Risk Factors Associated with the Spatiotemporal Spread of the SARS-CoV-2 Omicron BA.2 Variant - Shanghai Municipality, China, 2022.

What is already known about this topic?: Previous studies have explored the spatial transmission patterns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have assessed the associated risk factors. However, none of these studies have quantitatively described the spatiotemporal transmission patterns and risk factors for Omicron BA.2 at the micro (within-city) scale. What is added by this report?: This study highlights the heterogeneous spread of the 2022 Omicron BA.2 epidemic in Shanghai, and identifies associations between different metrics of spatial spread at the subdistrict level and demographic and socioeconomic characteristics of the population, human mobility patterns, and adopted interventions. What are the implications for public health practice?: Disentangling different risk factors might contribute to a deeper understanding of the transmission dynamics and ecology of coronavirus disease 2019 and an effective design of monitoring and management strategies.

Estimating Changes in Contact Patterns in China Over the First Year of the COVID-19 Pandemic: Implications for SARS-CoV-2 Spread - Four Cities, China, 2020.

Introduction: Previous studies have demonstrated significant changes in social contacts during the first-wave coronavirus disease 2019 (COVID-19) in Chinese mainland. The purpose of this study was to quantify the time-varying contact patterns by age in Chinese mainland in 2020 and evaluate their impact on the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: Diary-based contact surveys were performed for four periods: baseline (prior to 2020), outbreak (February 2020), post-lockdown (March-May 2020), and post-epidemic (September-November 2020). We built a Susceptible-Infected-Recovered (SIR) model to evaluate the effect of reducing contacts on transmission. Results: During the post-epidemic period, daily contacts resumed to 26.7%, 14.8%, 46.8%, and 44.2% of the pre-COVID levels in Wuhan, Shanghai, Shenzhen, and Changsha, respectively. This suggests a moderate risk of resurgence in Changsha, Shenzhen, and Wuhan, and a low risk in Shanghai. School closure alone was not enough to interrupt transmission of SARS-CoV-2 Omicron BA.5, but with the addition of a 75% reduction of contacts at the workplace, it could lead to a 16.8% reduction of the attack rate. To control an outbreak, concerted strategies that target schools, workplaces, and community contacts are needed. Discussion: Monitoring contact patterns by age is key to quantifying the risk of COVID-19 outbreaks and evaluating the impact of intervention strategies.

Modeling the Prediction on the Efficacy of a Homologous Third Dose of CoronaVac Against SARS-CoV-2 Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5 - China, 2020-2021.

What is already known about this topic?: Previous studies have reported vaccine efficacy or effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants for several vaccine platforms. However, there are currently few data on estimates of inactivated platform coronavirus disease 2019 (COVID-19) vaccines, especially against the globally dominant subvariant - Omicron BA.5. What is added by this report?: The study predicts vaccine efficacy against four Omicron subvariants - Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5 - after vaccination with a homologous third dose of CoronaVac across clinical endpoints and age groups. What are the implications for public health practice?: The results suggest that CoronaVac-elicited immunity may not provide adequate protection against Omicron subvariants after the homologous third dose, and a heterologous booster and Omicron-specific vaccination may be alternative strategies.

Analysis of COVID-19 Guideline Quality and Change of Recommendations: A Systematic Review

Background Hundreds of coronavirus disease 2019 (COVID-19) clinical practice guidelines (CPGs) and expert consensus statements have been developed and published since the outbreak of the epidemic. However, these CPGs are of widely variable quality. So, this review is aimed at systematically evaluating the methodological and reporting qualities of COVID-19 CPGs, exploring factors that may influence their quality, and analyzing the change of recommendations in CPGs with evidence published. Methods We searched five electronic databases and five websites from 1 January to 31 December 2020 to retrieve all COVID-19 CPGs. The assessment of the methodological and reporting qualities of CPGs was performed using the AGREE II instrument and RIGHT checklist. Recommendations and evidence used to make recommendations in the CPGs regarding some treatments for COVID-19 (remdesivir, glucocorticoids, hydroxychloroquine/chloroquine, interferon, and lopinavir-ritonavir) were also systematically assessed. And the statistical inference was performed to identify factors associated with the quality of CPGs. Results We included a total of 92 COVID-19 CPGs developed by 19 countries. Overall, the RIGHT checklist reporting rate of COVID-19 CPGs was 33.0%, and the AGREE II domain score was 30.4%. The overall methodological and reporting qualities of COVID-19 CPGs gradually improved during the year 2020. Factors associated with high methodological and reporting qualities included the evidence-based development process, management of conflicts of interest, and use of established rating systems to assess the quality of evidence and strength of recommendations. The recommendations of only seven (7.6%) CPGs were informed by a systematic review of evidence, and these seven CPGs have relatively high methodological and reporting qualities, in which six of them fully meet the Institute of Medicine (IOM) criteria of guidelines. Besides, a rapid advice CPG developed by the World Health Organization (WHO) of the seven CPGs got the highest overall scores in methodological (72.8%) and reporting qualities (83.8%). Many CPGs covered the same clinical questions (it refers to the clinical questions on the effectiveness of treatments of remdesivir, glucocorticoids, hydroxychloroquine/chloroquine, interferon, and lopinavir-ritonavir in COVID-19 patients) and were published by different countries or organizations. Although randomized controlled trials and systematic reviews on the effectiveness of treatments of remdesivir, glucocorticoids, hydroxychloroquine/chloroquine, interferon, and lopinavir-ritonavir for patients with COVID-19 have been published, the recommendations on those treatments still varied greatly across COVID-19 CPGs published in different countries or regions, which may suggest that the CPGs do not make sufficient use of the latest evidence. Conclusions Both the methodological and reporting qualities of COVID-19 CPGs increased over time, but there is still room for further improvement. The lack of effective use of available evidence and management of conflicts of interest were the main reasons for the low quality of the CPGs. The use of formal rating systems for the quality of evidence and strength of recommendations may help to improve the quality of CPGs in the context of the COVID-19 pandemic. During the pandemic, we suggest developing a living guideline of which recommendations are supported by a systematic review for it can facilitate the timely translation of the latest research findings to clinical practice. We also suggest that CPG developers should register the guidelines in a registration platform at the beginning for it can reduce duplication development of guidelines on the same clinical question, increase the transparency of the development process, and promote cooperation among guideline developers all over the world. Since the International Practice Guideline Registry Platform has been created, developers could register guidelines prospectively and internationally on this platform.

Estimation of disease burden and clinical severity of COVID-19 caused by Omicron BA.2 in Shanghai, February-June 2022.

An outbreak of COVID-19 caused by the SARS-CoV-2 Omicron BA.2 sublineage occurred in Shanghai, China from February 26 to June 30, 2022. We use official reported data retrieved from Shanghai municipal Health Commissions to estimate the incidence of infections, severe/critical infections, and deaths to assess the disease burden. By adjusting for right censoring and RT-PCR sensitivity, we provide estimates of clinical severity, including the infection fatality ratio, symptomatic case fatality ratio, and risk of developing severe/critical disease upon infection. The overall infection rate, severe/critical infection rate, and mortality rate were 2.74 (95% CI: 2.73-2.74) per 100 individuals, 6.34 (95% CI: 6.02-6.66) per 100,000 individuals and 2.42 (95% CI: 2.23-2.62) per 100,000 individuals, respectively. The severe/critical infection rate and mortality rate increased with age, noted in individuals aged 80 years or older. The overall fatality ratio and risk of developing severe/critical disease upon infection were 0.09% (95% CI: 0.09-0.10%) and 0.27% (95% CI: 0.24-0.29%), respectively. Having received at least one vaccine dose led to a 10-fold reduction in the risk of death for infected individuals aged 80 years or older. Under the repeated population-based screenings and strict intervention policies implemented in Shanghai, our results found a lower disease burden and mortality of the outbreak compared to other settings and countries, showing the impact of the successful outbreak containment in Shanghai. The estimated low clinical severity of this Omicron BA.2 epidemic in Shanghai highlight the key contribution of vaccination and availability of hospital beds to reduce the risk of death.

Epidemiological characteristics and transmission dynamics of the outbreak caused by the SARS-CoV-2 Omicron variant in Shanghai, China: A descriptive study.

Background: In early March 2022, a major outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant spread rapidly throughout Shanghai, China. Here we aimed to provide a description of the epidemiological characteristics and spatiotemporal transmission dynamics of the Omicron outbreak under the population-based screening and lockdown policies implemented in Shanghai. Methods: We extracted individual information on SARS-CoV-2 infections reported between January 1 and May 31, 2022, and on the timeline of the adopted non-pharmaceutical interventions. The epidemic was divided into three phases: i) sporadic infections (January 1-February 28), ii) local transmission (March 1-March 31), and iii) city-wide lockdown (April 1 to May 31). We described the epidemic spread during these three phases and the subdistrict-level spatiotemporal distribution of the infections. To evaluate the impact on the transmission of SARS-CoV-2 of the adopted targeted interventions in Phase 2 and city-wide lockdown in Phase 3, we estimated the dynamics of the net reproduction number (Rt ). Findings: A surge in imported infections in Phase 1 triggered cryptic local transmission of the Omicron variant in early March, resulting in the largest outbreak in mainland China since the original wave. A total of 626,000 SARS-CoV-2 infections were reported in 99.5% (215/216) of the subdistricts of Shanghai until the end of May. The spatial distribution of the infections was highly heterogeneous, with 37% of the subdistricts accounting for 80% of all infections. A clear trend from the city center towards adjacent suburban and rural areas was observed, with a progressive slowdown of the epidemic spread (from 463 to 244 meters/day) prior to the citywide lockdown. During Phase 2, Rt remained well above 1 despite the implementation of multiple targeted interventions. The citywide lockdown imposed on April 1 led to a marked decrease in transmission, bringing Rt below the epidemic threshold in the entire city on April 14 and ultimately leading to containment of the outbreak. Interpretation: Our results highlight the risk of widespread outbreaks in mainland China, particularly under the heightened pressure of imported infections. The targeted interventions adopted in March 2022 were not capable of halting transmission, and the implementation of a strict, prolonged city-wide lockdown was needed to successfully contain the outbreak, highlighting the challenges for containing Omicron outbreaks. Funding: Key Program of the National Natural Science Foundation of China (82130093); Shanghai Rising-Star Program (22QA1402300).

Detection of SARS-CoV-2 Specific Antibodies in Saliva Samples.

Molecular assays on nasopharyngeal swabs act as a confirmatory test in coronavirus disease (COVID-19) diagnosis. However, the technical requirements of nasopharyngeal sampling and molecular assays limit the testing capabilities. Recent studies suggest the use of saliva for the COVID-19 diagnostic test. In this study, 44 patients diagnosed with COVID-19 in The Third People's Hospital of Shenzhen were enrolled. Saliva and serum specimens were obtained at different time points and the immunoglobulins against SARS-CoV-2 were measured. The results showed that saliva IgA presented a higher COI value than IgG and IgM. In matched saliva and serum samples, all saliva samples presented lower IgG levels than serum samples, and only one saliva sample presented a higher IgM level. The conversion rates of saliva IgA and the detection of viral nucleic acids were analyzed in the first and second weeks after hospitalization. The positive rates increased when combining saliva IgA and viral nucleic acid detection. In conclusion, our results provide evidence that saliva IgA could serve as a useful index for the early diagnosis of COVID-19.

Assessing the transition of COVID-19 burden towards the young population while vaccines are rolled out in China.

SARS-CoV-2 infection causes most cases of severe illness and fatality in older age groups. Over 92% of the Chinese population aged ≥12 years has been fully vaccinated against COVID-19 (albeit with vaccines developed against historical lineages). At the end of October 2021, the vaccination programme has been extended to children aged 3-11 years. Here, we aim to assess whether, in this vaccination landscape, the importation of Delta variant infections could shift COVID-19 burden from adults to children. We developed an age-structured susceptible-infectious-removed model of SARS-CoV-2 transmission to simulate epidemics triggered by the importation of Delta variant infections and project the age-specific incidence of SARS-CoV-2 infections, cases, hospitalizations, intensive care unit admissions, and deaths. In the context of the vaccination programme targeting individuals aged ≥12 years, and in the absence of non-pharmaceutical interventions, the importation of Delta variant infections could have led to widespread transmission and substantial disease burden in mainland China, even with vaccination coverage as high as 89% across the eligible age groups. Extending the vaccination roll-out to include children aged 3-11 years (as it was the case since the end of October 2021) is estimated to dramatically decrease the burden of symptomatic infections and hospitalizations within this age group (39% and 68%, respectively, when considering a vaccination coverage of 87%), but would have a low impact on protecting infants. Our findings highlight the importance of including children among the target population and the need to strengthen vaccination efforts by increasing vaccine effectiveness.

Risk of COVID-19 Transmission Aboard Aircraft: An Epidemiological Analysis Based on the National Health Information Platform.

OBJECTIVES: This study aims to investigate the risk of COVID-19 transmission on aircraft. METHODS: We obtained data on all international flights to Lanzhou, China, from June 1, 2020, to August 1, 2020, through the Gansu Province National Health Information Platform and the official website of the Gansu Provincial Center for Disease Control and Prevention. We then performed the statistical analysis. RESULTS: Three international flights arrived in Lanzhou. The flights had a total of 700 passengers, of whom 405 (57.9%) were male, and 80 (11.4%) were children under the age of 14 years. Twenty-seven (3.9%) passengers were confirmed to have COVID-19. Confirmed patients were primarily male (17, 65.4%) with a median age of 27.0 years. Most confirmed cases were seated in the middle rows of economy class or near public facility areas such as restrooms and galleys. The prevalence of COVID-19 did not differ between passengers sitting in the window, aisle, or middle seats. However, compared with passengers sitting in the same row up to 2 rows behind a confirmed case, passengers seated in the 2 rows in front of a confirmed case were at a slightly higher risk of being infected. CONCLUSIONS: COVID-19 may be transmitted during a passenger flight, although there is still no direct evidence.

Investigating vaccine-induced immunity and its effect in mitigating SARS-CoV-2 epidemics in China.

BACKGROUND: To allow a return to a pre-COVID-19 lifestyle, virtually every country has initiated a vaccination program to mitigate severe disease burden and control transmission. However, it remains to be seen whether herd immunity will be within reach of these programs. METHODS: We developed a compartmental model of SARS-CoV-2 transmission for China, a population with low prior immunity from natural infection. Two vaccination programs were tested and model-based estimates of the immunity level in the population were provided. RESULTS: We found that it is unlikely to reach herd immunity for the Delta variant given the relatively low efficacy of the vaccines used in China throughout 2021 and the lack of prior natural immunity. We estimated that, assuming a vaccine efficacy of 90% against the infection, vaccine-induced herd immunity would require a coverage of 93% or higher of the Chinese population. However, even when vaccine-induced herd immunity is not reached, we estimated that vaccination programs can reduce SARS-CoV-2 infections by 50-62% in case of an all-or-nothing vaccine model and an epidemic starts to unfold on December 1, 2021. CONCLUSIONS: Efforts should be taken to increase population's confidence and willingness to be vaccinated and to develop highly efficacious vaccines for a wide age range.

Model-based evaluation of alternative reactive class closure strategies against COVID-19.

There are contrasting results concerning the effect of reactive school closure on SARS-CoV-2 transmission. To shed light on this controversy, we developed a data-driven computational model of SARS-CoV-2 transmission. We found that by reactively closing classes based on syndromic surveillance, SARS-CoV-2 infections are reduced by no more than 17.3% (95%CI: 8.0-26.8%), due to the low probability of timely identification of infections in the young population. We thus investigated an alternative triggering mechanism based on repeated screening of students using antigen tests. Depending on the contribution of schools to transmission, this strategy can greatly reduce COVID-19 burden even when school contribution to transmission and immunity in the population is low. Moving forward, the adoption of antigen-based screenings in schools could be instrumental to limit COVID-19 burden while vaccines continue to be rolled out.

Social contact patterns and implications for infectious disease transmission - a systematic review and meta-analysis of contact surveys.

Background: Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focused on high-income settings. Methods: Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys, we explored how contact characteristics (number, location, duration, and whether physical) vary across income settings. Results: Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, with low-income settings characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income strata on the frequency, duration, and type of contacts individuals made. Conclusions: These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens and the effectiveness of different non-pharmaceutical interventions. Funding: This work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1).

Infectious diseases, particularly those caused by airborne pathogens like SARS-CoV-2, spread by social contact, and understanding how people mix is critical in controlling outbreaks. To explore these patterns, researchers typically carry out large contact surveys. Participants are asked for personal information (such as gender, age and occupation), as well as details of recent social contacts, usually those that happened in the last 24 hours. This information includes, the age and gender of the contact, where the interaction happened, how long it lasted, and whether it involved physical touch. These kinds of surveys help scientists to predict how infectious diseases might spread. But there is a problem: most of the data come from high-income countries, and there is evidence to suggest that social contact patterns differ between places. Therefore, data from these countries might not be useful for predicting how infections spread in lower-income regions. Here, Mousa et al. have collected and combined data from 27 contact surveys carried out before the COVID-19 pandemic to see how baseline social interactions vary between high- and lower-income settings. The comparison revealed that, in higher-income countries, the number of daily contacts people made decreased with age. But, in lower-income countries, younger and older individuals made similar numbers of contacts and mixed with all age groups. In higher-income countries, more contacts happened at work or school, while in low-income settings, more interactions happened at home and people were also more likely to live in larger, intergenerational households. Mousa et al. also found that gender affected how long contacts lasted and whether they involved physical contact, both of which are key risk factors for transmitting airborne pathogens. These findings can help researchers to predict how infectious diseases might spread in different settings. They can also be used to assess how effective non-medical restrictions, like shielding of the elderly and workplace closures, will be at reducing transmissions in different parts of the world.

Guidelines on the treatment with integrated traditional Chinese medicine and western medicine for severe coronavirus disease 2019.

Severe Coronavirus Disease 2019 (COVID-19) is characterized by numerous complications, complex disease, and high mortality, making its treatment a top priority in the treatment of COVID-19. Integrated traditional Chinese medicine (TCM) and western medicine played an important role in the prevention, treatment, and rehabilitation of COVID-19 during the epidemic. However, currently there are no evidence-based guidelines for the integrated treatment of severe COVID-19 with TCM and western medicine. Therefore, it is important to develop an evidence-based guideline on the treatment of severe COVID-19 with integrated TCM and western medicine, in order to provide clinical guidance and decision basis for healthcare professionals, public health personnel, and scientific researchers involved in the diagnosis, treatment, and care of COVID-19 patients. We developed and completed the guideline by referring to the standardization process of the "WHO handbook for guideline development", the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT).

Time-varying optimization of COVID-19 vaccine prioritization in the context of limited vaccination capacity.

Dynamically adapting the allocation of COVID-19 vaccines to the evolving epidemiological situation could be key to reduce COVID-19 burden. Here we developed a data-driven mechanistic model of SARS-CoV-2 transmission to explore optimal vaccine prioritization strategies in China. We found that a time-varying vaccination program (i.e., allocating vaccines to different target groups as the epidemic evolves) can be highly beneficial as it is capable of simultaneously achieving different objectives (e.g., minimizing the number of deaths and of infections). Our findings suggest that boosting the vaccination capacity up to 2.5 million first doses per day (0.17% rollout speed) or higher could greatly reduce COVID-19 burden, should a new wave start to unfold in China with reproduction number ≤1.5. The highest priority categories are consistent under a broad range of assumptions. Finally, a high vaccination capacity in the early phase of the vaccination campaign is key to achieve large gains of strategic prioritizations.

Despite vaccination, China needs non-pharmaceutical interventions to prevent widespread outbreaks of COVID-19 in 2021.

COVID-19 vaccination is being conducted in over 200 countries and regions to control SARS-CoV-2 transmission and return to a pre-pandemic lifestyle. However, understanding when non-pharmaceutical interventions (NPIs) can be lifted as immunity builds up remains a key question for policy makers. To address this, we built a data-driven model of SARS-CoV-2 transmission for China. We estimated that, to prevent the escalation of local outbreaks to widespread epidemics, stringent NPIs need to remain in place at least one year after the start of vaccination. Should NPIs alone be capable of keeping the reproduction number (Rt) around 1.3, the synergetic effect of NPIs and vaccination could reduce the COVID-19 burden by up to 99% and bring Rt below the epidemic threshold in about 9 months. Maintaining strict NPIs throughout 2021 is of paramount importance to reduce COVID-19 burden while vaccines are distributed to the population, especially in large populations with little natural immunity.

The impact of relaxing interventions on human contact patterns and SARS-CoV-2 transmission in China.

Nonpharmaceutical interventions to control SARS-CoV-2 spread have been implemented with different intensity, timing, and impact on transmission. As a result, post-lockdown COVID-19 dynamics are heterogeneous and difficult to interpret. We describe a set of contact surveys performed in four Chinese cities (Wuhan, Shanghai, Shenzhen, and Changsha) during the pre-pandemic, lockdown and post-lockdown periods to quantify changes in contact patterns. In the post-lockdown period, the mean number of contacts increased by 5 to 17% as compared to the lockdown period. However, it remains three to seven times lower than its pre-pandemic level sufficient to control SARS-CoV-2 transmission. We find that the impact of school interventions depends nonlinearly on the intensity of other activities. When most community activities are halted, school closure leads to a 77% decrease in the reproduction number; in contrast, when social mixing outside of schools is at pre-pandemic level, school closure leads to a 5% reduction in transmission.

The impact of relaxing interventions on human contact patterns and SARS-CoV-2 transmission in China.

Non-pharmaceutical interventions to control COVID-19 spread have been implemented in several countries with different intensity, timing, and impact on transmission. As a result, post-lockdown COVID-19 dynamics are heterogenous and difficult to interpret. Here we describe a set of contact surveys performed in four Chinese cities (Wuhan, Shanghai, Shenzhen, and Changsha) during the pre-pandemic, lockdown, and post-lockdown period to quantify the transmission impact of relaxing interventions via changes in age-specific contact patterns. We estimate that the mean number of contacts increased 5%-17% since the end of the lockdown but are still 3-7 times lower than their pre-pandemic levels. We find that post-lockdown contact patterns in China are still sufficiently low to keep SARS-CoV-2 transmission under control. We also find that the impact of school interventions depends non-linearly on the share of other activities being resumed. When most community activities are halted, school closure leads to a 77% decrease in the reproductive number; in contrast, when social mixing outside of schools is at pre-pandemic level, school closure leads to a 5% reduction in transmission. Moving forward, to control COVID-19 spread without resorting to a lockdown, it will be key to dose relaxation in social mixing in the community and strengthen targeted interventions.

Case fatality risk of the first pandemic wave of novel coronavirus disease 2019 (COVID-19) in China

OBJECTIVE: To assess the case fatality risk (CFR) of COVID-19 in mainland China, stratified by region and clinical category, and estimate key time-to-event intervals. METHODS: We collected individual information and aggregated data on COVID-19 cases from publicly available official sources from December 29, 2019 to April 17, 2020. We accounted for right-censoring to estimate the CFR and explored the risk factors for mortality. We fitted Weibull, gamma, and lognormal distributions to time-to-event data using maximum-likelihood estimation. RESULTS: We analyzed 82,719 laboratory-confirmed cases reported in mainland China, including 4,632 deaths, and 77,029 discharges. The estimated CFR was 5.65% (95%CI: 5.50%-5.81%) nationally, with highest estimate in Wuhan (7.71%), and lowest in provinces outside Hubei (0.86%). The fatality risk among critical patients was 3.6 times that of all patients, and 0.8-10.3 fold higher than that of mild-to-severe patients. Older age (OR 1.14 per year;95%CI: 1.11-1.16), and being male (OR 1.83;95%CI: 1.10-3.04) were risk factors for mortality. The time from symptom onset to first healthcare consultation, time from symptom onset to laboratory confirmation, and time from symptom onset to hospitalization were consistently longer for deceased patients than for those who recovered. CONCLUSIONS: Our CFR estimates based on laboratory-confirmed cases ascertained in mainland China suggest that COVID-19 is more severe than the 2009 H1N1 influenza pandemic in hospitalized patients, particularly in Wuhan. Our study provides a comprehensive picture of the severity of the first wave of the pandemic in China. Our estimates can help inform models and the global response to COVID-19.

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.

Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension.

The dysfunction of the renin-angiotensin system (RAS) has been observed in coronavirus infection disease (COVID-19) patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs), are associated with clinical outcomes remains unknown. COVID-19 patients with hypertension were enrolled to evaluate the effect of RAS inhibitors. We observed that patients receiving ACEI or ARB therapy had a lower rate of severe diseases and a trend toward a lower level of IL-6 in peripheral blood. In addition, ACEI or ARB therapy increased CD3 and CD8 T cell counts in peripheral blood and decreased the peak viral load compared to other antihypertensive drugs. This evidence supports the benefit of using ACEIs or ARBs to potentially contribute to the improvement of clinical outcomes of COVID-19 patients with hypertension.