ABSTRACT
ImportanceThere is an unprecedented need to rapidly identify safe and effective treatments for the novel coronavirus disease 2019 (COVID-19). ObjectiveTo systematically investigate if any of the available drugs in Electronic Health Record (EHR), including prescription drugs and dietary supplements, can be repurposed as potential treatment for COVID-19. Design, Setting, and ParticipantsBased on a retrospective cohort analysis of EHR data, drug-wide association studies (DrugWAS) were performed on COVID-19 patients at Vanderbilt University Medical Center (VUMC). For each drug study, multivariable logistic regression with overlap weighting using propensity score was applied to estimate the effect of drug exposure on COVID-19 disease outcomes. ExposuresPatient exposure to a drug during 1-year prior to the pandemic and COVID-19 diagnosis was chosen as exposure of interest. Natural language processing was employed to extract drug information from clinical notes, in addition to the prescription drug data available in structured format. Main Outcomes and MeasuresAll-cause of death was selected as primary outcome. Hospitalization, admission to the intensive care unit (ICU), and need for mechanical ventilation were identified as secondary outcomes. ResultsThe study included 7,768 COVID-19 patients, of which 509 (6.55%) were hospitalized, 82 (1.06%) were admitted to ICU, 64 (0.82%) received mechanical ventilation, and 90 (1.16%) died. Overall, 15 drugs were significantly associated with decreased COVID-19 severity. Previous exposure to either Streptococcus pneumoniae vaccines (adjusted odds ratio [OR], 0.38; 95% CI, 0.14-0.98), diphtheria toxoid vaccine (OR, 0.39; 95% CI, 0.15-0.98), and tetanus toxoid vaccine (OR, 0.39; 95% CI, 0.15-0.98) were significantly associated with a decreased risk of death (primary outcome). Secondary analyses identified several other significant associations showing lower risk for COVID-19 outcomes: 2 vaccines (acellular pertussis, Streptococcus pneumoniae), 3 dietary supplements (turmeric extract, flaxseed extract, omega-3 fatty acids), methylprednisolone acetate, pseudoephedrine, ethinyl estradiol, estradiol, ibuprofen, and fluticasone. Conclusions and RelevanceThis cohort study leveraged EHR data to identify a list of drugs that could be repurposed to improve COVID-19 outcomes. Further randomized clinical trials are needed to investigate the efficacy of the proposed drugs. Key PointsO_ST_ABSQuestionC_ST_ABSCan Electronic Health Records (EHRs) be used to search for drug candidates that could be repurposed to treat the coronavirus disease 2019 (COVID-19)? FindingsDrug-wide association studies (DrugWAS) of COVID-19 severity outcomes were conducted on a cohort of 7,768 COVID-19 patients. The study found 15 drug ingredients that are significantly associated with a decreased risk of death and other severe COVID-19 outcomes. MeaningThe list of drugs proposed by this study could provide additional insights into developing new candidates for COVID-19 treatment.
ABSTRACT
ObjectiveIdentifying symptoms highly specific to COVID-19 would improve the clinical and public health response to infectious outbreaks. Here, we describe a high-throughput approach - Concept-Wide Association Study (ConceptWAS) that systematically scans a diseases clinical manifestations from clinical notes. We used this method to identify symptoms specific to COVID-19 early in the course of the pandemic. MethodsUsing the Vanderbilt University Medical Center (VUMC) EHR, we parsed clinical notes through a natural language processing pipeline to extract clinical concepts. We examined the difference in concepts derived from the notes of COVID-19-positive and COVID-19-negative patients on the PCR testing date. We performed ConceptWAS using the cumulative data every two weeks for early identifying specific COVID-19 symptoms. ResultsWe processed 87,753 notes 19,692 patients (1,483 COVID-19-positive) subjected to COVID-19 PCR testing between March 8, 2020, and May 27, 2020. We found 68 clinical concepts significantly associated with COVID-19. We identified symptoms associated with increasing risk of COVID-19, including "absent sense of smell" (odds ratio [OR] = 4.97, 95% confidence interval [CI] = 3.21-7.50), "fever" (OR = 1.43, 95% CI = 1.28-1.59), "with cough fever" (OR = 2.29, 95% CI = 1.75-2.96), and "ageusia" (OR = 5.18, 95% CI = 3.02-8.58). Using ConceptWAS, we were able to detect loss sense of smell or taste three weeks prior to their inclusion as symptoms of the disease by the Centers for Disease Control and Prevention (CDC). ConclusionConceptWAS is a high-throughput approach for exploring specific symptoms of a disease like COVID-19, with a promise for enabling EHR-powered early disease manifestations identification.
