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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Dr. Florian Krammer on vaccines. "Do any of the vaccine candidates look promising?
I am very positive about what we are seeing so far. We’ve seen pretty encouraging results from preclinical models, the phase 1 and phase 2 trials. But none of this means anything yet because the proof will be in the results from the phase 3 trials. That’s where we will learn about the actual efficacy and safety. In terms of efficacy, I don’t think we will end up with a vaccine that gives us 100 percent protection from infection (meaning sterilizing immunity). But we do not need a perfect vaccine, and I am relatively hopeful that several vaccine candidates will lead to solid protection from disease. I think a vaccine will probably also dampen transmission. This will help people who aren’t able to get vaccinated or mount a strong response after they are vaccinated.
What can go wrong in a phase 3 trial?
If you don’t see efficacy, you don’t go forward. A lot of other things can go wrong. Vaccines can trigger an unintended neurological issue or an autoimmune disease in rare cases. You wouldn’t see this in a few hundred people in phase 1/2 trials, but you would see one, two, or three cases in a few thousand people. An example of this happened in 1976, after an outbreak of swine flu among soldiers at Fort Dix, New Jersey, led to massive vaccination campaigns and increased cases of Guillain-Barré syndrome.
What could complicate the rollout of an effective vaccine?
Large-scale production is difficult, and a couple of front runners in this race have never produced a vaccine for the market. A lot of the technologies being used are new and there is little experience with scaling them up. Also, we don’t know who will get the vaccine first. Probably health care workers and high-risk individuals, but I would like to see a discussion about this and understand what the public thinks. Also, distribution and administration of that many vaccine doses needs to coordinated well and will be a huge effort. You also have to take into account that there will not be instantaneous protection. You may need two shots, and it could take a few weeks to a month until you mount protective immunity. In the United States alone we will need 660 million doses (two shots per person). Globally, we will need 16 billion doses. It’s almost unimaginable how much vaccine we will need."
Source: https://health.mountsinai.org/blog/vaccines-for-covid-19-how-protective-are-they-when-will-they-be-ready-a-leading-vaccinologist-at-mount-sinai-weighs-in/
Commentary: It's interesting to note that the discussion of efficacy right now is about blunting the disease, as opposed to what Dr. Krammer referred to as sterilizing efficacy - meaning that the vaccine recipient is completely immune to the disease. There's something to that. Imagine being chased by a rabid Tyrannosaurus. The ideal would be to shoot it dead immediately. However, if the best you could do was a solid shot to the knee, enough that it's less dangerous and would have a hard time running after you, that might be enough for now. That's what it sounds like the vaccines are going after immediately - impair the disease enough to disable its infectivity while we perfect a sterilizing efficacy vaccine down the road.
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Another study on Tocilizumab; not peer-reviewed yet. "BACKGROUND COVID-19 is associated with immune dysregulation and hyperinflammation. Tocilizumab is an anti-interleukin-6 receptor antibody. METHODS Patients hospitalized with severe COVID-19 pneumonia receiving standard care were randomized (2:1) to double-blinded intravenous tocilizumab 8 mg/kg or placebo. The primary outcome measure was clinical status on a 7-category ordinal scale at day 28 (1, discharged/ready for discharge; 7, death). RESULTS Overall, 452 patients were randomized; the modified-intention-to-treat population included 294 tocilizumab-treated and 144 placebo-treated patients. Clinical status at day 28 was not statistically significantly improved for tocilizumab versus placebo (P=0.36). Median (95% CI) ordinal scale values at day 28: 1.0 (1.0 to 1.0) for tocilizumab and 2.0 (1.0 to 4.0) for placebo (odds ratio, 1.19 [0.81 to 1.76]). There was no difference in mortality at day 28 between tocilizumab (19.7%) and placebo (19.4%) (difference, 0.3% [95% CI, -7.6 to 8.2]; nominal P=0.94). Median time to hospital discharge was 8 days shorter with tocilizumab than placebo (20.0 and 28.0, respectively; nominal P=0.037; hazard ratio 1.35 [95% CI 1.02 to 1.79]). Median duration of ICU stay was 5.8 days shorter with tocilizumab than placebo (9.8 and 15.5, respectively; nominal P=0.045). In the safety population, serious adverse events occurred in 34.9% of 295 patients in the tocilizumab arm and 38.5% of 143 in the placebo arm. CONCLUSIONS In this randomized placebo-controlled trial in hospitalized COVID-19 pneumonia patients, tocilizumab did not improve clinical status or mortality. Potential benefits in time to hospital discharge and duration of ICU stay are being investigated in ongoing clinical trials."
Source: https://www.medrxiv.org/content/10.1101/2020.08.27.20183442v1
Commentary: Tocilizumab is another therapeutic being investigated for mitigating severe cases of COVID-19. While the initial results show that it reduces time in the hospital, it does not show that it improved clinical status or reduce mortality.
These therapeutic investigations are vital for reducing the overall mortality and severity of the disease. The ideal, while we wait for a vaccine, is to reduce COVID-19's mortality rates to that of influenza or less; while it is deadlier than the flu by a factor of 10x, if therapeutics give us the ability to cut that down, it could become a manageable chronic disease like the flu over time.
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Mink farms may be a problem. "The zoonotic origin of the SARS-CoV-2 pandemic is still unknown. Animal experiments have shown that non-human primates, cats, ferrets, hamsters, rabbits and bats can be infected by SARS-CoV-2. In addition, SARS-CoV-2 RNA has been detected in felids, mink and dogs in the field. Here, we describe an in-depth investigation of outbreaks on 16 mink farms and humans living or working on these farms, using whole genome sequencing. We conclude that the virus was initially introduced from humans and has evolved, most likely reflecting widespread circulation among mink in the beginning of the infection period several weeks prior to detection. At the moment, despite enhanced biosecurity, early warning surveillance and immediate culling of infected farms, there is ongoing transmission between mink farms with three big transmission clusters with unknown modes of transmission. We also describe the first animal to human transmissions of SARS-CoV-2 in mink farms."
Source: https://www.biorxiv.org/content/10.1101/2020.09.01.277152v1
Commentary: This is a matter for concern. We know with reasonable certainty that SARS-CoV-2 came from an animal, and animals can contract and spread it. We also know that coronaviruses in general have good potential for mutation on their genes; the D614G mutation that occurred in Europe made it potentially more infectious.
Why mink farms - and other animal reserves - are a problem is because once the animal group is infected, they spread the disease rapidly among themselves and in the case above, spread it back to humans. That introduces substantial potential for mutation; the nature of any virus is that the more generations it goes through, the more it's likely to mutate. And you're not going to be putting masks and keeping your minks six feet apart.
If you work near any of the animals listed, be sure you are wearing maximum protective equipment not only for the humans around you, but also the animals you work with.
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More data on aerosols. "In the second study, researchers in Rotterdam and Utrecht, the Netherlands, wrote a research letter documenting a COVID-19 outbreak that sickened 17 residents and 17 healthcare staff in one of seven wards in a nursing home for people with psychiatric or behavioral conditions. None of the 95 residents or 106 healthcare staff in the other six wards tested positive.
The authors noted that the Netherlands was experiencing a low prevalence of COVID-19 the week of the outbreak, with only 493 of that country's residents testing positive, compared with 8,391 cases during the most intense week of the outbreak in April.
To prevent coronavirus transmission, all healthcare workers were assigned to specific wards and required to wear surgical masks during patient care starting Apr 26. Residents lived in individual rooms and spent part of each day in shared living rooms; some residents were mobile.
Suspecting that the ventilation system of the affected ward could have contributed to the outbreak, investigators found that an energy-efficient system had been installed in which indoor air was refreshed only when indoor carbon dioxide (CO2) concentrations detected elevated levels. If CO2 levels didn't exceed a certain threshold, unfiltered indoor air was simply recirculated throughout the ward. In contrast, the six unaffected wards were refreshed regularly with outside air.
The researchers noted that low CO2 levels produced by inactive patients may have led to stale air in the affected ward, which was cooled by two air conditioning units that also recirculated the air in the shared living areas. SARS-CoV-2 RNA was found in dust on the mesh dust filter of living room air conditioners and in four filters from three of eight ventilation units."
Source: https://www.cidrap.umn.edu/news-perspective/2020/08/yet-more-data-support-covid-19-aerosol-transmission
Commentary: At this point it's safe to say that you should ignore distancing ALONE as a countermeasure for any indoor space. You MUST wear the best mask you have available in addition to keeping distance, washing your hands, and spending as little time indoors in places that are not your home. Being inside at any distance from others is unsafe without a mask.
Remember my smoking rule: if someone could light up a cigarette and smoke it near you indoors, would you smell it? If so, you're breathing the same air as them in a concentration high enough to likely be infectious.
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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. Remember that cleaners are never to be ingested or injected.
2. Always wear a mask when out of your home and if going to a high risk area, wear goggles. Respirators are back in stock at online retailers, too.
3. Stay home as much as possible. Minimize your contact with others and maintain physical distance of at LEAST 6 feet / 2 meters, preferably more. Avoid indoor places as much as you can; indoor spaces spread the disease through aerosols and distance is less effective at mitigating your risks.
4. Get your personal finances in order now. Cut all unnecessary costs.
5. Replenish your supplies as you use them. Avoid reducing your stores to pre-pandemic levels in case an outbreak causes unexpected supply chain disruptions.
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Common misinformation debunked!
There is no genomic evidence at all that COVID-19 arrived before 2020 in the United States and therefore no hidden herd immunity:
Source:
There is no evidence SARS-CoV-2 was engineered, nor that it escaped a lab somewhere.
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
Source: https://www.nationalgeographic.com/science/2020/05/anthony-fauci-no-scientific-evidence-the-coronavirus-was-made-in-a-chinese-lab-cvd/
There is no evidence a flu shot increases your COVID-19 risk.
Source: https://www.factcheck.org/2020/04/no-evidence-that-flu-shot-increases-risk-of-covid-19/
Source: https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa626/5842161
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A common request I'm asked is who I follow. Here's a public Twitter list of many of the sources I read.
https://twitter.com/i/lists/1260956929205112834
This list is biased by design. It is limited to authors who predominantly post in the English language. It is heavily biased towards individual researchers and away from institutions. It is biased towards those who publish or share research, data, papers, etc. I have made an attempt to follow researchers from different countries, and also to make the list reasonably gender-balanced, because multiple, diverse perspectives on research data are essential.