Risk factors for developing severe COVID-19 in China: an analysis of disease surveillance data.

BACKGROUND: COVID-19 has posed an enormous threat to public health around the world. Some severe and critical cases have bad prognoses and high case fatality rates, unraveling risk factors for severe COVID-19 are of significance for predicting and preventing illness progression, and reducing case fatality rates. Our study focused on analyzing characteristics of COVID-19 cases and exploring risk factors for developing severe COVID-19. METHODS: The data for this study was disease surveillance data on symptomatic cases of COVID-19 reported from 30 provinces in China between January 19 and March 9, 2020, which included demographics, dates of symptom onset, clinical manifestations at the time of diagnosis, laboratory findings, radiographic findings, underlying disease history, and exposure history. We grouped mild and moderate cases together as non-severe cases and categorized severe and critical cases together as severe cases. We compared characteristics of severe cases and non-severe cases of COVID-19 and explored risk factors for severity. RESULTS: The total number of cases were 12 647 with age from less than 1 year old to 99 years old. The severe cases were 1662 (13.1%), the median age of severe cases was 57 years [Inter-quartile range(IQR): 46-68] and the median age of non-severe cases was 43 years (IQR: 32-54). The risk factors for severe COVID-19 were being male [adjusted odds ratio (aOR) = 1.3, 95% CI: 1.2-1.5]; fever (aOR = 2.3, 95% CI: 2.0-2.7), cough (aOR = 1.4, 95% CI: 1.2-1.6), fatigue (aOR = 1.3, 95% CI: 1.2-1.5), and chronic kidney disease (aOR = 2.5, 95% CI: 1.4-4.6), hypertension (aOR = 1.5, 95% CI: 1.2-1.8) and diabetes (aOR = 1.96, 95% CI: 1.6-2.4). With the increase of age, risk for the severity was gradually higher [20-39 years (aOR = 3.9, 95% CI: 1.8-8.4), 40-59 years (aOR = 7.6, 95% CI: 3.6-16.3), ≥ 60 years (aOR = 20.4, 95% CI: 9.5-43.7)], and longer time from symtem onset to diagnosis [3-5 days (aOR = 1.4, 95% CI: 1.2-1.7), 6-8 days (aOR = 1.8, 95% CI: 1.5-2.1), ≥ 9 days(aOR = 1.9, 95% CI: 1.6-2.3)]. CONCLUSIONS: Our study showed the risk factors for developing severe COVID-19 with large sample size, which included being male, older age, fever, cough, fatigue, delayed diagnosis, hypertension, diabetes, chronic kidney diasease, early case identification and prompt medical care. Based on these factors, the severity of COVID-19 cases can be predicted. So cases with these risk factors should be paid more attention to prevent severity.

Dynamics of Rodent and Rodent-borne Disease during Construction of the Three Gorges Reservoir from 1997 to 2012.

OBJECTIVE: To investigate the impact of impoundment and active public health interventions on rodent populations and rodent-borne diseases in the Three Gorges reservoir region from 1997 to 2012. METHODS: Surveillance data from 1997 to 2012 were extracted from the Public Health Surveillance System of The Three Gorges established in 1997. Temporal changes in the incidences of hemorrhagic fever with renal syndrome (HFRS) and leptospirosis, rodent density, pathogen-carrying rates, and their correlations were analyzed. RESULTS: The average indoor and outdoor rodent densities decreased overall from 1997 to 2012. The average densities decreased by 47.72% (from 4.38% to 2.29%) and 39.68% (from 4.41% to 2.66%), respectively, after impoundment (2003-2012) compared with before impoundment (1997-2002). The average annual incidence rates of HFRS and leptospirosis were 0.29/100,000 and 0.52/100,000, respectively, and decreased by 85.74% (from 0.68/100,000 to 0.10/100,000) and 95.73% (from 1.47/100,000 to 0.065/100,000), respectively, after impoundment compared with before impoundment. Incidences of HFRS and leptospirosis appear to be positively correlated with rodent density in the reservoir area. CONCLUSION: This study demonstrated that rodent density and incidences of rodent-borne diseases decreased and were maintained at low levels during construction of the Three Gorges dam. Measures that reduce rodent population densities could be effective in controlling rodent-borne diseases during large-scale hydraulic engineering construction.

[Epidemiological features of typhoid/paratyphoid fever in provinces with high incidence rate and in the whole country, in 2012].

OBJECTIVE: Through analyzing the national statutory reporting data on typhoid, paratyphoid fever in 2012, we were trying to understand the whole picture of typhoid, paratyphoid fever at the national level as well as to understand the trends and characteristics of typhoid and paratyphoid fever in provinces with high incidence rate, so as to the development of prevention and control strategies of the diseases in those high-incidence rate provinces. METHODS: We descriptively analyzed the national typhoid and paratyphoid fever statutory reporting data which was reported through disease surveillance information reporting system in 2012. RESULTS: 11 998 cases with typhoid and paratyphoid fever were reported with 3 fatal ones, in 2012 in the whole country. The incidence rate was 0.89 per 100 000. Compared to the data gathered in 2011, the incidence rates of typhoid/ paratyphoid fever increased by 1.20%. The total number of the confirmed cases on typhoid and paratyphoid fever was 6522 and was accounted for 54.36% of the total cases, in which paratyphoid fever accounted for 36.86%. Cases were mainly involved farmers and followed by students and children. Incidence rates of typhoid and paratyphoid fever in children aged 0-4 years old appeared the highest (respectively 1.31/100 000 and 0.46/100 000). Yunnan,Guizhou,Guangdong,Guangxi, Zhejiang, Hunan and Xinjiang provinces (autonomous regions)were identified as provinces with high-incidence rates of typhoid and paratyphoid fever. During 2005-2012, the incidence rates in most of the above high-incidence provinces showed a downward trend, except for in Guangdong which had only showed a slight change. There were variations on peak period and highly-hit population in seven high-incidence provinces. CONCLUSION: The incidence rate of typhoid/paratyphoid fever was in a relatively low level in China. Prevention and control strategies on the diseases in children under 5 years old remained a challenge, warranted more work to be done. The epidemiological situation is still severe in some high-incidence rate provinces.

[Epidemiological features of hand, foot and mouth disease in China, 2008 - 2009].

OBJECTIVE: To clarify the seasonal and geographical difference and pathogen patterns so as to provide reference of prevention and control of the disease through analyzing the epidemic characteristics of reported hand-foot-mouth disease (HFMD) cases in China, 2008 - 2009. METHODS: We analysed the epidemiological data of HFMD from the Chinese national notifiable infectious diseases reporting system in 2008 and 2009. RESULTS: There were 488 955 and 1 155 525 reported HFMD cases in 2008 and 2009, in China, of which 1165 and 13 810 were severe and 126 and 353 were fatal, respectively. The notification rates were 50.09/10 million, 68.47/10 million and 59.04/10 million in high, medium and low latitudes areas, respectively. The epidemic periods in Medium and Low latitude were from 12 to 24 weeks in 2009, and in high latitude it was from 23 to 35 weeks. HFMD cases were concentrated mainly in 5 year-old or even younger children, accounted for 92.23% of the total cases. The incidence rate of two years old appeared to be the highest. The features of severe and death case concentrated in lower age groups were more evident, and the proportion of severe case and case fatality rate under 1 years old was higher than that in other age groups. We also noticed that with the increasing of age, the proportion of severe case and case fatality rate had a decreasing trend. There was a difference between the pathogens seen. The relative risk (RR) for an human enterovirus 71 (HEV71) isolate was higher among severe case than in common cases (RR = 1.82), whereas the RR for an EV71 isolate was higher among the death cases than in common cases (RR = 2.11). There was seasonal variation of pathogen composition. There were 477 clusters of cases from 2008 to 2009, of which 389 found in preschools, 47 in rural villages, outbreaks of clusters were mainly from April to July. CONCLUSION: The HFMD epidemics was increasing in 2009. The epidemic of HFMD in different latitudes area and seasons was different. Children of five year old or under were the major population groups at risk, of HFMD. The younger ones had higher risk of becoming severe and death cases. HEV71 and coxsackievirus A16 were both the major etiologic agents of HFMD. The preschool and rural villages were the main settings of clusters of cases.

[Surveillance on the health status regarding vector-borne disease among people living in the Three Gorges Reservoir Area (1997 - 2009)].

OBJECTIVE: To evaluate the impact on the health status of population in the area where the 'Three Gorges Reservoir Water Storage Project' had been operated and to provide references for the development of related disease control strategies. METHODS: In the Three Gorges Reservoir Area, 17 towns/streets in nine counties were chosen as surveillance points. Data on surveillance program would include infectious diseases, birth, death, biological agents etc. METHODS: related to time and spatial analysis and the comparison on pre- and post-water storage were used to analyze and describe the long-term changing trend of meteorological index, distribution of biological agent and diseases, and human health status. Relationships between number of infectious diseases and media biological density and meteorological parameters were also analyzed. RESULTS: When the water storage program came into being in 2003, the indoor (2.22%) and outdoor (2.76%) densities of rats were significantly lower than pre-water storage period (indoor 4.38% vs. outdoor 4.43%) and the annual average density of mosquito (35.09 mosquitoes per room and per hour) was also lower than before (54.24 mosquitoes per room and per hour). The incidence rates of encephalitis B, malaria, leptospirosis, and hemorrhagic fever had reduces 22.88%, 84.85%, 95.03% and 81.82% than before. The incidence rates of malaria, leptospirosis, and hemorrhagic fever were all below 0.4/100 000 and the incidence of encephalitis B was below 2/100 000. The average infant mortality was 11.83‰. The annual infant mortalities, after adjusted by missing report numbers, were between 13.07‰ and 23.88‰ which were lower than the national annual average level. The thirteen year standard mortalities were 3.77‰ - 5.12‰, with the total rate lower than the national average level in the same years. CONCLUSION: In 2003, the incidence rates of malaria, encephalitis B, leptospirosis, epidemic hemorrhagic fever kept going down in the surveillance sites in the Three Gorges Reservoir Area, and the overall population's health status was well enough to show that there was no negative impact on the health status of population living in the area after the water storage project was inplemented.

[Outbreaks of noroviral gastroenteritis and their molecular characteristics in China, 2006 - 2007].

OBJECTIVE: To acknowledge the epidemiology of gastroenteritis outbreaks caused by noroviruses and their genotypes. METHODS: Epidemiologic data and specimens were collected from 19 gastroenteritis outbreaks. 201 specimens were detected for norovirus, rotavirus, astrovirus, adenovirus and sapovirus by RT-PCR methods and PCR products were sequenced. Sequence alignment and phylogenetic analysis were performed by Clustal X 1.83 and MEGA 4.0 programs. RESULTS: Noroviruses were one of the most predominant pathogens causing viral gastroenteritis outbreaks (12 of 19 outbreaks, accounting for 63.2%). Variant GII-4/2006b was the predominant strain responsible for 11 of the 12 NV-associated outbreaks. Other genotypes would include GII-17, GII-6 and GII-3. The NV-associated gastroenteritis outbreaks occurred mainly in winter and spring between December 2006 and April 2007. These gastroenteritis outbreaks caused by noroviruses would involve all age groups in various locations. Meantime, 2 out of 12 outbreaks were caused by norovirus or other viruses. In addition, multiple viruses and multiple genotypes of noroviruses were found in the same outbreak. CONCLUSION: Noroviruses were one of the most major pathogens causing gastroenteritis outbreaks while GII-4/2006b variant was identified as the predominant strain in China.

[Analysis on bacillary dysentery surveillance data collected from the National Surveillance System in 2007.].

OBJECTIVE: To improve the national surveillance plan on bacillary dysentery and to increase the sensitivity of the surveillance system on the disease. METHODS: Data was collected through China Disease Reporting Information System (CDRIS) and National Sentinel Surveillance Sites on bacillary dysentery. Data from the CDRIS was compared with the data from the National Sentinel Surveillance to identify the exiting problems. RESULTS: Data from the monitoring sites showed that the detection rate of infant cases of bacillary dysentery infection was 1%, less than that of other age groups. The highest rates were seen in children aged 3 through 9 years. Rate on misdiagnosis in all age group was 23.38%, when using the surveillance case definition of clinical cases and suspect case. The rate of misdiagnosis on infant cases of bacillary dysentery infection by clinical diagnosis was 50%. It showed that Shigella flexneri and Shigella sonnei were dominant with the positive rates as 57.21% and 42.41%, respectively. From the national sentinel surveillance sites, the confirmed cases taking up 43.39% which did not match the figure from the CDRIS. CONCLUSION: The diagnostic criterion for bacillary dysentery fit well on other age groups in surveillance system except on infants. Active surveillance on bacillary dysentery that combining both clinical and laboratory diagnosis seems quite necessary on CDRIS, especially for infants.

[Study on the health status and affecting factors among people living in the surveillance sites of three Gorges Reservoir Areas, in 2007].

OBJECTIVE: To understand the health status and potential impact resulted in the second stage of Three Gorges Reservoir Areas sluicing. METHODS: Data were collected on deaths, prevalence rates of infectious and endemic diseases, as well as on vector surveillance through the project entitled 'Three Gorges Population Health Survey System'. RESULTS: The main causes of death in the population living in the Three Gorges Reservoir Areas would include: circulatory system diseases, tumors, respiratory system diseases, injuries/poison and digestive system diseases. The number of deaths caused by the above said five kind of diseases accounted for 90.94% of the total number of deaths. The prevalence rates on Water-born diseases related to the sluicing of reservoir and zoonosis-borne diseases related to the changes of vectors were still low. The indoor and outdoor densities of rodents were 3.11% and 3.16%, both were higher than that in 2006 but lower than the average numbers in the five years prior to the sluicing. The constituent ratio of Apodemus agrarius had constantly risen since 2006. The density of mosquitoes found in livestock barns and human households was higher than that in 2006 but lower than the average number of the five-year studies prior to the sluicing. CONCLUSION: Environment change after the sluicing of the Three Gorges Reservoir Areas did not seem to have obvious impact on the health status of the people living in the areas. However, to strengthen the surveillance on the biological features of the vectors which might have related to the transmission of diseases would be highly recommended.

[Analysis of epidemiologic feature and genetic sequence of Sapovirus in China].

To investigate epidemiologic feature and genetic variance of Sapovirus among children in China, fecal specimens were collected from children under 5 years old with acute diarrhea from Feb 2006 to Jan 2007 in nine provinces including Anhui, Fujian et al. A total of 1,110 fecal samples were detected for Sapovirus by reverse transcriptase-PCR (RT-PCR). Ten samples (0.9%) were positive for Sapovirus. The PCR products were then sequenced and analysed by phylogenetic tree. The results indicated that the detected Sapovirus strains were classified into two genogroups and three genotypes, including G I/1, G I/3, G II/3.

[Identification and molecular study on vibrio cholerae in sea products].

OBJECTIVE: To investigate the serologic type, phage-biotype and toxic factor of Vibrio cholerae isolated from different sea products, analyze the relation between the Vibrio cholerae in sea products and cholera epidemiology, and provide references for forecasting cholera epidemic situation and drawing out a preventing plan. METHOD: The biotype of strains isolated was analyzed by using type and phage-biotype serological methods. The toxic gene was detected by PCR. RESULTS: The constituent ratio of V. cholerae O139, Ogawa and Inaba were, respectively, 48.44%, 20.31% and 31.25% in 64 strains of V. cholerae. The result of phage-biotype showed that the 26 strains of V. cholerae O1 were all non-epidemic strains. The result of toxic gene detecting showed that positive rate of V. cholerae O139 was higher than those of Ogawa and Inaba. CONCLUSION: The positive rate of toxic gene in V. cholerae O139 was high and the V. cholerae O139 was mainly in turtle, breed aquatics water and crustacean, so these sea products were the important sectors in cholera prevention and control.

[Analysis on the status of Shigella spp antimicrobial resistance through data from the National Shigellosis Surveillance System in China, in 2005].

OBJECTIVE: The Ministry of Public Health released the National Surveillance project on Shigellosis in August, 2005. This study was to reveal the antimicrobial resistance status of Shigella isolates through the National Shigellosis Surveillance System in 2005 in China, so as to provide evidence for the development of surveillance, prevention and cure of Shigellosis. METHODS: All the lab assistants received training from Chinese Center for Disease Control and Prevention. The project prescribed the uniform experimentation, quality control method, reagent, etc. Disc diffusion test(K-B) was carried out, following the CLSI methods. Data were analyzed by WHONET 5.4 software. RESULTS: (1) 3 serotypes were identified and S. flexneri was common that accounted for 75.5% of all Shigella isolates followed by 24.4% of S. sonnei, but only 1 strain of S. dysenteriae was separated. (2) The resistant rates to tetracycline and ampicillin in Shigella spp were quite high, as over 90.0%. However, the resistant rate to Cefotaxime was the lowest, only 6.1%. The resistant rates were different between serotypes with the resistant rates of S. flexneri to ampicillin, ampicillin/clavulanate and ciprofloxacin were higher than those of S. sonnei (P < 0.001). (3) The multiple-antibiotic-resistance status in Shigella spp was quite serious and the resistant rate to five and more antimicrobials was 54.9%. The most common resistant patterns were seen on ampicillin, nalidixin, tetracycline and sulfamethoxazole. (4) There were some differences in subtypes and antimicrobial resistance among different provinces. CONCLUSION: Cefotaxime seemed the best in curing Shigellosis at the clinic level. Programs regarding monitoring subtypes and antimicrobial resistance of Shigella should be in a continuous manner so as to understand the pathogens timely and to control the disease pertinently.

[Investigation on status of pollution of vibrio cholera in seafood and aquatic products in 12 provinces of China in 2005].

OBJECTIVE: To understand the pollution rates of vibrio cholera (V. cholera) in different seafood, aquatic products and their circulatory processes, so as to help making measures for cholera control and prevention. METHODS: Different seafood, aquatic products and breed water specimen collected from 12 provinces of China were tested from July to September in 2005. RESULT: A total of 12 104 samples of seafood and aquatic products were tested and the average pollution rate of vibrio cholera was 0.52%. The positive isolate rate of turtle sample (1.72%) was the highest among all samples. The second higher isolated rate was 1.14% in water specimen of turtle breed pool. The positive rate of bullfrog was 0.50%. The percentage of toxin strains was 47.54% and 79.31% of them were isolated from turtle and water samples of turtle breed pool. The important sector of the pollution of vibrio cholera was in turtle breed pool (2.38%). CONCLUSION: The average pollution rate of vibrio cholera in seafood and aquatic products in 12 provinces of China was low. It should be very necessary to supervise the sanitation in turtle breed for controlling and preventing the vibrio cholera.

[Study on the RNA of severe acute respiratory syndrome (SARS) associated coronavirus in the blood and excretion of convalescent patients with SARS].

OBJECTIVE: To examine the RNA of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) in the blood and excretion of convalescent patient with SARS for prevention and treatment of the disease. METHODS: A total of 276 samples, including plasma, urine, feces and sputum, obtained from 23 convalescent patients with SARS were studied at 3 time-points at least 21 days after the onset of symptoms. RNA was extracted and nested reverse transcription-polymerase chain reaction (RT-PCR) was carried out using SARS-CoV specific primers. RESULTS: Among the 276 samples, SARS-CoV RNA was detected in 6 cases (38.8%) by nested RT-PCR. The positive rates of SARS-CoV RNA was 5.8% in feces and 2.9% in sputum samples but SARS-CoV RNA was not detectable in plasma and urine of all the cases. CONCLUSION: The existence of SARS-CoV RNA in the excretion of some convalescent patients with SARS showed that the excretion from these patients should be carefully treated whilthe re-transmission of SARS by which, should be further studied.

[Preparation and characterization of monoclonal antibodies against SARS-associated coronavirus nucleocapsid protein].

OBJECTIVE: To obtain monoclonal antibodies (McAbs) against severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) nucleocapsid (N) protein to develop diagnostic test for SARS and study the pathogenesis of the disease. METHODS: BALB/c mice were immunized with purified N protein of SARS-CoV. Hybridoma cell lines secreting monoclonal antibodies against SARS-associated coronavirus nucleocapsid were established after cell fusion with mouse splenic cells and SP2/0 cells. The specificity of the McAbs obtained was examined by Western blot and indirect fluorescence assay. Epitopes reacted with the McAbs were preliminarily located through Western blot by expressing truncated N proteins. RESULTS: After cell fusion and three rounds of cell cloning, six hybridoma cell lines secreting monoclonal antibodies specifically against SARS-CoV nucleocapsid were obtained. Western blot and indirect fluorescence assay showed that the McAbs reacted specifically with nucleocapsid protein and SARS-CoV. Among the six McAbs, three recognize the epitopes located in the N-terminus of the protein, whereas the others reacted with those located in the C-terminus. CONCLUSION: The anti-SARS-CoV nucleocapsid McAbs were developed and these McAbs may be useful in the development of diagnosis assays and basic research of SARS.