Pathogenicity analysis of one avian infectious bronchitis virus stain isolated from Shanxi

In order to perform the isolation of avian infectious bronchitis virus (IBV) and study the pathogenicity of IBV isolate, the RT-PCR was used to detect nucleic acid extracted from a clinical sample of chickens, which were suspected to be infected with infectious bronchitis virus (IBV) and provided by a farmer in Yuncheng, Shanxi province. And the sample was detected as IBV positive by RT-PCR. Then 9-11-day-old SPF chicken embryonated eggs were inoculated with the sample filtered from the grinding fluid, and the obtained allantoic fluid was blindly passed by three generations (F3) and was also tested as IBV positive;The F11 generation passaged in embryonated eggs caused typical "dwarf embryo" lesions to SPF chicken embryonated eggs, and induced the loss of cilia in tracheal rings. The results showed that an IBV strain was isolated and named as YC181031. The S1 gene amplification and sequencing analysis showed that YC181031 strain belonged to IBV GI-22 genotype, which is also nephropathogenic type IBV. Seven-day-old SPF chicks were used to test the pathogenicity of the isolate. The results showed that several clinical symptoms were showed in chicks infected with YC181031, such as breathing with difficulty, depression, excreting watery droppings and death. The mortality of infected chicks was 20%. Typical pathological changes such as enlargement of kidney and urate deposition in the kidney were observed in infected chicks. The immunohistochemical assay and viral load detection were performed for the tissue samples from infected and dead chicks. The tissue lesions and distribution of virus were observed in the kidney, trachea, lung, glandular stomach, spleen and liver samples of infected chicks. RT-PCR detection of pharyngeal anal swabs showed that the virus shedding by infected chicks could be continuously detected within 14 days of the test period;The viral loads of various tissues were detected by RT-qPCR and the results showed that the viral load from high to low was kidney, trachea, lung, stomach, spleen and liver. The viral load of kidney was significantly higher than that of other tissues (P < 0.05).In this study, the pathogenicity characteristics of GI-22 genotype strain were systematically studied for the first time, providing a reference for the prevention and treatment of the disease.

The impacts of COVID-19 outbreak on mental health in general population in different areas in China.

BACKGROUND: This study aimed to explore the impacts of COVID-19 outbreak on mental health status in general population in different affected areas in China. METHODS: This was a comparative study including two groups of participants: (1) general population in an online survey in Ya'an and Jingzhou cities during the COVID-19 outbreak from 10-20 February 2020; and (2) matching general population selected from the mental health survey in Ya'an in 2019 (from January to May 2019). General Health Questionnaire (GHQ-12), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS) were used. RESULTS: There were 1775 participants (Ya'an in 2019 and 2020: 537 respectively; Jingzhou in 2020: 701). Participants in Ya'an had a significantly higher rate of general health problems (GHQ scores ⩾3) in 2020 (14.7%) than in 2019 (5.2%) (p < 0.001). Compared with Ya'an (8.0%), participants in Jingzhou in 2020 had a significantly higher rate of anxiety (SAS scores ⩾50, 24.1%) (p < 0.001). Participants in Ya'an in 2020 had a significantly higher rate of depression (SDS scores ⩾53, 55.3%) than in Jingzhou (16.3%) (p < 0.001). The risk factors of anxiety symptoms included female, number of family members (⩾6 persons), and frequent outdoor activities. The risk factors of depression symptoms included participants in Ya'an and uptake self-protective measures. CONCLUSIONS: The prevalence of psychological symptoms has increased sharply in general population during the COVID-19 outbreak. People in COVID-19 severely affected areas may have higher scores of GHQ and anxiety symptoms. Culture-specific and individual-based psychosocial interventions should be developed for those in need during the COVID-19 outbreak.

Psychological symptoms and correlates of Chinese healthcare professionals in the intensive care unit before and after the COVID-19 outbreak: A comparison of two cross-sectional studies.

BACKGROUND: The outbreak of COVID-19 disarranged lives across mainland China. No study has examined changes in psychological symptoms of healthcare professionals in the intensive care unit (ICU) before and after the outbreak of COVID-19. The aim of this study was to estimate changes in psychological symptoms of ICU healthcare professionals before and after the COVID-19 outbreak, and to analyze factors related to psychological symptoms. METHODS: Two waves' administrations were implemented between December 13 and December 14, 2018, and between April 5 and April 7, 2020, respectively. The symptom checklist-90 (SCL-90) were used to evaluate psychological symptoms. Multiple logistical regression was used to reveal the risk of psychological symptoms. RESULTS: A total of 3902 and 3908 ICU healthcare professionals took part in the first and second surveys. The mean total score of the SCL-90 was 179.27 (70.02) at wave 1 and 147.75 (58.40) at wave 2, respectively. The proportion of psychological symptoms was 55.6 % (95%CI = 54.0-57.1) at wave 1. But rates of psychological symptoms decreased to 36.6 % (95%CI = 35.1-38.2) at wave 2. ICU healthcare professionals with western economic belt and 6-10 years of work were more likely to develop psychological symptoms, while ICU healthcare professionals with the later survey and doctoral degree were less likely to develop psychological symptoms. CONCLUSION: Although COVID-19 period benefited psychological symptoms of ICU healthcare professionals, psychological symptoms still had a related high prevalence. Regular screening and appropriate interventions should still be implemented to decrease the risk for psychological symptoms among Chinese ICU healthcare professionals.

Efficacy and Safety of a Booster Vaccination with Two Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults: Results of a Double-Blind, Randomized, Placebo-Controlled, Phase 3 Trial in Abu Dhabi.

IMPORTANCE: The protective efficacy of COVID-19 vaccinations has declined over time such that booster doses are required. OBJECTIVE: To evaluate the efficacy and adverse events of booster doses of two inactivated COVID-19 vaccines. DESIGN: This is a double-blind, randomized, placebo-controlled phase 3 trial aiming to evaluate the protective efficacy, safety, and immunogenicity of inactivated SARS-CoV-2 vaccine (Vero cells) after inoculation with booster doses of inactivated COVID-19 vaccine. SETTING: Healthy volunteers were recruited in an earlier phase 3 trial of two doses of inactivated vaccine. The participants in Abu Dhabi maintained the blind state of the trial and received a booster dose of vaccine or placebo at least six months after the primary immunization. PARTICIPANTS: Adults aged 18 and older with no history of SARS-CoV, SARS-CoV-2, or Middle East respiratory syndrome infection (via onsite inquiry) were screened for eligibility. INTERVENTIONS: A total of 9370 volunteers were screened and randomly allocated, of which 61 voluntarily withdrew from the screening stage without booster inoculation; 9309 received the booster vaccination, with 3083 in the WIV04 group, 3150 in the HB02 group, and 3076 in the alum-only group. Further, 5µg and 4µg of inactivated SARS-CoV-2 virion was adsorbed into aluminum hydroxide in a 0.5 mL aqueous suspension for WIV04 and HB02 vaccines. MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was the prevention of PCR-confirmed symptomatic COVID-19 from 14 days after the booster vaccine in the per-protocol population. A safety analysis was performed in the intention-to-treat population. RESULTS: Symptomatic COVID-19 was identified in 36 participants in the WIV04 group (9.9 [95% CI, 7.2-13.8] per 1000 person-years), 28 in the HB02 group (7.6 [95% CI, 5.2-11.0] per 1000 person-years), and 193 in the alum-only group (55.2 [95% CI, 47.9-63.5] per 1000 person-years), resulting in a vaccine efficacy of 82.0% (95% CI, 74.2-87.8%) for WIV04 and 86.3% (95% CI, 79.6-91.1%) for HB02. One severe case of COVID-19 occurred in the alum-only group, and none occurred in the vaccine groups. Adverse reactions within seven days after vaccination occurred in 29.4% to 34.3% of participants in the three groups. Serious adverse events were rare and not related to vaccines (WIV04: 17 [0.5%]; HB02: 11 [0.4%]; alum only: 40 [1.3%]). CONCLUSIONS AND RELEVANCE: This study evaluated the safety of the booster dose, which was well tolerated by participants. Booster doses given over six months after the completion of primary immunization can help to provide more-effective protection against COVID-19 in healthy people 18 years of age or older. At the same time, the anti-SARS-CoV-2 antibodies produced by the two groups of experimental vaccines exhibited extensive cross-neutralization against representative SARS-CoV-2 variants. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov (NCT04510207).

Safety and immunogenicity of a mosaic vaccine booster against Omicron and other SARS-CoV-2 variants: a randomized phase 2 trial.

An ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate, named NVSI-06-09, as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had administered two or three doses of inactivated vaccine BBIBP-CorV at least 6 months prior to enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. Between May 25 and 30, 2022, 516 adults received booster vaccination with 260 in NVSI-06-09 group and 256 in BBIBP-CorV group. Interim results showed a similar safety profile between two booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 post-booster, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those by BBIBP-CorV. Our findings indicated that a booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against divergent SARS-CoV-2 variants, including Omicron and its sub-lineages.

Symptomatic and Asymptomatic SARS-CoV-2 Infection and Follow-up of Neutralizing Antibody Levels.

Objective: To investigate neutralizing antibody levels in symptomatic and asymptomatic patients with coronavirus disease 2019 (COVID-19) at 6 and 10 months after disease onset. Methods: Blood samples were collected at three different time points from 27 asymptomatic individuals and 69 symptomatic patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Virus-neutralizing antibody titers against SARS-CoV-2 in both groups were measured and statistically analyzed. Results: The symptomatic and asymptomatic groups had higher neutralizing antibodies at 3 months and 1-2 months post polymerase chain reaction confirmation, respectively. However, neutralizing antibodies in both groups dropped significantly to lower levels at 6 months post-PCR confirmation. Conclusion: Continued monitoring of symptomatic and asymptomatic individuals with COVID-19 is key to controlling the infection.

Application of ultrasonography in neonatal lung disease: An updated review.

Lung disease is often life-threatening for both preterm and term newborns. Therefore, an accurate and rapid diagnosis of lung diseases in newborns is crucial, as management strategies differ with different etiologies. To reduce the risk of radiation exposure derived from the conventionally used chest x-ray as well as computed tomography scans, lung ultrasonography (LUS) has been introduced in clinical practice to identify and differentiate neonatal lung diseases because of its radiation-free characteristic, convenience, high accuracy, and low cost. In recent years, it has been proved that LUS exhibits high sensitivity and specificity for identifying various neonatal lung diseases. Here, we offer an updated review of the applications of LUS in neonatal lung diseases based on the reports published in recent years (2017 to present).

A Chess and Card Room-Induced COVID-19 Outbreak and Its Agent-Based Simulation in Yangzhou, China.

Objective: To evaluate epidemiological characteristics of the COVID-19 outbreak that resurged in Yangzhou and to simulate the impact of different control measures at different regional scales. Methods: We collected personal information from 570 laboratory-confirmed cases in Yangzhou from 28 July to 26 August 2021, and built a modified susceptible-exposed-infected-removed (SEIR) model and an agent-based model. Results: The SEIR model showed that for passengers from medium-high risk areas, pre-travel nucleic acid testing within 3 days could limit the total number of infected people in Yangzhou to 50; among elderly persons, a 60% increase in vaccination rates could reduce the estimated infections by 253. The agent-based model showed that when the population density of the chess and card room dropped by 40%, the number of infected people would decrease by 54 within 7 days. A ventilation increase in the chess and card room from 25 to 50% could reduce the total number of infections by 33 within 7 days; increasing the ventilation from 25 to 75% could reduce the total number of infections by 63 within 7 days. Conclusions: The SEIR model and agent-based model were used to simulate the impact of different control measures at different regional scales successfully. It is possible to provide references for epidemic prevention and control work.

Intranasal vaccination with lipid-conjugated immunogens promotes antigen transmucosal uptake to drive mucosal and systemic immunity.

To combat the HIV epidemic and emerging threats such as SARS-CoV-2, immunization strategies are needed that elicit protection at mucosal portals of pathogen entry. Immunization directly through airway surfaces is effective in driving mucosal immunity, but poor vaccine uptake across the mucus and epithelial lining is a limitation. The major blood protein albumin is constitutively transcytosed bidirectionally across the airway epithelium through interactions with neonatal Fc receptors (FcRn). Exploiting this biology, here, we demonstrate a strategy of "albumin hitchhiking" to promote mucosal immunity using an intranasal vaccine consisting of protein immunogens modified with an amphiphilic albumin-binding polymer-lipid tail, forming amph-proteins. Amph-proteins persisted in the nasal mucosa of mice and nonhuman primates and exhibited increased uptake into the tissue in an FcRn-dependent manner, leading to enhanced germinal center responses in nasal-associated lymphoid tissue. Intranasal immunization with amph-conjugated HIV Env gp120 or SARS-CoV-2 receptor binding domain (RBD) proteins elicited 100- to 1000-fold higher antigen-specific IgG and IgA titers in the serum, upper and lower respiratory mucosa, and distal genitourinary mucosae of mice compared to unmodified protein. Amph-RBD immunization induced high titers of SARS-CoV-2-neutralizing antibodies in serum, nasal washes, and bronchoalveolar lavage. Furthermore, intranasal amph-protein immunization in rhesus macaques elicited 10-fold higher antigen-specific IgG and IgA responses in the serum and nasal mucosa compared to unmodified protein, supporting the translational potential of this approach. These results suggest that using amph-protein vaccines to deliver antigen across mucosal epithelia is a promising strategy to promote mucosal immunity against HIV, SARS-CoV-2, and other infectious diseases.

Safety and immunogenicity of a hybrid-type vaccine booster in BBIBP-CorV recipients in a randomized phase 2 trial.

NVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluate the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in BBIBP-CorV recipients in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates (NCT05069129). Three groups of healthy adults over 18 years of age (600 participants per group) who have administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, are randomized 1:1 to receive either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The incidence of adverse reactions is low, and the overall safety profile is quite similar between two booster regimens. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster are significantly higher than those by BBIBP-CorV booster against not only SARS-CoV-2 prototype strain but also multiple variants of concerns (VOCs). Especially, the neutralizing antibody GMT against Omicron variant induced by heterologous NVSI-06-08 booster reaches 367.67, which is substantially greater than that boosted by BBIBP-CorV (GMT: 45.03). In summary, NVSI-06-08 is safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which is immunogenically superior to the homologous boost with another dose of BBIBP-CorV.

Efficacy and Safety of Chinese Medicine Lianhua Qingwen for Treating COVID-19: An Updated meta-Analysis.

The traditional Chinese medicine formula Lianhua Qingwen (LQ) combined with western medicine therapy is beneficial to coronavirus disease-19 (COVID-19), but there is still a lack of strong evidence-based. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of LQ combined with western medicine for patients with COVID-19. Seven databases (Chinese and English) were searched by two independent reviewers. Search for relevant keywords such as "Chinese medicine," "Chinese herbal medicine," and "Lianhua Qingwen" in the titles and abstracts of articles retrieved in the databases. Randomized controlled trials or case-control studies that reported sufficient data of participants before and after the intervention were included. Two researchers independently reviewed the studies and extracted the data. Fixed-or random-effect model was used to calculate the overall pooled risk estimates. Forest plots were generated to show pooled results. Seven studies involving 916 participants were included in the meta-analysis. Overall, compared with the control group, the total efficacy (OR = 2.23, 95% CI 1.56, 3.18), adverse events (OR = 0.42, 95% CI 0.18, 0.97), chest computed tomography manifestations (OR = 1.74, 95% CI 1.12, 2.72), and aggravation rate of conversion to severe cases (OR = 0.47, 95% CI 0.30, 0.75) of the intervention group were better. Moreover, the intervention group has an advantage over the control group in improving clinical symptoms (fever, cough, fatigue, chest tightness, shortness of breath, and expectoration) and shortening the fever duration (p < 0.05). Our findings indicate that LQ combined with western medicine may be more effective in treating COVID-19. However, due to the urgency of SARS-CoV-2 outbreaks leading to low methodological quality and not rigorous designs. This meta-analysis cannot draw clear conclusions. PROSPERO registration number: CRD42020190757.

Assessment of the Benefits of Targeted Interventions for Pandemic Control in China Based on Machine Learning Method and Web Service for COVID-19 Policy Simulation.

Taking the Chinese city of Xiamen as an example, simulation and quantitative analysis were performed on the transmissions of the Coronavirus Disease 2019 (COVID-19) and the influence of intervention combinations to assist policymakers in the preparation of targeted response measures. A machine learning model was built to estimate the effectiveness of interventions and simulate transmission in different scenarios. The comparison was conducted between simulated and real cases in Xiamen. A web interface with adjustable parameters, including choice of intervention measures, intervention weights, vaccination, and viral variants, was designed for users to run the simulation. The total case number was set as the outcome. The cumulative number was 4,614,641 without restrictions and 78 under the strictest intervention set. Simulation with the parameters closest to the real situation of the Xiamen outbreak was performed to verify the accuracy and reliability of the model. The simulation model generated a duration of 52 days before the daily cases dropped to zero and the final cumulative case number of 200, which were 25 more days and 36 fewer cases than the real situation, respectively. Targeted interventions could benefit the prevention and control of COVID-19 outbreak while safeguarding public health and mitigating impacts on people's livelihood.

Immunogenicity and safety of NVSI-06-07 as a heterologous booster after priming with BBIBP-CorV: a phase 2 trial.

The increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccination. We conducted a randomised, double-blinded, controlled, phase 2 trial to assess the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated COVID-19 vaccine (BBIBP-CorV) followed by a recombinant protein-based vaccine (NVSI-06-07), using homologous boost with BBIBP-CorV as control. Three groups of healthy adults (600 individuals per group) who had completed two-dose BBIBP-CorV vaccinations 1-3 months, 4-6 months and ≥6 months earlier, respectively, were randomly assigned in a 1:1 ratio to receive either NVSI-06-07 or BBIBP-CorV boost. Immunogenicity assays showed that in NVSI-06-07 groups, neutralizing antibody geometric mean titers (GMTs) against the prototype SARS-CoV-2 increased by 21.01-63.85 folds on day 28 after vaccination, whereas only 4.20-16.78 folds of increases were observed in control groups. For Omicron variant, the neutralizing antibody GMT elicited by homologous boost was 37.91 on day 14, however, a significantly higher neutralizing GMT of 292.53 was induced by heterologous booster. Similar results were obtained for other SARS-CoV-2 variants of concerns (VOCs), including Alpha, Beta and Delta. Both heterologous and homologous boosters have a good safety profile. Local and systemic adverse reactions were absent, mild or moderate in most participants, and the overall safety was quite similar between two booster schemes. Our findings indicated that NVSI-06-07 is safe and immunogenic as a heterologous booster in BBIBP-CorV recipients and was immunogenically superior to the homologous booster against not only SARS-CoV-2 prototype strain but also VOCs, including Omicron.

The incidence of COVID-19 infection following emergency use authorization of BBIBP-CORV inactivated vaccine in frontline workers in the United Arab Emirates.

Based on the findings from the Phase III clinical trials of inactivated SARS COV-2 Vaccine, (BBIBP-CORV) emergency use authorization (EUA) was granted for the vaccine to frontline workers in the UAE. A prospective cohort study was conducted among frontline workers to estimate the incidence rate and risk of symptomatic COVID-19 infection 14 days after the second dose of inoculation with BBIBP-CORV inactivated vaccine. Those who received two doses of the BBIBP-CORV vaccine in the period from 14th of September 2020 (first dose) to 21st of December 2020 (second dose) were followed up for COVID-19 infections. 11,322 individuals who received the two-dose BBIBP-CORV vaccine were included and were followed up post the second dose plus fourteen days. The incidence rate of symptomatic infection was 0.08 per 1000-person days (95% CI 0.07, 0.10). The estimated absolute risk of developing symptomatic infection was 0.97% (95% CI 0.77%, 1.17%). The confirmed seroconversion rate was 92.8%. There were no serious adverse events reported and no individuals suffered from severe disease. Our findings show that vaccinated individuals are likely to remain protected against symptomatic infection or becoming PCR positive for SARS COV 2 following the second dose of the vaccination.

Prediction of in-hospital recurrence and false-negative results in patients with COVID-19 by red blood cell values on admission.

The clinical characteristics and risk factors of patients with coronavirus disease 2019 (COVID-19) with re-positive or false-negative test results have so far remained to be determined. The present study provides a cross-sectional observational study on 134 hospitalized patients selected from Huoshenshan Hospital (Wuhan, China) using cluster sampling. A total of 68 patients had reduced red blood cell (RBC) counts, 55 a decrease in the hemoglobin concentration (HBC) and 73 a decline in hematocrit (HCT). The false-negative rate of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA detection in pharyngeal swab specimens was 18.7%. The absolute lymphocyte count (ALC), RBC, HBC and HCT levels in false-negative patients were significantly higher than those in patients who tested positive for viral nucleic acids. Multivariate logistic regression analysis indicated that RBC [odds ratio (OR)=0.43, 95% CI: 0.18-0.99], HBC (OR=0.97, 95% CI: 0.94-0.99) and ALC (OR=0.43, 95% CI: 0.20-0.91) were the factors influencing the negative testing results for viral nucleic acid. The rate of re-positive patients was 16.4%. The white blood cell, RBC, HBC and HCT values in re-positive patients were lower than those in non-re-positive patients. The median (interquartile range) values for RBC, HBC and HCT of male re-positive patients were 3.95 (3.37, 4.2) x1012/l, 123 (103, 133) g/l and 36.6 (31.1, 39.2)%, respectively, while the RBC, HBC and HCT of female re-positive patients were 3.54 (3.13, 3.74) x1012/l, 115 (102, 118) g/l and 34.2 (28.5, 34.9)%, respectively. It was determined that RBC, HBC and HCT values had moderate accuracy in predicting SARS-CoV-2 recurrence in patients with COVID-19 using receiver operating curve analysis. The present study suggested that RBC may have an important role in the pathogenesis of COVID-19.

Effect of 2 Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults: A Randomized Clinical Trial.

Importance: Although effective vaccines against COVID-19 have been developed, additional vaccines are still needed. Objective: To evaluate the efficacy and adverse events of 2 inactivated COVID-19 vaccines. Design, Setting, and Participants: Prespecified interim analysis of an ongoing randomized, double-blind, phase 3 trial in the United Arab Emirates and Bahrain among adults 18 years and older without known history of COVID-19. Study enrollment began on July 16, 2020. Data sets used for the interim analysis of efficacy and adverse events were locked on December 20, 2020, and December 31, 2020, respectively. Interventions: Participants were randomized to receive 1 of 2 inactivated vaccines developed from SARS-CoV-2 WIV04 (5 µg/dose; n = 13 459) and HB02 (4 µg/dose; n = 13 465) strains or an aluminum hydroxide (alum)-only control (n = 13 458); they received 2 intramuscular injections 21 days apart. Main Outcomes and Measures: The primary outcome was efficacy against laboratory-confirmed symptomatic COVID-19 14 days following a second vaccine dose among participants who had no virologic evidence of SARS-CoV-2 infection at randomization. The secondary outcome was efficacy against severe COVID-19. Incidence of adverse events and reactions was collected among participants who received at least 1 dose. Results: Among 40 382 participants randomized to receive at least 1 dose of the 2 vaccines or alum-only control (mean age, 36.1 years; 32 261 [84.4%] men), 38 206 (94.6%) who received 2 doses, contributed at least 1 follow-up measure after day 14 following the second dose, and had negative reverse transcriptase-polymerase chain reaction test results at enrollment were included in the primary efficacy analysis. During a median (range) follow-up duration of 77 (1-121) days, symptomatic COVID-19 was identified in 26 participants in the WIV04 group (12.1 [95% CI, 8.3-17.8] per 1000 person-years), 21 in the HB02 group (9.8 [95% CI, 6.4-15.0] per 1000 person-years), and 95 in the alum-only group (44.7 [95% CI, 36.6-54.6] per 1000 person-years), resulting in a vaccine efficacy, compared with alum-only, of 72.8% (95% CI, 58.1%-82.4%) for WIV04 and 78.1% (95% CI, 64.8%-86.3%) for HB02 (P < .001 for both). Two severe cases of COVID-19 occurred in the alum-only group and none occurred in the vaccine groups. Adverse reactions 7 days after each injection occurred in 41.7% to 46.5% of participants in the 3 groups; serious adverse events were rare and similar in the 3 groups (WIV04: 64 [0.5%]; HB02: 59 [0.4%]; alum-only: 78 [0.6%]). Conclusions and Relevance: In this prespecified interim analysis of a randomized clinical trial, treatment of adults with either of 2 inactivated SARS-CoV-2 vaccines significantly reduced the risk of symptomatic COVID-19, and serious adverse events were rare. Data collection for final analysis is pending. Trial Registration: ClinicalTrials.gov Identifier: NCT04510207; Chinese Clinical Trial Registry: ChiCTR2000034780.

Genomic epidemiology of SARS-CoV-2 in the UAE reveals novel virus mutation, patterns of co-infection and tissue specific host immune response.

To unravel the source of SARS-CoV-2 introduction and the pattern of its spreading and evolution in the United Arab Emirates, we conducted meta-transcriptome sequencing of 1067 nasopharyngeal swab samples collected between May 9th and Jun 29th, 2020 during the first peak of the local COVID-19 epidemic. We identified global clade distribution and eleven novel genetic variants that were almost absent in the rest of the world and that defined five subclades specific to the UAE viral population. Cross-settlement human-to-human transmission was related to the local business activity. Perhaps surprisingly, at least 5% of the population were co-infected by SARS-CoV-2 of multiple clades within the same host. We also discovered an enrichment of cytosine-to-uracil mutation among the viral population collected from the nasopharynx, that is different from the adenosine-to-inosine change previously reported in the bronchoalveolar lavage fluid samples and a previously unidentified upregulation of APOBEC4 expression in nasopharynx among infected patients, indicating the innate immune host response mediated by ADAR and APOBEC gene families could be tissue-specific. The genomic epidemiological and molecular biological knowledge reported here provides new insights for the SARS-CoV-2 evolution and transmission and points out future direction on host-pathogen interaction investigation.

PTP-MEG2 regulates quantal size and fusion pore opening through two distinct structural bases and substrates.

Tyrosine phosphorylation of secretion machinery proteins is a crucial regulatory mechanism for exocytosis. However, the participation of protein tyrosine phosphatases (PTPs) in different exocytosis stages has not been defined. Here we demonstrate that PTP-MEG2 controls multiple steps of catecholamine secretion. Biochemical and crystallographic analyses reveal key residues that govern the interaction between PTP-MEG2 and its substrate, a peptide containing the phosphorylated NSF-pY83 site, specify PTP-MEG2 substrate selectivity, and modulate the fusion of catecholamine-containing vesicles. Unexpectedly, delineation of PTP-MEG2 mutants along with the NSF binding interface reveals that PTP-MEG2 controls the fusion pore opening through NSF independent mechanisms. Utilizing bioinformatics search and biochemical and electrochemical screening approaches, we uncover that PTP-MEG2 regulates the opening and extension of the fusion pore by dephosphorylating the DYNAMIN2-pY125 and MUNC18-1-pY145 sites. Further structural and biochemical analyses confirmed the interaction of PTP-MEG2 with MUNC18-1-pY145 or DYNAMIN2-pY125 through a distinct structural basis compared with that of the NSF-pY83 site. Our studies thus provide mechanistic insights in complex exocytosis processes.