strategies such as social distancing in order to reduce transmission. Such strategies could include isolating ill persons (including voluntary isolation at home), school closures, and telecommuting where possible.9 A robust research effort is currently under way to develop a vaccine against Covid-19.10 We anticipate that the first candidates will enter phase 1 trials by early spring. Therapy currently consists of supportive care while a variety of investigational approaches are being explored.11 Among these are the antiviral medication lopinavir–ritonavir, interferon-1β, the RNA polymerase inhibitor remdesivir, chloroquine, and a variety of traditional Chinese medicine products.11 Once available, intravenous hyperimmune globulin from recovered persons and monoclonal antibodies may be attractive candidates to study in early intervention. Critical to moving the field forward, even in the context of an outbreak, is ensuring that investigational products are evaluated in scientifically and ethically sound studies.12 Every outbreak provides an opportunity to gain important information, some of which is associated with a limited window of opportunity. For example, Li et al. report a mean interval of 9.1 to 12.5 days between the onset of illness and hospitalization. This finding of a delay in the progression to serious disease may be telling us something important about the pathogenesis of this new virus and may provide a unique window of opportunity for intervention. Achieving a better understanding of the pathogenesis of this disease will be invaluable in navigating our responses in this uncharted arena. Furthermore, genomic studies could delineate host factors that predispose persons to acquisition of infection and disease progression. The Covid-19 outbreak is a stark reminder of the ongoing challenge of emerging and reemerging infectious pathogens and the need for constant surveillance, prompt diagnosis, and robust research to understand the basic biology of new organisms and our susceptibilities to them, as well as to develop effective countermeasures. Author Affiliations From the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (A.S.F., H.C.L.); and the Centers for Disease Control and Prevention, Atlanta (R.R.R.). Edited March 28, 2020 by Qanoil 2 Quote Share this post Link to post Share on other sites
Qanoil + 116 QA March 28, 2020 (edited) A plain English analysis of the above article. America’s Corona Tsar, Andrew Fauci, Concedes Covid-19 May Be Just a Bad Flu With a Fatality Rate of 0.1% On Thursday Dr. Fauci co-authored a report on the coronavirus in the New England Journal of Medicine. The report, entitled “Covid-19 — Navigating the Uncharted”, was co-authored by Anthony S. Fauci, M.D., H. Clifford Lane, M.D., and Robert R. Redfield, M.D. Here’s a direct quote from that report: “If one assumes that the number of asymptomatic or minimally symptomatic cases is several times as high as the number of reported cases, the case fatality rate may be considerably less than 1%. This suggests that the overall clinical consequences of Covid-19 may ultimately be more akin to those of a severe seasonal influenza (which has a case fatality rate of approximately 0.1%) or a pandemic influenza (similar to those in 1957 and 1968) rather than a disease similar to SARS or MERS, which have had case fatality rates of 9 to 10% and 36%, respectively.2“ Please note that the case fatality rate is not ten percent, not five percent, not even one percent, but far, far lower than that. According to the authors, the case fatality rate is only 0.1 percent (only one-tenth of one percent). Are we willing to destroy America over a bad case of the flu? See report in the New England Journal of Medicine: Link Edited March 28, 2020 by Qanoil 2 Quote Share this post Link to post Share on other sites
Enthalpic + 1,496 March 28, 2020 (edited) 12 minutes ago, Qanoil said: According to the authors, the case fatality rate is only 0.1 percent (only one-tenth of one percent). It does not say that, read it again. Hints: "assumes" , "this suggests", "may". 0.1% is only the case IF there were a whole bunch of asymptomatic people. People who actually present with the disease are dying above 1%... and a lot of people are presenting with the disease. It's basically diluting true case statistics with imaginary case outcomes. Let's hope this is true but we need more data. Edited March 28, 2020 by Enthalpic Quote Share this post Link to post Share on other sites
Qanoil + 116 QA March 28, 2020 (edited) 26 minutes ago, Enthalpic said: It does not say that, read it again. Noted. It is best to refer back to the Editorial for the full wording, rather than try to summarize. The key paragraph again says "On the basis of a case definition requiring a diagnosis of pneumonia, the currently reported case fatality rate is approximately 2%. In another article in the Journal, Guan et al. report mortality of 1.4% among 1099 patients with laboratory-confirmed Covid-19; these patients had a wide spectrum of disease severity. If one assumes that the number of asymptomatic or minimally symptomatic cases is several times as high as the number of reported cases, the case fatality rate may be considerably less than 1%. This suggests that the overall clinical consequences of Covid-19 may ultimately be more akin to those of a severe seasonal influenza (which has a case fatality rate of approximately 0.1%) or a pandemic influenza (similar to those in 1957 and 1968) rather than a disease similar to SARS or MERS, which have had case fatality rates of 9 to 10% and 36%, respectively." Edited March 28, 2020 by Qanoil 1 2 Quote Share this post Link to post Share on other sites
Gerry Maddoux + 3,627 GM March 28, 2020 ^ Your points are good ones. I think the primary driver of fear is that this thing behaves differently than anything the world population has experienced before: very long incubation period, selective behavior, incites a cytokine storm in some that destroys the lungs within hours. We're all used to good ole influenza--which kills just as many people. We're not used to what appear to be stealth, cunning, conniving characteristics of this new virus. Additionally, while we have vaccines against influenza, the thing mutates so fluidly that each of us has had a "touch of the flu" from year to year. With just a few antibodies, we can survive it. I rather imagine that when the influenza was first unleashed on an unsuspecting public, they were just as decimated, just not as scared because they didn't have minute-to-minute coverage. People died at home. They were of a "dying age." Unfortunately, influenza still likes to take babies and young children. The utter skipping over this demographic is the only good news from this virus. We should not let America's economy be destroyed by this virus. Those of us in the vulnerable category--and I'm squarely in it--should step up with a bit of courage and say, you can take us, if you must, but you damn sure can't take down my country. That's why it's appropriate to start reopening America to business as usual. This is not such a cruel virus, after all, because it doesn't harvest our future. 2 2 2 Quote Share this post Link to post Share on other sites
Qanoil + 116 QA March 28, 2020 34 minutes ago, Enthalpic said: It does not say that, read it again. Hints: "assumes" , "this suggests", "may". 0.1% is only the case IF there were a whole bunch of asymptomatic people. People who actually present with the disease are dying above 1%... and a lot of people are presenting with the disease. It's basically diluting true case statistics with imaginary case outcomes. Let's hope this is true but we need more data. You mean as opposed to the Mainstream Media panic headlines blared around the world, which many are taking as the gospel truth. 'Terrifying' New Research Warns 2.2 Million Could Die From Coronavirus in US Without Drastic Action A report that helped convince Trump to take coronavirus seriously projected that 2.2 million people could die in the US if we don't act 2 1 Quote Share this post Link to post Share on other sites
Ward Smith + 6,615 March 28, 2020 39 minutes ago, Gerry Maddoux said: ^ Your points are good ones. I think the primary driver of fear is that this thing behaves differently than anything the world population has experienced before: very long incubation period, selective behavior, incites a cytokine storm in some that destroys the lungs within hours. We're all used to good ole influenza--which kills just as many people. We're not used to what appear to be stealth, cunning, conniving characteristics of this new virus. Additionally, while we have vaccines against influenza, the thing mutates so fluidly that each of us has had a "touch of the flu" from year to year. With just a few antibodies, we can survive it. I rather imagine that when the influenza was first unleashed on an unsuspecting public, they were just as decimated, just not as scared because they didn't have minute-to-minute coverage. People died at home. They were of a "dying age." Unfortunately, influenza still likes to take babies and young children. The utter skipping over this demographic is the only good news from this virus. We should not let America's economy be destroyed by this virus. Those of us in the vulnerable category--and I'm squarely in it--should step up with a bit of courage and say, you can take us, if you must, but you damn sure can't take down my country. That's why it's appropriate to start reopening America to business as usual. This is not such a cruel virus, after all, because it doesn't harvest our future. As I recall, the Spanish Flu had a massive cytokine response. Unfortunately it seemed to attack the young and healthy the most, because their systems responded to the invader the fastest. If they'd have had it, hydroxychloroquine might have helped in 1918 also. 1 Quote Share this post Link to post Share on other sites
Marcin2 + 726 MK March 28, 2020 (edited) To stop further speculations: The editorial was published in NEJM on 28 February 2020. There were 4,214 cases globally outside China and 68 deaths in the evening of 27 February 2020. China has not given access for foreigners to epicenter in Hubei. So all that Dr. Fauci had at hand when writing this article were very limited third party sources and his general medical knowledge. So he was just speculating. And because he is the honest researcher he titled the article: CoVID19 Navigating the uncharted. While showing this article on 28 March is just FAKE NEWS. Edited March 28, 2020 by Marcin2 Typo 1 Quote Share this post Link to post Share on other sites
Gerry Maddoux + 3,627 GM March 28, 2020 ^ Who knows? The heroics of even thinking about HCQ have to do with the immune suppression of a patient who would normally need his immune system going on all cylinders. It sounds as if the unique property of this Covid-19 is that it releases all these fever molecules--cytokines and all--that trigger such an unexpectedly hyped-up immune reaction that it destroys the lung parenchyma. This virus is flabbergasting on so many fronts that Satan himself must have spawned this little bastard. What boggles the mind, always, is that viruses have no cellular machinery whatsoever--just nucleic acids. The fact that they use our cellular machinery in the most intrusive manner possible, manufacturing devious methods of making us miserable, is always just astounding to me. Oh well, due to the magic of vaccines, we will eventually pretty well knock this one off its perch . . . but at what cost. Man, so far, the economy has taken a massive hit while mankind itself has taken only a little gut-punch. Tell that to someone who just lost a father or a husband and you're in trouble but the mortality rate has been very low for such a massive scare. Lots of that has to do, of course, with the incredible contagion of the damn thing. I hope HCQ/Z works. As a global community, we can gear up and manufacture massive amounts in short time. I rather suspect this is going to be like the Marshal Plan (Barron's today), whereby Remdesivir and/or Kaletra are used for the really sick ones and HCQ/Z for the barely ill. HCQ for the Spanish flu? Like having penicillin available during the Civil War, it might have changed history. 2 Quote Share this post Link to post Share on other sites
Gerry Maddoux + 3,627 GM March 28, 2020 For the record, Anthony Fauci has been a godsend, pure and simple. He has been a singular voice of reason. During his career, he could have been accurately accused of being political, too cautious, too driven by numbers--but he could never be convincingly accused of being dishonest or asleep at the wheel. However this goes, this country will always owe a massive debt to Dr. Fauci. 1 Quote Share this post Link to post Share on other sites
Enthalpic + 1,496 March 28, 2020 7 minutes ago, Gerry Maddoux said: ^ Who knows? The heroics of even thinking about HCQ have to do with the immune suppression of a patient who would normally need his immune system going on all cylinders. It sounds as if the unique property of this Covid-19 is that it releases all these fever molecules--cytokines and all--that trigger such an unexpectedly hyped-up immune reaction that it destroys the lung parenchyma. This virus is flabbergasting on so many fronts that Satan himself must have spawned this little bastard. What boggles the mind, always, is that viruses have no cellular machinery whatsoever--just nucleic acids. The fact that they use our cellular machinery in the most intrusive manner possible, manufacturing devious methods of making us miserable, is always just astounding to me. Oh well, due to the magic of vaccines, we will eventually pretty well knock this one off its perch . . . but at what cost. Man, so far, the economy has taken a massive hit while mankind itself has taken only a little gut-punch. Tell that to someone who just lost a father or a husband and you're in trouble but the mortality rate has been very low for such a massive scare. Lots of that has to do, of course, with the incredible contagion of the damn thing. I hope HCQ/Z works. As a global community, we can gear up and manufacture massive amounts in short time. I rather suspect this is going to be like the Marshal Plan (Barron's today), whereby Remdesivir and/or Kaletra are used for the really sick ones and HCQ/Z for the barely ill. HCQ for the Spanish flu? Like having penicillin available during the Civil War, it might have changed history. Anyone try prednisone that you know of? Quote Share this post Link to post Share on other sites
Enthalpic + 1,496 March 28, 2020 1 hour ago, Qanoil said: You mean as opposed to the Mainstream Media panic headlines blared around the world, which many are taking as the gospel truth. 'Terrifying' New Research Warns 2.2 Million Could Die From Coronavirus in US Without Drastic Action A report that helped convince Trump to take coronavirus seriously projected that 2.2 million people could die in the US if we don't act I still think it could be 1 to 1.2 million with distancing, perhaps 1.8 with return to work. Quote Share this post Link to post Share on other sites
Gerry Maddoux + 3,627 GM March 28, 2020 26 minutes ago, Enthalpic said: Anyone try prednisone that you know of? Yes, lots, with so-so response. This cytokine storm phenomenon--the release of all sorts of infection-fighting molecules that produce astounding inflammation in the lungs--is apparently so vicious that it leads to ARDS--Adult Respiratory Distress Syndrome--within a couple of hours in some cases. It doesn't occur uniformly, and by the time it is apparent that it is occurring, it is often too late. HCQ works completely differently and apart from Prednisone. Conjecture that that is the way it prevents lung damage: stops the immune response gone wild. 1 1 Quote Share this post Link to post Share on other sites
0R0 + 6,251 March 28, 2020 57 minutes ago, Gerry Maddoux said: Oh well, due to the magic of vaccines, we will eventually pretty well knock this one off its perch . . . but at what cost. Man, so far, the economy has taken a massive hit while mankind itself has taken only a little gut-punch. Tell that to someone who just lost a father or a husband and you're in trouble but the mortality rate has been very low for such a massive scare. Lots of that has to do, of course, with the incredible contagion of the damn thing. Again, I doubt vaccines for this version of SARS will be any more effective than the previous failures. The vaccinated had FASTER Cytokine storm response after less exposure to the SARS or related CV viruses for which vaccines were developed. The incredible contagion is the main problem. Particularly the surfaces problem where it survives so long. It would be smart to go for gloves for this season's fashion shows. I see 10 packs of cotton gloves at Walmart in no time flat after the seasonal non-show in Milan or Paris. Quote Share this post Link to post Share on other sites
0R0 + 6,251 March 28, 2020 25 minutes ago, Gerry Maddoux said: Yes, lots, with so-so response. This cytokine storm phenomenon--the release of all sorts of infection-fighting molecules that produce astounding inflammation in the lungs--is apparently so vicious that it leads to ARDS--Adult Respiratory Distress Syndrome--within a couple of hours in some cases. It doesn't occur uniformly, and by the time it is apparent that it is occurring, it is often too late. HCQ works completely differently and apart from Prednisone. Conjecture that that is the way it prevents lung damage: stops the immune response gone wild. Anyone look into DHA (from fish oil) as a mitigator for the cytokine storm? It is good for slowing inflammatory responses in the immune cascade that causes the cytokine storm. Quote Share this post Link to post Share on other sites
Gerry Maddoux + 3,627 GM March 28, 2020 4 minutes ago, 0R0 said: Again, I doubt vaccines for this version of SARS will be any more effective than the previous failures. The vaccinated had FASTER Cytokine storm response after less exposure to the SARS or related CV viruses for which vaccines were developed. Maybe not. But Inovio, Moderna and Novavax all are going for messenger-RNA vaccines--which should work. Moderna has apparently filled their first quota of 45 healthy volunteers up in Seattle, so we'll know very soon. Inovio is in a clinical trial in China (Dr. Kim has connections there). I don't know about Novavax. Quote Share this post Link to post Share on other sites
0R0 + 6,251 March 28, 2020 40 minutes ago, Enthalpic said: I still think it could be 1 to 1.2 million with distancing, perhaps 1.8 with return to work. It is already so well established that there is no way it can be that far above 1-1.2 million symptomatics not to speak of deaths. NY and NJ are showing >30% positive results in testing, take out the upstate NY and Southern NJ cases and you have about 40% positives in NY Metro. So this is already the sharp rise in the virus symptomatics. Lower density cities with less public transport and high rise buildings will eventually get us to a more uniform spread of the virus, but much more slowly and without overwhelming the medical system. Refraining from school and dense crowds and public transport is all you need to keep the propagation slow in low density areas. Quote Share this post Link to post Share on other sites
Qanoil + 116 QA March 28, 2020 1 hour ago, Marcin2 said: To stop further speculations: The editorial was published in NEJM on 28 February 2020. There were 4,214 cases globally outside China and 68 deaths in the evening of 27 February 2020. China has not given access for foreigners to epicenter in Hubei. So all that Dr. Fauci had at hand when writing this article were very limited third party sources and his general medical knowledge. So he was just speculating. And because he is the honest researcher he titled the article: CoVID19 Navigating the uncharted. While showing this article on 28 March is just FAKE NEWS. You should tell this to The New England Journal of Medicine, who listed the date as March 26 2020. Quote Share this post Link to post Share on other sites
Enthalpic + 1,496 March 28, 2020 1 minute ago, Qanoil said: You should tell this to The New England Journal of Medicine, who listed the date as March 26 2020. Official publish date versus pre-official release. Quote Share this post Link to post Share on other sites
Marcin2 + 726 MK March 28, 2020 (edited) 7 minutes ago, Qanoil said: You should tell this to The New England Journal of Medicine, who listed the date as March 26 2020. I noticed just by reading the article that it must be old, cause No later publications than from Feb 2020 about CoVID19 were referenced and there are tons of good & comprehensive, large sample papers NOW. So I came to : Funding and disclosure and there you can find the 28 Feb 2020 date of publication. You acted bona fide cause the date is really misleading I am sorry for this fake news designation. Edited March 28, 2020 by Marcin2 Typo 1 Quote Share this post Link to post Share on other sites
Gerry Maddoux + 3,627 GM March 28, 2020 Just read this off Medscape; don't know how to transfer. To paraphrase this infectious diseases doctor from Johns Hopkins: 1) Not very hot on HCQ. Thought to prevent viral assembly due to acidification of phagolysosome. Has some cardiotoxicity, and since the Covid-19 produces cardiomyopathy in some, worried about it. Did say that it was a pretty benign drug and worth a shot if you have any. 2) ARDS with Covid not the usual neutrophil-mediated process but instead T-Regulatory cell-mediated. Anti-IL-6 monoclonal antibodies being used. 3) He feels that Remdesivir is the antiviral with the most promise, on basis of studies of this drug against MERS-CoV. {Please don't shoot the messenger.} 😃 1 Quote Share this post Link to post Share on other sites
Enthalpic + 1,496 March 28, 2020 5 minutes ago, Gerry Maddoux said: Just read this off Medscape; don't know how to transfer. To paraphrase this infectious diseases doctor from Johns Hopkins: 1) Not very hot on HCQ. Thought to prevent viral assembly due to acidification of phagolysosome. Has some cardiotoxicity, and since the Covid-19 produces cardiomyopathy in some, worried about it. Did say that it was a pretty benign drug and worth a shot if you have any. 2) ARDS with Covid not the usual neutrophil-mediated process but instead T-Regulatory cell-mediated. Anti-IL-6 monoclonal antibodies being used. 3) He feels that Remdesivir is the antiviral with the most promise, on basis of studies of this drug against MERS-CoV. {Please don't shoot the messenger.} 😃 Name the author I can probably find an abstract on pubmed Quote Share this post Link to post Share on other sites
Qanoil + 116 QA March 28, 2020 16 minutes ago, Enthalpic said: Official publish date versus pre-official release. Good to know, thanks. 11 minutes ago, Marcin2 said: I noticed just by reading the article that it must be old, cause No later publications than from Feb 2020 about CoVID19 were referenced and there are tons of good & comprehensive, large sample papers NOW. So I came to : Funding and disclosure and there you can find the 28 Feb 2020 date of publication. You acted bona fide cause the date is really misleading I am sorry for this fake news designation. Thanks, I was not trying to be misleading. The article date at the top says March 26. Quote Share this post Link to post Share on other sites
Gerry Maddoux + 3,627 GM March 28, 2020 May be just like the Spanish flu: Convalescent Serum may turn out to be the best treatment (the only treatment back then). If so, it might not take very much plasma for antibody protection. I still hold out hope for the HCQ/Z combo. Mainly because it's cheap and available (kind of like my first wife). 1 Quote Share this post Link to post Share on other sites
Gerry Maddoux + 3,627 GM March 28, 2020 11 minutes ago, Enthalpic said: Name the author I can probably find an abstract on pubmed Paul G. Auwaerter Quote Share this post Link to post Share on other sites