A 10-valent composite mRNA vaccine against both influenza and COVID-19 (preprint)

The COVID-19 pandemic caused by SARS-CoV-2 viruses has had a persistent and significant impact on global public health for four years. Recently, there has been a resurgence of seasonal influenza transmission worldwide. The co-circulation of SARS-CoV-2 and seasonal influenza viruses results in a dual burden on communities. Additionally, the pandemic potential of zoonotic influenza viruses, such as avian Influenza A/H5N1 and A/H7N9, remains a concern. Therefore, a combined vaccine against all these respiratory diseases is in urgent need. mRNA vaccines, with their superior efficacy, speed in development, flexibility, and cost-effectiveness, offer a promising solution for such infectious diseases and potential future pandemics. In this study, we present FLUCOV-10, a novel 10-valent mRNA vaccine created from our proven platform. This vaccine encodes hemagglutinin (HA) proteins from four seasonal influenza viruses and two avian influenza viruses with pandemic potential, as well as spike proteins from four SARS-CoV-2 variants. A two-dose immunization with the FLUCOV-10 elicited robust immune responses in mice, producing IgG antibodies, neutralizing antibodies, and antigen-specific cellular immune responses against all the vaccine-matched viruses of influenza and SARS-CoV-2. Remarkably, the FLUCOV-10 immunization provided complete protection in mouse models against both homologous and heterologous strains of influenza and SARS-CoV-2. These results highlight the potential of FLUCOV-10 as an effective vaccine candidate for the prevention of influenza and COVID-19.

The Impact of New SARS-CoV-2 Variants on Vaccine Breakthrough: a pilot study on spreading infection in the communities (preprint)

BackgroundCoronavirus disease 2019 (COVID-19) vaccines are effective at helping protect against severe disease and death from variants; however, incident of breakthrough infection in vaccinated patients has been increased. Therefore, we aimed to assess the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) new variants of concern in the communities and investigate vaccine breakthrough cases on our laboratory (Ayass Bioscience LLC) confirmed detection of COVID-19 variants in Dallas-Fort Worth (DFW), Texas. MethodsEpidemiologic study has been performed at our laboratory. We studied the viral whole-genome sequence and genotyping analysis on 166 symptomatic cases of COVID-19 which were randomly selected from nasal swab positive cases assessed from June 1st to August 30th, 2021, by reverse transcription polymerase chain reaction (RT-PCR) cycle threshold (CT) values. COVID-19 variants were identified to be dominated by B.1.617.2 (89.2%) and followed by AY.3 (1.8%), B.1.1.7 (4.8%), a combination of B.1.526.1 and B.1.617.2 (3%), B.1.621 (0.6%), and P.2 (0.6%). ResultThe CT values showed significant difference among the three age groups: <30 years, 31-60 years, and >60 years by one-way ANOVA (N1: F (2, 118) =4.96, p=0.009; N2: F (2, 118) =4.95, p=0.009). No significant difference was observed by symptom, status of immunization, or vaccine manufacturer. A two-way ANOVA was performed to examine the effect of gender and variant group (Delta and other variants) on the CT values. The analyses revealed a statistically significant interaction between the effect of gender and variant group (N1, F (1.117) = 3.906, p = 0.05; N2, F (1, 117) = 7.402, p = 0.008). ConclusionOur study shows that Delta, the dominant variant of COVID-19, is spreading in the communities, and vaccine breakthrough cases occurred in the majority of Delta variant (91%) followed by AY.3 (5%), B.1.1.7 (2%) and 2% of the double variant of B.1.526.1 and B.1.617.2. The incidence of the breakthrough cases was not linked to a specific manufacturer. The CT value is likely to associate with age. This study also supports our laboratorys ongoing efforts to sequence the SARS-CoV-2 virus from positive patient samples to identify the new viral variants and possible vaccine breakthrough mutations in the community.

Forecast possible risk for COVID-19 epidemic dissemination under current control strategies in Japan

COVID-19 has globally spread to over 4 million people and the epidemic situation in Japan is very serious. The purpose of this research was to assess the risk of COVID-19 epidemic dissemination in Japan by estimating the current state of epidemic dissemination and providing some epidemic prevention and control recommendations. Firstly, the period from 6 January to 31 March 2020 was divided into four stages and the relevant parameters were estimated according to the imported cases in Japan. The basic reproduction number of the current stage is 1.954 (95% confidence interval (CI) 1.851-2.025), which means COVID-19 will spread quickly, and the self-healing rate of Japanese is about 0.495 (95% CI 0.437-0.506), with small variations in the four stages. Secondly, the results were applied to the actual reported cases from 1 to 5 April 2020, verifying the reliability of the estimated data using the accumulated reported cases located within the 95% confidence interval and the relative error of forecast data of five days being less than 2.5% 2.5%. Thirdly, considering the medical resources in Japan, the times the epidemic beds and ventilators become fully occupied are predicted as 5 and 15 May 2020, respectively. Keeping with the current situation, the final death toll in Japan may reach into the millions. Finally, based on experience with COVID-19 prevention and control in China, robust measures such as nationwide shutdown, store closures, citizens isolating themselves at home, and increasing PCR testing would quickly and effectively prevent COVID-19 spread.

Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2).

PURPOSE: Lianhuaqingwen (LH) as traditional Chinese medicine (TCM) formula has been used to treat influenza and exerted broad-spectrum antiviral effects on a series of influenza viruses and immune regulatory effects Ding et al. (2017). The goal of this study is to demonstrate the antiviral activity of LH against the novel SARS-CoV-2 virus and its potential effect in regulating host immune response. METHODS: The antiviral activity of LH against SARS-CoV-2 was assessed in Vero E6 cells using CPE and plaque reduction assay. The effect of LH on virion morphology was visualized under transmission electron microscope. Pro-inflammatory cytokine expression levels upon SARS-CoV-2 infection in Huh-7 cells were measured by real-time quantitative PCR assays. RESULTS: LH significantly inhibited SARS-CoV-2 replication in Vero E6 cells and markedly reduced pro-inflammatory cytokines (TNF-α, IL-6, CCL-2/MCP-1 and CXCL-10/IP-10) production at the mRNA levels. Furthermore, LH treatment resulted in abnormal particle morphology of virion in cells. CONCLUSIONS: LH significantly inhibits the SARS-COV-2 replication, affects virus morphology and exerts anti-inflammatory activity in vitro. These findings indicate that LH protects against the virus attack, making its use a novel strategy for controlling the COVID-19 disease.

Mental Disorders of Healthcare Workers Fighting COVID-19: Little Relieved After One Month (preprint)

Background: More than 210,000 medical workers have fought against the Coronavirus Disease 2019 (COVID-19) in Hubei of China since December 2019. However, it was unknown if the mental health disorders for frontline medical staff was relieved one month later. Methods: Medical workers in Wuhan and other cities in Hubei Province was requested to fill out an online survey, which assessed their degrees of anxiety, insomnia, depression, and post-traumatic stress disorder (PTSD). Outcomes: A total of 1,091 respondents (32·63% male, 67·37% female) were valid for statistical analysis. The prevalence was anxiety (52·98% with male 50·84% and female 54·01%), insomnia (78·83% with male 78·09% and female 79·18%), depression (56·10% with male 55·34% and female 56·46%) and PTSD (11·09% with male 10·11% and female 11·56%). For educational attainment, those with doctoral and masters’ degrees (D/M) may suffer from more anxiety (median 7·0 [IQR 2·0-8·5] vs. median 5·0 [IQR 5·0-8·0], P =0·02) and PTSD (median 26·0 [IQR 19·5-33·0] vs. median 23·0 [IQR 19·0-31·0], P =0·04) than those with lower educational degrees. Interpretation: Mental disorders of healthcare workers were little relieved one month after they had ended fighting COVID-19, and potential mitigating factors and interventions is necessary.Funding Statement: The study was financially supported by the National Natural Science Foundation of China (8174356); the Open Project of Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine) (WDCM2018002); the Key Discipline Project of Hubei University of Medicine and the Foundation for Innovative Research Team of Hubei University of Medicine (2018YHKT01).Declaration of Interests: The authors declared no interest conflict in this study.Ethics Approval Statement: This study was approved by the Ethic Committee of Renmin Hospital of Hubei University of Medicine.

A Multi-hospital Study in Wuhan, China：Protective Effects of Non-menopause and Female Hormones on SARS-CoV-2 infection (preprint)

Objective To determine the correlation between menstruation status/sex hormones and prognosis of COVID-19, and to identify potential protective factors for female patients. Design, Setting, and Participants A cross-sectional study of COVID-19 patients who were hospitalized at Tongji and Mobile Cabin Hospitals from Jan 28, 2020 to March 8, 2020. Sex differences in severity and composite endpoints (admission to intensive care unit (ICU), use of mechanical ventilation, or death) of COVID-19 patients were compared. The correlation analysis and cox/logistic regression modeling of menstruation status/sex hormones and prognosis were conducted. Correlation between cytokines related to immunity and inflammation and disease severity or estradiol (E2) was revealed.Results Chi square test indicated significant differences in distribution of composite endpoints (p<0.01) and disease severity (p=0.05) between male and female patients (n=1902). 435 female COVID-19 patients with menstruation records were recruited. By the end of Mar 8, 111 patients recovered and discharged (25.3%). Multivariate Cox regression model adjusted for age and severity indicated that post-menopausal patients show the greater risk of hospitalization time than non-menopausal patients (relative hazard [RH], 1.91; 95% confidence interval [CI], 1.06-3.46)Logistic regression model showed that higher AMH as a control for age increases the risk of severity of COVID-19 (HR=0.146, 95%CI= (0.026-0.824) p=0.029). E2 showed protective effect against disease severity (HR=0.335, 95%CI= (0.105-1.070), p=0.046).In the Mann-Whitney U test, the higher levels of IL6 and IL8 were found in severe group (p=0.040, 0.033).The higher levels of IL2R, IL6, IL8 and IL10 were also observed in patients with composite end points(p<0.001,<0.001, =0.009, = 0.040).E2 levels were negatively correlated with IL2R, IL6, IL8 and TNF in luteal phase (Pearson Correlation=-0.592, -0.558, -0.545, -0.623; p=0.033, 0.048, 0.054, 0.023) and with C3 in follicular phase (Pearson Correlation=-0.651; p=0.030). Conclusions and Relevance Menopause is an independent risk factor for COVID-19. E2 and AMH are negatively correlated with COVID-19 severity probably due to their regulation of cytokines related to immunity and inflammation.

Clinical features and sexual transmission potential of SARS-CoV-2 infected female patients: a descriptive study in Wuhan, China (preprint)

Background: As of March 2, 2020, SARS-CoV-2 has infected more than 80174 people and caused 2915 deaths in China. This virus rapidly spreads to 56 countries worldwide. Thus, in order to effectively block its transmission, it is urgent to uncover all the possible transmission routes of SARS-CoV-2. Methods: From January 28 to February 18, 2020, 35 female patients diagnosed with COVID-19 in Tongji Hospital were included in this descriptive study. The gynecologic history, clinical characteristics, laboratory findings and chest computed tomography (CT) of all patients were recorded in detail. To examine whether there is sexual transmission through vaginal from female to her partner, we employed real-time polymerase chain reaction testing (RT-PCR) to detect SARS-CoV-2 in vaginal environment (including vaginal discharge, cervical or vaginal residual exfoliated cells) and anal swab samples, and inquired recent sexual behaviors from the patients. Findings: The age range of the 35 patients with COVID-19 was 37-88 years. Over 50% patients infected with SARS-CoV-2 had chronic diseases. We tested the vaginal environment and anal swabs from the 35 female patients with COVID-19 and found that only an anal swab sample from one patient was positive for SARS-CoV-2. All the samples from vaginal environment were negative for SARS-CoV-2. The infection rate of the patients' sexual partner was 42.9%. Additionally, two female patients admitted having sex with their partners during a possible infection incubation period, while one patient's partner was uninfected and the other patient's partner was diagnosed with COVID-19 (after the diagnosis of the female patient). Conclusion: No positive RT-PCR result was found in the vaginal environment perhaps due to the lack of ACE2 expression, which is the receptor of SARS-CoV-2, in the vagina and cervix tissues (human protein atlas). The results from this study show no evidence of transmission of SARS-CoV-2 through vaginal sex from female to her partner. However, the risk of infection of non vaginal sex and other intimate contacts during vaginal sex should not be ignored.