The severity of symptoms in individuals with COVID-19 infection varies widely, with up to 40% of patients globally1 remaining asymptomatic while others develop severe and sometimes fatal complications.2 This heterogeneity in illness presentation, along with the overwhelming demands on health care resources in treating patients with COVID-19, highlights the need for strategies to predict which individuals are at risk for greater symptom severity.
Such measures could help to improve the efficiency of prevention, triage, and treatment efforts in fighting the pandemic. “Identification of risk factors for disease severity is critical to identify those who may require priority in testing, close observation, early treatment, or hospitalization…,” wrote Merzon et al in a study published in April 2021 in the Journal of Attention Disorders.2
It is well-known that elderly patients and individuals with medical comorbidities such as cardiovascular disease and diabetes are vulnerable to worse outcomes associated with COVID-19 infection.2 In addition, researchers have found similar risks in individuals with psychiatric illness, with one study showing a 1.5-fold increase in the risk of death related to COVID-19 among patients with a psychiatric diagnosis compared with those with no psychiatric diagnosis.3
In other findings based on a large set of US health records, COVID-19 infection rates, morbidity, and mortality were higher among patients recently diagnosed with a mental disorder, including attention-deficit hyperactivity disorder (ADHD) (adjusted odds ratio [aOR] for acquiring COVID-19: 7.31; 95% CI, 6.78-7.87; P <.001).4
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In the study by Merzon et al, they examined patterns of COVID-19 symptom severity specifically among patients with ADHD. The sample consisted of 1870 COVID-19-positive Israeli patients aged 5-60 years (mean age, 29.03, SD = 14.80 years), including 231 individuals diagnosed with ADHD by a senior physician per DSM-IV or DSM-5 criteria.2
Using logistic regression analyses and controlling for variables including age, sex, socioeconomic status, and various pre-existing medical and psychiatric comorbidities, the authors determined that ADHD was associated with greater COVID-19 symptom severity (aOR, 1.81; 95% CI, 1.29-2.52; P =.<.05) and rates of referral to hospitalization (aOR, 1.93; 95% CI, 1.06-3.51; P =.03).2
Among the range of medical and psychiatric illnesses examined, ADHD was the only variable predictive of symptomatic presentation with COVID-19 infection. ADHD was also linked to a significantly greater increase in the rate of hospitalization for COVID-19 compared with several other diagnoses (18.8% compared with 10.3% for cardiovascular disease and 4.3% for schizophrenia, for example). Additionally, patients with ADHD were substantially more likely to present with fever above 38 °C and suspected pneumonia compared with patients without ADHD.2
In post hoc analyses of differences by age group, those aged 5-20 years who had ADHD demonstrated higher rates of symptomatic presentation compared with patients in the same age group without ADHD (aOR, 3.22; 95% CI, 2.04-5.09; P <.001).2
In subsequent research, Merzon et al found higher rates of ADHD among patients who tested positive for COVID-19 infection (aOR, 1.58; 95% CI, 1.27-1.96; P <.001) compared with those who tested negative.5 However, this association appears to be mediated by ADHD treatment status, as the risk of infection was higher for patients with untreated ADHD vs non-ADHD patients (crudeOR, 1.61; 95% CI, 1.36-1.89; P <.001), while this difference was not found in a comparison between treated ADHD patients and non-ADHD patients (crudeOR, 1.07; 95% CI, 0.78-1.48; P =.65). Compared with untreated ADHD patients, treated ADHD patients showed a significantly lower risk of COVID-19 infection (aOR, 0.63; 95% CI, 0.42–0.94; P <.001).
We interviewed Rachel E. Dew, MD, MHSc, assistant professor of psychiatry and behavioral sciences in the division of child and adolescent psychiatry at Duke University Medical Center in Durham, North Carolina, to gauge her thoughts on the general connection observed between ADHD and COVID-19 risk.
“It makes sense that those with ADHD would be more likely to be exposed to the virus, as this population would be prone to inconsistent use of personal protective equipment and other safety guidelines,” she said. “Many patients had a terrible time adjusting to pandemic circumstances like virtual learning and working at home, so this may have limited effective social distancing practices.”
Dr Dew explained that several factors could potentially lead to worse COVID-19 outcomes in this population. For example, asymptomatic or mildly symptomatic patients with ADHD may be less likely to present for care and be referred for testing, in part because ADHD can interfere with employment and community connections, which represent reliable sources of public health information.
“Finally, in this study, smoking seems to have been analyzed as a dichotomous variable, but those with ADHD tend to consume more cigarettes than non-ADHD smokers, so it is possible that ADHD smokers were more susceptible to complications than non-ADHD smokers,” she said.
Regarding the implications of these findings for clinicians, Dr Dew stated that a higher index of suspicion for COVID-19 exposure may be warranted in patients with ADHD, as well as more directives and support around self-care in the early stages of infection. As for the long-term implications, she believes these results provide a good example of why depending on self-referral for testing and treatment may not be sufficient to control the COVID-19 pandemic.
While preliminary results indicate similar rates of vaccination in individuals with psychiatric illness compared with the general population, it is “likely that when vaccination rates are examined in detail, those with psychiatric illness will show lower uptake as well,” she stated.6
On a broader note, Dr Dew finds it “encouraging to see the medical community starting to recognize ADHD as an important risk factor for many aspects of health and safety, rather than something that only matters in the educational setting.”
References
1. Ma Q, Liu J, Liu Q, et al. Global percentage of asymptomatic SARS-CoV-2 infections among the tested population and individuals with confirmed COVID-19 diagnosis: a systematic review and meta-analysis. JAMA Netw. Open. Published online December 14, 2021. doi:10.1001/jamanetworkopen.2021.37257
2. Merzon E, Weiss MD, Cortese S, et al. The association between ADHD and the severity of COVID-19 infection. J Atten Disord. Published online April 2, 2021. doi:10.1177/10870547211003659
3. Li L, Li F, Fortunati F, Krystal JH. Association of a prior psychiatric diagnosis with mortality among hospitalized patients with coronavirus disease 2019 (COVID-19) infection. JAMA Netw Open. Published online September 1, 2020. doi:10.1001/jamanetworkopen.2020.23282
4. Wang Q, Xu R, Volkow ND. Increased risk of COVID-19 infection and mortality in people with mental disorders: analysis from electronic health records in the United States. World Psychiatry. Published online October 7, 2020. doi:10.1002/wps.20806
5. Merzon E, Manor I, Rotem A, et al. ADHD as a risk factor for infection with COVID-19. J Atten Disord. Published online July 22, 2020. doi:10.1177/10870547209432716. Mazereel V, Vanbrabant T, Desplenter F, De Hert M. COVID-19 vaccine uptake in patients with psychiatric disorders admitted to or residing in a university psychiatric hospital. Lancet Psychiatry. Published online August 17, 2021. doi:10.1016/S2215-0366(21)00301-1.
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