Immune damage mechanisms of COVID-19 and novel strategies in prevention and control of epidemic.

Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19) has diverse clinical manifestations, which is the main feature of the disease, and the fundamental reason is the different immune responses in different bodies among the population. The damage mechanisms of critical illness by SARS-CoV-2 and its variants, such as hyperinflammatory response, a double-edged function of type I interferon, and hyperactivation of the complement system, are the same as other critical illnesses. Targeting specific immune damage mechanisms of COVID-19, we scored the first to put forward that the responses of T cells induced by acute virus infection result in "acute T-cell exhaustion" in elderly patients, which is not only the peripheral exhaustion with quantity reduction and dysfunction of T cells but also the central exhaustion that central immune organs lost immune homeostasis over peripheral immune organs, whereas the increased thymic output could alleviate the severity and reduce the mortality of the disease with the help of medication. We discovered that immune responses raised by SARS-CoV-2 could also attack secondary lymphoid organs, such as the spleen, lymphoid nodes, and kidneys, in addition to the lung, which we generally recognize. Integrated with the knowledge of mechanisms of immune protection, we developed a coronavirus antigen diagnostic kit and therapeutic monoclonal antibody. In the future, we will further investigate the mechanisms of immune damage and protection raised by coronavirus infection to provide more scientific strategies for developing new vaccines and immunotherapies.

Cardiovascular safety of COVID-19 vaccines in real-world studies: a systematic review and meta-analysis.

OBJECTIVES: To evaluate the cardiovascular safety of COVID-19 vaccines in the real world. METHODS: Studies reported on any COVID-19 vaccine-related cardiovascular events in the population aged ≥12 years between 1 January 2020 and 15 June 2022 were included. RESULTS: A total of 42 studies were included in this meta-analysis. Myocarditis risk was mainly seen after the second (risk ratio [RR], 2.09; 95% confidence interval [CI]: 1.59-2.58) and third (RR, 2.02; 95% CI: 1.04-2.91) dose. A total of 5 vaccines were analyzed, among which mRNA-1273 (RR, 3.13; 95% CI: 2.11-4.14) and BNT162b2 (RR, 1.57; 95% CI: 1.30-1.85) vaccines were associated with myocarditis risk. No significant increase in risk of myocardial infarction (RR, 0.96) or arrhythmia (RR, 0.98) events was observed following vaccination. The risk of cardiovascular events (myocarditis, RR, 8.53; myocardial infarction, RR, 2.59; arrhythmia, RR, 4.47) after SARS-CoV-2 infection was much higher than after vaccination. CONCLUSIONS: The risk of myocarditis was observed after COVID-19 vaccination, but it was much lower than that following the SARS-CoV-2 infection. No significant increased risk of myocardial infarction or arrhythmia was found after COVID-19 vaccination.

One-step synthesis of triethanolamine-capped Pt nanoparticle for colorimetric and electrochemiluminescent immunoassay of SARS-CoV spike proteins.

Platinum nanoparticles (PtNPs) have been attracted worldwide attention due to their versatile application potentials, especially in the catalyst and sensing fields. Herein, a facile synthetic method of triethanolamine (TEOA)-capped PtNPs (TEOA@PtNP) for electrochemiluminescent (ECL) and colorimetric immunoassay of SARS-CoV spike proteins (SARS-CoV S-protein, a target detection model) is developed. Monodisperse PtNPs with an average diameter of 2.2 nm are prepared by a one-step hydrothermal synthesis method using TEOA as a green reductant and stabilizer. TEOA@PtNPs can be used as a nanocarrier to combine with antigen by the high-affinity antibody, which leads to a remarkable inhibition of electron transfer efficiency and mass transfer processes. On the basis of its peroxidase-like activity and easy-biolabeling property, the TEOA@PtNP can be used to establish a colorimetric immunosensor of SARS-CoV S-protein thought catalyzing the reaction of H2O2 and 3,3',5,5'-tetramethylbenzidine (TMB). Especially, the Ru(bpy)3 2+ ECL reaction is well-achieved with the TEOA@PtNPs due to their great conductivity and loading abundant TEOA co-reactants, resulting in an enhancing ECL signal in immunoassay of SARS-CoV S-protein. As a consequence, two proposed methods could achieve sensitive detection of SARS-CoV S-protein in wide ranges, the colorimetric and ECL detection limits were as low as 8.9 fg /mL and 4.2 fg /mL (S/N = 3), respectively. We believe that the proposed colorimetric and ECL immunosesors with high sensitivity, good reproducibility, and good stability will be a promising candidate for a broad spectrum of applications.

Effects of Dust Event Days on Influenza: Evidence from Arid Environments in Lanzhou

Airborne aerosol is believed to be an important pathway for infectious disease transmissions like COVID-19 and influenza. However, the effects of dust event days on influenza have been rarely explored, particularly in arid environments. This study explores the effects of ambient particulate matter (PM) and dust events on laboratory-confirmed influenza in a semi-arid city. A descriptive analysis of daily laboratory-confirmed influenza (influenza) cases, PM (PM10 and PM2.5), meteorological parameters, and dust events were conducted from 2014 to 2019 in Lanzhou, China. The case-crossover design combined with conditional Poisson regression models was used to estimate the lagging effects of PM and dust events on influenza. In addition, a hierarchical model was used to quantitatively evaluate the interactive effect of PM with ambient temperature and absolute humidity on influenza. We found that PM and dust events had a significant effect on influenza. The effects of PM10 and PM2.5 on influenza became stronger as the cumulative lag days increased. The greatest estimated relative risks (RRs) were 1.018 (1.011,1.024) and 1.061 (1.034,1.087), respectively. Compared with the non-dust days, the effects of dust events with duration ≥ 1 day and with duration ≥ 2 days on influenza were the strongest at lag0 day, with the estimated RRs of 1.245 (95% CI: 1.061–1.463) and 1.483 (95% CI: 1.232–1.784), respectively. Subgroup analysis showed that pre-school children and school-aged children were more sensitive to PM and dust events exposure. Besides, we also found that low humidity and temperature had an interaction with PM to aggravate the risk of influenza. In summary, ambient PM and dust events exposure may increase the risk of influenza, and the risk of influenza increases with the dust events duration. Therefore, more efforts from the government as well as individuals should be strengthened to reduce the effect of PM on influenza, particularly in cold and dry weather.

Chemical explosion, COVID-19, and environmental justice: Insights from low-cost air quality sensors.

OBJECTIVES: To examine the impact of the Intercontinental Terminals Company (ITC) fire and COVID-19 on airborne particulate matter (PM) concentrations and the PM disproportionally affecting communities in Houston using low-cost sensors. METHODS: We compared measurements from a network of low-cost sensors with a separate network of monitors from the Environmental Protection Agency (EPA) in the Houston metropolitan area from Mar 18, 2019, to Dec 31, 2020. Further, we examined the associations between neighborhood-level sociodemographic status and air pollution patterns by linking the low-cost sensor data to EPA environmental justice screening and mapping systems. FINDINGS: We found increased PM levels during ITC fire and pre-COVID-19, and lower PM levels after the COVID-19 lockdown, comparable to observations from the regulatory monitors, with higher variations and a greater number of locations with high PM levels detected. In addition, the environmental justice analysis showed positive associations between higher PM levels and the percentage of minority, low-income population, and demographic index. IMPLICATION: Our study indicates that low-cost sensors provide pollutant measures with higher spatial variations and a better ability to identify hot spots and high peak concentrations. These advantages provide critical information for disaster response and environmental justice studies. SYNOPSIS: We used measurements from a low-cost sensor network for air pollution monitoring and environmental justice analysis to examine the impact of anthropogenic and natural disasters.

Preclinical immunogenicity and efficacy of a candidate COVID-19 vaccine based on a vesicular stomatitis virus-SARS-CoV-2 chimera.

BACKGROUND: To investigate a vaccine technology with potential to protect against coronavirus disease 2019 (COVID-19) and reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a single vaccine dose, we developed a SARS-CoV-2 candidate vaccine using the live vesicular stomatitis virus (VSV) chimeric virus approach previously used to develop a licensed Ebola virus vaccine. METHODS: We generated a replication-competent chimeric VSV-SARS-CoV-2 vaccine candidate by replacing the VSV glycoprotein (G) gene with coding sequence for the SARS-CoV-2 Spike glycoprotein (S). Immunogenicity of the lead vaccine candidate (VSV∆G-SARS-CoV-2) was evaluated in cotton rats and golden Syrian hamsters, and protection from SARS-CoV-2 infection also was assessed in hamsters. FINDINGS: VSV∆G-SARS-CoV-2 delivered with a single intramuscular (IM) injection was immunogenic in cotton rats and hamsters and protected hamsters from weight loss following SARS-CoV-2 challenge. When mucosal vaccination was evaluated, cotton rats did not respond to the vaccine, whereas mucosal administration of VSV∆G-SARS-CoV-2 was found to be more immunogenic than IM injection in hamsters and induced immunity that significantly reduced SARS-CoV-2 challenge virus loads in both lung and nasal tissues. INTERPRETATION: VSV∆G-SARS-CoV-2 delivered by IM injection or mucosal administration was immunogenic in golden Syrian hamsters, and both vaccination methods effectively protected the lung from SARS-CoV-2 infection. Hamsters vaccinated by mucosal application of VSV∆G-SARS-CoV-2 also developed immunity that controlled SARS-CoV-2 replication in nasal tissue. FUNDING: The study was funded by Merck Sharp & Dohme, Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and The International AIDS Vaccine Initiative, Inc. (IAVI), New York, USA. Parts of this research was supported by the Biomedical Advanced Research and Development Authority (BARDA) and the Defense Threat Reduction Agency (DTRA) of the US Department of Defense.

Incomplete occlusion and visual symptoms of peri-ophthalmic aneurysm after treatment with a pipeline embolization device: a multi-center cohort study.

OBJECTIVE: Peri-ophthalmic aneurysm is a special type of aneurysm. We assessed the relationship between ophthalmic artery (OA) origin and aneurysm and examined the effect of a pipeline embolization device (PED, Covidien/Medtronic) with or without coils on aneurysm occlusion rate and visual outcomes. METHODS: We retrospectively analyzed 194 peri-ophthalmic aneurysms in 189 patients among 1171 patients treated with a PED in a Chinese post-market multi-center registry study from November 2014 to October 2019. Peri-ophthalmic aneurysms were defined as carotid-ophthalmic segment aneurysms arising from the internal carotid artery dorsal wall at, or distal to, the OA origin, with a superior or superomedial projection. The relationship between OA origin and the aneurysm was classified as follows: type A, OA originating separate from the aneurysm; type B, OA originating from the aneurysm neck or dome. Patients with aneurysm were divided into the PED-only group and the PED + coils group according to treatment. RESULTS: The median follow-up time was 6.8 months (range, 5.3-20.2 months). There were 163 occluded aneurysms (84%) and 31 aneurysms with incomplete occlusion (16%). A multivariate analysis showed that type B aneurysm was a risk factor for incomplete occlusion in the PED-only group (odds ratio [OR] 4.854, 95% confidence interval [CI] 1.878-12.548, P = 0.001). Visual symptoms at final follow-up correlated with preoperative visual symptoms (OR 22.777, 95% CI 3.115-166.555, P = 0.002). CONCLUSIONS: Type B aneurysm is associated with a lower occlusion rate after PED-only treatment. Patients with preoperative visual symptoms should be treated promptly to avoid permanent visual symptoms.

Pipeline Embolization device for intracranial aneurysms in a large Chinese cohort: factors related to aneurysm occlusion.

BACKGROUND AND PURPOSE: The Pipeline Embolization Device (PED, Covidien/Medtronic) is widely used to treat intracranial aneurysms. This PED in China post-market multi-center registry study (PLUS) investigated safety and effectiveness of the PED for intracranial aneurysms in the Chinese population. METHODS: This was a panoramic, consecutive, real-world cohort registry study. Patients treated with PED with or without coils between November 2014 and October 2019 at 14 centers in China were included, and those treated by parent vessel occlusion or other stents were excluded. Study outcomes included angiographic evaluation of aneurysm occlusion, complications, in-stent stenosis, and predictors of aneurysm occlusion. A central committee reviewed all imaging and endpoint events. RESULTS: In total, 1171 patients with 1322 intracranial aneurysms were included. The total occlusion rate was 81.4% (787/967) at mean follow-up of 8.96 ± 7.50 months, with 77.1% (380/493) occlusion in the PED alone and 85.9% (407/474) in the PED plus coiling group. On multi-variate analysis, female sex, hyperlipidemia, vertebral aneurysms, PED plus coiling, and blood flow detained to venous phase were significant predictors of aneurysm occlusion. In posterior circulation cohort, there was no variable associated with aneurysm occlusion. In-stent stenosis predictors included current smoking and cerebral sclerosis/stenosis. CONCLUSION: In the largest series on PED of multi-center date of China, data suggest that treatment with the flow-diverting PED in intracranial aneurysms was efficacious. The treatment of PED combined coiling and blood flow detained to venous phase after PED implant were associated with aneurysmal occlusion. The occlusion rate of vertebral aneurysms was higher than other location aneurysms. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03831672.

Type 2 diabetes attributable to PM2.5: A global burden study from 1990 to 2019.

BACKGROUND: Long-term exposure to fine particulate matter (PM2.5) is associated with an increased risk of type 2 diabetes (T2D). However, limited data on trends in the global burden of T2D attributed to PM2.5, particularly in different regions by social-economic levels. We evaluated the spatio-temporal changes in the disease burden of T2D attributed to PM2.5 from 1990 to 2019 in 204 countries and regions with different socio-demographic indexes (SDI). METHODS: This is a retrospective analysis with data from the Global Burden of Disease Study 2019 (GBD2019) database. The burden of T2D attributed to PM2.5, age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life year rate (ASDR) were estimated according to sex, age, nationality and SDI. The annual percentage change (APCs) and the average annual percentage change (AAPCs) were calculated by using the Joinpoint model to evaluate the changing trend of ASMR and ASDR attributed to PM2.5 from 1990 to 2019. The Gaussian process regression model was used to estimate the relationship of SDI with ASMR and ASDR. RESULTS: Overall, the global burden of T2D attributable to PM2.5 increased significantly since 1990, particularly in the elderly, men, Africa, Asia and low-middle SDI regions. The ASMR and ASDR of T2D attributable to PM2.5 in 2019 were 2.47 (95% CI: 1.71, 3.24) per 100,000 population and 108.98 (95% CI: 74.06, 147.23) per 100,000 population, respectively. From 1990 to 2019, the global ASMR and ASDR of T2D attributed to T2D increased by 57.32% and 86.75%, respectively. The global AAPCs of ASMR and ASDR were 1.57 (95% CI: 1.46, 1.68) and 2.17 (95% CI: 2.02, 2.32), respectively. Declining trends were observed in North America, South America, Europe, Australia, and other regions with high SDI. CONCLUSIONS: Over this 30-years study, the global T2D burden attributable to PM2.5 has increased particularly in regions with low-middle SDI. PM2.5 remains a great concern on the global burden of diabetes.

Meteorological factors, governmental responses and COVID-19: Evidence from four European countries.

With the global lockdown, meteorological factors are highly discussed for COVID-19 transmission. In this study, national-specific and region-specific data sets from Germany, Italy, Spain and the United Kingdom were used to explore the effect of temperature, absolute humidity and diurnal temperature range (DTR) on COVID-19 transmission. From February 1st to November 1st, a 7-day COVID-19 case doubling time (Td), meteorological factors with cumulative 14-day-lagged, government response index and other factors were fitted in the distributed lag nonlinear models. The overall relative risk (RR) of the 10th and the 25th percentiles temperature compared to the median were 0.0074 (95% CI: 0.0023, 0.0237) and 0.1220 (95% CI: 0.0667, 0.2232), respectively. The pooled RR of lower (10th, 25th) and extremely high (90th) absolute humidity were 0.3266 (95% CI: 0.1379, 0.7734), 0.6018 (95% CI: 0.4693, 0.7718) and 0.3438 (95% CI: 0.2254, 0.5242), respectively. While the DTR did not have a significant effect on Td. The total cumulative effect of temperature (10th) and absolute humidity (10th, 90th) on Td increased with the change of lag days. Similarly, a decline in temperature and absolute humidity at cumulative 14-day-lagged corresponded to the lower RR on Td in pooled region-specific effects. In summary, the government responses are important factors in alleviating the spread of COVID-19. After controlling that, our results indicate that both the cold and the dry environment also likely facilitate the COVID-19 transmission.

Airborne particulate matter, population mobility and COVID-19: a multi-city study in China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease, which has caused numerous deaths and health problems worldwide. This study aims to examine the effects of airborne particulate matter (PM) pollution and population mobility on COVID-19 across China. METHODS: We obtained daily confirmed cases of COVID-19, air particulate matter (PM2.5, PM10), weather parameters such as ambient temperature (AT) and absolute humidity (AH), and population mobility scale index (MSI) in 63 cities of China on a daily basis (excluding Wuhan) from January 01 to March 02, 2020. Then, the Generalized additive models (GAM) with a quasi-Poisson distribution were fitted to estimate the effects of PM10, PM2.5 and MSI on daily confirmed COVID-19 cases. RESULTS: We found each 1 unit increase in daily MSI was significantly positively associated with daily confirmed cases of COVID-19 in all lag days and the strongest estimated RR (1.21, 95% CIs:1.14 ~ 1.28) was observed at lag 014. In PM analysis, we found each 10 µg/m3 increase in the concentration of PM10 and PM2.5 was positively associated with the confirmed cases of COVID-19, and the estimated strongest RRs (both at lag 7) were 1.05 (95% CIs: 1.04, 1.07) and 1.06 (95% CIs: 1.04, 1.07), respectively. A similar trend was also found in all cumulative lag periods (from lag 01 to lag 014). The strongest effects for both PM10 and PM2.5 were at lag 014, and the RRs of each 10 µg/m3 increase were 1.18 (95% CIs:1.14, 1.22) and 1.23 (95% CIs:1.18, 1.29), respectively. CONCLUSIONS: Population mobility and airborne particulate matter may be associated with an increased risk of COVID-19 transmission.

COVID-19: Challenges to GIS with Big Data

The outbreak of the 2019 novel coronavirus disease (COVID-19) has caused more than 100,000 people infected and thousands of deaths. Currently, the number of infections and deaths is still increasing rapidly. COVID-19 seriously threatens human health, production, life, social functioning and international relations. In the fight against COVID-19, Geographic Information Systems (GIS) and big data technologies have played an important role in many aspects, including the rapid aggregation of multi-source big data, rapid visualization of epidemic information, spatial tracking of confirmed cases, prediction of regional transmission, spatial segmentation of the epidemic risk and prevention level, balancing and management of the supply and demand of material resources, and social-emotional guidance and panic elimination, which provided solid spatial information support for decision-making, measures formulation, and effectiveness assessment of COVID-19 prevention and control. GIS has developed and matured relatively quickly and has a complete technological route for data preparation, platform construction, model construction, and map production. However, for the struggle against the widespread epidemic, the main challenge is finding strategies to adjust traditional technical methods and improve speed and accuracy of information provision for social management. At the data level, in the era of big data, data no longer come mainly from the government but are gathered from more diverse enterprises. As a result, the use of GIS faces difficulties in data acquisition and the integration of heterogeneous data, which requires governments, businesses, and academic institutions to jointly promote the formulation of relevant policies. At the technical level, spatial analysis methods for big data are in the ascendancy. Currently and for a long time in the future, the development of GIS should be strengthened to form a data-driven system for rapid knowledge acquisition, which signifies that GIS should be used to reinforce the social operation parameterization of models and methods, especially when providing support for social management.

Impact of meteorological factors on the COVID-19 transmission: A multi-city study in China.

The purpose of the present study is to explore the associations between novel coronavirus disease 2019 (COVID-19) case counts and meteorological factors in 30 provincial capital cities of China. We compiled a daily dataset including confirmed case counts, ambient temperature (AT), diurnal temperature range (DTR), absolute humidity (AH) and migration scale index (MSI) for each city during the period of January 20th to March 2nd, 2020. First, we explored the associations between COVID-19 confirmed case counts, meteorological factors, and MSI using non-linear regression. Then, we conducted a two-stage analysis for 17 cities with more than 50 confirmed cases. In the first stage, generalized linear models with negative binomial distribution were fitted to estimate city-specific effects of meteorological factors on confirmed case counts. In the second stage, the meta-analysis was conducted to estimate the pooled effects. Our results showed that among 13 cities that have less than 50 confirmed cases, 9 cities locate in the Northern China with average AT below 0 °C, 12 cities had average AH below 4 g/m3, and one city (Haikou) had the highest AH (14.05 g/m3). Those 17 cities with 50 and more cases accounted for 90.6% of all cases in our study. Each 1 °C increase in AT and DTR was related to the decline of daily confirmed case counts, and the corresponding pooled RRs were 0.80 (95% CI: 0.75, 0.85) and 0.90 (95% CI: 0.86, 0.95), respectively. For AH, the association with COVID-19 case counts were statistically significant in lag 07 and lag 014. In addition, we found the all these associations increased with accumulated time duration up to 14 days. In conclusions, meteorological factors play an independent role in the COVID-19 transmission after controlling population migration. Local weather condition with low temperature, mild diurnal temperature range and low humidity likely favor the transmission.

Guide to forensic pathology practice for death cases related to coronavirus disease 2019 (COVID-19) (Trial draft).

Autopsy is of great significance for elucidating the pathological changes, pathogenesis and cause of death of Coronavirus Disease 2019 (COVID-19) and can provide a theoretical basis for scientific and accurate prevention and control of its outbreak. Based on related laws and regulations, such as the Law of the People's Republic of China on Prevention and Control of Infectious Diseases, clinical manifestations and epidemiological characteristics of COVID-19 and guidelines on the prevention and control of this epidemic, combined with the practical work of forensic pathology examinations, we developed the Guide to Forensic Pathology Practice for Death Cases Related to Coronavirus Disease 2019 (COVID-19) (Trial Draft). This guide describes the background investigation of the death cases, autopsy room requirements, personal prevention and protections, external examinations, autopsy practices and auxiliary examinations, and thus offers a reference for forensic and pathological examination institutions and staff.