A comprehensive health effects assessment of the use of sanitizers and disinfectants during COVID-19 pandemic: a global survey.

COVID-19 has affected all aspects of human life so far. From the outset of the pandemic, preventing the spread of COVID-19 through the observance of health protocols, especially the use of sanitizers and disinfectants was given more attention. Despite the effectiveness of disinfection chemicals in controlling and preventing COVID-19, there are critical concerns about their adverse effects on human health. This study aims to assess the health effects of sanitizers and disinfectants on a global scale. A total of 91,056 participants from 154 countries participated in this cross-sectional study. Information on the use of sanitizers and disinfectants and health was collected using an electronic questionnaire, which was translated into 26 languages via web-based platforms. The findings of this study suggest that detergents, alcohol-based substances, and chlorinated compounds emerged as the most prevalent chemical agents compared to other sanitizers and disinfectants examined. Most frequently reported health issues include skin effects and respiratory effects. The Chi-square test showed a significant association between chlorinated compounds (sodium hypochlorite and per-chlorine) with all possible health effects under investigation (p-value <0.001). Examination of risk factors based on multivariate logistic regression analysis showed that alcohols and alcohols-based materials were associated with skin effects (OR, 1.98; 95%CI, 1.87-2.09), per-chlorine was associated with eye effects (OR, 1.83; 95%CI, 1.74-1.93), and highly likely with itching and throat irritation (OR, 2.00; 95%CI, 1.90-2.11). Furthermore, formaldehyde was associated with a higher prevalence of neurological effects (OR, 2.17; 95%CI, 1.92-2.44). Furthermore, formaldehyde was associated with a higher prevalence of neurological effects (OR, 2.17; 95%CI, 1.92-2.44). The use of sodium hypochlorite and per-chlorine also had a high chance of having respiratory effects. The findings of the current study suggest that health authorities need to implement more awareness programs about the side effects of using sanitizers and disinfectants during viral epidemics especially when they are used or overused.

COVID-19 Phobia among Korean, Chinese, and Japanese students: An international comparative study.

This study aimed to identify the characteristic differences and potential contributing factors of coronavirus disease 2019 (COVID-19) phobia between undergraduate and graduate students in Korea, Japan, and China. We used the online survey tool, we retained 460 responses from Korea, 248 responses from Japan, and 788 responses from China for analysis. We performed the statistical analysis; ANOVA F-test and Multiple linear regression. We visualized the results of these calculations using GraphPad PRISM 9. The mean COVID-19 phobia score was highest in Japan at 50.5 points. Psychological fear was identically prevalent in Japan and China, at an average of 17.3 points. Psychosomatic fear was highest in Japan at 9.2 points. Further, economic fear was highest in Korea at 13 points, whereas social fear was highest in China at 13.1 points. In Korea, COVID-19 phobia scores were significantly higher among women than in men. In Japan, COVID-19 phobia scores were significantly higher in individuals who complied with social distancing mandates. In China, a lack of previous experience with self-administered testing kits was associated with significantly lower phobia scores. Individuals who were avoiding crowded places had significantly higher scores in 3 countries. This implies that the students knew that it was necessary to comply with COVID-19 preventive behaviors to prevent infections. The findings of this study could be used as a reference when establishing an approach strategy to reduce COVID-19 phobia among Chinese, Japanese, and Korean students.

Global Trends in Social Prescribing: Web-Based Crawling Approach.

BACKGROUND: Social loneliness is a prevalent issue in industrialized countries that can lead to adverse health outcomes, including a 26% increased risk of premature mortality, coronary heart disease, stroke, depression, cognitive impairment, and Alzheimer disease. The United Kingdom has implemented a strategy to address loneliness, including social prescribing-a health care model where physicians prescribe nonpharmacological interventions to tackle social loneliness. However, there is a need for evidence-based plans for global social prescribing dissemination. OBJECTIVE: This study aims to identify global trends in social prescribing from 2018. To this end, we intend to collect and analyze words related to social prescribing worldwide and evaluate various trends of related words by classifying the core areas of social prescribing. METHODS: Google's searchable data were collected to analyze web-based data related to social prescribing. With the help of web crawling, 3796 news items were collected for the 5-year period from 2018 to 2022. Key topics were selected to identify keywords for each major topic related to social prescribing. The topics were grouped into 4 categories, namely Healthy, Program, Governance, and Target, and keywords for each topic were selected thereafter. Text mining was used to determine the importance of words collected from new data. RESULTS: Word clouds were generated for words related to social prescribing, which collected 3796 words from Google News databases, including 128 in 2018, 432 in 2019, 566 in 2020, 748 in 2021, and 1922 in 2022, increasing nearly 15-fold between 2018 and 2022 (5 years). Words such as health, prescribing, and GPs (general practitioners) were the highest in terms of frequency in the list for all the years. Between 2020 and 2021, COVID, gardening, and UK were found to be highly related words. In 2022, NHS (National Health Service) and UK ranked high. This dissertation examines social prescribing-related term frequency and classification (2018-2022) in Healthy, Program, Governance, and Target categories. Key findings include increased "Healthy" terms from 2020, "gardening" prominence in "Program," "community" growth across categories, and "Target" term spikes in 2021. CONCLUSIONS: This study's discussion highlights four key aspects: (1) the "Healthy" category trends emphasize mental health, cancer, and sleep; (2) the "Program" category prioritizes gardening, community, home-schooling, and digital initiatives; (3) "Governance" underscores the significance of community resources in social prescribing implementation; and (4) "Target" focuses on 4 main groups: individuals with long-term conditions, low-level mental health issues, social isolation, or complex social needs impacting well-being. Social prescribing is gaining global acceptance and is becoming a global national policy, as the world is witnessing a sharp rise in the aging population, noncontagious diseases, and mental health problems. A successful and sustainable model of social prescribing can be achieved by introducing social prescribing schemes based on the understanding of roles and the impact of multisectoral partnerships.

Particle Deposition in Large-Scale Human Tracheobronchial Airways Predicted by Single-Path Modelling.

The health effects of particles are directly related to their deposition patterns (deposition site and amount) in human airways. However, estimating the particle trajectory in a large-scale human lung airway model is still a challenge. In this work, a truncated single-path, large-scale human airway model (G3-G10) with a stochastically coupled boundary method were employed to investigate the particle trajectory and the roles of their deposition mechanisms. The deposition patterns of particles with diameters (dp) of 1-10 µm are investigated under various inlet Reynolds numbers (Re = 100-2000). Inertial impaction, gravitational sedimentation, and combined mechanism were considered. With the increasing airway generations, the deposition of smaller particles (dp < 4 µm) increased due to gravitational sedimentation, while that of larger particles decreased due to inertial impaction. The obtained formulas of Stokes number and Re can predict the deposition efficiency due to the combined mechanism in the present model, and the prediction can be used to assess the dose-effect of atmospheric aerosols on the human body. Diseases in deeper generations are mainly attributed to the deposition of smaller particles under lower inhalation rates, while diseases at the proximal generations mainly result from the deposition of larger particles under higher inhalation rates.

Validation of the Chinese version of the COVID-19 Phobia Scale among Chinese college students.

Background and objective: Different languages and versions of the COVID-19 Phobia Scale (C19P-S) have been developed and tested in several countries. Chinese college students are a large vulnerable group and are susceptible to psychological problems during the COVID-19 pandemic. However, no studies had yet examined the reliability and validity of the C19P-S in China among college students group. This study aims to evaluate the COVID-19-related phobia of Chinese college students and examine the reliability and validity of this scale. Methods: A total of 1689 Chinese college students participated in this study from April 27 to May 7, 2022. They finished the online questionnaire including demographic information and C19P-S. Cronbach's alpha and split-half reliability were used to examine the internal consistency of the scale. Confirmatory factor analysis was further used to examine the scale's construct validity. Convergence validity was also confirmed. Results: This scale in Chinese had high reliability and validity. The Cronbach's alpha and split-half reliability of the total scale were 0.960 and 0.935, respectively. The construct validity-related indicators of the total scale met the standards (RMSEA = 0.064, IFI = 0.907, TLI = 0.906, and CFI = 0.907). Regarding the subscales, the composite reliability (CR) and average variance extracted (AVE) also met the cutoff values (CR > 0.7 and AVE >0.5). Comparison between gender groups showed that total and subscale scores between male and female students differed significantly. Conclusion: The Chinese version of the C19P-S was appropriate for evaluating phobic symptoms among Chinese college students. Therefore, this tool could be used to evaluate the mental health of college students in the future.

Digital geographies of the bug: A case study of China's contact tracing systems in the COVID-19.

The COVID-19 pandemic has radically expanded the role of algorithmic governance in everyday mobility. In China, urban and provincial governments have introduced health codes app as a national contract tracing and quarantine enforcement method to restrict the movements of "risky" individuals through malls, subways, railways, as well as between regions. Yet the health codes have been implemented with uneven efficacy and unexpected consequences. Drawing on glitch politics, we read these unintended consequences as "bugs" emerging from the introduction of platform-based management into everyday life. These bugs mediated individuals' lived experiences of the digital app and the hybrid space constituted by population governance, individual digital navigation, and technology. Drawing on a database of posts scraped from Zhihu, a popular Chinese question-and-answer site, we examine three dimensions of the bug: the algorithmic bug, the territorial bug, and the corporeal bug. This paper sheds light on the significance of end-user experiences in digital infrastructure and contributes to our understanding of the digital geographies of bugs in algorithmic governance and platform urbanism.

Successful Treatment of Subacute Thyroiditis After Recombinant COVID-19 Vaccination Using Traditional Chinese Medicine: A Case Report.

Subacute thyroiditis (SAT) is a thyroid inflammatory disease, which can be triggered by viral infection. The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is considered to be a potent SAT-triggering factor in this COVID-19 pandemic. However, SAT occurring after SARS-CoV-2 vaccination is rarely reported. Despite the high availability of diagnostic tools, the recurrence and steroid dependence as well as delayed diagnosis of SAT remain. This paper reports a rare case where a patient was diagnosed with SAT post receiving a recombinant novel coronavirus vaccine (Anhui Zhifei Longcom Biopharmaceutical Co.Ltd., China), and efficiently treated with traditional Chinese medicine rather than prednisone. We hope that this case report not only contributes to raising awareness of SAT related to the COVID-19 vaccine but also provides an effective remedy in addition to glucocorticoid (GC).

Psychological research of the children with chronic kidney disease and their guardians during the COVID-19 pandemic.

Background: There is great mental stress due to the coronavirus disease 2019 (COVID-19) pandemic. However, there are no detailed psychological studies of the children with chronic kidney disease (CKD) and their guardians during the COVID-19 pandemic. Objective: This study explores the psychological pressure on children with CKD and their guardians. Methods: An online survey was conducted at 20 of the largest pediatric nephropathy departments in China, including the Rutter Parent Questionnaire, Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). Overall, 885 children (589 children with CKD associated with 296 children of the control group) completed the survey together with their guardians. Results: There was no statistical difference between CKD children and control children regarding their Rutter behavior scores and abnormal behaviors. Nevertheless, the abnormal behavior of children might aggravate the anxiety and depression of guardians in both CKD and control groups (p < 0.05). We confirmed that the anxiety and depression of guardians in the CKD group were both significantly higher than those in the control group (p < 0.05). The guardians in the CKD group with lower annual income were more likely to experience anxiety (p < 0.05). Furthermore, the guardians whose children were older than 11 years old might be more anxious than those who were 6-11 years old. Besides, the guardians in the CKD group who watched the news for 30-60 min daily were less likely to have depression than those who watched < 10 min (p < 0.05). The subgroup results showed that the gender, the time of watching the news, the annual income of guardians, and children's age might be the most critical factors influencing guardians' psychological burden. Conclusion: The guardians in the CKD group have more severe anxiety and depression during the pandemic. The children's abnormal behavior, adolescents' pressure, low household income, and the panic about the pandemic may be the main reasons for the anxiety and depression of guardians.

Removal performance of SARS-CoV-2 in wastewater treatment by membrane bioreactor, anaerobic-anoxic-oxic, and conventional activated sludge processes.

The potential risk of SARS-CoV-2 in treated effluent from a wastewater treatment plant (WWTP) is concerned since SARS-CoV-2 is contained in wastewater during the COVID-19 outbreak. However, the removal of SARS-CoV-2 in WWTP has not been well investigated. The objectives of this study were (i) to clarify the removal performance of SARS-CoV-2 during wastewater treatment, (ii) to compare the removal performance of different secondary treatment processes, and (iii) to evaluate applicability of pepper mild mottle of virus (PMMoV) as a performance indicator for the reduction of SARS-CoV-2 RNA in wastewater treatment. Influent wastewater, secondary-treatment effluent (before chlorination), and final effluent (after chlorination) samples were collected from a WWTP from May 28 to September 24, 2020, during the COVID-19 outbreak in Japan. The target WWTP had three parallel treatment systems employing conventional activated sludge (CAS), anaerobic-anoxic -oxic (A2O), and membrane bioreactor (MBR) processes. SARS-CoV-2 in both the liquid and solid fractions of the influent wastewater was concentrated and quantified using RT-qPCR. SARS-CoV-2 in treated effluent was concentrated from 10 L samples to achieve a detection limit as low as 10 copies/L. The log reduction value (LRV) of SARS-CoV-2 was 2.7 ± 0.86 log10 in CAS, 1.6 ± 0.50 log10 in A2O, and 3.6 ± 0.62 log10 in MBR. The lowest LRV observed during the sampling period was 2.8 log10 in MBR, 1.2 log10 in CAS, and 1.0 log10 in A2O process, indicating that the MBR had the most stable reduction performance. PMMoV was found to be a good indicator virus to evaluate reduction performance of SARS-CoV-2 independent of the process configuration because the LRV of PMMoV was significantly lower than that of SARS-CoV-2 in the CAS, A2O and MBR processes.

Assessing Knowledge, Preventive Practices, and Depression Among Chinese International Students and Local Korean Students in South Korea During the COVID-19 Pandemic: An Online Cross-Sectional Study.

Depression among university students and international university students is an increasing problem globally. This study aimed to clarify the differences on the conditions and determinants of the knowledge, preventive practices and depression of the Chinese international students and local Korean students in South Korea during the COVID-19 pandemic. An online cross-sectional questionnaire including general demographic characteristics, COVID-19-related knowledge, preventive practice, and the Patient Health Questionnaire (PHQ-9) was applied from March 23 to April 22, 2020. A total of 533 university students (171 Chinese international students and 362 local South Korean students) were included in the study. The majority of both Chinese international students and local South Korean students had a good comprehension of COVID-19. Chinese international students in South Korea showed better preventive practice than local Korean students, while the proportion of moderate to severe depression of Chinese international students was relatively higher (28.07%) than that of local Korean students (22.38%). Determinants of depression of Chinese international students in South Korea were information satisfaction, likelihood of survival after infection, symptoms of a cough and feelings of discrimination, while for local Korean students were gender, educational level, family, suspected symptoms, self-assessed physical health status, COVID-19 detection, population contact history and online sources of information. These results could be used as a reference for decreasing the depressive symptoms among the university students.

ORF8 protein of SARS-CoV-2 reduces male fertility in mice.

As one of the most rapidly evolving proteins of the genus Betacoronavirus, open reading frames (ORF8's) function and potential pathological consequence in vivo are still obscure. In this study, we show that the secretion of ORF8 is dependent on its N-terminal signal peptide sequence and can be inhibited by reactive oxygen species scavenger and endoplasmic reticulum-Golgi transportation inhibitor in cultured cells. To trace the effect of its possible in vivo secretion, we examined the plasma samples of coronavirus disease 2019 (COVID-19) convalescent patients and found that the patients aged from 40 to 60 had higher antibody titers than those under 40. To explore ORF8's in vivo function, we administered the mice with ORF8 via tail-vein injection to simulate the circulating ORF8 in the patient. Although no apparent difference in body weight, food intake, and vitality was detected between vehicle- and ORF8-treated mice, the latter displayed morphological abnormalities of testes and epididymides, as indicated by the loss of the central ductal lumen accompanied by a decreased fertility in 5-week-old male mice. Furthermore, the analysis of gene expression in the testes between vehicle- and ORF8-treated mice identified a decreased expression of Col1a1, the loss of which is known to be associated with mice's infertility. Although whether our observation in mice could be translated to humans remains unclear, our study provides a potential mouse model that can be used to investigate the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the human reproductive system.

Public Health Financing and Responses to COVID-19: Lessons from South Korea.

Health financing strategies contribute significantly to containing the outbreak of the Coronavirus disease 2019 (COVID-19). This study aims to reassess Korea's financing strategies in response to COVID-19 in 2020, to ascertain its effects and sustainability. The Joint External Evaluation tool was adopted to analyze the data collected from government reports, official statistics, and other sources. Findings show that Korea could maintain a low incidence and fatality rate compared with other countries, at low costs. It was a result of rapidly procured healthcare resources based on laws and policies established after the 2015 epidemic, and the National Health Insurance. However, to achieve long-term sustainability, it is important to enhance the financial stability of the national health insurance and increase the proportion of the public sector in healthcare resources.

Knowledge, Attitudes, and Practices Toward Coronavirus and Associated Anxiety Symptoms Among University Students: A Cross-Sectional Study During the Early Stages of the COVID-19 Pandemic in Bangladesh.

Background: University students' knowledge, attitude, and practice (KAP) toward COVID-19 are vital to prevent the spread of the virus, especially in the context of developing countries. Consequently, the present study aimed to determine the KAP levels of university students and associated anxiety during the earlier stage of the pandemic in Bangladesh. Methods: A cross-sectional, online study with 544 university students was conducted during April 17-May 1, 2020. The questionnaire incorporated several KAP-related test items aligned with the World Health Organization (WHO) guidelines. Anxiety was measured with the 2-item Generalized Anxiety Disorder scale (GAD-2). Multivariable logistic regression analysis was performed to determine the association between KAP levels and anxiety adjusting for sociodemographic variables. Subgroup analyses included rerunning models stratified by gender and quarantine status. Results: Approximately 50% of students showed high levels of knowledge about COVID-19 guidelines, 59% reported behavioral practices that aligned with COVID-19 guidelines, and 39% had negative attitudes toward COVID-19 guidelines. Attitudes differed by anxiety (χ2 = 23.55, p < 0.001); specifically, negative attitudes were associated with higher anxiety (OR: 2.40, 95% CI = 1.66-3.46, p < 0.001). Associations were significant for male (OR = 2.36; 95% CI = 1.45-3.84, p < 0.001) and female (OR = 2.45; 95% CI = 1.3-4.34; p < 0.001) students. Stratified analyses found non-quarantined students with negative attitudes had three times the chance of experiencing anxiety (OR = 3.14, 95% CI: 1.98-4.98, p < 0.001). Non-quarantined students with low levels of knowledge had half the chance of developing anxiety (OR = 0.49, 95% CI: 0.31-0.78, p < 0.01). Conclusion: Based on these findings, it is recommended that university authorities continue to prioritize proactive and effective measures to develop higher levels of knowledge, more positive attitudes and better behavioral practices regarding COVID-19 for the mental health of their students.

“Small” analysis of Big Data: An evaluation of the effects of social distancing in the United States

This paper proposes a ?small? contextual analysis approach to big data and reports our experimental application of this approach in evaluating the effects of social distancing on focused subpopulations in U.S. society. We recognize the common and critical limitations of big data, especially the unrepresentativeness and the unpublished methodology of accessible datasets. Our proposed methodological approach is built upon recent works on data ontology, especially the recognition that big data are essentially remaining digital footprints of human life in need of additional data of contextual factors for valid and meaningful interpretation. It guides the selection and processing of big data to make big data small and structured and thus articulable with traditional social sciences data and usable to conventional social sciences methods. In our experimental case study, we apply our sampling strategy developed from traditional social science data to Google?s mobility dataset for our analysis using primarily a Difference In Difference (DID) model. The results of this case study are of timely value to policy evaluation and public decision-making in the pandemic. We call for more proactive methodological innovations that confront the critical limitations of accessible big data especially in times of urgent needs.

Extended cohort for e-health, environment and DNA (exceed) COVID-19 focus

Background: New data collection in established longitudinal population studies provides an opportunity for studying the risk factors and sequelae of the novel coronavirus disease 2019 (COVID-19), plus the indirect impacts of the COVID-19 pandemic on wellbeing. The Extended Cohort for E-health, Environment and DNA (EXCEED) cohort is a population-based cohort (N>11,000), recruited from 2013 in Leicester, Leicestershire and Rutland. EXCEED includes consent for electronic healthcare record (EHR) linkage, spirometry, genomic data, and questionnaire data.

Exploring the spatial disparity of home-dwelling time patterns in the USA during the COVID-19 pandemic via Bayesian inference.

In this study, we aim to reveal hidden patterns and confounders associated with policy implementation and adherence by investigating the home-dwelling stages from a data-driven perspective via Bayesian inference with weakly informative priors and by examining how home-dwelling stages in the USA varied geographically, using fine-grained, spatial-explicit home-dwelling time records from a multi-scale perspective. At the U.S. national level, two changepoints are identified, with the former corresponding to March 22, 2020 (9 days after the White House declared the National Emergency on March 13) and the latter corresponding to May 17, 2020. Inspections at U.S. state and county level reveal notable spatial disparity in home-dwelling stage-related variables. A pilot study in the Atlanta Metropolitan area at the Census Tract level reveals that the self-quarantine duration and increase in home-dwelling time are strongly correlated with the median household income, echoing existing efforts that document the economic inequity exposed by the U.S. stay-at-home orders. To our best knowledge, our work marks a pioneering effort to explore multi-scale home-dwelling patterns in the USA from a purely data-driven perspective and in a statistically robust manner.

Brucellosis prevalence in yaks in China in 1980-2019: A systematic review and meta-analysis.

In the Qinghai-Tibet Plateau of China, the yak is an animal of particular economic interest, which provides protein and income for herders in daily life. Brucellosis is a bacterial disease that can infect humans and animals, including yaks. It can damage the yak reproductive system, causing miscarriage and orchitis. At the same time, brucellosis threatens the health of herders. We performed this meta-analysis using R software to explore the combined prevalence and risk factors of brucellosis in yak in China. Variability was assessed by the I2 statistic and Cochran Q statistic. We identified 52 publications of related research from four databases (Wanfang Data, VIP Chinese Journal Database, China National Knowledge Infrastructure, and of PubMed). The pooled prevalence of yak brucellosis was 8.39 %. Prevalence was highest in Southwestern China (11.1 %). The point estimate of brucellosis in yak from 2012 to 2016 was the highest (11.47 %). The point estimate of age ≤ 12 months (1.44 %) was lower than that of age > 12 months (15.6 %). This study shows that yak brucellosis is serious, and its incidence is higher than before 2012. We recommend carrying out large-scale yak brucellosis investigations in Western China and conducting comprehensive testing planning. The detection of brucellosis in adult animals should be strengthened to reduce the economic loss caused by brucellosis to herders and to improve public health.

Relevant mediators involved in and therapies targeting the inflammatory response induced by activation of the NLRP3 inflammasome in ischemic stroke.

The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome is a member of the NLR family of inherent immune cell sensors. The NLRP3 inflammasome can detect tissue damage and pathogen invasion through innate immune cell sensor components commonly known as pattern recognition receptors (PRRs). PRRs promote activation of nuclear factor kappa B (NF-κB) pathways and the mitogen-activated protein kinase (MAPK) pathway, thus increasing the transcription of genes encoding proteins related to the NLRP3 inflammasome. The NLRP3 inflammasome is a complex with multiple components, including an NAIP, CIITA, HET-E, and TP1 (NACHT) domain; apoptosis-associated speck-like protein containing a CARD (ASC); and a leucine-rich repeat (LRR) domain. After ischemic stroke, the NLRP3 inflammasome can produce numerous proinflammatory cytokines, mediating nerve cell dysfunction and brain edema and ultimately leading to nerve cell death once activated. Ischemic stroke is a disease with high rates of mortality and disability worldwide and is being observed in increasingly younger populations. To date, there are no clearly effective therapeutic strategies for the clinical treatment of ischemic stroke. Understanding the NLRP3 inflammasome may provide novel ideas and approaches because targeting of upstream and downstream molecules in the NLRP3 pathway shows promise for ischemic stroke therapy. In this manuscript, we summarize the existing evidence regarding the composition and activation of the NLRP3 inflammasome, the molecules involved in inflammatory pathways, and corresponding drugs or molecules that exert effects after cerebral ischemia. This evidence may provide possible targets or new strategies for ischemic stroke therapy.

Oxidative stress transforms 3CLpro into an insoluble and more active form to promote SARS-CoV-2 replication.

3CLpro is a key proteinase for SARS-CoV-2 replication and serves as an important target for antiviral drug development. However, how its activity is regulated intracellularly is still obscure. In this study, we developed a 3CLpro protease activity reporter system to examine the impact of various factors, including nutrient supplements, ions, pHs, or oxidative stress inducers, on 3CLpro protease activity. We found that oxidative stress could increase the overall activity of 3CLpro. Not altering the expression, oxidative stress decreased the solubility of 3CLpro in the lysis buffer containing 1% Triton-X-100. The Triton-X-100-insoluble 3CLpro was correlated with aggregates' formation and responsible for the increased enzymatic activity. The disulfide bonds formed between Cys85 sites of 3CLpro protomers account for the insolubility and the aggregation of 3CLpro. Besides being regulated by oxidative stress, 3CLpro impaired the cellular antioxidant capacity by regulating the cleavage of GPx1 at its N-terminus. This cleavage could further elevate the 3CLpro-proximate oxidative activity, favor aggregation and activation of 3CLpro, and thus lead to a positive feedback loop. In summary, we reported that oxidative stress transforms 3CLpro into a detergent-insoluble form that is more enzymatically active, leading to increased viral replication/transcription. Our study provided mechanistic evidence that suggests the therapeutic potential of antioxidants in the clinical treatment of COVID-19 patients.