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Background SARS-CoV-2 has been identified in the fecal matter of COVID-19 patients. However, sewage transmission has never been shown. In April 2020, a COVID-19 outbreak occurred in a densely populated community in Guangzhou, China. We investigated this outbreak to identify the mode of transmission. Method A home quarantined order was issued in the community. We collected throat swab samples from the residents and environmental samples from the surfaces inside and around the houses, and conducted RT-PCR testing and genome sequencing. We defined a case as a resident in this community with a positive RT-PCR test, with or without symptoms. We conducted a retrospective cohort study of all residents living in the same buildings as the cases to identify exposure risk factors. Result We found eight cases (four couples) in this community of 2888 residents (attack rate=2.8/1000), with onset during April 5–21, 2020. During their incubation periods, Cases 1-2 frequented market T with an ongoing outbreak. Cases 3-8 never visited market T during incubation period, lived in separate buildings from, and never interacted with, Cases 1-2. Retrospective cohort study showed that working as cleaners or waste picker (RR=13, 95% CIexact: 2.3-180), not changing to clean shoes after returning home (RR=7.4, 95% CIexact: 1.8-34), collating and cleaning dirty shoes after returning home (RR=6.3, 95% CIexact: 1.4-30) were significant exposure risk factors. Of 63 samples collected from street-sewage puddles and sewage-pipe surfaces, 19% tested positive for SARS-CoV-2. Of 50 environmental samples taken from cases’ apartments, 24% tested positive. Viral genome sequencing showed that the viruses identified from the squat toilet and shoe-bottom dirt inside the apartment of Cases 1-2 were homologous with those from Cases 3-8 and those identified from sewage samples. The sewage pipe leading from the apartment of Cases 1-2 to the drainage had a large hole above ground. Rainfalls after the onset of Cases 1-2 flooded the streets. Conclusion Our investigation has for the first time pointed to the possibility that SARS-CoV-2 might spread by sewage. This finding highlighted the importance of sewage management, especially in densely-populated places with poor hygiene and sanitation measures, such as urban slums and other low-income communities in developing countries.

Some patients retested positive for SARS-CoV-2 following negative testing results and discharge. However, the potential risk factors associated with redetectable positive test results in a large sample of patients who recovered from COVID-19 have not been well estimated. A total of 745 discharged COVID-19 patients were enrolled between January 30, 2020, and September 9, 2020, in Guangzhou, China. Data on the clinical characteristics, comorbidities, drug therapy, RT-PCR testing, and contact modes to close contacts were collected. Patients who tested positive for SARS-CoV-2 after discharge (positive retest patients) were confirmed by guidelines issued by China. The repositive rate in different settings was calculated. Among 745 discharged patients, 157 (21.1%; 95% CI, 18.2% to 24.0%) retested positive, of which 55 (35.0%) were asymptomatic, 15 (9.6%) had mild symptoms, 83 (52.9%) had moderate symptoms and 4 (2.6%) had severe symptoms at the first admission. The median time from discharge to repositivity was 8.0 days (IQR, 8.0 to 14.0 days). Most positive retest patients were without clinical symptoms, and lymphocyte cell counts were higher than before being discharged. The likelihood of repositive testing for SARS-CoV-2 RNA was significantly higher among patients who were younger age (OR, 3.88; 95% CI, 1.74 to 8.66, 0 to 17 years old), had asymptomatic severity (OR, 4.36; 95% CI, 1.47 to 12.95) and did not have clinical symptoms (OR, 1.89; 95% CI, 1.32 to 2.70, without fever). We found that the positive retest rate of COVID-19 was relatively high, and these patients tested positive again with a median of 8.0 to 14.0 days after discharge. Positive retest results were mainly observed in young patients without severe clinical symptoms. These findings suggest that a significant proportion of patients could carry viral fragments for a long time, and effective management, such as a prolonged quarantine phase for discharged patients, is necessary.

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 (&chi, 2 = 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 &lt, 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&ndash, 1.009). In conclusion, the serum IgG antibodies of previous dengue fever cases can persist for a long time.

Hand, foot and mouth disease (HFMD) primarily affects children younger than 5 years of age. Recently, HFMD has ranked as the top notifiable infectious disease in China. In December 2015, China approved two novel inactivated enterovirus 71 vaccines (EV71 vaccines) for HFMD. Parents’ acceptance is often essential for vaccination program success. The goal of this study was to identify willingness and influential factors to vaccinate among parents of kindergarteners in Guangzhou, China. A cross-sectional survey of face-to-face interviews was conducted from March to July 2016. Fifty-five kindergartens were randomly selected from 11 districts of Guangzhou. An anonymous self-designed questionnaire was used to investigate awareness, knowledge and attitude towards HFMD and EV71 vaccines. A total of 868 parents participated in the survey. Mean(±standard deviation) knowledge score of HFMD was 6.32(±1.70). Approximately 32.03% of parents had heard of the EV71 vaccines with 22.58% receiving information before this study. Nearly 44.24% of parents showed willingness to vaccinate their children. Previously receiving EV71 vaccine-related information [adjusted odds ratio (aOR) = 1.48, 95% confidence interval (CI): 1.04–2.11], no fear of adverse effects (aOR = 4.25, 95%CI: 2.77–6.53), perceived susceptibility of children to HFMD (aOR = 2.15, 95%CI: 1.42–3.25) and children not previously diagnosed with HFMD (aOR = 1.56, 95%CI: 1.07–2.27) were positively associated with EV71 vaccination acceptability. However, parental education background (aOR = 0.54, 95%CI: 0.37–0.80) was negatively correlated with vaccination acceptability. Our study provides baseline information for future vaccination campaigns to help improve the EV71 vaccine uptake rate. Special efforts are urgently needed to improve the awareness and knowledge of EV71 vaccines in China.

The severe acute respiratory syndrome coronavirus 2 has caused a worldwide pandemic. Control measures differ among countries and have a varying degree of effectiveness, which requires assessment. To evaluate the effectiveness of public health interventions of the coronavirus disease 2019 (COVID-19) in Guangzhou by 3 periods according to interventions: January 7 to 22 (no intervention), January 23 to February 23 (implemented intensive interventions), and February 24 to May 17 (the normalization mode of COVID-19 prevention and control).We collected the information of 745 COVID-19 patients and their close contacts as well as control measures in Guangzhou from January 7 to May 17, 2020. We estimated the epidemiological characteristics, disease spectrum of COVID-19 cases, key time-to-event intervals, and effective reproduction number over the 3 periods. The basic reproduction number of severe acute respiratory syndrome coronavirus 2 was also calculated over period 1.Approximately 45.8%, 49.8%, and 4.4% of cases from close contacts were asymptomatic, symptomatic, and severe, respectively. The median incubation period was 5.3 days (the percentiles of 2.5-97.5, 1.5-18.4 days) and the median serial interval fitted with gamma distribution was 5.1 days (the percentiles of 2.5-97.5, 0.8-15.9 days). The estimated median of onset-to-quarantined time in Period 1 to 3 were 7.5, 3.4, and 2.9 days (the percentiles of 2.5-97.5, 2.1-14.2, 3.9-14.7, and 6.0-20.0 days) respectively and the median of onset-to-confirmation time in period 1 to 3 were 8.9, 4.9 and 2.4 days (the percentiles of 2.5-97.5, 2.6-16.6, 0.9-14.6, and 0.5-11.8 days). In period 1, the reproduction number was 0.9 (95% confidence interval, 0.5-1.4) and fluctuated below 1.0 before January 22 except for January 14. The effective reproduction number gradually decreased in the period 2 with the lowest point of 0.1 on February 20, then increased again since March 27 and reach a spike of 1.8 on April 12. The number decreased to below 1.0 after April 17 and decreased further to0.2 after May 7 in the period 3.Under prospective dynamic observation, close contacts turned into infected cases could provide a spectrum of COVID-19 cases from real-world settings. The lockdown of Wuhan and closed-loop management of people arriving Guangzhou were effective in halting the spread of the COVID-19 cases to Guangzhou. The spread of COVID-19 was successfully controlled in Guangzhou by social distancing, wearing a face mask, handwashing, disinfection in key places, mass testing, extensive contact tracing, and strict quarantine of close contacts.

Background: Some cases retested positive for SARS-CoV-2 following negative testing results and discharge, which attracted widespread concern. However, the potential risk factors associated with re-detectable positive tests in a large sample of cases who recovered from COVID-19 has not been well estimated. Methods: A total of 745 discharged COVID-19 cases were enrolled between 30 January and 9 September 2020 in Guangzhou, China. Data on the clinical characteristics, comorbidities, drug therapy, RT-PCR testing, and contact modes to close contacts were collected. Re-positive cases were confirmed by guidelines issued by China. The re-positive rate of in different settings was calculated. Univariable and multivariable logistic regression models were used to explore the potential risk factors associated with COVID-19 re-positivity. Findings: Among 745 discharged cases, 157 (21.1%; 95%CI, 18.2% to 24.0%) were retested positive with 55 (35.0%) of asymptomatic, 15 (9.6%) of mild, 83 (52.9%) of moderate and 4 (2.6%) of severe at the first admission. The median time from discharge to re-positivity was 8.0 days (IQR, 8.0 to 14.0 days). Most re-positive cases were without clinical symptoms and lymphocyte cell counts increased than before. The likelihood of re-positive testing for SARS-CoV-2 RNA was significantly higher among cases with younger age (OR, 3.88; 95%CI, 1.74 to 8.66, 0 to 17 years old), asymptomatic severity (OR, 4.36; 95%CI, 1.47 to 12.95) and without clinical symptoms (OR, 1.89; 95%CI, 1.32 to 2.70, without fever). Interpretation: We found that the re-positive rate of COVID-19 was relatively high, and they were re-tested positive with median days 8.0 to 14.0 post-discharge. Re-positive results were mainly observed in young cases without severe clinical symptoms. These findings suggest that a significant proportion of cases could carry virus fragments for a long time, and effective management, such as prolonged quarantine phase of discharged cases, is necessary. Funding Statement: The Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme; the Construction of High-level University of Guangdong; Young Elite Scientists Sponsorship Program by CAST; the National Natural Science Foundation of China; the Zhejiang University special scientific research fund for COVID-19 prevention and control. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: This study was reviewed and approved by the Ethics Committee of GZCDC. As required by the National Health Commission of China, CDCs were responsible for the work for an ongoing public health response to COVID-19, and our cohort study was based on the data by GZCDC. Patients were informed about the surveillance before providing written consent, and data were collected and anonymized for analysis. All analysis of personally identifiable data took place onsite at the GZCDC.

Background: SARS-CoV-2 has been identified in the feces of COVID-19 patients. However, fecal transmission has never been shown epidemiologically. In April 2020, a COVID-19 outbreak occurred in a low-income community in Guangzhou, China. We investigated this outbreak to identify the mode of transmission. Methods: A home quarantined order was issued in the community. We collected throat swab samples from the residents and environmental samples from the surfaces inside and around the houses, and conducted RT-PCR testing and genome sequencing. We defined a case as a resident in this community with a positive RT-PCR test. We conducted a retrospective cohort study among the residents living in the same building as the cases to identify transmission risk factors. Findings: We found eight cases (four couples) in this community of 2888 residents (attack rate=2.8/1000), with onset from April 5 to 21, 2020. During their incubation periods, Cases 1 and 2 frequented a Market T, where an outbreak was ongoing. Cases 3-8 never visited Market T during incubation periods, lived in separate buildings from, and never interacted with, Cases 1 and 2. Retrospective cohort study showed that working as cleaners or street scavengers (RR=13, 95% CI: 1.8-99), not changing to clean shoes after returning home (RR=7.4, 95% CI: 1.7-33), collating and cleaning dirty shoes after returning home (RR=6.3, 95% CI: 1.4-28) were significant exposure risk factors. Of 63 samples collected from street sewage puddles and sewage pipes, 19% tested positive for SARS-CoV-2. Of 50 samples taken from the cases’ apartments, 24% tested positive. RNA sequencing showed that the viruses identified from the squat toilet and the shoe-bottom dirt from the apartments of Cases 1 and 2 are homologous with those from Cases 3-8 and those identified from the sewage samples. The sewage pipe leading from the apartment of Cases 1 and 2 down to the drainage had a large crack above the ground. Rainfalls after the onset of Cases 1 and 2 flooded the streets. Interpretation: Our investigation has for the first time provided epidemiologic evidence that SARS-CoV-2 can be spread by sewage. This finding highlighted the importance of sewage management, especially in densely-populated places with poor hygiene and sanitation measures, such as urban slums and other low-income communities in developing countries. Funding: No. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was approved by the ethics committees of GZCDC (approval number GZCDC-ECHR-2020A0004).

The incidence of dengue is increasing in Guangdong, China, with the largest outbreak to date in 2014. Widespread awareness of epidemiological and molecular characteristics of the dengue virus (DENV) is required. In 2014, we isolated the virus from patients and sequenced its genome. The sequences of DENV isolated from Guangdong and other countries screened since 2005 were studied to establish molecular evolutionary databases along with epidemiological data to explore its epidemiological, phylogenetic, and molecular characteristics. Causes underlying the occurrence of the dengue epidemic included importation and localization of the virus. The number of indigenous cases significantly exceeded that of imported cases. Dengue virus 1 is the most important serotype and caused the long-term epidemic locally. Based on the data available since 2005, DENV1 was divided into three genotypes (I, IV, and V). Only genotypes I and V were detected in 2014. In 2014, an epidemic involving old lineages of DENV1 genotype V occurred after 2 years of silence. The genotype was previously detected from 2009 to 2011. Genotype I, which caused recent epidemics, demonstrated a continuation of new lineages, and a predictive pattern of molecular evolution since 2005 among the four lineages was present. The DENV isolated from Guangdong was closely related to those causing large-scale epidemics in neighboring countries, suggesting the possibility of its import from these countries. The lack of sufficient epidemiological data and evidence on the local mosquito-borne DENV emphasizes the importance of studying the molecular evolutionary features and establishing a well-established phylogenetic tree for dengue prevention and control in Guangdong.

Objective Dengue has become a serious public health problem in southern China particularly with a record-breaking outbreak in 2014. Serological evidence from areas with no known dengue cases reported prior to 2014 could provide information on possible unrecognized circulation of dengue virus (DENV) before this outbreak. Method Between March and May 2015, we performed a cross-sectional serosurvey using a stratified random sampling method among individuals aged 1–84 years-old in 7 communities in Guangzhou with no reported dengue cases before 2014. Sera of subjects were initially screened with the indirect DENV IgG enzyme-linked immunosorbent assay, and positive samples were further tested by the indirect immunofluorescence assay to identify specific serotypes. Results A total of 850 subjects had complete information available. The overall seroprevalence against DENV was 6.59% (56 of 850; 95% CI, 4.92%–8.26%). The seroprevalence increased with age in general (3.86%, 4.58%, 8.72%, 7.22%, and 10.69% among participants in ≤14, 15–29, 30–44, 45–59 and ≥60 years age group, respectively). Living in rural or peri-urban communities and longer years of residence therein were risk factors for higher seroprevalence, whereas wearing long sleeves and pants when outdoors was associated with lower seroprevalence. Of the total subjects, 55.36% (31 of 56) sera were successfully identified with specific serotypes, with 12.90% (4 of 31) being coinfected with 2 serotypes. Conclusions Dengue transmission in the study communities had occurred prior to the 2014 massive outbreak, possibly for many years, but went undiagnosed and unreported. A proportion of the study population experienced secondary infection as different serotypes of DENV increased the risk for severe diseases. Active surveillance and education of both healthcare providers and the general population should be conducted in areas at risk for dengue emergence in order to better reduce disease burden., The 2015 cross-sectional, stratified random sampling serosurvey in areas with no reported cases before the large outbreak in 2014 in Guangzhou indicated dengue transmission occurred prior to the 2014 for many years, but went undiagnosed and unreported.

Objective To explore the relationship between meteorological factors and scarlet fever incidence from 2006 to 2017 in Guangzhou, the largest subtropical city of Southern China, and assist public health prevention and control measures. Methods Data for weekly scarlet fever incidence and meteorological variables from 2006 to 2017 in Guangzhou were collected from the National Notifiable Disease Report System (NNDRS) and the Guangzhou Meteorological Bureau (GZMB). Distributed lag nonlinear models (DLNMs) were conducted to estimate the effect of meteorological factors on weekly scarlet fever incidence in Guangzhou. Results We observed nonlinear effects of temperature, relative humidity, and wind velocity. The risk was the highest when the weekly mean temperature was 31 °C during lag week 14, yielding a relative risk (RR) of 1.48 (95% CI: 1.01–2.17). When relative humidity was 43.5% during lag week 0, the RR was 1.49 (95% CI: 1.04–2.12); the highest RR (1.55, 95% CI: 1.20–1.99) was reached when relative humidity was 93.5% during lag week 20. When wind velocity was 4.4 m/s during lag week 13, the RR was highest at 3.41 (95% CI: 1.57–7.44). Positive correlations were observed among weekly temperature ranges and atmospheric pressure with scarlet fever incidence, while a negative correlation was detected with aggregate rainfall. The cumulative extreme effect of meteorological variables on scarlet fever incidence was statistically significant, except for the high effect of wind velocity. Conclusion Weekly mean temperature, relative humidity, and wind velocity had double-trough effects on scarlet fever incidence; high weekly temperature range, high atmospheric pressure, and low aggregate rainfall were risk factors for scarlet fever morbidity. Our findings provided preliminary, but fundamental, information that may be useful for a better understanding of epidemic trends of scarlet fever and for developing an early warning system. Laboratory surveillance for scarlet fever should be strengthened in the future.

• We reported the case of the first patient worldwide to survive an infection with influenza A (H5N6) virus.

Background Guangzhou reported its first laboratory-confirmed case of influenza A (H7N9) on January 10, 2014. A total of 25 cases were reported from the first wave of the epidemic until April 8, 2014. The fatality rate was much higher than in previous reports. The objective of the current work was to describe the clinical and epidemiological characteristics of A (H7N9) patients in Guangzhou and explore possible reasons for the high fatality rate. Methods Clinical and epidemiological information regarding A (H7N9) cases in Guangzhou was collected through review of medical records and field research. Data regarding clinical and laboratory features, treatment, and outcomes were extracted. Results Of the 25 patients, 84 % (21/25) had one or more underlying diseases. Fifteen patients (60.0 %) developed moderate to severe acute respiratory distress syndrome (ARDS), and 14 (56 %) died of the ARDS or multiorgan failure. Patients with longer delay between onset of illness and initiation of oseltamivir treatment were more likely to develop ARDS. Elevated C-creative protein, aspartate aminotransferase, creatine kinase, and lymphocytopenia predicted a higher risk of developing ARDS. Conclusions The presence of underlying diseases and clinical complications predicted poor clinical outcome. Early oseltamivir treatment was associated with a reduced risk of developing ARDS.

To analyze the results of nine-round environmental specimen surveillance programs in five live poultry markets pre-, during and post the 'closing days' and to evaluate the effects of 'closing days' on live poultry markets regarding the control against avian influenza pollution.In January 2014, control measures including culling poultry, completely cleaning and disinfecting and a 'three-day-closing' measure were conducted in five live poultry markets which were found positive for H7N9 nucleic acid in the 1(st) round environmental specimen surveillance program. Second surveillance program was conducted after a thorough disinfection campaign was launched. Several times surveillance were conducted in one week, after the markets were reopened. RT-PCR was used to test the nucleic acid of HA, H5, H7 and H9 viruses.654 specimens from the environment were collected and tested. During the first round surveillance program, positive rates for influenza A and H5/H7/H9 nucleic acid of poultry stalls appeared to be 94.44% and 61.11% respectively. The positive rates of poultry stalls reduced to 0 after the disinfection campaign but increased again after the markets reopened. The positive rate for influenza A of poultry stalls slightly increased from 50.00% in the third surveillance to 72.22% in the ninth surveillance (P0.05). The positive rate for H5/H7/H9 of poultry stalls showed a significantly increasing trend, from 0 in the third surveillance to 44.44% in the ninth surveillance (P0.01). The positive rates for influenza A and H5/H7/H9 nucleic acid of specimens were 28.89% and 17.78% respectively. The positive rate of specimens reduced to 0 after disinfection while increased again after reopening of the markets. The positive rate for influenza A of specimens slightly increased from 19.67% in the third surveillance to 27.54% in the ninth surveillance programs (P0.05). The positive rate for H5/H7/H9 of specimen showed a significant increasing trend, from 0 in the third surveillance to 8.70% in the ninth-round surveillance programs (P0.01). The positive rate for influenza A was the highest for slaughter- related specimens of 22.4% (35/156). The positive rates for influenza A from sewage and drinking water being collected on the later stage after the markets reopened (25.9%, 12.4%)were higher than those on the early stage (8.3%, 8.6%) (P0.05). The positive rate for influenza A of poultry stalls with overnight poultry storage (91.7%) was significant higher than that of poultry stalls without the overnight storage (33.3%). The positive rate for influenza A of poultry stalls in which simultaneously selling different kinds of poultry (85.7%) was significant higher than that of poultry stalls in which selling only one kind of poultry at one time (25.0%) (P0.05).Slaughter in live poultry markets posed a large risk of pollution diffusion. Sewage and drinking water showed an accumulation effect for avian influenza virus. Overnight poultry storage and selling different kinds of poultry at one time at the poultry stalls seemed the risk factors for avian influenza virus transmission. Complete cleaning, disinfecting and several 'closing days' for live poultry markets seemed effective in eliminating avian influenza virus. Once the markets were reopened, they seemed to be soon polluted again.