Project description:BackgroundThere is inconclusive and controversial evidence of the association between allergic diseases and the risk of adverse clinical outcomes of coronavirus disease 2019 (COVID-19).ObjectiveWe sought to determine the association of allergic disorders with the likelihood of a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result and with clinical outcomes of COVID-19 (admission to intensive care unit, administration of invasive ventilation, and death).MethodsA propensity-score-matched nationwide cohort study was performed in South Korea. Data obtained from the Health Insurance Review & Assessment Service of Korea from all adult patients (age, >20 years) who were tested for SARS-CoV-2 in South Korea between January 1, 2020, and May 15, 2020, were analyzed. The association of SARS-CoV-2 test positivity and allergic diseases in the entire cohort (n = 219,959) and the difference in clinical outcomes of COVID-19 were evaluated in patients with allergic diseases and SARS-CoV-2 positivity (n = 7,340).ResultsIn the entire cohort, patients who underwent SARS-CoV-2 testing were evaluated to ascertain whether asthma and allergic rhinitis were associated with an increased likelihood of SARS-CoV-2 test positivity. After propensity score matching, we found that asthma and allergic rhinitis were associated with worse clinical outcomes of COVID-19 in patients with SARS-CoV-2 test positivity. Patients with nonallergic asthma had a greater risk of SARS-CoV-2 test positivity and worse clinical outcomes of COVID-19 than patients with allergic asthma.ConclusionsIn a Korean nationwide cohort, allergic rhinitis and asthma, especially nonallergic asthma, confers a greater risk of susceptibility to SARS-CoV-2 infection and severe clinical outcomes of COVID-19.
Project description:Objective: To evaluate the association between common biomarkers, death and intensive care unit (ICU) admission in patients with COVID-19.Design: Retrospective cohort study. From electronic national registry data, we used Cox analysis and bootstrapping to evaluate associations between baseline levels of biomarkers and standardised absolute risks of death/ICU admission, adjusted for age and gender.Setting: All hospitals in Denmark.Participants: 1310 patients aged ?18 years admitted to hospital with COVID-19 from 27th of February to 1st of May 2020, with available biochemistry data.Main outcome measures: A composite of death/ICU admission occurring within 30 days.Results: Of the 1310 patients admitted to hospital (54.6% men; median age 73.6 years), 352 (26.9%) experienced the composite endpoint and 263 (20.1%) died. For the composite endpoint, the absolute risks for moderately and severely elevated C reactive protein (CRP) were significantly higher, 21.5% and 39.2%, respectively, compared with 5.0% for those with normal CRP. Moderately and severely elevated leucocytes were significantly higher, 34.5% and 46.6% risk, respectively, compared with 23.2% for those with normal leucocytes. Moderately and severely decreased estimated glomerular filtration rates (eGFR) were significantly higher, 41.5% and 45.9% risk, respectively, compared with 30.4% for those with normal/mildly decreased eGFR. Normal and elevated ureas were significantly higher, 22.3% and 40.6% risk, respectively, compared with 7.3% for those with low urea. Elevated D-dimer was significantly higher, 31.8% risk, compared with 17.5% for those with normal D-dimer. Moderately and severely elevated troponins were significantly higher, 27.7% and 57.3% risk, respectively, compared with 9.4% for those with normal troponin. Elevated procalcitonin was significantly higher, 52.1% risk, compared with 28.0% for those with normal procalcitonin.Conclusion: In this nationwide study of patients admitted with COVID-19, elevated levels of CRP, leucocytes, procalcitonin, urea, troponins and D-dimer, and low levels of eGFR were associated with higher standardised absolute risk of death/ICU admission within 30 days.
Project description:ObjectiveTo determine the potential association of age-related macular degeneration (AMD), a representative chronic age-related degenerative disease of the retina associated with inflammation and aging, with susceptibility to SARS-CoV-2 infection and severe COVID-19 outcomes.DesignNationwide cohort study with propensity-score matching.SettingPopulation-based nationwide cohort in Korea.Study populationData were obtained from the Health Insurance Review & Assessment Service of Korea, including all patients older than 40 years who underwent SARS-CoV-2 testing in South Korea between January 1, 2020, and May 15, 2020 (excluding self-referral).Main outcome measuresSARS-CoV-2 test positivity was the primary outcome and severe clinical outcome of COVID-19 was the secondary outcome.ResultsThe unmatched cohort consisted of 135,435 patients who were tested for SARS-CoV-2; 4531 (3.3%) tested positive for SARS-CoV-2; 5493 (4.1%) patients had AMD. After propensity score matching, exudative AMD was associated with an increased likelihood of susceptibility to SARS-CoV-2 infection (adjusted odds ratio [aOR], 1.50; 95% confidence interval [CI], 1.03-2.25), and a considerably greater risk of severe clinical outcomes of COVID-19 (aOR, 2.26; 95% CI, 1.02 to 5.26), but not any AMD and non-exudative AMD.ConclusionsIn a Korean nationwide cohort, our data suggest that clinicians should be aware of the greater risk of susceptibility to severe clinical outcomes of COVID-19 in patients with exudative AMD. Our findings provide an improved understanding of the relationship between the pathogenesis of COVID-19 and chronic neurological disorders.
Project description:ObjectivesThe prevalence of rheumatoid arthritis (RA) among patients with COVID-19 and the association between RA and the outcome of COVID-19 remain unclear. We aimed to compare the prevalence of RA between participants with and without COVID-19; we then analysed the association between the presence of RA and the severity of COVID-19.DesignA cross-sectional study.SettingData from a nationwide COVID-19 cohort database by the Korea National Health Insurance Corporation were used.Participants and interventionsA total of 8070 patients with COVID-19 (1 January 2020 through 4 June 2020) were matched with 32 280 control participants with regard to age, sex and income. Patients with COVID-19 were confirmed by SARS-CoV-2 PCR and controls were collected from the database. RA was confirmed using the diagnostic code (International Classification of Disease, Tenth Revision) and medication claim codes. Conditional/unconditional logistic regression was applied to analyse the association between RA and COVID-19.Primary outcome and secondary outcomeLaboratory confirmation of SARS-CoV-2 infection was defined as the primary outcome. The secondary outcome was severe COVID-19 defined as a history of intensive care unit admission, invasive ventilation or death.ResultsThe prevalence of RA in the COVID-19 (0.4%, 35/8070) and control (0.4%, 121/32,280) groups did not differ (p=0.446). After adjusting for underlying diseases, no association between RA and COVID-19 was observed (adjusted OR=1.14, 95% CI: 0.78 to 1.67) and COVID-19 severity was not associated with RA (adjusted OR=0.62, 95% CI: 0.14 to 7.29). The overall mortality rate was 2.9% (237/8070) and RA was not significantly associated with mortality (adjusted OR=1.64, 95% CI: 0.33 to 8.15).ConclusionWe did not find an association between the presence of RA and COVID-19. In addition, RA was not associated with the severity of COVID-19.
Project description:Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19), exhibit a wide spectrum of disease behavior. Since DNA methylation has been implicated in the regulation of viral infections and the immune system, we performed an epigenome- wide association study (EWAS) to identify candidate loci regulated by this epigenetic mark that could be involved in the onset of COVID-19 in patients without comorbidities.
Project description:ObjectivesRecent studies suggested obesity to be a possible risk factor for COVID-19 disease in the wake of the coronavirus (SARS-CoV-2) infection. However, the causality and especially the role of body fat distribution in this context is still unclear. Thus, using a univariable as well as multivariable two-sample Mendelian randomization (MR) approach, we investigated for the first time the causal impact of body composition on the susceptibility and severity of COVID-19.MethodsAs indicators of overall and abdominal obesity we considered the measures body mass index (BMI), waist circumference (WC), and trunk fat ratio (TFR). Summary statistics of genome-wide association studies (GWASs) for these body composition measures were drawn from the GIANT consortium and UK Biobank, while for susceptibility and severity due to COVID-19 disease data from the COVID-19 Host Genetics Initiative was used. For the COVID-19 cohort neither age nor gender was available. Total and direct causal effect estimates were calculated using Single Nucleotide Polymorphisms (SNPs), sensitivity analyses were done applying several robust MR techniques and mediation effects of type 2 diabetes (T2D) and cardiovascular diseases (CVD) were investigated within multivariable MR analyses.ResultsGenetically predicted BMI was strongly associated with both, susceptibility (OR = 1.31 per 1 SD increase; 95% CI: 1.15-1.50; P-value = 7.3·10-5) and hospitalization (OR = 1.62 per 1 SD increase; 95% CI: 1.33-1.99; P-value = 2.8·10-6) even after adjustment for genetically predicted visceral obesity traits. These associations were neither mediated substantially by T2D nor by CVD. Finally, total but not direct effects of visceral body fat on outcomes could be detected.ConclusionsThis study provides strong evidence for a causal impact of overall obesity on the susceptibility and severity of COVID-19 disease. The impact of abdominal obesity was weaker and disappeared after adjustment for BMI. Therefore, obese people should be regarded as a high-risk group. Future research is necessary to investigate the underlying mechanisms linking obesity with COVID-19.
Project description:The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has currently spread worldwide, leading to high morbidity and mortality. As the putative receptor of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2) is widely distributed in various tissues and organs of the human body. Simultaneously, ACE2 acts as the physiological counterbalance of ACE providing homeostatic regulation of circulating angiotensin II levels. Given that some ACE2 variants are known to cause an increase in the ligand-receptor affinity, their roles in acquisition, progression and severity of COVID-19 disease have aroused widespread concerns. Therefore, we summarized the latest literature and explored how ACE2 variants and epigenetic factors influence an individual’s susceptibility to SARS-CoV-2 infection and disease outcome in aspects of ethnicity, gender and age. Meanwhile, the possible mechanisms for these phenomena were discussed. Notably, recombinant human ACE2 and ACE2-derived peptides may have special benefits for combating SARS-CoV-2 variants and further studies are warranted to confirm their effects in later stages of the disease process. As the uncertainty regarding the severity and transmissibility of disease rises, a more in-depth understanding of the host genetics and functional characteristics of ACE2 variants will not only help explain individual clinical differences of the disease, but also contribute to providing effective measures to develop solutions and manage future outbreaks of SARS-CoV-2.
Project description:BackgroundEvidence for the associations between mental illness and the likelihood of a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result and the clinical outcomes of COVID-19 is scarce. We aimed to investigate these associations with data from a national register in South Korea.MethodsA nationwide cohort study with propensity score matching was done in South Korea using data collected from the Health Insurance Review and Assessment Service of Korea. We defined mental illness as present if one of the relevant ICD-10 codes was recorded at least twice within 1 year for an outpatient or inpatient. Severe mental illness was considered as non-affective or affective disorders with psychotic features. We included all patients aged older than 20 years who were tested for SARS-CoV-2 through services facilitated by the Korea Centers for Disease Control and Prevention, the Health Insurance Review and Assessment Service of Korea, and the Ministry of Health and Welfare, South Korea. We investigated the primary outcome (SARS-CoV-2 test positivity) in the entire cohort and the secondary outcomes (severe clinical outcomes of COVID-19: death, admission to the intensive care unit, or invasive ventilation) among those who tested positive.FindingsBetween Jan 1 and May 15, 2020, 216 418 people were tested for SARS-CoV-2, of whom 7160 (3·3%) tested positive. In the entire cohort with propensity score matching, 1391 (3·0%) of 47 058 patients without a mental illness tested positive for SARS-CoV-2, compared with 1383 (2·9%) of 48 058 with a mental illness (adjusted odds ratio [OR] 1·00, 95% CI 0·93-1·08). Among the patients who tested positive for SARS-CoV-2, after propensity score matching, 109 (8·3%) of 1320 patients without a mental illness had severe clinical outcomes of COVID-19 compared with 128 (9·7%) of 1320 with a mental illness (adjusted OR 1·27, 95% CI 1·01-1·66).InterpretationDiagnosis of a mental illness was not associated with increased likelihood of testing positive for SARS-CoV-2. Patients with a severe mental illness had a slightly higher risk for severe clinical outcomes of COVID-19 than patients without a history of mental illness. Clinicians treating patients with COVID-19 should be aware of the risk associated with pre-existing mental illness.FundingNational Research Foundation of Korea.
Project description:Background: Carnitine, a potential substitute or supplementation for dexamethasone, might protect against COVID-19 based on its molecular functions. However, the correlation between carnitine and COVID-19 has not been explored yet, and whether there exists causation is unknown. Methods: A two-sample Mendelian randomization (MR) analysis was conducted to explore the causal relationship between carnitine level and COVID-19. Significant single nucleotide polymorphisms from genome-wide association study on carnitine (N = 7,824) were utilized as exposure instruments, and summary statistics of the susceptibility (N = 1,467,264), severity (N = 714,592) and hospitalization (N = 1,887,658) of COVID-19 were utilized as the outcome. The causal relationship was evaluated by multiplicative random effects inverse variance weighted (IVW) method, and further verified by another three MR methods including MR Egger, weighted median, and weighted mode, as well as extensive sensitivity analyses. Results: Genetically determined one standard deviation increase in carnitine amount was associated with lower susceptibility (OR: 0.38, 95% CI: 0.19-0.74, P: 4.77E-03) of COVID-19. Carnitine amount was also associated with lower severity and hospitalization of COVID-19 using another three MR methods, though the association was not significant using the IVW method but showed the same direction of effect. The results were robust under all sensitivity analyses. Conclusions: A genetic predisposition to high carnitine levels might reduce the susceptibility and severity of COVID-19. These results provide better understandings on the role of carnitine in the COVID-19 pathogenesis, and facilitate novel therapeutic targets for COVID-19 in future clinical trials.