Mask-related adverse skin reactions in orientals during COVID-19: Prevalence, social-psychological impacts and risk factors for acne exacerbation.

BACKGROUND: COVID-19 pandemic has caused mask-related skin problems on health-care professions, yet very few studies have investigated the prevalence in oriental general population. OBJECTIVE: To investigate the prevalence of mask-related adverse skin reactions in Orientals, to explore psychological influence, to identify risk factors for mask-related acne exacerbation. METHODS: We performed a survey through social media. Participant demographics, skin condition before and after COVID-19, and the influence of adverse skin on social-psychological conditions were collected. We compared characteristics between individuals with or without acne exacerbation, and we performed a logistic regression to identify risk factors. RESULTS: Six hundred and six participants (62.3%) responded the survey and 23.3% complained their facial acnes become exacerbated since COVID-19. The social-psychological impact of acnes is more prevalent in women. Risk factors for mask-related acne exacerbation were occupation as health-care workers (OR = 1.861, p = 0.027), prolonged wearing of N95 masks (OR = 3.167, p = 0.001), and touching of acnes (OR = 2.65, p = 0.002). Sex, pre-existed acnes, and prolonged wearing time per day are also associated with acne exacerbation. CONCLUSIONS: Mask-related adverse skin reactions are common in Orientals, and could lead to negative social-psychological effects.

Effects of coronavirus disease 2019 lockdown on metabolic syndrome and its components among Chinese employees: A retrospective cohort study

Objective Coronavirus disease 2019 (COVID-19) and the accompanying isolation have changed resident life rhythms and behaviors. This study investigated the effects of the COVID-19 pandemic on metabolic syndrome (MetS) and its components in employees in southwestern China. Methods This retrospective cohort study included 3,777 employees of five institutions who underwent physical examinations at the Affiliated Hospital of Southwest Medical University for three consecutive years from 2018 to 2020. We collected data on participant age and sex and measured the component indices of metabolic syndrome, including waist circumference, blood pressure (systolic and diastolic), fasting blood glucose level, and blood lipid (triglyceride and high-density lipoprotein cholesterol) level. We applied t-, chi-square, Mann–Whitney U, and Friedman's M tests to compare metabolic variables at different times. Results The incidence of MetS in 2020 was 18.6%, significantly higher than the prevalence of 15.7% before the epidemic. The number of abnormal MetS components following the COVID-19 lockdown was much greater than those in 2018 (P < 0.001) and 2019 (P < 0.001), with no significant variations between the two years (P = 0.142). All metabolic parameters, except for fasting blood glucose, were significantly worse than those pre-lockdown. The increase in the prevalence of MetS and all its abnormal components except for fasting glucose from 2019 to 2020 was significantly higher than that from 2018 to 2019. The change values between 2019–2020 and 2018–2019 for all indices except for diastolic blood pressure did not differ significantly between men and women. For all component indicators except for waist circumference, we observed no significant age differences in the growth differentials between the two periods (2019–2020 and 2018–2019). Conclusions COVD-19 lockdown have increased metabolic health risks among Chinese adults. Targeted measures, such as health education, are urgently needed to address poor metabolic health caused by the COVID-19 pandemic.

Ligand/Receptor-mediated Cell Communication Alteration Causes the Lung Inflammation Microenvironment and the Redistribution of Inter-tissue Immune Cells in COVID-19 Patients (preprint)

How SARS-CoV-2 causes disturbances of the lung microenvironment and systemic immune response remains a mystery. Here, we first analyze detailedly paired single-cell transcriptome data of the lungs, blood and bone marrow of two patients who died of COVID-19. Second, our results demonstrate that SARS-CoV-2 infection significantly increases the cellular communication frequency between AT1/AT2 cells and highly inflammatory myeloid cells, and induces the pulmonary inflammation microenvironment, and drives the disorder of fibroblasts, club and ciliated cells, thereby causing the increase of pulmonary fibrosis and mucus accumulation. Third, our works reveal that the increase of the lung T cell infiltration is mainly recruited by myeloid cells through certain ligands/receptors (ANXA1/FPR1, C5AR1/RPS19 and CCL5/CCR1), rather than AT1/AT2. Fourth, we find that some ligands and receptors such as ANXA1/FPR1, CD74/COPA, CXCLs/CXCRs, ALOX5/ALOX5AP, CCL5/CCR1, are significantly activated and shared among patients’ lungs, blood and bone marrow, implying that dysregulated ligands and receptors may cause the migration, redistribution and the inflammatory storm of immune cells in different tissues. Overall, our study reveals a latent mechanism by which the disorders of ligands and receptors caused by SARS-CoV-2 infection drive cell communication alteration, the pulmonary inflammatory microenvironment and systemic immune responses across tissues in COVID-19 patients.

Disinfection tackling the COVID-19 pandemic causes disinfection by-products (DBPs) accumulation and threatens aquatic ecosystems (preprint)

Abstract To fight against the coronavirus infectious disease-2019 (COVID-19), chlorine-based disinfectants are extensively or even over used for water, surface and personal care decontamination. The risks of disinfection by-products (DBPs) have been alerted to cause serious secondary pollution; however, there is still lack of evidence. This study collected 110 water samples from nine lakes and two rivers in Wuhan during the COVID-19 pandemic and comprehensively analyzed the occurrence of eighteen DBPs. Trihalomethanes, halonitromethanes, halogen acetonitriles and nitrosamines had a high detection frequency and were 0.99-14.26, ND-4.62, ND-1.09 and 0.0414-0.0861 μg/L, respectively, all lower than the maximum contamination level (MCL) suggested by China and USA. Haloacetic acids were detected in all lakes and Yangtze River and ranged from 33.8 to 856.1 μg/L, much higher than the MCL. Haloacetic acids and halogen acetonitriles accounted for 74.2-95.1% of the total cytotoxicity (0.38-3.62×105); halonitromethanes (94.0-98.7%) contributed to the majority of genotoxicity (0.52-5.17×104). Dichloroacetic acid exhibited significant ecological risks to green algae in two lakes and Yangtze River (risk quotient >10), and all the other DBPs showed negligible risks (risk quotient <0.01) to fish, daphnid or green algae. Correlation and redundancy analysis identified strong correlations between total organic carbon, conductivity, NH3-N, turbidity and DBPs. DBP composition and the fluorescence indices of dissolved organic matters together categorized all lakes into two types. Type-I lakes contained all DBP categories, driven by total organic carbon and secondarily formed by residual active chlorine with natural organic matters; Type-II lakes and Yangtze River only had high levels of haloacetic acids and small amounts of trihalomethanes, explained by the primary formation of DBPs in sewage. Our findings for the first time uncovered the significant accumulation and risks of DBPs in lakes and rivers of Wuhan during the COVID-19, provided the evidence of secondary pollution from intensive disinfection activities with chlorine-based disinfectants, evaluated the potential the ecological risks of DBPs in Wuhan and along Yangtze River, and raised our re-consideration of disinfection strategy in the pandemics and post-COVID-19 era.

Mutation and Virulence of SARS-CoV-2 Strains Circulating in Anhui Province, China (preprint)

Background: The genome of SARS-CoV-2 has shown considerable variation during its spreading. Monitoring variations in the virus genome to understand the evolution and spread of the virus is extremely important. Methods: Seven SARS-CoV-2 strains (BB127, BB183, HB030, MAS525, HF3028, FY1494, and SZ005) circulating in Anhui Province, China were isolated and sequenced for evolutionary analysis. Five strains were further cultured in vitro and were subjected to viral growth assay, TCID50 assay, and detection of spike protein expression. Next generation sequence (NGS) analysis were applied to investigate the mutation frequencies throughout the whole genome at different time gradients in vitro. Findings: Our observations revealed that in vitro cultured SARS-CoV-2 virus had much higher mutation frequency (up to ~20 times) than that in infected patients, and the mutation in nonstructural protein 14 (nsp14) might increase the genomic mutation frequency. Different strains had various amount of spike protein which may positively correlated with the virus replication capacity but may be influenced by other viral factors. Interpretation: Our study suggested that SARS-CoV-2 has the potential to diversify under favorable conditions. Monitoring viral mutations is not only helpful for better understanding of virus evolution and virulence change, but also the key to prevent virus transmission and disease progression. SARS-CoV-2 genomic variation analysis may also provide potential ideas for more efficient vaccine development and clinical treatment. Funding: This work is funded by Special Project for Emergency Scientific and Technological Research on New Coronavirus Infection (YG, No. YD9110002001), Emergency Research Project of Novel Coronavirus Infection of Anhui Province (Grant numbers 202004a07020002; 202004a07020004), Postdoctoral Research Foundation of China (2020M670084ZX) and the Fundamental Research Funds for the Central Universities (WK9110000166; WK9110000167).Declaration of Interests: We declare no competing interests.Ethics Approval Statement: The study was conformed to the principles of the Declaration ofHelsinki and approved by the Ethics Committee of the First Affiliated Hospital of USTC..

Molecular epidemiology of SARS-CoV-2 clusters caused by asymptomatic cases in Anhui Province, China (preprint)

Background: COVID-19 is a newly emerging disease caused by a novel coronavirus (SARS-CoV-2), which spread globally in early 2020. Asymptomatic carriers of the virus contribute to the propagation of this disease, and the existence of asymptomatic infection has caused widespread fear and concern in the control of this pandemic. Methods: : In this study, we investigated the origin and transmission route of SARS-CoV-2 in Anhui’s two clusters, analyzed the role and infectiousness of asymptomatic patients in disease transmission, and characterized the complete spike gene sequences in the Anhui strains. Results: : We conducted an epidemiological investigation of two clusters caused by asymptomatic infections sequenced the spike gene of viruses isolated from 12 patients. All cases of the two clusters we investigated had clear contact histories, both from Wuhan, Hubei province. The viruses isolated from two outbreaks in Anhui were found to show a genetically close link to the virus from Wuhan. In addition, new single nucleotide variations were discovered in the spike gene. Conclusions: : Both clusters may have resulted from close contact and droplet-spreading and asymptomatic infections were identified as the initial cause. We also analyzed the infectiousness of asymptomatic cases and the challenges to the current epidemic to provided information for the development of control strategies.

Clinical Efficacy of Convalescent Plasma Therapy on Treating COVID-19 Patients: Evidence from Matched Study and a Meta-Analysis (preprint)

Background: COVID-19 has infected tens of millions of people worldwide since its pandemic. CPT is one of the promising treatment methods and is favored by more and more researchers. However, the clinical efficacy and safety of CPT in COVID-19 remains unclear.Methods: We performed a matched control study by PSM analysis (including 163 cases with CPT and 163 controls with the standard treatment) and meta-analysis (including 498 cases and 557 controls) estimate the clinical efficacy and security of CPT and COVID-19, which will help inform clinical management of COVID-19 infection.Results: We found that days of hospital stay in case with CPT groups were significantly higher than matched control group (P< 0.0001). A significant reduction in mortality (OR= 0.496, 95%CI= 0.342-0.719, P< 0.0001) was found in the CPT group compared with the standard treatment group, and a true positive result was also found in sequential analysis. In terms of adverse events, sequential analysis found a false positive, although meta-analysis found a significant increase in the incidence of adverse events in patients treated with CPT compared to the control group. No differences between the two groups in terms of length of stay, improvement of clinical symptoms, and discharge were found.Conclusions: This study is the first to systematically review and meta-analysis the efficacy and safety of CPT in patients with COVID-19 in the largest sample size. Our results showed that CPT could significantly reduce the mortality rate of COVID-19 patients, and there was no significant increase in the incidence of adverse events. These data provide evidence favoring the efficacy and safety of CPT as a therapeutic agent in COVID-19 patients and provide comprehensive reference for COVID-19 treatment.Funding Statement: This work was supported by Scientific Research Project of Jiangsu Commission of Health (H2019065), Key Foundation of Wuhan Huoshenshan Hospital (2020[18]), Key Research & Development Program of Jiangsu Province (BE2018713), Medical Innovation Project of Logistics Service (18JS005).Declaration of Interests: The authors declare no conflicts of interest with this work.Ethics Approval Statement: The authors were approved by the ethics committee of Huoshenshan hospital, and were conducted in accordance with the tenets of the Declaration of Helsinki and its amendments. All participants provided written informed consent for the collection of samples and their subsequent analysis.

Aspergillus But Not Candida: Fatal Fungus Infection in COVID-19 Critical Patients (preprint)

Objectives: Earlier researches suggested patients should be routinely screened for bacteria and fungi infection after COVID-19 being confirmed. Here, we enrolled 236 patients with COVID-19 to analyze the clinical characteristics, fungal strains, mortality, and laboratory data of different groups.Design: Single center retrospective studyPatients: A total of 236 COVID-19 patients from Huoshenshan Hospital were included in this study, consisting of 14(6%) died cases, 222(94%) discharged cases.Results: The result revealed that 5 mortality in positive group were all related to aspergillus infection while candida infection rarely caused death. Aspergillus was most common in non-survivors while candida was most common in survivors. In terms of interleukin-6 (IL6), viral loads, nucleic acid clearance time, etc, fungal serologically positive group had a higher level than negative group.Conclusions: Non-survivors of Covid-19 with fungal infection were almost associated with aspergillus infection. Aspergillus infection, instead of candida infection might be fatal for critical ill patients with COVID-19. There is great significance to carry out routine screening for fungal infection especially for critical patients to enable early treatment to be implemented.Funding Statement: This study was financially supported by grants Key Foundation of Wuhan Huoshenshan Hospital (2020[18]), Key Research& Development Program of Jiangsu Province (BE2018713), Medical Innovation Project of Logistics Service (18JS005).Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: This study was approved by the Medical Ethical Committee of Wuhan Huoshenshan Hospital (No. HSSLL011). Written informed consent was obtained from each patient.

SARS-CoV-2 suppresses mRNA expression of selenoproteins associated with ferroptosis, ER stress and DNA synthesis (preprint)

A significant, positive association between selenium status and prognosis of SARS-CoV-2 infection has been identified among COVID-19 patients in China. Moreover, a German study revealed a pronounced deficit of serum selenium and SELENOP concentrations in COVID-19 patients, and selenium deficiency was associated with mortality risk from COVID-19. The present study investigated the influence of SARS-CoV-2 on gene expression of host selenoproteins which mediate many beneficial actions of selenium. We found that SARS-CoV-2 suppressed mRNA expression of selenoproteins associated with ferroptosis (GPX4), endoplasmic reticulum stress (SELENOF, SELENOK, SELENOM and SELENOS) and DNA synthesis (TXNRD3), while SARS-CoV-2 increased gene expression of IL-6 (an inflammatory cytokine positively correlated with severity of COVID-19), in Vero cells. These results provide a deeper insight into the connection between selenium and SARS-CoV-2 pathogenesis.

Diabetes Patients of COVID-19 Infection Treated with Convalescent Plasma Transfusion in Wuhan, China (preprint)

Background: The coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 had spread all over the world, causing public health emergency. Although the diagnosis for COVID-19 such as nucleic acid test and antibody detection have been well defined, there is still a big gap of knowledge regarding for COVID-19 patients receiving convalescent plasma transfusion (CPT) therapy, especially patients with comorbidity of diabetes. Method: In this study, out of 3059 COVID-19 patients admitted in Wuhan Huoshenshan Hospital of China, we described the characteristics of 39 diabetes patients receiving the transfusion of ABO-compatible convalescent plasma, and compared the baseline information and clinical outcome with that of 328 diabetes patients receiving traditional treatment. Results: It was found that the intervention of CPT therapy was effective and beneficial for COVID-19 patients, including severe or critical patients with comorbidity of diabetes, without obvious adverse effects observing during the treatments. The CPT therapy significantly improved the clinical outcome of diabetes patients with COVID-19 infection, especially the duration based on six categories compared to the patients with traditional therapy. Conclusions: This study not only provided a better understanding of COVID-19 in diabetes people receiving CPT, but also highlighted the CPT therapy was helpful for COVID-19 patients with comorbidity of diabetes.

Distributions and risks of SARS-CoV-2 in hospital outdoor environment (preprint)

The outbreak of coronavirus infectious disease-2019 (COVID-19) pandemic has rapidly spread throughout over 200 countries, posing a global threat to human health. Till 15th May 2020, there are over 4.5 million confirmed cases, with roughly 300,000 death1. To date, most studies focus on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in indoor environment owing to its main transmission routes via human respiratory droplets and direct contact2,3. It remains unclear whether SARS-CoV-2 can spill over and impose transmission risks to outdoor environments despite potential threats to people and communities. Here, we investigated the presence of SARS-CoV-2 by measuring viral RNA in 73 samples from outdoor environment of three hospitals in Wuhan. We detected SARS-CoV-2 in soils (205-550 copies/g), aerosols (285-1,130 copies/m3) and wastewaters (255 to 18,744 copies/L) in locations close to hospital departments receiving COVID-19 patients or in wastewater treatment sectors. These findings reveal significant viral spillover in hospital outdoor environments that was possibly caused by respiratory droplets from patients or aerosolized particles from wastewater containing SARS-CoV-2. In contrast, SARS-CoV-2 was not detected in other areas or on surfaces with regular disinfection implemented. Soils may behave as viral warehouse through deposition and serve as a secondary source spreading SARS-CoV-2 for a prolonged time. For the first time, our findings demonstrate that there are high-risk areas in hospital outdoor environments to spread SARS-CoV-2, calling for sealing of wastewater treatment unit and complete sanitation to prevent COVID-19 transmission risks.

CRISPR-Assisted DNA Detection, a novel dCas9-based DNA detection technique (preprint)

Nucleic acid detection techniques are always critical to diagnosis, especially in the background of the present COVID-19 pandemic. The simple and rapid detection techniques with high sensitivity and specificity are always urgently needed. However, the current nucleic acid detection techniques are still limited the traditional amplification and hybridization. To overcome the limitation, we here develop a CRISPR/Cas9-assisted DNA detection (CADD). In this detection, DNA sample is incubated with a pair of capture sgRNAs (sgRNAa and sgRNAb) specific to a target DNA, dCas9, a signal readout-related probe, and an oligo-coated solid support beads or microplate at room temperature for 15 min. During this incubation, the dCas9-sgRNA-DNA complex is formed and captured on solid support by the capture sequence of sgRNAa and the signal readout-related probe is captured by the capture sequence of sgRNAb. Finally the detection result is reported by a fluorescent or colorimetric signal readout. This detection was verified by detecting DNA of bacteria, cancer cell and virus. Especially, by designing a set of sgRNAs specific to 15 high-risk human papillomaviruses (HPVs), the HPV infection in 64 clinical cervical samples were successfully detected by the method. All detections can be finished in 30 minutes at room temperature. This detection holds promise for rapid on-the-spot detection or point-of-care testing (POCT).

Potential spreading risks and disinfection challenges of medical wastewater by the presence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viral RNA in septic tanks of fangcang hospital (preprint)

The outbreak of coronavirus infectious disease-2019 (COVID-19) pneumonia raises the concerns of effective deactivation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in medical wastewater by disinfectants. In this study, we evaluated the presence of SARS-CoV-2 viral RNA in septic tanks of Wuchang Fangcang Hospital and found the high level of (0.05-1.87)*10^4 copies/L after disinfection with sodium hypochlorite. Embedded viruses in stool particles might be released in septic tanks, behaving as a source of SARS-CoV-2 and potentially contributing to its spread through drainage pipelines. Current recommended disinfection strategy (free chlorine above 6.5 mg/L after 1.5-hour contact) needs to be reevaluated to completely remove SARS-CoV-2 viral RNA in non-centralized disinfection system and effectively deactivate SARS-CoV-2. The effluents showed negative results for SARS-CoV-2 viral RNA when overdosed with sodium hypochlorite but had high a level of disinfection by-product residuals, possessing significant ecological risks.