Basic Clin Pharmacol Toxicol. 2022 Aug 16. doi: 10.1111/bcpt.13779. Online ahead of print.

ABSTRACT

Genetic factors have long been recognized as important determinants of inter-individual variability in drug efficacy and toxicity. However, despite the increasing number of established gene-drug associations, candidate polymorphisms can only explain a fraction of the genetically encoded functional variability in drug disposition. Advancements in genetic profiling methods now allow to analyse the landscape of human pharmacogenetic variations comprehensively, which opens new opportunities to identify novel factors that could explain the "missing heritability". Here, we provide an updated overview of the landscape of pharmacogenomic variability based on recent analyses of population-scale sequencing projects. We then summarize the current state-of-the-art how the functional consequences of variants with unknown effects can be quantitatively estimated while discussing challenges and peculiarities that are specific to pharmacogenes. In the last sections, we discuss the importance of considering ethnogeographic diversity to provide equitable benefits of pharmacogenomics and summarize current roadblocks for the implementation of sequencing-based guidance of clinical decision-making. Based on the current state of the field, we conclude that testing is likely to gradually shift from the interrogation of selected candidate polymorphisms to comprehensive sequencing, which allows to consider the full spectrum of pharmacogenomic variations for a true personalization of genomic prescribing.

PMID:35971800 | DOI:10.1111/bcpt.13779

Pharmacogenomics. 2022 Aug 15. doi: 10.2217/pgs-2022-0044. Online ahead of print.

ABSTRACT

Introduction: Atorvastatin exhibits wide interindividual variability in treatment response, limiting the drug efficacy in coronary artery disease patients. Aim: To study the effect of genetic variants involved in atorvastatin transport/metabolism and correlate their lipid-lowering efficacy. Materials & methods: Genotyping was performed using 5'-hydrolysis probe method (n = 412), and the study evaluated the treatment response in 86 patients. Results: Significant reduction in total cholesterol and low-density lipoprotein cholesterol (LDL-C) were observed in SLCO1B1-rs4149056, rs4363657 and ABCB1-rs1045642 genotypes. The combined genotypes of ABCB1 and SLCO1B1 showed a strong synergistic effect in reducing the total cholesterol and LDL-C. Diabetes and smoking were observed to influence the LDL-C reduction. Conclusion: The genetic variants of SLCO1B1 and ABCB1 predict the lipid-lowering efficacy of atorvastatin, and this may be useful in genotype-guided statin therapy for coronary artery disease patients.

PMID:35968761 | DOI:10.2217/pgs-2022-0044

Expert Rev Clin Pharmacol. 2022 Aug 13. doi: 10.1080/17512433.2022.2112949. Online ahead of print.

ABSTRACT

INTRODUCTION: The efficacy of antidepressants for patients with major depressive disorder (MDD) varies from individual to individual, making the prediction of therapeutic outcomes difficult. Better methods for predicting antidepressant outcomes are needed. However, complex interactions between biological, psychological, and environmental factors affect outcomes, presenting immense computational challenges for prediction. Using machine learning (ML) techniques with pharmacogenomics data provides one pathway towards individualized prediction of therapeutic outcomes of antidepressants.

AREAS COVERED: This report systematically reviews the methods, results, and limitations of individual studies of ML and pharmacogenomics for predicting response and/or remission with antidepressants in patients with MDD. Future directions for research and pragmatic considerations for the clinical implementation of ML-based pharmacogenomic algorithms are also discussed.

EXPERT OPINION: ML methods utilizing pharmacogenomic and clinical data demonstrate promising results for predicting short-term antidepressant response. However, predictions of antidepressant treatment outcomes depend on contextual factors that ML algorithms may not be able to capture. As such, ML-driven prediction is best viewed as a companion to clinical judgment, not its replacement. Successful implementation and adoption of methods predicting antidepressant response warrants provider education about ML and close collaborations between computing scientists, pharmacogenomic experts, health system engineers, laboratory medicine experts and clinicians.

PMID:35968639 | DOI:10.1080/17512433.2022.2112949

Front Cardiovasc Med. 2022 Jul 28;9:887705. doi: 10.3389/fcvm.2022.887705. eCollection 2022.

ABSTRACT

Radiotherapy (RT) is one of the pillars of cancer therapy. High-dose radiation exposure on the thorax is mainly used in the context of adjuvant RT after breast surgery, in lung and esophageal cancer, and as a complement to systemic treatment in lymphoma. Due to the anatomical proximity, the heart inevitably receives some radiation that can result in acute and chronic cardiotoxicity, leading to heart failure, coronary artery disease, pericardial and valvular heart disease. Current evidence suggests there is no safe radiation dose to the heart, which poses a need for early recognition of RT-induced cardiac injury to initiate cardioprotective treatment and prevent further damage. Multimodality cardiac imaging provides a powerful tool to screen for structural and functional abnormalities secondary to RT. Left ventricular ejection fraction, preferably with three-dimensional echocardiography or cardiovascular magnetic resonance (CMR), and global longitudinal strain with speckle-tracking echocardiography are currently the key parameters to detect cardiotoxicity. However, several novel imaging parameters are tested in the ongoing clinical trials. CMR parametric imaging holds much promise as T1, T2 mapping and extracellular volume quantification allow us to monitor edema, inflammation and fibrosis, which are fundamental processes in RT-induced cardiotoxicity. Moreover, the association between serum biomarkers, genetic polymorphisms and the risk of developing cardiovascular disease after chest RT has been demonstrated, providing a platform for an integrative screening approach for cardiotoxicity. The present review summarizes contemporary evidence of RT-induced cardiac injury obtained from multimodality imaging-echocardiography, cardiovascular computed tomography, CMR and nuclear cardiology. Moreover, it identifies gaps in our current knowledge and highlights future perspectives to screen for RT-induced cardiotoxicity.

PMID:35966531 | PMC:PMC9366112 | DOI:10.3389/fcvm.2022.887705

Front Oncol. 2022 Jul 29;12:972718. doi: 10.3389/fonc.2022.972718. eCollection 2022.

NO ABSTRACT

PMID:35965582 | PMC:PMC9372610 | DOI:10.3389/fonc.2022.972718

Allergol Int. 2022 Aug 11:S1323-8930(22)00081-8. doi: 10.1016/j.alit.2022.07.003. Online ahead of print.

NO ABSTRACT

PMID:35965193 | DOI:10.1016/j.alit.2022.07.003

Chem Biol Interact. 2022 Aug 11:110097. doi: 10.1016/j.cbi.2022.110097. Online ahead of print.

ABSTRACT

Remdesivir (RDV, Veklury®) is an FDA-approved prodrug for the treatment of hospitalized patients with COVID-19. Recent in vitro studies have indicated that human carboxylesterase 1 (CES1) is the major metabolic enzyme catalyzing RDV activation. COVID-19 treatment for hospitalized patients typically also involves a number of antibiotics and anti-inflammatory drugs. Further, individuals who are carriers of a CES1 variant (polymorphism in exon 4 codon 143 [G143E]) may experience impairment in their ability to metabolize therapeutic agents which are CES1 substrates. The present study assessed the potential influence of nine therapeutic agents (hydroxychloroquine, ivermectin, erythromycin, clarithromycin, roxithromycin, trimethoprim, ciprofloxacin, vancomycin, and dexamethasone) commonly used in treating COVID-19 and 5 known CES1 inhibitors on the metabolism of RDV. Additionally, we further analyzed the mechanism of inhibition of cannabidiol (CBD), as well as the impact of the G143E polymorphism on RDV metabolism. An in vitro S9 fraction incubation method and in vitro to in vivo pharmacokinetic scaling were utilized. None of the nine therapeutic agents evaluated produced significant inhibition of RDV hydrolysis; CBD was found to inhibit RDV hydrolysis by a mixed type of competitive and noncompetitive partial inhibition mechanism. In vitro to in vivo modeling suggested a possible reduction of RDV clearance and increase of AUC when coadministration with CBD. The same scaling method also suggested a potentially lower clearance and higher AUC in the presence of the G143E variant. In conclusion, a potential CES1-mediated DDI between RDV and the nine assessed medications appears unlikely. However, a potential CES1-mediated DDI between RDV and CBD may be possible with sufficient exposure to the cannabinoid. Patients carrying the CES1 G143E variant may exhibit a slower biotransformation and clearance of RDV. Further clinical studies would be required to evaluate and characterize the clinical significance of a CBD-RDV interaction.

PMID:35964681 | DOI:10.1016/j.cbi.2022.110097

Cancer Cell Int. 2022 Aug 13;22(1):256. doi: 10.1186/s12935-022-02667-y.

NO ABSTRACT

PMID:35964054 | DOI:10.1186/s12935-022-02667-y

Pharmacogenomics J. 2022 Aug 13. doi: 10.1038/s41397-022-00286-4. Online ahead of print.

ABSTRACT

This pilot study is aimed at implementing an approach for comprehensive clinical pharmacogenomics (PGx) profiling. Fifty patients with cardiovascular diseases and 50 healthy individuals underwent whole-exome sequencing. Data on 1800 PGx genes were extracted and analyzed through deep filtration separately. Theoretical drug induced phenoconversion was assessed for the patients, using sequence2script. In total, 4539 rare variants (including 115 damaging non-synonymous) were identified. Four publicly available PGx bioinformatics algorithms to assign PGx haplotypes were applied to nine selected very important pharmacogenes (VIP) and revealed a 45-70% concordance rate. To ensure availability of the results at point-of-care, actionable variants were stored in a web-hosted database and PGx-cards were developed for quick access and handed to the study subjects. While a comprehensive clinical PGx profile could be successfully extracted from WES data, available tools to interpret these data demonstrated inconsistencies that complicate clinical application.

PMID:35963939 | DOI:10.1038/s41397-022-00286-4

BMC Cancer. 2022 Aug 13;22(1):884. doi: 10.1186/s12885-022-09989-0.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is a fatal disease characterized by early genetic alterations in telomerase reverse transcriptase promoter (TERTp) and β-catenin (CTNNB1) genes and immune cell activation in the tumor microenvironment. As a novel approach, we wanted to assess patient survival influenced by combined presence of mutations and densities of CD8+ cytotoxic T cells.

METHODS: Tissue samples were obtained from 67 HCC patients who had undergone resection. We analysed CD8+ T cells density, TERTp mutations, rs2853669 polymorphism, and CTNNB1 mutations. These variables were evaluated for time to recurrence (TTR) and disease free survival (DFS).

RESULTS: TERTp mutations were found in 75.8% and CTNNB1 mutations in 35.6% of the patients. TERTp mutations were not associated with survival but polymorphism rs2853669 in TERTp was associated with improved TTR and DFS. CTNNB1 mutations were associated with improving TTR. High density of CD8+ T-lymphocytes in tumor center and invasive margin correlated with longer TTR and DFS. Combined genetic and immune factors further improved survival showing higher predictive values. E.g., combining CTNNB1 mutations and high density of CD8+ T-lymphocytes in tumor center yielded HRs of 0.12 (0.03-0.52), p = 0.005 for TTR and 0.25 (0.09-0.74), p = 0.01 for DFS.

CONCLUSION: The results outline a novel integrative approach for prognostication through combining independent predictive factors from genetic and immune cell profiles. However, larger studies are needed to explore multiple cell types in the tumor microenvironment.

PMID:35962322 | DOI:10.1186/s12885-022-09989-0

Ir J Med Sci. 2022 Aug 13. doi: 10.1007/s11845-022-03112-9. Online ahead of print.

ABSTRACT

Patients presenting with degenerative spinal changes are often poor surgical candidates due to associated co-morbidities, frailty, or sarcopenia. Additionally, surgeries of a degenerative spine can prove difficult due to the distortion of normal surgical anatomy. Therefore, many patients are managed conservatively with a variety of modalities, including over-the-counter and prescription medications. Nevertheless, several patients do not experience adequate relief from pain with analgesic medications, precipitating multiple hospital visits, and usage of resources. As a result, back pain is regarded as a major economic burden, with total costs of associated treatment exceeding $100 billion annually. Pharmacogenetics is a relatively novel method of evaluating an individual's response to analgesic medications, through analysis of germline polymorphisms. It entails obtaining a genetic sample, often via buccal swab or peripheral blood sample, and genetic analysis achieved through either polymerase chain reaction +/- Sanger sequencing, microassays, restriction length fragment polymorphism analysis, or genetic library preparation and next generation sequencing. The potential efficacy of pharmacogenetic analysis has been highlighted across several specialities to date. However, a paucity of evidence exists regarding spine surgery populations. Nevertheless, regular prospective pharmacogenetic analysis may ultimately prove beneficial when concerning degenerative spinal cohorts due to aforementioned surgical and economic considerations. The purpose of this narrative review is to outline how metaboliser profile variants affect the pharmacokinetics of specific analgesia used to treat back pain, and to discuss the current potential and limitations of employing regular pharmacogenetic analysis for spine surgery populations with degenerative conditions.

PMID:35962253 | DOI:10.1007/s11845-022-03112-9

Tuberculosis (Edinb). 2022 Aug 8;136:102246. doi: 10.1016/j.tube.2022.102246. Online ahead of print.

ABSTRACT

Despite updated recommendations for weight-based isoniazid dosing in children with drug-susceptible tuberculosis (TB) and higher dose isoniazid in regimens for adults with drug-resistant TB, individual pharmacokinetic variability can lead to sub-target isoniazid exposure. Host pharmacogenetics and isoniazid exposure remain understudied, especially in the East African population. We therefore employed a real-time polymerase chain reaction (qPCR) assay system to test genomic DNA extracted from saliva samples targeting the NAT2 gene responsible for isoniazid metabolism to describe the frequency of human single nucleotide polymorphisms in NAT2 within populations of children and adults in Tanzania, ascribe those polymorphisms to acetylator phenotype, and correlate to serum isoniazid exposures. In adults treated with higher dose isoniazid, genotypes with a predicted allelic phenotype of slow or intermediate acetylation were able to achieve a 0.41 μg/mL higher Cmax (p = 0.018) and a 2.9h*μg/mL higher AUC0-12 (p = 0.003) per mg/kg increase in isoniazid dosage versus adults with rapid acetylation phenotype. A similar relationship was not found in the younger age population as predicted by timing of NAT2 maturation. This saliva based qPCR assay was fieldable to guide personalized isoniazid dosing in adults but not young children that may not have full NAT2 maturation and activity.

PMID:35961094 | DOI:10.1016/j.tube.2022.102246

High Blood Press Cardiovasc Prev. 2022 Aug 12. doi: 10.1007/s40292-022-00536-3. Online ahead of print.

ABSTRACT

INTRODUCTION: ABCB1 gene polymorphisms are associated with rivaroxaban distribution changes and adverse reactions but the data are controversial.

AIM: To evaluate the influence of ABCB1 (rs1045642 and rs4148738) gene polymorphisms on rivaroxaban pharmacokinetics in patients aged 80 years and older with nonvalvular atrial fibrillation (NAF).

METHODS: 128 patients aged 80 years and older (median [Me] age 87.5 [83.0-90.0] years) with NAF were included. We performed ABCB1 (rs1045642 and rs4148738) genotyping, measured the trough steady-state plasma concentration (Cmin,ss) of rivaroxaban and prothrombin time (PT) and analyzed prior medical records for clinically relevant non-major bleeding (CRNMB).

RESULTS: CC genotype carriers had no differences in Cmin,ss (p > 0.05) compared with the CT and TT rs1045642 and rs4148738 genotypes carriers. CC genotype carriers had no differences in PT (p > 0.05) compared with the CT rs1045642 and rs4148738 and TT rs4148738 genotypes carriers. In the TT genotype PT levels were higher than in the CC rs1045642 genotype: Me 14.2 [13.0-16.1] sec vs 13.3 [12.4-14.5] sec (p = 0.049). Incidence of CRNMB was higher in patients with the TT genotype compared with the CC rs1045642 (29.3% vs 4.5%, p = 0.021) and rs4148738 (39.3% vs 8.1%, p = 0.008) and the CT genotype rs4148738 (39.3% vs 14.3%, p = 0.002).

CONCLUSION: ABCB1 (rs1045642 and rs4148738) polymorphisms didn't influence rivaroxaban pharmacokinetics in patients aged 80 years and older with NAF. TT carriers developed CRNMB more frequently compared with the CC rs1045642 and the CC and CT rs4148738 genotypes. The haplotype TT-TT haplotype was associated with a higher frequency of CRNMB.

PMID:35960493 | DOI:10.1007/s40292-022-00536-3

Blood Cancer Discov. 2022 Aug 12:BCD-22-0011. doi: 10.1158/2643-3230.BCD-22-0011. Online ahead of print.

ABSTRACT

Despite the expanding portfolio of targeted therapies for adults with acute myeloid leukemia (AML), direct implementation in children is challenging due to inherent differences in underlying genetics. Here we established the pharmacological profile of pediatric AML by screening myeloblast sensitivity to approved and investigational agents, revealing candidates of immediate clinical relevance. Drug responses ex vivo correlated with patient characteristics, exhibited age-specific alterations, and concorded with activities in xenograft models. Integration with genomic data uncovered new gene-drug associations, suggesting actionable therapeutic vulnerabilities. Transcriptome profiling further identified gene expression signatures associated with on- and off-target drug responses. We also demonstrated the feasibility of drug screening-guided treatment for children with high-risk AML, with two evaluable cases achieving remission. Collectively, this study offers a high-dimensional gene-drug-clinical dataset that could be leveraged to research the unique biology of pediatric AML, and sets the stage for realizing functional precision medicine for clinical management of the disease.

PMID:35960210 | DOI:10.1158/2643-3230.BCD-22-0011

Am Heart J Plus. 2022 May;17:100152. doi: 10.1016/j.ahjo.2022.100152. Epub 2022 Jun 14.

ABSTRACT

BACKGROUND: Ischemic coronary heart disease (IHD) is the leading cause of death worldwide. Genetic variation is presumed to be a major factor underlying sex differences for IHD events, including mortality. The purpose of this study was to identify sex-specific candidate genes associated with all-cause mortality among people diagnosed with coronary artery disease (CAD).

METHODS: We performed a sex-stratified, exploratory genome-wide association (GWAS) screen using existing data from CAD-diagnosed males (n = 510) and females (n = 174) who reported European ancestry from the Duke Catheterization Genetics biorepository. Extant genotype data for 785,945 autosomal SNPs generated with the Human Omni1-Quad BeadChip (Illumina, CA, USA) were analyzed using an additive inheritance model. We estimated instantaneous risk of all-cause mortality by genotype groups across the 11-year follow-up using Cox multivariate regression, covarying for age and genomic ancestry.

RESULTS: The top GWAS hits associated with all-cause mortality among people with CAD included 8 SNPs among males and 15 among females (p = 1 × 10-6 or 10-7), adjusted for covariates. Cross-sex comparisons revealed distinct candidate genes. Biologically relevant candidates included rs9932462 (EMP2/TEKT5) and rs2835913 (KCNJ6) among males and rs7217169 (RAP1GAP2), rs8021816 (PRKD1), rs8133010 (PDE9A), and rs12145981 (LPGAT1) among females.

CONCLUSIONS: We report 20 sex-specific candidate genes having suggestive association with all-cause mortality among CAD-diagnosed subjects. Findings demonstrate proof of principle for identifying sex-associated genetic factors that may help explain differential mortality risk in people with CAD. Replication and meta-analyses in larger studies with more diverse samples will strengthen future work in this area.

PMID:35959094 | PMC:PMC9365120 | DOI:10.1016/j.ahjo.2022.100152

Int J Mol Sci. 2022 Aug 4;23(15):8686. doi: 10.3390/ijms23158686.

ABSTRACT

Cardiovascular diseases (CVDs) are a group of disorders of the heart and blood vessels. In addition to environmental risk factors, genetic predisposition increases the risk; this includes alterations in the vitamin D receptor gene (VDR). These alterations play a key role in modifying vitamin D uptake, being able to modify its function and increasing susceptibility to cardiovascular disorders. The aim of this study was to evaluate the association of polymorphisms in the VDR gene and risk of CVD in a Caucasian population. A retrospective case-control study was conducted comprising 246 CVD patients and 246 controls of Caucasian origin from Southern Spain. The genetic polymorphisms BsmI (rs1544410), TaqI (rs731236), ApaI (rs7975232), FokI (rs2228570) and Cdx2 (rs11568820) were determined by means of real-time polymerase chain reaction (PCR) for allelic discrimination using TaqMan® probes. The logistic regression analysis adjusted for body mass index and diabetes revealed that the TT genotype was associated with a higher risk of CVD in both the genotypic model (p = 0.0430; OR = 2.30; 95% CI = 1.06-5.37; TT vs. CC) and the recessive model (p = 0.0099; OR = 2.71; 95% CI = 1.31-6.07; TT vs. C). Haplotype analysis revealed that the haplotype GAC (p = 0.047; OR = 0.34; 95% CI = 0.12-0.98) was associated with increased risk of CVD. The VDR polymorphisms FokI (rs2228570) was significantly associated with the development of CVD. No influence was observed of the VDR polymorphisms BsmI (rs1544410), TaqI (rs731236), ApaI (rs7975232) and Cdx2 (rs11568820) on the risk of developing CVD in the patients studied.

PMID:35955825 | DOI:10.3390/ijms23158686

Int J Mol Sci. 2022 Jul 28;23(15):8360. doi: 10.3390/ijms23158360.

ABSTRACT

Clinical responses to anticancer therapies in advanced soft tissue sarcoma (STS) are unluckily restricted to a small subgroup of patients. Much of the inter-individual variability in treatment efficacy is as result of polymorphisms in genes encoding proteins involved in drug pharmacokinetics and pharmacodynamics. The nucleotide excision repair (NER) system is the main defense mechanism for repairing DNA damage caused by carcinogens and chemotherapy drugs. Single nucleotide polymorphisms (SNPs) of NER pathway key genes, altering mRNA expression or protein activity, can be significantly associated with response to chemotherapy, toxicities, tumor relapse or risk of developing cancer. In the present study, in a cohort of STS patients, we performed DNA extraction and genotyping by SNP assay, RNA extraction and quantitative real-time reverse transcription PCR (qPCR), a molecular dynamics simulation in order to characterize the NER pathway in STS. We observed a severe deregulation of the NER pathway and we describe for the first time the effect of SNP rs1047768 in the ERCC5 structure, suggesting a role in modulating single-stranded DNA (ssDNA) binding. Our results evidenced, for the first time, the correlation between a specific genotype profile of ERCC genes and proficiency of the NER pathway in STS.

PMID:35955506 | DOI:10.3390/ijms23158360

Int J Mol Sci. 2022 Jul 28;23(15):8364. doi: 10.3390/ijms23158364.

ABSTRACT

Statins are drugs widely prescribed in high-risk patients for cerebrovascular or cardiovascular diseases and are, usually, safe and well tolerated. However, these drugs sometimes may cause neuromuscular side effects that represent about two-third of all adverse events. Muscle-related adverse events include cramps, myalgia, weakness, immune-mediated necrotizing myopathy and, more rarely, rhabdomyolysis. Moreover, they may lead to peripheral neuropathy and induce or unmask a preexisting neuromuscular junction dysfunction. A clinical follow up of patients assuming statins could reveal early side effects that may cause neuromuscular damage and suggest how to better modulate their use. In fact, statin dechallenge or cessation, or the alternative use of other lipid-lowering agents, can avoid adverse events. This review summarizes the current knowledge on statin-associated neuromuscular adverse effects, diagnosis, and management. It is conceivable that the incidence of neuromuscular complications will increase because, nowadays, use of statins is even more diffused than in the past. On this purpose, it is expected that pharmacogenomic and environmental studies will help to timely predict neuromuscular complications due to statin exposure, leading to a more personalized therapeutic approach.

PMID:35955495 | DOI:10.3390/ijms23158364

Cells. 2022 Jul 29;11(15):2329. doi: 10.3390/cells11152329.

ABSTRACT

Prostate cancer (PCa) is the second most diagnosed cancer in the United States and is associated with metabolic reprogramming and significant disparities in clinical outcomes among African American (AA) men. While the cause is likely multi-factorial, the precise reasons for this are unknown. Here, we identified a higher expression of the metabolic enzyme UGT2B28 in localized PCa and metastatic disease compared to benign adjacent tissue, in AA PCa compared to benign adjacent tissue, and in AA PCa compared to European American (EA) PCa. UGT2B28 was found to be regulated by both full-length androgen receptor (AR) and its splice variant, AR-v7. Genetic knockdown of UGT2B28 across multiple PCa cell lines (LNCaP, LAPC-4, and VCaP), both in androgen-replete and androgen-depleted states resulted in impaired 3D organoid formation and a significant delay in tumor take and growth rate of xenograft tumors, all of which were rescued by re-expression of UGT2B28. Taken together, our findings demonstrate a key role for the UGT2B28 gene in promoting prostate tumor growth.

PMID:35954173 | DOI:10.3390/cells11152329

J Neurol Neurosurg Psychiatry. 2022 Aug 11:jnnp-2021-328516. doi: 10.1136/jnnp-2021-328516. Online ahead of print.

ABSTRACT

OBJECTIVES: Long COVID is a major public health issue. Whether long COVID is comorbid with psychiatric disorders remains unclear. Here, we investigate the association between long COVID, psychiatric symptoms and psychiatric disorders.

DESIGN: Cross-sectional.

SETTINGS: Bicêtre Hospital, France, secondary care.

PARTICIPANTS: One hundred seventy-seven patients admitted in intensive care unit during acute phase and/or reporting long COVID complaints were assessed 4 months after hospitalisation for an acute COVID.

MAIN OUTCOME MEASURES: Eight long COVID complaints were investigated: fatigue, respiratory and cognitive complaints, muscle weakness, pain, headache, paraesthesia and anosmia. The number of complaints, the presence/absence of each COVID-19 complaint as well as lung CT scan abnormalities and objective cognitive impairment) were considered. Self-reported psychiatric symptoms were assessed with questionnaires. Experienced psychiatrists assessed Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-based diagnoses of psychiatric disorders.

RESULTS: One hundred and fifteen (65%) patients had at least one long COVID complaint. The number of long COVID complaints was associated with psychiatric symptoms. The number of long COVID complaints was higher in patients with psychiatric disorders (mean (m) (SD)=2.47 (1.30), p<0.05), new-onset psychiatric disorders (m (SD)=2.41 (1.32), p<0.05) and significant suicide risk (m (SD)=2.67 (1.32), p<0.05) than in patients without any psychiatric disorder (m (SD)=1.43 (1.48)). Respiratory complaints were associated with a higher risk of psychiatric disorder and new-onset psychiatric disorder, and cognitive complaints were associated with a higher risk of psychiatric disorder.

CONCLUSIONS: Long COVID is associated with psychiatric disorders, new-onset psychiatric disorders and suicide risk. Psychiatric disorders and suicide risk should be systematically assessed in patients with long COVID.

PMID:35953265 | DOI:10.1136/jnnp-2021-328516