Expression of angiotensin converting enzyme 2 mRNA in different SARS-CoV-2 infection states and times.

To measure the expression of angiotensin converting enzyme 2 (ACE2) mRNA in SARS-CoV-2 infection with different infection status and at different stages during infection, we used RT-qP CR to measure the expression of ACE2 mRNA. Measurements were analyzed by two-way repeated measures analysis of variance (RMANOVA). Expression of ACE2 mRNA was downregulated in initial stages of SARS-CoV-2 infection both in the asymptomatic infection (ASY) group and the confirmed cases (CON) group (t=-8.0845, P < 0.0001; t=-8.1904, P < 0.0001, respectively). The expression of ACE2 mRNA in the incubation period of CON group was lower compared with the intinal period of ASY group (F = 6.084, p = 0.016, partialη2 = 0.070). Relative expression of ACE2 mRNA was upregulated at the late stage of SARS-CoV-2 infection in the ASY and CON groups (F = 23.489, p = 0.000, partialη2 = 0.225; F = 46.555, p = 0.000, partialη2 = 0.365, respectively). The relative expression of ACE2 mRNA was down-regulated (mean ± SEM:0.69 ± 0.03) after inoculation with SARSCoV- 2 Spike pseudovirus, and there was a statistical difference (one-way t test, mean diffience =-0.31, 95%CI: -0.37˜-0.24, t=-8.1904, P < 0.0001). The expression of ACE2 mRNA is downregulated in the initial stage of SARS-CoV-2 infection, and then upregulated in the late stage of SARS-CoV-2 infection. The lower expression of ACE2 mRNA during the incubation period can lead to clinical symptoms. Downregulation of ACE2 mRNA was related to the interaction between SARS-CoV-2 S protein and ACE2.Communicated by Ramaswamy H. Sarma.

Investigating time, strength, and duration of measures in controlling the spread of COVID-19 using a networked meta-population model.

Policy makers around the world are facing unprecedented challenges in making decisions on when and what degrees of measures should be implemented to tackle the COVID-19 pandemic. Here, using a nationwide mobile phone dataset, we developed a networked meta-population model to simulate the impact of intervention in controlling the spread of the virus in China by varying the effectiveness of transmission reduction and the timing of intervention start and relaxation. We estimated basic reproduction number and transition probabilities between health states based on reported cases. Our model demonstrates that both the time of initiating an intervention and its effectiveness had a very large impact on controlling the epidemic, and the current Chinese intense social distancing intervention has reduced the impact substantially but would have been even more effective had it started earlier. The optimal duration of the control measures to avoid resurgence was estimated to be 2 months, although would need to be longer under less effective controls.

One Year after the Flood: Prevalence and Correlates of Post-Traumatic Stress Disorder among Residents in Fort McMurray.

BACKGROUND: The 2020 Fort McMurray (FMM) and area flood caused more than $228 million in insured damage, affected over 1200 structures, and more than 13,000 people were evacuated. OBJECTIVE: This study sought to determine the prevalence of post-traumatic stress disorder (PTSD)-like symptoms and the risk predictors among the population of FMM one year after the 2020 flooding. METHODS: An online quantitative cross-sectional survey was distributed to residents of FMM via REDCap between 24 April to 2 June 2021 to collect sociodemographic, clinical, and flood-related information. The PTSD checklist for DSM-5 (PCL-C) was used to assess likely PTSD among respondents. RESULTS: 186 of 249 respondents completed all essential self-assessment questionnaires in the analysis, yielding a response rate of 74.7%. The prevalence of likely PTSD was 39.6% (65). Respondents with a history of depression were more likely to develop PTSD symptoms (OR = 5.71; 95% CI: 1.68-19.36). Similarly, responders with limited and no family support after the disaster were more prone to report PTSD symptoms ((OR = 2.87; 95% CI: 1.02-8.05) and (OR = 2.87; 95% CI: 1.06-7.74), respectively). CONCLUSIONS: Our research indicated that history of depression and the need for mental health counseling significantly increased the risk of developing PTSD symptoms following flooding; family support is protective. Further studies are needed to explore the relations between the need to receive counseling and presenting with likely PTSD symptoms.

Association of smartphone addiction with daily behaviors and mental health during the COVID-19 pandemic among medical college students

Objective: To investigate the smartphone addiction among college students during the Coronavirus Disease 2019 (COVID-19) pandemic and its association with daily behaviors and mental health, and to provide reference for heath education and psychological counseling for college students.

25-Hydroxycholesterol-Conjugated EK1 Peptide with Potent and Broad-Spectrum Inhibitory Activity against SARS-CoV-2, Its Variants of Concern, and Other Human Coronaviruses.

The COVID-19 pandemic caused by SARS-CoV-2 infection poses a serious threat to global public health and the economy. The enzymatic product of cholesterol 25-hydroxylase (CH25H), 25-Hydroxycholesterol (25-HC), was reported to have potent anti-SARS-CoV-2 activity. Here, we found that the combination of 25-HC with EK1 peptide, a pan-coronavirus (CoV) fusion inhibitor, showed a synergistic antiviral activity. We then used the method of 25-HC modification to design and synthesize a series of 25-HC-modified peptides and found that a 25-HC-modified EK1 peptide (EK1P4HC) was highly effective against infections caused by SARS-CoV-2, its variants of concern (VOCs), and other human CoVs, such as HCoV-OC43 and HCoV-229E. EK1P4HC could protect newborn mice from lethal HCoV-OC43 infection, suggesting that conjugation of 25-HC with a peptide-based viral inhibitor was a feasible and universal strategy to improve its antiviral activity.

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.

Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18 years or older: A randomized, double-blind, placebo-controlled, phase 1/2 trial.

BACKGROUND: We aimed to assess the safety and immunogenicity of an inactivated vaccine against COVID-19 in Chinese adults aged ≥18 years. METHODS: This is an ongoing randomized, double-blind, placebo-controlled, phase 1/2 clinical trial among healthy adults aged ≥18 years in Henan Province, China. Participants (n = 336 in 18-59 age group and n = 336 in ≥60 age group) were enrolled between April 12 and May 17 2020, and were equally randomized to receive vaccine or placebo (aluminum hydroxide adjuvant) in a three-dose schedule of 2·5, 5, or 10 µg on days 0, 28, and 56. Another 448 adults aged 18-59 years were equally allocated to four groups (a one-dose schedule of 10 µg, and two-dose schedules of 5 µg on days 0 and 14/21/28) and received vaccine or placebo (ratio 3:1 within each group). The primary outcomes were 7-day post-injection adverse reactions and neutralizing antibody titres on days 28 and 90 after the whole-course vaccination. Trial registration: www.chictr.org.cn #ChiCTR2000031809. FINDINGS: The 7-day adverse reactions occurred in 4·8% to 32·1% of the participants in various groups, and most adverse reactions were mild, transient, and self-limiting. Twenty participants reported 68 serious adverse events which were judged to be unrelated to the vaccine. The 90-day post-injection geometric mean titres of neutralizing antibody ranged between 87 (95% CI: 61-125) and 129 (99-169) for three-dose schedule among younger and older adults; 20 (14-27), 53 (38-75), and 44 (32-61) in 5 µg days 0 and 14/21/28 groups, respectively, and 7 (6-9) in one-dose 10 µg group. There were no detectable antibody responses in all placebo groups. INTERPRETATION: The inactivated vaccine against COVID-19 was well tolerated and immunogenic in both younger and older adults. The two-dose schedule of 5 µg on days 0 and 21/28 and three-dose schedules on days 0, 28, and 56 could be further evaluated for long-term safety and efficacy in the phase 3 trials.

Associations of healthy lifestyle and socioeconomic status with mortality and incident cardiovascular disease: two prospective cohort studies.

OBJECTIVE: To examine whether overall lifestyles mediate associations of socioeconomic status (SES) with mortality and incident cardiovascular disease (CVD) and the extent of interaction or joint relations of lifestyles and SES with health outcomes. DESIGN: Population based cohort study. SETTING: US National Health and Nutrition Examination Survey (US NHANES, 1988-94 and 1999-2014) and UK Biobank. PARTICIPANTS: 44 462 US adults aged 20 years or older and 399 537 UK adults aged 37-73 years. EXPOSURES: SES was derived by latent class analysis using family income, occupation or employment status, education level, and health insurance (US NHANES only), and three levels (low, medium, and high) were defined according to item response probabilities. A healthy lifestyle score was constructed using information on never smoking, no heavy alcohol consumption (women ≤1 drink/day; men ≤2 drinks/day; one drink contains 14 g of ethanol in the US and 8 g in the UK), top third of physical activity, and higher dietary quality. MAIN OUTCOME MEASURES: All cause mortality was the primary outcome in both studies, and CVD mortality and morbidity in UK Biobank, which were obtained through linkage to registries. RESULTS: US NHANES documented 8906 deaths over a mean follow-up of 11.2 years, and UK Biobank documented 22 309 deaths and 6903 incident CVD cases over a mean follow-up of 8.8-11.0 years. Among adults of low SES, age adjusted risk of death was 22.5 (95% confidence interval 21.7 to 23.3) and 7.4 (7.3 to 7.6) per 1000 person years in US NHANES and UK Biobank, respectively, and age adjusted risk of CVD was 2.5 (2.4 to 2.6) per 1000 person years in UK Biobank. The corresponding risks among adults of high SES were 11.4 (10.6 to 12.1), 3.3 (3.1 to 3.5), and 1.4 (1.3 to 1.5) per 1000 person years. Compared with adults of high SES, those of low SES had higher risks of all cause mortality (hazard ratio 2.13, 95% confidence interval 1.90 to 2.38 in US NHANES; 1.96, 1.87 to 2.06 in UK Biobank), CVD mortality (2.25, 2.00 to 2.53), and incident CVD (1.65, 1.52 to 1.79) in UK Biobank, and the proportions mediated by lifestyle were 12.3% (10.7% to 13.9%), 4.0% (3.5% to 4.4%), 3.0% (2.5% to 3.6%), and 3.7% (3.1% to 4.5%), respectively. No significant interaction was observed between lifestyle and SES in US NHANES, whereas associations between lifestyle and outcomes were stronger among those of low SES in UK Biobank. Compared with adults of high SES and three or four healthy lifestyle factors, those with low SES and no or one healthy lifestyle factor had higher risks of all cause mortality (3.53, 3.01 to 4.14 in US NHANES; 2.65, 2.39 to 2.94 in UK Biobank), CVD mortality (2.65, 2.09 to 3.38), and incident CVD (2.09, 1.78 to 2.46) in UK Biobank. CONCLUSIONS: Unhealthy lifestyles mediated a small proportion of the socioeconomic inequity in health in both US and UK adults; therefore, healthy lifestyle promotion alone might not substantially reduce the socioeconomic inequity in health, and other measures tackling social determinants of health are warranted. Nevertheless, healthy lifestyles were associated with lower mortality and CVD risk in different SES subgroups, supporting an important role of healthy lifestyles in reducing disease burden.

Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes: Interim Analysis of 2 Randomized Clinical Trials.

Importance: A vaccine against coronavirus disease 2019 (COVID-19) is urgently needed. Objective: To evaluate the safety and immunogenicity of an investigational inactivated whole-virus COVID-19 vaccine in China. Interventions: In the phase 1 trial, 96 participants were assigned to 1 of the 3 dose groups (2.5, 5, and 10 µg/dose) and an aluminum hydroxide (alum) adjuvant-only group (n = 24 in each group), and received 3 intramuscular injections at days 0, 28, and 56. In the phase 2 trial, 224 adults were randomized to 5 µg/dose in 2 schedule groups (injections on days 0 and 14 [n = 84] vs alum only [n = 28], and days 0 and 21 [n = 84] vs alum only [n = 28]). Design, Setting, and Participants: Interim analysis of ongoing randomized, double-blind, placebo-controlled, phase 1 and 2 clinical trials to assess an inactivated COVID-19 vaccine. The trials were conducted in Henan Province, China, among 96 (phase 1) and 224 (phase 2) healthy adults aged between 18 and 59 years. Study enrollment began on April 12, 2020. The interim analysis was conducted on June 16, 2020, and updated on July 27, 2020. Main Outcomes and Measures: The primary safety outcome was the combined adverse reactions 7 days after each injection, and the primary immunogenicity outcome was neutralizing antibody response 14 days after the whole-course vaccination, which was measured by a 50% plaque reduction neutralization test against live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results: Among 320 patients who were randomized (mean age, 42.8 years; 200 women [62.5%]), all completed the trial up to 28 days after the whole-course vaccination. The 7-day adverse reactions occurred in 3 (12.5%), 5 (20.8%), 4 (16.7%), and 6 (25.0%) patients in the alum only, low-dose, medium-dose, and high-dose groups, respectively, in the phase 1 trial; and in 5 (6.0%) and 4 (14.3%) patients who received injections on days 0 and 14 for vaccine and alum only, and 16 (19.0%) and 5 (17.9%) patients who received injections on days 0 and 21 for vaccine and alum only, respectively, in the phase 2 trial. The most common adverse reaction was injection site pain, followed by fever, which were mild and self-limiting; no serious adverse reactions were noted. The geometric mean titers of neutralizing antibodies in the low-, medium-, and high-dose groups at day 14 after 3 injections were 316 (95% CI, 218-457), 206 (95% CI, 123-343), and 297 (95% CI, 208-424), respectively, in the phase 1 trial, and were 121 (95% CI, 95-154) and 247 (95% CI, 176-345) at day 14 after 2 injections in participants receiving vaccine on days 0 and 14 and on days 0 and 21, respectively, in the phase 2 trial. There were no detectable antibody responses in all alum-only groups. Conclusions and Relevance: In this interim report of the phase 1 and phase 2 trials of an inactivated COVID-19 vaccine, patients had a low rate of adverse reactions and demonstrated immunogenicity; the study is ongoing. Efficacy and longer-term adverse event assessment will require phase 3 trials. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000031809.