The Bivalent COVID-19 Booster Immunization after Three Doses of Inactivated Vaccine Augments the Neutralizing Antibody Response against Circulating Omicron Sublineages.

A fourth dose of a COVID-19 vaccine has been recommended by a number of authorities due to waning immunity over time and the emergence of immune-escaping variants. Here, we evaluated the safety and immunogenicity of the bivalent BV-01-B5 or V-01D-351 or the prototype V-01 for heterologous boosting in three-dose inactivated COVID-19 vaccine (ICV) recipients, in comparison with ICV homologous boosting. One pilot study (NCT05583357) included 20 participants randomized at 1:1, either receiving V-01D-351 or CoronaVac. The other one (NCT05585567) recruited 36 participants randomized at 2:1, either receiving BV-01-B5 or V-01, respectively. BV-01-B5, V-01D-351, and V-01 were safe and well-tolerated as heterologous booster shots after three doses of ICV, with adverse reactions predominantly being mild and moderate in severity, similar to the safety profile of ICV boosters. The bivalent V-01D-351 and BV-01-B5 and prototype V-01 booster demonstrated remarkable cross-reactive immunogenicity against the prototype and multiple emerging variants of concern (VOCs), with the geometric mean ratio (versus CoronaVac) in particular being 31.3 (500 vs. 16), 12.0 (192 vs. 16) and 8.5 (136 vs.16) against BA.4/5 14 days after the booster, respectively. Taken together, the modified bivalent-formulation V-01 boosters induced robust neutralizing responses against multiple Omicron sublineages, better than V-01 and remarkably superior to ICV booster, without compromising the safety and tolerability.

Guanylate-binding protein 1 restricts avian coronavirus infectious bronchitis virus-infected HD11 cells.

The Infectious Bronchitis Virus (IBV), a coronavirus, is a key avian pathogen that causes acute and highly infectious viral respiratory diseases. IBV is an enveloped, positive-sense RNA virus, and the host factors that restrict infection and replication of the virus remain poorly understood. Guanylate-binding protein 1 (GBP1), an interferon-gamma (IFN-γ)-inducible guanosine triphosphatase (GTPase), is a major player in host immunity and provides defense against viral replication. However, the role of chicken GBP1 (chGBP1) in the IBV-life cycle is not well understood. Therefore, this study aimed to reveal the potential role of IFN-γ-induced chGBP1 in mediating host anti-IBV infection responses. We identified the host restriction factor, chGBP1, in IBV-infected chicken macrophages HD11 cell lines. We showed that chGBP1 was upregulated by treatment with both IFN-γ and IBV in HD11 cells. chGBP1 inhibited IBV replication in a dose-dependent manner and enhanced IFN-γ anti-IBV activity. Importantly, the GTPase domain of chGBP1 played a pivotal role in its anti-IBV activity. Furthermore, chGBP1 interacts with IBV Nucleocapsids protein to degrade IBV-N protein through the autophagy pathway. Taken together, our results demonstrate a critical role of chGBP1 in anti-IBV in macrophages HD11 cells.

Identification and quantitative analysis of bioactive components from Potentilla kleiniana Wight et Arn with anti HIV-1 proteases activity.

Potentilla kleiniana Wight et Arn（PK, 'Wu Pi Feng' in Chinese） was recorded as Miao ethnic medicine for treatment of fever, cough, ulcer, and erysipelas for thousands years. This study aimed to evaluate the antiviral activity of four PK extracts and seven compounds by using HIV-1 protease (HIV-1 PR). In addition, Ultra-High Performance Liquid Chromatography and High Resolution Mass Spectrometry (UPLC-HRMS) was employed to identify the bioactive components. The toxicity assessment of the extracts was done before antiviral screening using a highly specific human aspartyl protease, renin protease by fluorimetric method. As a result, seven compounds and four extracts of PK inhibited HIV-1 PR with IC50 range from 0.009 to 0.36 mg/mL, and did not appreciably inhibit the general human protease renin. This study first demonstrated that four PK extracts, ellagic acid and ursolic acid potent inhibit HIV-1 protease, could be used as an efficacious drug candidate to treat SARS-CoV-2 infection.

Individual bat viromes reveal the co-infection, spillover and emergence risk of potential zoonotic viruses (preprint)

Bats are reservoir hosts for many zoonotic viruses. Despite this, relatively little is known about the diversity and abundance of viruses within bats at the level of individual animals, and hence the frequency of virus co-infection and inter-species transmission. Using an unbiased meta-transcriptomics approach we characterised the mammalian associated viruses present in 149 individual bats sampled from Yunnan province, China. This revealed a high frequency of virus co-infection and species spillover among the animals studied, with 12 viruses shared among different bat species, which in turn facilitates virus recombination and reassortment. Of note, we identified five viral species that are likely to be pathogenic to humans or livestock, including a novel recombinant SARS-like coronavirus that is closely related to both SARS-CoV-2 and SARS-CoV, with only five amino acid differences between its receptor-binding domain sequence and that of the earliest sequences of SARS-CoV-2. Functional analysis predicts that this recombinant coronavirus can utilize the human ACE2 receptor such that it is likely to be of high zoonotic risk. Our study highlights the common occurrence of inter-species transmission and co-infection of bat viruses, as well as their implications for virus emergence.

Maternal Perinatal Telemonitoring in the Context of the Coronavirus Disease 2019 Pandemic in a Tertiary Health Center in Peru.

OBJECTIVE: This study aimed to describe the characteristics of a telemonitoring program that was rapidly implemented in our institution as a response to the coronavirus disease 2019 (COVID-19) pandemic, as well as the maternal and perinatal outcomes of women who attended this program. STUDY: DESIGN: Retrospective study of patients via phone-call telemonitoring during the peak period of the COVID-19 pandemic (May 2020-August 2020). Maternal and perinatal outcomes were collected and described. Health providers' satisfaction with the telemonitoring program was assessed via an email survey. RESULTS: Twenty-three (69.7%) health providers answered the survey. The mean age was 64.5 years, 91.3% were OB/GYN (obstetrician-gynecologist) doctors, and 95% agreed that telemonitoring is an adequate method to provide health care when in-person visits are difficult. The 78.7% of scheduled telemonitoring consultations were finally completed. We performed 2,181 telemonitoring consultations for 616 pregnant women and 544 telemonitoring consultations for puerperal women. Other medical specialties offering telemonitoring included gynecology, reproductive health, family planning, cardiology, endocrinology, and following up with patients with reactive serology to severe respiratory syndrome coronavirus 2 (SARS-CoV-2). The majority of the population attending our telemonitoring program were categorized as the lowest strata, i.e., III and IV, according to the Human Development Index, and approximately 42% were deemed as high-risk pregnant women. Additionally, we reported the perinatal outcomes of 424 (63%) pregnant women, the most relevant finding being that approximately 53% of them had cesarean sections. CONCLUSION: Telemonitoring is an adequate method of continuing the provision of prenatal care when in-person visits are difficult in situations such as the COVID-19 pandemic. Telemonitoring is feasible even in institutions with no or little experience in telemedicine. The perinatal outcomes in women with telemonitoring seem to be similar to that in the general population. KEY POINTS: · Telemonitoring for prenatal care is feasible even in low-income countries and in a critical scenario.. · OB/GYN doctors agreed with that telemonitoring is an adequate method to provide prenatal care.. · Maternal and perinatal outcomes are similar in women attending a telemonitoring program..

Symptomatic and asymptomatic transmission of SARS-CoV-2 in K-12 schools, British Columbia, April to June 2021 (preprint)

We prospectively studied SARS-CoV-2 transmission at schools in an era of Variants of Concern (VoCs), offering all close contacts serial viral asymptomatic testing up to 14 days. Of 229 school close contacts, 3 tested positive (1.3%), of which 2 were detected through asymptomatic testing. Most secondary transmission (90%) occurred in households. Routine asymptomatic testing of close contacts should be examined in the context of local testing rates, preventive measures, programmatic costs, and health impacts of asymptomatic transmission.

Immunogenicity and safety of the homogenous booster shot of a recombinant fusion protein vaccine (V-01) against COVID-19 in healthy adult participants primed with a two-dose regimen (preprint)

Background: Rising concerns over waning immunity and reduction in neutralizing activity against variants of concern (VOCs) have contributed to deploying booster doses by different strategies to tackle the COVID-19 pandemic. Preliminary findings from Phase I and II have shown that V-01, a recombinant fusion protein vaccine against COVID-19, exhibited favorable safety and immunogenicity profiles in 1060 adult participants of both younger and senior age. Herein, we aimed to assess the immunogenicity and safety for a booster dose in participants previously primed with a two-dose 10mcg V-01 regimen (day 0, 21) from phase I trial, providing reassuring data for necessity and feasibility of a homogenous booster dose. Methods: We conducted a single-arm, open-label trial at the Guangdong Provincial Center for Disease Control and Prevention (Gaozhou, China). Forty-three eligible participants who were previously primed 4-5 months earlier with two-dose 10mcg V-01 regimen from phase I trial received booster vaccination. We primarily assessed the immunogenicity post-booster vaccination, measured by RBD-binding antibodies using ELISA and neutralizing activity against wild-type SARS-CoV-2 and emerging variants of concern (VOCs) using neutralization assays. We secondarily assessed the safety and reactogenicity of the booster vaccination. Results: The third dose of V-01 exhibited significant boosting effects of humoral immune response in participants primed with two-dose 10g V-01 regimen regarding both wild-type SARS-CoV-2 and VOCs. We observed a 60.4-folds increase in neutralizing titres against SARS-CoV-2 of younger adults, with GMTs of 17 (95%CI: 12-23) prior to booster vaccination in comparison to 1017 (95%CI: 732-1413) at day 14 post booster vaccination; and a 53.6-folds increase in that of older adults, with GMTs of 14 (95%CI: 9-20) before booster vaccination in comparison to 729(95%CI: 397-1339) at day 14 post-booster vaccination. The neutralizing titres against SARS-CoV-2 Delta strain also demonstrated a sharp increase from the day of pre booster vaccination to day 14 post booster vaccination, with GMTs of 11 (95%CI:8-15) versus 383 (95%CI:277-531) in younger adults (35.4-folds increase), and 6.5(95%CI: 5-8) versus 300(95%CI:142-631) in older adults (46.0-folds increase), respectively. We also observed a considerable and consistent increase of pseudovirus neutralizing titres against emerging VOCs from day 28 post second vaccination to day 14 post booster vaccination, with GMTs of 206 (95%CI:163-259) versus 607 (95%CI: 478-771) for Alpha strain, 54 (95%CI:38-77) versus 329 (95%CI: 255-425) for Beta strain, 219 (95%CI:157-306) versus 647 (95%CI: 484-865) for Delta strain. Our preliminary findings indicate a homogenous booster dose of V-01 was safe and well-tolerated, with overall adverse reactions being absent or mild-to-moderate in severity, and no grade 3 or worse AEs were related to booster vaccination. Conclusions: A homogenous booster immunization in participants receiving a primary series of two-dose V-01 elicited a substantial humoral immune response against wild-type SARS-CoV-2 and emerging VOCs, along with a favorable safety and reactogenicity profile. Our study provided promising data for a homogenous prime-boost strategy using recombinant protein vaccine to tackle the ongoing pandemic, potentially providing broad protection against emerging VOCs and overcoming waning immunity.

Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2 (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used solely for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLN. A low dose of I-R-F induces not only high titer long-lasting neutralizing antibodies but also comprehensive T cell responses than RBD, and even provides comprehensive protection in one dose without adjuvant. This study shows that the I-R-F vaccine provides rapid and complete protection throughout upper and lower respiratory tracts against high dose SARS-CoV-2 challenge in rhesus macaques. Due to its potency and safety, this engineered vaccine may become one of the next-generation vaccine candidates in the global race to defeat COVID-19.

Early Improvement of Acute Respiratory Distress Syndrome in Patients With COVID-19 in the Intensive Care Unit: Retrospective Analysis.

BACKGROUND: Since the start of the COVID-19 pandemic, there have been over 2 million deaths globally. Acute respiratory distress syndrome (ARDS) may be the main cause of death. OBJECTIVE: This study aimed to describe the clinical features, outcomes, and ARDS characteristics of patients with COVID-19 admitted to the intensive care unit (ICU) in Chongqing, China. METHODS: The epidemiology of COVID-19 from January 21, 2020, to March 15, 2020, in Chongqing, China, was analyzed retrospectively, and 75 ICU patients from two hospitals were included in this study. On day 1, 56 patients with ARDS were selected for subgroup analysis, and a modified Poisson regression was performed to identify predictors for the early improvement of ARDS (eiARDS). RESULTS: Chongqing reported a 5.3% case fatality rate for the 75 ICU patients. The median age of these patients was 57 (IQR 25-75) years, and no bias was present in the sex ratio. A total of 93% (n=70) of patients developed ARDS during ICU stay, and more than half had moderate ARDS. However, most patients (n=41, 55%) underwent high-flow nasal cannula oxygen therapy, but not mechanical ventilation. Nearly one-third of patients with ARDS improved (arterial blood oxygen partial pressure/oxygen concentration >300 mm Hg) in 1 week, which was defined as eiARDS. Patients with eiARDS had a higher survival rate and a shorter length of ICU stay than those without eiARDS. Age (<55 years) was the only variable independently associated with eiARDS, with a risk ratio of 2.67 (95% CI 1.17-6.08). CONCLUSIONS: A new subphenotype of ARDS-eiARDS-in patients with COVID-19 was identified. As clinical outcomes differ, the stratified management of patients based on eiARDS or age is highly recommended.

Impact of a long-term air pollution exposure on the case fatality rate of COVID-19 patients-A multicity study.

Evidence in the literature suggests that air pollution exposure affects outcomes of patients with COVID-19. However, the extent of this effect requires further investigation. This study was designed to investigate the relationship between long-term exposure to air pollution and the case fatality rate (CFR) of patients with COVID-19. The data on air quality index (AQI), PM2.5, PM10, SO2 , NO2 , and O3 from 14 major cities in China in the past 5 years (2015-2020) were collected, and the CRF of COVID-19 patients in these cities was calculated. First, we investigated the correlation between CFR and long-term air quality indicators. Second, we examined the air pollutants affecting CFR and evaluated their predictive values. We found a positive correlation between the CFR and AQI (1, 3, and 5 years), PM2.5 (1, 3, and 5 years), and PM10 (1, 3, and 5 years). Further analysis indicated the more significant correlation for both AQI (3 and 5 years) and PM2.5 (1, 3, and 5 years) with CFR, and moderate predictive values for air pollution indicators such as AQI (1, 3, and 5 years) and PM2.5 (1, 3, and 5 years) for CFR. Our results indicate that long-term exposure to severe air pollution is associated with higher CFR of COVID-19 patients. Air pollutants such as PM2.5 may assist with the prediction of CFR for COVID-19 patients.

Psychological Resilience as a Protective Factor for Depression and Anxiety Among the Public During the Outbreak of COVID-19.

BACKGROUND: Psychological resilience may reduce the impact of psychological distress to some extent. We aimed to investigate the mental health status of the public during the outbreak of coronavirus disease 2019 (COVID-19) and explore the level and related factors of anxiety and depression. METHODS: From February 8 to March 9, 2020, 3,180 public completed the Zung's Self-Rating Anxiety Scale (SAS) for anxiety, Zung's Self-Rating Depression Scale (SDS) for depression, the Connor-Davidson resilience scale (CD-RISC) for psychological resilience, and the Simplified Coping Style Questionnaire (SCSQ) for the attitudes and coping styles. RESULTS: The number of people with depressive symptoms (SDS > 53) was 1,303 (the rate was 41.0%). The number of people with anxiety symptoms (SAS > 50) was 1,184 (the rate was 37.2%). The depressed group and anxiety group had less education, more unmarried and younger age, as well as had significant different in SDS total score (P < 0.001), SAS total score (P < 0.001), CD-RISC total score (P < 0.001), and SCSQ score (P < 0.001). The binary logistic regression showed that female (B = -0.261, P = 0.026), strength (B = -0.079, P = 0.000), and the subscales of active coping style in SCSQ (B = -0.983, P = 0.000) remained protective factors and passive coping style (B = 0.293, P = 0.003) and higher SAS score (B = 0.175, P = 0.000) were risk factors for depression. Optimism (B = -0.041, P = 0.015) in CD-RISC was a protective factor, and passive coping styles (B = 0.483, P = 0.000) and higher SDS score (B = 0.134, P = 0.000) were risk factors for anxiety. LIMITATIONS: This study adopted a cross-sectional design and used self-report questionnaires. CONCLUSION: The mental health of the public, especially females, the younger and less educational populations, and unmarried individuals, should be given more attention. Individuals with high level of mental resilience and active coping styles would have lower levels of anxiety and depression during the outbreak of COVID-19.

Game analysis on the evolution of COVID-19 epidemic under the prevention and control measures of the government.

In this paper, the interaction strategies and the evolutionary game analysis of the actions taken by the government and the public in the early days of the epidemic are incorporated into the natural transmission mechanism model of the epidemic, and then the transmission frequency equations of COVID-19 epidemic is established. According to the cumulative confirmed cases of COVID-19 in the UK and China, the upper limit of the spread of COVID-19 in different evolutionary scenarios is set. Using SPSS to perform logistic curve fitting, the frequency fitting equations of cumulative confirmed cases under different evolution scenarios are obtained respectively. The analysis result shows that the emergency response strategy adopted by the government in the early days of the epidemic can effectively control the spread of the epidemic. Combined with the transmission frequency equation of COVID-19 epidemic, measures taken by the government are analyzed. The influence of each measure on the frequency variable is judged and then the influence on the spread of the epidemic is obtained. Finally, based on the above analysis, the government is advised to adhere to the principles of scientific, initiative and flexibility when facing major epidemics.

CT radiomics can help screen the Coronavirus disease 2019 (COVID-19): a preliminary study

The Coronavirus disease 2019 (COVID-19) is raging across the world. The radiomics, which explores huge amounts of features from medical image for disease diagnosis, may help the screen of the COVID-19. In this study, we aim to develop a radiomic signature to screen COVID-19 from CT images. We retrospectively collect 75 pneumonia patients from Beijing Youan Hospital, including 46 patients with COVID-19 and 29 other types of pneumonias. These patients are divided into training set (n = 50) and test set (n = 25) at random. We segment the lung lesions from the CT images, and extract 77 radiomic features from the lesions. Then unsupervised consensus clustering and multiple cross-validation are utilized to select the key features that are associated with the COVID-19. In the experiments, while twenty-three radiomic features are found to be highly associated with COVID-19, four key features are screened and used as the inputs of support vector machine to build the radiomic signature. We use area under the receiver operating characteristic curve (AUC) and calibration curve to assess the performance of our model. It yields AUCs of 0.862 and 0.826 in the training set and the test set respectively. We also perform the stratified analysis and find that its predictive ability is not affected by gender, age, chronic disease and degree of severity. In conclusion, we investigate the value of radiomics in screening COVID-19, and the experimental results suggest the radiomic signature could be a potential tool for diagnosis of COVID-19.