Unveiling causal connections: Long-term particulate matter exposure and type 2 diabetes mellitus mortality in Southern China.

Evidence of the potential causal links between long-term exposure to particulate matters (PM, i.e., PM1, PM2.5, and PM1-2.5) and T2DM mortality based on large cohorts is limited. In contrast, the existing evidence usually suffers from inherent bias with the traditional association assessment. A prospective cohort of 580,757 participants in the southern region of China were recruited during 2009 and 2015 and followed up through December 2020. PM exposure at each residential address was estimated by linking to the well-established high-resolution simulation dataset. Hazard ratios (HRs) were calculated using time-varying marginal structural Cox models, an established causal inference approach, after adjusting for potential confounders. During follow-up, a total of 717 subjects died from T2DM. For every 1 µg/m3 increase in PM2.5, the adjusted HRs and 95% confidence interval (CI) for T2DM mortality was 1.036 (1.019-1.053). Similarly, for every 1 µg/m3 increase in PM1 and PM1-2.5, the adjusted HRs and 95% CIs were 1.032 (1.003-1.062) and 1.085 (1.054-1.116), respectively. Additionally, we observed a generally more pronounced impact among individuals with lower levels of education or lower residential greenness which as measured by the Normalized Difference Vegetation Index (NDVI). We identified substantial interactions between NDVI and PM1 (P-interaction = 0.003), NDVI and PM2.5 (P-interaction = 0.019), as well as education levels and PM1 (P-interaction = 0.049). The study emphasizes the need to consider environmental and socio-economic factors in strategies to reduce T2DM mortality. We found that PM1, PM2.5, and PM1-2.5 heighten the peril of T2DM mortality, with education and green space exposure roles in modifying it.

Prior water availability modifies the effect of heavy rainfall on dengue transmission: a time series analysis of passive surveillance data from southern China.

Introduction: Given the rapid geographic spread of dengue and the growing frequency and intensity of heavy rainfall events, it is imperative to understand the relationship between these phenomena in order to propose effective interventions. However, studies exploring the association between heavy rainfall and dengue infection risk have reached conflicting conclusions, potentially due to the neglect of prior water availability in mosquito breeding sites as an effect modifier. Methods: In this study, we addressed this research gap by considering the impact of prior water availability for the first time. We measured prior water availability as the cumulative precipitation over the preceding 8 weeks and utilized a distributed lag non-linear model stratified by the level of prior water availability to examine the association between dengue infection risk and heavy rainfall in Guangzhou, a dengue transmission hotspot in southern China. Results: Our findings suggest that the effects of heavy rainfall are likely to be modified by prior water availability. A 24-55 day lagged impact of heavy rainfall was associated with an increase in dengue risk when prior water availability was low, with the greatest incidence rate ratio (IRR) of 1.37 [95% credible interval (CI): 1.02-1.83] occurring at a lag of 27 days. In contrast, a heavy rainfall lag of 7-121 days decreased dengue risk when prior water availability was high, with the lowest IRR of 0.59 (95% CI: 0.43-0.79), occurring at a lag of 45 days. Discussion: These findings may help to reconcile the inconsistent conclusions reached by previous studies and improve our understanding of the complex relationship between heavy rainfall and dengue infection risk.

Prior water availability modifies the effect of heavy rainfall on dengue transmission: a time series analysis of passive surveillance data from southern China.

Background: Given the rapid geographic spread of dengue and the growing frequency and intensity of heavy rainfall events, it is imperative to understand the relationship between these phenomena in order to propose effective interventions. However, studies exploring the association between heavy rainfall and dengue infection risk have reached conflicting conclusions. Methods: In this study, we use a distributed lag non-linear model to examine the association between dengue infection risk and heavy rainfall in Guangzhou, a dengue transmission hotspot in southern China, stratified by prior water availability. Results: Our findings suggest that the effects of heavy rainfall are likely to be modified by prior water availability. A 24-55 day lagged impact of heavy rainfall was associated with an increase in dengue risk when prior water availability was low, with the greatest incidence rate ratio (IRR) of 1.37 (95% credible interval (CI): 1.02-1.83) occurring at a lag of 27 days. In contrast, a heavy rainfall lag of 7-121 days decreased dengue risk when prior water availability was high, with the lowest IRR of 0.59 (95% CI: 0.43-0.79), occurring at a lag of 45 days. Conclusions: These findings may help to reconcile the inconsistent conclusions reached by previous studies and improve our understanding of the complex relationship between heavy rainfall and dengue infection risk.

Epidemiological and genomic analysis of dengue cases in Guangzhou, China, from 2010 to 2019.

With a long epidemic history and a large number of dengue cases, Guangzhou is a key city for controlling dengue in China. The demographic information regarding dengue cases, and the genomic characteristics of the envelope gene of dengue viruses, as well as the associations between these factors were investigated from 2010 to 2019, to improve the understanding of the epidemiology of dengue in Guangzhou. Demographic data on 44,385 dengue cases reported to the Notifiable Infectious Disease Report System were analyzed using IBM SPSS Statistics v. 20. Dengue virus isolates from patient sera were sequenced, and phylogenetic trees were constructed using PhyML 3.1. There was no statistical difference in the risk of dengue infection between males and females. Unlike other areas in which dengue is endemic, the infection risk in Guangzhou increased with age. Surveillance identified four serotypes responsible for dengue infections in Guangzhou. Serotype 1 remained prevalent for most of the study period, whereas serotypes 3 and 4 were prevalent in 2012 and 2010, respectively. Different serotypes underwent genotype and sublineage shifts. The epidemiological characteristics and phylogeny of dengue in Guangzhou suggested that although it has circulated in Guangzhou for decades, it has not been endemic in Guangzhou. Meanwhile, shifts in genotypes, rather than in serotypes, might have caused dengue epidemics in Guangzhou.

Effect of Vaccination Time Intervals on SARS-COV-2 Omicron Variant Strain Infection in Guangzhou: A Real-World Matched Case-Control Study.

In April 2022, a COVID-19 outbreak caused by the Omicron variant emerged in Guangzhou. A case-control study was conducted to explore the relationship between vaccination intervals and SARS-CoV-2 infection in the real world. According to the vaccination dose and age information of the cases, a 1:4 matched case-control sample was established, finally including n = 242 for the case group and n = 968 for the control group. The results indicated that among the participants who received three vaccine doses, those with an interval of more than 300 days between the receipt of the first vaccine dose and infection (or the first contact with a confirmed case) were less likely to be infected with SARS-CoV-2 than those with an interval of less than 300 days (OR = 0.67, 95% CI = 0.46-0.99). After age-stratified analysis, among participants aged 18-40 years who received two doses of vaccine, those who received the second dose more than 30 days after the first dose were less likely to be infected with SARS-CoV-2 (OR = 0.53, 95% CI = 0.30-0.96). Our findings suggest that we need to extend the interval between the first dose and the second dose and further explore the optimal interval between the first and second and between the second and third doses in order to improve vaccine efficacy.

A unified global genotyping framework of dengue virus serotype-1 for a stratified coordinated surveillance strategy of dengue epidemics.

BACKGROUND: Dengue is the fastest spreading arboviral disease, posing great challenges on global public health. A reproduceable and comparable global genotyping framework for contextualizing spatiotemporal epidemiological data of dengue virus (DENV) is essential for research studies and collaborative surveillance. METHODS: Targeting DENV-1 spreading prominently in recent decades, by reconciling all qualified complete E gene sequences of 5003 DENV-1 strains with epidemiological information from 78 epidemic countries/areas ranging from 1944 to 2018, we established and characterized a unified global high-resolution genotyping framework using phylogenetics, population genetics, phylogeography, and phylodynamics. RESULTS: The defined framework was discriminated with three hierarchical layers of genotype, subgenotype and clade with respective mean pairwise distances 2-6%, 0.8-2%, and ≤ 0.8%. The global epidemic patterns of DENV-1 showed strong geographic constraints representing stratified spatial-genetic epidemic pairs of Continent-Genotype, Region-Subgenotype and Nation-Clade, thereby identifying 12 epidemic regions which prospectively facilitates the region-based coordination. The increasing cross-transmission trends were also demonstrated. The traditional endemic countries such as Thailand, Vietnam and Indonesia displayed as persisting dominant source centers, while the emerging epidemic countries such as China, Australia, and the USA, where dengue outbreaks were frequently triggered by importation, showed a growing trend of DENV-1 diffusion. The probably hidden epidemics were found especially in Africa and India. Then, our framework can be utilized in an accurate stratified coordinated surveillance based on the defined viral population compositions. Thereby it is prospectively valuable for further hampering the ongoing transition process of epidemic to endemic, addressing the issue of inadequate monitoring, and warning us to be concerned about the cross-national, cross-regional, and cross-continental diffusions of dengue, which can potentially trigger large epidemics. CONCLUSIONS: The framework and its utilization in quantitatively assessing DENV-1 epidemics has laid a foundation and re-unveiled the urgency for establishing a stratified coordinated surveillance platform for blocking global spreading of dengue. This framework is also expected to bridge classical DENV-1 genotyping with genomic epidemiology and risk modeling. We will promote it to the public and update it periodically.

Follow-up of patients with COVID-19 by the Delta variant after hospital discharge in Guangzhou, Guandong, China.

The B.1.617.2 (Delta) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has contributed to a new increment in cases across the globe. We conducted a prospective follow-up of COVID-19 cases to explore the recurrence and potential propagation risk of the Delta variant and discuss potential explanations for the infection recurrence. A prospective, non-interventional follow-up of discharged patients who had SARS-CoV-2 infections by the Delta variant in Guangdong, China, from May 2021 to June 2021 was conducted. The subjects were asked to complete a physical health examination and undergo nucleic acid testing and antibody detection for the laboratory diagnosis of COVID-19. In total, 20.33% (25/123) of patients exhibited recurrent positive results after discharge. All patients with infection recurrence were asymptomatic and showed no abnormalities in the pulmonary computed tomography. The time from discharge to the recurrent positive testing was usually between 1-33 days, with a mean time of 9.36 days. The cycle threshold from the real-time polymerase chain reaction assay that detected the recurrence of positivity ranged from 27.48 to 39.00, with an average of 35.30. The proportion of vaccination in the non-recurrent group was higher than that in the recurrently positive group (26% vs. 4%; χ2 = 7.902; P < 0.05). Two months after discharge, the most common symptom was hair loss and 59.6% of patients had no long-term symptoms at all. It is possible for the Delta variant SARS-CoV-2 patients after discharge to show recurrent positive results of nucleic acid detection; however, there is a low risk of continuous community transmission. Both, the physical and mental quality of life of discharged patients were significantly affected. Our results suggest that it makes sense to implement mass vaccination against the Delta variant of SARS-CoV-2.

Gut Microbiota and Metabolome Description of Antibiotic-Treated Neonates From Parturients With Intrauterine Infection.

Intrauterine infection is linked to adverse pregnancy outcomes in pregnant women. Neonates from parturients with intrauterine infection are usually treated with antibiotics, but their gut microbiota and metabolome are seldom studied. In this study, we collected fecal samples from antibiotic-treated neonates of parturients with intrauterine infection (intrauterine infection group), parturients with non-intrauterine infection (antibiotic group), and untreated neonates of healthy parturients (control group). 16S rRNA gene sequencing and untargeted metabolomics analyses were performed. Our results revealed that the α-diversity of intrauterine infection group differed from that of control group. There were significant differences in ß-diversity between intrauterine infection group and control group, between antibiotic group and the control group, but there was no difference between the intrauterine infection and antibiotic groups, implying that antibiotic use has an obvious effect on ß-diversity and that the effects of intrauterine infection on ß-diversity cannot be identified. Enterococcus was more abundant in intrauterine infection and antibiotic groups than in control group. Gut metabolite differences in intrauterine infection group and antibiotic group (only in negative ion mode) from control group were observed, but no difference between intrauterine infection group and antibiotic group was observed. N-formyl-L-methionine was the most discriminant metabolite between intrauterine infection group and control group. Primary and secondary bile acid biosynthesis, bile secretion, and cholesterol metabolism pathways were altered, and the abundances of bile acids and bile salts were altered in intrauterine infection group compared with control group. Alterations in cholesterol metabolism, arginine biosynthesis and bile secretion pathways were observed both in intrauterine infection and antibiotic groups, which might be caused by the use of antibiotics. In conclusion, we provided a preliminary description of the gut microbiota and gut metabolites in antibiotics-treated neonates from intrauterine infection parturients. Our findings did not show intrauterine infection has a separate role in neonatal gut microbiota dysbiosis, while supporting the idea that antibiotics should be used with caution during neonatal therapy.

Circulation of genotypes of dengue virus serotype 2 in Guangzhou over a period of 20 years.

BACKGROUND: The dengue epidemic in Guangzhou has imposed a rising burden on society and health infrastructure. Here, we present the genotype data for dengue virus serotype 2 (DENV-2) to improve understanding of this dengue epidemic. METHODS: We sequenced the envelope gene of DENV-2 obtained from patient serum samples and subsequently performed maximum-likelihood phylogenetic analysis using PhyMLv3.1, maximum clade credibility analysis using BEAST v.1.10.4, and selection pressure analysis using Datamonkey 2.0. RESULTS: The prevalent DENV-2 strains identified in Guangzhou region are related to those in Southeast Asian countries. In particular, the Malaysia/Indian subcontinent genotype is prevailing in Guangzhou with no apparent genotype shift having occurred over the past 20 years. However, episodic positive selection was detected at one site. CONCLUSIONS: Local control of the DENV-2 epidemic in Guangzhou requires effective measures to prevent and monitor imported cases. Moreover, the shift between the Malaysia/Indian subcontinent genotype lineages, which originated at different time points, may account for the rise in DENV-2 cases in Guangzhou. Meanwhile, the low rate of dengue haemorrhagic fever in Guangzhou may be explained by the dominance of the less virulent Malaysia/Indian subcontinent genotype.

A risk-prediction score for colorectal lesions on 12,628 participants at high risk of colorectal cancer.

BACKGROUND: The uptake of colonoscopy is low in individuals at risk of colorectal cancer (CRC). We constructed a risk-prediction score (RPS) in a large community-based sample at high risk of CRC to enable more accurate risk stratification and to motivate and increase the uptake rate of colonoscopy. METHODS: A total of 12,628 participants classified as high-risk according to positivity of immunochemical fecal occult blood tests or High-Risk Factor Questionnaire underwent colonoscopy. Logistic regression was used to derive a RPS and analysed the associations of the RPS with colorectal lesions, giving odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Of the participants, men (OR = 1.73, 95% CI = 1.58-1.90), older age (≥65 years; 1.41, 1.31-1.53), higher body mass index (≥28 kg/m2; 1.22, 1.07-1.39), ever smoking (1.47, 1.31-1.65), and weekly alcohol use (1.28, 1.09-1.52) were associated with a higher risk of colorectal lesions. We assigned 1 point to each of the above five risk factors and derived a RPS ranging from 0 to 5, with a higher score indicating a higher risk. Compared with a RPS of 0, a RPS of 1, 2, 3, and 4-5 showed a higher risk of colorectal lesions, with the OR (95% CI) being 1.50 (1.37-1.63), 2.34 (2.12-2.59), 3.58 (3.13-4.10), and 3.91 (3.00-5.10), respectively. The area under the receiver-operating characteristic curve of RPS in predicting colorectal lesions was 0.62. CONCLUSIONS: Participants with an increase in the RPS of ≥1 point had a significantly higher risk of colorectal lesions, suggesting the urgency for measuring colonoscopy in this very high-risk group. High-risk strategies incorporating RPS may be employed to achieve a higher colonoscopy-uptake rate.

Follow-up of patients with COVID-19 by the Delta variant after hospital discharge in Guangzhou, Guandong, China

ABSTRACT The B.1.617.2 (Delta) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has contributed to a new increment in cases across the globe. We conducted a prospective follow-up of COVID-19 cases to explore the recurrence and potential propagation risk of the Delta variant and discuss potential explanations for the infection recurrence. A prospective, non-interventional follow-up of discharged patients who had SARS-CoV-2 infections by the Delta variant in Guangdong, China, from May 2021 to June 2021 was conducted. The subjects were asked to complete a physical health examination and undergo nucleic acid testing and antibody detection for the laboratory diagnosis of COVID-19. In total, 20.33% (25/123) of patients exhibited recurrent positive results after discharge. All patients with infection recurrence were asymptomatic and showed no abnormalities in the pulmonary computed tomography. The time from discharge to the recurrent positive testing was usually between 1-33 days, with a mean time of 9.36 days. The cycle threshold from the real-time polymerase chain reaction assay that detected the recurrence of positivity ranged from 27.48 to 39.00, with an average of 35.30. The proportion of vaccination in the non-recurrent group was higher than that in the recurrently positive group (26% vs. 4%; χ2 = 7.902; P < 0.05). Two months after discharge, the most common symptom was hair loss and 59.6% of patients had no long-term symptoms at all. It is possible for the Delta variant SARS-CoV-2 patients after discharge to show recurrent positive results of nucleic acid detection; however, there is a low risk of continuous community transmission. Both, the physical and mental quality of life of discharged patients were significantly affected. Our results suggest that it makes sense to implement mass vaccination against the Delta variant of SARS-CoV-2.

Desulfovibrio is not always associated with adverse health effects in the Guangdong Gut Microbiome Project.

Desulfovibrio (DSV) is frequently found in the human intestine but limited knowledge is available regarding the relationship between DSV and host health. In this study, we analyzed large-scale cohort data from the Guangdong Gut Microbiome Project to study the ecology of DSV and the associations of DSV and host health parameters. Phylogenetic analysis showed that Desulfovibrio piger might be the most common and abundant DSV species in the GGMP. Predominant sub-OTUs of DSV were positively associated with bacterial community diversity. The relative abundance of DSV was positively correlated with beneficial genera, including Oscillospira, Coprococcus,Ruminococcus,Akkermansia, Roseburia,Faecalibacterium, andBacteroides, and was negatively associated with harmful genera, such as Clostridium,Escherichia,Klebsiella, and Ralstonia. Moreover, the relative abundance of DSV was negatively correlated with body mass index, waist size, triglyceride levels, and uric acid levels. This suggests that DSV is associated with healthy hosts in some human populations.

Effectiveness of inactivated SARS-CoV-2 vaccines against the Delta variant infection in Guangzhou: a test-negative case-control real-world study.

The effectiveness of inactivated SARS-CoV-2 vaccines against the Delta variant, which has been associated with greater transmissibility and virulence, remains unclear. We conducted a test-negative case-control study to explore the vaccine effectiveness (VE) in real-world settings. We recruited participants aged 18-59 years who consisted of SARS-CoV-2 test-positive cases (n = 74) and test-negative controls (n = 292) during the outbreak of the Delta variant in May 2021 in Guangzhou city, China. Vaccination status was compared to estimate The VE of SARS-CoV-2 inactivated vaccines. A single dose of inactivated SARS-CoV-2 vaccine yielded the VE of only 13.8%. After adjusting for age and sex, the overall VE for two-dose vaccination was 59.0% (95% confidence interval: 16.0% to 81.6%) against coronavirus disease 2019 (COVID-19) and 70.2% (95% confidence interval: 29.6-89.3%) against moderate COVID-19 and 100% against severe COVID-19 which might be overestimated due to the small sample size. The VE of two-dose vaccination against COVID-19 reached 72.5% among participants aged 40-59 years, and was higher in females than in males against COVID-19 and moderate diseases. While single dose vaccination was not sufficiently protective, the two-dose dosing scheme of the inactivated vaccines was effective against the Delta variant infection in real-world settings, with the estimated efficacy exceeding the World Health Organization minimal threshold of 50%.

New genotype invasion of dengue virus serotype 1 drove massive outbreak in Guangzhou, China.

BACKGROUND: Dengue fever is a mosquito-borne infectious disease that has caused major health problems. Variations in dengue virus (DENV) genes are important features of epidemic outbreaks. However, the associations of DENV genes with epidemic potential have not been extensively examined. Here, we assessed new genotype invasion of DENV-1 isolated from Guangzhou in China to evaluate associations with epidemic outbreaks. METHODOLOGY/PRINCIPAL FINDINGS: We used DENV-1 strains isolated from sera of dengue cases from 2002 to 2016 in Guangzhou for complete genome sequencing. A neighbor-joining phylogenetic tree was constructed to elucidate the genotype characteristics and determine if new genotype invasion was correlated with major outbreaks. In our study, a new genotype invasion event was observed during each significant outbreak period in 2002-2003, 2006-2007, and 2013-2014. Genotype II was the main epidemic genotype in 2003 and before. Invasion of genotype I in 2006 caused an unusual outbreak with 765 cases (relative risk [RR] = 16.24, 95% confidence interval [CI] 12.41-21.25). At the middle and late stages of the 2013 outbreak, genotype III was introduced to Guangzhou as a new genotype invasion responsible for 37,340 cases with RR 541.73 (95% CI 417.78-702.45), after which genotypes I and III began co-circulating. Base mutations occurred after new genotype invasion, and the gene sequence of NS3 protein had the lowest average similarity ratio (99.82%), followed by the gene sequence of E protein (99.86%), as compared to the 2013 strain. CONCLUSIONS/SIGNIFICANCE: Genotype replacement and co-circulation of multiple DENV-1 genotypes were observed. New genotype invasion was highly correlated with local unusual outbreaks. In addition to DENV-1 genotype I in the unprecedented outbreak in 2014, new genotype invasion by DENV-1 genotype III occurred in Guangzhou.

Sewage as a Possible Transmission Vehicle During a Coronavirus Disease 2019 Outbreak in a Densely Populated Community: Guangzhou, China, April 2020.

BACKGROUND: Sewage transmission of SARS-CoV-2 has never been demonstrated. During a COVID-19 outbreak in Guangzhou, China in April 2020, we investigated the mode of transmission. METHODS: We collected clinical and environmental samples from quarantined residents and their environment for RT-PCR testing and genome sequencing. A case was a resident with a positive RT-PCR test regardless of symptoms. We conducted a retrospective cohort study of all residents of cases' buildings to identify risk factors. RESULTS: We found 8 cases (onset: 5-21 April). During incubation period, cases 1 and 2 frequented market T where a COVID-19 outbreak was ongoing; cases 3-8 never visited market T, lived in separate buildings and never interacted with cases 1 and 2. Working as a janitor or wastepicker (RR = 13; 95% CIexact, 2.3-180), not changing to clean shoes (RR = 7.4; 95% CIexact, 1.8-34) and handling dirty shoes by hand (RR = 6.3; 95% CIexact, 1.4-30) after returning home were significant risk factors. RT-PCR detected SARS-CoV-2 in 19% of 63 samples from sewage puddles or pipes, and 24% of 50 environmental samples from cases' apartments. Viruses from the squat toilet and shoe-bottom dirt inside the apartment of cases 1 and 2 were homologous with those from cases 3-8 and the sewage. Sewage from the apartment of cases 1 and 2 leaked out of a cracked pipe onto streets. Rainfall after the onset of cases 1 and 2 flooded the streets. CONCLUSIONS: SARS-CoV-2 might spread by sewage, highlighting the importance of sewage management during outbreaks.

Retrospective study identifies infection related risk factors in close contacts during COVID-19 epidemic.

OBJECTIVES: This study aimed to compare the risk of infection of children with that of adults and to explore risk factors of infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by following up close contacts of COVID-19 patients. METHOD: The retrospective cohort study was performed among close contacts of index cases diagnosed with COVID-19 in Guangzhou, China. Demographic characteristics, clinical symptoms and exposure information were extracted. Logistic regression analysis was employed to explore the risk factors. The restricted cubic spline was conducted to examine to the dose-response relationship between age and SARS-CoV-2 infection. RESULTS: The secondary attack rate (SAR) was 4.4% in 1,344 close contacts. The group of household contacts (17.2%) had the highest SAR. The rare-frequency contact (p < 0.001) and moderate-frequency contact (p < 0.001) were associated with lower risk of infection. Exposure to index cases with dry cough symptoms was associated with infection in close contacts (p = 0.004). Compared with children, adults had a significantly increased risk of infection (p = 0.014). There is a linear positive correlation between age and infection (p = 0.001). CONCLUSIONS: Children are probably less susceptible to COVID-19. Close contacts with frequent contact with patients and those exposed to patients with cough symptoms are associated with an increased risk of infection.

Kinetics of IgG Antibodies in Previous Cases of Dengue Fever-A Longitudinal Serological Survey.

Guangzhou is believed to be the most important epicenter of dengue outbreaks in southern China. In this study, a longitudinal serological investigation of previous cases of dengue fever in Guangzhou was conducted to explore the persistence of IgG antibodies and related factors affecting the changes of antibody level. We recruited 70 dengue virus type 1 (DENV-1) primary infection cases at two years post infection for serological investigation and conducted a second follow-up in the 5th year of prognosis. An enzyme-linked immunosorbent assay (ELISA) for DENV IgG antibody was examined in all study subjects. Potential factors associated with the concentration of serum total IgG antibody were determined by the generalized estimation equation (GEE). No significant difference in serum total IgG antibody positive rate between two follow-ups was observed (χ2 = 3.066, p = 0.080). However, there was a significant difference in the concentration of serum total IgG antibody between the two follow-ups (Z = 7.154, p < 0.001). The GEE showed that the antibody level in the five-year prognosis was mainly affected by the antibody level in the two-year prognosis (OR: 1.007, 95%CI: 1.005-1.009). In conclusion, the serum IgG antibodies of previous dengue fever cases can persist for a long time.

Contact Settings and Risk for Transmission in 3410 Close Contacts of Patients With COVID-19 in Guangzhou, China : A Prospective Cohort Study.

BACKGROUND: Risk for transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to close contacts of infected persons has not been well estimated. OBJECTIVE: To evaluate the risk for transmission of SARS-CoV-2 to close contacts in different settings. DESIGN: Prospective cohort study. SETTING: Close contacts of persons infected with SARS-CoV-2 in Guangzhou, China. PARTICIPANTS: 3410 close contacts of 391 index cases were traced between 13 January and 6 March 2020. Data on the setting of the exposure, reverse transcriptase polymerase chain reaction testing, and clinical characteristics of index and secondary cases were collected. MEASUREMENT: Coronavirus disease 2019 (COVID-19) cases were confirmed by guidelines issued by China. Secondary attack rates in different settings were calculated. RESULTS: Among 3410 close contacts, 127 (3.7% [95% CI, 3.1% to 4.4%]) were secondarily infected. Of these 127 persons, 8 (6.3% [CI, 2.1% to 10.5%]) were asymptomatic. Of the 119 symptomatic cases, 20 (16.8%) were defined as mild, 87 (73.1%) as moderate, and 12 (10.1%) as severe or critical. Compared with the household setting (10.3%), the secondary attack rate was lower for exposures in health care settings (1.0%; odds ratio [OR], 0.09 [CI, 0.04 to 0.20]) and on public transportation (0.1%; OR, 0.01 [CI, 0.00 to 0.08]). The secondary attack rate increased with the severity of index cases, from 0.3% (CI, 0.0% to 1.0%) for asymptomatic to 3.3% (CI, 1.8% to 4.8%) for mild, 5.6% (CI, 4.4% to 6.8%) for moderate, and 6.2% (CI, 3.2% to 9.1%) for severe or critical cases. Index cases with expectoration were associated with higher risk for secondary infection (13.6% vs. 3.0% for index cases without expectoration; OR, 4.81 [CI, 3.35 to 6.93]). LIMITATION: There was potential recall bias regarding symptom onset among patients with COVID-19, and the symptoms and severity of index cases were not assessed at the time of exposure to contacts. CONCLUSION: Household contact was the main setting for transmission of SARS-CoV-2, and the risk for transmission of SARS-CoV-2 among close contacts increased with the severity of index cases. PRIMARY FUNDING SOURCE: Guangdong Province Higher Vocational Colleges and Schools Pearl River Scholar Funded Scheme.

Household Secondary Attack Rate of COVID-19 and Associated Determinants.

BACKGROUND: As of April 2, 2020, the global reported number of COVID-19 cases has crossed over 1 million with more than 55,000 deaths. The household transmissibility of SARS-CoV-2, the causative pathogen, remains elusive. METHODS: Based on a comprehensive contact-tracing dataset from Guangzhou, we estimated both the population-level effective reproductive number and individual-level secondary attack rate (SAR) in the household setting. We assessed age effects on transmissibility and the infectivity of COVID-19 cases during their incubation period. RESULTS: A total of 195 unrelated clusters with 212 primary cases, 137 nonprimary (secondary or tertiary) cases and 1938 uninfected close contacts were traced. We estimated the household SAR to be 13.8% (95% CI: 11.1-17.0%) if household contacts are defined as all close relatives and 19.3% (95% CI: 15.5-23.9%) if household contacts only include those at the same residential address as the cases, assuming a mean incubation period of 4 days and a maximum infectious period of 13 days. The odds of infection among children (<20 years old) was only 0.26 (95% CI: 0.13-0.54) times of that among the elderly (≥60 years old). There was no gender difference in the risk of infection. COVID-19 cases were at least as infectious during their incubation period as during their illness. On average, a COVID-19 case infected 0.48 (95% CI: 0.39-0.58) close contacts. Had isolation not been implemented, this number increases to 0.62 (95% CI: 0.51-0.75). The effective reproductive number in Guangzhou dropped from above 1 to below 0.5 in about 1 week. CONCLUSION: SARS-CoV-2 is more transmissible in households than SARS-CoV and MERS-CoV, and the elderly ≥60 years old are the most vulnerable to household transmission. Case finding and isolation alone may be inadequate to contain the pandemic and need to be used in conjunction with heightened restriction of human movement as implemented in Guangzhou.

Household secondary attack rate of COVID-19 and associated determinants in Guangzhou, China: a retrospective cohort study.

BACKGROUND: As of June 8, 2020, the global reported number of COVID-19 cases had reached more than 7 million with over 400 000 deaths. The household transmissibility of the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains unclear. We aimed to estimate the secondary attack rate of SARS-CoV-2 among household and non-household close contacts in Guangzhou, China, using a statistical transmission model. METHODS: In this retrospective cohort study, we used a comprehensive contact tracing dataset from the Guangzhou Center for Disease Control and Prevention to estimate the secondary attack rate of COVID-19 (defined as the probability that an infected individual will transmit the disease to a susceptible individual) among household and non-household contacts, using a statistical transmission model. We considered two alternative definitions of household contacts in the analysis: individuals who were either family members or close relatives, such as parents and parents-in-law, regardless of residential address, and individuals living at the same address regardless of relationship. We assessed the demographic determinants of transmissibility and the infectivity of COVID-19 cases during their incubation period. FINDINGS: Between Jan 7, 2020, and Feb 18, 2020, we traced 195 unrelated close contact groups (215 primary cases, 134 secondary or tertiary cases, and 1964 uninfected close contacts). By identifying households from these groups, assuming a mean incubation period of 5 days, a maximum infectious period of 13 days, and no case isolation, the estimated secondary attack rate among household contacts was 12·4% (95% CI 9·8-15·4) when household contacts were defined on the basis of close relatives and 17·1% (13·3-21·8) when household contacts were defined on the basis of residential address. Compared with the oldest age group (≥60 years), the risk of household infection was lower in the youngest age group (<20 years; odds ratio [OR] 0·23 [95% CI 0·11-0·46]) and among adults aged 20-59 years (OR 0·64 [95% CI 0·43-0·97]). Our results suggest greater infectivity during the incubation period than during the symptomatic period, although differences were not statistically significant (OR 0·61 [95% CI 0·27-1·38]). The estimated local reproductive number (R) based on observed contact frequencies of primary cases was 0·5 (95% CI 0·41-0·62) in Guangzhou. The projected local R, had there been no isolation of cases or quarantine of their contacts, was 0·6 (95% CI 0·49-0·74) when household was defined on the basis of close relatives. INTERPRETATION: SARS-CoV-2 is more transmissible in households than SARS-CoV and Middle East respiratory syndrome coronavirus. Older individuals (aged ≥60 years) are the most susceptible to household transmission of SARS-CoV-2. In addition to case finding and isolation, timely tracing and quarantine of close contacts should be implemented to prevent onward transmission during the viral incubation period. FUNDING: US National Institutes of Health, Science and Technology Plan Project of Guangzhou, Project for Key Medicine Discipline Construction of Guangzhou Municipality, Key Research and Development Program of China.