Effect of the Timing of Amubarvimab/Romlusevimab (BRII-196/198) Administration on Progression to Severe Disease in Elderly Patients with COVID-19 Infection: A Retrospective Cohort Study

Objective Early intervention with neutralizing antibodies is considered to be effective in preventing disease progression in patients with mild to moderate COVID-19 infection. Elderly patients are the most susceptible and at a higher risk of COVID-19 infection. The present study aimed to assess the necessity and possible clinical benefits of the early administration of Amubarvimab/Romlusevimab (BRII-196/198) in the elderly population. Methods The present study was designed as a retrospective, multi-center cohort study conducted with 90 COVID-19 patients aged over 60, who were divided into two groups based on the timing of the administration of BRII-196/198 (administration at ≤ 3 days or > 3 days from the onset of infection symptoms). Results The ≤ 3 days group exhibited a greater positive effect (HR 5.94, 95% CI, 1.42–24.83;P < 0.01), with only 2 patients among 21 patients (9.52%) exhibiting disease progression, compared to the 31 patients among the 69 patients (44.93%) of the > 3 days group who exhibited disease progression. The multivariate Cox regression analysis revealed low flow oxygen support prior to BRII-196/198 administration (HR 3.53, 95% CI 1.42–8.77, P < 0.01) and PLT class (HR 3.68, 95% CI 1.37–9.91, P < 0.01) as independent predictors of disease progression. Conclusions In elderly patients with mild or moderate COVID-19 disease, who do not require oxygen support and had the risk factors for disease progression to severe COVID-19 disease, the administration of BRII-196/198 within 3 days resulted in a beneficial trend in terms of preventing disease progression.

Influencing factors associated with quality of life and depression among COVID-19 survivors during convalescence.

This study aims to investigate influencing factors of quality of life (QoL) and depression among COVID-19 survivors during convalescence. A cross-sectional study was conducted in November 2020 in Wuhan, China. Information on social support, physical activity, QoL and depressive symptoms were assessed using self-administered questionnaires. Multivariate linear regression and multivariate logistic regression were used to assess the risk factors of subdomains of QoL (physical component score (PCS) and mental component score (MCS)) and depression, respectively. A total of 151 COVID-19 survivors (68 males) aged 53.21 (SD: 12.70) years participated in the study. Multivariate linear regression showed that age (ß=-0.241), history of chronic disease (ß=-0.4.774), physical activity (ß = 2.47) and social support (ß = 0.147) were significantly associated with PCS, while having a spouse (ß = 9.571), monthly income (ß = 0.043) and social support (ß = 0.337) were significantly associated with MCS. Logistic regression suggested that participants aged 40-60 years (OR = 10.20, 95%CI: 1.41-73.82) or above 60 years (OR = 15.63, 95%CI: 1.87-131.00), with high school or above education (OR = 5.81, 95%CI: 1.24-27.20), with low/moderate physical activity (low, OR = 2.97, 95%CI: 1.14-7.77; moderate, OR = 3.42, 95%CI: 1.07-10.91) and low/medium social support (low, OR = 4.81, 95% CI: 2.02-11.43; medium, OR = 9.70, 95%CI: 1.17-80.10) were more likely to be depressed, while higher monthly income (≥3000 Yuan RMB/month) was associated with lower risk for depression (OR = 0.27, 95%CI: 0.09-0.82). These findings indicate COVID-19 survivors with older age, having chronic conditions, without a spouse, low monthly income, low level of physical activity and social support had significantly increased risks for poor QoL and depression, and more attention should be given to this population.

The clinical significance of macrolide resistance in pediatric Mycoplasma pneumoniae infection during COVID-19 pandemic.

Background: Mycoplasma pneumoniae (MP) is a commonly occurring pathogen causing community-acquired pneumonia (CAP) in children. The global prevalence of macrolide-resistant MP (MRMP) infection, especially in Asian regions, is increasing rapidly. However, the prevalence of MRMP and its clinical significance during the COVID-19 pandemic is not clear. Methods: This study enrolled children with molecularly confirmed macrolide-susceptible MP (MSMP) and MRMP CAP from Beijing Children's Hospital Baoding Hospital, Capital Medical University between August 2021 and July 2022. The clinical characteristics, laboratory findings, chest imaging presentations, and strain genotypes were compared between patients with MSMP and MRMP CAP. Results: A total of 520 hospitalized children with MP-CAP were enrolled in the study, with a macrolide resistance rate of 92.7%. Patients with MRMP infection exhibited more severe clinical manifestations (such as dyspnea and pleural effusion) and had a longer hospital stay than the MSMP group. Furthermore, abnormal blood test results (including increased LDH and D-dimer) were more common in the MRMP group (P<0.05). Multilocus variable-number tandem-repeat analysis (MLVA) was performed on 304 samples based on four loci (Mpn13-16), and M3562 and M4572 were the major types, accounting for 74.0% and 16.8% of the strains, respectively. The macrolide resistance rate of M3562 strains was up to 95.1%. Conclusion: The prevalence of MRMP strains in hospitalized CAP patients was extremely high in the Baoding area, and patients infected with MRMP strains exhibited more severe clinical features and increased LDH and D-dimer. M3562 was the predominant resistant clone.

Anxiety, depression, insomnia symptoms & associated factors among young to middle-aged adults during the resurgent epidemic of COVID-19: a cross-sectional study.

The coronavirus disease 2019 (COVID-19) pandemic is a public health emergency of international concern. However, its stress on the mental health of young to middle-aged adults is largely unexplored. This study aimed to evaluate the mental health difficulties during the resurgent phase of COVID-19 among young to middle-aged adults in China. There were 1,478 participants with a median age of 26 years (IQR, 23 - 30), including 535 males (36.2%). The prevalence of anxiety, depression, and insomnia were 8.6%, 11.4%, and 13.7%, respectively. Participants aged 29 - 59 years (OR, 95% CI: 2.46, 1.23 - 4.91) and females (2.49, 1.55 - 4.01) had a higher risk of anxiety. Education status, worried level about the current COVID-19, and the level of COVID-19's impact on life were significantly associated with the prevalence of anxiety. Besides, the level of COVID-19's impact on life was positively related to the prevalence of depression and insomnia. Our study provided novel evidence of psychological difficulties among young to middle-aged adults during the resurgent stage of the COVID-19 epidemic. Psychological intervention should be continuously implemented to prevent long-term psychological comorbidities during the COVID-19 epidemic.

The Association Between Inhaled Corticosteroid and the Risks of SARS-COV-2 infection: A systematic review and meta-analysis

Background The effect of inhaled corticosteroid (ICS) on the risk of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection is unclear. Methods We performed a systematic review and meta-analysis of clinical studies that assessed the association between the use of ICS and the risk of SARS-COV-2 infection. PubMed, Web of Science, Scopus, Cochrane Library and Google Scholar were searched to January 1st, 2023. ROBINS-I was used to assess risk of bias of included studies. The outcome of interest was the risk of SARS-COV-2 infection in patients and odds ratio (OR) with 95% confidence interval (95% CI) were calculated using Comprehensive Meta-analysis software version 3. Results Twelve studies involving seven observational cohort studies, three case-control studies, and two cross-sectional studies were included in this meta-analysis. Overall, compared to non-ICS use, the pooled odds ratio (OR) of the risk of SARS-COV-2 infection was 0.997 (95% confidence interval [CI] 0.664-1.499;p=0.987) for patients with ICS use. Subgroup analyses demonstrated no statistical significance in the increased risk of SARS-COV-2 infection in patients with ICS monotherapy or in combination with bronchodilators (pooled OR=1.408;95% CI=0.693-2.858;p=0.344 in ICS monotherapy, and pooled OR=1.225;95% CI=0.533-2.815;p=0.633 in ICS combination, respectively). In addition, no significant association was observed between ICS use and the risk of SARS-COV-2 infection for patients with COPD (pooled OR=0.715;95% CI=0.415-1.230;p=0.225) and asthma (pooled OR=1.081;95% CI=0.970-1.206;p=0.160). Conclusions The use of ICS, either monotherapy or in combination with bronchodilators, does not have impact on the risk of SARS-COV-2 infection. Data availability The datasets used and analysed in the current study are available from the corresponding author on reasonable request.

Using multi-focus group method as an effective tool for eliciting business system requirements: Verified by a case study.

This research aims to explore the multi-focus group method as an effective tool for systematically eliciting business requirements for business information system (BIS) projects. During the COVID-19 crisis, many businesses plan to transform their businesses into digital businesses. Business managers face a critical challenge: they do not know much about detailed system requirements and what they want for digital transformation requirements. Among many approaches used for understanding business requirements, the focus group method has been used to help elicit BIS needs over the past 30 years. However, most focus group studies about research practices mainly focus on a particular disciplinary field, such as social, biomedical, and health research. Limited research reported using the multi-focus group method to elicit business system requirements. There is a need to fill this research gap. A case study is conducted to verify that the multi-focus group method might effectively explore detailed system requirements to cover the Case Study business's needs from transforming the existing systems into a visual warning system. The research outcomes verify that the multi-focus group method might effectively explore the detailed system requirements to cover the business's needs. This research identifies that the multi-focus group method is especially suitable for investigating less well-studied, no previous evidence, or unstudied research topics. As a result, an innovative visual warning system was successfully deployed based on the multi-focus studies for user acceptance testing in the Case Study mine in Feb 2022. The main contribution is that this research verifies the multi-focus group method might be an effective tool for systematically eliciting business requirements. Another contribution is to develop a flowchart for adding to Systems Analysis & Design course in information system education, which may guide BIS students step by step on using the multi-focus group method to explore business system requirements in practice.

Use of YouTube by academic medical centres during the COVID-19 pandemic: an observational study in Taiwan.

OBJECTIVES: YouTube has been of immense importance in conveying essential information on COVID-19 and promoting the latest healthcare policies during the outbreak. However, there have been few studies that have focused on how healthcare organisations have used YouTube to communicate with the public and increase their awareness during the pandemic, as well as its effectiveness. DESIGN: A nationwide observational study. SETTINGS: We analysed all YouTube video posts culled from the official accounts of all medical centres in Taiwan from December 2019 to August 2021. PARTICIPANTS: All YouTube videos were categorised as either COVID-19 or non-COVID-19 related. The COVID-19-related videos were divided into five categories, and detailed metrics for each video were recorded. For comparison, we also surveyed all YouTube video posts placed by the Ministry of Health and Welfare and the Taiwan Centers for Disease Control (TCDC). RESULTS: We analysed official YouTube channels from 17 academic medical centres, involving a total of 943 videos. We found a relationship between the quantity of YouTube videos uploaded by the TCDC and the trend of confirmed cases (Pearson's correlation coefficient was 0.25, p=0.02). Data from private hospitals revealed that they posted more COVID-19 videos (103 vs 56) when compared with public hospitals. In addition, multivariate linear regression showed that more 'likes' (estimate 41.1, 95% CI 38.8 to 43.5) and longer lengths (estimate 10 800, 95% CI 6968.0 to 14 632.0) of COVID-19-related videos correlated significantly with an increased number of 'views'. CONCLUSIONS: This nationwide observational study, performed in Taiwan, demonstrates well the trend and effectiveness of academic medical centres in promoting sound healthcare advice regarding COVID-19 through YouTube due to the channel's easy accessibility and usability.

Digital Magnetic Detection of Biomolecular Interactions with Single Nanoparticles.

Biomolecular interactions compose a fundamental element of all life forms and are the biological basis of many biomedical assays. However, current methods for detecting biomolecular interactions have limitations in sensitivity and specificity. Here, using nitrogen-vacancy centers in diamond as quantum sensors, we demonstrate digital magnetic detection of biomolecular interactions with single magnetic nanoparticles (MNPs). We first developed a single-particle magnetic imaging (SiPMI) method on 100 nm-sized MNPs with negligible magnetic background, high signal stability, and accurate quantification. The single-particle method was performed on biotin-streptavidin interactions and DNA-DNA interactions in which a single-base mismatch was specifically differentiated. Subsequently, SARS-CoV-2-related antibodies and nucleic acids were examined by a digital immunomagnetic assay derived from SiPMI. In addition, a magnetic separation process improved the detection sensitivity and dynamic range by more than 3 orders of magnitude and also the specificity. This digital magnetic platform is applicable to extensive biomolecular interaction studies and ultrasensitive biomedical assays.

The association between inhaled corticosteroid and the risks of SARS-COV-2 infection: A systematic review and meta-analysis.

BACKGROUND: The effect of inhaled corticosteroid (ICS) on the risk of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection is unclear. METHODS: We performed a systematic review and meta-analysis of clinical studies that assessed the association between the use of ICS and the risk of SARS-COV-2 infection. PubMed, Web of Science, Scopus, Cochrane Library and Google Scholar were searched to January 1st, 2023. ROBINS-I was used to assess risk of bias of included studies. The outcome of interest was the risk of SARS-COV-2 infection in patients and odds ratio (OR) with 95% confidence interval (95% CI) were calculated using Comprehensive Meta-analysis software version 3. RESULTS: Twelve studies involving seven observational cohort studies, three case-control studies, and two cross-sectional studies were included in this meta-analysis. Overall, compared to non-ICS use, the pooled odds ratio (OR) of the risk of SARS-COV-2 infection was 0.997 (95% confidence interval [CI] 0.664-1.499; p = 0.987) for patients with ICS use. Subgroup analyses demonstrated no statistical significance in the increased risk of SARS-COV-2 infection in patients with ICS monotherapy or in combination with bronchodilators (pooled OR=1.408; 95% CI=0.693-2.858; p = 0.344 in ICS monotherapy, and pooled OR=1.225; 95% CI=0.533-2.815; p = 0.633 in ICS combination, respectively). In addition, no significant association was observed between ICS use and the risk of SARS-COV-2 infection for patients with COPD (pooled OR=0.715; 95% CI=0.415-1.230; p = 0.225) and asthma (pooled OR=1.081; 95% CI=0.970-1.206; p = 0.160). CONCLUSIONS: The use of ICS, either monotherapy or in combination with bronchodilators, does not have impact on the risk of SARS-COV-2 infection.

Blood transcriptome responses in patients correlate with severity of COVID-19 disease.

Background: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infected individuals display a wide spectrum of disease severity, as defined by the World Health Organization (WHO). One of the main factors underlying this heterogeneity is the host immune response, with severe COVID-19 often associated with a hyperinflammatory state. Aim: Our current study aimed to pinpoint the specific genes and pathways underlying differences in the disease spectrum and outcomes observed, through in-depth analyses of whole blood transcriptomics in a large cohort of COVID-19 participants. Results: All WHO severity levels were well represented and mild and severe disease displaying distinct gene expression profiles. WHO severity levels 1-4 were grouped as mild disease, and signatures from these participants were different from those with WHO severity levels 6-9 classified as severe disease. Severity level 5 (moderate cases) presented a unique transitional gene signature between severity levels 2-4 (mild/moderate) and 6-9 (severe) and hence might represent the turning point for better or worse disease outcome. Gene expression changes are very distinct when comparing mild/moderate or severe cases to healthy controls. In particular, we demonstrated the hallmark down-regulation of adaptive immune response pathways and activation of neutrophil pathways in severe compared to mild/moderate cases, as well as activation of blood coagulation pathways. Conclusions: Our data revealed discrete gene signatures associated with mild, moderate, and severe COVID-19 identifying valuable candidates for future biomarker discovery.

Blood transcriptome responses in patients correlate with severity of COVID-19 disease

Background Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infected individuals display a wide spectrum of disease severity, as defined by the World Health Organization (WHO). One of the main factors underlying this heterogeneity is the host immune response, with severe COVID-19 often associated with a hyperinflammatory state. Aim Our current study aimed to pinpoint the specific genes and pathways underlying differences in the disease spectrum and outcomes observed, through in-depth analyses of whole blood transcriptomics in a large cohort of COVID-19 participants. Results All WHO severity levels were well represented and mild and severe disease displaying distinct gene expression profiles. WHO severity levels 1-4 were grouped as mild disease, and signatures from these participants were different from those with WHO severity levels 6-9 classified as severe disease. Severity level 5 (moderate cases) presented a unique transitional gene signature between severity levels 2-4 (mild/moderate) and 6-9 (severe) and hence might represent the turning point for better or worse disease outcome. Gene expression changes are very distinct when comparing mild/moderate or severe cases to healthy controls. In particular, we demonstrated the hallmark down-regulation of adaptive immune response pathways and activation of neutrophil pathways in severe compared to mild/moderate cases, as well as activation of blood coagulation pathways. Conclusions Our data revealed discrete gene signatures associated with mild, moderate, and severe COVID-19 identifying valuable candidates for future biomarker discovery.

IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study.

Purpose: Robust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness. Methods: We conducted a multi-cohort observational study to investigate the biology and the prognostic role of interferon alpha-inducible protein 27 (IFI27) in COVID-19 patients. Results: We show that IFI27 is expressed in the respiratory tract of COVID-19 patients and elevated IFI27 expression in the lower respiratory tract is associated with the presence of a high viral load. We further demonstrate that the systemic host response, as measured by blood IFI27 expression, is associated with COVID-19 infection. For clinical outcome prediction (e.g., respiratory failure), IFI27 expression displays a high sensitivity (0.95) and specificity (0.83), outperforming other known predictors of COVID-19 outcomes. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For example, in the pandemic H1N1/09 influenza virus infection, IFI27-like genes were highly upregulated in the blood samples of severely infected patients. Conclusion: These data suggest that prognostic biomarkers targeting the family of IFI27 genes could potentially supplement conventional diagnostic tools in future virus pandemics, independent of whether such pandemics are caused by a coronavirus, an influenza virus or another as yet-to-be discovered respiratory virus.

Pathway and Network Analyses Identify Growth Factor Signaling and MMP9 as Potential Mediators of Mitochondrial Dysfunction in Severe COVID-19.

Patients with preexisting metabolic disorders such as diabetes are at a higher risk of developing severe coronavirus disease 2019 (COVID-19). Mitochondrion, the very organelle that controls cellular metabolism, holds the key to understanding disease progression at the cellular level. Our current study aimed to understand how cellular metabolism contributes to COVID-19 outcomes. Metacore pathway enrichment analyses on differentially expressed genes (encoded by both mitochondrial and nuclear deoxyribonucleic acid (DNA)) involved in cellular metabolism, regulation of mitochondrial respiration and organization, and apoptosis, was performed on RNA sequencing (RNASeq) data from blood samples collected from healthy controls and patients with mild/moderate or severe COVID-19. Genes from the enriched pathways were analyzed by network analysis to uncover interactions among them and up- or downstream genes within each pathway. Compared to the mild/moderate COVID-19, the upregulation of a myriad of growth factor and cell cycle signaling pathways, with concomitant downregulation of interferon signaling pathways, were observed in the severe group. Matrix metallopeptidase 9 (MMP9) was found in five of the top 10 upregulated pathways, indicating its potential as therapeutic target against COVID-19. In summary, our data demonstrates aberrant activation of endocrine signaling in severe COVID-19, and its implication in immune and metabolic dysfunction.

Possible transmission of COVID-19 epidemic by a dog as a passive mechanical carrier of SARS-CoV-2, Chongqing, China, 2022.

An outbreak of coronavirus disease 2019 (COVID-19) was reported in Yongchuan district of Chongqing, China in March 2022, while the source was unknown. We aimed to investigate the origin and transmission route of the virus in the outbreak. We conducted field investigations for all cases and collected their epidemiological and clinical data. We performed gene sequencing and phylogenetic analysis for the cases, and draw the epidemic curve and the case relationship chart to analyze interactions and possible transmission mode of the outbreak. A total of 11 cases of COVID-19, including 5 patients and 6 asymptomatic cases were laboratory-confirmed in the outbreak. The branch of the virus was Omicron BA.2 which was introduced into Yongchuan district by a traveler in early March. Patient F and asymptomatic case G had never contact with other positive-infected individuals, but close contact with their pet dog that sniffed the discarded cigarette butts and stepped on the sputum of patient B. Laboratory test results showed that the dog hair and kennel were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the 10 isolates were highly homologous to an epidemic strain in a province of China. The investigation suggested that the contaminated dog by SARS-CoV-2 can act as a passive mechanical carrier of the virus and might transmit the virus to humans through close contact. Our findings suggest that during the COVID-19 pandemic, increasing hygiene measures and hand washing after close contact with pets is essential to minimize the risk of community spread of the virus.

COVID-19 Information Overload, Negative Emotions and Posttraumatic Stress Disorder: A Cross-Sectional Study.

Background: Under the context of the COVID-19 pandemic, a large amount of COVID-19-related information can cause an individual's perceived information overload, further halting the individual's psychological health. As a minor psychological discomfort could develop severe mental disorders such as posttraumatic stress disorder, it is necessary to understand the chain linkage of COVID-19 information overload turn to posttraumatic stress disorder to ensure timely intervention can be offered at each point of mental state transformation. Hence, we examined the negative outcomes of COVID-19 information overload and investigated the direct and indirect effects of COVID-19 on posttraumatic stress disorder. Methods: A convenient sample of Chinese adults (n = 1150) was investigated by an online survey from July 2020 to March 2021. The extent of COVID-19 information overload was measured by the information overload severity scale on the text of the COVID-19 pandemic. Psychological distress symptoms were measured using a 7-item anxiety scale (GAD-7), the 9-item Patient Health Questionnaire depression module (PHQ-9), and the psychometric properties of the PTSD Checklist (PCL-C). Structural equation modeling and bootstrap methods were utilized to analyze the relationships between variables. Results: COVID-19 information overload is positively related to an individual's anxiety, depression, and posttraumatic stress disorder. Furthermore, COVID-19 information overload can indirectly affect an individual's PTSD symptoms by increasing the feeling of depression. R2 values of anxiety, depression, and PTSD were 0.471, 0.324, and 0.795, respectively. Conclusion: COVID-19 information overload, anxiety, depression, and PTSD are negative psychological states, and each variable is closely linked with the others, suggesting the need for potential psychological interventions at specific times. Practical public training, such as crisis coping and information filtering, is essential. Regulation of technology companies is also essential.

Volatile Organic Compound (VOC) Reduction from Face Mask Wastes via a Microwave Plasma Reactor

Since the outbreak of the COVID-19 pandemic, the driven of face masks as personal protective equipment has increased significantly. Thus, disposed face masks from users should be handled properly for preventing the contamination of medical waste and the potential spread of viruses to the environment. This study gives information for dealing with face masks and assessing the volatile organic compounds (VOCs) concentrations via an atmospheric-pressure microwave plasma reactor. Face mask samples were mixed with the flux agents, namely cullet/glass, Al2O3, SiO2 and CaCO3. Samples were compared with control (no addition of flux agents) and the addition of only cullet. Moreover, microwave power, gas flow rate and pyrolysis duration were controlled at 1000 W, 9 standard liter per minute (SLM) and 5 min, respectively. The total concentration of VOC with the absence of flux agents was 448.04 ppm. Furthermore, the fuse of cullet and SiO2-Al2O3-cullet in the mask reduced the concentration of VOCs by 314.77 ppm and 54.7 ppm, respectively. Furthermore, the combination of CaCO3-SiO2-Al2O3-cullet creates the vitrification of material with the presence of crystalline structure, where the compositions of Ca and Si were 13.55% and 19.12%, respectively. Moreover, the final composition of carbon from the flux agents was 17.92 ± 10.08%. This study confirms that the fuse of CaCO3-SiO2-Al2O3-glass/cullet reduced the VOC via plasma technology, which is a promising method to be implemented in order to reduce the concentration of VOC from the face mask waste.

Impact of Daycare Service Interruption during COVID-19 Pandemic on Physical and Mental Functions and Nutrition in Older People with Dementia.

This study evaluated changes of cognitive, physical, and nutritional status before and after the interruption and resumption of daycare services during the COVID-19 pandemic in older dementia people in a daycare center. Comprehensive geriatric assessment data were analyzed before and after the lockdown of daycare center services, including mini-mental state examination, activities of daily living (ADL) scores, mini-nutritional assessment-short forms (MNA-SF), and timed up-and-go (TUG) tests. Among 19 dementia people participating in daycare services, 17 participants were enrolled in the study with, finally, two excluded because of incomplete follow-ups. They had a median age of 81 years; their MNA-SF scores and TUG values deteriorated significantly after a 3-month closure of daycare services (p < 0.05), and after resumption of daycare services the MNA-SF scores and TUG values recovered to near the pre-lockdown levels (p < 0.05). Besides, baseline ADL scores predicted a decline and recovery of TUG and MNA-SF values. Our findings suggest that planning continuous support for older dementia adults is important for daycare facilities during COVID-19 pandemic confinement.

The Clinical Efficacy and Safety of Anti-Viral Agents for Non-Hospitalized Patients with COVID-19: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

This network meta-analysis compared the clinical efficacy and safety of anti-viral agents for the prevention of disease progression among non-hospitalized patients with COVID-19. PubMed, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched from their inception to 28 May 2022. Only randomized controlled trials (RCTs) that investigated the clinical efficacy of anti-viral agents for non-hospitalized patients with COVID-19 were included. Three RCTs involving 4241 patients were included. Overall, anti-viral agents were associated with a significantly lower risk of COVID-19 related hospitalization or death compared with the placebo (OR, 0.23; 95% CI: 0.06-0.96; p = 0.04). Compared with the placebo, patients receiving nirmatrelvir plus ritonavir had the lowest risk of hospitalization or death (OR, 0.12; 95% CI: 0.06-0.24), followed by remdesivir (OR, 0.13; 95% CI: 0.03-0.57) and then molnupiravir (OR, 0.67; 95% CI: 0.46-0.99). The rank probability for each treatment calculated using the P-score revealed that nirmatrelvir plus ritonavir was the best anti-viral treatment, followed by remdesivir and then molnupiravir. Finally, anti-viral agents were not associated with an increased risk of adverse events compared with the placebo. For non-hospitalized patients with COVID-19 who are at risk of disease progression, the currently recommended three anti-viral agents, nirmatrelvir plus ritonavir, molnupiravir and remdesivir, should continue to be recommended for the prevention of disease progression. Among them, oral nirmatrelvir plus ritonavir and intravenous remdesivir seem to be the better choice, followed by molnupiravir, as determined by this network meta-analysis. Additionally, these three anti-viral agents were shown to be as tolerable as the placebo in this clinical setting.