3044 Cases reveal important prognosis signatures of COVID-19 patients.

Critical patients and intensive care unit (ICU) patients are the main population of COVID-19 deaths. Therefore, establishing a reliable method is necessary for COVID-19 patients to distinguish patients who may have critical symptoms from other patients. In this retrospective study, we firstly evaluated the effects of 54 laboratory indicators on critical illness and death in 3044 COVID-19 patients from the Huoshenshan hospital in Wuhan, China. Secondly, we identify the eight most important prognostic indicators (neutrophil percentage, procalcitonin, neutrophil absolute value, C-reactive protein, albumin, interleukin-6, lymphocyte absolute value and myoglobin) by using the random forest algorithm, and find that dynamic changes of the eight prognostic indicators present significantly distinct within differently clinical severities. Thirdly, our study reveals that a model containing age and these eight prognostic indicators can accurately predict which patients may develop serious illness or death. Fourthly, our results demonstrate that different genders have different critical illness rates compared with different ages, in particular the mortality is more likely to be attributed to some key genes (e.g. ACE2, TMPRSS2 and FURIN) by combining the analysis of public lung single cells and bulk transcriptome data. Taken together, we urge that the prognostic model and first-hand clinical trial data generated in this study have important clinical practical significance for predicting and exploring the disease progression of COVID-19 patients.

COVID-19-associated monocytic encephalitis (CAME): histological and proteomic evidence from autopsy.

Severe neurological symptoms are associated with Coronavirus disease 2019 (COVID-19). However, the morphologic features, pathological nature and their potential mechanisms in patient brains have not been revealed despite evidence of neurotropic infection. In this study, neuropathological damages and infiltrating inflammatory cells were quantitatively evaluated by immunohistochemical staining, ultrastructural examination under electron microscopy, and an image threshold method, in postmortem brains from nine critically ill COVID-19 patients and nine age-matched cadavers of healthy individuals. Differentially expressed proteins were identified by quantitative proteomic assays. Histopathological findings included neurophagocytosis, microglia nodules, satellite phenomena, extensive edema, focal hemorrhage, and infarction, as well as infiltrating mononuclear cells. Immunostaining of COVID-19 brains revealed extensive activation of both microglia and astrocytes, severe damage of the blood-brain barrier (BBB) and various degrees of perivascular infiltration by predominantly CD14+/CD16+/CD141+/CCR7+/CD11c+ monocytes and occasionally CD4+/CD8+ T lymphocytes. Quantitative proteomic assays combined with bioinformatics analysis identified upregulated proteins predominantly involved in immune responses, autophagy and cellular metabolism in COVID-19 patient brains compared with control brains. Proteins involved in brain development, neuroprotection, and extracellular matrix proteins of the basement membrane were downregulated, potentially caused by the activation of transforming growth factor ß receptor and vascular endothelial growth factor signaling pathways. Thus, our results define histopathological and molecular profiles of COVID-19-associated monocytic encephalitis (CAME) and suggest potential therapeutic targets.

Structural Attention Graph Neural Network for Diagnosis and Prediction of COVID-19 Severity.

With rapid worldwide spread of Coronavirus Disease 2019 (COVID-19), jointly identifying severe COVID-19 cases from mild ones and predicting the conversion time (from mild to severe) is essential to optimize the workflow and reduce the clinician's workload. In this study, we propose a novel framework for COVID-19 diagnosis, termed as Structural Attention Graph Neural Network (SAGNN), which can combine the multi-source information including features extracted from chest CT, latent lung structural distribution, and non-imaging patient information to conduct diagnosis of COVID-19 severity and predict the conversion time from mild to severe. Specifically, we first construct a graph to incorporate structural information of the lung and adopt graph attention network to iteratively update representations of lung segments. To distinguish different infection degrees of left and right lungs, we further introduce a structural attention mechanism. Finally, we introduce demographic information and develop a multi-task learning framework to jointly perform both tasks of classification and regression. Experiments are conducted on a real dataset with 1687 chest CT scans, which includes 1328 mild cases and 359 severe cases. Experimental results show that our method achieves the best classification (e.g., 86.86% in terms of Area Under Curve) and regression (e.g., 0.58 in terms of Correlation Coefficient) performance, compared with other comparison methods.

Effectiveness of a Brief Mindfulness-Based Intervention of "STOP touching your face" During the COVID-19 Pandemic: a Randomized Controlled Trial.

Objectives: Avoiding touching the eyes, nose, and mouth (T-zone) is a strategy to reduce the spread of COVID-19. This study evaluated the effectiveness of a brief mindfulness-based intervention (MBI) named "STOP (Stop, Take a Breath, Observe, Proceed) touching your face" for reducing face-touching behavior. Methods: In this online-based, two-arm, wait-list, randomized controlled trial, eligible participants were randomly assigned to the intervention (n = 545) or control group (n = 545). The results of 60-min self-monitoring of face-touching behavior were reported before and after the intervention. Reduction of the percentage of T-zone touching was the primary outcome, and reduction of face-touching frequency was a key secondary outcome. Outcomes were analyzed on an intention-to-treat (ITT) basis with a complete case analysis (CCA). Results: ITT analysis revealed that the percentage of T-zone touching was significantly reduced by 8.1% in the intervention group (from 81.1 to 73.0%, RR = 0.901, OR = 0.631, RD = - 0.081, p = 0.002), and insignificantly reduced by 0.6% in the control group (from 80.0 to 79.4%, p = 0.821). Fewer participants performed T-zone touching in the intervention group than in the control group (73.0% vs. 79.4%, RR = 0.919, OR = 0.700, RD = - 0.064, p = 0.015) after the intervention, and there was a greater reduction of T-zone touching frequency in the intervention group than in the control group [mean ± SD: 1.7 ± 5.13 vs. 0.7 ± 3.98, mean difference (95% CI): 1.03 (0.48 to 1.58), p < 0.001, Cohen's d = - 0.218]. The above results were further confirmed by CCA. Conclusions: This brief mindfulness-based intervention was potentially effective at reducing the spread of COVID-19 and could be further investigated as an intervention for preventing other infectious diseases spread by hand-to-face touching. Trial Registration: ClinicalTrials.gov NCT04330352. Supplementary Information: The online version contains supplementary material available at 10.1007/s12671-022-02019-x.

Bipolar silica nanochannel array confined electrochemiluminescence for ultrasensitive detection of SARS-CoV-2 antibody.

Ultrasensitive, specific, and early identification of Coronavirus Disease (2019) (COVID-19) infection is critical to control virus spread and remains a global public health problem. Herein, we present a novel solid-state electrochemiluminescence (ECL) platform targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody with rapidity and ultrahigh sensitivity, in which a bipolar silica nanochannel array (bp-SNA) is fabricated on indium tin oxide (ITO) electrode for the first time to stably confine the ECL probe of tris(2,2'-bipyridyl) ruthenium (Ru(bpy)32+) under dual electrostatic force. The bp-SNA consists of tightly packed bilayer silica nanochannel array (SNA) with asymmetric surface charges, namely an inner negatively charged SNA (n-SNA) and an outer positively charged SNA (p-SNA), serving as an "electrostatic lock" to enrich and stabilize the cationic Ru(bpy)32+ probe without leakage from the electrode surface. The detection of SARS-CoV-2 IgG antibody could be realized via immobilization of SARS-CoV-2 spike protein on the utmost of Ru(bpy)32+-confined solid-state ECL platform (Ru@bp-SNA). Upon the capture of target SARS-CoV-2 IgG by immune recognition, the formed immunocomplex will block the nanochannel, leading to the hindered diffusion of the co-reactant (tri-n-propylamine, TPrA) and further producing a decreased ECL signal. The developed solid-stated ECL immunosensor is able to determine SARS-CoV-2 IgG with a wide linear range (5 pg mL-1 to 1 µg mL-1), a low limit-of-detection (2.9 pg mL-1), and a short incubation time (30 min). Furthermore, accurate analysis of SARS-CoV-2 IgG in real serum samples is also obtained by the sensor.

Gaming in China Before the COVID-19 Pandemic and After the Lifting of Lockdowns: a Nationwide Online Retrospective Survey.

With the lockdown and social distancing during the outbreak of coronavirus disease 2019 (COVID-19), gaming has become a popular leisure activity. This study aimed to explore changes in gaming behavior after the lifting of COVID-19 lockdowns and risk factors for increased gaming behavior. This online retrospective study included 5268 gamers. A total of 5% gamers scored 32 or higher on the 9-item Internet Gaming Disorder Scale-Short-Form (IGDS9-SF), suggesting diagnosis of internet gaming disorder (IGD). Over one-third of gamers reported an increase in time spent on gaming per day after the lockdowns were lifted. Logistic regression analysis revealed that gamers who were female, students, experienced stress, or scored higher on IGDS9-SF were more likely to spend more time on gaming per day after the lifting of lockdowns. These findings highlighted the needs for more effective coping strategies or interventions to prevent excessive gaming, especially for females and students.

Efficacy and Safety of Tocilizumab Treatment COVID-19 Patients: A Case-Control Study and Meta-Analysis.

INTRODUCTION: As the pandemic progresses, the pathophysiology of COVID-19 is becoming more apparent, and the potential for tocilizumab is increasing. However, the clinical efficacy and safety of tocilizumab in the treatment of COVID-19 patients remain unclear. METHODS: To assess the efficacy and safety of tocilizumab treatment in COVID-19 patients, we performed a retrospective case-control study. The study was conducted, including 95 patients treated with tocilizumab plus standard treatment and matched controls with 95 patients treated with standard treatment therapy by propensity score from February to April 2020. We searched some databases using the search terms for studies published from January 1, 2020, to June 1, 2021. RESULTS: Our case-control study found a lower mortality rate in the tocilizumab treatment group than in the standard treatment group (9.47% versus 16.84%, P = 0.134), but the results were not statistically significant. We also found that the mortality rate in tocilizumab treatment groups was significantly lower than in the standard treatment group in the stratified ICU analysis (OR 0.52, 95% CI 0.44-0.61, P = 0.048 and OR 0.31, 95% CI 0.10-0.99, P = 0.044). We selected 49 studies (including 6568 cases and 11,660 controls) that met the inclusion criteria in the meta-analysis. In the overall analysis, we performed a meta-analysis that showed significantly decreased mortality after patients received tocilizumab (OR 0.81, 95% CI 0.69-0.95, P = 0.008). We also revealed significant associations within some subgroups. The sequential trial analysis showed a true-positive result. No significant associations were observed between tocilizumab and elevated secondary infection risk, discharge, adverse events, and mechanical ventilation in the overall analysis. CONCLUSION: Tocilizumab significantly decreased mortality in COVID-19 patients with no increased discharge, secondary infection risk, adverse events, and mechanical ventilation in a meta-analysis. Our data suggest that clinicians should pay attention to tocilizumab therapy as an effective and safe treatment for COVID-19 patients.

A cohort autopsy study defines COVID-19 systemic pathogenesis.

Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood-air barrier, blood-testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.

Social media use in China before and during COVID-19: Preliminary results from an online retrospective survey.

BACKGROUND: More people reported symptoms of stress, anxiety and depression during the outbreak of the coronavirus (COVID-19). They might have increased their social media use during the outbreak of COVID-19 compared to before COVID-19. METHODS: An online retrospective survey was conducted on a total sample of 10,963 participants. Social media use patterns before and during COVID-19, Social media addiction (SMA), and mental health problems (stress, anxiety, and depression) were assessed. RESULTS: This study found that, compared with before COVID-19, weekly social media use was significantly increased during COVID-19 (from 17.2 to 21.4 h). Nearly 40% of SMA respondents increased their weekly social media use ≥3.5 h. The prevalence rate of was 6.8%, and the prevalence rates of moderate or severe stress, anxiety, and depression were 10.8%, 26.4%, and 18.2%, respectively, during COVID-19. Female gender, experiencing moderate or severe stress, and SMA were associated with increased weekly social media use ≥3.5 h. Male gender, experiencing moderate or severe stress, anxiety, depression, and increased weekly social media use ≥3.5 h were associated with SMA. CONCLUSIONS: This study suggests a significant increase in social media use and a relatively high prevalence rate of SMA in China during COVID-19. Our findings identify factors associated with increased social media use and SMA that could be used to develop psychological interventions to prevent SMA during the COVID-19 epidemic.

Upregulated IL-6 Indicates a Poor COVID-19 Prognosis: A Call for Tocilizumab and Convalescent Plasma Treatment.

A comprehensive understanding of the dynamic changes in interleukin-6 (IL-6) levels is essential for monitoring and treating patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). By analyzing the correlations between IL-6 levels and health conditions, underlying diseases, several key laboratory detection indices, and the prognosis of 1,473 patients with the coronavirus disease 2019 (COVID-19), the role of IL-6 during SARS-CoV-2 infection was demonstrated. Our results indicated that IL-6 levels were closely related to age, sex, body temperature, oxygen saturation (SpO2) of blood, and underlying diseases. As a stable indicator, the changes in IL-6 levels could indicate the inflammatory conditions during a viral infection. Two specific treatments, namely, tocilizumab and convalescent plasma therapy (CPT), decreased the level of IL-6 and relieved inflammation. CPT has an important role in the therapy for patients with critical COVID-19. We also found that patients with IL-6 levels, which were 30-fold higher than the normal level, had a poor prognosis compared to patients with lower levels of IL-6.

Pathological changes in the lungs and lymphatic organs of 12 COVID-19 autopsy cases.

Systematic autopsy and comprehensive pathological analyses of COVID-19 decedents should provide insights into the disease characteristics and facilitate the development of novel therapeutics. In this study, we report the autopsy findings from the lungs and lymphatic organs of 12 COVID-19 decedents-findings that evaluated histopathological changes, immune cell signature and inflammatory factor expression in the lungs, spleen and lymph nodes. Here we show that the major pulmonary alterations included diffuse alveolar damage, interstitial fibrosis and exudative inflammation featured with extensive serous and fibrin exudates, macrophage infiltration and abundant production of inflammatory factors (IL-6, IP-10, TNFα and IL-1ß). The spleen and hilar lymph nodes contained lesions with tissue structure disruption and immune cell dysregulation, including lymphopenia and macrophage accumulation. These findings provide pathological evidence that links injuries of the lungs and lymphatic organs with the fatal systematic respiratory and immune malfunction in critically ill COVID-19 patients.

Potential False-Positive and False-Negative Results for COVID-19 IgG/IgM Antibody Testing After Heat-Inactivation.

Objectives: With the worldwide spread of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), various antibody detection kits have been developed to test for SARS-CoV-2- specific IgG, IgM, and total antibody. However, the use of different testing methods under various heat-inactivation conditions might affect the COVID-19 detection results. Methods: Seven different antibody detection kits produced by four manufacturers for detection of SARS-CoV-2 IgG, IgM, and total antibody were tested at Wuhan Huoshenshan Hospital, China. Most of the kits used the indirect immunity, capture, and double-antigen sandwich methods. The effects of various heat-inactivation conditions on SARS-CoV-2-specific IgG, IgM, and total antibody detection were analyzed for the different test methods. Results: Using the indirect immunity method, values for SARS-CoV-2 IgG antibody significantly increased and those for IgM antibody decreased with increasing temperature of heat-inactivation using indirect immunity method. However, values for SARS-CoV-2 IgM and total antibody showed no change when the capture and double-antigen sandwich methods were used. The changes in IgG and IgM antibody values with the indirect immunity method indicated that heat-inactivation could affect COVID-19 detection results obtained using this method. In particular, 18 (22.2%) SARS-CoV-2 IgM positive samples were detected as negative with heat-inactivation at 65°C for 30 min, and one (25%) IgG negative sample was detected as positive after heat-inactivation at 56°C for 60 min and 60°C for 30 min. Conclusions: Heat-inactivation could increase SARS-CoV-2 IgG antibody values, and decrease IgM antibody values, causing potential false-positive or false-negative results for COVID-19 antibody detection using the indirect immunity method. Thus, before conducting antibody testing, the testing platforms should be evaluated in accordance with the relevant requirements to ensure accurate COVID-19 detection results.

The paradoxical problem with COVID-19 ocular infection: Moderate clinical manifestation and potential infection risk.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which induced mainly the respiratory damage also caused ocular surface symptoms. However, the detailed description of ocular manifestations, severity fluctuations in confirmed COVID-19 adult patients still lacked. We analyzed onset clinical symptoms and duration, ocular symptoms, needs for medication, outcomes in 28 conjunctivitis patients who were extracted from 3198 COVID-19 patients hospitalized in Huoshenshan Hospital and Taikangtongji Hospital, Wuhan, China. The expression levels of ACE2, TMPRSS2, ANPEP, DPP4, NRP1 on fetal and adult ocular surface and mouse lacrimal glands were assessed by single cell seq analysis. Our results indicated that conjunctivitis was a rare and self-limited complication in adults with COVID-19 while the existence of coronavirus receptors on human ocular surface and mouse lacrimal glands indicated the risk of SARS-CoV-2 infection. Our research firstly examined SARS-CoV-2 receptors, including the new discovered one, NRP1, on the fetal ocular surface and in the mouse lacrimal glands.

CRISPR-Assisted DNA Detection: A Novel dCas9-Based DNA Detection Technique.

Nucleic acid detection techniques are always critical to diagnosis, especially in the background of the present coronavirus disease 2019 pandemic. Simple and rapid detection techniques with high sensitivity and specificity are always urgently needed. However, current nucleic acid detection techniques are still limited by traditional amplification and hybridization. To overcome this limitation, here we developed CRISPR-Cas9-assisted DNA detection (CADD). In this detection, a DNA sample is incubated with a pair of capture single guide RNAs (sgRNAs; sgRNAa and sgRNAb) specific to a target DNA, dCas9, a signal readout-related probe, and an oligo-coated solid support beads or microplate at room temperature (RT) for 15 min. During this incubation, the dCas9-sgRNA-DNA complex is formed and captured on solid support by the capture sequence of sgRNAa, and the signal readout-related probe is captured by the capture sequence of sgRNAb. Finally, the detection result is reported by a fluorescent or colorimetric signal readout. This detection was verified by detecting DNA of bacteria, cancer cells, and viruses. In particular, by designing a set of sgRNAs specific to 15 high-risk human papillomaviruses (HPVs), the HPV infection in 64 clinical cervical samples was successfully detected by the method. All detections can be finished in 30 min at RT. This detection holds promise for rapid on-the-spot detection or point-of-care testing.

Alcohol Consumption in China Before and During COVID-19: Preliminary Results From an Online Retrospective Survey.

Background: Alcohol is an important aspect of Chinese culture, and alcohol use has been traditionally accepted in China. People with stress, anxiety, and depression may use more alcohol. More people reported symptoms of anxiety and depression during the outbreak of COVID-19. Thus, people may drink more alcohol during the outbreak of COVID-19 than before COVID-19. Methods: An online retrospective survey was conducted on a total sample of 2,229 participants. Drinking behaviors before and during COVID-19, current risky drinking and hazardous drinking, and the association between high-risk drinking and mental health problems (depression, anxiety, and stress) were assessed via self-reported measures on the Alcohol Use Disorders Identification Test (AUDIT) and the 21-item Depression Anxiety Stress Scales (DASS-21). Results: This study found that, compared with before COVID-19, alcohol consumption was slightly decreased during COVID-19 (from 3.5 drinks to 3.4 drinks, p = 0.035) in the overall sample. Most (78.7%) alcohol drinkers were males. Before and during COVID-19, males consumed more drinks per week (4.2 and 4.0 vs. 1.3 and 1.2 drinks), had a higher percentage of heavy drinking (8.1 and 7.7% vs. 4.4 and 2.7%), and more drinking days per week (2.1 and 2.1 vs. 1.0 and 0.9 days). Males also had more risky drinking (43.2 vs. 9.3%) and hazardous drinking (70.2 vs. 46.6%) than female counterparts. This study also found that high-risk drinking predicted anxiety in females. Conclusions: This study suggests a slight reduction in alcohol consumption during COVID-19. However, hazardous drinking is common, especially among male alcohol drinkers. Males consumed more alcohol, had more risky and hazardous drinking than female counterparts both before and during COVID-19. Public health policy makers should pay more attention to developing effective, population-based strategies to prevent harmful alcohol consumption.

Clinical outcomes for COVID-19 patients with diabetes mellitus treated with convalescent plasma transfusion in Wuhan, China.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is wreaking havoc on public health systems worldwide. The diagnosis of COVID-19 is well defined, but efficacious treatment is lacking. There is a big gap in knowledge regarding COVID-19 patients receiving convalescent plasma transfusion (CPT), especially those also suffering from diabetes mellitus (DM). In this study, among 3059 COVID-19 patients admitted to Wuhan Huoshenshan Hospital of China, we documented the characteristics of 39 COVID-19 patients with DM receiving CPT and compared their baseline information and clinical outcomes to COVID-19 patients with DM receiving conventional treatment. We also performed the propensity-matched comparison of COVID-19 patients with DM between conventional treatment and CPT. The CPT was efficacious and beneficial for COVID-19 patients with DM, including severe or critically ill patients, without obvious adverse effects. Our data demonstrated that CPT significantly improved the clinical outcomes of COVID-19 patients with DM, especially the cure rate and duration of hospitalization compared with that in COVID-19 patients with DM receiving conventional treatment. This study not only provided a deeper understanding of characteristics in COVID-19 patients with DM receiving CPT but also highlighted the efficaciousness of CPT for COVID-19 patients with DM.