In the late summer of 2019 -- months before COVID-19 was on anyone's radar -- another deadly, previously unseen respiratory illness dominated the headlines.
By mid-December, the vaping-related lung disease named EVALI by the CDC had hospitalized 2,500 people across the U.S. and killed 54 -- weeks before the first case of the novel coronavirus was reported in Wuhan, China.
By late February of 2020, as the first COVID-19-related deaths were being reported in the U.S., cases of EVALI had been reported in all 50 states, and the death toll had climbed to 68.
But by the end of March, as COVID-19 raged in New York City and the nation locked down, EVALI had largely disappeared from the news and new cases were rare in hospital emergency departments.
More than half of patients hospitalized with EVALI during the outbreak peak in the fall of 2019 were teens and young adults under age 25. Not so for COVID-19, which has hospitalized and killed mostly older adults.
But the many similarities between the two illnesses have some questioning whether they are related, and if some cases of EVALI might have actually been very early, unrecognized cases of COVID-19.
"There is no evidence of that that I am aware of, but COVID-19 has made the diagnosis of EVALI more challenging," pediatric pulmonologist Mikhail Kazachkov, MD, of NYU Langone Health in New York City, told ľֱ.
Symptoms of EVALI closely mimic those of COVID-19. They're a mix of systemic symptoms such as fever, vomiting and chills, and respiratory symptoms, including shortness of breath and other breathing issues, cough, chest pain, and hypoxia. Radiological features of the two diseases are also similar.
"It's important to keep in mind that EVALI is a diagnosis of exclusion," said Kiran Nandalike, MD, who practices pediatric pulmonology at the UC Davis Health System in Sacramento, California. "That's why taking a careful history and having a suspicion of EVALI in teens and young adults who test negative for COVID-19 is important."
EVALI in the Era of COVID-19
Nandalike recently published who presented to the health system with EVALI early in 2020 showing symptoms mimicking those of COVID-19.
Chest imaging resembled COVID-19 with non-specific ground glass opacities and interstitial prominence patterns, but all three patients tested negative twice for the viral disease.
Nandalike told ľֱ that because treatments for COVID-19 and EVALI differ, differentiating between the two conditions is clinically important. He noted that early initiation of steroids in EVALI patients has been shown to shorten the duration and severity of the disease.
EVALI cases fell dramatically following their September 2019 peak, but they did not disappear.
Investigations identified vaping products containing tetrahydrocannabinol (THC) and the dilutant vitamin E acetate as a likely cause of the sharp spike in EVALI cases that summer, but .
"We are seeing fewer cases, but we can't really say why this is," Kazachkov told ľֱ. "Certainly EVALI is still out there."
In a exploring the challenges of diagnosing EVALI in the era of COVID-19, Kazachkov and NYU Langone colleagues Melodi Pirzada, MD, proposed testing bronchoalveolar lavage fluid for vitamin E acetate in patients with suspected EVALI to confirm a diagnosis.
They noted that the recent identification of multisystem inflammatory syndrome in children (MIS-C) with COVID-19 has further complicated the diagnostic landscape.
"At least present with shortness of breath and other respiratory syndromes, not unlike those of EVALI," they wrote. "The overlap of similar clinical features, use of vape products and probably SARS-CoV-2 exposure make distinguishing the differential diagnosis of EVALI from MIS-C challenging in both children and adults, particularly when MIS-C presents with respiratory symptoms."
Kazachkov said while MIS-C has been seen most often in younger children, it has also been reported in older children and adolescents. Symptoms tend to appear in the weeks after a COVID-19 diagnosis.
"Hundreds of thousands of adolescents and young adults use e-cigarettes," he said. "Distinguishing EVALI from MIS-C in those who vape could be very challenging because the two are very similar in terms of presentation and x-ray findings."
Does Vaping Increase COVID Risk?
The impact of vaping on COVID-19 has not been widely studied, but a nationally representative online survey conducted last May involving 4,351 teens and young adults .
Half the respondents had a history of e-cigarette or regular cigarette use and half were never-users.
The respondents were asked about their use of e-cigarettes and combustible cigarettes and whether they had recently experienced symptoms associated with COVID-19 or had been diagnosed with the viral disease.
Compared with never-users, ever-users of e-cigarettes were 5 times more likely to have been diagnosed with COVID-19 (95% CI 1.82 to 13.96) and dual e-cigarette and combustible cigarette ever users were 7 times more likely to have a COVID-19 diagnosis (95% CI 1.98 to 24.55). Recent (past 30 days) dual users were 6.8 times more likely to have been diagnosed than never-users.
Senior author Bonnie Halpern-Felsher, PhD, of Stanford University, told ľֱ that the survey did not ask about COVID-19 symptom severity. The observational findings can only suggest a causal role for e-cigarette use and smoking in COVID-19.
"But we know from other studies that e-cigarettes can harm the lungs and possibly even compromise the immune system," she said. "With regard to exposure, teens who vape may be more vulnerable because they are doing so without a mask on or, possibly, sharing these products with others. It is also possible that the aerosol that results from vaping transports the virus."