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1.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323746

ABSTRACT

Background: Emerging evidence shows that periodontal disease (PD) may increase the risk of Coronavirus disease 2019 (COVID-19) complications. Here, we undertook a two-sample Mendelian randomization (MR) study, and investigated for the first time the possible causal impact of PD on host susceptibility to COVID-19 and its severity.Methods: Summary statistics of COVID-19 susceptibility and severity was retrieved from the COVID-19 Host Genetics Initiative and used as outcomes in this study. As for exposures, Single Nucleotide Polymorphisms (SNPs) with genome-wide significant variants from genome wide association study (GWAS) of PD were included in the MR analysis. Inverse-variance weighted (IVW) method was employed as the main approach to analyzing the causal relationships between PD and COVID-19. Three additional methods were adopted, allowing the existence of horizontal pleiotropy including MR-Egger regression, weighted median and weighted mode methods. Comprehensive sensitivity analyses were also conducted for estimating the robustness of the identified associations.Findings: The MR estimates showed that PD was markedly associated with a higher susceptibility to COVID-19 using IVW (OR = 1.024, P = 0.017) and weighted median method (OR = 1.029, P = 0.024). Furthermore, it revealed that PD was significantly linked to COVID-19 severity based on the comparison of hospitalization versus population controls (IVW: OR = 1.025, P = 0.039;weighted median, OR = 1.030, P = 0.027). No such association was observed in the cohort of highly severe cases confirmed versus those not hospitalized due to COVID-19.Interpretation: This study provides genetic evidence on the possible causality of periodontal disease accounting for the host susceptibility to COVID-19 and its severity, thereby highlighting the importance of disease prevention and oral/periodontal healthcare for general wellbeing during the pandemic and beyond.Funding Information: This work was supported by the Natural Science Foundation of Zhejiang Province (LY18H160050, LQ20H140002), Medical and Health Science and Technology Planning Project of Zhejiang Province (2018KY518), National Natural Science Foundation of China (31771390, 81972261, 32070151), Wenzhou Science and Technology Bureau (ZY2020007, 2020Y0536, Y20190147).Declaration of Interests: The authors declare that no competing interests exist.Ethics Approval Statement: This study only used publicly available data and the relevant ethical approval can be found in the corresponding studies referenced in the Methods section.

2.
J Transl Med ; 19(1): 528, 2021 12 24.
Article in English | MEDLINE | ID: covidwho-1638964

ABSTRACT

BACKGROUND: Emerging evidence shows that periodontal disease (PD) may increase the risk of Coronavirus disease 2019 (COVID-19) complications. Here, we undertook a two-sample Mendelian randomization (MR) study, and investigated for the first time the possible causal impact of PD on host susceptibility to COVID-19 and its severity. METHODS: Summary statistics of COVID-19 susceptibility and severity were retrieved from the COVID-19 Host Genetics Initiative and used as outcomes. Single nucleotide polymorphisms associated with PD in Genome-wide association study were included as exposure. Inverse-variance weighted (IVW) method was employed as the main approach to analyze the causal relationships between PD and COVID-19. Three additional methods were adopted, allowing the existence of horizontal pleiotropy, including MR-Egger regression, weighted median and weighted mode methods. Comprehensive sensitivity analyses were also conducted for estimating the robustness of the identified associations. RESULTS: The MR estimates showed that PD was significantly associated with significantly higher susceptibility to COVID-19 using IVW (OR = 1.024, P = 0.017, 95% CI 1.004-1.045) and weighted median method (OR = 1.029, P = 0.024, 95% CI 1.003-1.055). Furthermore, it revealed that PD was significantly linked to COVID-19 severity based on the comparison of hospitalization versus population controls (IVW, OR = 1.025, P = 0.039, 95% CI 1.001-1.049; weighted median, OR = 1.030, P = 0.027, 95% CI 1.003-1.058). No such association was observed in the cohort of highly severe cases confirmed versus those not hospitalized due to COVID-19. CONCLUSIONS: We provide evidence on the possible causality of PD accounting for the susceptibility and severity of COVID-19, highlighting the importance of oral/periodontal healthcare for general wellbeing during the pandemic and beyond.


Subject(s)
COVID-19 , Periodontal Diseases , COVID-19/genetics , Genome-Wide Association Study , Humans , Mendelian Randomization Analysis , Periodontal Diseases/complications , Periodontal Diseases/genetics , Polymorphism, Single Nucleotide
3.
Nat Microbiol ; 5(11): 1439-1448, 2020 11.
Article in English | MEDLINE | ID: covidwho-841871

ABSTRACT

SARS-CoV-2 is causing a pandemic of COVID-19, with high infectivity and significant mortality1. Currently, therapeutic options for COVID-19 are limited. Historically, metal compounds have found use as antimicrobial agents, but their antiviral activities have rarely been explored. Here, we test a set of metallodrugs and related compounds, and identify ranitidine bismuth citrate, a commonly used drug for the treatment of Helicobacter pylori infection, as a potent anti-SARS-CoV-2 agent, both in vitro and in vivo. Ranitidine bismuth citrate exhibited low cytotoxicity and protected SARS-CoV-2-infected cells with a high selectivity index of 975. Importantly, ranitidine bismuth citrate suppressed SARS-CoV-2 replication, leading to decreased viral loads in both upper and lower respiratory tracts, and relieved virus-associated pneumonia in a golden Syrian hamster model. In vitro studies showed that ranitidine bismuth citrate and its related compounds exhibited inhibition towards both the ATPase (IC50 = 0.69 µM) and DNA-unwinding (IC50 = 0.70 µM) activities of the SARS-CoV-2 helicase via an irreversible displacement of zinc(II) ions from the enzyme by bismuth(III) ions. Our findings highlight viral helicase as a druggable target and the clinical potential of bismuth(III) drugs or other metallodrugs for the treatment of SARS-CoV-2 infection.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Bismuth/pharmacology , Coronavirus Infections/virology , Pneumonia, Viral/virology , Ranitidine/analogs & derivatives , Virus Replication/drug effects , Animals , Betacoronavirus/physiology , COVID-19 , Chemokines/metabolism , Chlorocebus aethiops , Coronavirus Infections/drug therapy , Cytokines/metabolism , Disease Models, Animal , HEK293 Cells , Humans , Lung/pathology , Lung/virology , Mesocricetus , Pandemics , Pneumonia, Viral/drug therapy , RNA Helicases/metabolism , Ranitidine/pharmacology , SARS-CoV-2 , Vero Cells , Viral Load
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