Dataset Information

Informing selection of drugs for COVID-19 treatment through adverse events analysis.

ABSTRACT: Coronavirus disease 2019 (COVID-19) is an ongoing pandemic and there is an urgent need for safe and effective drugs for COVID-19 treatment. Since developing a new drug is time consuming, many approved or investigational drugs have been repurposed for COVID-19 treatment in clinical trials. Therefore, selection of safe drugs for COVID-19 patients is vital for combating this pandemic. Our goal was to evaluate the safety concerns of drugs by analyzing adverse events reported in post-market surveillance. We collected 296 drugs that have been evaluated in clinical trials for COVID-19 and identified 28,597,464 associated adverse events at the system organ classes (SOCs) level in the FDA adverse events report systems (FAERS). We calculated Z-scores of SOCs that statistically quantify the relative frequency of adverse events of drugs in FAERS to quantitatively measure safety concerns for the drugs. Analyzing the Z-scores revealed that these drugs are associated with different significantly frequent adverse events. Our results suggest that this safety concern metric may serve as a tool to inform selection of drugs with favorable safety profiles for COVID-19 patients in clinical practices. Caution is advised when administering drugs with high Z-scores to patients who are vulnerable to associated adverse events.

SUBMITTER: Guo W

PROVIDER: S-EPMC8263777 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Informing selection of drugs for COVID-19 treatment through adverse events analysis.

Guo Wenjing W Pan Bohu B Sakkiah Sugunadevi S Ji Zuowei Z Yavas Gokhan G Lu Yanhui Y Komatsu Takashi E TE Lal-Nag Madhu M Tong Weida W Patterson Tucker A TA Hong Huixiao H

Scientific reports 20210707 1

Coronavirus disease 2019 (COVID-19) is an ongoing pandemic and there is an urgent need for safe and effective drugs for COVID-19 treatment. Since developing a new drug is time consuming, many approved or investigational drugs have been repurposed for COVID-19 treatment in clinical trials. Therefore, selection of safe drugs for COVID-19 patients is vital for combating this pandemic. Our goal was to evaluate the safety concerns of drugs by analyzing adverse events reported in post-market surveilla ...[more]

PMID: 34234253

Similar Datasets

Project description:BackgroundOral adverse events (AEs) following COVID-19 vaccination have been sporadically reported during the previous months, warranting further investigation for their prevalence and suspected relationship with vaccine-elicited immune response.MethodsA retrospective analysis using the Vaccine Adverse Event Reporting System (VAERS) data was conducted to evaluate AEs within the oral cavity (mucosa, tongue, lips, palate, dentition, salivary glands) and AEs involving taste and other sensations. Oral AEs reported after receiving COVID-19 vaccination (test group) and seasonal influenza vaccination (control group) were extracted and cross-tabulated to assess their relative prevalence.ResultsAmong the 128 solicited (suspected) oral AEs, oral paresthesia (0.872%) was most reported after receiving COVID-19 vaccines, followed by the swelling of lips (0.844%), ageusia (0.722%), oral hypoesthesia (0.648%), swollen tongue (0.628%), and dysgeusia (0.617%). The reported prevalence of oral AEs was higher in the COVID-19 vaccine group than in the seasonal influenza group. The distribution pattern of the most reported oral AEs was similar for both COVID-19 and seasonal influenza vaccines. Female sex, older age (>39 years old), primer doses, and mRNA-based COVID-19 vaccines exhibited a higher reported prevalence of oral AEs.ConclusionWithin the limitations of this study, COVID-19 vaccines were found to be associated with rare oral AEs that are predominantly similar to those emerging following seasonal influenza vaccines. The most commonly reported oral AEs were oral paraesthesia (mouth-tingling), lip swelling, and ageusia, representing various pathophysiologic pathways that remain unclear. Taste-related AEs should be acknowledged in the context of the COVID-19 pandemic and the public should be adequately informed about a potential taste dysfunction after receiving the COVID-19 vaccination. Dentists and dental teams need to be aware of the prevalence, severity, and prognosis of oral AEs to inform their patients and increase public confidence in vaccines.

Project description:ImportanceSafety surveillance of vaccines against COVID-19 is critical to ensure safety, maintain trust, and inform policy.ObjectivesTo monitor 23 serious outcomes weekly, using comprehensive health records on a diverse population.Design, setting, and participantsThis study represents an interim analysis of safety surveillance data from Vaccine Safety Datalink. The 10 162 227 vaccine-eligible members of 8 participating US health plans were monitored with administrative data updated weekly and supplemented with medical record review for selected outcomes from December 14, 2020, through June 26, 2021.ExposuresReceipt of BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) COVID-19 vaccination, with a risk interval of 21 days for individuals after vaccine dose 1 or 2 compared with an interval of 22 to 42 days for similar individuals after vaccine dose 1 or 2.Main outcomes and measuresIncidence of serious outcomes, including acute myocardial infarction, Bell palsy, cerebral venous sinus thrombosis, Guillain-Barré syndrome, myocarditis/pericarditis, pulmonary embolism, stroke, and thrombosis with thrombocytopenia syndrome. Incidence of events that occurred among vaccine recipients 1 to 21 days after either dose 1 or 2 of a messenger RNA (mRNA) vaccine was compared with that of vaccinated concurrent comparators who, on the same calendar day, had received their most recent dose 22 to 42 days earlier. Rate ratios (RRs) were estimated by Poisson regression, adjusted for age, sex, race and ethnicity, health plan, and calendar day. For a signal, a 1-sided P < .0048 was required to keep type I error below .05 during 2 years of weekly analyses. For 4 additional outcomes, including anaphylaxis, only descriptive analyses were conducted.ResultsA total of 11 845 128 doses of mRNA vaccines (57% BNT162b2; 6 175 813 first doses and 5 669 315 second doses) were administered to 6.2 million individuals (mean age, 49 years; 54% female individuals). The incidence of events per 1 000 000 person-years during the risk vs comparison intervals for ischemic stroke was 1612 vs 1781 (RR, 0.97; 95% CI, 0.87-1.08); for appendicitis, 1179 vs 1345 (RR, 0.82; 95% CI, 0.73-0.93); and for acute myocardial infarction, 935 vs 1030 (RR, 1.02; 95% CI, 0.89-1.18). No vaccine-outcome association met the prespecified requirement for a signal. Incidence of confirmed anaphylaxis was 4.8 (95% CI, 3.2-6.9) per million doses of BNT162b2 and 5.1 (95% CI, 3.3-7.6) per million doses of mRNA-1273.Conclusions and relevanceIn interim analyses of surveillance of mRNA COVID-19 vaccines, incidence of selected serious outcomes was not significantly higher 1 to 21 days postvaccination compared with 22 to 42 days postvaccination. While CIs were wide for many outcomes, surveillance is ongoing.

Project description:IntroductionIn early 2020, the coronavirus disease 2019 (COVID-19) pandemic spread worldwide, overwhelming hospitals with severely ill patients and posing the urgent need for clinical evidence to guide patient care. First treatment options available were repurposed drugs to fight inflammation, coagulopathy, and viral replication. A vast number of clinical studies were launched globally to test their efficacy and safety. Our analysis describes the development of global evidence on repurposed drugs, in particular corticosteroids, anticoagulants, and (hydroxy)chloroquine in hospitalized COVID-19 patients based on different study types. We track the incorporation of clinical data in international and national treatment guidelines and identify factors that characterize studies and analyses with the greatest impact on treatment recommendations.MethodsA literature search in MEDLINE was conducted to assess the clinical evidence on treatment with corticosteroids, anticoagulants, and (hydroxy)chloroquine in hospitalized COVID-19 patients during the first year of the pandemic. Adoption of the evidence from this clinical data in treatment guidelines of the World Health Organization (WHO), Germany, and United States (US) was evaluated over time.ResultsWe identified 106 studies on corticosteroids, 141 studies on anticoagulants, and 115 studies on (hydroxy)chloroquine. Most studies were retrospective cohort studies; some were randomized clinical trials (RCTs), and a few were platform trials. These studies were compared to studies directly and indirectly referred to in WHO (7 versions), German (5 versions), and US (21 versions) guidelines. We found that initially large, well-adjusted, mainly retrospective cohort studies and ultimately large platform trials or coordinated meta-analyses of RCTs provided best available clinical evidence supporting treatment recommendations.DiscussionParticularly early in the pandemic, evidence for the efficacy and safety of repurposed drugs was of low quality, since time and scientific rigor seemed to be competing factors. Pandemic preparedness, coordinated efforts, and combined analyses were crucial to generating timely and robust clinical evidence that informed national and international treatment guidelines on corticosteroids, anticoagulants, and (hydroxy)chloroquine. Multi-arm platform trials with master protocols and coordinated meta-analyses proved particularly successful, with researchers joining forces to answer the most pressing questions as quickly as possible.

Project description:Background The active pursuit of network medicine for drug repurposing, particularly for combating Covid-19, has stimulated interest in the concept of structural controllability in cellular networks. We sought to extend this theory, focusing on the defense rather than control of the cell against viral infections. Accordingly, we extended structural controllability to total structural controllability and introduced the concept of control hubs. Perturbing any control hub may render the cell uncontrollable by exogenous stimuli like viral infections, so control hubs are ideal drug targets. Results We developed an efficient algorithm to identify all control hubs, applying it to a largest homogeneous network of human protein interactions, including interactions between human and SARS-CoV-2 proteins. Our method recognized 65 druggable control hubs with enriched antiviral functions. Utilizing these hubs, we categorized potential drugs into four groups: antiviral and anti-inflammatory agents, drugs acting on the central nervous system, dietary supplements, and compounds enhancing immunity. An exemplification of our approach’s effectiveness, Fostamatinib, a drug initially developed for chronic immune thrombocytopenia, is now in clinical trials for treating Covid-19. Preclinical trial data demonstrated that Fostamatinib could reduce mortality rates, ICU stay length, and disease severity in Covid-19 patients. Conclusions Our findings confirm the efficacy of our novel strategy that leverages control hubs as drug targets. This approach provides insights into the molecular mechanisms of potential therapeutics for Covid-19, making it a valuable tool for interpretable drug discovery. Our new approach is general and applicable to repurposing drugs for other diseases. Supplementary Information The online version contains supplementary material available at 10.1186/s13062-023-00410-9. Key points Extend network structural controllability to total network controllability, providing a practical method for identifying critical nodes that must be protected to maintain network controllability. Extend and apply the new method to identifying drug targets in human protein-protein interaction networks. Apply the new method to identify drugs that can be reused for Covid-19 treatment. Supplementary Information The online version contains supplementary material available at 10.1186/s13062-023-00410-9.

Dataset Information

Informing selection of drugs for COVID-19 treatment through adverse events analysis.

Publications

Informing selection of drugs for COVID-19 treatment through adverse events analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets