Is COVID-19 masking the ongoing youth vaping crisis?

E-cigarette, or vaping, product use-associated lung injury (EVALI) is a life-threatening, acute respiratory illness that came to international prominence in 2019 [1,2]. Starting that spring, public health officials recognized a series of mysterious respiratory illnesses predominantly affecting adolescents and young adults who used electronic nicotine delivery systems (ENDS) [3,4]. While EVALI diagnoses continue to be recognized, reported cases decreased by the start of 2020, owing to law enforcement efforts to curb adulteration with vitamin E acetate (VEA), an illicit additive found to have strong links to the outbreak [5,6]. By February 2020, the number of reported EVALI cases exceeded 2800, and 68 patients had died [7,8].

Memories of EVALI quickly faded with the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its clinical manifestation, coronavirus disease 2019 (COVID-19), which has diverted the attention of both the medical and lay community. As of May 2021, COVID-19 has killed 581,000 Americans, infected over 32 million, and resulted in severe economic contraction [9,10]. Anxiety and depression increased as people reached for ways of coping with stress while socially isolating, which included a surge in substance abuse and increased nicotine use [11,12]. Some vape manufacturers and vendors exploited the COVID-19 pandemic to market e-cigarettes aggressively [13]. During this pandemic, diagnosing EVALI has become more challenging, given the overlap in symptoms and the variable availability and sensitivity of SARS-CoV-2 tests [6].

With the rapid spread of disinformation, many EVALI survivors have reported to us and colleagues that they did not have EVALI and instead had COVID a year or more prior to the first reported case of that virus. Additionally, many on social media have incorrectly alleged that EVALI was undetected COVID-19 [14,15]. Conspiracy theories and disinformation campaigns, combined with the COVID-19 pandemic, have created more challenges both in the recognition of EVALI and our youth’s will to change vaping behavior. While many of the nonspecific clinical features of COVID-19 and EVALI overlap, namely pulmonary infiltrates and hypoxemia, these syndromes are distinct with regard to epidemiology, demographics, and response to treatment. It is simply not true that the 2019 EVALI outbreak was unrecognized early COVID.

Today, physicians are now better-equipped to answer questions regarding the risks and benefits of using ENDS. For years, ENDS advocates have touted vaping as a healthier alternative to traditional combustible cigarette use [16], boasting presumably safer chemical profiles, a potential role in facilitating combustible smoking cessation, and seemingly years of safe vaping prior to 2019. However, emerging advancements in our understanding of e-cigarettes have shown increased risk to the lungs. Vaping alters innate defense systems [17,18], predisposes to higher pro-inflammatory cytokine levels [19], and in at least one case has been associated with significant pulmonary architectural distortion [20].

Why then, if ENDS are so disruptive and have circulated since the late 2000s, did the U.S. see such a massive spike in ENDS-associated respiratory failure in 2019, whereas other countries were largely spared? An all-encompassing explanation remains elusive. Considerable data support VEA’s role in the outbreak. EVALI rates diminished substantially after federal efforts intensified to eliminate VEA from product circulation [21]. VEA was identified in the vast majority of EVALI-confirmed patients’ bronchoalveolar lavage samples [22,23]. Similar lung injury has been replicated in murine models exposed to VEA [19,24]. Multiple lines of evidence thus point to VEA-driven pathology, and application of epidemiologic principles support the proposition VEA was the main causal agent of the 2019 EVALI outbreak [25].

Alternative mechanisms of acute lung injury are plausible, including propylene glycol and vegetable glycerin (VG/PG), metals, and excessively high temperatures that can occur when users manipulate their devices [26–29]. ENDS liquid samples from confirmed EVALI patients, seized by law enforcement agencies, frequently – but not always – contain VEA [30]. EVALI case series identify 10–20% of patients with no tetrahydrocannabinol (THC) use, where VEA might be used as an adulterant [1,2,31,32]. Even the preeminent paper on the 2019 EVALI outbreak’s pathophysiologic underpinnings by Blount, et al, could not identify a common, unifying agent in the bronchoalveolar lavage specimens from all patients with EVALI, identifying VEA in ‘only’ 94% of patients. Until investigators routinely perform urine/serum THC testing in individuals with EVALI, it is unknown whether these patients are accurately self-reporting. We urge caution assuming individuals are lying about THC use, owing to the mechanistic plausibility of lung injury from non-VEA-containing sources, myriad uncertainties regarding e-liquid constituents, and the recognition of EVALI in states in which recreational marijuana is legal where e-cigarette liquids should be ‘clean’ [33].

Despite known harms, vaping is increasingly pervasive in our country, with a recent survey demonstrating 27.5% of high school students and 10.5% of middle school students currently use them, with 7.6% and 0.44%, respectively, endorsing use most days of the month³⁰. By comparison, ENDS use by high school students in 2011 was 1.5%, indicating substantial growth in fewer than ten years [34]. Many adults, too, have started vaping in order to facilitate combustible smoking cessation. It is our opinion the data supporting this strategy are – at best – mixed, and frequently these individuals become dual-users instead of former smokers [35,36]. Unlike the United Kingdom, where governing bodies set stringent nicotine limits, the U.S. allows much greater nicotine concentrations and the addition of less caustic nicotine salts to e-cigarettes. Together, these practices have contributed to high rates of nicotine addiction in those who use e-cigarettes [37].

Given vaping’s newfound ubiquity in U.S. society we should question the so-called ‘years of safety’ of which ENDS advocates remind us. It took decades and insurmountable scientific evidence of harm before the ads for combustible cigarettes as a treatment for asthma and good health gave way to surgeon general health warnings [38]. The extreme variation in reported EVALI cases among states in the US suggests that EVALI is often unreported [8]. We suspect that many cases of EVALI may have previously been unrecognized and continue to remain so. Additionally, there is emerging evidence that those ‘years of safety’ were likely erroneous – a smattering of e-cigarette-associated acute lung injury cases existed prior to 2019 [39], and syndromic surveillance suggests ENDS use was at least correlated with episodes of respiratory failure prior to the EVALI outbreak [40]. In addition, a growing body of evidence supports the notion e-cigarette use is associated with higher rates of persistent respiratory conditions like chronic bronchitis and asthma, as well as greater disease severity [41,42]. Amplification of these chronic diseases, though not as visible or exciting as the episodes of acute respiratory failure with EVALI, may potentially lead to substantial morbidity. Last, not only does ENDS use predispose to respiratory infections, but available evidence suggests young ENDS users are more likely to receive a COVID-19 diagnosis [43].

Where do we go with all this newfound knowledge? One sorely needed measure is additional legislation. Despite initial enthusiasm to overhaul the U.S. e-cigarette market, the eventual response was restrained. Politicians responded to EVALI with increasing the age one can purchase tobacco products from 18 to 21 and banning all flavored e-cigarettes sold in ‘pod’ form (excluding flavors tobacco and menthol) [44]. While important, these legislative changes left major holes in a coordinated public health response, notably the continued sale of flavored products in disposable and refillable tank vape systems. These policies did nothing to address major concerns scientists had regarding other harmful constituents in ENDS, such as VG/PG, the remaining ‘allowed’ flavorings, and temperatures the devices could achieve. In addition, if one accepts VEA as the major driver of the 2019 EVALI outbreak, these policies did nothing to prevent a recurrence of major respiratory illnesses. Dealers spike THC fluids with VEA to stretch profit margins since marijuana is the most expensive part of the product. THC remains illegal in most states, ensuring users will, by definition, seek illicit sources, and dealers will continue to have an incentive to adulterate these products.

COVID-19 has wrought massive global destruction, particularly in the U.S. where mortality has been high. Its emergence coincided with a decrease in EVALI cases, though people continue to get sick with EVALI during the pandemic. Physicians and public health officials should recognize numerous concerning patterns still trending in American society: 1) vaping rates are still high, and increasing particularly among youths, 2) pandemic-exacerbated psychiatric disease may fuel even higher rates of e-cigarette use, and 3) many of the systemic issues that led to the 2019 EVALI outbreak have not been addressed by key decision-makers, meaning the U.S. can experience a resurgence of EVALI cases. Scientists continue to make headway understanding the physiologic sequelae of e-cigarette use, and every incremental improvement in our knowledge base shows increases in respiratory infections and declines in respiratory function. In 2021, the real ‘vaping crisis’ is no longer EVALI; rather, the world now knows enough about ENDS to suspect that real injury, either acute or chronic, may occur in a disproportionately young population that is vaping more. Instead, the ‘crisis’ is our collective inaction to respond to this reality.

Disclosure statement

No potential conflict of interest was reported by the author(s).