Abstract:Recommendations regarding ibuprofen use in relation to coronavirus disease 2019 (COVID-19) have been conflicting. We examined the risk of severe COVID-19 between ibuprofen-prescribed and non-ibuprofen patients with COVID-19 in a nationwide register-based study of patients with COVID-19 in Denmark between the end of February 2020 and May 16, 2020. Patients with heart failure (n = 208), < 30 years (n = 575), and prescribed other nonsteroidal anti-inflammatory drugs (n = 57) were excluded. Patients with ibuprofen… Show more
“…[47][48][49] More recent studies, however, found no significant evidence to suggest that ibuprofen is associated with severe COVID-19 outcomes. 50,51 Further, an observational study using EHR data from 6 hospitals indicated that exposure to ibuprofen is associated with a lower risk of hospitalization due to COVID-19 (OR, 0.73; 95% CI, 0.64-0.84). 52 A retrospective study using EHR data showed a decreased fatality rate for women 50+ years old receiving estradiol therapy (OR, 0.33; 95% CI, 0.18-0.62).…”
Importance: There is an unprecedented need to rapidly identify safe and effective treatments for the novel coronavirus disease 2019 (COVID-19).
Objective: To 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 Participants: Based 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.
Exposures: Patient 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 Measures: All-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.
Results: The 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 Relevance: This 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.
“…[47][48][49] More recent studies, however, found no significant evidence to suggest that ibuprofen is associated with severe COVID-19 outcomes. 50,51 Further, an observational study using EHR data from 6 hospitals indicated that exposure to ibuprofen is associated with a lower risk of hospitalization due to COVID-19 (OR, 0.73; 95% CI, 0.64-0.84). 52 A retrospective study using EHR data showed a decreased fatality rate for women 50+ years old receiving estradiol therapy (OR, 0.33; 95% CI, 0.18-0.62).…”
Importance: There is an unprecedented need to rapidly identify safe and effective treatments for the novel coronavirus disease 2019 (COVID-19).
Objective: To 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 Participants: Based 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.
Exposures: Patient 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 Measures: All-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.
Results: The 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 Relevance: This 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.
“…These preliminary findings are consistent with the findings of no increased risk of severe illness in the available studies to date. For instance, Kragholm et al ( 2020 ) reported in their retrospective database review that patients with pre-diagnosis use of NSAIDs had no increased risk for a composite outcome of severe disease, intensive care unit admission, or death, relative to non-use of NSAIDs (risk ratio = 0.96; 95% confidence interval 0.72–1.23). Fig.…”
The notion that the use of non-steroidal anti-inflammatory drugs (NSAIDs) may lead to adverse outcomes upon acquisition of coronavirus disease 2019 (COVID-19) should be discredited with a review of the real-life evidence. We aimed to perform a meta-analysis to summarize the risk of mortality with the preadmission/pre-diagnosis use of NSAIDs in patients with COVID-19. A systematic literature search was performed to identify eligible studies in electronic databases. The outcome of interest was the development of a fatal course of COVID-19. Adjusted hazard ratio or odds ratio/relative risk and the corresponding 95% confidence interval from each study were pooled using a random-effects model to produce pooled hazard ratio and pooled odds ratio, along with 95% confidence interval. The meta-analysis of 3 studies with a total of 2414 patients with COVID-19 revealed no difference in the hazard for the development of a fatal course of COVID-19 between NSAID users and non-NSAID users (pooled hazard ratio = 0.86; 95% confidence interval 0.49–1.51). Therefore, NSAIDs should not be avoided in patients who are appropriately indicated during the COVID-19 pandemic.
“…As a result, they have no information about ibuprofen in asymptomatic carriers, and whether antipyretics can influence their clinical course 16 . Third, the main analysis of these studies compared NSAID users with non-NSAID users, but confounding indicators may have influenced the results 14 , whereas ibuprofen users were defined based on prescription fills and information on whether or how many ibuprofen pills the patients actually took is not available 15 . Ibuprofen also can be purchased as an over-the-counter drug, they cannot exclude potential misclassification of ibuprofen exposure, as patients in the non-ibuprofen group may have used over-the-counter ibuprofen 15 .…”
Section: Discussionmentioning
confidence: 99%
“…Neither the acute nor the chronic use of NSAIDs resulted in increased mortality or severe COVID-19 14 . Also, Kragholm and colleagues reported the data of a retrospective, Danish-based cohort study, including 4002 adults with COVID-19 of whom 264 (6.6%) were treated with ibuprofen 15 . Again, no significant association between ibuprofen and severe COVID-19 was found.…”
Coronavirus disease 2019 (COVID-19), is a rapidly spreading infectious illness that causes a debilitating respiratory syndrome. Supportive therapy remains the standard for mild-to-moderate cases, including treatment with non-steroidal anti-inflammatory drugs (NSAIDs) e.g. ibuprofen, however such medications may increase COVID-19 complications when used in patients with acute viral respiratory infections. P450 enzyme CYP2C9 are known to be involved in the metabolism of NSAIDs, however, their pharmacogenetic data are limited. This study aims to better understand the genetic landscape of CYP2C9 sequence variation across different ethnic and geographic groups, in correlation with ibuprofen dosing guidelines. A cohort of 101 Jordanian Arab samples were retrospectively recruited and genotyped using Affymetrix DMET Plus Premier Package. This study identified 18 single nucleotide polymorphisms (SNPs) within CYP2C9 in these Jordanian Arabs, within the context of over 100,000 global subjects in 417 published reports. Genetic structure analysis across populations revealed that Jordanian Arabs share the closest CYP2C9 sequence homology to Near East and European populations. However, European populations are 7.2x more likely to show impaired ibuprofen metabolism than Sub-Saharan populations, and 4.5x more likely than East Asian ancestry populations.. This is the most comprehensive and up-to-date analysis for CYP2C9 allele frequencies across multi-ethnic populations world-wide. The use of modern genomic tools coupled with a proactive assessment of the most likely gene-drug candidates will lead to a better understanding of the role of pharmacogenetics for COVID-19 and more effective treatments.
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