Discussion
This case series describes twelve pediatric patients with EVALI who presented during the COVID-19 pandemic surge in New Jersey. All patients presented with clinical, laboratory and/or radiological findings that raised suspicion of COVID-19 but subsequently tested negative for COVID-19 by RT-PCR nasopharyngeal swab, in some cases multiple times(Cases# 9,10). According to the CDC, confirmed cases of EVALI have history of e-cigarette use 90 days prior to presentation, pulmonary infiltrates on CXR or CT scan, absence of pulmonary infection at initial presentation either by culture or respiratory viral panel, no alternate plausible diagnosis9.Our patients reported vaping anywhere from 3 months to 5 years prior to admission. All but one of our patients(Case #8) fit the CDC definition of EVALI.
It is possible that some of the patients had COVID-19 but their tests were false negatives, either due to the sensitivities in the RT-PCR test or errors in collecting the sample.17,18 However, many of the patients were tested multiple times and remained negative making the diagnosis of COVID pneumonia much less likely. Additionally, cases 10,11 and 12 had SARS-COV-2 IgG antibody testing done, which was also negative, however the antibody was done within a week of presentation. Antibody testing was not available when the cases 1-9 presented. However SARS-COV-2 IgG antibody was negative in case#8 six weeks after onset of symptoms.
Studies describing the clinical features of EVALI and COVID-19 in pediatric patients are relatively recent. Both EVALI and COVID-19 pediatric patients can present with fever, cough, shortness of breath and chest pain10-12. Both can also present with nonspecific gastrointestinal symptoms such as abdominal pain, nausea vomiting and diarrhea 5. We are not aware of any studies that have compared the clinical presentation of these two entities in children.
Radiological findings in EVALI pediatric patients can show diffuse bilateral symmetric ground-glass lung opacities, consolidation and a lower lobe predominance on CT.13. While the data on pediatric COVID-19 CT imaging is scarce, a large study in the adult population by Bernheim et.al. described that the typical COVID-19 CT scan would show “bilateral and peripheral ground-glass and consolidative pulmonary opacities” however many patients had CT scans that lacked all or some of those features14,15. Radiological features are not specific to these conditions and there are no specific features to distinguish EVALI from COVID-19 on chest imaging. Figure 2 shows CT images of a 19 year old patient who was admitted with EVALI and a 21 year old male who was admitted at the same time with COVID pneumonia.
Laboratory findings in both COVID-19 and EVALI can show elevated liver function tests, inflammatory markers such as ferritin, d-dimer, C-reactive protein, and procalcitonin and coagulopathy16-18.Coagulation abnormalities and inflammatory dysregulation have been described in both EVALI and COVID-19. Khanijo and colleagues described elevated inflammatory markers such as CPR, ESR and procalcitonin in their series of 24 patients with EVALI. Hematological,biochemical , inflammatory and immune marker abnormalities have been described in COVID-19 and they are used for risk stratification in the disease19 . All patients in our series demonstrated abnormalities in coagulation profile.
Lymphopenia has been described as a feature of COVID-19.20This has not been described in EVALI and could be a helpful distinguishing feature between the two conditions. None of our patients had lymphopenia. However, in pediatric COVID-19 cases only a small proportion of patients exhibit Lymphopenia.21
In our series, patients who presented early in the COVID surge were started on Hydroxychloroquine, which was the recommendation at that time7. Many of these patients were tested multiple times (up to 3 times) and were treated with therapies aimed at treating COVID-19 such as Hydroxychloroquine. Early in the surge steroids were contraindicated in patients with COVID-19 and were therefore withheld till results became available. Only after a thorough history uncovered vaping use and other causes of pneumonia ruled out was treatment with steroids begun, generally on hospital day 2 or 3, depending on when the results of COVID testing were available. The currently recommended treatment of EVALI includes use of dexamethasone22with several studies showing short term benefit including decreasing mortality rates. Steroids were contraindicated for the treatment of COVID early in the pandemic however recent emerging data are supporting the use of steroids.
There are several factors that have been implicated in the higher susceptibility of smokers and vapers to COVID-19.Vaping causes increased mucosal permeability and impaired muco-ciliary clearance, which is the first line of defense23. Additionally, smokers are shown to have a higher surface expression of ACE2 receptors, which is the binding site for SARS-CoV224.
It is possible that due to the shelter in place order in our area with schools and workplaces closed during the pandemic surge, adolescents are finding more opportunities to vape beyond the reach of principals and teachers9. This is likely exacerbated by the fact that those who vape are more likely to have underlying anxiety and depression and isolation has been shown to cause increased stress and depression25,26Four of the 12 patients in this series had an underlying mental health diagnosis.
Given the commonalities in presentations, but differences in treatments between the two relatively new diseases, COVID-19 and EVALI, it remains crucial to elicit a detailed social and substance use history in patients presenting with ‘typical’ COVID pneumonia like illness. Given the ongoing pandemic, Pediatricians and other health care providers need to be aware of other conditions that can masquerade as SARS-CoV-2.