To investigate the changing patterns of respiratory viral infections within the context of COVID-19 pandemic. The etiological surveillance data of eight respiratory viral pathogens among patients with ARIs in Shanghai between 2013 and 2023 were analyzed to evaluate the dynamic patterns of respiratory viral infections in Shanghai compared to global other regions during pre-pandemic (period 1), pandemic (period 2), and post-pandemic (period 3) periods of COVID-19. In Shanghai and various other global regions, there was a delay of 2‒4 months in the peak positive rate of IFV and a reverse seasonality for RSV, HMPV, and HBoV was observed following the relaxation of NPIs. The proportion of patients infected with any of these eight viruses experiencing fever or high fever notably increased. During the entire study period, IFV was consistently identified as the most prevalent virus, with IFV-B as the predominant stain during period 2, and IFV-A regained its dominance following the lifting of NPIs. The proportion of RSV among children significantly increased during period 2 compared to period 1. With the relaxation of NPIs, there has been a resurgence of certain viral pathogens, accompanied by notable alterations in seasonal patterns and the spectrum of viral pathogens.

BACKGROUND: Air pollutionisamajorriskfactorforplanetaryhealthandhaslongbeensuspectedofpredisposinghumanstorespiratorydiseases induced bypathogenslikeinfluenza viruses. However, epidemiologicalevidenceremainselusiveduetolackoflongitudinaldatafromlargecohorts. OBJECTIVE: Our aimistoquantifytheshort-termassociationofinfluenza incidencewithexposuretoambientairpollutantsinChinesecities. METHODS: Based onairpollutantdataandinfluenza surveillancedatafrom82citiesinChinaoveraperiodof5years, weappliedatwo-stagetime series analysistoassesstheassociationofdailyincidenceofreportedinfluenza caseswithsixcommonairpollutants[particulatematterwithaerodynamic diameter = 2:5 lm (PM2:5), particulatematterwithaerodynamicdiameter <= 10 mu m (PM10), NO2, SO2, CO, andO(3)], whileadjustingforpotential confoundersincludingtemperature, relativehumidity, seasonality, andholidayeffects. WebuiltadistributedlagPoissonmodelforoneor multiple pollutantsineachindividualcityinthe first stageandconductedameta-analysistopoolcity-specific estimatesinthesecondstage. RESULTS: A totalof3,735,934influenza caseswerereportedin82citiesfrom2015to2019, accountingfor72.71% oftheoverallcasenumber reported inthemainlandofChina. Thetimeseriesmodelsforeachpollutantaloneshowedthatthedailyincidenceofreportedinfluenza caseswas positively associatedwithalmostallairpollutantsexceptforozone. Themostprominentshort-termassociationswerefoundforSO(2) and NO2 with cumulative riskratiosof1.094[95% confidence interval(CI): 1.054,1.136] and1.093(95% CI: 1.067,1.119), respectively, foreach10 mu g/m(3) increase intheconcentrationateachofthelagsof1-7 d. OnlyNO(2) showed asignificant associationwiththedailyincidenceofinfluenza casesin the multipollutantmodelthatadjustsallsixairpollutantstogether. Theimpactofairpollutantsoninfluenza wasgenerallyfoundtobegreaterinchildren, insubtropicalcities, andduringcoldmonths. DISCUSSION: Increased exposuretoambientairpollutants, particularlyNO(2), isassociatedwithahigherriskofinfluenza-associated illness. Policies on reducingairpollutionlevelsmayhelpalleviatethediseaseburdenduetoinfluenza infection. https://doi.org/10.1289/EHP12146

BACKGROUND:Air pollution is a major risk factor for planetary health and has long been suspected of predisposing humans to respiratory diseases induced by pathogens like influenza viruses. However, epidemiological evidence remains elusive due to lack of longitudinal data from large cohorts. OBJECTIVE:Our aim is to quantify the short-term association of influenza incidence with exposure to ambient air pollutants in Chinese cities. METHODS:Based on air pollutant data and influenza surveillance data from 82 cities in China over a period of 5 years, we applied a two-stage time series analysis to assess the association of daily incidence of reported influenza cases with six common air pollutants [particulate matter with aerodynamic diameter ≤2.5μm (PM2.5), particulate matter with aerodynamic diameter ≤10μm (PM10), NO2, SO2, CO, and O3], while adjusting for potential confounders including temperature, relative humidity, seasonality, and holiday effects. We built a distributed lag Poisson model for one or multiple pollutants in each individual city in the first stage and conducted a meta-analysis to pool city-specific estimates in the second stage. RESULTS:A total of 3,735,934 influenza cases were reported in 82 cities from 2015 to 2019, accounting for 72.71% of the overall case number reported in the mainland of China. The time series models for each pollutant alone showed that the daily incidence of reported influenza cases was positively associated with almost all air pollutants except for ozone. The most prominent short-term associations were found for SO2 and NO2 with cumulative risk ratios of 1.094 [95% confidence interval (CI): 1.054, 1.136] and 1.093 (95% CI: 1.067, 1.119), respectively, for each 10 μg/m3 increase in the concentration at each of the lags of 1-7 d. Only NO2 showed a significant association with the daily incidence of influenza cases in the multipollutant model that adjusts all six air pollutants together. The impact of air pollutants on influenza was generally found to be greater in children, in subtropical cities, and during cold months. DISCUSSION:Increased exposure to ambient air pollutants, particularly NO2, is associated with a higher risk of influenza-associated illness. Policies on reducing air pollution levels may help alleviate the disease burden due to influenza infection. https://doi.org/10.1289/EHP12146.

BackgroundA viral infection can modify the risk to subsequent viral infections via cross-protective immunity, increased immunopathology, or disease-driven behavioral change. There is limited understanding of virus-virus interactions due to lack of long-term population-level data.MethodsOur study leverages passive surveillance data of 10 human acute respiratory viruses from Beijing, Chongqing, Guangzhou, and Shanghai collected during 2009 to 2019: influenza A and B viruses; respiratory syncytial virus A and B; human parainfluenza virus (HPIV), adenovirus, metapneumovirus (HMPV), coronavirus, bocavirus (HBoV), and rhinovirus (HRV). We used a multivariate Bayesian hierarchical model to evaluate correlations in monthly prevalence of test-positive samples between virus pairs, adjusting for potential confounders.ResultsOf 101,643 lab-tested patients, 33,650 tested positive for any acute respiratory virus, and 4,113 were co-infected with multiple viruses. After adjusting for intrinsic seasonality, long-term trends and multiple comparisons, Bayesian multivariate modeling found positive correlations for HPIV/HRV in all cities and for HBoV/HRV and HBoV/HMPV in three cities. Models restricted to children further revealed statistically significant associations for another ten pairs in three of the four cities. In contrast, no consistent correlation across cities was found among adults. Most virus-virus interactions exhibited substantial spatial heterogeneity.ConclusionsThere was strong evidence for interactions among common respiratory viruses in highly populated urban settings. Consistent positive interactions across multiple cities were observed in viruses known to typically infect children. Future intervention programs such as development of combination vaccines may consider spatially consistent virus-virus interactions for more effective control.

Abstract Background Emerging mite-borne pathogens and associated disease burdens in recent decades are raising serious public health concerns, yet their distributions and ecology remain under-investigated. We aim to describe the geographical distributions of blood-sucking mites and mite-borne agents and to assess their ecological niches in China. Methods We mapped 549 species of blood-sucking mites belonging to 100 genera at the county level and eight mite-associated agents detected from 36 species of blood-sucking mites in China during 1978–2020. Impacts of climatic and environmental factors on the ecology of 21 predominant vector mites and a leading pathogen, Orientia tsutsugamushi, were assessed using boosted regression tree (BRT) models, and model-predicted risks were mapped. We also estimated the model-predicted number, area and population size of affected counties for each of the 21 mite species in China. Results Laelaps echidninus is the leading mite species that potentially affects 744 million people, followed by La. jettmari (517 million) and Eulaelaps stabularis (452 million). Leptotrombidium scutellare is the mite species harboring the highest variety of mite-borne agents including four Rickettsia species and two viruses, followed by Eu. stabularis (2 agents), L. palpale (2) and La. echidninus (2). The top two agents that parasitize the largest number of mite species are O. tsutsugamushi (28 species) and hantavirus (8). Mammalian richness, annual mean temperature and precipitation of the driest quarter jointly determine the ecology of the mites, forming four clusters of major mite species with distinct geographic distributions. High-risk areas of O. tsutsugamushi are mainly distributed in southern and eastern coastal provinces where 71.5 million people live. Conclusions Ecological niches of major mite species and mite-borne pathogens are much more extensive than what have been observed, necessitating expansion of current filed surveillance. Graphic Abstract

The geographic expansion of mosquitos is associated with a rising frequency of outbreaks of mosquito-borne diseases (MBD) worldwide. We collected occurrence locations and times of mosquito species, mosquito-borne arboviruses, and MBDs in the mainland of China in 1954−2020. We mapped the spatial distributions of mosquitoes and arboviruses at the county level, and we used machine learning algorithms to assess contributions of ecoclimatic, socioenvironmental, and biological factors to the spatial distributions of 26 predominant mosquito species and two MBDs associated with high disease burden. Altogether, 339 mosquito species and 35 arboviruses were mapped at the county level. Culex tritaeniorhynchus is found to harbor the highest variety of arboviruses (19 species), followed by Anopheles sinensis (11) and Culex pipiens quinquefasciatus (9). Temperature seasonality, annual precipitation, and mammalian richness were the three most important contributors to the spatial distributions of most of the 26 predominant mosquito species. The model-predicted suitable habitats are 60–664% larger in size than what have been observed, indicating the possibility of severe under-detection. The spatial distribution of major mosquito species in China is likely to be under-estimated by current field observations. More active surveillance is needed to investigate the mosquito species in specific areas where investigation is missing but model-predicted probability is high.

NAD(P)H:quinone oxidoreductase (NQO1) is a flavoprotein which catalyzes the two-electron reduction of quinones and azo-dyes and thus prevents the formation of free radicals and toxic oxygen metabolites that may be generated by the one-electron reductions catalyzed by cytochrome P450 reductase. Analysis of RNA indicated 20- to 50-fold higher levels of NQO1 gene expression in the liver tumors and in the tissue surrounding the tumors of patients with hepatocarcinoma than in normal individuals. An approximately 50-fold higher level of NQO1 mRNA was also observed in human hepatoblastoma (Hep-G2) cells than in normal liver. By deletion mutagenesis in the human NQO1 gene promoter and subsequent transfection into hepatic and nonhepatic cell lines, a 1.42 kb DNA segment has been identified to contain cis-acting elements responsible for high levels of expression of the NQO1 gene in tumor cells.

Objectives: Selenium deficiency can be associated with increased susceptibility to some viral infections and even more severe diseases. In this study, we aimed to examine whether this association applies to severe fever with thrombocytopenia syndrome (SFTS). Method: An observational study was conducted based on the data of 13,305 human SFTS cases reported in mainland China from 2010 to 2020. The associations among incidence, case fatality rate of SFTS, and crop selenium concentration at the county level were explored. The selenium level in a cohort of patients with SFTS was tested, and its relationship with clinical outcomes was evaluated. Results: The association between selenium-deficient crops and the incidence rate of SFTS was confirmed by multivariate Poisson analysis, with an estimated incidence rate ratio (IRR, 95% confidence interval [CI]) of 4.549 (4.215-4.916) for moderate selenium-deficient counties and 16.002 (14.706-17.431) for severe selenium-deficient counties. In addition, a higher mortality rate was also observed in severe selenium deficient counties with an IRR of 1.409 (95% CI: 1.061-1.909). A clinical study on 120 patients with SFTS showed an association between serum selenium deficiency and severe SFTS (odds ratio, OR: 2.94; 95% CI: 1.00-8.67) or fatal SFTS (OR: 7.55; 95% CI: 1.14-50.16). Conclusion: Selenium deficiency is associated with increased susceptibility to SFTS and poor clinical outcomes. (C) 2022 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

Abstract Background To quantitatively assess the impact of the onset-to-diagnosis interval (ODI) on severity and death for coronavirus disease 2019 (COVID-19) patients. Methods This retrospective study was conducted based on the data on COVID-19 cases of China over the age of 40 years reported through China’s National Notifiable Infectious Disease Surveillance System from February 5, 2020 to October 8, 2020. The impacts of ODI on severe rate (SR) and case fatality rate (CFR) were evaluated at individual and population levels, which was further disaggregated by sex, age and geographic origin. Results As the rapid decline of ODI from around 40 days in early January to < 3 days in early March, both CFR and SR of COVID-19 largely dropped below 5% in China. After adjusting for age, sex, and region, an effect of ODI on SR was observed with the highest OR of 2.95 (95% CI 2.37‒3.66) at Day 10–11 and attributable fraction (AF) of 29.1% (95% CI 22.2‒36.1%) at Day 8–9. However, little effect of ODI on CFR was observed. Moreover, discrepancy of effect magnitude was found, showing a greater effect from ODI on SR among patients of male sex, younger age, and those cases in Wuhan. Conclusion The ODI was significantly associated with the severity of COVID-19, highlighting the importance of timely diagnosis, especially for patients who were confirmed to gain increased benefit from early diagnosis to some extent.

BACKGROUND:Previous studies have evaluated treatment efficacy of various antibiotics for patients with mild-to-moderate scrub typhus (ST). However, the efficacy of different antibiotics for treating severe ST remains uncertain.METHODS:A retrospective study of patients with severe ST was undertaken in China. The treatment efficacy rates of doxycycline, azithromycin and chloramphenicol were compared, using treatment failure and time to defervescence as primary outcomes.RESULTS:In total, 876 patients with severe ST who initially received doxycycline, azithromycin or chloramphenicol were recruited. The treatment failure rate did not differ significantly between patients receiving doxycycline and patients receiving azithromycin (6.0% vs 11.4%; P=0.109). However, a higher treatment failure rate was observed for chloramphenicol compared with doxycycline (14.6% vs 6.0%; P=0.004). No significant difference in time to defervescence was observed between patients receiving doxycycline, azithromycin or chloramphenicol. Further subgroup analysis revealed a higher risk of treatment failure for chloramphenicol compared with doxycycline in patients with acute kidney injury, pneumonia and shock; and a higher risk of treatment failure for azithromycin compared with doxycycline in patients with meningitis. Significant correlation was found between azithromycin resistance and meningitis (P=0.009), and between chloramphenicol resistance and acute respiratory distress syndrome (ARDS) (P<0.001) using Cramer's V correlation coefficient. Multi-variate Cox regression analysis revealed significant associations between time to defervescence and presence of ARDS, shock, myocarditis, meningitis and acute kidney injury.CONCLUSION:Azithromycin and doxycycline were found to have significant therapeutic effects in patients with severe ST. In contast, chloramphenicol was less efficacious for the treatment of these patients.

BACKGROUND:To combat the coronavirus disease 2019 (COVID-19) pandemic, nonpharmaceutical interventions (NPIs) were implemented worldwide, which impacted a broad spectrum of acute respiratory infections (ARIs). METHODS:Etiologically diagnostic data from 142 559 cases with ARIs, who were tested for 8 viral pathogens (influenza virus [IFV], respiratory syncytial virus [RSV], human parainfluenza virus [HPIV], human adenovirus [HAdV], human metapneumovirus [HMPV], human coronavirus [HCoV], human bocavirus [HBoV], and human rhinovirus [HRV]) between 2012 and 2021, were analyzed to assess the changes in respiratory infections in China during the first COVID-19 pandemic year compared with pre-pandemic years. RESULTS:Test-positive rates of all respiratory viruses decreased during 2020, compared to the average levels during 2012-2019, with changes ranging from -17.2% for RSV to -87.6% for IFV. Sharp decreases mostly occurred between February and August when massive NPIs remained active, although HRV rebounded to the historical level during the summer. While IFV and HMPV were consistently suppressed year-round, RSV, HPIV, HCoV, HRV, and HBoV resurged and went beyond historical levels during September 2020-January 2021, after NPIs were largely relaxed and schools reopened. Resurgence was more prominent among children <18 years and in northern China. These observations remain valid after accounting for seasonality and long-term trend of each virus. CONCLUSIONS:Activities of respiratory viral infections were reduced substantially in the early phases of the COVID-19 pandemic, and massive NPIs were likely the main driver. Lifting of NPIs can lead to resurgence of viral infections, particularly in children.

This study is performed to figure out how the presence of diabetes affects the infection, progression and prognosis of 2019 novel coronavirus disease (COVID-19), and the effective therapy that can treat the diabetes-complicated patients with COVID-19. A multicentre study was performed in four hospitals. COVID-19 patients with diabetes mellitus (DM) or hyperglycaemia were compared with those without these conditions and matched by propensity score matching for their clinical progress and outcome. Totally, 2444 confirmed COVID-19 patients were recruited, from whom 336 had DM. Compared to 1344 non-DM patients with age and sex matched, DM-COVID-19 patients had significantly higher rates of intensive care unit entrance (12.43% vs. 6.58%, P = 0.014), kidney failure (9.20% vs. 4.05%, P = 0.027) and mortality (25.00% vs. 18.15%, P < 0.001). Age and sex-stratified comparison revealed increased susceptibility to COVID-19 only from females with DM. For either non-DM or DM group, hyperglycaemia was associated with adverse outcomes, featured by higher rates of severe pneumonia and mortality, in comparison with non-hyperglycaemia. This was accompanied by significantly altered laboratory indicators including lymphocyte and neutrophil percentage, C-reactive protein and urea nitrogen level, all with correlation coefficients >0.35. Both diabetes and hyperglycaemia were independently associated with adverse prognosis of COVID-19, with hazard ratios of 10.41 and 3.58, respectively.

Severe fever with thrombocytopenia syndrome (SFTS), an emerging tick-borne disease first reported in rural areas of central China, has become a major public health concern in endemic areas. The epidemic dynamic and ecologic factors of SFTS incidence at a village scale remain unclear. Here we analyzed the epidemiological characteristics of SFTS cases in Shangcheng County, the first reported areas of SFTS in China. A retrospective space-time cluster analysis was conducted to identify the dynamics of hotspot areas, and the negative binomial regression model was conducted to examine potential factors contributing to the incidence of SFTS at the village level. A total of 1,219 SFTS cases were reported in Shangcheng County from 2011 to 2020, with a case fatality rate of 12.0%. The median age of patients was 64 years, and 81.7% of patients were over 50 years old. Women accounted for 60.3% of all cases, and the incidence rate was significantly higher than that of men (Pearson χ2 test, P<0.001). Five spatial-temporal clusters were identified, and mostly distributed in the central part of the county. Higher risk of SFTS incidence was shown in villages with higher percentage coverages of forest and tea plantation, and higher goat density. In villages where the ratio of cultivated land area to forest land area was between 0.2 and 1.2, the risk of SFTS incidence increased significantly, with an incidence rate ratio of 1.33 (95% CI: 1.04‒1.72, p = 0.024). Our findings indicated that ecotone between forest and cultivated land might be the most important risk settings for exposure and infection with SFTS virus in endemic areas of central China. Precise identification of risk factors and high-risk areas at a suitable scale is conducive to carrying out targeted measures and improving the surveillance of the disease.

Additional file 4. The number of mite species recorded in each county and seven biogeographic regions in China.

Background In the past few decades, globalization has rendered more frequent and intensive population movement between countries, which has changed the original disease spectrum and brought a huge health impact on the global population including China. This study aims to describe the spectrum and epidemiological characteristics of imported infections among foreign travelers travelling to China. Methods The data on imported infections among foreign travelers were obtained from Custom Inbound Screening System (CISS) and the National Notifiable Infectious Disease Reporting System (NNIDRS). All the infections were classified into respiratory, gastrointestinal, vector-borne, blood/sex-transmitted and mucocutaneous diseases, of which case numbers and incidences were calculated and the proportions were compared among subgroups. Results In total, 17,189 travelers diagnosed with 58 imported infectious diseases were reported from 2014 to 2018, with an overall incidence of 122.59 per million. Respiratory infection (7,351 cases, mainly influenza) and blood/sex-transmitted diseases (6,114 cases mainly Hepatitis B and HIV infection) were the most frequently diagnosed diseases, followed by vector-borne infections (3,128 cases, mainly dengue fever and malaria). The highest case number was from Asia and Europe, while the highest incidence rate was from Africa (296.00 per million). When specific diagnosis was compared, both the highest absolute case number and incidence were observed for influenza. An obvious seasonal pattern was observed for vector-borne diseases, with the annual epidemic spanning from July to November. The origin-destination matrices disclosed the movement of imported infection followed specific routes. Conclusions Our study provided a profile of infectious diseases among foreign travelers travelling to China and pinpointed the target regions, seasons and populations for prevention and control, to attain an informed control of imported infections in China.

Abstract Background Increasing number of travel-related infections were reported in China, but the spectrum, dynamics and disease burden of imported infections among foreign travelers remain vague. Methods We obtained the data on imported infections among foreign travelers from Custom Inbound Screening System (CISS) and the National Notifiable Infectious Disease Reporting System (NNIDRS). All the infections were classified into respiratory, gastrointestinal, vector-borne, blood/sex-transmitted and mucocutaneous diseases. The epidemiological characteristics and disease burden of imported infections among foreign travelers were investigated. Results In total, 17,189 travelers diagnosed with 58 imported infectious diseases were reported from 2014 to 2018, with an overall incidence rate of 122.59 per million. Respiratory infection (7,351 cases, mainly influenza) and Blood/sex-transmitted diseases (6,114 cases mainly Hepatitis B and HIV infection) were the most frequently diagnosed diseases, followed by vector-borne infections (3,128 cases, mainly dengue fever and malaria). The highest case number was imported from Asia and Europe, while the highest incidence rate was from Africa (296.0 per million). When specific diagnosis was compared, both the highest absolute case number and incidence rate were observed for influenza. An obvious seasonal pattern was observed for vector-borne diseases, with the epidemic spanning from July to November. The origin-destination matrices disclosed the movement of imported infection followed specific routes. Conclusions Our study gave a profile of infectious diseases among foreign travelers traveled into China and pinpointed the priority regions, seasons, populations for prevention and control.

BACKGROUND:Scrub typhus (ST) is a life-threatening infectious disease if appropriate treatment is unavailable. Large discrepancy of clinical severity of ST patients was reported among age groups, and the underlying risk factors for severe disease are unclear.METHODS:Clinical and epidemiological data of ST patients were collected in 55 surveillance hospitals located in Guangzhou City, China, from 2012 to 2018. Severe prognosis and related factors were determined and compared between pediatric and elderly patients.RESULTS:A total of 2,074 ST patients including 209 pediatric patients and 1,865 elderly patients were included, with a comparable disease severity rate of 11.0% (95% CI 7.1%-16.1%) and 10.3% (95% CI 9.0%-11.8%). Different frequencies of clinical characteristics including lymphadenopathy, skin rash, enlarged tonsils, etc. were observed between pediatric and elderly patients. Presence of peripheral edema and decreased hemoglobin were the most important predictors of severe illness in pediatric patients with adjusted ORs by 38.99 (9.96-152.67, p<0.001) and 13.22 (1.54-113.50, p = 0.019), respectively, while presence of dyspnea and increased total bilirubin were the potential determinants of severe disease in elderly patients with adjusted ORs by 11.69 (7.33-18.64, p<0.001) and 3.17 (1.97-5.11, p<0.001), respectively. Compared with pediatric patients, elderly patients were more likely to receive doxycycline (64.8% v.s 9.9%, p<0.001), while less likely to receive azithromycin therapy (5.0% v.s 41.1%, p<0.001).CONCLUSION:The disease severity rate is comparable between pediatric and elderly ST patients, while different clinical features and laboratory indicators were associated with development of severe complications for pediatric and elderly patients, which is helpful for diagnosis and progress assessment of disease for ST patients.

Human parechoviruses (HPeVs) are important causes of infection in children. However, without a comprehensive and persistent surveillance, the epidemiology and clinical features of HPeV infection remain ambiguous. We performed a hospital-based surveillance study among three groups of pediatric patients with acute respiratory infection (Group 1), acute diarrhea (Group 2), and hand, foot and mouth disease (Group 3) in Chongqing, China, from 2009 to 2015. Among 10,212 tested patients, 707 (6.92%) were positive for HPeV, with the positive rates differing significantly among three groups (Group 1, 3.43%; Group 2, 14.94%; Group 3, 3.55%; P < 0.001). The co-infection with other pathogens was detected in 75.2% (531/707) of HPeV-positive patients. Significant negative interaction between HPeV and Parainfluenza virus (PIV) ( P = 0.046, OR = 0.59, 95% CI = 0.34–0.98) and positive interactions between HPeV and Enterovirus (EV) ( P = 0.015, OR = 2.28, 95% CI = 1.23–4.73) were identified. Among 707 HPeV-positive patients, 592 (83.73%) were successfully sequenced, and 10 genotypes were identified, with HPeV1 ( n = 396), HPeV4 ( n = 86), and HPeV3 ( n = 46) as the most frequently seen. The proportion of genotypes differed among three groups ( P < 0.001), with HPeV1 and HPeV4 overrepresented in Group 2 and HPeV6 overrepresented in Group 3. The spatial patterns of HPeV genotypes disclosed more close clustering of the currently sequenced strains than those from other countries/regions, although they were indeed mixed. Three main genotypes (HPeV1, HPeV3, and HPeV4) had shown distinct seasonal peaks, highlighting a bi-annual cycle of all HpeV and two genotypes (HPeV 1 and HPeV 4) with peaks in odd-numbered years and with peaks in even-numbered years HPeV3. Significantly higher HPeV1 viral loads were associated with severe diarrhea in Group 2 ( P = 0.044), while associated with HPeV single infection than HPeV-EV coinfection among HFMD patients ( P = 0.001). It’s concluded that HPeV infection was correlated with wide clinical spectrum in pediatric patients with a high variety of genotypes determined. Still no clinical significance can be confirmed, which warranted more molecular surveillance in the future.

Abstract Background COVID-19 patients with long incubation period were reported in clinical practice and tracing of close contacts, but their epidemiological or clinical features remained vague. Methods We analyzed 11,425 COVID-19 cases reported between January–August, 2020 in China. The accelerated failure time model, Logistic and modified Poisson regression models were used to investigate the determinants of prolonged incubation period, as well as their association with clinical severity and transmissibility, respectively. Result Among local cases, 268 (10.2%) had a prolonged incubation period of > 14 days, which was more frequently seen among elderly patients, those residing in South China, with disease onset after Level I response measures administration, or being exposed in public places. Patients with prolonged incubation period had lower risk of severe illness (ORadjusted = 0.386, 95% CI: 0.203–0.677). A reduced transmissibility was observed for the primary patients with prolonged incubation period (50.4, 95% CI: 32.3–78.6%) than those with an incubation period of ≤14 days. Conclusions The study provides evidence supporting a prolonged incubation period that exceeded 2 weeks in over 10% for COVID-19. Longer monitoring periods than 14 days for quarantine or persons potentially exposed to SARS-CoV-2 should be justified in extreme cases, especially for those elderly.

Background COVID-19 has impacted populations around the world, with the fatality rate varying dramatically across countries. Selenium, as one of the important micronutrients implicated in viral infections, was suggested to play roles. Methods An ecological study was performed to assess the association between the COVID-19 related fatality and the selenium content both from crops and topsoil, in China. Results Totally, 14,045 COVID-19 cases were reported from 147 cities during 8 December 2019–13 December 2020 were included. Based on selenium content in crops, the case fatality rates (CFRs) gradually increased from 1.17% in non-selenium-deficient areas, to 1.28% in moderate-selenium-deficient areas, and further to 3.16% in severe-selenium-deficient areas ( P = 0.002). Based on selenium content in topsoil, the CFRs gradually increased from 0.76% in non-selenium-deficient areas, to 1.70% in moderate-selenium-deficient areas, and further to 1.85% in severe-selenium-deficient areas ( P < 0.001). The zero-inflated negative binomial regression model showed a significantly higher fatality risk in cities with severe-selenium-deficient selenium content in crops than non-selenium-deficient cities, with incidence rate ratio (IRR) of 3.88 (95% CIs: 1.21–12.52), which was further confirmed by regression fitting the association between CFR of COVID-19 and selenium content in topsoil, with the IRR of 2.38 (95% CIs: 1.14–4.98) for moderate-selenium-deficient cities and 3.06 (1.49–6.27) for severe-selenium-deficient cities. Conclusions Regional selenium deficiency might be related to an increased CFR of COVID-19. Future studies are needed to explore the associations between selenium status and disease outcome at individual-level.