A phenome‐wide investigation of risk factors for severe COVID‐19

Baranova, Ancha; Cao, Hongbao; Teng, Shaolei; Zhang, Fuquan

doi:10.1002/jmv.28264

Cited by 33 publications

(25 citation statements)

References 75 publications

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“…A meta-analysis concluded that asthma was not associated with higher SARS-CoV-2 infection or a worse prognosis and that patients with asthma had lower mortality than those without asthma 39 . Previous MR analysis studies have also suggested that asthma was a protective factor for SARS-CoV-2 infection and severe COVID-19 7,8 . Although similar results were obtained only in the multivariate MR analysis with AR and AD as references, the two-sample MR analysis of asthma-severe COVID-19 in this study was negative.…”

Section: Discussionmentioning

confidence: 90%

“…Importantly, in contrast to traditional epidemiologic methods, the MR study can suggest the directionality of exposure and outcome, and thus a causal relationship rather than an association 6 . A relatively comprehensive MR study showed that physical activity, high education level, never smoking, and asthma were protective factors against hospitalized COVID-19 7 . It was also suggested through MR analysis that asthma was a protective factor for SARS-CoV-2 infection 8 .…”

Section: Introductionmentioning

confidence: 99%

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Allergic disease as a causal protective factor for severe covid-19: a multivariable mendelian randomization study

2023

Preprint

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Allergic diseases were recently reported related to both SARS-CoV-2 infection and severe COVID-19 through observational studies. However, their causal relationship remains unclear. Herein, we performed univariate and multivariate Mendelian randomization (MR) studies to investigate the causal association between various allergic diseases and COVID-19. Genome-wide association studies (GWAS) summaries were used in this study, with 360838 participants in the allergic disease database, 455449 in asthma, 217914 in allergic rhinitis (AR), and 205764 in atopic dermatitis (AD). In univariate MR analysis, the allergic disease was not causally in connection with SARS‐CoV‐2 infection but have a causal protective effect on severe COVID-19. In contrast, no significant causal effect was found of SARS-CoV-2 infection/severe COVID-19 on the allergic disease. AD, mixed asthma, and childhood asthma were causal protective factors for severe COVID-19. Multivariate MR analysis further revealed the dominant role of asthma in allergic diseases and the dominance of childhood asthma in asthma subtypes. In summary, this study, based on the population genetic variation model, pointed out the protective effect of allergic diseases against severe COVID-19, which may provide some inspiration for further exploration of the pathophysiological mechanisms of COVID-19.

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Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Allergic disease as a causal protective factor for severe covid-19: a multivariable mendelian randomization study

2023

Preprint

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“…(3) This article focuses on brain cell-types but it must be acknowledged that there are many other risk factors for Long Covid. E.g., in 456 422 participants from the UK Biobank, Baranova et al performed a Mendelian randomization analysis to examine relationships between COVID-19 hospitalization and health conditions, finding that a set of body fat-related traits, maternal smoking around birth, basal metabolic rate, lymphocyte count, peripheral enthesopathies and allied syndromes, blood clots in the legs, and arthropathy, are causal risk factors for severe COVID-19, while higher education attainment, physical activity, asthma, and never smoking status protect against the illness [87]. In order for these to affect mental functions, they must relate to brain cell-types, although the molecular connections are unclear.…”

Section: Discussionmentioning

confidence: 99%

Fluoxetine plus lithium for treatment of mental health impairment in Long Covid

Fessel

2023

Discov Ment Health

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Purposes (1) To summarize the mental conditions that may accompany persistent symptoms following acute infection by SARS-CoV-2, often termed Long Covid; (2) to formulate treatment based upon the brain cells that are dominantly affected. Methods (1) Review the reports relating to the mental symptoms occurring in Long Covid. (2) Review the drugs that address the brain cells affected in Long Covid, and suggest pharmacotherapy for those patients whose response to psychotherapy is suboptimal. Results Long Covid affects ~ 10% of patients infected by SARS-CoV-2, and mental symptoms affect ~ 20% of persons with Long Covid. The brain cell-types that have been demonstrated as dominantly affected in Long Covid are astrocytes, oligodendrocytes, neurons, endothelial cells/pericytes, and microglia. Lithium and fluoxetine each address all of those four cell-types. Low dosage of each is likely to be well-tolerated and to cause neither clinically important adverse events (AE) nor serious adverse events (SAE). Conclusion For those patients whose response to psychotherapy is suboptimal, lithium and fluoxetine should be administered in combination for both depth of benefit and reduction of dosages.

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“…MR can diminish the issues of unmeasured confounding and reverse causation, because genetic variants are randomly assorted at conception and are not modified by the progression of disease (Smith and Ebrahim, 2003). Recently, the MR approach has been successfully applied to shed light on the causal roles of smoking and alcohol consumption in a wide range of health outcomes (Rao et al, 2021;Larsson and Burgess, 2022;van de Luitgaarden et al, 2022;Zhang and Baranova, 2022;Baranova et al, 2023). Herein, we applied the MR design to explore the potential causal associations of smoking as well as alcohol consumption with frailty.…”

Section: Reviewed Bymentioning

confidence: 99%

Smoking, alcohol consumption, and frailty: A Mendelian randomization study

Wu²,

Sun³

et al. 2023

Front. Genet.

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Background: Tobacco smoking and alcohol consumption have been associated with frailty in observational studies. We sought to examine whether these associations reflect causality using the two-sample Mendelian randomization (MR) design.Methods: We used summary genome-wide association statistics for smoking initiation (N = 2,669,029), alcohol consumption (N = 2,428,851), and the frailty index (FI, N = 175,226) in participants of European ancestry. Both univariable and multivariable MR were performed to comprehensively evaluate the independent effects of smoking and alcohol consumption on the FI, accompanied by multiple sensitivity analyses. Results were verified using lifetime smoking and alcohol use disorder. Reverse direction MR was undertaken to assess the potential for reverse causation.Results: Genetic predisposition to smoking initiation was significantly associated with increased FI (univariable MR: β = 0.345; 95% confidence interval [CI] = 0.316 to 0.374; p = 1.36E-113; multivariable MR: β = 0.219; 95% CI = 0.197 to 0.241; p = 2.44E-83). Genetically predicted alcohol consumption showed a suggestive association with the FI (univariable MR: β = −0.090; 95% CI = −0.151 to −0.029; p = 0.003; multivariable MR β = −0.153; 95% CI = −0.212 to −0.094; p = 2.03E-07), with inconsistent results in sensitivity analyses. In complementary analysis, genetic predicted lifetime smoking, but not alcohol use disorder was associated with the FI. There is no convincing evidence for reverse causation.Conclusion: The present MR study supported smoking as a causal risk factor of frailty. Further research is warranted to investigate whether alcohol consumption has a causal role in frailty.

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A phenome‐wide investigation of risk factors for severe COVID‐19

Cited by 33 publications

References 75 publications

Allergic disease as a causal protective factor for severe covid-19: a multivariable mendelian randomization study

Allergic disease as a causal protective factor for severe covid-19: a multivariable mendelian randomization study

Fluoxetine plus lithium for treatment of mental health impairment in Long Covid

Smoking, alcohol consumption, and frailty: A Mendelian randomization study

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