IDDF2023-ABS-0045 Spatiotemporal immune landscape of Mas-driven pro-inflammatory microenvironment with hyperactivated glycolysis in acetaminophen-induced liver injury

IDDF2023-ABS-0045 Figure 1 IDDF2023-ABS-0045 Figure 2 IDDF2023-ABS-0045 Figure 3 IDDF2023-ABS-0045 Figure 4

American ginseng with different processing methods ameliorate immunosuppression induced by cyclophosphamide in mice via the MAPK signaling pathways.

This study aimed to clarify the effects of two processed forms of American ginseng (Panax quinquefolius L.) on immunosuppression caused by cyclophosphamide (CTX) in mice. In the CTX-induced immunosuppressive model, mice were given either steamed American ginseng (American ginseng red, AGR) or raw American ginseng (American ginseng soft branch, AGS) by intragastric administration. Serum and spleen tissues were collected, and the pathological changes in mice spleens were observed by conventional HE staining. The expression levels of cytokines were detected by ELISA, and the apoptosis of splenic cells was determined by western blotting. The results showed that AGR and AGS could relieve CTX-induced immunosuppression through the enhanced immune organ index, improved cell-mediated immune response, increased serum levels of cytokines (TNF-α, IFN-γ, and IL-2) and immunoglobulins (IgG, IgA, and IgM), as well as macrophage activities including carbon clearance and phagocytic index. AGR and AGS downregulated the expression of BAX and elevated the expression of Bcl-2, p-P38, p-JNK, and p-ERK in the spleens of CTX-injected animals. Compared to AGS, AGR significantly improved the number of CD4+CD8-T lymphocytes, the spleen index, and serum levels of IgA, IgG, TNF-α, and IFN-γ. The expression of the ERK/MAPK pathway was markedly increased. These findings support the hypothesis that AGR and AGS are effective immunomodulatory agents capable of preventing immune system hypofunction. Future research may investigate the exact mechanism to rule out any unforeseen effects of AGR and AGS.

A novel photoelectrochemical immunosensor based on TiO2@Bi2WO6 hollow microspheres and Ag2S for sensitive detection of SARS-COV-2 nucleocapsid protein.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) is a cluster of ß coronaviruses. The 2019 coronavirus disease (COVID-19) caused by SARS-COV-2 is emerging as a global pandemic. Thus, early diagnosis of SARS-COV-2 is essential to prevent severe outbreaks of the disease. In this experiment, a novel label-free photoelectrochemical (PEC) immunosensor was obtained based on silver sulfide (Ag2S) sensitized titanium dioxide@bismuth tungstate (TiO2@Bi2WO6) nanocomposite for quantitative detection of SARS-COV-2 nucleocapsid protein. The constructed TiO2@Bi2WO6 hollow microspheres had large specific surface area and could produce high photocurrent intensity under visible light illumination. Ag2S was in-situ grown on the surface of thioglycolic acid (TGA) modified TiO2@Bi2WO6. In particular, TiO2@Bi2WO6 and Ag2S formed a good energy level match, which could effectively enhance the photocurrent conversion efficiency and strength the photocurrent response. Ascorbic acid (AA) acted as an effective electron donor to effectively eliminate photogenerated holes. Under optimal experimental conditions, the constructed immunosensor presented a supersensitive response to SARS-COV-2 nucleocapsid protein, with a desirable linear relationship ranged from 0.001 to 50 ng/mL for nucleocapsid protein and a lower detection limit of 0.38 pg/mL. The fabricated sensor exhibited a wide linear range, excellent selectivity, specificity and stability, which provided a valuable referential idea for the detection of SARS-COV-2.

Non-pharmaceutical interventions for COVID-19 reduced the incidence of infectious diseases: a controlled interrupted time-series study.

BACKGROUND: Non-pharmaceutical interventions (NPIs) have been implemented worldwide to suppress the spread of coronavirus disease 2019 (COVID-19). However, few studies have evaluated the effect of NPIs on other infectious diseases and none has assessed the avoided disease burden associated with NPIs. We aimed to assess the effect of NPIs on the incidence of infectious diseases during the COVID-19 pandemic in 2020 and evaluate the health economic benefits related to the reduction in the incidence of infectious diseases. METHODS: Data on 10 notifiable infectious diseases across China during 2010-2020 were extracted from the China Information System for Disease Control and Prevention. A two-stage controlled interrupted time-series design with a quasi-Poisson regression model was used to examine the impact of NPIs on the incidence of infectious diseases. The analysis was first performed at the provincial-level administrative divisions (PLADs) level in China, then the PLAD-specific estimates were pooled using a random-effect meta-analysis. RESULTS: A total of 61,393,737 cases of 10 infectious diseases were identified. The implementation of NPIs was associated with 5.13 million (95% confidence interval [CI] 3.45‒7.42) avoided cases and USD 1.77 billion (95% CI 1.18‒2.57) avoided hospital expenditures in 2020. There were 4.52 million (95% CI 3.00‒6.63) avoided cases for children and adolescents, corresponding to 88.2% of total avoided cases. The top leading cause of avoided burden attributable to NPIs was influenza [avoided percentage (AP): 89.3%; 95% CI 84.5‒92.6]. Socioeconomic status and population density were effect modifiers. CONCLUSIONS: NPIs for COVID-19 could effectively control the prevalence of infectious diseases, with patterns of risk varying by socioeconomic status. These findings have important implications for informing targeted strategies to prevent infectious diseases.

Long-term impacts of non-occupational wildfire exposure on human health: A systematic review.

The intensity and frequency of wildfires is increasing globally. The systematic review of the current evidence on long-term impacts of non-occupational wildfire exposure on human health has not been performed yet. To provide a systematic review and identify potential knowledge gaps in the current evidence of long-term impacts of non-occupational exposure to wildfire smoke and/or wildfire impacts on human health. We conducted a systematic search of the literature via MEDLINE, Embase and Scopus from the database inception to July 05, 2022. References from the included studies and relevant reviews were also considered. The Newcastle-Ottawa Scale (NOS) and a validated quality assessment framework were used to evaluate the quality of observational studies. Study results were synthesized descriptively. A total of 36 studies were included in our systematic review. Most studies were from developed countries (11 in Australia, 9 in Canada, 7 in the United States). Studies predominantly focused on mental health (21 studies, 58.33%), while evidence on long-term impacts of wildfire exposure on health outcomes other than mental health is limited. Current evidence indicated that long-term impacts of non-occupational wildfire exposure were associated with mortality (COVID-19 mortality, cardiovascular disease mortality and acute myocardial disease mortality), morbidity (mainly respiratory diseases), mental health disorders (mainly posttraumatic stress disorder), shorter height of children, reduced lung function and poorer general health status. However, no significant associations were observed for long-term impacts of wildfire exposure on child mortality and respiratory hospitalizations. The population-based high-quality evidence with quantitative analysis on this topic is still limited. Future well-designed studies considering extensive wildfire smoke air pollutants (e.g., particulate matter, ozone, nitrogen oxides) and estimating risk coefficient values for extensive health outcomes (e.g., mortality, morbidity) are warranted to fill current knowledge gaps.

Biofilms possibly harbor occult SARS-CoV-2 may explain lung cavity, re-positive and long-term positive results.

During the COVID-19 pandemic, there have been an increasing number of COVID-19 patients with cavitary or cystic lung lesions, re-positive or long-term positive nucleic acid tests, but the mechanism is still unclear. Lung cavities may appear at long time interval from initial onset of coronavirus infection, generally during the absorption phase of the disease. The main histopathological characteristic is diffuse alveolar damage and may have more severe symptoms after initial recovery from COVID-19 and an increased mortality rate. There are many possible etiologies of pulmonary cavities in COVID-19 patients and we hypothesize that occult SARS-CoV-2, in the form of biofilm, is harbored in the airway lacuna with other pathogenic microorganisms, which may be the cause of pulmonary cavities and repeated and long-term positive nucleic acid tests.

Biofilms possibly harbor occult SARS-CoV-2 may explain lung cavity, re-positive and long-term positive results

During the COVID-19 pandemic, there have been an increasing number of COVID-19 patients with cavitary or cystic lung lesions, re-positive or long-term positive nucleic acid tests, but the mechanism is still unclear. Lung cavities may appear at long time interval from initial onset of coronavirus infection, generally during the absorption phase of the disease. The main histopathological characteristic is diffuse alveolar damage and may have more severe symptoms after initial recovery from COVID-19 and an increased mortality rate. There are many possible etiologies of pulmonary cavities in COVID-19 patients and we hypothesize that occult SARS-CoV-2, in the form of biofilm, is harbored in the airway lacuna with other pathogenic microorganisms, which may be the cause of pulmonary cavities and repeated and long-term positive nucleic acid tests.

Long-term improvement of air quality associated with lung function benefits in Chinese young adults: A quasi-experiment cohort study.

INTRODUCTION: Long-term exposure to air pollution is associated with lung function impairment. However, whether long-term improvements in air quality could improve lung function is unclear. OBJECTIVES: To examine whether the reduction of long-term air pollution was associated with lung function improvement among Chinese young adults. METHODS: We conducted a prospective quasi-experiment cohort study with 1731 college students in Shandong, China from September 2019 to September 2020, covering COVID-19 lockdown period. Data on air pollution concentrations were obtained from China Environmental Monitoring Station. Lung function indicators included forced vital capacity (FVC), forced expiratory volume in 1st second (FEV1) and forced expiratory flow at 50 % of FVC (FEF50%). We used linear mixed-effects model to examine the associations between the change of air pollutants concentrations and the change of lung function, and additional adjustments for indoor air pollution (IAP) source. We also conducted stratified analysis by sex. RESULTS: Compared with 2019, the mean FVC, FEV1 and FEF50% were elevated by 414.4 ml, 321.5 ml, and 28.4 ml/s respectively in 2020. Every 5 µg/m3 decrease in annual average PM2.5 concentrations was associated with 36.0 ml [95 % confidence interval (CI):6.0, 66.0 ml], 46.1 ml (95 % CI:16.7, 75.5 ml), and 124.2 ml/s (95 % CI:69.5, 178.9 ml/s) increment in the FVC, FEV1, and FEF50%, respectively. Similar associations were found for PM10. The estimated impact was almost unchanged after adjusting for IAP source. There was no significant effect difference between males and females. CONCLUSION: Long-term improvement of air quality can improve lung function among young adults. Stricter policies on improving air quality are needed to protect human health.

Highly efficient antifogging/antimicrobial dual-functional chitosan based coating for optical devices.

The coating is frequently adopted to modify the product surface without influencing the essential features of the pristine products. Recently, significant demand has existed for efficient anti-fogging/anti-microbial surfaces in various applications to inhibit microbial growth with high transparency in high-humidity environments, especially in pandemics such as COVID-19. The current study used dual-functional chitosan (Ch) polysaccharide coating with highly hydrophilic properties to be progressively incorporated onto the glass substrates using a simple one-pot technique. Utilizing hot/cold fogging tests and plate count method, the dual-functional Ch/SiO2(3) layer possesses excellent antifogging performance and anti-microbial activity. The hydrogen bonds and electrostatic attractions formed between MSN and Ch result in a higher bound water ratio, as confirmed by the low field nuclear magnetic resonance (LF-NMR). Therefore, based on the chitosan/silica layer, 95 % is the minimum proportion of bound water necessary in the final layer structure to completely inhibit microbial and fogging activities.

Mortality burden due to long-term exposure to ambient PM2.5 above the new WHO air quality guideline based on 296 cities in China.

OBJECTIVE: Quantifying the spatial and socioeconomic variation of mortality burden attributable to particulate matters with aerodynamic diameter ≤ 2.5 µm (PM2.5) has important implications for pollution control policy. This study aims to examine the regional and socioeconomic disparities in the mortality burden attributable to long-term exposure to ambient PM2.5 in China. METHODS: Using data of 296 cities across China from 2015 to 2019, we estimated all-cause mortality (people aged ≥ 16 years) attributable to the long-term exposure to ambient PM2.5 above the new WHO air quality guideline (5 µg/m3). Attributed fraction (AF), attributed deaths (AD), attributed mortality rate (AMR) and total value of statistical life lost (VSL) by regional and socioeconomic levels were reported. RESULTS: Over the period of 2015-2019, 17.0% [95% confidence interval (CI): 7.4-25.2] of all-cause mortality were attributable to long-term exposure to ambient PM2.5, corresponding to 1,425.2 thousand deaths (95% CI: 622.4-2,099.6), 103.5/105 (95% CI: 44.9-153.3) AMR, and 1006.9 billion USD (95% CI: 439.8-1483.4) total VSL per year. The AMR decreased from 120.5/105 (95% CI: 52.9-176.6) to 92.7/105 (95% CI:39.9-138.5) from 2015 to 2019. The highest mortality burden was observed in the north region (annual average AF = 24.2%, 95% CI: 10.8-35.1; annual average AMR = 137.0/105, 95% CI: 60.9-198.5). The highest AD and economic loss were observed in the east region (annual average AD = 390.0 thousand persons, 95% CI: 170.3-574.6; annual total VSL = 275.6 billion USD, 95% CI: 120.3-406.0). Highest AMR was in the cities with middle level of GDP per capita (PGDP)/urbanization. The majority of the top ten cities of AF, AMR and VSL were in high and middle PGDP/urbanization regions. CONCLUSION: There were significant regional and socioeconomic disparities in PM2.5 attributed mortality burden among Chinese cities, suggesting differential mitigation policies are required for different regions in China.

Accelerating PERx reaction enables covalent nanobodies for potent neutralization of SARS-CoV-2 and variants.

The long-lasting COVID-19 pandemic and increasing SARS-CoV-2 variants demand effective drugs for prophylactics and treatment. Protein-based biologics offer high specificity, yet their noncovalent interactions often lead to drug dissociation and incomplete inhibition. Here, we have developed covalent nanobodies capable of binding with SARS-CoV-2 irreversibly via a proximity-enabled reactive therapeutic (PERx) mechanism. A latent bioreactive amino acid (FFY) was designed and genetically encoded into nanobodies to accelerate the PERx reaction rate. Compared with the noncovalent wild-type nanobody, the FFY-incorporated covalent nanobodies neutralized both wild-type SARS-CoV-2 and its Alpha, Delta, Epsilon, Lambda, and Omicron variants with drastically higher potency. This PERx-enabled covalent-nanobody strategy and the related insights into increased potency can be valuable to developing effective therapeutics for various viral infections.

Satisfaction Levels of Young Urban Residents With Public Sports Services in China During the COVID-19 Epidemic.

The extensive changes in public and private life caused by the ongoing COVID-19 epidemic in China have created a "new normal." To understand urban residents' satisfaction with public sports services under these conditions and to identify factors that influence satisfaction, urban residents in several major Chinese cities were randomly sampled with an online questionnaire to measure their level of satisfaction with public sports services in China during the COVID-19 epidemic. With the response rate of 87.9%, 703 valid questionnaires out of 800 questionnaires distributed were analyzed. A structural equation model was constructed where health literacy and the residents' expectations were independent variables, residents' participation was a mediating variable, and residents' satisfaction was the dependent variable. Cronbach's α test and Kaiser-Meyer-Olkin test confirmed that the questionnaire was reliable and valid. Survey results suggest that young urban residents' participation in public sports services is influenced by personal health literacy and residents' expectations. Participation serves a mediating role between health literacy and residents' satisfaction, but not between residents' expectations and their satisfaction. Young urban residents' satisfaction with public sports services may be improved by increasing access to health information, improving hardware and software platforms to support those services, and catering the services to the interests of the population.

Global, regional, and national burden of mortality associated with short-term temperature variability from 2000-19: a three-stage modelling study.

BACKGROUND: Increased mortality risk is associated with short-term temperature variability. However, to our knowledge, there has been no comprehensive assessment of the temperature variability-related mortality burden worldwide. In this study, using data from the MCC Collaborative Research Network, we first explored the association between temperature variability and mortality across 43 countries or regions. Then, to provide a more comprehensive picture of the global burden of mortality associated with temperature variability, global gridded temperature data with a resolution of 0·5°â€ˆ× 0·5° were used to assess the temperature variability-related mortality burden at the global, regional, and national levels. Furthermore, temporal trends in temperature variability-related mortality burden were also explored from 2000-19. METHODS: In this modelling study, we applied a three-stage meta-analytical approach to assess the global temperature variability-related mortality burden at a spatial resolution of 0·5°â€ˆ× 0·5° from 2000-19. Temperature variability was calculated as the SD of the average of the same and previous days' minimum and maximum temperatures. We first obtained location-specific temperature variability related-mortality associations based on a daily time series of 750 locations from the Multi-country Multi-city Collaborative Research Network. We subsequently constructed a multivariable meta-regression model with five predictors to estimate grid-specific temperature variability related-mortality associations across the globe. Finally, percentage excess in mortality and excess mortality rate were calculated to quantify the temperature variability-related mortality burden and to further explore its temporal trend over two decades. FINDINGS: An increasing trend in temperature variability was identified at the global level from 2000 to 2019. Globally, 1 753 392 deaths (95% CI 1 159 901-2 357 718) were associated with temperature variability per year, accounting for 3·4% (2·2-4·6) of all deaths. Most of Asia, Australia, and New Zealand were observed to have a higher percentage excess in mortality than the global mean. Globally, the percentage excess in mortality increased by about 4·6% (3·7-5·3) per decade. The largest increase occurred in Australia and New Zealand (7·3%, 95% CI 4·3-10·4), followed by Europe (4·4%, 2·2-5·6) and Africa (3·3, 1·9-4·6). INTERPRETATION: Globally, a substantial mortality burden was associated with temperature variability, showing geographical heterogeneity and a slightly increasing temporal trend. Our findings could assist in raising public awareness and improving the understanding of the health impacts of temperature variability. FUNDING: Australian Research Council, Australian National Health & Medical Research Council.

The Impact of Perceptions of Positive COVID-19 Information on Travel Motivation and Intention: Evidence From Chinese University Students.

The COVID-19 pandemic has influenced the tourism industry in various ways, including tourists' travel motivations and intentions. Unlike previous studies that have focused on the dark side of the pandemic, this study adds the dimension of perceptions of positive information on COVID-19 to the Theory of Planned Behavior to explore their influence on travel motivation and intention. A total of 470 valid questionnaires were collected from a sample of Chinese university students. The results showed that the students' perceptions of positive COVID-19 information positively impacted their travel intentions through the variables of perceived behavioral control, travel attitudes, and travel motivations. Perceived behavioral control was the mediating variable that most explained the impact of perceptions of positive COVID-19 information on travel motivation and intention. This study contributes to the understanding of the influence of the COVID-19 pandemic on tourism and of university students' travel motivations and intentions. It also offers implications for the tourism industry to formulate relevant recovery strategies during and after the pandemic.

Effect of Sensory Deprivation of Nasal Respiratory on Behavior of C57BL/6J Mice.

Nasal breathing is a dynamic cortical organizer involved in various behaviors and states, such as locomotion, exploration, memory, emotion, introspection. However, the effect of sensory deprivation of nasal respiratory breath (NRD) on behavior remain poorly understood. Herein, general locomotor activity, emotion, learning and memory, social interaction, and mechanical pain were evaluated using a zinc sulfate nasal irrigation induced nasal respiratory sensory deprivation animal model (ZnSO4-induced mouse model). In the open field test, the elevated O-maze test, and forced swim test, NRD mice exhibited depressive and anxiety-like behaviors. In memory-associated tests, NRD mice showed cognitive impairments in the hippocampal-dependent memory (Y maze, object recognition task, and contextual fear conditioning (CFC)) and amygdala-dependent memory (the tone-cued fear conditioning test (TFC)). Surprisingly, NRD mice did not display deficits in the acquisition of conditional fear in both CFC and TFC tests. Still, they showed significant memory retrieval impairment in TFC and enhanced memory retrieval in CFC. At the same time, in the social novelty test using a three-chamber setting, NRD mice showed impaired social and social novelty behavior. Lastly, in the von Frey filaments test, we found that the pain sensitivity of NRD mice was reduced. In conclusion, this NRD mouse model showed a variety of behavioral phenotypic changes, which could offer an important insight into the behavioral impacts of patients with anosmia or those with an impaired olfactory bulb (OB) (e.g., in COVID-19, Alzheimer's disease, Parkinson's disease, etc.).

Mental health of new undergraduate students before and after COVID-19 in China.

The purpose of this study was to examine the changes in severity of anxiety and depression symptoms, stress and sleeping quality after three months of mass quarantine for COVID-19 among undergraduate fresh students compared to their pre-COVID-19 measures. We used participants from the Chinese Undergraduate Cohort (CUC), a national prospective longitudinal study to examine the changes in anxiety and depression symptoms severity, stress and sleep quality after being under mass quarantine for three months. Wilcoxon matched pair signed-rank test was used to compare the lifestyle indicators. Severity of anxiety, depression symptoms, stress and sleep quality were compared with Wilcoxon signed-rank test. We used generalized estimating equation (GEE) to further quantify the change in mental health indicators and sleep quality after the COVID-19 mass quarantine compared to baseline. This study found that there was no deterioration in mental health status among Chinese new undergraduate students in 2020 after COVID-19 mass quarantine compared with the baseline measures in 2019. There was an improvement in sleep quality and anxiety symptoms. After adjusting for age, sex, exercise habit, time spent on mobile gadgets, and time spent outdoors, year 2020 was significantly associated with severity of depression symptoms in males (OR:1.52. 95%CI:1.05-2.20, p-value = 0.027). Year 2020 was significantly associated with the improvement of sleeping quality in total (OR:0.45, 95%CI:0.38-0.52, p < 0.001) and in all the subgroups. This longitudinal study found no deterioration in mental health status among Chinese new undergraduate students after three months of mass quarantine for COVID-19.

Cryo-EM and antisense targeting of the 28-kDa frameshift stimulation element from the SARS-CoV-2 RNA genome.

Drug discovery campaigns against COVID-19 are beginning to target the SARS-CoV-2 RNA genome. The highly conserved frameshift stimulation element (FSE), required for balanced expression of viral proteins, is a particularly attractive SARS-CoV-2 RNA target. Here we present a 6.9 Å resolution cryo-EM structure of the FSE (88 nucleotides, ~28 kDa), validated through an RNA nanostructure tagging method. The tertiary structure presents a topologically complex fold in which the 5' end is threaded through a ring formed inside a three-stem pseudoknot. Guided by this structure, we develop antisense oligonucleotides that impair FSE function in frameshifting assays and knock down SARS-CoV-2 virus replication in A549-ACE2 cells at 100 nM concentration.

Trends in Food Preferences and Sustainable Behavior during the COVID-19 Lockdown: Evidence from Spanish Consumers.

The COVID-19 pandemic poses a threat to global food security, and it changes consumers' food buying and consumption behavior. This research not only investigates trends in Spanish consumers' general food shopping and consumption habits during the lockdown, but also investigates these trends from the perspective of sustainable purchasing. Specifically, total food consumption (C), food expenditure (E), and purchase of food with sustainable attributes (S) were measured. Data were collected from a semi-structured questionnaire which was distributed online among 1203 participants. The logit models showed that gender, age, employment status, and consumers' experiences were associated with total food consumption and expenditure during the lockdown. In addition, consumers' risk perceptions, shopping places, trust level in information sources, and risk preference were highly essential factors influencing consumers' preferences and sustainable behavior. Consumers' objective knowledge regarding COVID-19 was related to expenditure. Furthermore, family structure only affected expenditure, while income and place of residence influenced food consumption. Mood was associated with expenditure and the purchase of sustainable food. Household size affected purchasing behavior towards food with sustainable attributes. This research provides references for stakeholders that help them to adapt to the new COVID-19 situation.

Temperature-mortality association during and before the COVID-19 pandemic in Italy: A nationwide time-stratified case-crossover study.

OBJECTIVES: To identify the associations of temperature with non-COVID-19 mortality and all-cause mortality in the pandemic 2020 in comparison with the non-COVID-19 period in Italy. METHODS: The data on 3,189,790 all-cause deaths (including 3,134,137 non-COVID-19 deaths) and meteorological conditions in 107 Italian provinces between February 1st and November 30th in each year of 2015-2020 were collected. We employed a time-stratified case-crossover study design combined with the distributed lag non-linear model to investigate the relationships of temperature with all-cause and non-COVID-19 mortality in the pandemic and non-pandemic periods. RESULTS: Cold temperature exposure contributed higher risks for both all-cause and non-COVID-19 mortality in the pandemic period in 2020 than in 2015-2019. However, no different change was found for the impacts of heat. The relative risk (RR) of non-COVID-19 deaths and all-cause mortality at extremely cold (2 °C) in comparison with the estimated minimum mortality temperature (19 °C) in 2020 were 1.63 (95% CI: 1.55-1.72) and 1.45 (95%CI: 1.31-1.61) respectively, which were higher than all-cause mortality risk in 2015-2019 with RR of 1.19 (95%CI: 1.17-1.21). CONCLUSION: Cold exposure indicated stronger impacts than high temperatures on all-cause and non-COVID-19 mortality in the pandemic year 2020 compared to its counterpart period in 2015-2019 in Italy.

The Potential of Glycyrrhizinate in the Management of COVID-19: A Systematic Review of the Efficacy and Safety of Glycyrrhizin Preparations in the Treatment of SARS and MERS.

The SARS-CoV-2 outbreak in 2019 highlighted the fact that no specific medications providing effective treatment have been identified and approved. We explored the possibilities for COVID-19 by systematically reviewing evidence on the efficacy and safety of glycyrrhizin preparations for SARS and MERS. Electronic databases were systematically searched from inception to February 2020 for eligible studies that evaluated the efficacy and safety of glycyrrhizin preparations for SARS and MERS. A quantitative analysis or descriptive analysis was applied. Five retrospective cohort studies were included, and NOS scores ranged from 5-7 points. The clinical symptoms of dry cough, chest distress and dyspnoea improved quickly, and elevated serum levels of aminotransferase decreased after compound glycyrrhizin treatment. The SARS-CoV antibody appeared earlier in the treated group than in the control group ([Formula: see text][Formula: see text]d). Compared to that with conventional medications, the average period from peak to 50% improvement of lesions, in terms of X-ray manifestations, was shorter with compound glycyrrhizin treatment ([Formula: see text]2.1[Formula: see text]d), and treatment reduced the dosage ([Formula: see text][Formula: see text]mg/d) and duration of the corticosteroids used, without other serious adverse reactions. Based on the available evidence regarding glycyrrhizin preparations for treating SARS and MERS, we infer that compound glycyrrhizin could be an optional therapeutic strategy for SARS-CoV-2 infections, especially those complicated with liver damage. Further research using well-designed randomized clinical trials (RCTs) is warranted to determine the dosage and duration of use of compound glycyrrhizin and to monitor its specific adverse effects.