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ru848789

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  1. Well, my former company (and current one, as I'm doing some consulting for them, part-time) Merck, finally broke radio silence today. Great to see, as I've been wondering when we would, as I knew we had a few irons in the fire. Anyway, Merck, the 2nd largest vaccine maker, announced it is developing two vaccines for COVID (including one from Themis, whom Merck is buying) and is licensing a phase II drug for COVID. See the excerpt below and the link, which goes into much more detail on the two vaccines. https://www.statnews.com/2020/05/26/merck-aims-to-begin-human-tests-of-two-different-covid-19-vaccines-this-year/ Merck is buying Vienna-based Themis, which is developing an experimental Covid-19 vaccine based on a measles vaccine that could begin human studies soon. It is also partnering with the nonprofit IAVI on the development of a vaccine related to Merck’s existing Ebola vaccine that could enter human studies later this year. And it is licensing an experimental drug from a small company called Ridgeback Biotherapeutics. “We are committed to making a contribution to the eradication of Covid-19,” Roger Perlmutter, who heads Merck Research Laboratories, the company’s research and development division, said in an interview. Merck executives see the company’s history of developing vaccines and treatments against infectious diseases as central to its identity, often citing the decision three decades ago to donate a treatment for river blindness as a pivotal moment in the 129-year-old company’s history. But until now, Merck has been conspicuously absent from the efforts to develop a Covid-19 vaccine. It’s not that the company wasn’t working on the problem, Perlmutter said, but that it simply wasn’t ready to speak.
  2. Trump's gross incompetence in leading any semblance of a Federal effort to prevent and combat this virus will go down as the single worst failure in the history of the United States of America. It's borderline criminal, even. The man is and always has been unfit to be POTUS. Full stop. By the way, to augment your post on Japan, mask culture is probably the biggest reason they've been able to keep the virus largely at bay so far (tracing was important too) with an estimated 95% complying with wearing masks and largely without being told as they've had a mask wearing culture for decades. The excerpt below is key, to me. "Three of the motivating factors that induce Japanese nationals to adhere are courtesy, obligation and shame. Courtesy is the willingness to act out of genuine concern for others. Obligation involves placing the needs of the group before those of oneself. Shame is fear of what others might think if one does not comply to group or societal norms. There is no shortage of courtesy among the silent majority of the West, as unlikely as that can sometimes seem. A sense of obligation also exists, but typically toward groups less large than society as a whole. Shame, on the other hand, is not a dominant Western trait. Additionally, in some regions of the West, anti-collectivist behavior can be a source of identity and pride. Not everyone within Japan plays the collectivist game. Personal observation suggests that present-day mask wearing runs at around 95 percent, but one wonders how those abstainers would respond if confronted by a TV crew. Probably with a sheepish reply. This differs from the United States, where mask-less demonstrators have been rejecting the notion of social distancing as anti-libertarian, as, indeed, has President Donald Trump himself." https://www.japantimes.co.jp/.../covid-19-versus.../... This Bloomberg article on Japan is also good. https://www.bloomberg.com/news/articles/2020-05-22/did-japan-just-beat-the-virus-without-lockdowns-or-mass-testing?fbclid=IwAR3SeyGj5vAcYrV0xVjqFO6E6tZzmf9KzFaDmsH6csRbT2riYlg3uY_bmak
  3. The other day, the CDC published a suite of transmission/infection scenarios that included lower, more conservative assumptions than they had been using recently, including an estimate for the "symptomatic infection fatality ratio" (SIFR) - of those with symptoms, not just all infected (since we know there are asymptomatic infections and they're assuming that's 35% of the population) - of 0.4%. That would be relatively good news. If it were true - and keep in mind that if it were true, it would "only" mean 520K total deaths over the next 12-24 months, assuming no cure/vaccine (and no interventions) if ~60% become infected (herd immunity level) and only 65% of those have symptoms and 0.4% of those with symptoms dies (so 330MM Americans x 0.6 x 0.65 = 130MM symptomatic Americans x 0.4% fatality rate = 520MM deaths). https://www.cdc.gov/coronavirus/2019-ncov/hcp/planning-scenarios.html https://www.npr.org/sections/health-shots/2020/05/22/860981956/scientists-say-new-lower-cdc-estimates-for-severity-of-covid-19-are-optimistic Here's the problem with this calculation. It flies completely in the face of the best data we have on total overall IFR (vs. all infections) from NY/Spain, which is actually more conservative than the CDC's symptomatic IFR (as the NY/Spain calcs include both symptomatic and asymptomatic people). We have pretty solid antibody population testing now in NY and Spain, with NY showing 12.3% infected, via antibody testing (which includes all infected, whether symptomatic or asymptomatic) and Spain showing 5.0% infected. In NY, when the study was done in late April, there were 19K confirmed deaths (not even using the 24.5K confirmed + presumed deaths), so the IFR was 19.5K/2.46MM infected (12.3% of 20MM in NY) or 0.8%; if one includes the presumed dead, which most do (and most think that's still an underestimate based on excess deaths), then the IFR jumps to 24.5K/2.46MM infected or 1.0%. In Spain, as of about 5/15, their antibody population testing showed an infection rate of 5.0%, so their 27K deaths/2.33MM infected (5% of 46.7MM) equals an IFR of 1.16%. On the CDC's basis (excluding 35% of the population), these 1.0-1.2% IFR estimates would be 1.6-1.8% (vs. just symptomatic people), so hard to imagine that number coming down to 0.4% for the US. Of course, it's possible that areas like these that were hit harder than most other areas and have much higher deaths per capita than everywhere else, have led to a higher percentage of vulnerable people being infected, artificially raising death rates a bit. What we really need to know is the antibody levels in some less impacted states to see if they only have maybe 1-3% infected, as many experts think. This would be about 1/5th to 1/10th the NY infection rate and could explain why so many states have per capita fatality rates that are 1/5th to 1/10th of NYs (NY's is around 1500/1MM and the US, not including NY/NJ has a rate of 200/1MM or 1/7th of NYs). Meaning it's very likely that the reason so many states have lower per capita death rates is that they simply have proportionally lower infection rates, which is not surprising given far less density and regional commuting traffic, especially in NYC metro. Having said all that, I've been saying in previous posts that the overall final IFR (vs. all infections) would likely be between 0.5-1.0% and if that is multiplied by the 60% of 330MM (which = 198MM) that would get the virus at herd immunity, eventually, that's 1-2MM dead in the US. So yes, 500K would be "great" relatively speaking, but it's likely too low of an estimate. https://www.33andrain.com/topic/1934-covid19-global-pandemic-3500000-confirmed-cases/?do=findComment&comment=201325https://rutgers.forums.rivals.com/t...ocial-distancing.191275/page-111#post-4557369 There is one possible saving grace here (outside of a cure/vaccine) which I mentioned last week based on the evaluation of immunological responses in people that have been tested for antibodies, both those infected previously and uninfected previously. It turns out that 40-60% of uninfected people who do not possess any antibodies do have some CD4+ T-cell activity against this coronavirus, likely due to previous exposure to other coronaviruses, in a phenomenon known as cross-reactivity. If, somehow, some percentage of these people were actually immune to the virus or if it only gave them a very mild case, that would be beyond huge, but it's impossible to know that yet and impossible to rely on. https://www.33andrain.com/topic/1934-covid19-global-pandemic-3500000-confirmed-cases/?do=findComment&comment=201701
  4. Insightful commentary about the crisis in nursing home care exposed by COVID with lots of good ideas on how to improve things. https://jamanetwork.com/journals/jama/fullarticle/2766599
  5. SIAP, but interesting research from Singapore saying that COVID positive patients are no long infectious 11 days after their first symptoms and they've removed their requirement for two consecutive negative PCR virus tests before discharge from the hospital (most other countries do the same), especially since patients can test positive well beyond that point (false positives - reports from South Korea of reinfection have been shown to not be actual reinfections, as these were explained by the PCR tests detecting viral RNA, but not active viruses), but they've shown that none of them have viral loads that are capable of infection, in lab viral culture studies. A German study they cited had this point of not being infectious as 8 days after first symptoms. Not having to do viral PCR tests for discharge will be of significant benefit. https://www.ams.edu.sg/view-pdf.aspx?file=media\5556_fi_331.pdf&ofile=Period+of+Infectivity+Position+Statement+(final)+23-5-20+(logos).pdf
  6. No, National Security and emergency response to pandemics is largely in the hands of the executive branch, not Congress and the White House screwed this up badly as I said and have been saying. But, yes, D's and R's in Congress should have been brought into the Federal response, like Obama did with H1N1 and Ebola so effectively (Obama got high marks from several R's back then). If we only had a coordinated, coherent Federal response instead of a POTUS who completely downplayed the threat for 6+ weeks, after making his one good decision of banning travel from China. We completely failed to follow the Pandemic Playbook we had (from HHS in 2019, as well as from the bipartisan CSIS think tank), starting with the testing debacle. Most of the stay at home orders went into effect between 3/15 and 3/20, so 2 weeks earlier on about 3/2 would've been great - and probably defensible (and supported by the Governors if we had the data) if we had been doing massive testing starting in mid/late Feb and known we had tens of thousands of infections by early March. We also would've known that many cases of "flu" deaths in Feb were actually COVID deaths as we're starting to see, so it wouldn't have been zero deaths in NY/NJ and other states until the 2nd week in March. Could've saved somewhere between 75-90% of the lives lost if we had done that, as I've posted previously (with links but too lazy to repost).
  7. Great post and by the way, we love NYC too and go in very often and are thinking of renting there for a year, just to live in the City (now that I'm retired); we also have about a dozen friends who live there and mostly love it. Great point on crime too, which continues to go down in NYC. PB was way out of line earlier - missed it all as I was enjoying the day. Was he banned?
  8. Since a few people have asked about transmission of the coronavirus through the eyes, here is a bit of insight. While it's certainly possible, it's very likely a rare occurrence, due to the very circuitous route required to get to the lungs (vs. simply breathing in from the mouth or nose) but can't be ruled out completely. The advice in this link is good: wear eye protection if you are going to be working very closely (within 1-2 feet) with someone, but don't worry about it if you're more than maybe 2-3 feet away (standard talking distance and beyond). But absolutely wear the mask within 6 feet of anyone and anywhere that you can't be sure you can always be >6 feet from everyone, like in a store or on the boardwalk. Also, keep in mind (as per my post on Thursday) that masks are nowhere near foolproof, as cloth masks are maybe 50-70% effective in preventing infection from a cough/sneeze within 6 feet of someone, and worse if not worn properly or in a very crowded situation, like mass transit. Still disappoints me that the US didn't stock up on hundreds of millions of the more effective N95 respirators (>95% effective in virus filtration) for everyone, especially as they can be reused on a rotational basis (every 3 days, since any viruses will be deactivated within 72 hours). https://www.npr.org/sections/goatsa...i-catch-it-through-the-eyes-will-googles-help
  9. Some of us did, which is why we went into lockdown on 3/3, 1-2 weeks before almost everyone else, despite there being zero deaths in NY/NJ on 3/3 and there being 1 case between the two states - which is part of why politicians were saying things were ok, which they probably shouldn't have done, but it's at least understandable. Due to the historic failures of the Trump Administration to have testing in place (due to the CDC failures and inability to realize how important this was and get test kits from other countries), we had no idea there were tens of thousands of infected people, since we had no tests befrore 3/2 and <200 tests in NY on 3/7. If we had known and had strong Federal leadership on this National Security threat, we likely shut everything down 1-2 weeks earlier and save 40-80% of the lives lost.
  10. As per the AP article, Louisiana barred COVID patients from going back to LTC facilities and had 40% of their deaths in LTC facilities, while NYC very strongly encouraged (not forced) LTC facilities to take back recovering COVID patients and had about 5400 LTC deaths or 20% of total deaths in the state through 5/11, when NY changed the directive, not 10,000. You tell me which state did better and per capita is the best way to compare such things on an apples to apples basis. Also, CDC guidance is for recovering patients to wait at least 72 hours before resuming "normal" activities. Yes, I think NY and Cuomo probably should have sent recovering patients elsewhere, but unless it's determined that they were sent back before the CDC guidance would have recommended, then I don't think there's an issue here, other than maybe the CDC guidance is inappropriate for protecting others. Cuomo at least answers tough questions, unlike Trump, who simply berates the questioner - he basically said let the Feds start a probe, as it's not his decision anyway. If there needs to be an investigation, so be it, but let's get the right info before "convicting" anyone. Recommendation: For persons recovered from COVID-19 illness, CDC recommends that isolation be maintained for at least 10 days after illness onset and at least 3 days (72 hours) after recovery. Illness onset is defined as the date symptoms begin. Recovery is defined as resolution of fever without the use of fever-reducing medications with progressive improvement or resolution of other symptoms. Ideally, isolation should be maintained for this full period to the extent that it is practicable under rapidly changing circumstances. https://www.foxnews.com/us/ap-count-over-4300-virus-patients-sent-to-ny-nursing-homes
  11. Lots of misinformation out there on there being "little risk" of being infected outside. That's mostly wrong. the risks are only reduced from touching surfaces (which is only a minor transmission route), as the sun's UV rays will deactivate virus particles in minutes. However, the risk of person to person transmission is about the same inside or outside. The sun's UV rays will not instantly deactivate virus particles coming from another person's sneeze/cough/breath in the second or two it takes for them to reach you, assuming they're close by. It takes almost 7 minutes to deactivate 90% of SARS-CoV-2 with simulated summer solstice 40N sunlight (best case), meaning almost none of it would be deactivated in the 1-2 seconds it takes virus-laden droplets to go from person A to person B. So please keep wearing masks and practicing social distancing, especially if you're not wearing a mask, to protect both yourself and others, in case you're infected. https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiaa274/5841129 Previous studies have demonstrated that SARS-CoV-2 is stable on surfaces for extended periods under indoor conditions. In the present study, simulated sunlight rapidly inactivated SARS-CoV-2 suspended in either simulated saliva or culture media and dried on stainless steel coupons. Ninety percent of infectious virus was inactivated every 6.8 minutes in simulated saliva and every 14.3 minutes in culture media when exposed to simulated sunlight representative of the summer solstice at 40oN latitude at sea level on a clear day.
  12. And more promising efficacy results on convalescent plasma, this time in the best controlled experiment possible without being truly controlled/randomized, as they used a "matched control study" giving 39 patients in various stages of infection severity in the hospital CP and matching them retrospectively as best as possible to 39 other patients who did not receive plasma, which the authors said was not hard to do, given the huge numbers of infected people coming into NYC hospitals in late March/early April. The mortality rate in the treated group was about half that of the control group and the authors stated that, "convalescent plasma transfusion was significantly associated with improved survival in non-intubated patients." More data coming soon, I'm sure, as they've now infused almost 15,000 patients across the country under the direction of the Mayo Clinic. https://www.newswise.com/coronavirus/convalescent-plasma-is-a-potentially-effective-treatment-option-for-patients-hospitalized-with-covid-19-according-to-early-data/?article_id=732039 For this study, plasma recipients and control patients were 100 percent matched on their supplemental oxygen requirement on day zero, in addition to other baseline demographic factors and comorbidities. Of them, 69.2 percent were receiving high-flow oxygen and 10.3 percent were receiving invasive mechanical ventilation. By day 14, clinical condition had worsened in 18 percent of the plasma patients and 24.3 percent of the control patients. On days one and seven, the plasma group also showed a reduction in the proportion of patients with worsened oxygenation status, but that difference was not statistically significant. As of May 1, 12.8 percent of plasma recipients and 24.4 percent of the 1:4 matched control patients had died, with 71.8 percent and 66.7 percent, respectively, being discharged alive.
  13. I don't have time to go back and see who was trashing Cuomo on LTC facilities, but NY ranks as the 16th best state in per capita deaths in LTC facilities at only 20% of total state deaths vs. the national average of 35% of deaths being in LTC facilities. NJ is much worse, at 13th worst on the list (52%). My only point in bringing this up is that the savaging of Cuomo over LTC deaths is unfair, IMO. Very few states with appreciable outbreaks have done well on this count, but singling out NY makes little sense to me. Hopefully the states have learned how to better protect the most vulnerable among us. https://www.nytimes.com/interactive/2020/05/09/us/coronavirus-cases-nursing-homes-us.html
  14. The Lancet just published what is, by far, the largest retrospective observational study on hydroxychloroquine/chloroquine (HCQ/CQ) with or without a macrolide (Azithromycin, for example), evaluating 96,032 patients (14.9K treated with HCQ/CQ and 81.4K patients in the control group). The data clearly show that HCQ treatment resulted in statistically significant higher mortality rates. This is the kind of data we've been looking for and as I've been saying for over a month, given how many people HCQ is being given to, if it had been a "cure" (or even moderately effective) we'd know by now. Now we know. It's not. I now even have an issue with continuing ongoing controlled clinical trials (see edit below), but we should stop giving this drug alone or in combo to patients outside of those trials. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31180-6/fulltext Findings 96,032 patients (mean age 53.8 years, 46.3% women) with COVID-19 were hospitalised during the study period and met the inclusion criteria. Of these, 14,888 patients were in the treatment groups (1868 received chloroquine, 3783 received chloroquine with a macrolide, 3016 received hydroxychloroquine, and 6221 received hydroxychloroquine with a macrolide) and 81,144 patients were in the control group. 10,698 (11.1%) patients died in hospital. After controlling for multiple confounding factors (age, sex, race or ethnicity, body-mass index, underlying cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition, and baseline disease severity), when compared with mortality in the control group (9.3%), hydroxychloroquine (18.0%; hazard ratio 1.335, 95% CI 1.223–1.457), hydroxychloroquine with a macrolide (23.8%; 1.447, 1.368–1.531), chloroquine (16.4%; 1.365, 1.218–1.531), and chloroquine with a macrolide (22.2%; 1.368, 1.273–1.469) were each independently associated with an increased risk of in-hospital mortality. Compared with the control group (0.3%), hydroxychloroquine (6.1%; 2.369, 1.935–2.900), hydroxychloroquine with a macrolide (8.1%; 5.106, 4.106–5.983), chloroquine (4.3%; 3.561, 2.760–4.596), and chloroquine with a macrolide (6·.%; 4.011, 3.344–4.812) were independently associated with an increased risk of de-novo ventricular arrhythmia during hospitalisation. Edit: elsewhere, someone said to me that the fix was in to which I replied that they essentially included everyone in a bunch of hospitals who was PCR-positive for COVID and started HCQ treatment within 48 hours of admission (so as not to bias the HCQ group with patients who were started later and potentially more seriously ill) and compared those people to all others who were admitted and not treated with HCQ, so “bias” would be really hard to achieve. This also means it was a trial with at most moderate symptoms, since they all started treatment within 48 hours of admission, so it’s not a case of HCQ doesn’t work in severely ill patients. Been saying for over a month that given the huge numbers being treated with HCQ, if this were a cure or even moderately effective, we’d absolutely know about it by now. Nope. This is the death knell for HCQ whether people like it or not. In fact, I’d go so far as to say we should probably stop any clinical trials using HCQ post-admission to a hospital, as we shouldn’t be subjecting anyone to roughly a 1.3-1.5X greater mortality rate (adjusted) treatment. I’d only continue HCQ trials pre-hospitalization at this point and grudgingly so.
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