Parainfluenza virus 5 is a next-generation vaccine vector for human infectious pathogens.

Parainfluenza virus 5 (PIV5) is a negative-sense, single-stranded RNA virus that can infect humans and many species of animals. Infection in these reservoir hosts is generally asymptomatic and has few safety concerns. Emerging evidence has shown that PIV5 is a promising vector for developing vaccines against human infectious diseases caused by coronaviruses, influenza, respiratory syncytial virus, rabies, HIV, or bacteria. In this review, we summarize recent progress and highlight the advantages and strategies of PIV5 as a vaccine vector to improve future vaccine design and application for clinical trials.

A retrospective study of Pupingqinghua prescription versus Lianhuaqingwen in Chinese participants infected with SARS-CoV-2 Omicron variants

Background: Coronavirus disease (COVID-19) seriously endangers global public health. Pupingqinghua prescription (PPQH) is an herbal formula from traditional Chinese medicine used for treatment of SARS-CoV-2 infection. This study aims to evaluate the clinical efficacy and safety of PPQH in Chinese participants infected with the SARS-CoV-2 Omicron variant. Methods: A total of 873 SARS-CoV-2 (Omicron)-infected patients were included. Among them, the patients were divided into the PPQH group (653 cases) and LHQW group (220 cases) according to different medications. The effectiveness indicators (hematological indicators, Ct values of novel Coronavirus nucleic acid tests, and viral load-shedding time) and safety indicators (liver and kidney function and adverse events) were analyzed. Results: There was no significant difference in baseline characteristics between the PPQH group and the LHQW group, except the gender;After the treatment, the levels of IL-5, IL-6, IL-10, NK cells, and INF-α of the patients in the PPQH group showed a downward trend (p < 0.05);The viral load shedding time was 5.0 (5.0, 7.0) in the PPQH group and 5.0 (4.0, 7.0) in the LHQW group;both PPQH and LHQW can shorten the duration of symptoms of fever, cough, and sore throat. The re-positive rate of COVID-19 test was 1.5 % in the PPQH group and 2.3 % in the LHQW group. In terms of safety, the levels of γ-GTT decreased significantly (p < 0.01);gastrointestinal reaction was the primary adverse reaction, and the reaction rate was 4.7 % in the PPQH group and 9.5 % in the LHQW group. Conclusion: PPQH can shorten the length of hospital stay and improve clinical symptoms of patients with SARS-COV-2 (Omicron), and it also has a good safety profile.

Identification of hACE2-interacting sites in SARS-CoV-2 spike receptor binding domain for antiviral drugs screening.

The key structure of the interface between the spike protein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and human angiotensin-converting enzyme 2 (hACE2) acts as an essential switch for cell entry by the virus and drugs targets. However, this is largely unknown. Here, we tested three peptides of spike receptor binding domain (RBD) and found that peptide 391-465 aa is the major hACE2-interacting sites in SARS-CoV-2 spike RBD. We then identified essential amino acid residues (403R, 449Y, 454R) of peptide 391-465 aa that were critical for the interaction between the RBD and hACE2. Additionally, a pseudotyped virus containing SARS-CoV-2 spike with individual mutation (R454G, Y449F, R403G, N439I, or N440I) was determined to have very low infectivity compared with the pseudotyped virus containing the wildtype (WT) spike from reference strain Wuhan 1, respectively. Furthermore, we showed the key amino acids had the potential to drug screening. For example, molecular docking (Docking) and infection assay showed that Cephalosporin derivatives can bind with the key amino acids to efficiently block infection of the pseudoviruses with wild type spike or new variants. Moreover, Cefixime inhibited live SARS-CoV-2 infection. These results also provide a novel model for drug screening and support further clinical evaluation and development of Cephalosporin derivatives as novel, safe, and cost-effective drugs for prevention/treatment of SARS-CoV-2.

Research on older people's health information search behavior based on risk perception in social networks-A case study in China during COVID-19.

Objective: COVID-19 has caused great loss of human life and livelihoods. The dissemination of health information in online social networks increased during the pandemic's quarantine. Older people are the most vulnerable group in sudden public health emergencies, and they have the disadvantage of infection rates and online search for health information. This study explores the relationship between the health risk perception and health information search behavior of older people in social networks, to help them make better use of the positive role of social networks in public health emergencies. Method: Based on the Risk Information Search and Processing model, and in the specific context of COVID-19, this study redefines health risk perception as a second-order construct of four first-order factors (perceived probability, perceived severity, perceived controllability, and perceived familiarity), and constructs a research model of the health risk perception and health information search behavior of older people. An online survey of people over 55 years old was conducted through convenience sampling in China from February 2020 to March 2020. Results: A total of 646 older adults completed the survey. The structural equation model showed that health risk perception is a second-order factor (H1), that health risk perception has significant positive effects on health information search behavior (H2: ß = 0.470, T = 11.577, P < 0.001), and that health risk perception has significant positive effects on affective response (H3: ß = 0.536, T = 17.356, P < 0.001). In addition, affective response has a significant positive mediating effect on information sufficiency (H4: ß = 0.435, T = 12.231, P < 0.001), and information sufficiency has a significant positive mediating effect on health information search behavior (H5: ß = 0.136, T = 3.081, P = 0.002). Conclusion: The study results indicate that the health risk perception of older people during the COVID-19 outbreak not only directly affected their health information search behavior, but also had an indirect impact on their health information search behavior by affecting affective response and information sufficiency.

Oridonin Inhibits SARS‐CoV‐2 by Targeting Its 3C‐Like Protease

Oridonin Inhibits SARS‐CoV‐2 Oridonin, a natural product extracted from Rabdosia rubescens, possesses a wide range of pharmacological properties, including anti‐inflammatory, anti‐cancer, anti‐microbial, neuroprotection, immunoregulation, etc. In article number 2100124, Baisen Zhong, Litao Sun, and co‐workers demonstrate that Oridonin targets the SARS‐CoV‐2 3CL protease by covalently binding to cysteine145 in its active pocket to exert an anti‐SARS‐CoV‐2 effect, which provides a novel candidate for the treatment of COVID‐19. © 2022 WILEY‐VCH GmbH

Comparison of Use of Neoadjuvant Systemic Treatment for Breast Cancer and Short-term Outcomes Before vs During the COVID-19 Era in Ontario, Canada.

Importance: In response to an increase in COVID-19 infection rates in Ontario, several systemic treatment (ST) regimens delivered in the adjuvant setting for breast cancer were temporarily permitted for neoadjuvant-intent to defer nonurgent breast cancer surgical procedures. Objective: To examine the use and compare short-term outcomes of neoadjuvant-intent vs adjuvant ST in the COVID-19 era compared with the pre-COVID-19 era. Design, Setting, and Participants: This was a retrospective population-based cohort study in Ontario, Canada. Patients with cancer starting selected ST regimens in the COVID-19 era (March 11, 2020, to September 30, 2020) were compared to those in the pre-COVID-19 era (March 11, 2019, to March 10, 2020). Patients were diagnosed with breast cancer within 6 months of starting systemic therapy. Main Outcomes and Measures: Estimates were calculated for the use of neoadjuvant vs adjuvant ST, the likelihood of receiving a surgical procedure, the rate of emergency department visits, hospital admissions, COVID-19 infections, and all-cause mortality between treatment groups over time. Results: Among a total of 10 920 patients included, 7990 (73.2%) started treatment in the pre-COVID-19 era and 7344 (67.3%) received adjuvant ST; the mean (SD) age was 61.6 (13.1) years. Neoadjuvant-intent ST was more common in the COVID-19 era (1404 of 2930 patients [47.9%]) than the pre-COVID-19 era (2172 of 7990 patients [27.2%]), with an odds ratio of 2.46 (95% CI, 2.26-2.69; P < .001). This trend was consistent across a range of ST regimens, but differed according to patient age and geography. The likelihood of receiving surgery following neoadjuvant-intent chemotherapy was similar in the COVID-19 era compared with the pre-COVID-19 era (log-rank P = .06). However, patients with breast cancer receiving neoadjuvant-intent hormonal therapy were significantly more likely to receive surgery in the COVID-19 era (log-rank P < .001). After adjustment, there were no significant changes in the rate of emergency department visits over time between patients receiving neoadjuvant ST, adjuvant ST, or ST only during the ST treatment period or postoperative period. Hospital admissions decreased in the COVID-19 era for patients who received neoadjuvant ST compared with adjuvant ST or ST alone (P for interaction = .01 for both) in either setting. Conclusions and Relevance: In this cohort study, patients were more likely to start neoadjuvant ST in the COVID-19 era, which varied across the province and by indication. There was limited evidence to suggest any substantial impact on short-term outcomes.

Occurrence and risk assessment of triclosan in freshwater lakes in the middle Yangtze River basin (Wuhan, Central China)

Triclosan (TCS) is an endocrine disrupting chemical which is commonly used as a disinfectant in pharmaceuticals and personal care products (PPCP's). Since early 2020, the worldwide outbreak of COVID-19 has increased the use of PPCP's, so the occurrence and impact of TCS on freshwater lakes should be considered. However, little attention has been given to the effect of TCS on freshwater lakes in China. This study is the first attempt at a risk assessment focusing on the temporal and spatial occurrence of TCS in freshwater lakes in the middle Yangtze River basin. The surface water and sediments of Donghu Lake and Liangzi Lake (Wuhan, Central China) were collected from October 2020 to August 2021. The maximum concentrations of TCS were 466 ng/L and 239 ng/L in surface water, 71 ng/g and 25 ng/g (dry weight) in sediments of Donghu Lake and Liangzi Lake, respectively. Significant temporal and spatial differences of TCS were observed within and between the lakes, with the highest concentrations measured in winter. Furthermore, higher concentrations of TCS were observed in areas that are more impacted by human activities. There was a significant positive correlation between TCS and nitrogen in the surface water. A risk assessment using the risk quotient (RQ) method showed that a potentially high risk (RQ > 1) was found only in surface waters from Donghu Lake, and that the sediments posed a lower risk than the surface waters. These results provide timely data on the temporal and spatial occurrence of TCS in freshwater lakes in China following the outbreak of COVID-19 and demonstrate a possible high risk of exposure to TCS for aquatic biota.

Altered development of face recognition among infants born amid the COVID-19 pandemic (preprint)

To effectively contain the spread of Coronavirus disease (COVID-19), public health agencies mandated special regulations. Though they protect us from COVID-19, these restrictions have inevitably changed the environment around us. It remains unclear how these changes may have impacted early cognitive development among infants born during the pandemic. Thus, this study examined how the COVID-19 restrictions have affected infants’ face recognition ability, a hallmark of their cognitive capacities. Specifically, we used the familiarization and visual pair comparison paradigm to examine face recognition performance among infants between 6 and 14 months of age amid the second wave of the pandemic (February to July 2021). Experiment 1 investigated the recognition of unmasked faces and found that only younger infants, but not older infants, recognized faces by showing a novelty preference. Experiment 2 examined the recognition of faces wearing a mask and found that only older infants, but not younger ones, recognized faces by exhibiting a familiarity preference. These results suggest that with limited interactions during the pandemic, infants could have developed an overly specialized face processing ability that failed to recognize the faces of strangers. Moreover, infants could have obtained more information on masked faces during the pandemic and adapted to the current situation. We further confirmed the restriction on infants’ interpersonal experiences with a survey conducted both before and during the pandemic. Overall, these findings demonstrated how the pandemic altered early perceptual development and further confirmed that interpersonal experiences during infancy are critical in their cognitive development.

Exploring the Antecedents to the Reputation of Chinese Public Sector Organizations During COVID-19: An Extension of Situational Crisis Communication Theory

The study is intended to examine the impact of crisis responsibility on the reputation of the Chinese public sector organization during the COVID-19 crisis. In addition to that, the study has also examined the mediating role of crisis response strategy in the relationship between crisis responsibility and the reputation of the Chinese public sector organization during the COVID-19 crisis. Lastly, the study has also examined the moderating role of internal crisis communication in the relationship between the crisis responsibility and crisis response strategy of the Chinese public sector organization during COVID-19. This study bases on a quantitative research approach along with a cross-sectional research design. The population of the study is the Chinese public sector organization companies. Data is collected from the employees working in Chinese public sector organizations. The current study used 500 sample sizes;205 valid responses are received which were used in data analysis. The SEM-PLS is used for the data analysis. The result of the study indicates that all the direct hypotheses are accepted significantly, which indicates that the crisis responsibility and crisis response strategy are significant determinants of organizational reputation during the COVID-19. In a similar vein, the crisis responsibility has placed a significant impact on the crisis response strategy of Chinese organizations during COVID-19. The study is among the pioneer studies on crisis responsibility in the Chinese public sector organization during COVID-19. The study has employed an extended framework encircling the literature on crisis responsibility, crisis response strategy, internal crisis communication, and organizational reputation. Theoretically, the study has extended the situational crisis communication theory framework by incorporating internal crisis communication in the framework.

The initial attempt at home hemodialysis in mainland China (preprint)

Background Observational studies showed home hemodialysis (HHD) to be associated with better survival than facility hemodialysis (HD) and peritoneal dialysis (PD). Patients on HHD have reported higher quality of life and independence. HHD is considered to be an economical way to manage end-stage kidney disease (ESKD). The coronavirus disease 2019 pandemic has had a significant impact on patients with ESKD. Patients on HHD may have an advantage over in-center HHD patients because of a lower risk of exposure to infection.Participants and Methods: We enrolled hemodialysis patients from our dialysis center. We estabilished HHD training center at first. The training center was approved by Chinese government. Doctors, nurses and engineers train and assess patients separately. There are three forms of patient monitoring: home visit, internet remote monitoring, and out-patient service. Demographic and medical data included age, gender, blood pressure, dialysis related data. Laboratory tests were conducted in our central testing laboratory including hemoglobin (Hgb), serum creatinine (Cr), urea nitrogen (BUN), uric acid (UA), albumin (Alb), calcium (Ca), phosphorus (P), parathyroid hormone (PTH), brain natriuretic peptide (BNP).Results Six patients who underwent regular dialysis in the hemodialysis center of our hospital were selected for HHD training. We enrolled 6 patients, including 4 males and 2 females. The mean age of the patients was 47.5 (34.7–55.7) years, the mean dialysis age was 33.5 (11.2–41.5) months. After an average of 16.0 (11.2–25.5) months of training, Alb, P and BNP were improved compared with baseline values. After training, three patients returned home to begin independent hemodialysis. During the follow-up, there are no serious adverse events leading to hospitalization or death, but there are several adverse events. They have been solved quickly by extra home visits of the technicians or online by remote monitoring. During the time, laboratory indicators of all the patients including Hgb, Alb, Ca, P, PTH, BNP, β2-MG remained stable before and after HHD treatment.Conclusion HHD is feasible and safe for ESRD in China, but larger-scale and longer-term studies are needed to further confirm.

Long-term exposure to ambient air pollution and incidence of depression: A population-based cohort study in China.

BACKGROUND: Long-term exposure to ambient air pollution was linked to depression incidence, although the results were limited and inconsistent. OBJECTIVES: To investigate the effects of long-term air pollution exposure on depression risk prospectively in China. METHODS: The present study used data from Yinzhou Cohort on adults without depression at baseline, and followed up until April 2020. Two-year moving average concentrations of particulate matter with a diameter ≤ 2.5 µm (PM2.5), ≤10 µm (PM10) and nitrogen dioxide (NO2) were measured using land-use regression (LUR) models for each participant. Depression cases were ascertained using the Health Information System (HIS) of the local health administration by linking the unique identifiers. We conducted Cox regression models with time-varying exposures to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of depression with each pollutant, after adjusting for a sequence of individual covariates as demographic characteristics, lifestyles, and comorbidity. Besides, physical activity, baseline potential depressive symptoms, cancer status, COVID-19 pandemic, different outcome definitions and air pollution exposure windows were considered in sensitivity analyses. RESULTS: Among the 30,712 adults with a mean age of 62.22 ± 11.25, 1024 incident depression cases were identified over totaling 98,619 person-years of observation. Interquartile range increments of the air pollutants were associated with increased risks of depression, and the corresponding HRs were 1.59 (95%CI: 1.46, 1.72) for PM2.5, 1.49 (95%CI: 1.35, 1.64) for PM10 and 1.58 (95%CI: 1.42, 1.77) for NO2. Subgroup analyses suggested that participants without taking any protective measures towards air pollution were more susceptible. The results remained robust in all sensitivity analyses. CONCLUSIONS: Long-term exposure to ambient air pollution was identified as a risk factor for depression onset. Strategies to reduce air pollution are necessary to decrease the disease burden of depression.

Development and validation of a quantitative, non-invasive, highly sensitive and specific, electrochemical assay for anti-SARS-CoV-2 IgG antibodies in saliva.

Amperial™ is a novel assay platform that uses immobilized antigen in a conducting polymer gel followed by detection via electrochemical measurement of oxidation-reduction reaction between H2O2/Tetrametylbenzidine and peroxidase enzyme in a completed assay complex. A highly specific and sensitive assay was developed to quantify levels of IgG antibodies to SARS-CoV-2 in saliva. After establishing linearity and limit of detection we established a reference range of 5 standard deviations above the mean. There were no false positives in 667 consecutive saliva samples obtained prior to 2019. Saliva was obtained from 34 patients who had recovered from documented COVID-19 or had documented positive serologies. All of the patients with symptoms severe enough to seek medical attention had positive antibody tests and 88% overall had positive results. We obtained blinded paired saliva and plasma samples from 14 individuals. The plasma was analyzed using an EUA-FDA cleared ELISA kit and the saliva was analyzed by our Amperial™ assay. All 5 samples with negative plasma titers were negative in saliva testing. Eight of the 9 positive plasma samples were positive in saliva and 1 had borderline results. A CLIA validation was performed as a laboratory developed test in a high complexity laboratory. A quantitative non-invasive saliva based SARS-CoV-2 antibody test was developed and validated with sufficient specificity to be useful for population-based monitoring and monitoring of individuals following vaccination.

Perioperative Mortality and Complications in Patients with COVID-19 Undergoing Surgery: A Meta-Regression and Meta-Analysis of 8 Cohort Studies (preprint)

Objectives: The novel coronavirus pneumonia (COVID-19)，spread rapidly world wide, was first reported in December 2019. Meanwhile, there are still a large number of patients who need to undergo various surgical treatments. However, the consensus on whether patients with COVID-19 receive emergency or elective surgery will influence their perioperative mortality and complications still cannot be reached. Therefore, we used meta-analysis to explore the impact of patients with COVID-19 perioperative mortality and complications, aiming to provide evidence for clinical decision-making.Methods: We searched PubMed, Embase, Web of Science, Wan Fang database, date from December 2019 to July 2020 for collecting clinical trail on the impact of patients with COVID-19 perioperative mortality and complications. According to the Cochrane system evaluation method, the data is meta-analyzed with RevMan5.3 software.Results: Eight studies involving 2037 patients, 261 (12.81%) patients with COVID-19 and 1776(87.19%) without COVID-19, were included. The results of meta-analysis showed: the COVID-19 group vs Non-COVID-19 group , perioperative mortality and postoperative pneumonia syndrome increased in COVID-19 group（OR:3.84，95%CI：2.10-7.02，I2 =46%， P <0.0001）, (OR: 33.42，95%CI：15.49-72.07，I 2 =0%， P <0.00001), The number of postoperative fever were significantly higher in COVID-19 , There were no significant difference in postoperative complications and ICU admission between the two groups.Conclusions: In our study, The risk of perioperative death and postoperative pulmonary is significantly increased in patients with COVID-19. These data suggested that consideration should be taken for postponing non-critical procedures and promoting nonoperative treatment to delay or avoid the need for surgery during the pandemic of COVID-19.Funding Statement: Natural Science Foundation of China, Grant number: 31760327/ 81760191Declaration of Interests: The authors declare no competing interests.

Associations between air pollution and COVID-19 epidemic during quarantine period in China.

The coronavirus disease (COVID-19) has become a global public health threaten. A series of strict prevention and control measures were implemented in China, contributing to the improvement of air quality. In this study, we described the trend of air pollutant concentrations and the incidence of COVID-19 during the epidemic and applied generalized additive models (GAMs) to assess the association between short-term exposure to air pollution and daily confirmed cases of COVID-19 in 235 Chinese cities. Disease progression based on both onset and report dates as well as control measures as potential confounding were considered in the analyses. We found that stringent prevention and control measures intending to mitigate the spread of COVID-19, contributed to a significant decline in the concentrations of air pollutants except ozone (O3). Significant positive associations of short-term exposure to air pollutants, including particulate matter with diameters ≤2.5 µm (PM2.5), particulate matter with diameters ≤10 µm (PM10), and nitrogen dioxide (NO2) with daily new confirmed cases were observed during the epidemic. Per interquartile range (IQR) increase in PM2.5 (lag0-15), PM10 (lag0-15), and NO2 (lag0-20) were associated with a 7% [95% confidence interval (CI): (4-9)], 6% [95% CI: (3-8)], and 19% [95% CI: (13-24)] increase in the counts of daily onset cases, respectively. Our results suggest that there is a statistically significant association between ambient air pollution and the spread of COVID-19. Thus, the quarantine measures can not only cut off the transmission of virus, but also retard the spread by improving ambient air quality, which might provide implications for the prevention and control of COVID-19.

International-focused Online Forum: A Good Way to Jointly Manage the COVID-19 Pandemic for Global Critical Care Community.

How to cite this article: Xiao-Bo H, Poonyathawon S, Semedi BP, Xiao-Yi Z, Wei F, Da-Wei W, et al. International-focused Online Forum: A Good Way to Jointly Manage the COVID-19 Pandemic for Global Critical Care Community. Indian J Crit Care Med 2020;24(4):283-284.