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1.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325271

ABSTRACT

Objectives: To describe the clinical sequelae and immunological features of COVID-19 survivors who have been discharged from the hospital for 5-8 months. Methods: This study is a cross-sectional study of confirmed COVID-19 patients aged ≥18 years who were discharged from hospitals in Wuhan from January to April 2020. The demographics, clinical features, and laboratory findings of the participants were collected from medical records in the hospital. The participants from the study completed an investigation of clinical sequelae, blood tests, a pulmonary function examination and an unarmed rehabilitation evaluation at Hubei Provincial Hospital of Traditional Chinese & Western Medicine. A group of volunteers who were free of COVID-19 and lived in Wuhan during the outbreak were recruited as the comparison group.Results: The average age of the 574 COVID-19 survivors was 57.7±11.4 years, and 348 (60.6%) survivors were female. The average number of days from the onset of symptoms was 241.79±16.16. The average number of days from discharge was 194.3±14.4. Clinical sequelae were common, including general symptoms (n=321, 55.9%), respiratory symptoms (n=265, 46.2%), digestive symptoms (n=84, 14.6%), nervous symptoms (n=75,13.1%) and psychosocial symptoms (n=201, 35%). A total of 190 (33.7%) survivors reported reduced exercise capacity. Through the results of pulmonary function examination, anomalies were noted in carbon monoxide diffusion capacity (DLCO)% in 110 cases (32.4%), maximal mid-expiratory flow (MMEF)% in 105 cases (30.7%), forced expired flow at 50% of forced vital capacity (FEF 50 )% in 128 cases (37.4%), and forced expired flow at 75% of forced vital capacity (FEF 75 )% in 240 cases (70.2%). The counts of T lymphocyte, CD4+ T lymphocyte counts, CD8+ T lymphocyte counts, B lymphocyte and NK cell in the survival group was significantly lower than that in the comparison group(all P < 0.05).There were 252 (43.9%) survivors whose total T lymphocyte counts had dropped, 260 (45.3%) whose CD4+T lymphocyte counts had dropped, 231 (40.2%) whose CD8+ T lymphocyte counts had dropped, 119 (20.7%) whose B lymphocyte counts had dropped, and 54 (9.4%) whose NK cell counts had dropped. But there were no statistically significant differences in the incidence of lymphocyte subsets reduction between severe and nonsevere groups (all P > 0.05). The T lymphocyte counts, CD4+ T lymphocyte counts and CD8+ T lymphocyte counts of the patients before discharge were significantly higher than those in the early stage of admission (P < 0.025). There were 319 (55.6%) survivors with positive or weakly positive IgG antibodies and 17 (2.9%) survivors with positive or weakly positive IgM antibodies.Conclusion: Even after 5 to 8 months of discharge, many survivors still have clinical sequelae, and some of them have impaired immune function. Therefore, the long-term rehabilitation of COVID-19 survivors remains a concern.Funding Statement: This study was funded by the National Key R&D Plan of China (2020YFC0841600), Guangdong Provincial Key Laboratory of Research on Emergency in TCM (2017B030314176), R&D plan in key areas of Guangdong Province (2020B1111300005), and National Administration of Traditional Chinese Medicine (2020ZYLCYJ05-11).Declaration of Interests: The authors declare that they have no competing interests.Ethics Approval Statement: This study was approved by the ethical committees of Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China (GPHCM;No. BF2020-205-01). All participants signed informed consent forms.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325248

ABSTRACT

Currently, there is a rapidly increasing need for high-quality biomedical knowledge graphs (BioKG) that provide direct and precise biomedical knowledge. In the context of COVID-19, this issue is even more necessary to be highlighted. However, most BioKG construction inevitably includes numerous conflicts and noises deriving from incorrect knowledge descriptions in literature and defective information extraction techniques. Many studies have demonstrated that reasoning upon the knowledge graph is effective in eliminating such conflicts and noises. This paper proposes a method BioGRER to improve the BioKG's quality, which comprehensively combines the knowledge graph embedding and logic rules that support and negate triplets in the BioKG. In the proposed model, the BioKG refinement problem is formulated as the probability estimation for triplets in the BioKG. We employ the variational EM algorithm to optimize knowledge graph embedding and logic rule inference alternately. In this way, our model could combine efforts from both the knowledge graph embedding and logic rules, leading to better results than using them alone. We evaluate our model over a COVID-19 knowledge graph and obtain competitive results.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315491

ABSTRACT

Background: COVID-19 is a multi-systemic disease that is highly contagious and pathogenic. The long-term consequences of it are not yet clear, as is whether society and life can return to a healthy state. Long-term assessment of their health-related quality of life (HRQoL) is essential. This study aimed to investigate HRQoL and its risk factors in COVID-19 survivors at a follow-up of 6-month. Methods: A multicenter cross-sectional survey was conducted among 192 COVID-19 patients with confirmed age ≥ 18 years who were discharged from various hospitals in Wuhan from January to April 2020. The demographic characteristics, clinical characteristics, and laboratory results of the study subjects were obtained from the hospital's medical records. Survivors' HRQoL was assessed using the Short Form 36 (SF-36), cognition was assessed using the ascertain dementia eight-item informant questionnaire (AD8), and survivors' pulmonary function were examined. All participants in this study completed the survey and testing at Hubei Provincial Hospital of Chinese and Western Medicine. SF-36 scores were compared with the Chinese norm, and logistic regression and multivariate analysis were used to investigate the factors affecting HRQoL in COVID-19 survivors. Results: SF-36 showed significant differences in HRQoL between COVID-19 survivors and the general Chinese population ( P< 0.05).Multiple linear regression demonstrated that age was negatively correlated with physical functioning (PF), role-physical limitation (RP) and social functioning (SF) ( P <0.05). Bodily pain (BP), vitality (VT), SF and role-emotional limitation (RE) were negatively correlated with females ( P <0.05). Length from discharge to follow‐up was positively correlated with PF and RP ( P <0.05). Abnormal cognitive function was negatively correlated with PF, RP, general health (GH), VT, SF, RE and mental health (MH) ( P <0.05). Abnormal Carbon Monoxide Diffusing Capacity (DLCO%<80%) was significantly negatively correlated with PF and SF ( P <0.05).In addition, there was a significant negative correlation between Coronary heart disease and RP, GH, VT and RE ( P <0.05).Logistic regression analysis demonstrated that age(OR 1.032) and AD8 scores (OR 1.203)were risk factors associated with a low physical component summary (PCS) score. Length from discharge to follow‐up (OR 0.971) was the protective factor for PCS score. Abnormal cognitive function (OR 1.543) was a significant determinant associated with a mental component summary (MCS)<50 in COVID-19 patients. Conclusions: The HRQoL of COVID-19 survivors remains to be improved at six-month follow-up. Future studies should track HRQoL in older adults, women, patients with abnormal DLCO, and abnormal cognitive function for a long time and provide them with rehabilitation advice and guidance.

4.
Atmosphere ; 12(4):422, 2021.
Article in English | MDPI | ID: covidwho-1154281

ABSTRACT

The absence of motor vehicle traffic and suspended human activities during the COVID-19 lockdown period in China produced a unique experiment to assess the efficiency of air pollution mitigation. Herein, we synthetically analyzed monitoring data of atmospheric pollutants together with meteorological parameters to investigate the impact of human activity pattern changes on air quality in Guiyang, southwestern China. The results show that the Air Quality Index (AQI) during the lockdown period decreased by 7.4% and 23.48% compared to pre-lockdown levels and the identical lunar period during the past 3 years, respectively, which exhibited optimal air quality due to reduced emissions. The sharp decrease in NO2 concentration reduced the “titration” effect and elevated the O3 concentration by 31.94% during the lockdown period. Meteorological conditions significantly impacted air quality, and serious pollution events might also occur under emission reductions. Falling wind speeds and increasing relative humidity were the direct causes of the pollution event on February 1st. The “first rain” increases the hygroscopicity of atmospheric particulate matter and then elevate its concentration, while continuous rainfall significantly impacted the removal of atmospheric particulate matter. As impacted by the lockdown, the spatial distribution of the NO2 concentration sharply decreased on the whole, while the O3 concentration increased significantly. The implications of this study are as follows: Measures should be formulated to prevent O3 pollution when emission reduction measures are being adopted to improve air quality, and an emphasis should be placed on the impact of secondary aerosols formation by gas-particle conversion.

5.
China Tropical Medicine ; 20(12):1223-1226, 2020.
Article in Chinese | GIM | ID: covidwho-1116450

ABSTRACT

To investigate the early diagnosis and treatment of secondary tuberculosis complicated with COVID-19. The clinical manifestation, auxiliary examination, diagnosis and treatment of one case of secondary tuberculosis complicated with COVID-19 admitted to Wuhan Pulmonary Hospital were analyzed retrospectively. The patient had a clear history of COVID-19 exposure. The clinical manifestations were cough, expectoration, fever and gasp. Chest CT showed multiple patch, nodule, spot, strip and cavity shadow in two lungs. COVID-19 was diagnosed as early as possible by detection of SARS-CoV-2 nucleic acid in respiratory specimens. After reasonable anti-tuberculosis combined with antiviral treatment, the detection of SARS-CoV-2 nucleic acid in respiratory specimens and acid-fast bacilli smear of sputum specimens turned negative, the symptoms were relieved and discharged. In the epidemic period of COVID-19, we should pay attention to the identification of secondary pulmonary tuberculosis with COVID-19, the formulation of drug programs for the treatment of two diseases, and avoid the use of rifampicin, a liver drug enzyme inducer, so as to avoid missed treatment due to the weakened efficacy of lopinavir/ritonavir and abidol, etc.

6.
Preprint in English | bioRxiv | ID: ppbiorxiv-433503

ABSTRACT

The recent COVID-19 pandemic poses a global health emergency. Cellular entry of the causative agent SARS-CoV-2 is mediated by its spike protein interacting with cellular receptor- human angiotensin converting enzyme 2 (ACE2). Here, we used lentivirus based pseudotypes bearing spike protein to demonstrate that entry of SARS-CoV-2 into host cells is dependent on clathrin-mediated endocytosis, and phosphoinositides play essential role during this process. In addition, we showed that the intracellular domain and the catalytic activity of ACE2 is not required for efficient virus entry. These results provide new insights into SARS-CoV-2 cellular entry and present potential targets for drug development.

8.
chemRxiv; 2020.
Preprint | ChemRxiv | ID: ppcovidwho-471

ABSTRACT

The pandemic caused by the novel coronavirus SARS-CoV-2 is rapidly spreading and infecting the population on the global scale, it is a global health threat due to its high infection rate, high mortality and the lack of clinically approved drugs and vaccines for treating the disease (COVID-19). Utilising the published structures and homologue remodelling for proteins from SARS-CoV-2, an in silico molecular docking based screening was conducted and deposited in the Shennong project database. The results from the screening could be used to explain the clinical observation of repurposing the Ritonavir and Lopinavir to treat patients in the early stage of COVID-19 infection, and the prescription of Remdisivir in the United States as the therapy. Additionally, this molecular docking identified natural compound candidates for drug repurposing. This in silico molecular docking screen may be used for the initatial evaluation and rationalisation for drug repurposing of other potential candidates, especially other natural compounds from traditional Chinese medicines.

9.
chemRxiv; 2020.
Preprint | ChemRxiv | ID: ppcovidwho-168

ABSTRACT

The spreading COVID-19 pandemic has brought the world to a halt in 2020. One of the major challenges is the lack of effective antiviral drugs. Drug and vaccine development typically takes years;a practical approach to formulate knowledge-based prescriptions is to conduct in silico screening for drugs and compounds that has the potential to disrupt viral protein functions. By evaluating the dataset from the “Shennong project”, an in silico screening of the DrugBank library against SARS-CoV-2 proteins, we identified chlorogenic acid and rutin displayed a strong affinity with diverse viral proteins. Chlorogenic acid is naturally present in coffee in large quantity, and rutin is available as nutraceutical products, both compounds are considered safe to consume, hence could potentially aid the recovery or treatment for COVID-19 patients at low health risk. We emphasise that the results require further clinical clarification, the impact of this work shall be examined by professionals carefully.

10.
chemRxiv; 2020.
Preprint | ChemRxiv | ID: ppcovidwho-84

ABSTRACT

The emergence of the new coronavirus (nCoV-19) has brought global impact on human health, whilst the interaction between the virus and the host is the foundation of the disease. The viral genome codes a cluster of proteins, each with a unique function in the event of host invasion or viral development. Under current adverse situation, we employ virtual screening tools in searching for drugs and nature products which have been already deposited in the DrugBank in attempt to accelerate the drug discovery process. This study provides an initial evaluation of current drug candidates from various reports using our systemic in silico drug screening based on structures of viral proteins and human ACE2 receptor. Besides, we built an interactive online platform ( a href="https://shennongproject.com:11443/#/home" https://shennongproject.com:11443/#/home /a ) for browsing these results with the visual display of small molecule docked on its potential target protein, without installing any specialized structural software. With continuous maintenance and incorporation of data from laboratory works, it may serve not only as the assessment tool for the new drug discovery but also an educational website to meet general interest from the public.

11.
Preprint in English | medRxiv | ID: ppmedrxiv-20187187

ABSTRACT

ObjectivesTo systematically analyze the chest CT imaging features of children with COVID-19 and provide references for clinical practice. MethodsWe searched PubMed, Web of Science, and Embase; data published by Johns Hopkins University; and Chinese databases CNKI, Wanfang, and Chongqing Weipu. Reports on chest CT imaging features of children with COVID-19 from January 1, 2020, to August 10, 2020, were analyzed retrospectively and a meta-analysis carried out using Stata12.0 software. ResultsThirty-seven articles (1747 children) were included in this study. The overall rate of abnormal lung CT findings was 63.2% (95% confidence interval [CI]: 55.8-70.6%), with a rate of 61.0% (95% CI: 50.8-71.2%) in China and 67.8% (95% CI: 57.1-78.4%) in the rest of the world in the subgroup analysis. The incidence of ground-glass opacities was 39.5% (95% CI: 30.7-48.3%), multiple lung lobe lesions 65.1% (95% CI: 55.1-67.9%), and bilateral lung lesions 61.5% (95% CI: 58.8-72.2%). Other imaging features included nodules (25.7%), patchy shadows (36.8%), halo sign(24.8%), consolidation (24.1%), air bronchogram signs (11.2%), cord-like shadows (9.7%), crazy-paving pattern (6.1%), and pleural effusion (9.1%). Two articles reported three cases of white lung, another reported two cases of pneumothorax, and another one case of bullae. CONCLUSIONThe lung CT results of children with COVID-19 are usually normal or slightly atypica, with a low sensitivity and specificity compared with that in adults. The lung lesions of COVID-19 pediatric patients mostly involve both lungs or multiple lobes, and the common manifestations are patchy shadows, ground-glass opacities, consolidation, partial air bronchogram signs, nodules, and halo signs; white lung, pleural effusion, and paving stone signs are rare. CLINICAL IMPACTTherefore, chest CT has limited value as a screening tool for children with COVID-19 and can only be used as an auxiliary assessment tool. RegistrationThis systematic review and meta-analysis was registered in the Prospero International Prospective Register of Systemic Reviews (CRD42020196602). Strengths and limitations of this studyThe lung CT findings of children with COVID-19 are usually normal or slightly atypical, with a low sensitivity and specificity compared with that in adults. From a systematic review of current literature, the overall rate of abnormal lung CT findings in children was revealed to be 63.2%. Chest CT has limited value as a screening tool for children with COVID-19 and can only be used as an auxiliary assessment tool. The sample size of some included studies is small, which may affect the results.

12.
Chinese Journal of Endocrinology and Metabolism ; (12): E003-E003, 2020.
Article in Chinese | WPRIM (Western Pacific), WPRIM (Western Pacific) | ID: covidwho-60176

ABSTRACT

A major infectious disease associated with severe acute respiratory syndrome coronavirus 2 (2019-nCoV)has emerged in Wuhan, China. Current clinical studies have shown that diabetes is commonly complicated with this disorder. Hyperglycemia is a risk factor for severe infection, and also an independent risk factor for the progression of mild infection to severe infection. This may be related to the immune deficiency of diabetics. Besides, virus may cause direct damage to the islets and induce acute stress hyperglycemia. Special attention should be payed to diabetics with 2019-nCoV infection. Systemic steroid hormones should be used with particular caution in patients with 2019-nCoV infection, especially those with diabetes.

13.
Preprint in English | bioRxiv | ID: ppbiorxiv-019075

ABSTRACT

The 2019 novel coronavirus, SARS-CoV-2, is a pathogen of critical significance to international public health. Knowledge of the interplay between molecular-scale virus-receptor interactions, single-cell viral replication, intracellular-scale viral transport, and emergent tissue-scale viral propagation is limited. Moreover, little is known about immune system-virus-tissue interactions and how these can result in low-level (asymptomatic) infections in some cases and acute respiratory distress syndrome (ARDS) in others, particularly with respect to presentation in different age groups or pre-existing inflammatory risk factors. Given the nonlinear interactions within and among each of these processes, multiscale simulation models can shed light on the emergent dynamics that lead to divergent outcomes, identify actionable "choke points" for pharmacologic interventions, screen potential therapies, and identify potential biomarkers that differentiate patient outcomes. Given the complexity of the problem and the acute need for an actionable model to guide therapy discovery and optimization, we introduce and iteratively refine a prototype of a multiscale model of SARS-CoV-2 dynamics in lung tissue. The first prototype model was built and shared internationally as open source code and an online interactive model in under 12 hours, and community domain expertise is driving regular refinements. In a sustained community effort, this consortium is integrating data and expertise across virology, immunology, mathematical biology, quantitative systems physiology, cloud and high performance computing, and other domains to accelerate our response to this critical threat to international health. More broadly, this effort is creating a reusable, modular framework for studying viral replication and immune response in tissues, which can also potentially be adapted to related problems in immunology and immunotherapy.

14.
Preprint in English | medRxiv | ID: ppmedrxiv-20044768

ABSTRACT

BackgroundCOVID-19 has been widely spreading. We aim to examine adaptive immune cells in non-severe patients with persistent SARS-CoV-2 shedding. Methods37 non-severe patients with persistent SARS-CoV-2 presence transferred to Zhongnan hospital of Wuhan University were retrospectively recruited to PP (persistently positive) group, which was further allocated to PPP group (n=19) and PPN group (n=18), according to their testing results after 7 days (N=negative). Epidemiological, demographic, clinical and laboratory data were collected and analyzed. Data from age- and sex-matched non-severe patients at disease onset (PA [positive on admission] patients, n=37), and lymphocyte subpopulation measurements from matched 54 healthy subjects were extracted for comparison. ResultsCompared with PA patients, PP patients had much improved laboratory findings, including WBCs, neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, albumin, AST, CRP, SAA, and IL-6. The absolute numbers of CD3+ T cells, CD4+ T cells, and NK cells were significantly higher in PP group than that in PA group, and were comparable to that in healthy controls. PPP subgroup had markedly reduced B cells and T cells compared to PPN group and healthy subjects. Finally, paired results of these lymphocyte subpopulations from 10 PPN patients demonstrated that the number of T cells and B cells significantly increased when the SARS-CoV-2 tests turned negative. ConclusionPersistent SARS-CoV-2 presence in non-severe COVID-19 patients is associated with reduced numbers of adaptive immune cells. Monitoring lymphocyte subpopulations could be clinically meaningful in identifying fully recovered COVID-19 patients. SummaryDefects in adaptive immune system, including reduced T cells and B cells, were frequently observed in non-severe COVID-19 patients with persistent SARS-CoV-2 shedding. Assessment of immune system could be clinically relevant for discharge management.

15.
Preprint in English | medRxiv | ID: ppmedrxiv-20027524

ABSTRACT

ObjectiveTo compare the sex differences in the clinical findings among patients with severe coronavirus disease 2019 (COVID-19). MethodsWe retrospectively collected data of 47 patients diagnosed as severe type of COVID-19 from February 8 to 22, 2020, including demographics, illness history, physical examination, laboratory test, management, and compared differences between men and women. ResultsOf the 47 patients, 28 (59.6%) were men. The median age was 62 years, and 30 (63.8%) had comorbidities. The initial symptoms were mainly fever (34 [72.3%]), cough (36 [76.6%]), myalgia (5 [10.6%]) and fatigue (7 [14.9%]). Procalcitonin level was higher in men than in women (0.08 vs. 0.04ng/ml, p=0.002). N-terminal-pro brain natriuretic peptide increased in 16 (57.1%) men and 5 (26.3%) women (p=0.037). Five men (17.9%) had detected positive influenza A antibody, but no women. During 2-week admission, 5 (17.9%) men and 1 (5.3%) woman were reclassified into the critical type due to deterioration. Mortality was 3.6% in men and 0 in women respectively. Four (21.1%) women and one man (3.6%) recovered and discharged from hospital. ConclusionSex differences may exist in COVID-19 patients of severe type. Men are likely to have more complicated clinical condition and worse in-hospital outcomes as compared to women.

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