Association between short-term exposure to ambient air pollutants and biomarkers indicative of inflammation and oxidative stress: a cross-sectional study using KoGES-HEXA data.

BACKGROUND: Air pollution-induced systemic inflammation and oxidative stress are hypothesized to be the major biological mechanisms underlying pathological outcomes. We examined the association between short-term exposure to ambient air pollutants and biomarkers of inflammation and oxidative stress in 2199 general middle-aged Korean population residing in metropolitan areas. METHODS: Serum levels of inflammatory cytokines (interleukin [IL]-1ß, IL-6, IL-8, IL-10, and tumor necrosis factor [TNF]-α) and urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured. Daily concentrations of a series of air pollutants (particulate matter [PM]10, PM2.5, SO2, NO2, CO, and O3) were predicted using the Community Multiscale Air Quality modeling system, and participant-level pollutant exposure was determined using geocoded residential addresses. Short-term exposure was defined as the 1- to 7-day moving averages. RESULTS: The multivariable-adjusted linear models controlling for the sociodemographic, lifestyle, temporal, and meteorological factors identified positive associations of PM with IL-1ß, IL-8, IL-10, TNF-α, and 8-OHdG levels; SO2 with IL-10 levels, CO with IL-1ß, IL-10, and TNF-α levels; and O3 with IL-1ß, IL-8, and 8-OHdG levels. O3 levels were inversely associated with IL-10 levels. For each pollutant, the strongest associations were observed for the 7-day average PM and CO with IL-1ß (per 10-µg/m3 increase in PM10: 2.7%, 95% confidence interval [CI] = 0.6-4.8; per 10-µg/m3 increase in PM2.5: 6.4%, 95% CI = 2.4-10.5; per 0.1-ppm increase in CO: 3.3%, 95% CI = 0.3-6.5); the 2-day average SO2 with IL-10 levels (per 1-ppb increase in SO2: 1.1%, 95% CI = 0.1-2.1); and the 7-day average O3 with IL-8 levels (per 1-ppb increase in O3: 1.3%, 95% CI = 0.7-1.9). CONCLUSIONS: Short-term exposure to ambient air pollutants may induce oxidative damage and pro-inflammatory roles, together with counter-regulatory anti-inflammatory response.

Integrated dataset of the Korean Genome and Epidemiology Study cohort with estimated air pollution data.

Public concern about the adverse health effects of air pollution has grown rapidly in Korea, and there has been increasing demand for research on ways to minimize the health effects of air pollution. Integrating large epidemiological data and air pollution exposure levels can provide a data infrastructure for studying ambient air pollution and its health effects. The Korean Genome and Epidemiology Study (KoGES), a large population-based study, has been used in many epidemiological studies of chronic diseases. Therefore, KoGES cohort data were linked to air pollution data as a national resource for air pollution studies. Air pollution data were produced using community multiscale air quality modeling with additional adjustment of monitoring data, satellite-derived aerosol optical depth, normalized difference vegetation index, and meteorological data to increase the accuracy and spatial resolution. The modeled air pollution data were linked to the KoGES cohort based on participants' geocoded residential addresses in grids of 1 km (particulate matter) or 9 km (gaseous air pollutants and meteorological variables). As the integrated data become available to all researchers, this resource is expected to serve as a useful infrastructure for research on the health effects of air pollution.

Long-Term Effects of Ambient Particulate and Gaseous Pollutants on Serum High-Sensitivity C-Reactive Protein Levels: A Cross-Sectional Study Using KoGES-HEXA Data.

Ambient air pollutants reportedly increase inflammatory responses associated with multiple chronic diseases. We investigated the effects of long-term exposure to ambient air pollution on high-sensitivity C-reactive protein (hs-CRP) using data from 60,581 participants enrolled in the Korean Genome and Epidemiology Study-Health Examinees Study between 2012 and 2017. Community Multiscale Air Quality System with surface data assimilation was used to estimate the participants' exposure to criteria air pollutants based on geocoded residential addresses. Long-term exposure was defined as the 2-year moving average concentrations of PM10, PM2.5, SO2, NO2, and O3. Multivariable linear and logistic regression models were utilized to estimate the percent changes in hs-CRP and odds ratios of systemic low-grade inflammation (hs-CRP > 3 mg/L) per interquartile range increment in air pollutants. We identified positive associations between hs-CRP and PM10 (% changes: 3.75 [95% CI 2.68, 4.82]), PM2.5 (3.68, [2.57, 4.81]), SO2 (1.79, [1.10, 2.48]), and NO2 (3.31, [2.12, 4.52]), while negative association was demonstrated for O3 (-3.81, [-4.96, -2.65]). Elevated risks of low-grade inflammation were associated with PM10 (odds ratio: 1.07 [95% CI 1.01, 1.13]), PM2.5 (1.08 [1.02, 1.14]), and SO2 (1.05 [1.01, 1.08]). The odds ratios reported indicated that the exposures might be risk factors for inflammatory conditions; however, they did not reflect strong associations. Our findings suggest that exposure to air pollutants may play a role in the inflammation process.

Effect of Short- to Long-Term Exposure to Ambient Particulate Matter on Cognitive Function in a Cohort of Middle-Aged and Older Adults: KoGES.

Exposure to ambient air pollution and its threat to human health is a global concern, especially in the elderly population. Therefore, more in-depth studies are required to understand the extent of the harmful effects of particulate matter (PM) based on duration and levels of exposure. An investigation was conducted to determine the association between short- (1-14 days), medium- (1, 3, and 6 months), and long-term (1, 2, and 3 years) exposure to air pollutants (PM2.5 and PM10) and cognitive function among Koreans (4175 participants, mean age 67.8 years, 55.2% women) aged over 50 years. Higher levels of PM2.5 exposure for short to long term and PM10 exposure for medium to long term were found to be associated with decreased cognitive function, as indicated by lower scores of the Mini-Mental State Examination adopted in Korean (K-MMSE). There were significant effect modifications by sex, age group, alcohol consumption, physical activity, and smoking status in the association between long-term PM2.5 and PM10 exposure and cognitive function. These findings, which underscore the importance of the efforts to reduce the exposure levels and durations of air pollutants, especially in the vulnerable elderly population, provide evidence for establishing more stringent policies for air pollution regulations.

Lower number of modifiable risk factors was associated with reduced atrial fibrillation incidence in an 18-year prospective cohort study.

Prevention strategies for atrial fibrillation (AF) are lacking. This study aimed to identify modifiable risk factors (MRFs) and estimate their impact on AF in the midlife general population. We assessed 9049 participants who were free of prevalent AF at baseline from the Korean Genome and Epidemiology Study. Cox models with time-varying assessment of risk factors were used to identify significant MRFs for incident AF. The MRF burden was defined as the proportion of visits with MRFs during follow-up. Over a median follow-up of 13.1 years, 182 (2.01%) participants developed AF. Three MRFs, including systolic blood pressure (SBP) ≥ 140 mmHg, obesity with central obesity, and an inactive lifestyle were significantly associated with incident AF. Among participants with 3, 2, 1, and 0 MRFs at baseline, 16 (3.9%), 51 (2.5%), 90 (1.8%) and 25 (1.5%) had incident AF, respectively. Compared to participants with three MRFs, those with one or no MRFs had a decreased risk of AF (hazard ratio [95% CI] for one MRF, 0.483 [0.256-0.914]; and for no MRF, 0.291 [0.145-0.583]). A decreasing MRF burden was associated with reduced AF risk (hazard ratio [95% CI] per 10% decrease in burden for SBP ≥ 140 mmHg, 0.937 [0.880-0.997]; for obesity with central obesity, 0.942 [0.907-0.978]; for inactivity, 0.926 [0.882-0.973]). Maintaining or achieving MRF ≤ 1 was associated with decreased AF risk, suggesting that minimizing the burden of MRF might help prevent AF.

Genome-wide gene and serum ferritin interaction in the development of type 2 diabetes in adults aged 40 years or older.

BACKGROUND AND AIMS: Elevated serum ferritin is associated with incident Type 2 diabetes (T2D), but the interactions between serum ferritin and genetic factors which may improve understanding underlying mechanism in the development of T2D are still unclear. We determined the gene-ferritin interactions on the development of T2D by genome-wide gene-ferritin interaction analyses. METHODS AND RESULTS: A total of 3405 participants from two prospective cohorts of community living residents were included, and the median follow-time was 3.99 years. Genome-wide gene-ferritin interactions were analyzed using the joint test with two degrees of freedom and the interaction test with one degree of freedom. There were 18 SNPs selected in the joint test. Finally, four independent variants [rs355140 (LINC00312), rs4075576 (nearby PDGFA), rs1332202 (PTPRD), and rs713157 (nearby LINC00900)] with low pairwise linkage disequilibrium (r2<0.2) and located at least 1000 kb from the index SNP showed interactions with serum ferritin level. In the association analyses between serum ferritin levels (tertiles of ferritin and ferritin status) and the incidence of T2D according to genotype, the Incidence Rate Ratios (IRRs) in the highest tertile of ferritin level (vs. the lowest tertile) were greater for participants with heterozygotes of risk alleles of each of the four SNP than IRRs for those with wild type. Compared with the normal group, the elevated ferritin group also had a higher risk of T2D for all genetic variants of risk alleles, particularly its homozygotes. CONCLUSION: Serum ferritin level interacts with genetic variants (rs355140, rs4075576, rs1332202, and rs713157) in the development of T2D.

Application of nano-graphene oxide as nontoxic disinfectant against alpha and betacoronaviruses.

New viruses are continuously emerging and recently there have been many great concerns on severe acute respiratory syndrome coronavirus (SARS-CoV-2). Nanographene oxide (nanoGO) has received much attention and is widely investigated to be utilised in therapy for infectious diseases by viruses. Thus, antiviral activity of nanoGO was evaluated using the porcine epidemic diarrhoea virus (PEDV), bovine coronavirus (BCoV), and SARS-CoV-2, which are all Alpha- and Beta-coronavirus. In a virus inhibition assay, the three viruses were inhibited by nanoGO in a dose-dependent manner, including attempts in the presence of high serum solution which partially mimicked biological fluid.

Presenting characteristics and clinical outcome of patients with COVID-19 in South Korea: A nationwide retrospective observational study.

BACKGROUND: More than 13,000 cases were reported to be infected with COVID-19 by RT-PCR in South Korea. Most studies report clinical characteristics of hospitalized patients with COVID-19; the full spectrum of disease severity has thus not yet been well described. METHODS: Using retrospective observational methods, this study analyzed factors affecting early clinical symptoms, clinical progress, and severity of disease for COVID-19 positive patients released from quarantine to provide information on establishing optimized care for new patients. The medical data of 7803 laboratory-confirmed patients who had been discharged or died by April 30, 2020 were analyzed using multivariate logistic regression analysis. FINDINGS: On admission, 7383 (94•5%) patients were asymptomatic or showed mild illness, and 372 (4•8%) patients were severe illness. Also, 48 (0 0•6%) were hospitalized with critically ill when diagnosed. Most patients with asymptomatic or mild illness on admission remained mild until discharge, 253 (3•4%) progressed to severe illness, and 83 (1•1%) died in hospital. However, the case fatality were 29•8% and 62•5% in severe and critically ill patients, respectively. At admission, 73•0% of hospitalized patients had symptoms; most common were cough (42•5%), sputum (28•8%), and fever (20•1%). Only 35•2% of laboratory confirmed patients admitted to the temporary care facility complained of symptoms. Increasing odds of being critically ill was associated with older age (OR 28•93, 95% CI 13•34-62•75 for age >70y, vs. age <50 y; p<0•0001), being male (OR 2•15, 95% CI1•59-2•89; p<0•0001), fever (OR 2•52, 95% CI 1.84-3•45; p<0•0001), and shortness of breath (OR 7•40, 95% CI 5•37-10•19; p<0•0001). Comorbid illness significantly increased risk of critical illness or death. INTERPRETATION: Most cases were discharged as asymptomatic or recovered from mild illness, and only 9•7% developed severe disease requiring oxygen therapy or more. Case fatality rate was 2•9%, and markedly increased in those over age 50. Risk factors such as age, sex, fever, shortness of breath, and underlying disease can be useful in predicting future clinical severity. Additionally, the number of confirmed asymptomatic COVID-19 patients significantly contribute to continued spread. FUNDING: none.

The Korea Biobank Array: Design and Identification of Coding Variants Associated with Blood Biochemical Traits.

We introduce the design and implementation of a new array, the Korea Biobank Array (referred to as KoreanChip), optimized for the Korean population and demonstrate findings from GWAS of blood biochemical traits. KoreanChip comprised >833,000 markers including >247,000 rare-frequency or functional variants estimated from >2,500 sequencing data in Koreans. Of the 833 K markers, 208 K functional markers were directly genotyped. Particularly, >89 K markers were presented in East Asians. KoreanChip achieved higher imputation performance owing to the excellent genomic coverage of 95.38% for common and 73.65% for low-frequency variants. From GWAS (Genome-wide association study) using 6,949 individuals, 28 associations were successfully recapitulated. Moreover, 9 missense variants were newly identified, of which we identified new associations between a common population-specific missense variant, rs671 (p.Glu457Lys) of ALDH2, and two traits including aspartate aminotransferase (P = 5.20 × 10-13) and alanine aminotransferase (P = 4.98 × 10-8). Furthermore, two novel missense variants of GPT with rare frequency in East Asians but extreme rarity in other populations were associated with alanine aminotransferase (rs200088103; p.Arg133Trp, P = 2.02 × 10-9 and rs748547625; p.Arg143Cys, P = 1.41 × 10-6). These variants were successfully replicated in 6,000 individuals (P = 5.30 × 10-8 and P = 1.24 × 10-6). GWAS results suggest the promising utility of KoreanChip with a substantial number of damaging variants to identify new population-specific disease-associated rare/functional variants.

Genetic Characteristics and Immunogenicity of Pandemic H1N1 Influenza Virus Isolate from Pig in Korea.

A pandemic influenza A (H1N1) virus strain was isolated from a pig farm in Korea in December 2009. The strain was propagated in and isolated from both the Madin-Darby canine kidney cell line and embryonated eggs. The partial and complete sequences of the strain were identical to those of A/California/04/2009, with >99% sequence similarity in the HA, NA, M, NS, NP, PA, PB1, and PB2 genes. The isolated strain was inactivated and used to prepare a swine influenza vaccine. This trial vaccine, containing the new isolate that has high sequence similarity with the pandemic influenza A (H1N1) virus, resulted in seroconversion in Guinea pigs and piglets. This strain could therefore be a potential vaccine candidate for swine influenza control in commercial farms.

A novel canine influenza H3N2 virus isolated from cats in an animal shelter.

The interspecies transmission of avian-origin H3N2 canine influenza virus (CIV) to dogs was first reported in 2007. The present study characterized a novel CIV H3N2 isolated from cats in an animal shelter. A comparative analysis of the deduced amino acid sequences of the A/Canine/Korea/CY009/2010(H3N2) (CY009) and A/Feline/Korea/FY028/2010 (H3N2) (FY028) strains isolated from dogs and cats, respectively, in the animal shelter identified point mutations in 18 amino acid positions within eight viral genes. Interestingly, CY009 and FY028 replicated well in specific pathogen-free embryonated chicken eggs and in mice, respectively. Mice infected with the FY028 strain exhibited significant over expression of IL-10, TNF-α, and IFN-γ (p<0.001) at 3 days postinfection. Thus, an emergency monitoring system should be developed to identify influenza mutations that occur during interspecies transmission in companion animals and for continuous public health surveillance.

Sublingual administration of bacteria-expressed influenza virus hemagglutinin 1 (HA1) induces protection against infection with 2009 pandemic H1N1 influenza virus.

Influenza viruses are respiratory pathogens that continue to pose a significantly high risk of morbidity and mortality of humans worldwide. Vaccination is one of the most effective strategies for minimizing damages by influenza outbreaks. In addition, rapid development and production of efficient vaccine with convenient administration is required in case of influenza pandemic. In this study, we generated recombinant influenza virus hemagglutinin protein 1 (sHA1) of 2009 pandemic influenza virus as a vaccine candidate using a well-established bacterial expression system and administered it into mice via sublingual (s.l.) route. We found that s.l. immunization with the recombinant sHA1 plus cholera toxin (CT) induced mucosal antibodies as well as systemic antibodies including neutralizing Abs and provided complete protection against infection with pandemic influenza virus A/CA/04/09 (H1N1) in mice. Indeed, the protection efficacy was comparable with that induced by intramuscular (i.m.) immunization route utilized as general administration route of influenza vaccine. These results suggest that s.l. vaccination with the recombinant non-glycosylated HA1 protein offers an alternative strategy to control influenza outbreaks including pandemics.

Complete Genome Sequence of a Canine-Origin H3N2 Feline Influenza Virus Isolated from Domestic Cats in South Korea.

A canine-origin Korean H3N2 feline influenza virus (FIV), A/feline/Korea/01/2010 (H3N2), was isolated in 2010 from a dead cat with severe respiratory disease. Here, we report the first complete genome sequence of this virus, containing 3' and 5' noncoding regions, which will help elucidate the molecular basis of the pathogenesis, transmission, and evolution of FIV.

Molecular epidemiology and phylogenetic analysis of porcine epidemic diarrhea virus (PEDV) field isolates in Korea.

Porcine epidemic diarrhea virus (PEDV) has caused devastating enteric disease in Korean pig farms since its first identification in 1992 in Korea. In the present study, the molecular epidemiology, genetic diversity, and phylogenetic relationship of Korean PEDV field isolates to other reference strains were analyzed using the complete E gene. Genetic analysis showed that each PEDV group had several unique characteristics, which indicated that a specific group PEDVs may be differentiated from another group PEDVs. Phylogenetic analysis showed that recent prevalent Korean PEDV field isolates are closely related to the Chinese field strains and differ genetically from the European strains and the vaccine strains used in Korea, which raises questions of whether a new-type PEDV vaccine may be necessary for preventing PEDV infection more effectively in Korea. Notably, a large deletion identified only in the attenuated DR13 can be utilized as a genetic marker, and the methods developed in this study will help to rapidly detect and differentiate PEDVs.

Antiviral activity of the plant extracts from Thuja orientalis, Aster spathulifolius, and Pinus thunbergii against influenza virus A/PR/8/34.

Influenza viruses cause significant morbidity and mortality in humans through epidemics or pandemics. Currently, two classes of anti-influenza virus drugs, M2 ion-channel inhibitors (amantadin and rimantadine) and neuraminidase inhibitors (oseltamivir and zanamivir), have been used for the treatment of the influenza virus infection. Since the resistance to these drugs has been reported, the development of a new antiviral agent is necessary. In this study, we examined the antiviral efficacy of the plant extracts against the influenza A/PR/8/34 infection. In vitro, the antiviral activities of the plant extracts were investigated using the cell-based screening. Three plant extracts, Thuja orientalis, Aster spathulifolius, and Pinus thunbergii, were shown to induce a high cell viability rate after the infection with the influenza A/PR/8/34 virus. The antiviral activity of the plant extracts also increased as a function of the concentration of the extracts and these extracts significantly reduced the visible cytopathic effect caused by virus infections. Furthermore, the treatment with T. orientalis was shown to have a stronger inhibitory effect than that with A. spathulifolius or P. thunbergii. These results may suggest that T. orientalis has anti-influenza A/PR/8/34 activity.

Simultaneous detection of canine respiratory disease associated viruses by a multiplex reverse transcription-polymerase chain reaction assay.

A multiplex reverse transcription polymerase chain reaction (mRT-PCR) assay was developed for the simultaneous detection of canine distemper virus (CDV), canine respiratory coronavirus (CRCoV) and canine influenza virus (CIV). These viral pathogens are all causative agents of canine infectious respiratory disease (CIRD). The sensitivity and specificity of the mRT-PCR were determined by comparing it to a rapid antigen test (RAT) or immuno-chromatography test kit and reverse transcription-polymerase chain reaction (RT-PCR) in the detection of CDV, CRCoV and CIV antigens present in 100 clinical samples (nasal swabs and whole blood samples) from 50 dogs with respiratory disease symptoms. This study revealed that mRT-PCR had almost exactly the same performance or results were almost 100% in agreement with that of RT-PCR and RAT both in terms of the assay sensitivity and specificity which was more highly evident in detecting CIV, CDV and CRCoV antigens present in canine nasal swab samples. Therefore, this assay could be a better alternative for the definitive and simultaneous ante-mortem detection of the three viral pathogens that cause CIRD by using nasal swabs.

Complete genome sequence of a mammalian species-infectious and -pathogenic H6N5 avian influenza virus without evidence of adaptation.

An H6N5 avian influenza virus (AIV) strain, designated A/aquatic bird/Korea/CN5/2009 (H6N5), was isolated from fecal swabs of aquatic birds in 2009, and surprisingly, it showed infectivity and pathogenicity in mammalian species without evidence of adaptation. In this study, we report the first complete genome sequence containing 3' and 5' noncoding regions (NCRs) of a mammalian species-infectious and pathogenic H6N5 AIV, which will help provide important insights into the molecular basis of pathogenesis, transmission, and evolution of AIV.

Complete genome sequence of an avian-origin H3N2 canine influenza virus isolated from dogs in South Korea.

An avian-origin Korean H3N2 canine influenza virus (CIV) strain, designated A/canine/Korea/01/2007 (H3N2), was isolated from nasal swabs of pet dogs exhibiting severe respiratory syndrome in 2007. In the present study, we report the first complete genome sequence containing 3' and 5' noncoding regions (NCRs) of H3N2 CIV, which will provide important insights into the molecular basis of pathogenesis, transmission, and evolution of CIV.

Seroprevalence of subtype H3 influenza A virus in South Korean cats.

To investigate the potential transmission of subtype H3 influenza virus to cats, a serological survey was carried out in South Korea. Serum samples (n=1027) were obtained from 809 pet cats and 218 domesticated cats living in urban colonies (D-cats) from 2008 to 2010, and tested using an influenza anti-nucleoprotein (NP)-specific enzyme-linked immunosorbent assay (ELISA) and the haemagglutination inhibition (HI) test, which was recommended by the World Organization for Animal Health. Anti-influenza virus antibodies were detected in 3.12% and 2.43% of cat sera tested using the NP-specific ELISA and HI test, respectively. Anti-H3 antibodies were also identified when the HI assay was used for influenza virus serotyping. These data may indicate the sporadic transmission of subtype H3 influenza virus from other infected species to cats in South Korea.

Kobuvirus in South Korean black goats.

Kobuviruses have been detected in humans and several animal species, including cattle, swine, sheep, canines, mice, and probably bats. While investigating the possibility of Kobuviruses infecting additional animal host species, we detected kobuvirus in three fecal samples from domestic Korean black goats. In a maximum parsimony tree and a Bayesian tree, the 08KG680 strain fell within the bovine kobuvirus lineage, but the 09KG172 and 10KG056 strains did not fall within any of the known animal kobuvirus lineages. Comparative analysis of the partial nucleotide sequences of the RNA-dependent RNA polymerase (RdRp) gene of the 08KG680 strain also revealed high amino acid sequence identity and a close genetic relationship with bovine kobuvirus, but the amino acid sequences of the other two strains had low similarity to those of known kobuvirus isolates from any animal species. The similarity of the sequence of the 08KG680 strains with the bovine kobuvirus indicate that the infectious may have originated from cattle, but the possible source for remaining strains could not be classified.