Potential Heterogeneities Research Articles

Investigating the impact of the COVID-19 pandemic on the nutritional status of infants and toddlers: insights from China

BackgroundA comprehensive understanding of the impact of the COVID-19 pandemic on childhood nutrition is crucial for devising effective mitigation strategies. However, existing knowledge regarding the pandemic’s effect on childhood nutritional status remains limited. Furthermore, research focusing on young children aged 0–3 years is scarce.MethodsLeveraging the outbreak that originated in Wuhan in Dec 2019, the epicenter of China’s first and largest outbreak, and national survey and statistical yearbook data, this study conducted a natural experimental analysis with the consideration of geographical exposure, temporal exposure and survey cohort effects to investigate the pandemic’s impacts on varying nutritional indicators of infants and toddlers aged 0–36 months. A comprehensive set of sensitivity analyses, robustness checks and falsification tests were conducted. The potential heterogeneities across socioeconomic and age groups were also examined.ResultsThe pandemic was robustly predictive of a higher weight-for-age z-score (WAZ) and length/height-for-age z-score (HAZ), and a lower likelihood of underweight. The effects of the pandemic on increasing WAZ and reducing underweight were more pronounced among children from economically disadvantaged backgrounds or aged 0–12 months. Additionally, the increasing HAZ was primarily among children from households with lower family income. Moreover, the pandemic was negatively linked to the body mass index (BMI)-for-age z-score (BAZ) of children residing in more developed cities, and positively linked to overweight/obesity among children aged 13–24 months.ConclusionsThis study adds to a more comprehensive understanding of the impact of the COVID-19 pandemic on childhood nutrition. Notably, the findings highlight that weight gain attributable to the pandemic was predominantly among vulnerable children from disadvantaged backgrounds and younger age groups, who were already at a higher risk of overweight/obesity before the pandemic. Consequently, our findings imply the necessity of greater caution to the widened gap in childhood malnutrition post-pandemic. Furthermore, the study emphasizes the importance of implementing adaptable strategies with the consideration of social justice to safeguard all children’s right to optimal growth from exogenous shocks and to achieve the children-related SDGs by 2030.

Association between weight-adjusted waist index with incident stroke in the elderly with hypertension: a cohort study

The objective of this study was to ascertain the relationship between the weight-adjusted waist index (WWI) and the risk of stroke in an elderly hypertensive population, a relationship that has not been previously elucidated. The Cox regression model was employed to assess the correlation between baseline WWI measurements and the incidence of stroke. To further elucidate the shape of the association between baseline WWI and stroke, restricted cubic splines were employed. Furthermore, subgroup analyses and interaction tests were carried out to investigate potential heterogeneities. Our study cohort comprised 4962 hypertensive individuals aged 60 years or older with no prior history of stroke. Over a median follow-up of 3.2 years, we found 547 new-onset stroke cases. After adjusting for confounding variables, the Cox regression analysis revealed a positive association between baseline WWI and the risk of stroke, with hazard ratios (HRs) escalating progressively as WWI values increased. When compared to the lowest quartile of WWI, the highest quartile demonstrated an HR of 1.87 (95% CI, 1.44–2.42) for stroke. Subgroup analyses confirmed the consistency of this relationship across different demographic and clinical strata. The study findings indicate that an elevated WWI is significantly related with a higher risk of new-onset stroke among elderly patients with hypertension. These results underscore the importance of WWI as a potential risk stratification tool. To confirm these results and explore the causal mechanisms behind the observed correlation, more study is necessary.

Multiple potential phase-separation paths in multi-principal element alloys

It is now well established that multi-principal element alloys (MPEAs) offer ample opportunities for exploring new compositions beyond those accessed previously by conventional alloys. However, there is one more realm of possibility presented by MPEAs that has not been touch upon thus far. Here we show that, different from conventional alloys based on a single host element, a given starting MPEA solid solution on its way towards equilibrium can take a rich variety of potential decomposition pathways via multi-stage phase separation, offering a wide range of composition destinations. If/when some of them are reached, assuming kinetically allowed, the multiple phase separation reactions one after another would lead to domains that are compositionally complex and spatially localized. This hypothetical scenario is demonstrated in this paper using a model that mimics Cr-Co-Ni MPEA, showing a preponderance of multiplicity even when assuming only fcc-based phases can form. The complex chemical heterogeneities created as such are expected to be an additional knob to turn for tuning spatially variable composition and chemical order and therefore mechanical properties. Our results thus advocate multiple phase separation possibilities with many potential paths and terminal chemical heterogeneities as yet another important characteristic that distinguishes MPEAs from conventional alloys.

Rains after the drought: the impact of VAT credit refund on corporate R&D expenditures in China

ABSTRACT This study investigates the impact of a major tax policy reform – the Value Added Tax (VAT) credit refund policy – on corporate R&D expenditures in China. We employ a difference-in-differences approach to analyse the causal effect of the policy and examine potential heterogeneities based on firm features. Our findings reveal a significant and positive effect of the VAT credit refund policy on corporate R&D expenditures, particularly for firms with private ownership, small size, and non-high-tech classification. Additionally, mediation analysis indicates that the policy alleviates financial constraints, facilitating increased R&D investment, while moderation analysis shows a more pronounced impact on firms with lower initial liquidity. These results underscore the significance of addressing internal financial constraints and firm characteristics in designing tax policies to stimulate corporate R&D investment.

Analyzing heterogeneity in biomarker discriminative performance through partial time-dependent receiver operating characteristic curve modeling.

This study investigates the heterogeneity of a biomarker's discriminative performance for predicting subsequent time-to-event outcomes across different patient subgroups. While the area under the curve (AUC) for the time-dependent receiver operating characteristic curve is commonly used to assess biomarker performance, the partial time-dependent AUC (PAUC) provides insights that are often more pertinent for population screening and diagnostic testing. To achieve this objective, we propose a regression model tailored for PAUC and develop two distinct estimation procedures for discrete and continuous covariates, employing a pseudo-partial likelihood method. Simulation studies are conducted to assess the performance of these procedures across various scenarios. We apply our model and inference procedure to the Alzheimer's Disease Neuroimaging Initiative data set to evaluate potential heterogeneities in the discriminative performance of biomarkers for early Alzheimer's disease diagnosis based on patients' characteristics.

Comparative genomic profiling of circulating tumor DNA and paired formalin-fixed paraffin-embedded (FFPE) DNA from Indian patients with breast cancer.

e14554 Background: Breast cancer (BC) is the most frequent malignancy and a leading cause of mortality in women worldwide. Although most BCs are treated with curative intent, 30-40 % patients experience disease progression or metastatic relapse. Considering high heterogeneity of BC, mutational profiling of solid biopsy may not be adequate for informed treatment decisions in all cases. Liquid biopsy based on circulating tumor DNA (ctDNA) analysis is emerging as an equivalent and alternative to tissue biopsy in clinical settings. Though extremely critical for management of BC, liquid biopsy is not a standard of care in India. Here we compared comprehensive genomic profiles of ctDNA and paired biopsy samples to determine the efficacy of ctDNA assay in detecting actionable mutational targets. Methods: Retrospectively, genomic DNA and matched ctDNA was isolated from both FFPE and blood samples of14 BC patients. The patients were confirmative with pathological findings, having metastatic infiltrating ductal carcinoma, or triple negative breast cancers. Genome-wide HRD, TMB and MSI scores based on the OncoIndx comprehensive gene panel (CGP) was determined. OncoIndx CGP targets 1080 cancer related genes along with 47 HRR genes and 1600 MSI signature sites. Libraries were prepared using a hybridization-capture method based on custom-designed OncoIndx 1080 CGP and sequenced (depth 5500 X) on Illumina Nextseq 2000 in a pair-end mode (150 x2). Variant calling was performed using a proprietary bioinformatics pipeline iCare. Results: All patients were diagnosed with metastatic infiltrating ductal carcinoma, or triple negative breast cancers. From the patient cohort, microsatellite instability (MSI) from ctDNA showed 100% concordance with FFPE DNA while tumor mutation burden (TMB) and homologous recombination deficiency (HRD) scores showed 71.4 % and 64.2 % concordance with FFPE DNA respectively. At the individual gene mutation level, the concordance TP53, BRCA1/2, PI3K family of genes, ESR1, PTEN, ERBB2, PALB2, and BRAF genes between ctDNA and FFPE DNA was 54.7%, 92.8%, 54.7%, 78.5%, 92.8%, 100%, 100%, and 100% respectively. Many important genomic alterations including PIK3CA:p.L334H, PIK3CA:p.E81K, ESR1:p.Q375L, BRCA2:p.X3040_splice, PTEN:p.D19H were exclusive to ctDNA thereby denoting potential tumor heterogeneities which could be missed from FFPE DNA. Conclusions: Our results suggest a high correlation between ctDNA and FFPE DNA detected by OncoIndx test in metastatic or triple negative breast cancer patients of Indian ethnicity. Although not a part of standard of care, liquid biopsy could be of significant potential for management of BC in the standard clinical settings. However, a thorough investigation of cancer stage, and clinical presentations are necessary to carefully evaluate the selection of ctDNA or FFPE DNA-based genomic profiling.

Land as a binding constraint to cluster-based development in Ethiopia: To cluster or not to cluster?

As one of the agglomeration models targeting cluster-based rural development, cluster farming has been promoted in Ethiopia and it is already reported to have significant welfare implications, but participation rates are not as high as expected. This study examines the role of land as a constraint to the development of cluster-based development in Ethiopia both using extensive and intensive measures of cluster farming. The study further disaggregates farm households based on their farm size to better understand potential heterogeneities in the relationship between farm size and cluster farming. The paper also documents other household socio-economic and network characteristics that may matter in cluster farming. We use a large-scale farm household data from 3,969 households coupled with some expert insights on cluster farming in Ethiopia. Households in the study areas grow major staples such as maize, wheat, teff, malt barley, and sesame in four main regions of Ethiopia. We employ a double hurdle model to examine both the decision to participate and the extent to which households participate in cluster farming. By extent of participation, we refer to the amount of land and share of land farm households contribute to cluster farming. For robustness purposes, we also estimate the Tobit and Linear Probability Models. We show a positive association between farm size and cluster farming both at the extensive and intensive margins. This relationship turns negative for large amounts of land. This shows that cluster farming increases with farm size up to a threshold beyond which it declines. We also find suggestive evidence that participation rates are lower for small-scale farms, but also declines for large-scale farms. In addition, we show that access to information and network characteristics also matter in enabling cluster farming. The findings of this study are relevant in the framework of plans to upscale the cluster-based development initiative in Ethiopia. Attention to landholding issues is key and may be an important area where policy action can be geared to boost cluster farming. Moreover, our results inform potential targeting plans that aim to increase the participation of small-scale farmers who are usually the intended targets of such programs.

Exploring Heterogeneous Effects of Victimization on Changes in Fear of Crime: The Moderating Role of Neighborhood Conditions

A growing research body shows that victimization increases victims’ fear of crime. Typically, this research estimates average effects, which may conceal that people respond differently to victimization or that ecological contexts shape the experience of crime. The current study is among the few that attempt to uncover potential heterogeneities in victimization effects by ecological contexts. It explores whether the victims’ neighborhood conditions (levels of crime, disorder, and concentrated disadvantage) moderate the impact of violent victimization close to home on fear of crime. For this purpose, longitudinal multilevel models were estimated using data from a two-wave panel survey of about 3300 adult respondents nested in 140 neighborhoods in two large German cities. The results suggest that individuals from more disadvantaged neighborhoods tend to increase their fear of crime more strongly after victimization than those from more advantaged areas. For the other neighborhood conditions, victimization effects were estimated to be more homogenous.

Nanoscale structural heterogeneities in metastable refractory high-entropy alloy

Most refractory high-entropy alloys (RHEAs) with the dominant body-centered-cubic (bcc) phase are lack of room temperature tensile ductility, which strictly limits their large-scale applications in industry and aerospace. Recently, it has been found that the strategy of metastability engineering can be utilized to ductilize the TiZrHf-based RHEAs. However, up to now, a nanoscale understanding of the potential structural heterogeneities in this system remains exclusive. Herein, through performing the transmission electronic microscope (TEM) characterization on a prototype TaZrHfTa0.5 RHEA with exceptional tensile properties, we have found that this alloy contains a high density of nanoscale structural heterogeneities that are randomly distributed throughout the bcc matrix, including the hexagonal ω phase forming by the collapse of {111}bcc atomic pairs and the orthorhombic α″ phase forming by coupled shuffle-shear mechanism. It may provide a microstructural basis for manipulating the macroscopic properties of metastable RHEAs.

Evidence for liquid-liquid phase separation during the early stages of Mg-struvite formation.

The precipitation of struvite, a magnesium ammonium phosphate hexahydrate (MgNH4PO4 · 6H2O) mineral, from wastewater is a promising method for recovering phosphorous. While this process is commonly used in engineered environments, our understanding of the underlying mechanisms responsible for the formation of struvite crystals remains limited. Specifically, indirect evidence suggests the involvement of an amorphous precursor and the occurrence of multi-step processes in struvite formation, which would indicate non-classical paths of nucleation and crystallization. In this study, we use synchrotron-based in situ x-ray scattering complemented by cryogenic transmission electron microscopy to obtain new insights from the earliest stages of struvite formation. The holistic scattering data captured the structure of an entire assembly in a time-resolved manner. The structural features comprise the aqueous medium, the growing struvite crystals, and any potential heterogeneities or complex entities. By analysing the scattering data, we found that the onset of crystallization causes a perturbation in the structure of the surrounding aqueous medium. This perturbation is characterized by the occurrence and evolution of Ornstein-Zernike fluctuations on a scale of about 1nm, suggesting a non-classical nature of the system. We interpret this phenomenon as a liquid-liquid phase separation, which gives rise to the formation of the amorphous precursor phase preceding actual crystal growth of struvite. Our microscopy results confirm that the formation of Mg-struvite includes a short-lived amorphous phase, lasting >10s.

Association of TIM-3 with anterior uveitis and associated systemic immune diseases: a Mendelian randomization analysis.

We aimed to investigate the causal association between TIM-3, an immune checkpoint inhibitor, and anterior uveitis (AU), as well as associated systemic immune diseases. We performed two-sample Mendelian randomization (MR) analyses to estimate the causal effects of TIM-3 on AU and three associated systemic diseases, namely ankylosing spondylitis (AS), Crohn's disease (CD), and ulcerative colitis (UC). Single-nucleotide polymorphisms (SNPs) associated with AU, AS, CD, and UC were selected as the outcomes: AU GWAS with 2,752 patients with acute AU accompanied with AS (cases) and 3,836 AS patients (controls), AS GWAS with 968 cases and 336,191 controls, CD GWAS with 1,032 cases and 336,127 controls, and UC GWAS with 2,439 cases and 460,494 controls. The TIM-3 dataset was used as the exposure (n = 31,684). Four MR methods, namely, inverse-variance weighting (IVW), MR-Egger regression, weighted median, and weighted mode, were used in this study. Comprehensive sensitivity analyses were conducted to estimate the robustness of identified associations and the potential impact of horizontal pleiotropy. Our studies show that TIM-3 is significantly associated with CD using the IVW method (OR = 1.001, 95% CI = 1.0002-1.0018, P-value = 0.011). We also found that TIM-3 may be a protective factor for AU although these results lacked significance (OR = 0.889, 95% CI = 0.631-1.252, P-value = 0.5). No association was observed between the genetic predisposition to particular TIM-3 and susceptibility to AS or UC in this study. No potential heterogeneities or directional pleiotropies were observed in our analyses. According to our study, a small correlation was observed between TIM-3 expression and CD susceptibility. Additional studies in different ethnic backgrounds will be necessary to further explore the potential roles and mechanisms of TIM-3 in CD.

Transmission dynamics of lyssavirus in Myotis myotis: mechanistic modelling study based on longitudinal seroprevalence data.

We investigated the transmission dynamics of lyssavirus in Myotis myotis and Myotis blythii, using serological, virological, demographic and ecological data collected between 2015 and 2022 from two maternity colonies in northern Italian churches. Despite no lyssavirus detection in 556 bats sampled over 11 events by reverse transcription-polymerase chain reaction (RT-PCR), 36.3% of 837 bats sampled over 27 events showed neutralizing antibodies to European bat lyssavirus 1, with a significant increase in summers. By fitting sets of mechanistic models to seroprevalence data, we investigated factors that influenced lyssavirus transmission within and between years. Five models were selected as a group of final models: in one model, a proportion of exposed bats (median model estimate: 5.8%) became infectious and died while the other exposed bats recovered with immunity without becoming infectious; in the other four models, all exposed bats became infectious and recovered with immunity. The final models supported that the two colonies experienced seasonal outbreaks driven by: (i) immunity loss particularly during hibernation, (ii) density-dependent transmission, and (iii) a high transmission rate after synchronous birthing. These findings highlight the importance of understanding ecological factors, including colony size and synchronous birthing timing, and potential infection heterogeneities to enable more robust assessments of lyssavirus spillover risk.

Apprentices or outsiders? Age-driven heterogeneities in access to political capital and reelection

Norms about what constitutes an ideal politician are shown to negatively affect the demand for young political candidates within political parties because they favor qualities that young people have yet to acquire. We ask whether this “youth bias” continues to shape the political opportunities of those young persons who get elected. Drawing on comprehensive, original data encompassing all Czech MPs elected between 1996 and 2021, we analyze potential age-driven heterogeneities in access to valuable political resources and reelection, both of which are subject to party gatekeeping. We find that young MPs are given a privileged access to assignments that facilitate learning about the legislative business and reelection, despite being more likely to cast a dissenting vote at roll call. These results suggest that young MPs, unlike some other political outgroups, are not marginalized by their superiors despite exhibiting certain traits typically associated with political outgroups.

Technology Focus: Well Testing (February 2023)

The energy transition is in a continuous pursuit of innovative technology applications from all corners of the oil and gas industry. With the exponential growth of carbon capture and sequestration (CCS) projects, similar subsurface appraisal objectives remain. Derisking dynamic reservoir performance and characterizing storage pore space are key enablers for prospective CCS projects. The mention of well testing often takes readers to a visualization of hydrocarbon disposition by a flare. Once a bright and vibrant spectacle of our industry’s exploration updates, the days of flaunting a chairman’s flow or banker’s burn are past. Waning application of well testing during our energy transition is a specious assumption, and it’s the optics that are transforming as the well testing discipline proves its value to long-term carbon storage projects. Injecting CO2 into the subsurface is hardly a new concept; operators have been doing this for decades as part of enhanced oil recovery. However, the application of injecting CO2 is changing in response to operators’ environmental, social, and governance ambitions. While carbon storage concepts exist in many forms, anchoring a storage project requires pore space of adequate quantity and quality in proximity to a fixed source of emissions. Carbon storage projects also must manage additional risks such as sustained injectivity performance, geologic seal integrity, and plume migration, to name a few. Enter well testing. Quantifying injection performance of supercritical fluids is crucial for optimizing wells to meet project needs while minimizing the number of required penetrations through a structural seal. Whether for a saline aquifer or a previously depleted field, pressure transient analysis enhances understanding of the pore space intended for storage and the potential heterogeneities within. Furthermore, integrating well testing with other reservoir-description tools may be used to monitor migration of stored fluids within the reservoir. With corporate and regulatory targets driving the unprecedented pace and scale of CCS opportunities, well testing is quickly reaffirming itself as a powerful tool in characterizing pore space essential to our lower-carbon goals. This month’s papers highlight ongoing developments within the well testing discipline and important reminders about how to properly use dynamic data. The application of these well testing fundamentals to a nascent carbon storage market is still evolving. Recommended additional reading at OnePetro: www.onepetro.org. SPE 208967 Rate-Pseudopressure Deconvolution Enhances Rate-Time Models Production History-Matches and Forecasts of Shale Gas Wells by L.M. Ruiz Maraggi, The University of Texas at Austin, et al. URTeC 3705570 Analysis of Multiple Flow/Buildup Tests Including a 5-year Buildup: Case Study of an Australian Shale Gas Well by Christopher R. Clarkson, University of Calgary, et al. OTC 31691 Challenges and Mitigation Strategies for High-Rate Gas Well Testing in High-Pressure/High-Temperature DST Operation by Jakpakorn Hemaprasertsuk, PTTEP, et al.

Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing

Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, whole-genome sequences and expression quantitative trait locus (eQTL) data from diverse ancestries. We developed a new approach, TESLA (multi-ancestry integrative study using an optimal linear combination of association statistics), to integrate an eQTL dataset with a multi-ancestry GWAS. By exploiting shared phenotypic effects between ancestries and accommodating potential effect heterogeneities, TESLA improves power over other TWAS methods. When applied to tobacco use phenotypes, TESLA identified 273 new genes, up to 55% more compared with alternative TWAS methods. These hits and subsequent fine mapping using TESLA point to target genes with biological relevance. In silico drug-repurposing analyses highlight several drugs with known efficacy, including dextromethorphan and galantamine, and new drugs such as muscle relaxants that may be repurposed for treating nicotine addiction.

THE CAUSALITY BETWEEN AGRICULTURAL RAW MATERIALS AND ECONOMIC POLICY UNCERTAINTY: EVIDENCE FROM THE TIME-VARYING GRANGER CAUSALITY

This paper aims to examine the time-varying dynamics of the causality interaction between agricultural raw materials commodity prices and the US economic policy uncertainty (EPU). To this end, we use monthly data for the period spanning from January 1992 to November 2021. We employ a time-varying Granger causality test to provide empirical evidence about the time-varying dynamics of the causality interaction and thereby revealing potential heterogeneities of these interactions during major historical events. The results show that causality running from EPU to agricultural raw materials, as well as causality running from agricultural raw materials to EPU, exhibits time-varying dynamics. More specifically, the findings reveal that causality generally tended to run from agricultural raw materials to EPU for most of the 2000-2014 period, but reversed with the US-China trade war and the Covid-19 pandemic period. This result highlights the importance of modeling the potential causality interactions in the economic uncertainty-commodity prices nexus within a dynamic framework and implies that these interactions cannot be considered independently of the prevailing economic, political and global conditions.

Implications of Access to Portable Water on Child Health Production in Cameroon

This study attempts to quantify the effects of access to portable water on child health outcome and to investigate potential heterogeneities in the effect of access to portable water on child health by age distribution. Methodologically, we used the 2011/2018 Cameroon demographic and health survey via 2SLS and ivprobit models. Results show that a positive marginal change in access to portable water will result to a corresponding increase in child health, Child health of age 24-36 months is strongly affected by access to portable water. Decision makers should intensify child health – access to portable water campaigns, following the WHO standards.

The Health of Immigrant Youth in Denmark: Examining Immigrant Generations and Origin

First-generation migrants tend to have better health than those of native ancestry, while second-generation migrants often are affected by negative health assimilation. Less is known about immigrants arriving before their teens, the 1.5 generation, or those with one native and one immigrant parent, the 2.5 generation. We apply logistic regression models to study physical and mental health outcomes for immigrant youth across generations using Danish register data. We take heterogeneities into account studying gender and origin differences. Our analysis shows that first- and 1.5-generation immigrants have better physical health than natives, while the physical health of the second and 2.5 generations is the same or worse than natives. For mental health, the 2.5 generation is the only group with worse outcomes than natives, which we relate to identification struggles translating into poorer mental health. When studying potential heterogeneities, we find that males belonging to the second generation with an African background have a higher likelihood of hospitalization for a mental health issue.

Beyond the interest rate pass-through: monetary policy and banks interest rates since the effective lower bound

ABSTRACT We investigate whether ECB monetary policy influences the retail interest rates in the Euro Area when the policy rate reaches the effective lower bound. We estimate a panel Error Correction Model that accounts for potential heterogeneities in the transmission of monetary policy. The analysis disentangles alternative balance-sheet policies implemented by the ECB. We find that unconventional measures have influenced banking interest rates beyond the pass-through of the current and expected policy rate. These effects are driven by liquidity provisions and by the covered bond purchase programmes. Those policies have been effective in the core and in the peripheral countries; however, the effect of purchases of covered-bond has been stronger in the periphery.

Relationship Between Plasma Vitamin C and COVID-19 Susceptibility and Severity: A Two-Sample Mendelian Randomization Study.

BackgroundConsidering the antioxidant function of Vitamin C, also called ascorbic acid, it is widely used against viral infections such as coronavirus disease (COVID-19) based on in vitro, observational, and ecological studies. Many confounding factors that can affect Vitamin C levels. Thus, the association described to date may not be causal. To determine the causal relationship between genetically predicted plasma Vitamin C and COVID-19 susceptibility and severity, we performed two-sample Mendelian randomization (MR) based on large samples.MethodsThe summary-level data for Vitamin C was obtained from a GWAS meta-analysis, which included 52,018 individuals from four studies of European ancestry. Data for COVID-19 HGI results were obtained from the meta-analysis of 35 GWASs with more than 1,000,000 subjects of European ancestry, including 32,494 cases with COVID-19 susceptibility and 1,316,207 controls, 9,986 cases with COVID-19 hospitalization and 1,877,672 controls, and 5,101 cases with COVID-19 severe disease and 1,383,241 controls. Mendelian randomization (MR) analysis was conducted to examine the effect of selected single nucleotide polymorphisms and COVID-19 susceptibility, hospitalization, disease severity. Several sensitivity analyses were performed with inverse-variance weighted (random-effect model), inverse variance weighted (fixed-effect model), weighted median, and maximum likelihood methods for estimating the causal effects.ResultsIn this MR study, genetic predisposition to the levels of plasma Vitamin C was not associated with COVID-19 susceptibility (OR: 0.99, 95% CI: 0.84–1.17, P = 0.91), hospitalization (OR: 1.10, 95% CI: 0.71–1.71, P = 0.67) and severity (OR: 0.83, 95% CI: 0.43–1.59, P = 0.58). The association was consistent in complementary analyses. No potential heterogeneities and directional pleiotropies were observed for the analysis results.ConclusionAccording to our study, no correlation was observed between plasma Vitamin C levels and COVID-19 susceptibility and severity. Further studies in different ethnics are necessary to explore the potential role and mechanisms of circulating serum Vitamin C levels on COVID-19.