Interruption of influenza transmission under public health emergency response based on real-world data, Beijing. (preprint)

Background: To estimate effect of COVID-19 control measures taken to mitigate community transmission in many regions, we analyzed data based on influenza surveillance system in Beijing from week 27th, 2014 to week 26th, 2020. Methods. We collected weekly number of influenza-like illness (ILI), weekly positive proportion of ILI and weekly ILI proportion in outpatients and the date of COVID-19 measures. We compared influenza activity indicators of influenza season 2019/2020 with preceding five seasons and built two ARIMAX models to estimate the effective of COVID-19 measures. Results. Compared with preceding five influenza seasons, ILIs, positive proportion of ILI, and duration of influenza epidemic period decreased from 13% to 54%, especially, the number of weeks from the peak to the end of influenza epidemic period, decreased from 12 to one. After natural decline considered, weekly ILIs decreased by 48.6% and weekly positive proportion dropped 15% in the second week after emergency response declared, and finally COVID-19 measures reduced 83%. Conclusions. We conclude public health emergency response can interrupt the transmission of influenza and other respiratory infectious diseases markedly. Keyword. COVID-19 control measures; influenza; ARIMAX

SARS-CoV-2 containment was achievable during the early stage of the pandemic: a retrospective modelling study of the Xinfadi outbreak in Beijing (preprint)

Prior to the emergence of the Omicron variant, many cities in China had been able to maintain a "Zero-COVID" policy. They were able to achieve this without blanket city-wide lockdown and through widespread testing and an extensive set of nonpharmaceutical interventions (NPIs), such as mask wearing, contact tracing, and social distancing. We wanted to examine the effectiveness of such a policy in containing SARS-CoV-2 in the early stage of the pandemic. Therefore, we developed a fully stochastic, spatially structured, agent-based model of SARS-CoV-2 ancestral strain and reconstructed the Beijing Xinfadi outbreak through computational simulations. We found that screening for symptoms and among high-risk populations served as methods to discover cryptic community transmission in the early stage of the outbreak. Effective contact tracing could greatly reduce transmission. Targeted community lockdown and temporal mobility restriction could slow down the spatial spread of the virus, with much less of the population being affected. Population-wide mass testing could further improve the speed at which the outbreak is contained. Our analysis suggests that the containment of SARS-CoV-2 ancestral strains was certainly possible. Outbreak suppression and containment at the beginning of the pandemic, before the virus had the opportunity to undergo extensive adaptive evolution with increasing fitness in the human population, could be much more cost-effective in averting the overall pandemic disease burden and socioeconomic cost.

Assessing the feasibility of sustaining a 'Zero-COVID' policy in China in the era of highly transmissible variants (preprint)

We developed a spatially structured, fully stochastic, individual-based SARS-CoV-2 transmission model to evaluate the feasibility of sustaining a 'Zero-COVID' policy in mainland China in light of currently dominant Omicron variants, China's current immunization level, and non-pharmaceutical intervention (NPI) strategies. We found that due to high transmissibility, neither Omicron BA.1 or BA.2 sublineages could be contained by China's Pre-Omicron non-pharmaceutical intervention strategies which were successful at sustaining the 'Zero-COVID' policy until March 2022. However, increased intervention intensity, such as enhanced population mobility restrictions and multi-round mass testing, could lead to containment success without the necessity of population-wide lockdown. As China's current vaccination has yet to reach high coverage in older populations, non-pharmaceutical interventions remain essential tools to maintain low levels of infection while building protective population immunity, ensuring a smooth transition out of the pandemic phase, and minimizing the overall disease burden and societal costs.

An immunocompetent 169-day prolonged SARS-CoV-2 shedding patient with high neutralizing antibody (preprint)

Information with prolonged SARS-CoV-2 shedding among immunocompetent patients is limited. We describe a twice repositive 169-day prolonged SARS-CoV-2 shedding in an immunocompetent patient and explore potential factors from clinical, immunological and genomic perspectives. We found that continuous viral replication and infectivity could exist in an immunocompetent COVID-19 patient with high neutralizing antibody.

A Population-Based Seroprevalence Survey of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Beijing, China (preprint)

BACKGOUND The spread of Coronavirus Disease 2019 (COVID-19) had been substantially controlled in China. As the capital of China, Beijing took a series of strict containment measures during the past several months. However, the seroprevalence of COVID-19 in Beijing has not been evaluated.METHODSDuring April 15-18, 2020, residents in Beijing were enrolled using a multi-stage cluster random sampling technique in four districts with top COVID-19 incidence and one district without case reported. Communities and households in each district were randomly selected based on probability proportional to size. Blood samples were collected and antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were tested by two kinds of colloidal gold kits. All colloidal gold positive serums and 20 randomly selected negative serums were then tested by Micro-neutralization assay. A likelihood ratio test was used to estimate 95% confidence intervals of seroprevalence with the Clopper-Pearson exact method.RESULTSA total of 2,184 residents participated in this survey, among which 13 were tested positive by colloidal gold tests. Of those who tested positive, 8 were IgM positive, 3 were IgG positive, 1 was total antibody positive, 1 was both IgM and total antibody positive. Among the 13 seropositive samples and 20 randomly selected seronegative samples, no positive sample was detected by micro-neutralization assay. The seroprevalence of COVID-19 in Beijing was estimated no higher than 0.17%.CONCLUSIONSThe seroprevalence of COVID-19 was low in April suggests that the comprehensive control measures to prevent and control further spread in Beijing was effective. However, the majority of the residents in Beijing were still susceptible to infection; the risk of rebound should be noted due to low population-level immunity.  

A population-based seroprevalence survey of severe acute respiratory syndrome coronavirus 2 infection in Beijing, China (preprint)

BACKGOUND The spread of Coronavirus Disease 2019 (COVID-19) had been controlled in China. The seroprevalence of COVID-19 in Beijing has not been evaluated. METHODS In April, residents in Beijing were randomly enrolled. Blood samples were collected and antibodies to SARS-CoV-2 were tested by two colloidal gold kits. All colloidal gold positive serums were then tested by Micro-neutralization assay. RESULTS None of 2,184 residents participated was tested positive by micro-neutralization assay. The seroprevalence of COVID-19 in Beijing was estimated < 0.17%. CONCLUSIONS The seroprevalence of COVID-19 was low in April suggesting that community-wide spread was prevented in Beijing.

Basic epidemiological parameter values from data of real-world in mega-cities: the characteristics of COVID-19 in Beijing, China (preprint)

Background: With the spread of SARS-CoV-2 worldwide, understanding the basic epidemiological parameter values of COVID-19 from real-world data in mega-cities is essential for disease prevention and control. Methods: . To investigate the epidemiological parameters in SARS-CoV-2 infected cases in Beijing, we studied all confirmed cases and close contacts in Beijing from Jan 1st to Apr 3rd 2020. The epidemiological and virological characteristics of SARS-CoV-2 were analyzed. Results: . A total of 602 cases were positive for SARS-CoV-2, including 585 confirmed patients and 17 asymptomatic infections. The imported cases were mainly from Wuhan initially and then from abroad. Among 585 confirmed case-patients, the median age was 39 years old. The mean incubation period was 6.3 days. The secondary attack rate among households was higher than social contacts (15.6 vs 4.6%). The secondary attack rate of healthcare workers (HCWs) was higher than non-HCWs’ (7.3 vs 4.2%). The basic reproduction number was 2.0, and the average serial interval was 7.6 days. No significant genetic variant was identified. Conclusions: . The transmissibility of SARS-CoV-2 was relatively high, especially among households and from HCWs, which draws specific public health attention. So far, no evidence of widespread circulation of SARS-CoV-2 in communities in Beijing was found.

Human coronavirus data from four clinical trials of masks and respirators.

There are few published data on the efficacy of masks or respirators against coronavirus infections. This is an important research question to inform the response to the COVID-19 epidemic. The transmission modes of human coronaviruses are similar, thought to be by droplet, contact, and sometimes airborne routes. There are several randomized clinical trials of masks and respirators, but most used clinical endpoints or tested only for influenza. In four trials that we conducted, we tested for human coronaviruses, but only composite viral endpoints were reported in the trials. We reviewed and analyzed the coronavirus data from four of our trials. Laboratory-confirmed coronavirus infections were identified in our community household trial (one case), health worker trials (eight cases), and trial of mask use by sick patients (19 cases). No coronavirus infections were transmitted in households to parents who wore P2 or surgical masks, but one child with coronavirus infection transmitted infection to a parent in the control arm. No transmissions to close contacts occurred when worn by sick patients with coronavirus infections. There was a higher risk of coronavirus infection in HCWs who wore a mask compared to a respirator, but the difference was not statistically significant. These are the only available clinical trial data on coronavirus infections associated with mask or respirator use. More clinical trials are needed to assess the efficacy of respiratory protection against coronavirus infections.

Neutralizing Antibodies Responses to SARS-CoV-2 in COVID-19 Inpatients and Convalescent Patients (preprint)

Background. COVID-19 is a pandemic with no specific antiviral treatments or vaccines. The urgent needs for exploring the neutralizing antibodies from patients with different clinical characteristics are emerging. Methods. A total of 117 blood samples were collected from 70 COVID-19 inpatients and convalescent patients. The presence of neutralizing antibody was determined with a modified cytopathogenic assay based on live SARS-CoV-2. The dynamics of neutralizing antibody levels at different with different clinical characteristics were analyzed. Results. The seropositivity rate reached up to 100.0% within 20 days since onset, and remained 100.0% till day 41-53. The total GMT was 1:163.7 (95% CI, 128.5 to 208.6), and the antibody level was highest during day 31-40 since onset, and then decreased slightly. Individual differences in changes of antibody levels were observed among 8 representative convalescent patients. In multivariate GEE analysis, patients at age of 31-60 and 61-84 had a higher antibody level than those at age of 16-30 ({beta}=1.0518, P=0.0152; {beta}=1.3718, P=0.0020). Patients with a worse clinical classification had a higher antibody titer ({beta}=0.4639, P=0.0227). Conclusions. The neutralizing antibodies were detected even at the early stage of disease, and a significant response showed in convalescent patients. Moreover, changes on antibody levels ware individual specific.

Highly accurate and sensitive diagnostic detection of SARS-CoV-2 by digital PCR (preprint)

BACKGROUND: The outbreak of COVID-19 caused by a novel Coronavirus (termed SARS-CoV-2) has spread to over 140 countries around the world. Currently, reverse transcription quantitative qPCR (RT-qPCR) is used as the gold standard for diagnostics of SARS-CoV-2. However, the positive rate of RT-qPCR assay of pharyngeal swab samples are reported to vary from 30~60%. More accurate and sensitive methods are urgently needed to support the quality assurance of the RT-qPCR or as an alternative diagnostic approach. METHODSWe established a reverse transcription digital PCR (RT-dPCR) protocol to detect SARS-CoV-2 on 194 clinical pharyngeal swab samples, including 103 suspected patients, 75 close contacts and 16 supposed convalescents. RESULTS: The limit of blanks (LoBs) of the RT-dPCR assays were ~1.6, ~1.6 and ~0.8 copies/reaction for ORF 1ab, N and E genes, respectively. The limit of detection (LoD) was 2 copies/reaction. For the 103 fever suspected patients, the sensitivity of SARS-CoV-2 detection was significantly improved from 28.2% by RT-qPCR to 87.4% by RT-dPCR. For close contacts, the suspect rate was greatly decreased from 21% down to 1%. The overall sensitivity, specificity and diagnostic accuracy of RT-dPCR were 90%, 100% and 93 %, respectively. In addition, quantification of the viral load for convalescents by RT-dPCR showed that a longer observation period was needed in the hospital for elderly patients. CONCLUSION: RT-dPCR could be a confirmatory method for suspected patients diagnosed by RT-qPCR. Furthermore, RT-dPCR was more sensitive and suitable for low viral load specimens from the both patients under isolation and those under observation who may not be exhibiting clinical symptoms.

Early evaluation of the Wuhan City travel restrictions in response to the 2019 novel coronavirus outbreak (preprint)

Respiratory illness caused by a novel coronavirus (COVID-19) appeared in China during December 2019. Attempting to contain infection, China banned travel to and from Wuhan city on 23 January and implemented a national emergency response. Here we evaluate the spread and control of the epidemic based on a unique synthesis of data including case reports, human movement and public health interventions. The Wuhan shutdown slowed the dispersal of infection to other cities by an estimated 2.91 days (95%CI: 2.54-3.29), delaying epidemic growth elsewhere in China. Other cities that implemented control measures pre-emptively reported 33.3% (11.1-44.4%) fewer cases in the first week of their outbreaks (13.0; 7.1-18.8) compared with cities that started control later (20.6; 14.5-26.8). Among interventions investigated here, the most effective were suspending intra-city public transport, closing entertainment venues and banning public gatherings. The national emergency response delayed the growth and limited the size of the COVID-19 epidemic and, by 19 February (day 50), had averted hundreds of thousands of cases across China.