Trends of SARS-CoV-2 Infection Among Couriers in Risky Business After the Optimization of Prevention and Control Measures - China, December 2022 to January 2023.

Introduction: On December 7, 2022, China implemented "Ten New Measures" to optimize prevention and control measures for coronavirus disease 2019 (COVID-19). The purpose of this study was to evaluate the national and regional trends of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among couriers in China from December 2022 to January 2023. Methods: Data from the National Sentinel Community-based Surveillance in China was utilized, including participants from 31 provincial-level administrative divisions and Xinjiang Production and Construction Corps. Participants were tested for SARS-CoV-2 infection twice a week from December 16, 2022 to January 12, 2023. Infection was defined as a positive result for SARS-CoV-2 nucleic acid or antigen. The daily average newly positive rate of SARS-CoV-2 infection and the estimated daily percentage change (EDPC) were calculated. Results: In this cohort, 8 rounds of data were collected. The daily average newly positive rate of SARS-CoV-2 infection decreased from 4.99% in Round 1 to 0.41% in Round 8, with an EDPC of -33.0%. Similar trends of the positive rate were also observed in the eastern (EDPC: -27.7%), central (EDPC: -38.0%) and western regions (EDPC: -25.5%). Couriers and community population showed a similar temporal trend, with the peak daily average newly positive rate of couriers being higher than that of community population. After Round 2, the daily average newly positive rate of couriers decreased sharply, becoming lower than that of community population in the same period. Conclusions: The peak of SARS-CoV-2 infection among couriers in China has passed. As couriers are a key population for SARS-CoV-2 infection, they should be monitored continuously.

Trends of SARS-CoV-2 Infection in Sentinel Community-Based Surveillance After the Optimization of Prevention and Control Measures - China, December 2022-January 2023.

Introduction: On December 7, 2022, China implemented the "Ten New Measures" to optimize its prevention and control measures for coronavirus disease 2019 (COVID-19). To provide the latest data after the optimization, we evaluated trends of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among the community population in China. Methods: We utilized data from the National Sentinel Community-Based Surveillance (NSCS) system in China to assess trends of SARS-CoV-2 infection. NSCS is a national community-based surveillance cohort with 0.42 million participants from all 31 provincial-level administrative divisions (PLADs) and Xinjiang Production and Construction Corps (XPCC). Participants were tested for infection twice a week (a total of eight rounds) from December 16, 2022 to January 12, 2023. SARS-CoV-2 infection was defined as testing positive for SARS-CoV-2 nucleic acid or antigen. We calculated the daily average of newly positive rates of SARS-CoV-2 infection. Results: In this national cohort, the daily average newly positive rate of SARS-CoV-2 infection decreased from 4.13% in Round 1 (December 16-19, 2022) to 0.69% in Round 8 (January 10-12, 2023). The epidemic peak occurred in Round 2 (December 20-22, 2022). Similar trends were observed in urban areas (decreasing from 4.65% to 0.73%), rural areas (decreasing from 2.83% to 0.57%), the eastern region (decreasing from 4.18% to 0.67%), the central region (decreasing from 5.43% to 0.61%), and the western region (decreasing from 3.01% to 0.77%). Conclusions: NSCS data showed that the peak of SARS-CoV-2 infection in China had passed. SARS-CoV-2 infection in community populations in China is currently at a low epidemic level.

Trends of SARS-CoV-2 Infection in Rural Area in Sentinel Community-Based Surveillance - China, December 2022 to January 2023.

Introduction: In late 2022, a rapid transmission of Omicron variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred throughout China. The purpose of this study was to provide the latest data and evaluate trends of SARS-CoV-2 infection in rural China among the community population. Methods: Data on SARS-CoV-2 infection among approximately 90,000 participants in rural China were collected by the National Sentinel Community-Based Surveillance (NSCS) system. Participants were tested for SARS-CoV-2 infection (defined as positive for SARS-CoV-2 nucleic acid or antigen) twice weekly from December 16, 2022 to January 12, 2023. The daily average of newly positive rate and its estimated daily percentage change were calculated to describe the national and regional trends of SARS-CoV-2 infection in rural China. Results: In rural China, the daily average new positive rate of SARS-CoV-2 infection peaked at 4.79% between December 20-22, 2022 and then decreased to 0.57% between January 10-12, 2023, with an average decrease of 29.95% per round. The peak of new SARS-CoV-2 infection was slightly earlier and lower in North China (5.28% between December 20-22, 2022) than in South China (5.63% between December 23-26, 2022), and then converged from December 30, 2022 to January 2, 2023. The peak of 6.09% occurred between December 20-22, 2022 in eastern China, while the peak of 5.99% occurred later, between December 27-29, 2022, in central China. Conclusions: Overall, the epidemic wave in rural China peaked between December 20-22, 2022, and passed quickly following the optimization of prevention and control measures. Currently, SARS-CoV-2 infection in community populations in rural China is sporadic.

Self-assembled multiepitope nanovaccine based on NoV P particles induces effective and lasting protection against H3N2 influenza virus.

Current seasonal influenza vaccines confer only limited coverage of virus strains due to the frequent genetic and antigenic variability of influenza virus (IV). Epitope vaccines that accurately target conserved domains provide a promising approach to increase the breadth of protection; however, poor immunogenicity greatly hinders their application. The protruding (P) domain of the norovirus (NoV), which can self-assemble into a 24-mer particle called the NoV P particle, offers an ideal antigen presentation platform. In this study, a multiepitope nanovaccine displaying influenza epitopes (HMN-PP) was constructed based on the NoV P particle nanoplatform. Large amounts of HMN-PP were easily expressed in Escherichia coli in soluble form. Animal experiments showed that the adjuvanted HMN-PP nanovaccine induced epitope-specific antibodies and haemagglutinin (HA)-specific neutralizing antibodies, and the antibodies could persist for at least three months after the last immunization. Furthermore, HMN-PP induced matrix protein 2 extracellular domain (M2e)-specific antibody-dependent cell-mediated cytotoxicity, CD4+ and CD8+ T-cell responses, and a nucleoprotein (NP)-specific cytotoxic T lymphocyte (CTL) response. These results indicated that the combination of a multiepitope vaccine and self-assembled NoV P particles may be an ideal and effective vaccine strategy for highly variable viruses such as IV and SARS-CoV-2. Electronic Supplementary Material: Supplementary material is available in the online version of this article at 10.1007/s12274-023-5395-6.

Safety and immunogenicity of a protein subunit COVID-19 vaccine (ZF2001) in healthy children and adolescents aged 3-17 years in China: a randomised, double-blind, placebo-controlled, phase 1 trial and an open-label, non-randomised, non-inferiority, phase 2 trial.

BACKGROUND: ZF2001 is a recombinant protein subunit vaccine against SARS-CoV-2 that has been approved for use in China, Colombia, Indonesia, and Uzbekistan in adults aged 18 years or older, but not yet in children and adolescents younger than 18 years. We aimed to evaluate the safety and immunogenicity of ZF2001 in children and adolescents aged 3-17 years in China. METHODS: The randomised, double-blind, placebo-controlled, phase 1 trial and the open-label, non-randomised, non-inferiority, phase 2 trial were done at the Xiangtan Center for Disease Control and Prevention (Hunan Province, China). Healthy children and adolescents aged 3-17 years, without a history of SARS-CoV-2 vaccination, without a history of COVID-19, without COVID-19 at the time of the study, and without contact with patients with confirmed or suspected COVID-19 were included in the phase 1 and phase 2 trials. In the phase 1 trial, participants were divided into three groups according to age (3-5 years, 6-11 years, and 12-17 years). Each group was randomly assigned (4:1), using block randomisation with five blocks, each with a block size of five, to receive three 25 µg doses of the vaccine, ZF2001, or placebo intramuscularly in the arm 30 days apart. The participants and investigators were masked to treatment allocation. In the phase 2 trial, participants received three 25 µg doses of ZF2001 30 days apart and remained stratified by age group. For phase 1, the primary endpoint was safety and the secondary endpoint was immunogenicity (humoral immune response on day 30 after the third vaccine dose: geometric mean titre [GMT] of prototype SARS-CoV-2 neutralising antibodies and seroconversion rate, and geometric mean concentration [GMC] of prototype SARS-CoV-2 receptor-binding domain [RBD]-binding IgG antibodies and seroconversion rate). For phase 2, the primary endpoint was the GMT of SARS-CoV-2 neutralising antibodies with seroconversion rate on day 14 after the third vaccine dose, and the secondary endpoints included the GMT of RBD-binding antibodies and seroconversion rate on day 14 after the third vaccine dose, the GMT of neutralising antibodies against the omicron BA.2 subvariant and seroconversion rate on day 14 after the third vaccine dose, and safety. Safety was analysed in participants who received at least one dose of the vaccine or placebo. Immunogenicity was analysed in the full-analysis set (ie, participants who received at least one dose and had antibody results) by intention to treat and in the per-protocol set (ie, participants who completed the whole vaccination course and had antibody results). Non-inferiority in the phase 2 trial (neutralising antibody titre of participants from this trial aged 3-17 years vs that of participants aged 18-59 years from a separate phase 3 trial) for clinical outcome assessment was based on the geometric mean ratio (GMR) and was considered met if the lower bound of the 95% CI for the GMR was 0·67 or greater. These trials are registered with ClinicalTrials.gov, NCT04961359 (phase 1) and NCT05109598 (phase 2). FINDINGS: Between July 10 and Sept 4, 2021, 75 children and adolescents were randomly assigned to receive ZF2001 (n=60) or placebo (n=15) in the phase 1 trial and were included in safety and immunogenicity analyses. Between Nov 5, 2021, and Feb 14, 2022, 400 participants (130 aged 3-7 years, 210 aged 6-11 years, and 60 aged 12-17 years) were included in the phase 2 trial and were included in the safety analysis; six participants were excluded from the immunogenicity analyses. 25 (42%) of 60 participants in the ZF2001 group and seven (47%) of 15 participants in the placebo group in phase 1, and 179 (45%) of 400 participants in phase 2, had adverse events within 30 days after the third vaccination, without a significant difference between groups in phase 1. Most adverse events were grade 1 or 2 (73 [97%] of 75 in the phase 1 trial, and 391 [98%] of 400 in the phase 2 trial). One participant in the phase 1 trial and three in the phase 2 trial who received ZF2001 had serious adverse events. One serious adverse event (acute allergic dermatitis) in the phase 2 trial was possibly related to the vaccine. In the phase 1 trial, on day 30 after the third dose, in the ZF2001 group, seroconversion of neutralising antibodies against SARS-CoV-2 was observed in 56 (93%; 95% CI 84-98) of 60 participants, with a GMT of 176·5 (95% CI 118·6-262·8), and seroconversion of RBD-binding antibodies was observed in all 60 (100%; 95% CI 94-100) participants, with a GMC of 47·7 IU/mL (95% CI 40·1-56·6). In the phase 2 trial, on day 14 after the third dose, seroconversion of neutralising antibodies against SARS-CoV-2 was seen in 392 (99%; 95% CI 98-100) participants, with a GMT of 245·4 (95% CI 220·0-273·7), and seroconversion of RBD-binding antibodies was observed in all 394 (100%; 99-100) participants, with a GMT of 8021 (7366-8734). On day 14 after the third dose, seroconversion of neutralising antibodies against the omicron subvariant BA.2 was observed in 375 (95%; 95% CI 93-97) of 394 participants, with a GMT of 42·9 (95% CI 37·9-48·5). For the non-inferiority comparison of participants aged 3-17 years with those aged 18-59 years for SARS-CoV-2 neutralising antibodies, the adjusted GMR was 8·6 (95% CI 7·0-10·4), with the lower bound of the GMR greater than 0·67. INTERPRETATION: ZF2001 is safe, well tolerated, and immunogenic in children and adolescents aged 3-17 years. Vaccine-elicited sera can neutralise the omicron BA.2 subvariant, but with reduced activity. The results support further studies of ZF2001 in children and adolescents. FUNDING: Anhui Zhifei Longcom Biopharmaceutical and the Excellent Young Scientist Program from National Natural Science Foundation of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Analysis of the Causes of Solitary Pulmonary Nodule Misdiagnosed as Lung Cancer by Using Artificial Intelligence: A Retrospective Study at a Single Center.

Artificial intelligence (AI) adopting deep learning technology has been widely used in the med-ical imaging domain in recent years. It realized the automatic judgment of benign and malig-nant solitary pulmonary nodules (SPNs) and even replaced the work of doctors to some extent. However, misdiagnoses can occur in certain cases. Only by determining the causes can AI play a larger role. A total of 21 Coronavirus disease 2019 (COVID-19) patients were diagnosed with SPN by CT imaging. Their Clinical data, including general condition, imaging features, AI re-ports, and outcomes were included in this retrospective study. Although they were confirmed COVID-19 by testing reverse transcription-polymerase chain reaction (RT-PCR) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), their CT imaging data were misjudged by AI to be high-risk nodules for lung cancer. Imaging characteristics included burr sign (76.2%), lobulated sign (61.9%), pleural indentation (42.9%), smooth edges (23.8%), and cavity (14.3%). The accuracy of AI was different from that of radiologists in judging the nature of be-nign SPNs (p < 0.001, κ = 0.036 < 0.4, means the two diagnosis methods poor fit). COVID-19 patients with SPN might have been misdiagnosed using the AI system, suggesting that the AI system needs to be further optimized, especially in the event of a new disease outbreak.

Efficacy and Safety of the RBD-Dimer-Based Covid-19 Vaccine ZF2001 in Adults.

BACKGROUND: The ZF2001 vaccine, which contains a dimeric form of the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 and aluminum hydroxide as an adjuvant, was shown to be safe, with an acceptable side-effect profile, and immunogenic in adults in phase 1 and 2 clinical trials. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to investigate the efficacy and confirm the safety of ZF2001. The trial was performed at 31 clinical centers across Uzbekistan, Indonesia, Pakistan, and Ecuador; an additional center in China was included in the safety analysis only. Adult participants (≥18 years of age) were randomly assigned in a 1:1 ratio to receive a total of three 25-µg doses (30 days apart) of ZF2001 or placebo. The primary end point was the occurrence of symptomatic coronavirus disease 2019 (Covid-19), as confirmed on polymerase-chain-reaction assay, at least 7 days after receipt of the third dose. A key secondary efficacy end point was the occurrence of severe-to-critical Covid-19 (including Covid-19-related death) at least 7 days after receipt of the third dose. RESULTS: Between December 12, 2020, and December 15, 2021, a total of 28,873 participants received at least one dose of ZF2001 or placebo and were included in the safety analysis; 25,193 participants who had completed the three-dose regimen, for whom there were approximately 6 months of follow-up data, were included in the updated primary efficacy analysis that was conducted at the second data cutoff date of December 15, 2021. In the updated analysis, primary end-point cases were reported in 158 of 12,625 participants in the ZF2001 group and in 580 of 12,568 participants in the placebo group, for a vaccine efficacy of 75.7% (95% confidence interval [CI], 71.0 to 79.8). Severe-to-critical Covid-19 occurred in 6 participants in the ZF2001 group and in 43 in the placebo group, for a vaccine efficacy of 87.6% (95% CI, 70.6 to 95.7); Covid-19-related death occurred in 2 and 12 participants, respectively, for a vaccine efficacy of 86.5% (95% CI, 38.9 to 98.5). The incidence of adverse events and serious adverse events was balanced in the two groups, and there were no vaccine-related deaths. Most adverse reactions (98.5%) were of grade 1 or 2. CONCLUSIONS: In a large cohort of adults, the ZF2001 vaccine was shown to be safe and effective against symptomatic and severe-to-critical Covid-19 for at least 6 months after full vaccination. (Funded by the National Science and Technology Major Project and others; ClinicalTrials.gov number, NCT04646590.).

Deep learning guided optimization of human antibody against SARS-CoV-2 variants with broad neutralization.

SignificanceSARS-CoV-2 continues to evolve through emerging variants, more frequently observed with higher transmissibility. Despite the wide application of vaccines and antibodies, the selection pressure on the Spike protein may lead to further evolution of variants that include mutations that can evade immune response. To catch up with the virus's evolution, we introduced a deep learning approach to redesign the complementarity-determining regions (CDRs) to target multiple virus variants and obtained an antibody that broadly neutralizes SARS-CoV-2 variants.

Scientific efforts on SARS-CoV-2 research: A global survey analysis.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has been a global pandemic. Researchers have made great efforts to investigate SARS-CoV-2. However, there are few studies analyzing the general situation of SARS-CoV-2 research at global level. This study aimed to characterize global scientific efforts based on SARS-CoV-2 publications. METHODOLOGY: SARS-CoV-2 -related publications were retrieved using Web of Science. The number of publications, citation, country, journal, study topic, total confirmed cases, and total deaths were analyzed. RESULTS: A total of 441 publications were identified. China contributed the largest number of publications (198, 44.90%), followed by USA (51, 11.56%), Italy (28, 6.35%), Germany (19, 4.31%), and South Korea (13, 2.95%). Upper-middle-income economies (51.70%) produced the most SARS-CoV-2 publications, followed by high-income (45.12%), lower-middle-income (2.95%), and low-income economies (0.23%). The research output had a significant correlations with total confirmed cases (r = 0.666, p = 0.000) and total deaths (r = 0.610, p = 0.000). China had the highest total citations (1947), followed by USA (204), and Germany (54). China also had the highest average citations (9.83), followed by Netherlands (5.80), and Canada (5.43). The most popular journals were Journal of Medical Virology, Eurosurveillance, and Emerging Microbes and Infections. The most discussed topic was the epidemiology of SARS-CoV-2. CONCLUSIONS: Scientific research on SARS-CoV-2 is from worldwide researchers' efforts, with some countries and journals having special contributions. The countries with more total confirmed cases and total deaths tend to have more research output in the field of SARS-CoV-2. China was the most prolific country, and had the highest quality of publications on SARS-CoV-2.

Lessons from a lumbar burst fracture patient infected with SARS-CoV-2.

In December 2019, the 2019 novel coronavirus (SARS-CoV-2) began spreading in China. At present, there are no special protocols for treating lumbar burst fracture (LBF) patients infected with SARS-CoV-2. Here, we present our lessons and experiences with a patient presenting with a severe LBF complicated by an occult SARS-CoV-2 infection. The clinical data for a 52-year-old male LBF patient were collected during the incubation period of COVID-19. The patient exhibited no obvious COVID-19-related symptoms prior to his surgery, and his vital signs were stable on the first day after the operation. By postoperative day 3, however, the patient was exhibiting chills and high fever. A chest CT showed a patchy high-density shadow surrounded by ground-glass opacity in the lower portion of his right lung. A nucleic acid test for SARS-CoV-2 was positive, and the patient was then transferred to the Department of Infectious Disease for further special treatment. This case taught that when treating patients with severe trauma within an epicenter of this pandemic, it is crucial for healthcare workers to be vigilant so as to avoid potential widespread outbreaks of COVID-19 within hospitals.