Viral infection and Transmission in a large well-traced outbreak caused by the Delta SARS-CoV-2 variant

We report the first local transmission of the SARS-CoV-2 Delta variant in mainland China. All 167 infections could be traced back to the first index case. Daily sequential PCR testing of the quarantined subjects indicated that the viral loads of Delta infections, when they first become PCR+, were on average [~]1000 times greater compared to A/B lineage infections during initial epidemic wave in China in early 2020, suggesting potentially faster viral replication and greater infectiousness of Delta during early infection. We performed high-quality sequencing on samples from 126 individuals. Reliable epidemiological data meant that, for 111 transmission events, the donor and recipient cases were known. The estimated transmission bottleneck size was 1-3 virions with most minor intra-host single nucleotide variants (iSNVs) failing to transmit to the recipients. However, transmission heterogeneity of SARS-CoV-2 was also observed. The transmission of minor iSNVs resulted in at least 4 of the 30 substitutions identified in the outbreak, highlighting the contribution of intra-host variants to population level viral diversity during rapid spread. Disease control activities, such as the frequency of population testing, quarantine during pre-symptomatic infection, and level of virus genomic surveillance should be adjusted in order to account for the increasing prevalence of the Delta variant worldwide.

Human-to-human transmission of 2019-novel coronavirus (2019-nCoV)

BackgroundOn December 31, 2019, an outbreak of COVID-19 in humans was reported in Wuhan, and then spread fast to other provinces, China. We analyzed data from field investigations and genetic sequencing to describe the evidence and characteristics of human-to-human transmission in Guangdong Province. MethodsA confirmed COVID-19 case was defined if a suspected case was verified with positive of SARS-CoV-2 in throat swabs, nasal swabs, bronchoalveolar lavage fluid (BALF), or endotracheal aspirates by real-time reverse transcriptase polymerase chain reaction assay (RT-PCR) or genetic sequencing. Field investigations were conducted for each confirmed case. Clinical and demographic data of confirmed cases were collected from medical records. Exposure and travel history were obtained by interview. ResultsA total of 1,151 confirmed cases were identified as of February 10, 2020 in Guangdong Province, China. Of them, 697 (60.1%) cases were from 234 cluster infections. Two hundred and fourteen (18.6%) were secondary cases, in which 144 cases were from family cluster infections. With the epidemic continuing, although familial cluster events were dominated, community cluster events increased with a nosocomial event. The whole genomes within the same family cluster infections were identical, and presented a few unique single nucleotide variants (SNVs) compared with SARS-CoV-2 identified on December 2019 in Wuhan. ConclusionsWe observed evident human-to-human transmissions of SARS-CoV-2 in Guangdong, China. Although most of them were from family cluster infections, community and nosocomial infections were increasing. Our findings indicate that human-to-human transmission risks are transferring from family to community in Guangdong Province.

Transmission dynamics of 2019 novel coronavirus (2019-nCoV)

RationaleSeveral studies have estimated basic production number of novel coronavirus pneumonia (NCP). However, the time-varying transmission dynamics of NCP during the outbreak remain unclear. ObjectivesWe aimed to estimate the basic and time-varying transmission dynamics of NCP across China, and compared them with SARS. MethodsData on NCP cases by February 7, 2020 were collected from epidemiological investigations or official websites. Data on severe acute respiratory syndrome (SARS) cases in Guangdong Province, Beijing and Hong Kong during 2002-2003 were also obtained. We estimated the doubling time, basic reproduction number (R0) and time-varying reproduction number (Rt) of NCP and SARS. Measurements and main resultsAs of February 7, 2020, 34,598 NCP cases were identified in China, and daily confirmed cases decreased after February 4. The doubling time of NCP nationwide was 2.4 days which was shorter than that of SARS in Guangdong (14.3 days), Hong Kong (5.7 days) and Beijing (12.4 days). The R0 of NCP cases nationwide and in Wuhan were 4.5 and 4.4 respectively, which were higher than R0 of SARS in Guangdong (R0=2.3), Hongkong (R0=2.3), and Beijing (R0=2.6). The Rt for NCP continuously decreased especially after January 16 nationwide and in Wuhan. The R0 for secondary NCP cases in Guangdong was 0.6, and the Rt values were less than 1 during the epidemic. ConclusionsNCP may have a higher transmissibility than SARS, and the efforts of containing the outbreak are effective. However, the efforts are needed to persist in for reducing time-varying reproduction number below one. At a Glance CommentaryO_ST_ABSScientific Knowledge on the SubjectC_ST_ABSSince December 29, 2019, pneumonia infection with 2019-nCoV, now named as Novel Coronavirus Pneumonia (NCP), occurred in Wuhan, Hubei Province, China. The disease has rapidly spread from Wuhan to other areas. As a novel virus, the time-varying transmission dynamics of NCP remain unclear, and it is also important to compare it with SARS. What This Study Adds to the FieldWe compared the transmission dynamics of NCP with SARS, and found that NCP has a higher transmissibility than SARS. Time-varying production number indicates that rigorous control measures taken by governments are effective across China, and persistent efforts are needed to be taken for reducing instantaneous reproduction number below one.

Risk assessment and early warning of imported COVID-19 in 21 cities, Guangdong province / 中华流行病学杂志

Objective To assess the imported risk of COVID-19 in Guangdong province and its cities, and conduct early warning. Methods Data of reported COVID-19 cases and Baidu Migration Index of 21 cities in Guangdong province and other provinces of China as of February 25, 2020 were collected. The imported risk index of each city in Guangdong province were calculated, and then correlation analysis was performed between reported cases and the imported risk index to identify lag time. Finally, we classified the early warming levels of epidemic by imported risk index. Results A total of 1 347 confirmed cases were reported in Guangdong province, and 90.0% of the cases were clustered in the Pearl River Delta region. The average daily imported risk index of Guangdong was 44.03. Among the imported risk sources of each city, the highest risk of almost all cities came from Hubei province, except for Zhanjiang from Hainan province. In addition, the neighboring provinces of Guangdong province also had a greater impact. The correlation between the imported risk index with a lag of 4 days and the daily reported cases was the strongest (correlation coefficient: 0.73). The early warning base on cumulative 4-day risk of each city showed that Dongguan, Shenzhen, Zhongshan, Guangzhou, Foshan and Huizhou have high imported risks in the next 4 days, with imported risk indexes of 38.85, 21.59, 11.67, 11.25, 6.19 and 5.92, and the highest risk still comes from Hubei province. Conclusions Cities with a large number of migrants in Guangdong province have a higher risk of import. Hubei province and neighboring provinces in Guangdong province are the main source of the imported risk. Each city must strengthen the health management of migrants in high-risk provinces and reduce the imported risk of Guangdong province.

Clinical outcomes of COVID-19 cases and influencing factors in Guangdong province / 中华流行病学杂志

Objective To analyze the clinical courses and outcomes of COVID-19 cases and the influencing factors in Guangdong province and provide basis for the formulation or adjustment of medical care and epidemic control strategy for COVID-19. Methods We collected demographic data, medical histories, clinical courses and outcomes of 1 350 COVID-19 patients reported in Guangdong as of 4 March 2020 via epidemiological investigation and process tracking. Disease severity and clinical course characteristics of the patients and influencing factors of severe illness were analyzed in our study. Results Among 1 350 cases of COVID-19 cases in Guangdong, 72 (5.3%) and 1049 (77.7%) were mild and ordinary cases, 164 (12.1%) were severe cases, 58 (4.3%) were critical cases and 7 (0.5%) were fatal. The median duration of illness were 23 days ( P 25 - P 75 : 18-31 days) and the median length of hospitalization were 20 days ( P 25 - P 75 : 15-27 days). For severe cases, the median time of showing severe manifestations was on the 12th day after onset ( P 25 - P 75 : 9th to 15th days), and the median time of severe manifestation lasted for 8 days P 25 - P 75 : 4-14 days). Among 1 066 discharged/fetal cases, 36.4% (36/99) and 1.0% (1/99) of the mild cases developed to ordinary cases and severe cases respectively after admission; and 5.2% (50/968) and 0.6% (6/968) of the ordinary cases developed to severe cases, and critical cases respectively after admission. In severe cases, 11.4% developed to critical cases (10/88). The influencing factors for severe illness or worse included male (a HR =1.87, 95% CI : 1.43-2.46), older age (a HR =1.67, 95% CI : 1.51-1.85), seeking medical care on day 2-3 after onset (a HR =1.73, 95% CI : 1.20-2.50) pre-existing diabetes (a HR =1.75, 95% CI : 1.12-2.73) and hypertension (a HR =1.49, 95% CI : 1.06-2.09). Conclusions The course of illness and length of hospitalization of COVID-19 cases were generally long and associated with severity of disease clinical outcomes. The severe cases were mainly occurred in populations at high risk. In the epidemic period, classified management of COVID-19 cases should be promoted according to needs for control and prevention of isolation and treatment for the purpose of rational allocation of medical resources.

Diagnostic value of linked color imaging for Helicobacter Pylori infection compared with white light imag-ing / 实用医学杂志

Objective To investigate the ability of linked color imaging(LCI)for diagnosing Helicobacter Pylori(Hp)infection compared with conventional white light imaging(WLI). Methods We prospectively collected subjects who underwent gastroscopy. Images under both WLI and LCI were recorded and analyzed. Software was used to measure pixel brightness for red(R),green(G),blue(B)of endoscopic images from suspected lesion sites. Biopsies were taken from these sites and Warthin-Starry silver staining was used to detect if Hp was present. R/(G+B)value was used to construct receiver operating characteristic curve(ROC)to predict Hp infec-tion and the area under curve(AUC),cut-off point,sensitivity,as well as specificity were calculated with the patho-logy as the gold standard. Results Forty-seven subjects(23 men,24 women;23 Uygur subjects,24 Han subjects) were included in a mean age of 49 years old. Ninety-one biopsies were obtained. Forty-four biopsies (48.4%)were Hp positive according to the pathology. The AUC of LCI was 0.616,with the cut-off point at 0.967 and sensitivity at 0.955 and specificity at 0.298. The AUC of WLI was 0.529,with cut-off point at 2.638 and sensi-tivity at 0.455 and specificity at 0.766. The AUC of Han and Uygur subjects were 0.650 and 0.549 by LCI. The AUC of atrophy gastritis subjects and non-atrophy gastritis subjects were 0.628 and 0.603. Conclusion LCI was superior to WLI in predicting Hp infection. LCI may act as an objective and quantified endoscopic diagnostic meth-od in Hp infection.

Sero-prevalence of antibodies against avian influenza virus among people in poultry occupations in Guangdong province / 中华微生物学和免疫学杂志

Objective To detect the positive rates of antibodies against avian influenza virus (AIV) subtypes H5, H6, H7 and H9 among people in poultry occupations in Guangdong province and to analyze the transmission of various subtypes of AIV from poultry to human contacts for the prevention and control of novel AIV infection in human beings.Methods Serum specimens were collected from 1066 peo-ple in poultry occupations ( occupational group) and 205 people not in poultry occupations ( non-occupational group) in 10 cities of Guangdong province.The inactivated AIV strains, isolated from poultry or environment of Guangdong province, were used as antigens to detect antibodies against AIV subtypes H5, H6, H7 and H9 by using the hemagglutination inhibition ( HI) assay.Results The positive rates of antibodies against AIV subtypes H5, H6, H7 and H9 carried by people from the occupational group were respectively 0.44%, 0%, 0.30%and 0.30%in 2013 and 1.08%, 0.0%, 0.0%and 0.27%in 2014.Only the anti-H9 anti-bodies were detected in serum samples collected form people in the non-occupational group in 2013 with a positive rate of 0.95%.No significant differences with the positive rates of anti-AIV antibodies were found between the occupational group and the non-occupational group.However, the geometric mean titer ( GMT) of anti-AVI antibodies in people from the occupational group was higher than that of the non-occupational group.Conclusion Although a grand spread of AIV from avian to human is not likely to happen yet, con-tacting with poultry is the risk factor for AIV infection in Guangdong population.A long-term surveillance of anti-AIV antibodies in serum should be strengthened among people in poultry occupations for the timely pre-vention and control of novel AIV outbreak.

Investigation of a family clustering of human infection with avian influenza A (H7N9) virus in Nanning, Guangxi / 中华流行病学杂志

<p><b>OBJECTIVE</b>To understand the transmission mode of human infection with avian influenza A (H7N9) virus.</p><p><b>METHODS</b>Field epidemiological investigation was conducted for a family clustering of human infection with H7N9 virus in Hengxian county, Guangxi Zhuang Autonomous Region in February 2014. Two patients and their 82 close contacts were surveyed. The samples collected from the patients, environments and poultry were tested by using real time reverse transcriptase-polymerase chain reaction (rRT-PCR), and the samples from patients were used for virus isolation. The samples from 5 close contacts were tested with RT-PCR. The clinical data, exposure histories of the patients and the detection results of the isolates and their homology were analyzed.</p><p><b>RESULTS</b>Patient A became ill 4 days after her last exposure to poultry in Zhongshan, Guangdong province, and returned to her hometown in Hengxian 2 days after onset. Patient B was patient A's 5 years old son, who had no known exposure to poultry but slept with patient A for 4 days. He developed symptoms 4 days after last contact with his mother. Two strains of H7N9 virus were isolated from the two patients. The 2 isolates were highly homogenous (almost 100%) indicated by gene sequencing and phylogenetic tree. None of the other 81 close contacts developed symptoms of H7N9 virus infection.</p><p><b>CONCLUSION</b>Patients B was infected through close contact with patient A, indicating that avian H7N9 virus can spread from person to person, but the transmissibility is limited and non-sustainable.</p>

Current infection status and epidemic risk analysis of Dengue fever and Chikungunya in Guangdong province, from 1990 to 2012 / 中华流行病学杂志

Objective To understand the status of infection and epidemic trend of Dengue fever and Chikungunya in Guangdong.Methods Retrospective survey and literature review were used to obtain data on the incidence,etiology of Dengue and Chikungunya.Serological survey was conducted to detect the specific-antibodies in healthy individuals for both Dengue virus (DENV) and Chikungunya virus (CHIKV).Results Three epidemics of Dengue fever were observed during 1990-2012,with the annual incidence rates as 9.75/100 000 in 1995,1.76/100 000 in 2002 and 1.25/100 000 in 2006,respectively.The predominant epidemic strains appeared to be DENV-2 and DENV-4 during 1990-1994.Since 1995,DENV-1 had become the predominant transmission strain which lasted for almost 13 years.Co-existence of multiple serotypes of DENV started in 2009.Of the 7 718 sera from healthy population during 2003-2012,180 specimens were detected positive for specific DENV-IgG antibody,ended with a sero-prevalence rate of 2.33％.All 2 132 sera in 2012 were detected negative for CHIKV-IgG antibody.Conclusion The overall exposure level to Dengue was considered to be low in Guangdong province.However,the predominant transmission mode caused by DENV-1 had been gradually changed into the co-existence of multiple serotypes with the endemic signs appeared in some part of the areas.Chikungunya was a newly emerging disease in Guangdong since local people were lack of basic immunity barrier.Surveillance and control programs thus seemed important.

Maiden outbreak of chikungunya in Dongguan city, Guangdong province, China: epidemiological characteristics.

BACKGROUND: This study was conducted to identify epidemiological characteristics of the first documented CHIK fever outbreak in China and evaluate the effect of the preventive measures taken. METHODOLOGY/PRINCIPAL FINDINGS: From September 1 to October 29, 2010, China's first documented outbreak of CHIK fever occurred in the Xincun community of Wanjiang District of Dongguan city, Guangdong province; 253 case-patients were recorded, of which 129 were laboratory confirmed, with an attack rate of 1%. Before September 18(th) the number of CHIK fever cases remained relatively low in the Xincun community; from September 19(th) onwards, the number of cases increased drastically, with an outbreak peak on October 4(th). Cases were distributed across nine small village groups in the Xincun community, with an attack rate of 0-12% at the village level. The household attack rates ranged between 20% and 100%. No significant difference was found in the attack rate between males and females. There was a significant difference in the attack rate in different age groups (chi-square=18.35, p=0.005); highest in patients aged 60 years or older and the lowest in patients aged under 10. The major clinical characteristics of patients are fever (100%), joint pain (79%) and rash (54%). Phylogenetic analysis of the E1 gene on the five earliest confirmed cases showed that the strains of CHIKV isolated from their sera were highly homologous (up to 99%) with isogeneic strains isolated in Thailand in 2009. After control measures were taken, including killing adult mosquitoes and cleaning breeding habitats of Aedes mosquitoes, the Breteau index and Mosq-ovitrap index decreased rapidly, and the outbreak ended on October 29. CONCLUSION/SIGNIFICANCE: The infection source of the outbreak was imported. Cases showed obvious temporal, spatial, and population aggregation during the outbreak. Comprehensive control measures based on reducing the density of Aedes mosquitoes were effective in controlling the epidemic.

Laboratory detection on severe acute respiratory syndrome / 中华检验医学杂志

Objective To provide scientific evidence to identify and confirm severe acute respiratory syndrome (SARS) by laboratory detection.Methods Multiple clinical specimens were collected serially and systematically from the 4 suspected SARS patients, which occurred between Dec.2003 to Jan.2004 in Guangdong Province. The samples were tested by serologic and molecular methods.Results IgM or IgG antibodies against SARS-CoV were detectable after 6—8 days of the onset in four patients. The four-fold or greater rising in antibodies was clearly detected in three of the four patients, while the fourth patient’s seroconversion was from negative to positive. The results analysed by enzyme-linked immunosorbent assay( ELISA), immunoflourescence assay (IFA), and neutralization test were highly correlated. SARS-CoV RNA was just detected in 3 throat swab specimens from case 1 by real-time PCR. M, N and S genes were amplified by reverse transcriptase polymerase chain reaction (RT-PCR) from the positive samples. Sequencing results showed that they were SARS-CoV gene segments, and most closely matched SARS-CoV gene sequences were isolated from civet cats in Guangdong Province. Nevertheless, SARS-CoV was not isolated from any samples of the 4 patients.Conclusion Based on these results, the 4 reported cases were laboratorily confirmed as SARS cases.