A dynamic model for elevator operation-induced spread of a respiratory infectious disease in an apartment building.

Residents have to use elevators to leave and enter their high-rise apartments frequently. An elevator car can easily spread respiratory infectious diseases, as it has a confined and small space. Therefore, studying how elevator operations promote epidemic transmission is of importance to public health. We developed an infectious disease dynamics model. First, we used homemade codes to simulate the operating state of an elevator and the dynamic process of infectious disease transmission in an apartment building due to elevator operations. Second, we analysed the temporal distribution patterns of infected individuals and patients. Finally, we validated the reliability of the model by performing continuous-time sensitivity analysis on important model parameters. We found that elevator operations can cause rapid spread of infectious diseases within an apartment building. Therefore, it is necessary to enhance elevator ventilation and disinfection mechanisms to prevent the outbreak of respiratory infections. Moreover, residents should reduce elevator use and wear masks.

Proxalutamide for the treatment of COVID-19 rebound following Paxlovid treatment: Report of four cases and review of the literature.

BACKGROUND: The pandemic the coronavirus disease 2019 (COVID-19) has created a global health crisis. Although Paxlovid is recommended for the early-stage treatment of mild-to-moderate COVID-19 in patients at increased risk of progression to severe COVID-19, more and more cases are reported a COVID-19 rebound after Paxlovid treatment. Currently, information on the additional treatment for COVID-19 rebound following Paxlovid treatment is limited. CASE REPORT: Here, we present four cases with COVID-19 who were mild on admission. All cases experienced a COVID-19 rebound and progressed to severe COVID-19, following treatment with Paxlovid (300 mg of nirmatrelvir with 100 mg ritonavir, twice daily for 5 days). After being treated with proxalutamide (300 mg/day), all cases finally turned real-time reverse transcription polymerase chain reaction (RT-PCR) negative. CONCLUSION: Our cases suggested that proxalutamide might be an effective remedial treatment option for patients experiencing a COVID-19 rebound after Paxlovid treatment.

Intranasal delivery of replicating mRNA encoding hACE2-targeting antibody against SARS-CoV-2 Omicron infection in the hamster.

The Omicron variant is sweeping the world, which displays striking immune escape potential through mutations at key antigenic sites on the spike protein, making broad-spectrum SARS-CoV-2 prevention or therapeutical strategies urgently needed. Previously, we have reported a hACE2-targeting neutralizing antibody 3E8, which could efficiently block both prototype SARS-CoV-2 and Delta variant infections in prophylactic mouse models, having the potential of broad-spectrum to prevent SARS-CoV-2. However, preparation of monoclonal neutralizing antibodies is severely limited by the time-consuming process and the relative high cost. Here, we utilized a modified VEEV replicon with two subgenomic (sg) promoters engineered to express the light and heavy chains of the 3E8 mAb. The feasibility and protective efficacy of replicating mRNA encoding 3E8 against Omicron infection in the hamster were demonstrated through the lung targeting delivery with the help of VEEV-VRP. Overall, we developed a safe and cost-effective platform of broad-spectrum to prevent SARS-CoV-2 infection.

Impact of the COVID-19 Pandemic and Lockdown on Anxiety, Depression and Nursing Burden of Caregivers in Alzheimer's Disease, Dementia With Lewy Bodies and Mild Cognitive Impairment in China: A 1-Year Follow-Up Study.

Background: Many countries have adopted lockdown strategies to prevent the spread of COVID-19. The goal of this study was to investigate the effects of the pandemic on anxiety, depression and care burden in caregivers of nursing patients with Alzheimer's disease (AD), Dementia with Lewy Bodies (DLB) and Mild Cognitive Impairment (MCI), over a one-year period. Methods: We collected data on consecutive patients and their caregivers recruited at T0 (from 30 September to 31 December 2019) before the pandemic of COVID-19 at the memory clinic of Tianjin Huanhu Hospital. The patients and caregivers were followed up on face-to-face at T1 (from 30 September to 31 December 2020) during the pandemic to assess changes in physical activity, social contact, sleep quality, caregiver burden, anxiety and depression. Results: A total of 105 AD, 22 DLB and 50 MCI patients and caregivers were enrolled. A total of 36.6 % of the AD, 81.6% of the DLB, 38% of the MCI caregivers had worsening ZBI, whereas 31.7 % of the AD, 54.4% of the DLB, 26 % of the MCI caregivers had worsening GAD-7, and 29.6 % of the AD, 54.4% of the DLB, and 32 % of the MCI caregivers had worsening PHQ-9. DLB caregivers exhibited a rapid deterioration of ZBI (by 4.27 ± 5.43, P < 0.001), GAD-7 (by 2.23 ± 3.26, P = 0.003) and PHQ-9 (by 1.32 ± 2.25, P = 0.003) compared to AD and MCI caregivers. Conclusion: Social isolation, physical inactivity and sleep disturbance after lockdown for at least 12 months were significantly related to increased caregiver burden and worsened psychological states of caregivers of AD, DLB and MCI sufferers, especially among DLB caregivers.

Prevalence and associated factors of suicidal ideation among college students during the COVID-19 pandemic in China: a 3-wave repeated survey.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic, a major public health crisis, harms individuals' mental health. This 3-wave repeated survey aimed to examine the prevalence and correlates of suicidal ideation at different stages of the COVID-19 pandemic in a large sample of college students in China. METHODS: Using a repeated cross-sectional survey design, we conducted 3 online surveys of college students during the COVID-19 pandemic at 22 universities in Guandong, China. The 3 surveys were conducted during the outbreak period (T1: 3 February to 10 February 2020, N = 164,101), remission period (T2: 24 March to 3 April 2020, N = 148,384), and normalized prevention and control period (T3: 1 June to 15 June 2020, N = 159,187). Suicidal ideation was measured by the ninth item of the Patient Health Questionnaire-9. A range of suicide-related factors was assessed, including sociodemographic characteristics, depression, anxiety, insomnia, pre-existing mental health problems, and COVID-19-related factors. RESULTS: The prevalence of suicidal ideation was 8.5%, 11.0% and 12.6% at T1, T2, and T3, respectively. Male sex (aOR: 1.35-1.44, Ps < 0.001), poor self-perceived mental health (aOR: 2.25-2.81, Ps < 0.001), mental diseases (aOR: 1.52-2.09, P < 0.001), prior psychological counseling (aOR: 1.23-1.37, Ps < 0.01), negative perception of the risk of the COVID-19 epidemic (aOR: 1.14-1.36, Ps < 0.001), depressive symptoms (aOR: 2.51-303, Ps < 0.001) and anxiety symptoms (aOR: 1.62-101.11, Ps < 0.001) were associated with an increased risk of suicidal ideation. CONCLUSION: Suicidal ideation appeared to increase during the COVID-19 pandemic remission period among college students in China. Multiple factors, especially mental health problems, are associated with suicidal ideation. Psychosocial interventions should be implemented during and after the COVID-19 pandemic to reduce suicide risk among college students.

Berbamine hydrochloride potently inhibits SARS-CoV-2 infection by blocking S protein-mediated membrane fusion.

COVID-19 caused by SARS-CoV-2 has posed a significant threat to global public health since its outbreak in late 2019. Although there are a few drugs approved for clinical treatment to combat SARS-CoV-2 infection currently, the severity of the ongoing global pandemic still urges the efforts to discover new antiviral compounds. As the viral spike (S) protein plays a key role in mediating virus entry, it becomes a potential target for the design of antiviral drugs against COVID-19. Here, we tested the antiviral activity of berbamine hydrochloride, a bis-benzylisoquinoline alkaloid, against SARS-CoV-2 infection. We found that berbamine hydrochloride could efficiently inhibit SARS-CoV-2 infection in different cell lines. Further experiments showed berbamine hydrochloride inhibits SARS-CoV-2 infection by targeting the viral entry into host cells. Moreover, berbamine hydrochloride and other bis-benzylisoquinoline alkaloids could potently inhibit S-mediated cell-cell fusion. Furthermore, molecular docking results implied that the berbamine hydrochloride could bind to the post fusion core of SARS-CoV-2 S2 subunit. Therefore, berbamine hydrochloride may represent a potential efficient antiviral agent against SARS-CoV-2 infection.

A new screening system for entry inhibitors based on cell-to-cell transmitted syncytia formation mediated by self-propagating hybrid VEEV-SARS-CoV-2 replicon.

The extremely high transmission rate of SARS-CoV-2 and severe cases of COVID-19 pose the two critical challenges in the battle against COVID-19. Increasing evidence has shown that the viral spike (S) protein-driven syncytia may be responsible for these two events. Intensive attention has thus been devoted to seeking S-guided syncytium inhibitors. However, the current screening campaigns mainly rely on either live virus-based or plasmid-based method, which are always greatly limited by the shortage of high-level biosafety BSL-3 facilities or too much labour-intensive work. Here, we constructed a new hybrid VEEV-SARS-CoV-2-S-eGFP reporter vector through replacement of the structural genes of Venezuelan equine encephalitis virus (VEEV) with the S protein of SARS-CoV-2 as the single structural protein. VEEV-SARS-CoV-2-S-eGFP can propagate steadily through cell-to-cell transmission pathway in S- and ACE2-dependent manner, forming GFP positive syncytia. In addition, a significant dose-dependent decay in GFP signals was observed in VEEV-SARS-CoV-2-S-eGFP replicating cells upon treatment with SARS-CoV-2 antiserum or entry inhibitors, providing further evidence that VEEV-SARS-CoV-2-S-eGFP system is highly sensitive to characterize the anti-syncytium-formation activity of antiviral agents. More importantly, the assay is able to be performed in a BSL-2 laboratory without manipulation of live SARS-CoV-2. Taken together, our work establishes a more convenient and efficient VEEV-SARS-CoV-2-S-eGFP replicating cells-based method for rapid screening of inhibitors blocking syncytium formation.

Intranasal delivery of replicating mRNA encoding neutralizing antibody against SARS-CoV-2 infection in mice.

The lung is the prophylaxis target against SARS-CoV-2 infection, and neutralizing antibodies are a leading class of biological products against various infectious viral pathogen. In this study, we develop a safe and cost-effective platform to express neutralizing antibody in the lung with replicating mRNA basing on alphavirus replicon particle (VRP) delivery system, to prevent SARS-CoV-2 infections. First, a modified VEEV replicon with two subgenomic (sg) promoters was engineered to translate the light and heavy chains of antibody simultaneously, for expression and assembly of neutralizing anti-SARS-CoV-2 antibody CB6. Second, the feasibility and protective efficacy of replicating mRNA against SARS-CoV-2 infection were demonstrated through both in vitro and in vivo assays. The lung target delivery with the help of VRP system resulted in efficiently block SARS-CoV-2 infection with reducing viral titer and less tissue damage in the lung of mice. Overall, our data suggests that expressing neutralizing antibodies in the lungs with the help of self-replicating mRNA could potentially be a promising prophylaxis approach against SARS-CoV-2 infection.

The Impact of the COVID-19 Pandemic and Lockdown on Mild Cognitive Impairment, Alzheimer's Disease and Dementia With Lewy Bodies in China: A 1-Year Follow-Up Study.

Background: While the lockdown strategies taken by many countries effectively limited the spread of COVID-19, those were thought to have a negative impact on older people. This study aimed to investigate the impact of lockdown on cognitive function and neuropsychiatric symptoms over a 1-year follow-up period in patients with mild cognitive impairment (MCI), Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Methods: We enrolled consecutive patients with MCI, probable AD or DLB who were receiving outpatient memory care before the COVID-19 pandemic and followed-up with them after 1 year by face-to-face during the COVID-19 pandemic to assess changes in physical activity, social contact, cognitive function and neuropsychiatric symptoms (NPS). Results: Total 105 probable AD, 50 MCI and 22 probable DLB patients were included and completed the 1-year follow-up between October 31 and November 30, 2020. Among the respondents, 42% of MCI, 54.3% of AD and 72.7% of DLB patients had a decline in MMSE scores and 54.4% of DLB patients had worsening Neuropsychiatric inventory (NPI) scores. Patients with DLB showed a more rapid decline of MMSE than those with AD. Diminished physical activity and social contact might have hastened the deterioration of cognition and the worsening of NPS. Conclusion: Social isolation and physical inactivity even after strict lockdown for at least 6 months were correlated with accelerated decline of cognitive function and NPS in patients with AD and DLB.

Sleep quality and mental health status of healthcare professionals during the outbreak of coronavirus disease 2019 (COVID-19).

To investigate the sleep quality and mental health status of healthcare professionals during the outbreak of coronavirus disease 2019 (COVID-19) in order to promote timely intervention and treatment. An Questionnaire Star of WeChat online survey was conducted at Hwamei Hospital, University of Chinese Academy of Sciences, NingBo, China. The questionnaire consisted of two parts including sociodemographic characteristics, and the Pittsburgh Sleep Quality Index (PSQI), the Generalized Anxiety Disorder (GAD-7) scale, a depression screening scale (Patient Health Questionnaire-9 [PHQ-9]) so as to investigate the sleep quality and mental health status of healthcare professionals during the outbreak of COVID-19.The data were analyzed with the t-test, χ2 test, one-way analysis of variance (ANOVA) and Pearson correlation, P < 0.05 was considered statistically significant. The mean score of PSQI is 5.8 ± 3.7 and the incidence of sleep disorders was 28.8% among the healthcare professionals and was related to occupation, title, education level, role and some underlying diseases. The positive rates for anxiety and depression among the healthcare professionals were 33.2% and 39.4% according to the GAD-7 and PHQ-9. Mental health status was related to occupation, education level, role and some underlying diseases. During the COVID-19 outbreak, sleep quality was significantly correlated with anxiety and depression among the healthcare professionals. The incidences of sleep disorder, anxiety and depression among healthcare professionals have been high. Furthermore, these disorders are interrelated and require timely intervention and treatment.

SARS-CoV-2 replicon for high-throughput antiviral screening.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus, which is highly pathogenic and classified as a biosafety level 3 (BSL-3) agent, has greatly threatened global health and efficacious antivirals are urgently needed. The high requirement of facilities to manipulate the live virus has limited the development of antiviral study. Here, we constructed a reporter replicon of SARS-CoV-2, which can be handled in a BSL-2 laboratory. The Renilla luciferase activity effectively reflected the transcription and replication levels of the replicon genome. We identified the suitability of the replicon in antiviral screening using the known inhibitors, and thus established the replicon-based high-throughput screening (HTS) assay for SARS-CoV-2. The application of the HTS assay was further validated using a few hit natural compounds, which were screened out in a SARS-CoV-2 induced cytopathic-effect-based HTS assay in our previous study. This replicon-based HTS assay will be a safe platform for SARS-CoV-2 antiviral screening in a BSL-2 laboratory without the live virus.

Maternal, placental and neonatal outcomes after asymptomatic SARS-CoV-2 infection in the first trimester of pregnancy: A case report.

The effects of SARS-CoV-2 infection in the first trimester on the pregnant woman and the fetus remain unclear. We describe the complete follow-up of a pregnant woman with asymptomatic SARS-CoV-2 infection in the first trimester. The woman tested positive for SARS-CoV-2 viral RNA in nasopharyngeal swabs in her seventh week of gestation and was admitted to a local hospital for treatment. Although the woman had a BMI above 28 and a total gestational weight gain of 21 kg, no pregnancy complications or severe complications related to SARS-CoV-2 were reported. An ultrasound scan identified no fetal abnormalities at 22 weeks. The pregnancy ended at term (37 weeks), and the newborn's birth weight was 3100 g. Placental insufficiency was revealed by placental histology examination but this appeared not to be related to the SARS-CoV-2 infection. In-situ hybridisation and immunohistochemical tests for SARS-CoV-2 RNA, spike protein 1, and nucleocapsid proteins were negative. However, ACE-2 was positive in samples of the placenta, umbilical cord and fetal membrane. The baby was followed up through to 10 days after birth and grew normally. Our results suggest that asymptomatic SARS-CoV-2 infection in the first trimester of pregnancy might not have significant harmful effects on the mother and the developing fetus. This finding may be of interest to the general public, midwives and general practitioners. However, large population studies are needed to confirm our findings.

Epidemiological analysis of asymptomatic SARS-CoV-2 transmission in the community: an individual-based model.

We established an individual-based computer model to simulate the occurrence, infection, discovery, quarantine, and quarantine release (recovery) of asymptomatic SARS-CoV-2 infected individuals or patients within the community. The model was used to explore the effects of control measures, such as active tracing, laboratory testing, active treatment, and home quarantine on the epidemic. Considering the condition that R0 = 1.2, when a case of an imported asymptomatic infected individual (AII) was reported in the community, the implementation of control measures reduced the number of AIIs and patients by 62.2% and 62.4%, respectively. The number of undetected AIIs and patients peaked at 302 days of the epidemic, reaching 53 and 20 individuals, respectively. The implementation of sustained active tracing, laboratory testing, active treatment, and home quarantine can significantly reduce the probability of disease outbreaks and block the spread of the COVID-19 epidemic caused by AIIs in the community.