Comparative miRNA Transcriptomics of Mouse and Macaque Reveals MYOC is An Inhibitor for C. neoformans Invasion into Brain (preprint)

Cryptococcal meningoencephalitis is an emerging infection shifted from primarily ART-naive to being ART-experienced HIV/AIDS patients, COVID-19 patients and also in immune competent individuals, mainly caused by the human opportunistic pathogen Cryptococcus neoformans , yet mechanisms of the brain or CNS dissemination remain to elucidate, which is the deadest process for the disease. Meanwhile, illustrations of clinically relevant responses in cryptococcosis were limited, as the low availabilities of clinical samples. In this study, macaque and mouse infection models were employed and miRNA-mRNA transcriptomes were performed and combined, which revealed cytoskeleton, a major feather in HIV/AIDS patients, was a centric pathway regulated in both two infection models. Notably, assays of clinical immune cells confirmed an enhanced “Trojan Horse” in HIV/AIDS patients, which can be shut down by cytoskeleton inhibitors. Furthermore, we identified a novel enhancer for macrophage “Trojan Horse”, myocilin, and an enhanced fungal burden was achieved in brains of MYOC transgenic mice. Taking together, this study reveals fundamental roles of cytoskeleton and MYOC in blocking fungal CNS dissemination, which not only helps to understand the high prevalence of cryptococcal meningitis in HIV/AIDS, but also facilitates the development of novel drugs for therapies of meningoencephalitis caused by C. neoformans and other pathogenic microorganisms.

Investigation of PTSD during the coronavirus epidemic

Aim: We investigated to understand post-traumatic stress disorder (PTSD) during the coronavirus epidemic, and related influential factors. We hoped to provide more basis for targeted services to improve public psychological health care. Methods: From the psychological aid platform set up by the Wuhan Mental Health Center, we obtained online sample data of Chinese residents during the coronavirus epidemic. We used the PTSD examination scale as the study tool and analyzed the data with SPSS. Results: A total of 376 data was collected. The PTSD degree of the public was 45.93 +/- 17.32, the positive detection rate was 63.56%, and the PTSD level increased with fluctuation. Participants' gender, educational level, and location were the influential factors. Specifically, women, lower educational backgrounds, and people in Wuhan were more likely to have PTSD. Conclusions: The epidemic had a great impact on people's psychological status. Although the epidemic has basically been brought under control, PTSD levels have not declined. Therefore, it is necessary to provide timely psychological assistance for people in need, and help them adapt to life as soon as possible. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Possible posttraumatic stress disorder in Chinese frontline healthcare workers who survived COVID-19 6 months after the COVID-19 outbreak: prevalence, correlates, and symptoms.

Suffering from COVID-19 and witnessing the suffering and deaths of patients with COVID-19 may place frontline healthcare workers (HCWs) at particularly high risk for posttraumatic stress disorder (PTSD); however, few data are available on the clinical characteristics of PTSD among frontline HCWs who survived COVID-19 ("surviving HCWs" hereafter). The present study examined the prevalence, correlates, and clinical symptoms of possible PTSD in surviving HCWs 6 months after the COVID-19 outbreak in China. A total of 291 surviving HCWs and 42 age- and gender-matched COVID-19-free frontline HCWs (control group) were recruited and administered the Chinese Essen Trauma Inventory, which was used to assess the presence of possible PTSD according to DSM-IV-TR criteria. Survivors' clinical data and characteristics of exposure to COVID-19 were collected via self-report questionnaires. Surviving HCWs had significantly higher rates of possible PTSD than controls (19.9% vs. 4.8%, P = 0.017). Correlates of PTSD in survivors were ICU admission (OR = 8.73, P = 0.003), >10 respiratory symptoms during the most symptomatic period of COVID-19 (OR = 3.08, P = 0.006), the residual symptom of dizziness (OR = 2.43, P = 0.013), the residual symptom of difficult breathing (OR = 2.23, P = 0.027), life in danger due to COVID-19 (OR = 16.59, P = 0.006), and exposure to other traumatic events (OR = 2.94, P = 0.035). Less commonly seen PTSD symptoms in survivors were having nightmares about the event (34.5%), suddenly feeling like they were living through the event suddenly (25.9%), being unable to remember an important part of the event (32.8%), and overalertness (31.0%). Nearly one-fifth of the surviving HCWs had possible PTSD 6 months after the COVID-19 outbreak. Mental health services for this vulnerable population should include periodic screening for PTSD, expanded social support, and, when necessary, psychotherapy and psychopharmacological treatment.

Systematic review and meta-analysis of tocilizumab in persons with coronavirus disease-2019 (COVID-19).

We performed a meta-analysis to determine safety and efficacy of tocilizumab in persons with coronavirus disease-2019 (COVID-19). We searched PubMed, Web of Science and Medline using Boolean operators for studies with the terms coronavirus OR COVID-19 OR 2019-nCoV OR SARS-CoV-2 AND tocilizumab. Review Manager 5.4 was used to analyze data and the modified Newcastle-Ottawa and Jadad scales for quality assessment. We identified 32 studies in 11,487 subjects including three randomized trials and 29 cohort studies with a comparator cohort, including historical controls (N = 5), a matched cohort (N = 12), or concurrent controls (N = 12). Overall, tocilizumab decreased risk of death (Relative Risk [RR] = 0.74; 95% confidence interval [CI], 0.59, 0.93; P = 0.008; I2 = 80%) but not of surrogate endpoints including ICU admission (RR = 1.40 [0.64,3.06]; P = 0.4; I2 = 88%), invasive mechanical ventilation (RR = 0.83 [0.57,1.22]; P = 0.34; I2 = 65%) or secondary infections (RR = 1.30 [0.97,1.74]; P = 0.08; I2 = 65%) and increased interval of hospitalization of subjects discharged alive(mean difference [MD] = 2 days [<1, 4 days]; P = 0.006; I2 = 0). RRs of death in studies with historical controls (RR = 0.28 [0.16,0.49; P < 0.001]; I2 = 62%) or a matched cohort (RR = 0.68 [0.53, 0.87]; P = 0.002; I2 = 42%) were decreased. In contrast, RRs of death in studies with a concurrent control (RR = 1.10 [0.77, 1.56]; P = 0.60; I2 = 85%) or randomized (RR = 1.18 [0.57,2.44]; P = 0.66; I2 = 0) were not decreased. A reduced risk of death was not confirmed in our analyses which questions safety and efficacy of tocilizumab in persons with COVID-19.

Feelings of loneliness and mental health needs and services utilization among Chinese residents during the COVID-19 epidemic.

BACKGROUND: Due to the implementation of social distancing and quarantine measures, loneliness has been a major public health concern during the COVID-19 pandemic. However, few studies have examined loneliness in Chinese residents during the COVID-19 epidemic, as well as its associations with mental health needs and services utilization. METHODS: The present study was a cross-sectional survey during the COVID-19 outbreak in China. A total of 7741 adults were invited and completed an online self-administered questionnaire. The Chinese 12-item General Health Questionnaire was used to screen for common mental health problems, loneliness was measured with a single-item self-report question ("How often do you feel lonely in recent days?"), and two standardized questions were used to assess perceived needs for and use of mental health services. RESULTS: In total, 24.2 % of the participants felt lonely in recent days. Age of 16-29 years (OR = 1.36, P = 0.020), marital status of never-married (OR = 1.47, P < 0.001), marital status of "others" (re-married, co-habiting, separated, divorced, and widowed) (OR = 1.72, P < 0.001), having infected family members or close relatives (OR = 1.64, P = 0.026), and having infected colleagues, friends, or classmates (OR = 1.62, P < 0.001) were significant correlates of loneliness. Rates of mental health needs (17.4 % vs. 4.9 %, P < 0.001) and services utilization (2.7 % vs. 1.0 %, P < 0.001) were significantly higher in lonely than not lonely participants. After adjusting for socio-demographic and epidemic characteristics and common mental health problems, loneliness was still significantly associated with mental health needs (OR = 2.50, P < 0.001) and services utilization (OR = 1.62, P = 0.020). CONCLUSIONS: Feelings of loneliness are prevalent among Chinese residents affected by the COVID-19 epidemic and the presence of loneliness is associated with high levels of mental health needs and greater services utilization. Effective measures aiming at preventing or reducing loneliness are potentially beneficial for the mental wellbeing of COVID-19-affected population and reducing the use of the limited mental health service resources during the COVID-19 pandemic.

Recommendations for physical activity during the COVID-19 pandemic

The coronavirus disease (COVID-19) outbreak has not only had severe social and economic effect but also has substantially affected the lifestyles of individuals. As the coronavirus pandemic rips through the world, many countries have implemented series of restrictions to control infection, such as the wearing of masks outside, social distancing, home isolation, home quarantine, group quarantine, and lockdowns, and these measures have inevitably limited physical activity and required more sedentary behavior. How a person can remain physically active and healthy during the COVID-19 pandemic is a crucial issue. The following procedure was implemented to review evidence regarding the COVID-19 outbreak and physical activity. First, the latest physical activity guidelines released by the United States, United Kingdom, and World Health Organization were reviewed, and the prevalence of insufficient physical activity was determined. Second, the effects of the COVID-19 outbreak on physical activity and amount of sedentary behavior were discussed using the obtained evidence. Finally, the current review suggests the following for individuals wishing to remain physically active and healthy: (1) Some physical activity is preferable to nothing. Engaging in some moderate-intensity physical activity, such as at least 4,000-5,000 steps per day (7,000-8,000 is better) at a pace of 100-130 steps per minute and resistance training twice a week to improve major muscle-group strength, is essential for everyone. (2) Daily sedentary time should be kept to less than 9 hours a day, and numerous breaks (e.g., every 50 minutes) in which sedentary time is replaced with light activity (e.g., 5to 10-minute walking or stretch exercise) should be taken. (3) Ideally, people should engage in different types of physical activity, including aerobic exercise, resistance training, stretching, and balance training. (4) Finally, people should select types of exercise (e.g., freehand exercise, equipment-assisted exercise, electronic exercise, or household work) that fit their interests and resources. These suggestions provide guidance for strengthening individuals' mental and physical well-being through physical activity in response to the COVID-19 pandemic or future similar outbreaks. (Taiwan J Public Health. 2020;39(4):364-372)

Differences in the clinical characteristics and outcomes of COVID-19 patients in the epicenter and peripheral areas of the pandemic from China: a retrospective, large-sample, comparative analysis (preprint)

Background: There is limited information on the difference in epidemiology, clinical characteristics and outcomes of the initial outbreak of the coronavirus disease (COVID-19) in Wuhan (the epicenter) and Sichuan (the peripheral area) in the early phase of the COVID-19 pandemic. This study was conducted to investigate the differences in the epidemiological and clinical characteristics of patients with COVID-19 between the epicenter and peripheral areas of pandemic and thereby generate information that would be potentially helpful in formulating clinical practice recommendations to tackle the COVID-19 pandemic. Methods: The Sichuan & Wuhan Collaboration Research Group for COVID-19 established two retrospective cohorts that separately reflect the epicenter and peripheral area during the early pandemic. The epidemiology, clinical characteristics and outcomes of patients in the two groups were compared. Multivariate regression analyses were used to estimate the adjusted odds ratios (aOR) with regard to the outcomes. Results: The Wuhan (epicenter) cohort included 710 randomly selected patients, and the peripheral (Sichuan) cohort included 474 consecutive patients. A higher proportion of patients from the periphery had upper airway symptoms, whereas a lower proportion of patients in the epicenter had lower airway symptoms and comorbidities. Patients in the epicenter had a higher risk of death (aOR=7.64), intensive care unit (ICU) admission (aOR=1.66), delayed time from illness onset to hospital and ICU admission (aOR=6.29 and aOR=8.03, respectively), and prolonged duration of viral shedding (aOR=1.64). Conclusions: The worse outcomes in the epicenter could be explained by the prolonged time from illness onset to hospital and ICU admission. This could potentially have been associated with elevated systemic inflammation secondary to organ dysfunction and prolonged duration of virus shedding independent of age and comorbidities. Thus, early supportive care could achieve better clinical outcomes.

Serum Cytokine and Chemokine Profile in Relation to the Severity of Coronavirus Disease 2019 in China.

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated the serum cytokine and chemokine levels in asymptomatic, mild, moderate, severe, and convalescent SARS-CoV-2-infected cases. Proinflammatory cytokine and chemokine production induced by SARS-CoV-2 were observed not only in symptomatic patients but also in asymptomatic cases, and returned to normal after recovery. IL-6, IL-7, IL-10, IL-18, G-CSF, M-CSF, MCP-1, MCP-3, IP-10, MIG, and MIP-1α were found to be associated with the severity of COVID-19. Moreover, a set of cytokine and chemokine profiles were significantly higher in SARS-CoV-2-infected male than female patients. The serum levels of MCP-1, G-CSF, and VEGF were weakly and positively correlated with viral titers. We suggest that combinatorial analysis of serum cytokines and chemokines with clinical classification may contribute to evaluation of the severity of COVID-19 and optimize the therapeutic strategies.

Mental health problems, needs, and service use among people living within and outside Wuhan during the COVID-19 epidemic in China.

BACKGROUND: Crisis mental health services for the general population are an essential component in combating the COVID-19 epidemic. To facilitate planning of mental health services, empirical data on mental health problems and service utilization of populations affected by the epidemic are urgently needed. This study investigated the prevalence of mental health problems of residents within and outside Wuhan, China, as well as their patterns of mental health service utilization. METHODS: From January 27 to February 2, 2020, an online cross-sectional survey recruited residents from 4 subpopulations: Wuhan residents (n=2,617), migrants from Wuhan (those who left Wuhan before lockdown, n=930), other Hubei residents (n=633), and residents of other provinces of China ("other residents", n=3,561). Participants' mental health problems and patterns of utilization of mental health services in recent days were assessed with standardized assessments. RESULTS: Among the 4 groups, Wuhan residents had the highest rate of any type of mental health problem (i.e., psychological distress: 41.9%), followed by migrants from Wuhan (34.2%), other Hubei residents (24.8%), and other residents (21.1%). Rates of perceived mental health needs and utilization of mental health services during recent days were 10.2% and 1.9% for Wuhan residents, 8.4% and 1.8% for migrants from Wuhan, 6.2% and 1.1% for other Hubei residents, and 6.4% and 1.0% for other residents, respectively. Overall, 63.0% mental health service users received services via internet and telephone, and 83.1% participants with perceived mental health needs ascribed their lack of help-seeking to barriers to accessibility and availability. CONCLUSIONS: The COVID-19 epidemic is associated with unprecedented levels of mental health problems and needs in affected residents. To address the unmet mental health needs, internet- and telephone-based mental health services should be widely provided to residents, especially those in the worst-affected regions.

COVID-19 and early-stage lung cancer both featuring ground-glass opacities: a propensity score-matched study.

BACKGROUND: Radiological manifestations of coronavirus disease 2019 (COVID-19) featured ground-glass opacities (GGOs), especially in the early stage, which might create confusion in differential diagnosis with early lung cancer. We aimed to specify the radiological characteristics of COVID-19 and early lung cancer and to unveil the discrepancy between them. METHODS: One hundred and fifty-seven COVID-19 patients and 374 early lung cancer patients from four hospitals in China were retrospectively enrolled. Epidemiological, clinical, radiological, and pathological characteristics were compared between the two groups using propensity score-matched (PSM) analysis. RESULTS: COVID-19 patients had more distinct symptoms, tended to be younger (P<0.0001), male (P<0.0001), and had a higher body mass index (P=0.014). After 1:1 PSM, 121 matched pairs were identified. Regarding radiological characteristics, patients with a single lesion accounted for 17% in COVID-19 and 89% in lung cancer (P<0.0001). Most lesions were peripherally found in both groups. Lesions in COVID-19 involved more lobes (median 3.5 vs. 1; P<0.0001) and segments (median 6 vs. 1; P<0.0001) and tended to have multiple types (67%) with patchy form (54%). Early lung cancer was more likely to have a single type (92%) with oval form (66%). Also, COVID-19 and early lung cancer either had some distinctive features on computed tomography (CT) images. CONCLUSIONS: Both COVID-19 and early lung cancers showed GGOs, with similar but independent features. The imaging characteristics should be fully understood and combined with epidemiological history, pathogen detection, laboratory tests, short-term CT reexamination, and pathological results to aid differential diagnosis.

Development of a lateral flow immunoassay strip for rapid detection of IgG antibody against SARS-CoV-2 virus.

The ongoing worldwide SARS-CoV-2 epidemic clearly has a tremendous influence on public health. Molecular detection based on oral swabs was used for confirmation of SARS-CoV-2 infection. However, high false negative rates were reported. We describe here the development of a point-of-care (POC) serological assay for the detection of IgG antibody against SARS-CoV-2. The principle of a lateral flow immunoassay strip (LFIAs) consists of fixing SARS-CoV-2 nucleocapsid protein to the surface of the strip and coupling anti-human IgG with colloidal gold nanoparticles (Au NPs). A series of parameters of this method were optimized, including the concentration of coating antigen, BSA blocking concentration and pH value for conjugation. The entire detection process took 15-20 min with a volume of 80 µL of the analyte solution containing 10 µL of serum and 70 µL sample diluent. The performance of the established assay was evaluated using serum samples of the clinically diagnosed cases of Coronavirus Disease 2019 (COVID-19). Our results indicated that the LFIAs for SARS-CoV-2 had satisfactory stability and reproducibility. As a result, our fast and easy LFIAs could provide a preliminary test result for physicians to make the correct diagnosis of SARS-CoV-2 infections along with alternative testing methods and clinical findings, as well as seroprevalence determination, especially in low-resource countries.

Rapid Detection of IgM Antibodies against the SARS-CoV-2 Virus via Colloidal Gold Nanoparticle-Based Lateral-Flow Assay.

Last year, the novel coronavirus disease (COVID-19) emerged in Wuhan, and it has rapidly spread to many other countries and regions. COVID-19 exhibits a strong human-to-human transmission infectivity and could cause acute respiratory diseases. Asymptomatic carriers are able to infect other healthy persons, and this poses a challenge for public health; the World Health Organization (WHO) has already announced COVID-19 as a global pandemic. Nucleic acid testing, considered as the current primary method for diagnosing COVID-19, might lead to false negatives and is difficult to be applied for every suspected patient because of the existence of asymptomatic carriers. Meanwhile, detecting specific antibodies in blood, such as the IgM antibody, against the SARS-CoV-2 virus is another choice for COVID-19 diagnosis, as it is widely accepted that IgM is an important indicator in the acute infection period. In this study, a colloidal gold nanoparticle-based lateral-flow (AuNP-LF) assay was developed to achieve rapid diagnosis and on-site detection of the IgM antibody against the SARS-CoV-2 virus through the indirect immunochromatography method. For preparing AuNP-LF strips, the SARS-CoV-2 nucleoprotein (SARS-CoV-2 NP) was coated on an analytical membrane for sample capture, and antihuman IgM was conjugated with AuNPs to form the detecting reporter. Optimization of AuNP-LF assay was carried out by altering the pH value and the amount of antihuman IgM. The performance of AuNP-LF assay was evaluated by testing serum samples of COVID-19 patients and normal humans. The results were compared with the real-time polymerase chain reaction. The sensitivity and specificity of AuNP-LF assay were determined to be 100 and 93.3%, respectively, and an almost perfect agreement was exhibited by Kappa statistics (κ coefficient = 0.872). AuNP-LF assay showed outstanding selectivity in the detection of IgM against the SARS-CoV-2 virus with no interference from other viruses such as severe fever with thrombocytopenia syndrome virus (SFTSV) and dengue virus (DFV). AuNP-LF assay was able to achieve results within 15 min and needed only 10-20 µL serum for each test. As a whole, in the light of its advantages such as excellent specificity and stability, easy operation, low cost, and being less time-consuming, AuNP-LF assay is a feasible method for the diagnosis of COVID-19 in primary hospitals and laboratories, especially in emergency situations in which numerous samples need to be tested on time.

Knowledge, attitudes, and practices towards COVID-19 among Chinese residents during the rapid rise period of the COVID-19 outbreak: a quick online cross-sectional survey.

Unprecedented measures have been adopted to control the rapid spread of the ongoing COVID-19 epidemic in China. People's adherence to control measures is affected by their knowledge, attitudes, and practices (KAP) towards COVID-19. In this study, we investigated Chinese residents' KAP towards COVID-19 during the rapid rise period of the outbreak. An online sample of Chinese residents was successfully recruited via the authors' networks with residents and popular media in Hubei, China. A self-developed online KAP questionnaire was completed by the participants. The knowledge questionnaire consisted of 12 questions regarding the clinical characteristics and prevention of COVID-19. Assessments on residents' attitudes and practices towards COVID-19 included questions on confidence in winning the battle against COVID-19 and wearing masks when going out in recent days. Among the survey completers (n=6910), 65.7% were women, 63.5% held a bachelor degree or above, and 56.2% engaged in mental labor. The overall correct rate of the knowledge questionnaire was 90%. The majority of the respondents (97.1%) had confidence that China can win the battle against COVID-19. Nearly all of the participants (98.0%) wore masks when going out in recent days. In multiple logistic regression analyses, the COVID-19 knowledge score (OR: 0.75-0.90, P<0.001) was significantly associated with a lower likelihood of negative attitudes and preventive practices towards COVID-2019. Most Chinese residents of a relatively high socioeconomic status, in particular women, are knowledgeable about COVID-19, hold optimistic attitudes, and have appropriate practices towards COVID-19. Health education programs aimed at improving COVID-19 knowledge are helpful for Chinese residents to hold optimistic attitudes and maintain appropriate practices. Due to the limited sample representativeness, we must be cautious when generalizing these findings to populations of a low socioeconomic status.