Application of weighted gene co-expression network and immune infiltration for explorations of key genes in the brain of elderly COVID-19 patients.

Introduction: Although many studies have demonstrated the existing neurological symptoms in COVID-19 patients, the mechanisms are not clear until now. This study aimed to figure out the critical molecular and immune infiltration situations in the brain of elderly COVID-19 patients. Methods: GSE188847 was used for the differential analysis, WGCNA, and immune infiltration analysis. We also performed GO, KEGG, GSEA, and GSVA for the enrich analysis. Results: 266 DEGs, obtained from the brain samples of COVID-19 and non-COVID-19 patients whose ages were over 70 years old, were identified. GO and KEGG analysis revealed the enrichment in synapse and neuroactive ligand-receptor interaction in COVID-19 patients. Further analysis found that asthma and immune system signal pathways were significant changes based on GSEA and GSVA. Immune infiltration analysis demonstrated the imbalance of CD8+ T cells, neutrophils, and HLA. The MEpurple module genes were the most significantly different relative to COVID-19. Finally, RPS29, S100A10, and TIMP1 were the critical genes attributed to the progress of brain damage. Conclusion: RPS29, S100A10, and TIMP1 were the critical genes in the brain pathology of COVID-19 in elderly patients. Our research has revealed a new mechanism and a potential therapeutic target.

Effectiveness of a booster dose of COVID-19 vaccines during an outbreak of SARS-CoV-2 Omicron BA.2.2 in China: A case-control study.

Real-world evidence on the effectiveness of COVID-19 vaccines marketed in China against the Omicron BA.2.2 variant remains scarce. A case-control study was conducted to estimate the vaccine effectiveness (VE) of COVID-19 vaccines marketed in China (inactivated vaccines, an Ad5-nCoV vaccine, and a recombinant protein vaccine). There were 414 cases infected with SARS-CoV-2 and 828 close contacts whose test results were consecutively negative as controls during the outbreak of the Omicron variant in Lu'an City, Anhui Province, China, in April 2022. The overall adjusted VE against Omicron BA.2.2 variant infection in the vaccinated group with any COVID-19 vaccine was 35.0% (95% CI: -9.1-61.3%), whereas the adjusted VE for booster vaccination was 51.6% (95% CI: 15.2-72.4%). Subgroup analysis showed that the overall adjusted VE of the Ad5-nCoV vaccine (65.8%, 95% CI: 12.8-86.6%) during the outbreak while any dose of inactivated vaccines and recombinant protein vaccine offered no protection. The adjusted VE of three-dose inactivated vaccines was 48.0% (95% CI: 8.0-70.6%), and the two-dose Ad5-nCoV vaccine was 62.9% (95% CI: 1.8-86%). There is no protection from a three-dose recombinant protein vaccine. COVID-19 vaccines offered 46.8% (95% CI: 9.5-68.7%) protection from infection within six months. There were statistically significant differences between the VEs of heterologous booster (VE = 76.4%, 95% CI: 14.3-93.5%) and homologous booster vaccination (VE = 51.8%, 95% CI: 9.6-74.3%) (P = .036). Booster vaccination of COVID-19 vaccines offered more protection than full vaccination. A booster vaccination campaign for a booster dose after three doses of a recombinant protein vaccine must be urgently conducted.

The acceptance to heterologous booster vaccination of COVID-19 vaccine among HCWs and targeted population: A cross-sectional study in central China

Background There are few studies reported on the acceptance of heterologous booster vaccination for the COVID-19 vaccine among healthcare workers (HCWs) and the general population. We aimed to address that gap and explore determinant factors of acceptance of the heterologous booster vaccination. Methods We conducted a cross-sectional study to examine the prevalence and determinant factors of the acceptance of heterologous booster vaccination for the COVID-19 vaccine among HCWs and the targeted population. Results A total of 364 HCWs and 1,898 targeted populations were investigated in our study. 76.4% HCWs would recommend heterologous booster vaccination to their patients and 59.8% targeted population endorsed a clear willingness to receive this strategy. Compared with the adenoviral vector vaccine (AD5-nCOV), recombinant protein vaccine (ZF2001) was more preferred by HCWs (79.1%) and the targeted population (72.0%) as a heterologous booster vaccine. HCWs who did not work in the vaccination clinics were more likely to recommend heterologous booster vaccination (OR = 3.3, CI: 1.5–7.3). The targeted population aged 18–59 years (OR = 1.5, 95% CI:1.1–2.3), had a positive attitude toward COVID-19 vaccination (OR = 3.8, 95% CI: 1.7–8.6), had confidence in the safety of COVID-19 vaccines (OR = 6.6, 95% CI: 4.2–10.2), followed the recommendation of HCWs (OR = 33.6, 95% CI: 22.0–51.2), took initiative in collecting booster shots information (OR = 2.1, 95% CI: 1.5–3.0), and were familiar with the heterologous strategy (OR = 1.9, 95% CI: 1.1–3.1) were more likely to choose heterologous booster vaccination. The history of side effects of inactivated COVID-19 vaccine was a negative factor in choosing heterologous booster vaccination (OR = 0.4, 95% CI: 0.4–1.0). Conclusions The heterologous booster vaccination strategy on the COVID-19 vaccine could be widely accepted among HCWs, whereas its acceptance among targeted population was only moderate. Public authorities should make efforts to communicate the public about the effectiveness and safety of the heterologous booster vaccination which could help increase their willingness to get vaccinated.

Safety and immunogenicity of COVID-19 vaccination in patients with hepatocellular carcinoma (CHESS-NMCID 2101): A multicenter prospective study.

Data on safety and immunogenicity of coronavirus disease 2019 (COVID-19) vaccinations in hepatocellular carcinoma (HCC) patients are limited. In this multicenter prospective study, HCC patients received two doses of inactivated whole-virion COVID-19 vaccines. The safety and neutralizing antibody were monitored. Totally, 74 patients were enrolled from 10 centers in China, and 37 (50.0%), 25 (33.8%), and 12 (16.2%) received the CoronaVac, BBIBP-CorV, and WIBP-CorV, respectively. The vaccines were well tolerated, where pain at the injection site (6.8% [5/74]) and anorexia (2.7% [2/74]) were the most frequent local and systemic adverse events. The median level of neutralizing antibody was 13.5 (interquartile range [IQR]: 6.9-23.2) AU/ml at 45 (IQR: 19-72) days after the second dose of vaccinations, and 60.8% (45/74) of patients had positive neutralizing antibody. Additionally, lower γ-glutamyl transpeptidase level was related to positive neutralizing antibody (odds ratio = 1.022 [1.003-1.049], p = 0.049). In conclusion, this study found that inactivated COVID-19 vaccinations are safe and the immunogenicity is acceptable or hyporesponsive in patients with HCC. Given that the potential benefits may outweigh the risks and the continuing emergences of novel severe acute respiratory syndrome coronavirus 2 variants, we suggest HCC patients to be vaccinated against COVID-19. Future validation studies are warranted.

CRISPR-Cas13-Mediated Knockdown of Regulator of G-Protein Signaling 8 (RGS8) Does Not Affect Purkinje Cell Dendritic Development.

CRISPR-Cas13 technology is rapidly evolving as it is a very specific tool for RNA editing and interference. Since there are no significant off-target effects via the Cas13-mediated method, it is a promising tool for studying gene function in differentiating neurons. In this study, we designed two crRNA targeting regulator of G-protein signaling 8 (RGS8), which is a signaling molecule associated with spinocerebellar ataxias. Using CRISPR-Cas13 technology, we found that both of crRNAs could specifically achieve RGS8 knockdown. By observing and comparing the dendritic growth of Purkinje cells, we found that CRISPR-Cas13-mediated RGS8 knockdown did not significantly affect Purkinje cell dendritic development. We further tested the role of RGS8 by classical RNAi. Again, the results of the RNAi-mediated RGS8 knockdown showed that reduced RGS8 expression did not significantly affect the dendritic growth of Purkinje cells. This is the first example of CRISPR-Cas13-mediated gene function study in Purkinje cells and establishes CRISPR-Cas13-mediated knockdown as a reliable method for studying gene function in primary neurons.

Safety and immunogenicity of SARS-CoV-2 vaccines in Chinese patients with cirrhosis: a prospective multicenter study.

BACKGROUND: Data on safety and immunogenicity of coronavirus disease 2019 (COVID-19) vaccination in patients with compensated (C-cirrhosis) and decompensated cirrhosis (D-cirrhosis) are limited. METHODS: In this prospective multicenter study, adult participants with C-cirrhosis and D-cirrhosis were enrolled and received two doses of inactivated whole-virion COVID-19 vaccines. Adverse events were recorded within 14 days after any dose of vaccination, and serum samples of enrolled patients were collected and tested for SARS-CoV-2 neutralizing antibodies at least 14 days after the second dose. Risk factors for negative neutralizing antibody were analyzed. RESULTS: In total, 553 patients were enrolled from 15 centers in China, including 388 and 165 patients with C-cirrhosis and D-cirrhosis. The vaccines were well tolerated, most adverse reactions were mild and transient, and injection site pain (23/388 [5.9%] vs 9/165 [5.5%]) and fatigue (5/388 [1.3%] vs 3/165 [1.8%]) were the most frequently local and systemic adverse events in both the C-cirrhosis and D-cirrhosis groups. Overall, 4.4% (16/363) and 0.3% (1/363) of patients were reported Grades 2 and 3 alanine aminotransferase (ALT) elevations (defined as ALT > 2 upper limit of normal [ULN] but ≤ 5 ULN, and ALT > 5 ULN, respectively). The positive rates of COVID-19 neutralizing antibodies were 71.6% (278/388) and 66.1% (109/165) in C-cirrhosis and D-cirrhosis groups. Notably, Child-Pugh score of B and C levels was an independent risk factor of negative neutralizing antibody. CONCLUSIONS: Inactivated COVID-19 vaccinations are safe with acceptable immunogenicity in cirrhotic patients, and Child-Pugh score of B and C levels is associated with hyporesponsive to COVID-19 vaccination.

Mycoplasma pneumoniae among Chinese Outpatient Children with Mild Respiratory Tract Infections during the Coronavirus Disease 2019 Pandemic.

Mycoplasma pneumoniae is a common pathogen causing respiratory disease in children. We sought to investigate the epidemiology of M. pneumoniae among outpatient children with mild respiratory tract infections (RTIs) during the coronavirus disease 2019 (COVID-19) pandemic. Eligible patients were prospectively enrolled from January 2020 to June 2021. Throat swabs were tested for M. pneumoniae RNA. M. pneumoniae IgM was tested by a colloidal gold assay. Macrolide resistance and the effect of the COVID-19 countermeasures on M. pneumoniae prevalence were assessed. Symptom scores, treatments, and outcomes were evaluated. Eight hundred sixty-two eligible children at 15 centers in China were enrolled. M. pneumoniae was detected in 78 (9.0%) patients. Seasonally, M. pneumoniae peaked in the first spring and dropped dramatically to extremely low levels over time until the next summer. Decreases in COVID-19 prevalence were significantly associated with decreases in M. pneumoniae prevalence (r = 0.76, P = 0.001). The macrolide resistance rate was 7.7%. The overall sensitivity and specificity of the colloidal gold assay used in determining M. pneumoniae infection were 32.1% and 77.9%, respectively. No more benefits for improving the severity of symptoms and outcomes were observed in M. pneumoniae-infected patients treated with a macrolide than in those not treated with a macrolide during follow-up. The prevalences of M. pneumoniae and macrolide resistance in outpatient children with mild RTIs were at low levels in the early stage of the COVID-19 pandemic but may have rebounded recently. The colloidal gold assay for M. pneumoniae IgM may be not appropriate for diagnosis of M. pneumoniae infection. Macrolides should be used with caution among outpatients with mild RTIs. IMPORTANCE This is the first and largest prospective, multicenter, active, population-based surveillance study of the epidemiology of Mycoplasma pneumoniae among outpatient children with mild respiratory tract infections (RTIs) during the COVID-19 pandemic. Nationwide measures like strict face mask wearing and restrictions on population movement implemented to prevent the spread of COVID-19 might also effectively prevent the spread of M. pneumoniae. The prevalence of M. pneumoniae and the proportion of drug-resistant M. pneumoniae isolates in outpatient children with mild RTIs were at low levels in the early stage of the COVID-19 pandemic but may have rebounded recently. The colloidal gold assay for M. pneumoniae IgM may be not appropriate for screening and diagnosis of M. pneumoniae infection. Macrolides should be used with caution among outpatients with mild RTIs.

Automated lung ultrasound scoring for evaluation of coronavirus disease 2019 pneumonia using two-stage cascaded deep learning model.

Coronavirus disease 2019 (COVID-19) pneumonia has erupted worldwide, causing massive population deaths and huge economic losses. In clinic, lung ultrasound (LUS) plays an important role in the auxiliary diagnosis of COVID-19 pneumonia. However, the lack of medical resources leads to the low using efficiency of the LUS, to address this problem, a novel automated LUS scoring system for evaluating COVID-19 pneumonia based on the two-stage cascaded deep learning model was proposed in this paper. 18,330 LUS images collected from 26 COVID-19 pneumonia patients were successfully assigned scores by two experienced doctors according to the designed four-level scoring standard for training the model. At the first stage, we made a secondary selection of these scored images through five ResNet-50 models and five-fold cross validation to obtain the available 12,949 LUS images which were highly relevant to the initial scoring results. At the second stage, three deep learning models including ResNet-50, Vgg-19, and GoogLeNet were formed the cascaded scored model and trained using the new dataset, whose predictive result was obtained by the voting mechanism. In addition, 1000 LUS images collected another 5 COVID-19 pneumonia patients were employed to test the model. Experiments results showed that the automated LUS scoring model was evaluated in terms of accuracy, sensitivity, specificity, and F1-score, being 96.1%, 96.3%, 98.8%, and 96.1%, respectively. They proved the proposed two-stage cascaded deep learning model could automatically score an LUS image, which has great potential for application to the clinics on various occasions.

The Influences of COVID-19 on Patients With Chronic Kidney Disease: A Multicenter Cross-Sectional Study

Background: The outbreak of coronavirus disease 2019 (COVID-19) has attracted global attention. During the lockdown period of COVID-19, follow-up of many patients with chronic disease had been interrupted, which brought severe challenges to better management of their disease. This study aimed at exploring the change of illness, daily life, and psychological responses during the COVID-19 pandemic among chronic kidney disease (CKD) patients. Methods: A total of 612 patients were enrolled in this study;282 patients were categorized into the CKD stage 1–2 group and 330 patients were categorized into the CKD stage 3–5 group. Among two groups, 168 (27.5%) and 177 (28.9%) patients were female with a median age of 42 and 45, respectively. The study was conducted by collecting the questionnaires in five nephrology centers. The questionnaire consisted of assessment of anxiety by using the Self-Rating Anxiety Scale and the influences of COVID-19, which included basic demographic data, the influences of COVID-19 on illness and daily life, as well as the patients' psychological responses during the epidemic. Results: A total of 612 patients were included and divided into two groups according to eGFR. Ninety-six patients (34%) in the CKD stage 1–2 group and 141 patients (42.7%) in the CKD stage 3–5 group had reduced their follow-up frequency (p = 0.031). More patients with CKD stages 1–2 consulted online (25.9%), p = 0.005. Besides, patients in the CKD stage 3–5 group tended to be more anxious about follow-up (p = 0.002), fearful of being infected with COVID-19 (p = 0.009), and more likely to feel symptoms getting worse (p = 0.006). The standard scores of SAS were 48.58 ± 7.082 and 51.19 ± 5.944 in the CKD stage 1–2 group and the CKD stage 3–5 group, respectively (p < 0.001). There were significant differences in the severity of anxiety (p = 0.004). Conclusion: COVID-19 had a greater impact on patients with CKD stages 3–5 than those with stages 1–2 in terms of illness, daily life, and psychological disorder. Patients with CKD stages 3–5 were more anxious during the COVID-19 pandemic.

The effect of urban morphological characteristics on the spatial variation of PM2.5 air quality in downtown Nanjing.

The effects of the urban morphological characteristics on the spatial variation of near-surface PM2.5 air quality were examined. Unlike previous studies, we performed the analyses in real urban environments using continuous observations covering the whole scale of urban densities typically found in cities. We included data from 31 measurement stations divided into 8 different wind sectors with individually defined morphological characteristics leading to highly varying urban characteristics. The urban morphological characteristics explained up to 73% of the variance in normalized PM2.5 concentrations in street canyons, indicating that the spatial variation of the near-surface PM2.5 air quality was mostly defined by the characteristics studied. The fraction of urban trees nearby the stations was found to be the most important urban morphological characteristic in explaining the PM2.5 air quality, followed by the height-normalized roughness length as the second important parameter. An increase in the fraction of trees within 50 m of the stations from 25 percentile to 75 percentile (i.e. by the interquartile range, IQR) increased the normalized PM2.5 concentration by up to 24% in the street canyons. In open areas, an increase in the trees by the IQR actually decreased the normalized PM2.5 by 6% during the pre-COVID period. An increase in the height-normalized roughness length by the IQR increased the normalized PM2.5 by 9% in the street canyons. The results obtained in this study can help urban planners to identify the key urban characteristics affecting the near-surface PM2.5 air quality and also help researchers to evaluate how representative the existing measurement stations are compared to other parts of the cities.

Diffusion capacity abnormalities for carbon monoxide in patients with COVID-19 at 3-month follow-up.

OBJECTIVE: To evaluate pulmonary function and clinical symptoms in coronavirus disease 2019 (COVID-19) survivors within 3 months after hospital discharge, and to identify risk factors associated with impaired lung function. METHODS AND MATERIAL: COVID-19 patients were prospectively followed-up with pulmonary function tests and clinical characteristics for 3 months following discharge from a hospital in Wuhan, China between January and February 2020. RESULTS: 647 patients were included. 87 (13%) patients presented with weakness, 63 (10%) with palpitations and 56 (9%) with dyspnoea. The prevalence of each of the three symptoms were markedly higher in severe patients than nonsevere patients (19% versus 10% for weakness, p=0.003; 14% versus 7% for palpitations, p=0.007; 12% versus 7% for dyspnoea, p=0.014). Results of multivariable regression showed increased odds of ongoing symptoms among severe patients (OR 1.7, 95% CI 1.1-2.6; p=0.026) or patients with longer hospital stays (OR 1.03, 95% CI 1.00-1.05; p=0.041). Pulmonary function test results were available for 81 patients, including 41 nonsevere and 40 severe patients. In this subgroup, 44 (54%) patients manifested abnormal diffusing capacity of the lung for carbon monoxide (D LCO) (68% severe versus 42% nonsevere patients, p=0.019). Chest computed tomography (CT) total severity score >10.5 (OR 10.4, 95% CI 2.5-44.1; p=0.001) on admission and acute respiratory distress syndrome (ARDS) (OR 4.6, 95% CI 1.4-15.5; p=0.014) were significantly associated with impaired D LCO. Pulmonary interstitial damage may be associated with abnormal D LCO. CONCLUSION: Pulmonary function, particularly D LCO, declined in COVID-19 survivors. This decrease was associated with total severity score of chest CT >10.5 and ARDS occurrence. Pulmonary interstitial damage might contribute to the imparied D LCO.

Vulnerability of the worldwide air transportation network to global catastrophes such as COVID-19.

This paper studies the vulnerability of the worldwide air transportation network (WATN) during a global catastrophe such as COVID-19. Considering the WATN as a weighted network, many airport connections could be completely or partially disrupted during such extreme events. However, it is found that existing weighted metrics cannot reflect the impact of connection capacity reduction on network connectivity. Therein, this work proposes a novel network efficiency metric termed as layered weighted network efficiency (LWNE) metric to measure the connectivity of the air transportation networks (ATNs) and study their vulnerability in response to different levels of disruptions, including airport level, country level, and global level. The most critical airport connections and their impact on network connectivity are identified. It is found that the critical connections are mostly between so-called bridge airports but not core airports in the WATN. By examining the impact of partial link disruptions, it is found that some connections mainly serve local travel demand and are very robust to partial disruptions, while the others connecting global hubs are sensitive to partial disruptions. Further, the WATN is robust to the individual disconnection of most countries; however, it is vulnerable to the simultaneous disconnection of countries that serve international transfers. Interestingly, the WATN is insensitive to the disconnection between any two countries, even those with sizeable domestic ATNs. Concerning global disconnections, as long as all the international connections hold 10% of their original flights, the WATN can still expect 40% of its pre-disruption performance. This paper deepens the understanding of ATNs under extreme events and provides a method for studying transportation networks' vulnerability facing global disruptions.

Air quality in Nanjing during COVID-19 lockdown period

In order to investigate the impact of COVID-19 lockdown on air quality in Nanjing, the air pollutants observed from January 25 to February 10, in 2020（COVID-19 lockdown period） in Nanjing and its surrounding cities was analyzed. During the lockdown period with poor atmospheric diffusion conditions, the concentrations of PM2.5, PM10, NO2, SO2, and CO decreased obviously, with the value of 36, 44, 5, 22μg/m3 and 1.1 mg/m3, whereasO3 increased by 4%. The net effectiveness of the emission reduction measures was calculated through comparisons of concentrations of air pollutants between and before COVID in the similar meteorological conditions. Concentrations of PM2.5, PM10, SO2, NO2 and CO decreased by 41.7%, 45.3%, 14.3%, 43.5% and 18.2%, respectively, whereasO3 increased by 4.8%. Compared to capital cities of the Yangtze River Delta in the same period, the largest decline of SO2 and the medium decline of the other pollutions were appeared in Nanjing. The diurnal variation concentration of PM2.5 and PM10 changed from double peak to single peak, due to the disappearance of nighttime sub-peak of particle. The concentration ofO3 increased significantly at night, which was resulted from that sharp reduction of traffic sources weaken the titration reaction of NO toO3. The peak ofO3 during the daytime depended on the variation of the ratio of VOCs to NOx due to the emission control.

The descriptive epidemiology of coronavirus disease 2019 during the epidemic period in Lu'an, China: achieving limited community transmission using proactive response strategies.

Hubei province in China has had the most confirmed coronavirus disease 2019 (COVID-19) cases and has reported sustained transmission of the disease. Although Lu'an city is adjacent to Hubei province, its community transmission was blocked at the early stage, and the impact of the epidemic was limited. Therefore, we summarised the overall characteristics of the entire epidemic course in Lu'an to help cities with a few imported cases better contain the epidemic. A total of 69 confirmed COVID-19 cases and 11 asymptomatic carriers were identified in Lu'an during the epidemic from 12 January to 21 February 2020. Fifty-two (65.0%) cases were male, and the median age was 40 years. On admission, 56.5% of cases had a fever as the initial symptom, and pneumonia was present in 89.9% of cases. The mean serial interval and the mean duration of hospitalisation were 6.5 days (95% CI: 4.8-8.2) and 18.2 days (95% CI: 16.8-19.5), respectively. A total of 16 clusters involving 60 cases (17 first-generation cases and 43 secondary cases) were reported during the epidemic. We observed that only 18.9% (7/37) index cases resulted in community transmission during the epidemic in Lu'an, indicating that the scale of the epidemic was limited to a low level in Lu'an city. An asymptomatic carrier caused the largest cluster, involving 13 cases. Spread of COVID-19 by asymptomatic carriers represents an enormous challenge for countries responding to the pandemic.

Enhanced secondary pollution offset reduction of primary emissions during COVID-19 lockdown in China.

To control the spread of the 2019 novel coronavirus (COVID-19), China imposed nationwide restrictions on the movement of its population (lockdown) after the Chinese New Year of 2020, leading to large reductions in economic activities and associated emissions. Despite such large decreases in primary pollution, there were nonetheless several periods of heavy haze pollution in eastern China, raising questions about the well-established relationship between human activities and air quality. Here, using comprehensive measurements and modeling, we show that the haze during the COVID lockdown was driven by enhancements of secondary pollution. In particular, large decreases in NOx emissions from transportation increased ozone and nighttime NO3 radical formation, and these increases in atmospheric oxidizing capacity in turn facilitated the formation of secondary particulate matter. Our results, afforded by the tragic natural experiment of the COVID-19 pandemic, indicate that haze mitigation depends upon a coordinated and balanced strategy for controlling multiple pollutants.

Understanding the Influence Factors in Viral Nucleic Acid Test of 2019 novel Coronavirus (2019-nCoV) / 中华检验医学杂志

At present, the prevention and control of new coronavirus has entered a critical period. However, the use of quantitative real-time PCR (qRT-PCR) assays for the detection of viral nucleic acid, as a crucial diagnostic approach, has been doubted in clinical practice. Herein, we have reviewed the current status of epidemic prevention and control, latest development of detection technologies, disease characteristics, clinical sampling and transport. We have also discussed the factors that may affect the performance of viral nucleic acid detection, and suggested some effective methods to improve the detection performance of the assays.