Lunchtime pandemic reading.
Standard disclaimer: this is a roundup of informative pieces I've read that interest me on the severity of the crisis and how to manage it. I am not a qualified medical expert in ANY sense; at best I am reasonably well-read laity. ALWAYS prioritize advice from qualified healthcare experts over some person on Facebook.
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No one is out of the woods yet. Dr. Scott Gottlieb: "Well, I think when you look at the southeast in the Sunbelt, you still need to be worried you haven't seen cases really spike in Texas or Georgia. In fact, it looks like cases are slowing there. But there's parts of those states that are hotspots, counties that are moving very quickly. Parts of the panhandle in Florida, you see cases growing very quickly. So the parts of the country that were later to enter their epidemic portion of this crisis, I think still are going to come out of it later. And you still have to be concerned about that. And in really any part of the country is vulnerable, even rural parts of the country. So that was South Dakota once a case gets into a situation where you have People tightly packed indoors, it can spread very quickly, you see these super spread situations, as you saw in South Dakota, Dakota. So I don't think anyone's out of the woods right now."
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Unofficial transcript: https://otter.ai/s/wHARyECWTra80oaEglQW1A
The challenge with a pandemic like COVID-19 is that different places are being impacted at different rates. What seems like a catastrophe in one place is a head scratcher in another, because the pandemic hasn't arrived in significant, discernible ways in that location.
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An excellent read by Peter Attia on why COVID-19 models seemed to have been very wrong: "Unfortunately, most of the models used to make COVID-19 projections were not built to incorporate uncertain data, nor were they capable of spitting out answers with varying degrees of uncertainty. And while I suspect the people building said models realized this shortcoming, the majority of the press is not really mathematically or scientifically literate enough to point this out in their reporting. The result was a false sense of certainty, based on the models. I should emphasize that the models were off target not because the people who made them are ignorant or incompetent, but because we had little to no viable data to put into the models to begin with. We didn’t have several months to painstakingly count the squirrels. We didn’t even have a method for counting them. The best we could do was make guesses about squirrels, which we had never seen before, based on our understanding of bunnies and mice."
Source: https://peterattiamd.com/covid-19-whats-wrong-with-the-models/
Peter's writeup was excellent and he's correct; many of the epidemiology models don't have confidence intervals at all. But at least the models were wrong in the sense that they overestimated key numbers like fatalities. Better to err on the side of caution than need millions of extra graves. The last part of his writeup is equally excellent - we have to determine whether our understanding of the virus was wrong, or whether social distancing is working really well. Without that, we risk opening up too soon.
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NEJM has the first clinical characteristics data from NYC. "Among these 393 patients with Covid-19 who were hospitalized in two New York City hospitals, the manifestations of the disease at presentation were generally similar to those in a large case series from China1; however, gastrointestinal symptoms appeared to be more common than in China (where these symptoms occurred in 4 to 5% of patients). This difference could reflect geographic variation or differential reporting. Obesity was common and may be a risk factor for respiratory failure leading to invasive mechanical ventilation. The percentage of patients in our case series who received invasive mechanical ventilation was more than 10 times as high as that in China; potential contributors include the more severe disease in our cohort (since testing and hospitalization in the United States is largely limited to patients with more severe disease) and the early-intubation strategy used in our hospitals. Regardless, the high demand for invasive mechanical ventilation has the potential to overwhelm hospital resources. Deterioration occurred in many patients whose condition had previously been stable; almost a third of patients who received invasive mechanical ventilation did not need supplemental oxygen at presentation. The observations that the patients who received invasive mechanical ventilation almost universally received vasopressor support and that many also received new renal replacement therapy suggest that there is also a need to strengthen stockpiles and supply chains for these resources."
Source: https://www.nejm.org/doi/full/10.1056/NEJMc2010419
This is the first clinical data I've seen that flags obesity itself (rather than the conditions it spawns such as diabetes and cardiac conditions) as a risk factor for respiratory failure. This bodes ill for a significant percentage of the US population.
The other standout is the decline of people who didn't seem that serious at the start - 1/3 of patients. COVID-19 seems to be hitting the US harder, possibly because our overall health is worse than many other nations.
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Sheer numbers of clinical trials isn't necessarily a good thing, according to The Lancet: "There are good reasons to build up a full pipeline of COVID-19 drugs. Up to 90% of new entrants into clinical trials never make it to approval, and so investigators want to have as many shots on goal as possible. Scientific understanding of COVID-19 is also changing so quickly that it makes sense to keep options open. But other motives, including public relations and financial gain, might also be in play. “During a crisis, some people will go out of their way to sacrifice their lives, and others will hoard medicines and be complete jerks. On institutional levels, we have the same span of good actors and bad actors”, says Bausch. And in the absence of comprehensive trial coordination mechanisms, signs of disarray are emerging. “The scale of these trials is too small, and the variation in terms of how they are being run is too large”, says John-Arne Røttingen, chief executive of the Research Council of Norway and proponent of a more collaborative approach. “These trials aren't really designed to answer the questions that need to be answered.” Clinical trial literature, moreover, is riddled with drugs that looked promising in small trials only to prove ineffective in bigger, more rigorous studies."
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30894-1/fulltext
It's a sign of hope that we've got so much in the pipeline, but the unevenness of clinical rigor is both problematic now and hopefully does not set precedents once the crisis has abated.
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COVID-19 is a planetary problem. The Lancet looks at the situation in Latin America: "Experts are more optimistic about Cuba. “Cuba is one of the best prepared locations anywhere in the world to deal with an outbreak”, said Wenham. “They have a very strong, integrated healthcare system which can respond the moment an infectious disease is detected.” The contrast with Venezuela is stark. “The situation in Venezuela is critical; when coronavirus hits, it is going to be impossible to contain”, said Tamara Taraciuk Broner, Human Rights Watch, Buenos Aires, Argentina. “Even in hospitals, there are not the facilities for hand-washing with soap.” Aside from a brief interruption in 2016, the Venezuelan government has not published epidemiological data for several years. The healthcare system has all but collapsed. The once-impressive laboratory system has been looted. Some 5 million Venezuelans have fled. “There is an ongoing humanitarian crisis, an access to food crisis, the surveillance system is not running properly, there is very limited diagnostic capacity and very limited access to healthcare”, said Rodríguez-Morales. “Now things are going to become even more complicated for Venezuela with COVID-19.” It is impossible to know how many cases the country has already seen, though the official tally is 171. There is also the issue of the favelas, home to around 13 million Brazilians. In the favelas, conditions are crowded and access to clean water is limited. In such circumstances, social distancing and hand-washing are virtually impossible. “The recommendations for preventing infection are based on assumptions that do not apply in the favelas”, said Clare Wenham, Assistant Professor of Global Health Policy, London School of Economics and Political Science, UK. “It is hard to see how they will be able to prevent infection or control the virus once it has been let loose.” The outlook is similar for slums elsewhere on the continent."
Source: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30303-0/fulltext
Consider this: until 70-80% of the population has had the disease and has antibodies, it's like sparks flying around in a dry forest. International travel will never be the same, and will not resume with any serious volume until a vaccine is available and deployed. Otherwise, the risk is too high.
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A study in The Lancet concludes that viral sepsis is a possibility in severe COVID-19 infections: "The uncontrolled virus infection leads to more macrophage infiltration and a further worsening of lung injury. Meanwhile, the direct attack on other organs by disseminated SARS-CoV-2, the immune pathogenesis caused by the systemic cytokine storm, and the microcirculation dysfunctions together lead to viral sepsis. Therefore, effective antiviral therapy and measures to modulate the innate immune response and restore the adaptive immune response are essential for breaking the vicious cycle and improving the outcome of the patients."
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30920-X/fulltext
Viral sepsis, viral hepatitis, cytokine storms - COVID-19 is a fascinating and troubling disease. We should all be thankful it's not more severe than it is. If this disease had a fatality rate of 10% or 20%, it'd be game over for a large chunk of our civilization.
Consider this the dry run for a serious pandemic. Urge your elected officials to vastly increase funding for public health and research, because the next time, we're not likely to be as lucky.
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A reminder of the simple daily habits we should all be taking.
1. Wash/sanitize your hands every time you are in or out of your home for any reason. Consider also spraying the bottoms of your shoes with a general disinfectant (alcohol/bleach/peroxide) when you return home.
2. Wear gloves and a mask when out of your home.
3. Stay home as much as possible.
4. Get your personal finances in order now. Cut all unnecessary costs.
5. Donate any PPE you can. https://getusppe.org/give/
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Common myths debunked. There is no genomic evidence at all that COVID-19 arrived before 2020 in the United States and therefore no hidden herd immunity:
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There is no evidence SARS-CoV-2 was engineered.
Source: https://www.washingtonpost.com/world/2020/01/29/experts-debunk-fringe-theory-linking-chinas-coronavirus-weapons-research/
Source: https://www.nature.com/articles/s41591-020-0820-9