Risk factors for acute kidney injury in COVID-19 patients: an updated systematic review and meta-analysis.

Objectives: Acute kidney injury (AKI) is associated with increased mortality among coronavirus disease 2019 (COVID-19) patients. This meta-analysis aimed to identify risk factors for the development of AKI in patients with COVID-19.Methods: A systematic literature search was conducted in PubMed and EMBASE from 1 December 2019 to 1 January 2023. Due to significant study heterogeneity, meta-analyses were conducted using random-effects models. Meta-regression and sensitivity analysis were also performed.Results: A total of 153,600 COVID-19 patients from 39 studies were included, and 28,003 patients developed AKI. By meta-analysis, we discovered that age, male sex, obesity, black race, invasive ventilation, and the use of diuretics, steroids and vasopressors, in addition to comorbidities such as hypertension, congestive heart failure, chronic kidney disease, acute respiratory distress syndrome, and diabetes, were significant risk factors for COVID-19-associated AKI.Conclusions: Early detection of these risk factors is essential to reduce the incidence of AKI and improve the prognosis of COVID-19 patients.

A human iPSC-array-based GWAS identifies a virus susceptibility locus in the NDUFA4 gene and functional variants.

Population-based studies to identify disease-associated risk alleles typically require samples from a large number of individuals. Here, we report a human-induced pluripotent stem cell (hiPSC)-based screening strategy to link human genetics with viral infectivity. A genome-wide association study (GWAS) identified a cluster of single-nucleotide polymorphisms (SNPs) in a cis-regulatory region of the NDUFA4 gene, which was associated with susceptibility to Zika virus (ZIKV) infection. Loss of NDUFA4 led to decreased sensitivity to ZIKV, dengue virus, and SARS-CoV-2 infection. Isogenic hiPSC lines carrying non-risk alleles of SNPs or deletion of the cis-regulatory region lower sensitivity to viral infection. Mechanistic studies indicated that loss/reduction of NDUFA4 causes mitochondrial stress, which leads to the leakage of mtDNA and thereby upregulation of type I interferon signaling. This study provides proof-of-principle for the application of iPSC arrays in GWAS and identifies NDUFA4 as a previously unknown susceptibility locus for viral infection.

Burnout and well-being of healthcare workers in the post-pandemic period of COVID-19: a perspective from the job demands-resources model.

BACKGROUND: The present study aimed 1) to examine the effects of epidemic-related job stressors, perceived social support and organizational support on the burnout and well-being of Chinese healthcare workers in the period of COVID-19 regular epidemic prevention and control and 2) to investigate the moderating effects of social support and organizational support on the relationship between job stressors and burnout and well-being within the theoretical framework of the Job Demands-Resources (JD-R) model. METHODS: A sample of healthcare workers (N = 3477) from 22 hospitals in Beijing, China participated in the cross-sectional investigation in October 2020 and reported epidemic-related job stressors, perceived social support, organizational support, burnout, anxiety and depression symptoms. RESULTS: 1) Medical doctors, females, people aged from 30 to 50, and those who worked in the second line during the pandemic reported higher scores of psychological symptoms and burnout in the period of regular epidemic prevention and control; 2) Epidemic-related job stressors positively predicted burnout, anxiety, and depression among healthcare workers; 3) Perceived social support and organizational support were negatively related to reported burnout, anxiety and depression symptoms; 4) Social support reduced the adverse effects of epidemic-related job stressors on anxiety and depression but enhanced the association between stressors and burnout; 5) Organizational support mitigated the adverse effects of epidemic-related job stressors on depression. CONCLUSION: The results shed light on preventing burnout and enhancing the psychological well-being of healthcare workers under epidemic prevention and control measures by reducing epidemic-related job stressors and strengthening personal and organizational support systems.

RPpocket: An RNA-Protein Intuitive Database with RNA Pocket Topology Resources.

RNA-protein complexes regulate a variety of biological functions. Thus, it is essential to explore and visualize RNA-protein structural interaction features, especially pocket interactions. In this work, we develop an easy-to-use bioinformatics resource: RPpocket. This database provides RNA-protein complex interactions based on sequence, secondary structure, and pocket topology analysis. We extracted 793 pockets from 74 non-redundant RNA-protein structures. Then, we calculated the binding- and non-binding pocket topological properties and analyzed the binding mechanism of the RNA-protein complex. The results showed that the binding pockets were more extended than the non-binding pockets. We also found that long-range forces were the main interaction for RNA-protein recognition, while short-range forces strengthened and optimized the binding. RPpocket could facilitate RNA-protein engineering for biological or medical applications.

[Clinical observation on filiform-fire needling of "Biaoben acupoint combination" for 33 cases of sequelae of coronavirus disease 2019 during recovery period].

OBJECTIVE: To observe the clinical therapeutic effect of filiform-fire needling of "Biaoben acupoint combination" on the sequelae of patients with coronavirus disease 2019 (COVID-19) during the recovery period. METHODS: A total of 33 patients with COVID-19 during the recovery period were treated with filiform-fire needling at the acupoints of Mingmen (GV 4), Shenzhu (GV 12), Gaohuang (BL 43), Zusanli (ST 36) and Shangjuxu (ST 37), etc., once every other day, 3 times a week, and 3 times was one course of treatment and totally 2 courses of treatment were required. The TCM symptom, Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) scores, pulmonary function indexes (forced vital capacity [FVC], forced expiratory volume in one second [FEV1], peak expiratory flow [PEF]) and chest CT imaging change were observed before and after treatment, and the therapeutic effect was evaluated. RESULTS: After treatment, the scores of TCM symptom, HAMA and HAMD were decreased compared with those before treatment (P<0.05), and the levels of FVC, FEV1 and PEF were increased compared with those before treatment (P<0.05), and the recovery rate of 22 patients with pulmonary ventilation dysfunction was 86.4% (19/22). After treatment, the lung shadow area was smaller than that before treatment (P<0.05). The effective rate of 25 patients with lung CT abnormalities was 84.0% (21/25). After treatment, 23 cases were cured, 5 cases were markedly effective, 4 cases were effective, 1 case was ineffective, the cured and markedly effective rate was 84.8%. CONCLUSION: The filiform-fire needling of "Biaoben acupoint combination" could significantly reduce the sequelae of cough, fatigue, chest tightness, etc. and mental symptoms such as anxiety and depression in patients with COVID-19 during the recovery period, and promote inflammatory exudation absorption of pulmonary lesion and improve lung ventilation function.

Short-Term Effects of Low-Level Ambient Air NO2 on the Risk of Incident Stroke in Enshi City, China.

Previous studies found that exposure to ambient nitrogen dioxide (NO2) was associated with an increased risk of incident stroke, but few studies have been conducted for relatively low NO2 pollution areas. In this study, the short-term effects of NO2 on the risk of incident stroke in a relatively low-pollution area, Enshi city of Hubei Province, China, were investigated through time-series analysis. Daily air-pollution data, meteorological data, and stroke incidence data of residents in Enshi city from 1 January 2015 to 31 December 2018 were collected. A time-series analysis using a generalised additive model (GAM) based on Poisson distribution was applied to explore the short-term effects of low-level NO2 exposure on the risk of incident stroke and stroke subtypes, as well as possible age, sex, and seasonal differences behind the effects. In the GAM model, potential confounding factors, such as public holidays, day of the week, long-term trends, and meteorological factors (temperature and relative humidity), were controlled. A total of 9122 stroke incident cases were included during the study period. We found that NO2 had statistically significant effects on the incidence of stroke and ischemic stroke, estimated by excess risk (ER) of 0.37% (95% CI: 0.04-0.70%) and 0.58% (95% CI: 0.18-0.98%), respectively. For the cumulative lag effects, the NO2 still had a statistically significant effect on incident ischemic stroke, estimated by ER of 0.61% (95% CI: 0.01-1.21%). The two-pollutant model showed that the effects of NO2 on incident total stroke were still statistically significant after adjusting for other air pollutants (PM2.5, PM10, SO2, CO, and O3). In addition, the effects of NO2 exposure on incident stroke were statistically significant in elderly (ER = 0.75%; 95% CI: 0.11-1.40%), males (ER = 0.47%; 95% CI: 0.05-0.89%) and cold season (ER = 0.83%; 95% CI: 0.15-1.51%) subgroups. Our study showed that, as commonly observed in high-pollution areas, short-term exposure to low-level NO2 was associated with an increased risk of incident stroke, including ischemic stroke. Males and elderly people were more vulnerable to the effects of NO2, and the adverse effects might be promoted in the cold season.

Trajectories of Neurologic Recovery 12 Months After Hospitalization for COVID-19: A Prospective Longitudinal Study.

BACKGROUND AND OBJECTIVE: Little is known about trajectories of recovery 12 months after hospitalization for severe COVID-19. METHODS: We conducted a prospective, longitudinal cohort study of patients with and without neurologic complications during index hospitalization for COVID-19 from March 10, 2020, to May 20, 2020. Phone follow-up batteries were performed at 6 and 12 months after COVID-19 onset. The primary 12-month outcome was the modified Rankin Scale (mRS) score comparing patients with or without neurologic complications using multivariable ordinal analysis. Secondary outcomes included activities of daily living (Barthel Index), telephone Montreal Cognitive Assessment (t-MoCA), and Quality of Life in Neurologic Disorders (Neuro-QoL) batteries for anxiety, depression, fatigue, and sleep. Changes in outcome scores from 6 to 12 months were compared using nonparametric paired-samples sign test. RESULTS: Twelve-month follow-up was completed in 242 patients (median age 65 years, 64% male, 34% intubated during hospitalization) and 174 completed both 6- and 12-month follow-up. At 12 months, 197/227 (87%) had ≥1 abnormal metric: mRS >0 (75%), Barthel Index <100 (64%), t-MoCA ≤18 (50%), high anxiety (7%), depression (4%), fatigue (9%), or poor sleep (10%). Twelve-month mRS scores did not differ significantly among those with (n = 113) or without (n = 129) neurologic complications during hospitalization after adjusting for age, sex, race, pre-COVID-19 mRS, and intubation status (adjusted OR 1.4, 95% CI 0.8-2.5), although those with neurologic complications had higher fatigue scores (T score 47 vs 44; p = 0.037). Significant improvements in outcome trajectories from 6 to 12 months were observed in t-MoCA scores (56% improved, median difference 1 point; p = 0.002) and Neuro-QoL anxiety scores (45% improved; p = 0.003). Nonsignificant improvements occurred in fatigue, sleep, and depression scores in 48%, 48%, and 38% of patients, respectively. Barthel Index and mRS scores remained unchanged between 6 and 12 months in >50% of patients. DISCUSSION: At 12 months after hospitalization for severe COVID-19, 87% of patients had ongoing abnormalities in functional, cognitive, or Neuro-QoL metrics and abnormal cognition persisted in 50% of patients without a history of dementia/cognitive abnormality. Only fatigue severity differed significantly between patients with or without neurologic complications during index hospitalization. However, significant improvements in cognitive (t-MoCA) and anxiety (Neuro-QoL) scores occurred in 56% and 45% of patients, respectively, between 6 and 12 months. These results may not be generalizable to those with mild or moderate COVID-19.

[Thumb-tack needles based on "Biaoben acupoint compatibility" for sequela of COVID-19 during recovery period].

OBJECTIVE: To observe the effect of thumb-tack needles based on "Biaoben acupoint compatibility" on sequela symptoms, mental state and pulmonary ventilation function in patients with coronavirus disease 2019 (COVID-19) during recovery period. METHODS: Fifty cases of COVID-19 during recovery period were randomly divided into an observation group and a control group, 25 cases in each group. The patients in the observation group were treated with thumb-tack needles at Guanyuan (CV 4), Zusanli (ST 36) and Taiyuan (LU 9). The patients in the control group were treated with sham thumb-tack needles at identical acupoints as the observation group. The treatment in the two groups was given once a day, 7-day treatment was taken as a course of treatment, and totally two courses of treatment were given. The TCM symptom score, Hamilton anxiety scale (HAMA) score, Hamilton depression scale (HAMD) score, pulmonary function (forced vital capacity [FVC], forced expiratory volume in the first second [FEV1], peak expiratory flow [PEF]), the severity of pulmonary ventilation dysfunction and pulmonary imaging changes in the two groups were compared before and after treatment. RESULTS: Compared before treatment, the total scores and each item scores of TCM symptom scale, HAMA scores and HAMD scores in the two groups were reduced after treatment (P<0.05). Except for the symptom scores of dry throat and dry stool, the total score and each item score of TCM symptom scale, HAMA score and HAMD score in the observation group were lower than those in the control group (P<0.05). Compared before treatment, FVC, FEV1 and PEF in the two groups were increased after treatment (P<0.05), and those in the observation group were higher than the control group (P<0.05). The severity of pulmonary ventilation dysfunction in the two groups was reduced after treatment (P<0.05), and the severity in the observation group was better than that in the control group (P<0.05). After treatment, the lung shadow area in the two groups was decreased (P<0.05), and that in the observation group was smaller than the control group (P<0.05). The improvement of imaging change in the observation group was better than that in the control group (P<0.05). CONCLUSION: The thumb-tack needles based on "Biaoben acupoint compatibility" could significantly reduce the sequela symptoms, anxiety and depression in patients with COVID-19 during recovery stage, and improve the pulmonary ventilation function.

Changes in Physical Fitness during COVID-19 Pandemic Lockdown among Adolescents: A Longitudinal Study.

The negative impact of COVID-19 on physical activity has been improved, while the research on changes in physical fitness that may be caused by physical inactivity is still scarce. This study aims to explore the impact of the COVID-19 pandemic lockdown on physical fitness, and the impact of initial physical fitness indicators on their changes during the lockdown in adolescents. A longitudinal study including 265 adolescents aged 14.1 ± 0.4 years old was conducted in China. Physical fitness measurement at baseline and follow-up were respectively measured before (November 2019) and after the lockdown (July 2020). Several physical fitness indicators including aerobic fitness (i.e., 800-m or 1000-m run) and explosive force (i.e., 50-m sprint) deteriorated during the lockdown. Whereas the performances of vital capacity, flexibility (i.e., sit and reach), and muscular strength (i.e., pull-ups) were significantly improved during the lockdown. Furthermore, the reduction in physical fitness for adolescents with higher physical fitness before the lockdown was greater than that for others. These findings may contribute to the development of targeted intervention strategies for physical fitness promotion during the lockdown caused by the public health emergency.

Risk Factors for Invasive Aspergillosis in Patients Admitted to the Intensive Care Unit With Coronavirus Disease 2019: A Multicenter Retrospective Study.

Background: Invasive pulmonary aspergillosis (IPA) is a life-threatening complication in coronavirus disease 2019 (COVID-19) patients admitted to intensive care units (ICUs), but risk factors for COVID-19-associated IPA (CAPA) have not been fully characterized. The aim of the current study was to identify factors associated with CAPA, and assess long-term mortality. Methods: A retrospective cohort study of adult COVID-19 patients admitted to ICUs from six hospitals was conducted in Hubei, China. CAPA was diagnosed via composite clinical criteria. Demographic information, clinical variables, and 180-day outcomes after the diagnosis of CAPA were analyzed. Results: Of 335 critically ill patients with COVID-19, 78 (23.3%) developed CAPA within a median of 20.5 days (range 13.0-42.0 days) after symptom onset. Compared to those without CAPA, CAPA patients were more likely to have thrombocytopenia (50 vs. 19.5%, p < 0.001) and secondary bacterial infection prior to being diagnosed with CAPA (15.4 vs. 6.2%, p = 0.013), and to receive vasopressors (37.2 vs. 8.6%, p < 0.001), higher steroid dosages (53.9 vs. 34.2%, p = 0.002), renal replacement therapy (37.2 vs. 13.6%, p < 0.001), and invasive mechanical ventilation (57.7 vs. 35.8%, p < 0.001). In multivariate analysis incorporating hazard ratios (HRs) and confidence intervals (CIs), thrombocytopenia (HR 1.98, 95% CI 1.16-3.37, p = 0.012), vasopressor use (HR 3.57, 95% CI 1.80-7.06, p < 0.001), and methylprednisolone use at a daily dose ≥ 40 mg (HR 1.69, 95% CI 1.02-2.79, p = 1.02-2.79) before CAPA diagnosis were independently associated with CAPA. Patients with CAPA had longer median ICU stays (17 days vs. 12 days, p = 0.007), and higher 180-day mortality (65.4 vs. 33.5%, p < 0.001) than those without CAPA. Conclusions: Thrombocytopenia, vasopressor use, and corticosteroid treatment were significantly associated with increased risk of incident IPA in COVID-19 patients admitted to ICUs. The occurrence of CAPA may increase the likelihood of long-term COVID-19 mortality.

COVID-19 exposure, pandemic-related appraisals, coping strategies, and psychological symptoms among the frontline medical staff and gender differences in coping processes.

This study sought to explore the effects of COVID-19 exposure, pandemic-related appraisals and coping strategies on psychological symptoms among the front-line healthcare workers based on the transactional theory of stress and coping. A cross-sectional study was conducted in a Wuhan hospital designated for inpatients with COVID-19, assessing COVID-19 exposure (whether or not exposed to confirmed patients at workplace), psychological symptoms, appraisals, and coping strategies in 311 participants. Results revealed that the pandemic markedly affected healthcare workers' mental well-being through appraisal and coping, with 38.9% reporting high levels of psychological symptoms. Primary appraisal related closely with COVID-19 exposure, especially in female, while secondary appraisal was associated with problem-focused coping. Both problem-focused and emotion-focused coping had a protective effect against psychological symptoms, but also showed gender differences in its relations with other variables. These findings could potentially benefit to enrich relevant theories, and to develop psychological programs for future epidemics.

Supporting Health-Care Workers and Patients in Quarantine Wards: Evidence From a Survey of Frontline Health-Care Workers and Inpatients With COVID-19 in Wuhan, China.

Objective: Frontline health-care workers and patients with COVID-19 have been identified as high-risk groups for psychological problems. Experience of working or staying in quarantine wards generated psychological stressors for health-care workers and patients with COVID-19. The present study aimed to investigate the psychological symptoms of hospitalized patients with COVID-19 and the health-care workers treating them during the outbreak period, examine the effects of psychological stressors on mental health in both populations and perceived coping resources for both sides. Methods: Three hundred and eleven health-care workers working in a COVID-19 designated hospital in Wuhan, China, and 148 hospitalized patients with COVID-19 in the same hospital participated in this cross-sectional survey conducted in February 2020. Psychological symptoms, psychological stressors, and perceived coping resources were reported by both groups. Results: Thirty-three percent of health-care workers and 35.2% of patients with COVID-19 had significant psychological symptoms that were indicative of a high risk for psychological disorders. Pandemic-related psychological stressors contributed to psychological symptoms for both populations. Concern about patients was one aspect of psychological stressors of frontline health-care workers and both groups perceived support from the opposite side as an important external coping resource. Conclusion: The results shed light on the need to provide psychological support to both frontline health-care workers and patients with COVID-19 and suggest enhancing the treatment alliance might be effective to improve mental health for both populations during the crisis.

The Abnormal Imaging of SARS-CoV-2: A Predictive Measure of Disease Severity.

To investigate the characteristics of SARS-CoV-2 pneumonia and evaluate whether CT scans, especially at a certain CT level, could be used to predict the severity of SARS-CoV-2 pneumonia. In total 118 confirmed patients had been enrolled. All data including epidemiological, clinical characteristics, laboratory results, and images were collected and analyzed when they were administrated for the first time. All patients were divided into two groups. There were 106 severe/critical patients and 12 common ones. A total of 38 of the patients were women. The mean age was 50.5 ± 11.5 years. Overall, 80 patients had a history of exposure. The median time from onset of symptoms to administration was 8.0 days. The main symptoms included fever, cough, anorexia, fatigue, myalgia, headaches, and chills. Lymphocytes and platelets decreased and lactate dehydrogenase increased with increased diseased severity (P < 0.05). Calcium and chloride ions were decreased more significantly in severe/critical patients than in common ones (P < 0.05). The main comorbidities were diabetes, chronic cardiovascular disease, and chronic pulmonary disease, which occurred in 47 patients. In all 69 patients had respiratory failure, which is the most common SARS-CoV-2 complication, and liver dysfunction presented in 37 patients. Nine patients received mechanical ventilation therapy. One patient received continuous blood purification and extracorporeal membrane oxygenation (EMCO) treatments. The average stay was 18.1 ± 10.8 days. Four patients died. The median of the radiographic score was four in common, and five in the severe/critical illness, which was a significant difference between the two groups. The radiographic score was in negative correlation with OI (ρ = -0.467, P < 0.01). The OI in severe/critically ill cases decreased significantly as the disease progressed, which was related to the lesion area in the left lung and right lungs (ρ = 0.688, R = 0.733). OI, the lesion area in the left lung and right lungs, lymphocytes, etc. were associated with different degrees of SARS-CoV-2 pneumonia (P < 0.05). The lesion area in both lungs were possible predictive factors for severe/critical cases. Patients with SARS-CoV-2 pneumonia showed obvious clinical manifestations and laboratory result changes. Combining clinical features and the quantity of the lesion area in the fourth level of CT could effectively predict severe/critical SARS-CoV-2 cases.

Analysis on the contribution rates of point and area source emissions to wuhan SO2, NO2, PM2.5 concentrations and atmospheric environmental capacity

Knowing the contribution rates and sharing rate of local source emissions to the atmospheric environmental capacity (AEC) is of great significance to the formulation of regional air pollution source control measures. Based on WRF-CALPUFF coupling models and the second pollution source survey data, Wuhan was taken as the research area, and the contribution rates of point and area source emissions to the SO2, NO2 and PM2.5 concentration in national pollutant control points (abbreviated as "national control points"), the AEC and its source emission sharing rate of each region were calculated. The results showed that WRF-CALPUFF had better reproducibility, the contribution rates of different pollution source emissions to the SO2, NO2 and PM2.5 concentration in national control points had obvious spatial distribution characteristics, and the contribution rates of key point sources to the SO2 concentration of each national control point exceeded 40%, while the contribution rates of the main urban area source to the NO2 and PM2.5 concentrations exceed 60%;the AEC of SO2, NO2 and PM2.5 in different regions had obvious seasonal and spatial changes, and the source emissions of NO2 and PM2.5 in the main urban area were 8.7 times and 3 times of its AEC, respectively. The calculation results from source sharing rate of regional AEC showed that the AEC of SO2 was mainly shared by point sources, and the AEC of NO2 and PM2.5 was mainly shared by area sources, but the sharing rate of SO2, NO2 and PM2.5 AEC from different regional source emissions showed different characteristics. The analysis of air quality improvement during the 7th Military World Games in 2019 and the COVID-19 pandemic in 2020 shows that the calculation formula about regional source sharing rate of AEC proposed in this paper is reasonable and the implementation of refined control to regional source emissions with the source sharing rate of regional AEC plays an important role on the continued improvement of Wuhan air quality.

RPocket: an intuitive database of RNA pocket topology information with RNA-ligand data resources.

BACKGROUND: RNA regulates a variety of biological functions by interacting with other molecules. The ligand often binds in the RNA pocket to trigger structural changes or functions. Thus, it is essential to explore and visualize the RNA pocket to elucidate the structural and recognition mechanism for the RNA-ligand complex formation. RESULTS: In this work, we developed one user-friendly bioinformatics tool, RPocket. This database provides geometrical size, centroid, shape, secondary structure element for RNA pocket, RNA-ligand interaction information, and functional sites. We extracted 240 RNA pockets from 94 non-redundant RNA-ligand complex structures. We developed RPDescriptor to calculate the pocket geometrical property quantitatively. The geometrical information was then subjected to RNA-ligand binding analysis by incorporating the sequence, secondary structure, and geometrical combinations. This new approach takes advantage of both the atom-level precision of the structure and the nucleotide-level tertiary interactions. The results show that the higher-level topological pattern indeed improves the tertiary structure prediction. We also proposed a potential mechanism for RNA-ligand complex formation. The electrostatic interactions are responsible for long-range recognition, while the Van der Waals and hydrophobic contacts for short-range binding and optimization. These interaction pairs can be considered as distance constraints to guide complex structural modeling and drug design. CONCLUSION: RPocket database would facilitate RNA-ligand engineering to regulate the complex formation for biological or medical applications. RPocket is available at http://zhaoserver.com.cn/RPocket/RPocket.html .

Current therapeutic strategies for respiratory diseases using mesenchymal stem cells.

Mesenchymal stromal/stem cells (MSCs) have a great potential to proliferate, undergo multi-directional differentiation, and exert immunoregulatory effects. There is already much enthusiasm for their therapeutic potentials for respiratory inflammatory diseases. Although the mechanism of MSCs-based therapy has been well explored, only a few articles have summarized the key advances in this field. We hereby provide a review over the latest progresses made on the MSCs-based therapies for four types of inflammatory respiratory diseases, including idiopathic pulmonary fibrosis, acute respiratory distress syndrome, chronic obstructive pulmonary disease, and asthma, and the uncovery of their underlying mechanisms from the perspective of biological characteristics and functions. Furthermore, we have also discussed the advantages and disadvantages of the MSCs-based therapies and prospects for their optimization.

Diverse functional autoantibodies in patients with COVID-19.

COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses1-6. Although pathological innate immune activation is well-documented in severe disease1, the effect of autoantibodies on disease progression is less well-defined. Here we use a high-throughput autoantibody discovery technique known as rapid extracellular antigen profiling7 to screen a cohort of 194 individuals infected with SARS-CoV-2, comprising 172 patients with COVID-19 and 22 healthcare workers with mild disease or asymptomatic infection, for autoantibodies against 2,770 extracellular and secreted proteins (members of the exoproteome). We found that patients with COVID-19 exhibit marked increases in autoantibody reactivities as compared to uninfected individuals, and show a high prevalence of autoantibodies against immunomodulatory proteins (including cytokines, chemokines, complement components and cell-surface proteins). We established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signalling and by altering peripheral immune cell composition, and found that mouse surrogates of these autoantibodies increase disease severity in a mouse model of SARS-CoV-2 infection. Our analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics. Our findings suggest a pathological role for exoproteome-directed autoantibodies in COVID-19, with diverse effects on immune functionality and associations with clinical outcomes.

A prospective study of long-term outcomes among hospitalized COVID-19 patients with and without neurological complications.

BACKGROUND: Little is known regarding long-term outcomes of patients hospitalized with COVID-19. METHODS: We conducted a prospective study of 6-month outcomes of hospitalized COVID-19 patients. Patients with new neurological complications during hospitalization who survived were propensity score-matched to COVID-19 survivors without neurological complications hospitalized during the same period. The primary 6-month outcome was multivariable ordinal analysis of the modified Rankin Scale(mRS) comparing patients with or without neurological complications. Secondary outcomes included: activities of daily living (ADLs;Barthel Index), telephone Montreal Cognitive Assessment and Neuro-QoL batteries for anxiety, depression, fatigue and sleep. RESULTS: Of 606 COVID-19 patients with neurological complications, 395 survived hospitalization and were matched to 395 controls; N = 196 neurological patients and N = 186 controls completed follow-up. Overall, 346/382 (91%) patients had at least one abnormal outcome: 56% had limited ADLs, 50% impaired cognition, 47% could not return to work and 62% scored worse than average on ≥1 Neuro-QoL scale (worse anxiety 46%, sleep 38%, fatigue 36%, and depression 25%). In multivariable analysis, patients with neurological complications had worse 6-month mRS (median 4 vs. 3 among controls, adjusted OR 1.98, 95%CI 1.23-3.48, P = 0.02), worse ADLs (aOR 0.38, 95%CI 0.29-0.74, P = 0.01) and were less likely to return to work than controls (41% versus 64%, P = 0.04). Cognitive and Neuro-QOL metrics were similar between groups. CONCLUSIONS: Abnormalities in functional outcomes, ADLs, anxiety, depression and sleep occurred in over 90% of patients 6-months after hospitalization for COVID-19. In multivariable analysis, patients with neurological complications during index hospitalization had significantly worse 6-month functional outcomes than those without.

Perceived organizational support and PTSD symptoms of frontline healthcare workers in the outbreak of COVID-19 in Wuhan: The mediating effects of self-efficacy and coping strategies.

The present study aimed to examine the effect of perceived organizational support on the PTSD symptoms of frontline healthcare workers, and to examine the mediating effects of coping self-efficacy and coping strategies in this relationship. A short-term longitudinal study design was used to conduct two waves of online surveys in March and April 2020. Participants comprised 107 medical staff in both waves of investigation. Self-efficacy, coping strategies, and perceived organizational support were reported at Wave 1, and PTSD symptoms were reported at Wave 2. Results indicated that (1) The prevalence of probable PTSD was 9.3% and 4.7% on the Chinese version of the Impact of Events Scale-Revised of 33 and 35, respectively. Local healthcare workers had greater risks of PTSD than the members of medical rescue teams. Doctors reported higher PTSD symptoms than nurses. (2) Perceived organizational support had a significant indirect effect on PTSD symptoms through the mediation of problem-focused coping strategies and the sequential mediating effect of coping self-efficacy and problem-focused coping strategies. The findings highlight the importance of providing adequate organizational support to reduce PTSD symptoms in frontline medical staff during the COVID-19 pandemic.

Toxic Metabolic Encephalopathy in Hospitalized Patients with COVID-19.

BACKGROUND: Toxic metabolic encephalopathy (TME) has been reported in 7-31% of hospitalized patients with coronavirus disease 2019 (COVID-19); however, some reports include sedation-related delirium and few data exist on the etiology of TME. We aimed to identify the prevalence, etiologies, and mortality rates associated with TME in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients. METHODS: We conducted a retrospective, multicenter, observational cohort study among patients with reverse transcriptase-polymerase chain reaction-confirmed SARS-CoV-2 infection hospitalized at four New York City hospitals in the same health network between March 1, 2020, and May 20, 2020. TME was diagnosed in patients with altered mental status off sedation or after an adequate sedation washout. Patients with structural brain disease, seizures, or primary neurological diagnoses were excluded. The coprimary outcomes were the prevalence of TME stratified by etiology and in-hospital mortality (excluding comfort care only patients) assessed by using a multivariable time-dependent Cox proportional hazards models with adjustment for age, race, sex, intubation, intensive care unit requirement, Sequential Organ Failure Assessment scores, hospital location, and date of admission. RESULTS: Among 4491 patients with COVID-19, 559 (12%) were diagnosed with TME, of whom 435 of 559 (78%) developed encephalopathy immediately prior to hospital admission. The most common etiologies were septic encephalopathy (n = 247 of 559 [62%]), hypoxic-ischemic encephalopathy (HIE) (n = 331 of 559 [59%]), and uremia (n = 156 of 559 [28%]). Multiple etiologies were present in 435 (78%) patients. Compared with those without TME (n = 3932), patients with TME were older (76 vs. 62 years), had dementia (27% vs. 3%) or psychiatric history (20% vs. 10%), were more often intubated (37% vs. 20%), had a longer hospital length of stay (7.9 vs. 6.0 days), and were less often discharged home (25% vs. 66% [all P < 0.001]). Excluding comfort care patients (n = 267 of 4491 [6%]) and after adjustment for confounders, TME remained associated with increased risk of in-hospital death (n = 128 of 425 [30%] patients with TME died, compared with n = 600 of 3799 [16%] patients without TME; adjusted hazard ratio [aHR] 1.24, 95% confidence interval [CI] 1.02-1.52, P = 0.031), and TME due to hypoxemia conferred the highest risk (n = 97 of 233 [42%] patients with HIE died, compared with n = 631 of 3991 [16%] patients without HIE; aHR 1.56, 95% CI 1.21-2.00, P = 0.001). CONCLUSIONS: TME occurred in one in eight hospitalized patients with COVID-19, was typically multifactorial, and was most often due to hypoxemia, sepsis, and uremia. After we adjustment for confounding factors, TME was associated with a 24% increased risk of in-hospital mortality.