Blood clots from the COVID vaccine... a real concern, or statistical noise?

Back in March, several European nations paused use of the AstraZeneca vaccine based on concerns about case reports of blood clots in recently vaccinated individuals. The specific blood clots formed in several of the patients were a rare and dangerous type of clot known as cerebral venous sinus thrombosis (CVST), resulting in strokes and occasionally seizures in patients. Whether in the brain or elsewhere, these blood clots were especially unusual because they were associated with low platelets (a condition known as thrombocytopenia) and sometimes bleeding. Even more concerning, the specific blood clot formed in many of the patients was. The same phenomenon was later observed with the Johnson & Johnson vaccine, resulting in a pause in the US in mid-April. Interestingly, almost all of the cases were identified in younger females aged 18-48 (although one case in a younger man has since been reported, as well as an earlier male case during clinical trials).

CFR, IFR, and You: What is the true COVID-19 death rate?

Approximately 6 months off from the official start of the COVID-19 outbreak in China (although the actual start of the outbreak is debated) and over 3 months from the initial nationwide shutdown in the United States, there is much uncertainty as to the true mortality rate of the disease. It is first important to define terms, as there are different types of “mortality” or “fatality” rates.

Defining Case Fatality Rate vs. Infection Fatality Rate

As shown in Figure 1, the reported number of COVID-19 cases does not necessarily represent the true number of infected individuals. The confirmed number of cases (positive tests for active infection) is smaller than the number of probable infected (sick patients believed to be infected based on symptoms and likely exposure but who never received a diagnostic test), which is smaller than the actual number of total infected individuals.

Figure 1. Relationships between measured number of COVID-19 cases via different metrics and number of deaths (not necessarily to scale)

A case fatality rate(CFR) is the proportion of deaths from a disease compared to the number of people diagnosed.

An infection fatality rate (IFR) is the proportion of deaths among all infected individuals, in other words the true fatality rate. While related to the CFR, an IFR attempts to estimate the mortality rate including non-diagnosed cases (e.g. not tested, asymptomatic). An IFR should be lower than the CFR, since the denominator would be expected to be larger.

 

Visually, these can be represented as shown in Figure 2 below, based on the relative differences in confirmed vs. total cases as shown in Figure 1. Note that deaths can be scored as either confirmed deaths or probable deaths. As testing becomes more widespread, the difference between “confirmed” and “total” infected shrinks, as does the difference between CFR and IFR.

Figure 2. Visual representation of Case Infection Rate (CFR) and Infection Fatality Rate (IFR)

Going Vape Shit Over E-cigarettes

Vaping History and Use

According to VapingDaily.com, vaping is “the act of inhaling vapor produced by a vaporizer or electronic cigarette. The vapor is produced from a material such as an e-liquid, concentrate, or dry herb.” An important distinction from traditional “smoking” is that vaping refers to breathing in heated water vapor, NOT the incineration products of a burning reaction. The earliest form of vaping traces all the way back to 440 BC, with stories of people inhaling the resulting vapor from marijuana placed onto hot stones. The hookah, invented in 1542, is also analogous to vaping. The first true vaporizer was invented by a Korean war veteran in 1962, although the idea for an e-cigarette comes from 1927. The modern e-cigarette was created by a Chinese pharmacist in 2003.

E-cigarettes (or “vapes”) work by using a battery to heat up vaping material until it becomes an inhalable vapor. While waxy concentrates and dry herb can be vaporized as well, vapes typically utilize an easily vaporizable liquid such as propylene glycol or vegetable glycerin. Flavoring and drugs, typically nicotine, can be dissolved within this liquid for easy inhalable delivery to the user upon heating. Often, the dissolved drug is nicotine. The presence of nicotine in these cigarettes is both functionally useful and problematic, depending on the user. Vapes come in many sizes, styles, and options (Figure 1). These options include various accessories and cartridges that may contain flavoring or recreational drugs.

Figure 1: Examples of vape designs. Source: https://www.cdc.gov/tobacco/basic_information/e-cigarettes/pdfs/Electronic-Cigarettes-Infographic-508.pdf

Nicotine in E-cigarettes

E-cigarettes can serve as an effective smoking cessation method. Use of nicotine e-cigarettes resulted in 7% of regular smokers remaining abstinent from smoking after 6 months, slightly higher than the rate from nicotine patches (5.8%) and higher still compared to e-cigarettes without nicotine (4.1%). Additionally, while the toxicity of vapes can vary depending on what they contain and the mechanics of heating, the UK government declared in 2015 that use of e-cigarettes is approximately 95% less harmful than traditional cigarettes. Heating of vape liquid can result in exposure to various carcinogenic metals and other toxic compounds, however vaporization is likely to produce much less harmful volatile organic compounds than traditional cigarettes. This is likely due to both the absence of tobacco and reduced release of chemical degradation products that would be produced from burning.

Vaping has been on the rise for the past several years, especially among young people. According to Pew Research (Figure 2), the percentage of 12^th graders who report having vaped at least once in the past month doubled from less than 14% to 27% between 2016 and 2018. A similar trend was presented in a study by the New England Journal of Medicine, which reported prevalence increases from 11.0% to 25.4% among 12^th graders between 2017 and 2019 (Figure 3). While the inclusion of nicotine in e-cigarettes can be beneficial for current smokers aiming to quit, it is obviously problematic for young non-smokers. In addition to promoting nicotine addiction in general, there is evidence that e-cigarette use is associated with a much greater likelihood to begin smoking traditional cigarettes as well (however this association cannot establish a causal relationship).

EVALI outbreak and causes

Beyond only these concerns, 2019 brought a very concerning spike in e-cigarette or vaping product use-associated lung injury, formally coined as EVALI. As of December 27, 2019, EVALI has resulted in 2,561 hospitalizations and 55 deaths. While cases have been gradually increasing since 2017, there was a sudden outbreak beginning in June 2019 prior to a decline in new cases as of September 2019. As described above, modern e-cigarettes have been in use since 2003. Based on this timeline, what could have been the cause? Could it simply be due to the rapid increase in prevalence of use (Figures 2-3), or did something change about either the e-cigarettes themselves or their content?

Figure 2: The percentage of 8^th grade, 10^th grade, 12^th grade, and college students who self-reported vaping during the last month. The highest rate exists among 12^th graders, however all grades increased at a similar rate between 2016 and 2018. Source: https://www.pewresearch.org/fact-tank/2019/09/26/vaping-survey-data-roundup/

Figure 3: Prevalence of nicotine vaping among adolescents over different time intervals. Results are presented for 2017, 2018, and 2019. Source: https://www.nejm.org/doi/full/10.1056/NEJMc1910739

An important consideration in discovering the cause of the outbreak was the fact that the outbreak was restricted to the United States, despite being used throughout the world. This suggested that the source of EVALI was not inherent to e-cigarettes overall, but must be something that is specifically being used in the United States. A CDC investigation found that the vast majority of EVALI cases were associated with products containing THC, the active ingredient in marijuana that makes you high. The presence of the chemical vitamin E acetate was a common component in the e-liquid of these THC-containing vapes. Researchers also identified vitamin E acetate in the lung fluid of 94% of examined patients, compared to 0% of controls. Vitamin E is naturally found in foods and also can be useful as a supplement (despite some risks), however the acetate form appears to be the cause of lung toxicity from vaping when inhaled.

Targeting to Youth

As would be expected, the majority of THC vapes are purchased off the black market and therefore are likely not subject to much quality control or oversight. Black market products are most likely to be used by youths who do not have legal access to legal products. Therefore, EVALI is even more concerning in that it is likely to affect children. Even certain legal products are more likely to be used by younger customers, including those who may have not otherwised smoked. Even though many of the major e-cigarette companies now claim that their products are only for adults, the use of social media advertising and fun flavors suggests that targeting youths was at least once an active strategy.

As discussed above, e-cigarettes may have actual health benefits for adult smokers and remain a potentially safer recreational option for all adults. However, in response to the EVALI outbreak and the rapid increase in youth usage, the FDA and local health departments have been under strong pressure to more regulate vaping access overall. San Francisco completely banned the sale of e-cigarettes to anyone beginning in 2020 and other localities are likely to follow. Most recently, President Trump announced on the last day of 2019 that he was planning to ban all e-cigarette flavoring except tobacco and menthol. Allowing these two flavors to remain, especially menthol, was a compromise in favor of both vape shops as well as adult customers who claim they are trying to get away from the tobacco smell and flavor. Time will tell whether this partial ban will adequately minimize youth vaping, however any regulation cannot prevent access to black market products.

For an interesting discussion with some more details on the issue from a nuanced perspective, I highly recommend the Freakonomics podcast episode about vaping regulation. The podcast additionally dives into some of the nuances of previous and existing FDA regulation of e-cigarettes, and how that actually restricts the ability of vape companies to advertise only as a smoking cessation aid.

Love Has No Labels, but GMO Foods Soon Will: The National Bioengineered Food Disclosure Standard

The relative benefits vs. risks of widespread bioengineered crops and other food sources is an often aggressively-debated issue between scientists, the agricultural industry, and consumers. Genetically Modified Organisms, or GMOs, are defined by the European Food Safety Authority as “an organism in which the genetic material has been altered in a way that does not occur naturally through fertilization and/or natural recombination. GMOs may be plants, animals or micro-organisms, such as bacteria, parasites and fungi.” “Genetic Engineering” (GE) is an alternative term used to refer to the manipulation of these species at the DNA level to produce or promote particular traits. GE crops are thus “genetically engineered”. There has been public resistance to the proliferation of GMO food, despite organizations such as the American Medical Association (AMA) and the American Association for the Advancement of Science (AAAS) declaring that genetically engineered foods do not present any appreciable risks.  Nonetheless, a large majority of Americans are in favor of GMO labeling in food products. While the AMA, AAAS, and other scientific organizations argue that GMO labeling will inappropriately imply that GMOs cause harm, consumer advocacy groups contend that people have a right to know what they are eating.

Ignore At Your Own Risk: A Risk Management Perspective on Climate Change

Gallons of digital ink has been spilled discussing and debating the legitimacy of concerns over climate change and global warming. Unfortunately, like many internet debates, both sides of the argument at times rely on emotional arguments, unrealistic assumptions, and overly simplistic outlooks, with a noticeable lack of nuance. While there is overwhelming scientific consensus that global climate is definitively warming, this alone provides only a small part the story. The Earth is indeed warming, but so what? Does it matter, and if so what are possible solutions?

Global warming has environmental, economic, and societal impacts. The projections of the specific timing and severity of those impacts result in a wide range of values, however. Given this, How can we pinpoint the required industrial and societal changes necessary for reducing those impacts if we cannot precisely quantify those impacts in the first place? An effective climate change policy must account for numerous scientific and socioeconomic uncertainties that are likely to substantially affect both the costs and benefits of any policy action.

2017 Nobel Prize Winners

The 2017 Nobel Prizes were recently awarded in early October. Annual Nobel Prizes are awarded for achievement in Physics, Chemistry, Physiology/Medicine, Economics, Literature, and Peace.

Trisodium Phosphate in Food: How I Learned to Stop Worrying and Love Paint Thinner

A recent internet freak-out that may have passed under the radar for many out there concerns the presence of a potentially toxic food additive in cereal that is also found in paint thinner and cleaning agents.

The ingredient in question is Trisodium Phosphate (TSP), a salt compound with many diverse uses including paint thinning, cleaning, other degreasing, and removing oxidized metal for soldering. Interestingly, and the source of controversy, TSP is also used as a food additive and a nutritional supplement for exercise.

While this conspiracy theory originally dates back to at least 2014, it has recently made the rounds on social media within the past month. Despite being thoroughly debunked by Snopes the meme continues. This serves as just a single example of an ongoing chemophobia – distrust of anything seen as an unnatural “chemical” – among esteemed internet dietary experts.

Much of TSP’s functionality comes from its strong basicity, as it has a pH=12 as a 1% solution. Its basic properties will promote reaction with fatty acids through saponification, breaking down grease and oil and thus serving as a cleaner and degreaser (or paint thinner). These functionalities also make it useful as a food additive, as its saponification ability is useful in cheese sauces and it can prevent acidification of food. It also prevents moisture buildup and has some antimicrobial properties. Interestingly, it is also used as an exercise enhancer, presumably due to the need for phosphates in aerobic metabolism.

While TSP use has dwindled due to phosphates being recognized as a major contributor to eutrophication (promoting algae growth in water bodies), it is “Generally Recognized As Safe” for human consumption by the US Food and Drug Administration. It can be very corrosive at high concentrations due to its basic properties, however there is no substantial evidence of long-term effects at low doses for TSP or other phosphates.

It is only natural (get it) to be concerned when a chemical involved in industrial processes appears in our food. However while in this case the food additive is in fact the active ingredient in cleaners/degreasers and not merely an unrelated component, it is the concentration and context that matter. The basicity and phosphate chemistry of TSP make it a useful compound for a diverse set of functions, however the chemical reactions necessary for those functions are restricted by the specifics of the chemical concentration, media, and form. It is often the important nuances and details that are left out of a tweet or meme.