Recent progress in online detection methods of bioaerosols

The aerosol transmission of coronavirus disease in 2019, along with the spread of other respiratory diseases, caused significant loss of life and property;it impressed upon us the importance of real-time bioaerosol detection. The complexity, diversity, and large spatiotemporal variability of bioaerosols and their external/internal mixing with abiotic components pose challenges for effective online bioaerosol monitoring. Traditional methods focus on directly capturing bioaerosols before subsequent time-consuming laboratory analysis such as culture-based methods, preventing the high-resolution time-based characteristics necessary for an online approach. Through a comprehensive literature assessment, this review highlights and discusses the most commonly used real-time bioaerosol monitoring techniques and the associated commercially available monitors. Methods applied in online bioaerosol monitoring, including adenosine triphosphate bioluminescence, laser/light-induced fluorescence spectroscopy, Raman spectroscopy, and bioaerosol mass spectrometry are summarized. The working principles, characteristics, sensitivities, and efficiencies of these real-time detection methods are compared to understand their responses to known particle types and to contrast their differences. Approaches developed to analyze the substantial data sets obtained by these instruments and to overcome the limitations of current real-time bioaerosol monitoring technologies are also introduced. Finally, an outlook is proposed for future instrumentation indicating a need for highly revolutionized bioaerosol detection technologies.

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.

Are Older People Really More Susceptible to SARS-CoV-2?

Since the outbreak, COVID-19 has spread rapidly across the globe due to its high infectivity and lethality. Age appears to be one of the key factors influencing the status and progression of SARS-CoV-2 infection, as multiple reports indicated that the majority of COVID-19 infections and severe cases are elderly. Most people simply assume that the elderly are more susceptible to SARS-CoV-2 than the young, but the mechanism behind it is still open to question. The older and younger people are at similar risk of infection because their infection process is the same and they must be exposed to the virus first. However, whether they will get sick after exposure to the virus and how their disease progresses depend on their immune mechanisms. In older populations, inflammation and immune aging reduce their ability to resist SARS-CoV-2 infection. Meanwhile, under the influence of comorbidities, ACE2 receptor and various cytokines undergo corresponding changes, thus accelerating the entry, replication, and transmission of SARS-CoV-2 in the body, promoting disease progression, and leading to severe illness and even death. In addition, the relatively fragile mental state of the elderly can also affect their timely recovery from COVID-19. Therefore, once older people are infected with SARS-CoV-2, they are more prone to severe illness and death with a poor prognosis, and they should strengthen protection to avoid exposure to the virus.

Development and clinical value evaluation of IgM-IgG antibody detection kit for SARS-CoV-2 infection in 15 cases. (Special Issue: Spatio-temporal dynamics analysis, risk assessment and emergency management for COVID-19 epidemic.) [Chinese]

Objective: To develop a colloidal gold kit for rapid detection of IgM-IgG antibodies of SARS-CoV-2, optimize the development and application strategy, and investigate the diagnostic value of SARS-CoV-2 IgM-IgG antibodies by detecting serum of clinically confirmed patients.

Efficacy and Safety of Lianhua Qingwen for Patients with COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: Corona virus disease 2019 (COVID-19) has spread around the world since its outbreak, and there is no ascertained effective drug up to now. Lianhua Qingwen (LHQW) has been widely used in China and overseas Chinese, which had some advantages in the treatment of COVID-19. OBJECTIVE: To evaluate the efficacy and safety of LHQW for COVID-19 by conducting a systematic review with meta-analysis. METHODS: A comprehensive literature search was conducted in 12 electronic databases from their establishment to October 30, 2021. Note Express 3.2.0 was used for screening of trials, and the data was independently extracted in duplicate by 2 researchers. The risk of bias of randomized controlled trials (RCTs) and retrospective studies were assessed by using the Cochrane collaboration tool and Newcastle Ottawa Scale, respectively, followed by data analysis using RevMan 5.3. The RCTs or retrospective studies to treat COVID-19 using LHQW were included. The intervention measures in the experimental group were LHQW alone or combined with chemical drugs (LCWC), and that in the control group were chemical drugs (CDs). Outcome measures included computed tomography (CT) recovery rate, disappearance rates of primary (fever, cough, fatigue), respiratory, gastrointestinal and other symptoms, exacerbation rate and adverse reaction. Subgroup analysis was conducted according to whether LHQW was combined with CDs and the different treatment methods in the control group. RESULTS: Nine trials with 1,152 participants with COVID-19 were included. The CT recovery rates of LHQW and LCWC were 1.36 and 1.32 times of CDs, respectively (P<0.05). Compared with CDs, LCWC remarkably increased the disappearance rates of fever, cough, fatigue, expectoration, shortness of breath, and muscle soreness (P<0.05). LHQW also obviously decreased the exacerbation rate, which was 0.45 times of CDs alone (P<0.05). There was no obvious difference between LCWC and CDs in adverse reaction (P>0.05). CONCLUSIONS: LHQW was more suitable for treating COVID-19 patients with obvious expectoration, shortness of breath and muscle soreness. LHQW had advantages in treating COVID-19 with no obvious exacerbation. (PROSPERO No. CRD42021235937).

Evolutionary Game Analysis of Co-Opetition Strategy in Energy Big Data Ecosystem under Government Intervention

This study discusses how to facilitate the barrier-free circulation of energy big data among multiple entities and how to balance the energy big data ecosystem under government supervision using dynamic game theory. First, we define the related concepts and summarize the recent studies and developments of energy big data. Second, evolutionary game theory is applied to examine the interaction mechanism of complex behaviors between power grid enterprises and third-party enterprises in the energy big data ecosystem, with and without the supervision of government. Finally, a sensitivity analysis is conducted on the main factors affecting co-opetition, such as the initial participation willingness, distribution of benefits, free-riding behavior, government funding, and punitive liquidated damages. The results show that both government supervision measures and the participants’ own will have an impact on the stable evolution of the energy big data ecosystem in the dynamic evolution process, and the effect of parameter changes on the evolution is more significant under the state of no government supervision. In addition, the effectiveness of the developed model in this work is verified by simulated analysis. The present model can provide an important reference for overall planning and efficient operation of the energy big data ecosystem.

Efficacy and Safety of "Three Chinese Patent Medicines and Three TCM Prescriptions" for COVID-19: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: To systematically evaluate the efficacy, safety, and precision of TMTP for COVID-19. METHODS: Randomized controlled trials and retrospective studies were searched in 11 electronic databases. This network meta-analysis included trials using TMTP to treat patients with COVID-19. The traditional pairwise meta-analysis was done by using Stata 15, and Bayesian network meta-analysis was done with WinBUGS. RESULTS: 18 trials were included with 2036 participants and 7 drugs. The results showed that LHQW had the most significant effects on improving expectoration, shortness of breath, sore throat, nausea, emesis, inappetence, muscle soreness, and headache, and it could produce the least adverse reactions. XBJ was the best drug for fever, fatigue, and diarrhea, which showed great advantages in lowering WBC levels. XFBD was the most effective drug for cough and chest distress, which had the least exacerbation rate. JHQG was the most effective for rhinobyon and rhinorrhea, while QFPD was the best drug in decreasing CRP levels. CONCLUSION: This study was the first most large-scale and comprehensive research of TMTP for COVID-19. The results showed that LHQW had good efficacy without obvious adverse reactions. Therefore, we believe that it should be firstly recommended for COVID-19 treatment. In addition, XBJ is recommended for patients with a severe fever, fatigue, and diarrhea, and JHQG is recommended for patients with obvious rhinobyon and rhinorrhea; then, XFBD is recommended for patients with cough and chest tightness as the main manifestation. Our findings will help experts develop new COVID-19 treatment guidelines to better guide clinical medication for protecting the health of COVID-19 patients.

Instance importance-Aware graph convolutional network for 3D medical diagnosis.

Automatic diagnosis of 3D medical data is a significant goal of intelligent healthcare. By exploiting the abundant pathological information of 3D data, human experts and algorithms can provide accurate predictions for patients. Considering the high cost of collecting exhaustive annotations for 3D data, a sustainable alternative is to develop diagnosis algorithms with merely patient-level labels. Motivated by the fact that 2D slices of 3D data hold explicit diagnostic efficacy, we propose the Instance Importance-aware Graph Convolutional Network (I2GCN) under the multi-instance learning (MIL). Specifically, we first calculate the instance importance of each slice towards diagnosis using a preliminary MIL classifier, which is further utilized to promote the refined diagnosis branch. In the refined diagnosis branch, we devise the Instance Importance-aware Graph Convolutional Layer (I2GCLayer) to exploit complementary features in both importance-based and feature-based topologies. Moreover, to alleviate the deficient supervision of 3D dataset, we propose the importance-based Sub-Graph Augmentation (SGA) to effectively regularize the framework training. Extensive experiments confirm the effectiveness of our method with different organs and modals on the CC-CCII and PROSTATEx datasets, which outperforms state-of-the-art methods by a large margin. The source code is available at https://github.com/CityU-AIM-Group/I2GCN.

Suppression and Activation of Intracellular Immune Response in Initial Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the most important emerging pathogen worldwide, but its early transcriptional dynamics and host immune response remain unclear. Herein, the expression profiles of viral interactions with different types of hosts were comprehensively dissected to shed light on the early infection strategy of SARS-CoV-2 and the host immune response against infection. SARS-CoV-2 was found to exhibit a two-stage transcriptional strategy within the first 24 h of infection, comprising a lag phase that ends with the virus being paused and a log phase that starts when the viral load increases rapidly. Interestingly, the host innate immune response was found not to be activated (latent period) until the virus entered the log stage. Noteworthy, when intracellular immunity is suppressed, SARS-CoV-2 shows a correlation with dysregulation of metal ion homeostasis. Herein, the inhibitory activity of copper ions against SARS-CoV-2 was further validated in in vitro experiments. Coronavirus disease 2019-related genes (including CD38, PTX3, and TCN1) were also identified, which may serve as candidate host-restricted factors for interventional therapy. Collectively, these results confirm that the two-stage strategy of SARS-CoV-2 effectively aids its survival in early infection by regulating the host intracellular immunity, highlighting the key role of interferon in viral infection and potential therapeutic candidates for further investigations on antiviral strategies.

A two-dose optimum for recombinant S1 protein-based COVID-19 vaccination.

BACKGROUND: Recombinant protein subunit vaccination is considered to be a safe, fast and reliable technique when combating emerging and re-emerging diseases such as coronavirus disease 2019 (COVID-19). Typically, such subunit vaccines require the addition of adjuvants to attain adequate immunogenicity. AS01, which contains adjuvants MPL and saponin QS21, is a liposome-based vaccine adjuvant system that is one of the leading candidates. However, the adjuvant effect of AS01 in COVID-19 vaccines is not well described yet. METHODS: In this study, we utilized a mixture of AS01 as the adjuvant for an S1 protein-based COVID-19 vaccine. RESULTS: The adjuvanted vaccine induced robust immunoglobulin G (IgG) binding antibody and virus-neutralizing antibody responses. Importantly, two doses induced similar levels of IgG binding antibody and neutralizing antibody responses compared with three doses and the antibody responses weakened only slightly over time up to six weeks after immunization. CONCLUSION: These results suggested that two doses may be enough for a clinical vaccine strategy design using MPL & QS21 adjuvanted recombinant protein, especially in consideration of the limited production capacity of COVID-19 vaccine in a public health emergency.

Patterns of Prostate-Specific Antigen Testing and Prostate Biopsies During the COVID-19 Pandemic.

PURPOSE: This study examined changes in prostate disease screening (prostatic-specific antigen [PSA] testing), prostate biopsy testing, and prostate cancer diagnoses during the COVID-19 pandemic through December 2020. MATERIALS AND METHODS: This analysis included test results from men ≥ 40 years, without prior International Classification of Diseases-10 record of prostate cancer since January 2016, who received PSA or prostate biopsy testing at Quest Diagnostics during January 2018-December 2020. Monthly trends were evaluated for three periods: prepandemic (January 2018-February 2020), early-pandemic (March-May 2020), and late-pandemic (June-December 2020). RESULTS: Meeting inclusion criteria were 16,365,833 PSA and 48,819 prostate biopsy results. The average monthly number of PSA tests declined from 465,187 prepandemic to 295,786 early-pandemic (36.4% decrease; P = .01) before rebounding to 483,374 (3.9% increase; P = .23) late-pandemic. The monthly average number of PSA results ≥ 50 ng/mL (23,356; 0.14% of all PSA results) dipped from 659 prepandemic to 506 early-pandemic (23.2% decrease; P = .02) and rebounded to 674 late-pandemic (2.3% increase; P = .65). The average monthly number of prostate biopsy results decreased from 1,453 prepandemic to 903 early-pandemic (37.9% decrease; P = .01) before rebounding to 1,190 late-pandemic (18.1% decrease; P = .01). The average monthly number for Gleason score ≥ 8 (6,241; 12.8% of all prostate biopsies) declined from 182 prepandemic to 130 early-pandemic (28.6% decrease; P = .02) and decreased to 161 late-pandemic (11.5% decrease; P = .02). CONCLUSION: The findings suggest that a substantial number of prostate screening opportunities and cancer diagnoses have been missed. Efforts are needed to bring such patients back for screening and diagnostic testing and to restore appropriate care for non-COVID-19-related medical conditions.

The Rite of Passage and Digital Mourning in Fang Fang’s Wuhan Diary

Using Van Gennep?s theory of Rite of Passage as its framework, this article examines the impact of Coronavirus (COVID-19) on Chinese culture as depicted through death and mourning in Wang Fang?s (penname Fang Fang) recently published Wuhan Diary: Dispatches from a Quarantined City. As part of the efforts to control the outbreak, the Chinese government took over the managing of the deceased, which triggered heated discussions on Chinese social media. Fang Fang?s diary, originally written as daily entries on Chinese social media platform Weibo, serves as a voice for those suffering during the pandemic, mediating between personal accounts, accounts of friends, family and those living in Wuhan during the pandemic. These flesh out how the virus has not only been disturbing for Chinese people?s lives but also disrupted the death rites and mourning rituals for those who have passed. Our article infuses a digital ontological reading with an anthropological twist that helps to understand how the diary mitigates the disturbances to mourning rituals inside and outside the confines of digital metaphysics. We argue that the digital diary mitigates these disruptions by allowing Chinese people to nourish their sorrow by identifying with the symbolic rites of passage and mourning rituals online at the heart of the COVID-19 pandemic in Wuhan. In doing so, this article examines three stages of rite of passage, including separation, liminality and integration as they unfold in the diary, through which discourses and subjectivities based on collective and individual traumatic experiences are built, as a form of digital mourning that could reconcile both the official and the alternative voices of anonymous narratives about the handling of this crisis.