Increased interleukin-6 is associated with long COVID-19: a systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can involve persistence, sequelae, and other clinical complications that last weeks to months to evolve into long COVID-19. Exploratory studies have suggested that interleukin-6 (IL-6) is related to COVID-19; however, the correlation between IL-6 and long COVID-19 is unknown. We designed a systematic review and meta-analysis to assess the relationship between IL-6 levels and long COVID-19. METHODS: Databases were systematically searched for articles with data on long COVID-19 and IL-6 levels published before September 2022. A total of 22 published studies were eligible for inclusion following the PRISMA guidelines. Analysis of data was undertaken by using Cochran's Q test and the Higgins I-squared (I2) statistic for heterogeneity. Random-effect meta-analyses were conducted to pool the IL-6 levels of long COVID-19 patients and to compare the differences in IL-6 levels among the long COVID-19, healthy, non-postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (non-PASC), and acute COVID-19 populations. The funnel plot and Egger's test were used to assess potential publication bias. Sensitivity analysis was used to test the stability of the results. RESULTS: An increase in IL-6 levels was observed after SARS-CoV-2 infection. The pooled estimate of IL-6 revealed a mean value of 20.92 pg/ml (95% CI = 9.30-32.54 pg/ml, I2 = 100%, P < 0.01) for long COVID-19 patients. The forest plot showed high levels of IL-6 for long COVID-19 compared with healthy controls (mean difference = 9.75 pg/ml, 95% CI = 5.75-13.75 pg/ml, I2 = 100%, P < 0.00001) and PASC category (mean difference = 3.32 pg/ml, 95% CI = 0.22-6.42 pg/ml, I2 = 88%, P = 0.04). The symmetry of the funnel plots was not obvious, and Egger's test showed that there was no significant small study effect in all groups. CONCLUSIONS: This study showed that increased IL-6 correlates with long COVID-19. Such an informative revelation suggests IL-6 as a basic determinant to predict long COVID-19 or at least inform on the "early stage" of long COVID-19.

Emergency Medical Services Scheduling During the Outbreak of Epidemics Via Improved Artifificial Bee Colony Algorithms (preprint)

This study investigates a novel emergency medical services scheduling problem (EMSSP) to address the outbreak of epidemics like COVID-19. The objective is to determine an optimal scheduling scheme to minimize the emergency service time for nucleic acid testing (NAT) and achieve rapid epidemic disruption. For the problem, we fifirst formulate the EMSSP into a mixed-integer linear programming (MILP) and analyze its complexity is NP-hard. However, due to the NP-hardness of the problem, existing optimization software such as CPLEX is diffiffifficult to solve large-scale problems in an acceptable time.To effiffifficiently address the EMSSP, we design two effffective improved artifificial bee colony algorithms (IABC) based on explored problem properties. Then, numerical experiments on a real-life case and randomly generated large-scale instances with up to 100 demand points are conducted. Finally, computational results show that the IABC algorithms can obtain a better scheduling scheme than CPLEX and two state-of-the-art evolutionary algorithms in only 16 seconds for large-scale instances, which helps decision-makers deal with the outbreak of epidemics in a short time.

Increased Interleukin-6 is Associated with Long COVID-19: Evidence from a Systematic Review and Meta-analysis (preprint)

Background: Coronavirus disease 2019 (COVID-19) can involve persistence, sequelae, and other clinical complications that last weeks to months to evolve into long COVID-19. Exploratory studies have suggested that interleukin-6 (IL-6) is related to COVID-19; however, no correlation between IL-6 and long COVID-19 is known. We designed a systematic review and meta-analysis to assess the relationship between IL-6 levels and long COVID-19. Methods: Databases were systematically searched for articles with data on long COVID-19 and IL-6 levels published before September 2022. A total of 22 published studies were eligible for inclusion following the PRISMA guidelines. Analysis of data was undertaken by using Cochran's Q test and the Higgins I-squared (I2) statistic for heterogeneity. Random-effect meta-analyses were conducted to pool the IL-6 levels of long COVID-19 patients and to compare the differences in IL-6 levels among the long COVID-19, healthy, non-post-acute sequelae of SARS-CoV-2 infection (non-PASC), and acute COVID-19 populations. The funnel plot and Egger's test were used to assess potential publication bias. Sensitivity analysis was used to test the stability of the results. Results: An increase in IL-6 levels was observed after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The pooled estimate of IL-6 revealed a mean value of 20.92 pg/ml (95% CI = 9.30 – 32.54 pg/ml, I2 = 100%, p < 0.01) for long COVID-19. The forest plot showed high levels of IL-6 for long COVID-19 compared with healthy controls (mean difference = 9.75 pg/ml, 95% CI = 5.75 – 13.75 pg/ml, I2 = 100%, p < 0.00001) and PASC category (mean difference = 3.32 pg/ml, 95% CI = 0.22 – 6.42 pg/ml, I2 = 88%, p = 0.04). The symmetry of the funnel plots was not obvious, and Egger’s test showed that there was no significant small study effect in all groups (long COVID-19 versus healthy controls, p = 0.24; long COVID-19 versus non-PASC, p = 0.31). Conclusions: This study showed that increased IL-6 correlates with long COVID-19. Such an informative revelation suggests IL-6 as a basic determinant to predict long COVID-19 or at least inform on “early stage” of long COVID-19.

Relationship Between Hardiness and Social Anxiety in Chinese Impoverished College Students During the COVID-19 Pandemic: Moderation by Perceived Social Support and Gender

During the COVID-19 epidemic, quarantine and financial disadvantages might exacerbate social anxiety among impoverished college students. Based on the hardiness model and the social support buffering model, the present study proposed and verified a dual moderation model to investigate the effects of hardiness on social anxiety and the moderating roles of gender and perceived social support. The hardiness scale, the perceived social support scale, and the social anxiety subscale of the self-consciousness scale were administered to 673 Chinese college students aged 18 to 23 years who were recognized as impoverished by the Chinese authorities and provided with funding. The results revealed that (1) hardiness had a significant negative effect on social anxiety, (2) perceived social support moderated the effect of hardiness on social anxiety, and (3) gender moderated the effect of hardiness on social anxiety. The dual moderated model proposed in the study provides practical implications for helping impoverished college students cope with social anxiety during the COVID-19 pandemic.

Immunogenicity and safety of the CoronaVac inactivated SARS-CoV-2 vaccine in people with underlying medical conditions in China: a retrospective study (preprint)

People living with chronic disease, particularly seniors older than 60 years old, are lagging behind in the national COVID-19 vaccination campaign in China due to the uncertainty of vaccine safety and effectiveness. However, this special population made up of most severe symptom and death cases among SARS-CoV-2 infected patients and should be prioritized in vaccination program. Thus, safety and immunogenicity data of COVID-19 vaccines in people with underlying medical conditions are needed to address the vaccine hesitancy in this special population. Here, we report a retrospective cohort study evaluating the immunogenicity and safety of the inactivated COVID-19 vaccine, CoronaVac, in people with at least one of the six common diseases, focusing on seniors (N = 969). We found that CoronaVac is as safe in people with chronic diseases as that in healthy control, without serious adverse event reported in this study. By day 14-28 post vaccination, we observed no significant difference for the antibody responses between disease groups and healthy control, except for the coronary artery disease (p=0.03) and chronic respiratory disease group (p=0.04) showing moderate reduction. Such difference diminished by day 90 and 180, as neutralizing antibodies significantly reduced in all participants. Most people showed detectable SARS-CoV-2-specific T cell response at day 90 and day 180 without significant difference between disease groups and healthy control. Overall, our results highlight the comparable safety, immunogenicity and cellular immunity memory of CoronaVac in seniors and people living with chronic diseases, addressing vaccine hesitancy for this special population.

The association of intensity and duration of non-pharmacological interventions and implementation of vaccination with COVID-19 infection, death, and excess mortality: Natural experiment in 22 European countries.

BACKGROUND: Critical questions remain regarding the need for intensity to continue NPIs as the public was vaccinated. We evaluated the association of intensity and duration of non-pharmaceutical interventions (NPIs) and vaccines with COVID-19 infection, death, and excess mortality in Europe. METHODS: Data comes from Our Word in Data. We included 22 European countries from January 20, 2020, to May 30, 2021. The time-varying constrained distribution lag model was used in each country to estimate the impact of different intensities and duration of NPIs on COVID-19 control, considering vaccination coverage. Country-specific effects were pooled through meta-analysis. RESULTS: This study found that high-intensity and long-duration of NPIs showed a positive main effect on reducing infection in the absence of vaccines, especially in the intensity above the 80th percentile and lasted for 7 days (RR = 0.93, 95% CI: 0.89-0.98). However, the adverse effect on excess mortality also increased with the duration and intensity. Specifically, it was associated with an increase of 44.16% (RR = 1.44, 95% CI: 1.27-1.64) in the excess mortality under the strict intervention (the intensity above the 80th percentile and lasted for 21 days). As the vaccine rollouts, the inhibition of the strict intervention on cases growth rate was increased (RR dropped from 0.95 to 0.87). Simultaneously, vaccination also alleviated the negative impact of the strict intervention on excess mortality (RR decreased from 1.44 to 1.25). Besides, maintaining the strict intervention appeared to more reduce the cases, as well as avoids more overall burden of death compared with weak intervention. CONCLUSIONS: Our study highlights the importance of continued high-intensity NPIs in low vaccine coverage. Lifting of NPIs in insufficient vaccination coverage may cause increased infections and death burden. Policymakers should coordinate the intensity and duration of NPIs and allocate medical resources reasonably with widespread vaccination.

Immunogenicity and safety of the CoronaVac inactivated SARS-CoV-2 vaccine in people with underlying medical conditions: a retrospective study (preprint)

Background: People living with chronic disease, particularly seniors older than 60 years old, are lagging behind in the national vaccination campaign in China due to uncertainty of safety and effectiveness. However, this special population made up of most severe symptom and death cases among infected patients and should be prioritized in vaccination program. In this retrospective study, we assessed the safety and immunogenicity of the CoronaVac inactivated vaccines in people with underlying medical conditions to address the vaccine hesitation in this special population. Methods: In this cohort study, volunteers aged 40 years and older, had received two doses of CoronaVac inactivated vaccines (3-5 weeks interval), been healthy or with at least one of the six diseases: coronary heart disease (CAD), hypertension, diabetes mellitus (DM), chronic respiratory disease (CRD), obesity and cancer, were recruited from 4 study sites in China. The primary safety outcome was the incidence of adverse events within 14 days after each dose of vaccination. The primary immunogenic outcome was geometric mean titer (GMT) of neutralizing antibodies to living SARS-CoV-2 virus at 14-28 days, 3 months, and 6 months after full two-dose vaccination. This study is registered with ChiCTR.org.cn (ChiCTR2200058281) and is active but no longer recruiting. Findings: Among 1,302 volunteers screened between Jul 5 and Dec 30, 2021, 969 were eligible and enrolled in our cohort, including 740 living with underlying medical conditions and 229 as healthy control. All of them formed the safety cohort. The overall incidence of adverse reactions was 150 (20.27%) of 740 in the comorbidities group versus 32 (13.97%) of 229 in the healthy group, with significant difference (P=0.0334). The difference was mainly contributed by fatigue and injection-site pain in some groups. Most adverse reactions were mild (Grade 1). We did not observe any serious adverse events related to vaccination. By day 14-28 post vaccination, the seroconversion rates and GMT of neutralizing antibody showed no significant difference between disease group and healthy group, except CAD group (P=0.03) and CRD group (P=0.04) showed slight reduction. By day 90, the neutralizing antibody GMTs were significantly reduced in each group, with no significant difference between diseases and healthy group. By day 180, the neutralizing antibody continued to decrease in each group, but with slower declination. Interpretation: For people living with chronic disease especially seniors older than 60 years, the CoronaVac vaccines are as safe as in healthy people. Although the immunogenicity is slightly different in subgroup of some diseases compared with that of the healthy population, the overall trend was consistent. Our findings highlight the evidence to address vaccine hesitancy for seniors and people living with chronic diseases. Funding: Yunnan Provincial Science and Technology Department (202102AA100051 and 202003AC100010, China), Sinovac Biotech Ltd (PRO-nCOV-4004).

Electrochemical oxygen generator with 99.9% oxygen purity and high energy efficiency (preprint)

Under the growing crisis of coronavirus disease 2019 pandemic, the global medical system is facing the predicament of an acute shortage of medical-grade oxygen (O2, ≥ 99.5% purity). Herein, we manufactured an oxygen generation device relying on electrochemical technology. The performance of electrochemical oxygen generator (EOG) was remarkably improved to a practically applicable level, achieving long-term (>200 h), stable, and quick production (>1.5L/min) of high purity O2 (99.9%) under high energy efficiency (496 L/kW·h), viasimultaneous optimizations for intrinsic electrochemical reaction mechanism, electrocatalysts, and external cell structure. The EOG also presents powerful competitiveness in user experience, which finds expression in high portability (4.7 kg), nearly instant O2 production (<1 s), and a quiet working condition (<39 dB). The EOG shows great potential to substitute commercial pressure swing adsorption O2 generation devices, which may significantly impact the traditional oxygen production industry.  

Visual recognition efficiency of handheld infrared thermometer interface information under low ambient illuminance

One of the symptoms of plagues, epidemics or pandemics is often a fever, so during such unprecedented times, handheld infrared thermometers are vital devices for monitoring symptomatic individuals. It is therefore very important to enhance reading efficiency when these thermometers are used for lengthy periods of time in a low illuminance environment. The need for the efficient reading of infrared thermometers or a fast reaction time when reading the information is even more relevant now during the COVID-19 pandemic. In this study, a target search experiment of digital characters is carried out through a simulated interface and use scenarios of a handheld thermometer based on three variables: the inclination angle or slant of the seven segment display characters, screen brightness, and ambient illuminance. The experimental results show that the inclination angle or slant of the characters and ambient illuminance have a significant effect on the reaction speed. In general, the slowest reaction time is found when reading characters with a slant of 10° to the left and the reaction time is the fastest with a right slant of 20°. A continued reduction in ambient illuminance does not affect the visual recognition performance but instead further enhances reading efficiency. Increasing the screen brightness increases the reaction time more in relatively low ambient illuminance conditions as opposed to relatively high ambient illuminance, which implies that in higher ambient illuminance conditions, a brighter screen needs to be used to obtain the same reaction speed as that in lower ambient illuminance conditions.

Effect of combined WeChat video and comprehensive medical therapy on severe COVID-19 with moderate Alzheimer's disease: A case report

Abstract Objective We present a case report of recovery from severe COVID - 19 (novel coronavirus 2019) in a patient with cognitive decline (84-year old, female), behavioral and psychiatric symptoms, hip arthroplasty, sacroiliac decubital necrosis, cachexia, after comprehensive therapy. Background Because of cognitive and behavioral disorders, patients with Alzheimer?s disease have poor coordination of treatment especially in an unfamiliar environment. Communicating with close family members through WeChat video can relieve patients' anxiety and other mental symptoms, leading to better cooperating with drug treatment and nasal feeding diet. Methods Patient received 1 hour daily WeChat video communication with her son at isolation ward, including psychological comfort, care and positive words. The WeChat video communication were last for 4 weeks, during this time, the elderly patient was also treated with methylprednisolone (for 5 days), immunoglobulin (for 5 days), ulinastatin, thymus methoxide (for twice a week), acetylcysteine, antibiotics, low molecular weight heparin, probiotics, nutrition and other symptomatic support therapy. Results Before WeChat video communication about 4 weeks, the patient refused medical treatment, consisting of extraction of infusion set and removal of gastric tube, which greatly affects the treatment of drugs and the nutritional intake of patients;and the state of the patient?s condition became even worse. However, after 4 weeks WeChat video communication, the patient showed a significant improvement in the Mini-mental state examination scores from 8 to 12 (Education: illiterate) and in the Neuropsychiatric questionnaire scores from 35 to 10. Besides, after 4 weeks WeChat video communication and comprehensive therapy, the patient?s pneumonia improved significantly and the nucleic acid test turned negative. Conclusions WeChat video communication may be a promising noninvasive approach for patients with Alzheimer?s Disease, which may help alleviate neuropsychiatric behavioral symptoms and can be more cooperative with medical workers.

Discovery of rhodomyrtone as a broad-spectrum antiviral inhibitor with anti-SARS-CoV-2 activity (preprint)

The outbreak of new viruses, such as serve acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as the emerging of drug-resistance viruses highlight the urgent need for the development of broad-spectrum antiviral drugs. Herein, we report the discovery of a plant-derived small molecule, 6,8-dihydroxy-9-isobutyl-2,2,4,4-tetramethyl-7-(3-methylbutanoyl)-4,9-dihydro-1H- xanthene-1,3(2H)-dione (rhodomyrtone, RDT), which exhibited potent broad-spectrum antiviral activities against several RNA and DNA viruses, including SARS-CoV-2, respiratory syncytial virus (RSV), herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and Kaposi's sarcoma-associated herpesvirus (KSHV). RDT can significantly suppress viral gene expression and show the low possibility to elicit drug-resistant variants. Mechanistic study implied that RDT inhibited viral infection by disturbing the cellular factors that essential for viral gene expression. Our results suggested that RDT might be a promising lead compound for the development of broad-spectrum antiviral drugs.

Analysis on clinical features of death patients with COVID-19: a retrospective, single-center study from Wuhan, China (preprint)

Background An ongoing global pandemic of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused thousands of deaths in China since December, 2019. We aimed to describe the clinical course of patients died of SARS-CoV-2 infection.Methods In this retrospective study, we reviewed 194 patients with SARS-CoV-2 infection, who died consecutively between Feb 3 to 24, 2020 in Tongji Hospital (Wuhan, China). Basic demographic and clinical information, laboratory findings, complications and treatments were extracted from electronic medical records of Hospital Information System. Unpaired t test was employed to evaluate the statistical differences of the serum level of high-sensitive cardiac troponin I (hs-cTnI) among different age or sex groups. The relationship between hs-cTnI and inflammatory cytokines were estimated using Spearman correlation analysis.Results The death patients aged 69.62 ± 10.98, in which 68.6% were male. 74.7% patients had underlying chronic illnesses. The most common symptoms were fever (83%), cough (69.3%), and dyspnea (65.6%). Decreased lymphocyte count (91.4%), elevated level of hs-cTnI (82.9%) and inflammatory parameters in serum were commonly seen. The hs-cTnI level was significantly higher in the group aged 60–79 and male patients. A week positive correlation was observed between hs-cTnI values and D-dimer values (r = 0.343, p༜0.05). Acute respiratory distress syndrome was the main complication. Assisted respiration, antimicrobial drugs, glucocorticoids and immune globulin were the major treatments.Conclusion Most non-survivors with SARS-CoV-2 infection were old with chronic illnesses, complicated by multiple organ dysfunction. Prevention is better than cure in high-risk population.