Analysis of Factors Influencing the Clinical Severity of Omicron and Delta Variants.

The Omicron variant is the dominant strain circulating globally, and studies have shown that Omicron cases have milder symptoms than Delta cases. This study aimed to analyze the factors that affect the clinical severity of Omicron and Delta variants, evaluate and compare the effectiveness of COVID-19 vaccines with different technological platforms, and assess the vaccine effectiveness against different variants. We retrospectively collected the basic information of all local COVID-19 cases reported by Hunan Province to the National Notifiable Infectious Disease Reporting System from January 2021 to February 2023, including gender, age, clinical severity, and COVID-19 vaccination history. From 1 January 2021 to 28 February 2023, Hunan Province reported a total of 60,668 local COVID-19 cases, of which, 134 were infected with the Delta variant and 60,534 were infected with the Omicron variant. The results showed that infection with the Omicron variant (adjusted OR (aOR): 0.21, 95% CI: 0.14-0.31), getting vaccinated (booster immunization vs. unvaccinated aOR: 0.30, 95% CI: 0.23-0.39) and being female (aOR: 0.82, 95% CI: 0.79-0.85) were protective factors for pneumonia, while old age (≥60 years vs. <3 years aOR: 4.58, 95% CI: 3.36-6.22) was a risk factor for pneumonia. Being vaccinated (booster immunization vs. unvaccinated aOR: 0.11, 95% CI: 0.09-0.15) and female (aOR: 0.54, 95% CI: 0.50-0.59) were protective factors for severe cases, while older age (≥60 years vs. < 3 years aOR: 4.95, 95% CI: 1.83-13.39) was a risk factor for severe cases. The three types of vaccines had protective effects on both pneumonia and severe cases, and the protective effect on severe cases was better than that on pneumonia. The recombinant subunit vaccine booster immunization had the best protective effect on pneumonia and severe cases, with ORs of 0.29 (95% CI: 0.2-0.44) and 0.06 (95% CI: 0.02-0.17), respectively. The risk of pneumonia from Omicron variant infection was lower than that from Delta. Chinese-produced vaccines had protective effects on both pneumonia and severe cases, with recombinant subunit vaccines having the best protective effect on pneumonia and severe pneumonia cases. Booster immunization should be advocated in COVID-19 pandemic-related control and prevention policies, especially for the elderly, and booster immunization should be accelerated.

Transmission Dynamics and Epidemiological Characteristics of the SARS-CoV-2 Delta Variant - Hunan Province, China, 2021.

What is already known about this topic?: Little is known about the epidemiology, natural history, and transmission patterns of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant. Monitoring the evolution of viral fitness of SARS-CoV-2 in the host population is key for preparedness and response planning. What is added by this report?: We analyzed a successfully contained local outbreak of Delta that took place in Hunan, China, and provided estimates of time-to-key event periods, infectiousness over time, and risk factors for SARS-CoV-2 infection and transmission for a still poorly understood variant. What are the implications for public health practice?: Our findings simultaneously shed light on both the characteristics of the Delta variant, by identifying key age groups, risk factors, and transmission pathways, and planning a future response effort against SARS-CoV-2.

Contact pattern, current immune barrier, and pathogen virulence determines the optimal strategy of further vaccination.

Background: The current outbreak of novel coronavirus disease 2019 has caused a serious disease burden worldwide. Vaccines are an important factor to sustain the epidemic. Although with a relatively high-vaccination worldwide, the decay of vaccine efficacy and the arising of new variants lead us to the challenge of maintaining a sufficient immune barrier to protect the population. Method: A case-contact tracking data in Hunan, China, is used to estimate the contact pattern of cases for scenarios including school, workspace, etc, rather than ordinary susceptible population. Based on the estimated vaccine coverage and efficacy, a multi-group vaccinated-exposed-presymptomatic-symptomatic-asymptomatic-removed model (VEFIAR) with 8 age groups, with each partitioned into 4 vaccination status groups is developed. The optimal dose-wise vaccinating strategy is optimized based on the currently estimated immunity barrier of coverage and efficacy, using the greedy algorithm that minimizes the cumulative cases, population size of hospitalization and fatality respectively in a certain future interval. Parameters of Delta and Omicron variants are used respectively in the optimization. Results: The estimated contact matrices of cases showed a concentration on middle ages, and has compatible magnitudes compared to estimations from contact surveys in other studies. The VEFIAR model is numerically stable. The optimal controled vaccination strategy requires immediate vaccination on the un-vaccinated high-contact population of age 30-39 to reduce the cumulative cases, and is stable with different basic reproduction numbers ( R 0 ). As for minimizing hospitalization and fatality, the optimized strategy requires vaccination on the un-vaccinated of both aged 30-39 of high contact frequency and the vulnerable older. Conclusion: The objective of reducing transmission requires vaccination in age groups of the highest contact frequency, with more priority for un-vaccinated than un-fully or fully vaccinated. The objective of reducing total hospitalization and fatality requires not only to reduce transmission but also to protect the vulnerable older. The priority changes by vaccination progress. For any region, if the local contact pattern is available, then with the vaccination coverage, efficacy, and disease characteristics of relative risks in heterogeneous populations, the optimal dose-wise vaccinating process will be obtained and gives hints for decision-making.

A follow up study of cycle threshold values of SARS-CoV-2 in Hunan Province, China.

Since the epidemic of the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), many governments have used reverse transcription polymerase chain reaction (RT-PCR) to detect the virus. However, there are fewer measures of CT values information based on RT-PCR results, and the relationship between CT values and factors from consecutive tests is not clear enough. So in this study, we analyzed the connection between CT values and the factors based on cohort data from Delta variant of SARS-CoV-2 in Hunan Province. Previous studies have showed that the mean age of the cases was 33.34 years (±18.72 years), with a female predominance (55.03%, n = 71), and the greatest proportion of clinical symptoms were of the common type (60.47%, n = 78). There were statistical differences between the N and ORF1ab genes in the CT values for the cases. Based on the analysis of the association between CT values and the factors, the lowest CT values were obtained for the unvaccinated, older and clinically symptomatic group at 3-10 days, the maximum peak of viral load occurred. Therefore, it is recommended to use patient information to focus on older, clinically symptomatic, unvaccinated patients and to intervene promptly upon admission.

Integrated Rabies Surveillance - Hunan Province, China, 2020.

Introduction: The objective of this paper was to assess the epidemiology of rabies in Hunan Province, analyze the associated factors, understand the status of prevention and treatment after rabies exposure, evaluate the effectiveness of prevention and treatment, and provide a scientific basis for formulating effective prevention and control measures. Methods: The surveillance data of rabies in Hunan Province in 2020 were collected and analyzed by descriptive epidemiological method. Results: In 2020, a total of 59 cases of rabies were reported in Hunan Province, with an incidence rate of 0.09/100,000. Overall, 42 cases (71.19%) were due to animal bites and 43 cases (72.88%) were of grade III. The proportion of hand and combined injury of hand was the highest (40.68%). A total of 603,261 cases of rabies exposure were reported from the rabies post-exposure prophylaxis (PEP) clinic in Hunan Province. Dogs were the main animal causing injuries, accounting for 74.21%. Only 83,418 (13.84%) of the animals had a clear immune history, and a total of 11 dog attacks were reported in Hunan Province. The average immunity rate of dogs in the whole province was 30.98%. In 2020, 554 dogs were sampled in the whole province; 20 of them were positive for a positivity rate of 3.61%. Conclusions: Rabies in Hunan Province in 2020 had a relatively low prevalence. Failure to treat wounds, immunoglobulin injections, and vaccination after exposure were the main causes of rabies. Therefore, post-exposure management of rabies should be further strengthened to reduce the risk of rabies for high-risk populations.

The transfer of maternal antibodies and dynamics of maternal and natural infection-induced antibodies against coxsackievirus A16 in Chinese children 0-13 years of age: a longitudinal cohort study.

BACKGROUND: A major hand-foot-and-mouth disease (HFMD) pathogen, coxsackievirus A16 (CVA16), has predominated in several of the last 10 years and caused the largest number of HFMD outbreaks between 2011 and 2018 in China. We evaluated the efficacy of maternal anti-CVA16 antibody transfer via the placenta and explored the dynamics of maternal and natural infection-induced neutralizing antibodies in children. METHODS: Two population-based longitudinal cohorts in southern China were studied during 2013-2018. Participants were enrolled in autumn 2013, including 2475 children aged 1-9 years old and 1066 mother-neonate pairs, and followed for 3 years. Blood/cord samples were collected for CVA16-neutralizing antibody detection. The maternal antibody transfer efficacy, age-specific seroprevalence, geometric mean titre (GMT) and immune response kinetics were estimated. RESULTS: The average maternal antibody transfer ratio was 0.88 (95% CI 0.80-0.96). Transferred maternal antibody levels declined rapidly (half-life: 2.0 months, 95% CI 1.9-2.2 months). The GMT decayed below the positive threshold (8) by 1.5 months of age. Due to natural infections, it increased above 8 after 1.4 years and reached 32 by 5 years of age, thereafter dropping slightly. Although the average duration of maternal antibody-mediated protection was < 3 months, the duration extended to 6 months on average for mothers with titres ≥ 64. CONCLUSIONS: Anti-CVA16 maternal antibodies are efficiently transferred to neonates, but their levels decline quickly. Children aged 0-5 years are the main susceptible population and should be protected by CVA16 vaccination, with the optimal vaccination time between 1.5 months and 1 year of age.

Humoral responses after inactivated COVID-19 vaccination in individuals with and without prior SARS-CoV-2 infection: A prospective cohort study.

We evaluated and compared humoral immune responses after inactivated coronavirus disease 2019 (COVID-19) vaccination among naïve individuals, asymptomatically infected individuals, and recovered patients with varying severity. In this multicenter, prospective cohort study, blood samples from 666 participants were collected before and after 2 doses of inactivated COVID-19 vaccination. Among 392 severe acute respiratory syndrome coronavirus 2-naïve individuals, the seroconversion rate increased significantly from 51.8% (median antispike protein pan-immunoglobulins [S-Igs] titer: 0.8 U/ml) after the first dose to 96% (median S-Igs titer: 79.5 U/ml) after the second dose. Thirty-two percent of naïve individuals had detectable neutralizing antibodies (NAbs) against the original strain but all of them lost neutralizing activity against the Omicron variant. In 274 individuals with natural infection, humoral immunity was significantly improved after a single vaccine dose, with median S-Igs titers of 596.7, 1176, 1086.5, and 1828 U/ml for asymptomatic infections, mild cases, moderate cases, and severe/critical cases, respectively. NAb titers also improved significantly. However, the second dose did not substantially increase antibody levels. Although a booster dose is needed for those without infection, our findings indicate that recovered patients should receive only a single dose of the vaccine, regardless of the clinical severity, until there is sufficient evidence to confirm the benefits of a second dose.

Transmission heterogeneities, kinetics, and controllability of SARS-CoV-2.

A long-standing question in infectious disease dynamics concerns the role of transmission heterogeneities, which are driven by demography, behavior, and interventions. On the basis of detailed patient and contact-tracing data in Hunan, China, we find that 80% of secondary infections traced back to 15% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primary infections, which indicates substantial transmission heterogeneities. Transmission risk scales positively with the duration of exposure and the closeness of social interactions and is modulated by demographic and clinical factors. The lockdown period increases transmission risk in the family and households, whereas isolation and quarantine reduce risks across all types of contacts. The reconstructed infectiousness profile of a typical SARS-CoV-2 patient peaks just before symptom presentation. Modeling indicates that SARS-CoV-2 control requires the synergistic efforts of case isolation, contact quarantine, and population-level interventions because of the specific transmission kinetics of this virus.

Transmission heterogeneities, kinetics, and controllability of SARS-CoV-2.

A long-standing question in infectious disease dynamics concerns the role of transmission heterogeneities, driven by demography, behavior and interventions. Based on detailed patient and contact tracing data in Hunan, China we find 80% of secondary infections traced back to 15% of SARS-CoV-2 primary infections, indicating substantial transmission heterogeneities. Transmission risk scales positively with the duration of exposure and the closeness of social interactions and is modulated by demographic and clinical factors. The lockdown period increases transmission risk in the family and households, while isolation and quarantine reduce risks across all types of contacts. The reconstructed infectiousness profile of a typical SARS-CoV-2 patient peaks just before symptom presentation. Modeling indicates SARS-CoV-2 control requires the synergistic efforts of case isolation, contact quarantine, and population-level interventions, owing to the specific transmission kinetics of this virus. ONE SENTENCE SUMMARY: Public health measures to control SARS-CoV-2 could be designed to block the specific transmission characteristics of the virus.

Age profile of susceptibility, mixing, and social distancing shape the dynamics of the novel coronavirus disease 2019 outbreak in China.

Strict interventions were successful to control the novel coronavirus (COVID-19) outbreak in China. As transmission intensifies in other countries, the interplay between age, contact patterns, social distancing, susceptibility to infection and disease, and COVID-19 dynamics remains unclear. To answer these questions, we analyze contact surveys data for Wuhan and Shanghai before and during the outbreak and contact tracing information from Hunan Province. Daily contacts were reduced 7-9 fold during the COVID-19 social distancing period, with most interactions restricted to the household. Children 0-14 years were 59% (95% CI 7-82%) less susceptible than individuals 65 years and over. A transmission model calibrated against these data indicates that social distancing alone, as implemented in China during the outbreak, is sufficient to control COVID-19. While proactive school closures cannot interrupt transmission on their own, they reduce peak incidence by half and delay the epidemic. These findings can help guide global intervention policies.

Changes in contact patterns shape the dynamics of the COVID-19 outbreak in China.

Intense nonpharmaceutical interventions were put in place in China to stop transmission of the novel coronavirus disease 2019 (COVID-19). As transmission intensifies in other countries, the interplay between age, contact patterns, social distancing, susceptibility to infection, and COVID-19 dynamics remains unclear. To answer these questions, we analyze contact survey data for Wuhan and Shanghai before and during the outbreak and contact-tracing information from Hunan province. Daily contacts were reduced seven- to eightfold during the COVID-19 social distancing period, with most interactions restricted to the household. We find that children 0 to 14 years of age are less susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than adults 15 to 64 years of age (odds ratio 0.34, 95% confidence interval 0.24 to 0.49), whereas individuals more than 65 years of age are more susceptible to infection (odds ratio 1.47, 95% confidence interval 1.12 to 1.92). Based on these data, we built a transmission model to study the impact of social distancing and school closure on transmission. We find that social distancing alone, as implemented in China during the outbreak, is sufficient to control COVID-19. Although proactive school closures cannot interrupt transmission on their own, they can reduce peak incidence by 40 to 60% and delay the epidemic.

Emerging Enteroviruses Causing Hand, Foot and Mouth Disease, China, 2010-2016.

Coxsackievirus A6 emerged as one of the predominant causative agents of hand, foot and mouth disease epidemics in many provinces of China in 2013 and 2015. This virus strain accounted for 25.9% of mild and 15.2% of severe cases in 2013 and 25.8% of mild and 16.9% of severe cases in 2015.

Outcomes following severe hand foot and mouth disease: A systematic review and meta-analysis.

BACKGROUND: Hand, foot and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) is associated with acute neurological disease in children. This study aimed to estimate the burden of long-term sequelae and death following severe HFMD. METHODS: This systematic review and meta-analysis pooled all reports from English and Chinese databases including MEDLINE and Wangfang on outbreaks of clinically diagnosed HFMD and/or laboratory-confirmed EV-A71 with at least 7 days' follow-up published between 1st January 1966 and 19th October 2015. Two independent reviewers assessed the literature. We used a random effects meta-analysis to estimate cumulative incidence of neurological sequelae or death. Studies were assessed for methodological and reporting quality. PROSPERO registration number: 10.15124/CRD42015021981. FINDINGS: 43 studies were included in the review, and 599 children from 9 studies were included in the primary analysis. Estimated cumulative incidence of death or neurological sequelae at maximum follow up was 19.8% (95% CI:10.2%, 31.3%). Heterogeneity (Iˆ2) was 88.57%, partly accounted for by year of data collection and reporting quality of studies. Incidence by acute disease severity was 0.00% (0.00, 0.00) for grade IIa; 17.0% (7.9, 28.2) for grade IIb/III; 81.6% (65.1, 94.5) for grade IV (p = 0.00) disease. CONCLUSIONS: HFMD with neurological involvement is associated with a substantial burden of long-term neurological sequelae. Grade of acute disease severity was a strong predictor of outcome. Strengths of this study include its bilingual approach and clinical applicability. Future prospective and interventional studies must use rigorous methodology to assess long-term outcomes in survivors. FUNDING: There was no specific funding for this study. See below for researcher funding.