Long-Term Effects of COVID-19 on Taste and Olfactory Functions in Individuals with a History of Substance Abuse: A Retrospective Cohort Study from the TriNetX US Collaborative Networks

Background: Substance use disorders not only subject individuals to increased suffering from chronic pain, poisonings, and economic hardships but also place a substantial burden on public health. Reports indicated that people with substance use disorder may be especially susceptible to COVID-19 and its complications. Long-term effects of COVID-19, known as Long-COVID, may heighten the susceptibility of individuals with substance abuse disorders to taste and smell impairments, consequently intensifying the strain on public health resources. This study aimed to determine the effect of substance abuse on olfactory and taste disorder in people with Long-COVID.Methods: The data used in this retrospective cohort study was aggregated from the TriNetX (a web–based cohort creation database). Data extract and analysis were done in February, 2023. We used the US collaborative network, the subnet of TriNetX network to perform the related analysis. From this cohort of more than 33 million records between January 1, 2020, and December 31, 2022, a total of 1,512,358 participators were recruited. Participants then divided into two groups based on substance abuse. Hazard ratio (HRs) and 95% Confidence intervals (CIs) of the incidental olfactory and taste outcome were calculated between substance abuse patients with versus without substance abuser. Subgroup analyses on gender, age, race, and whether receive COVID-19 vaccination were also conducted. Sensitivity analyses were performed using smoked or received relation surgeries (such as nose, tongue, larynx, or brain) to find out the severity of olfactory and taste disorder.Findings: Substance abuse was significantly associated with increased risk of olfactory and taste disorder in Long-COVID population, such as disturbances of taste (HR [95% CI] = 1·258 [1·072–1·477]), smell related disorder, anosmia (HR [95% CI] = 1·292 [1·065–1·566]). The risk of two composite endpoints, disturbances of taste event (HR [95% CI] = 1.258 [1·072–1·477]) and any disturbances of small (HR [95% CI] = 1·218 [1·013–1·464]), were both higher in the substance abuser than in the control cohorts. In addition, the survival probability of the substance abuser decreased in both disturbances of taste and smell. Furthermore, the risk of disorder of taste and smell was higher in the elderly (age ≧ 65 years) and female substance abuser than in the controls. Sensitivity analyses presented predictable results totally. Interestingly, the influence of Long-COVID on olfactory and taste disorders seemed more pronounced in smokers compared to substance abusers.Interpretation: The risk of incidental olfactory and taste disorder is substantially higher in the substance abuser than the non-substance abuser in long-COVID population. The clinicians should routinely screen COVID-19 recovered patients for underlying depression and anxiety, which can occur as a result of taste and olfactory dysfunction. Given the enduring nature of these consequences, early screening, diagnosis, and prompt interventions are crucial in delivering optimal care to patients.Funding: This study was supported by Chung Shan Medical University (RD11004 and CSMU-INT-111-18), Taiwan.Declaration of Interest: The authors declare no competing interests.Ethical Approval: TriNetX was granted a waiver by the Western Institutional Review Board (WIRB) because it only aggregated counts and statistical summaries of de-identified information. As a member of TriNetX's Health Care Organization (HCO), Chung Shan Medical University Hospital (CSMUH) is able to access de-identified data through the TriNetX platform. Furthermore, the Institutional Review Board of CSMUH approved the use of TriNetX for this study (No: CS2-21176). The reporting in this study adheres to the Reporting of studies Conducted using Observational Routinely-collected health Data (RECORD) Statement for cohort studies.