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1.
J Infect Dis ; 224(9): 1473-1488, 2021 11 16.
Article in English | MEDLINE | ID: covidwho-1522215

ABSTRACT

BACKGROUND: Postdischarge immunity and its correlation with clinical features among patients recovered from coronavirus disease 2019(COVID-19) are poorly described. This prospective cross-sectional study explored the inflammatory profiles and clinical recovery of patients with COVID-19 at 3 months after hospital discharge. METHODS: Patients with COVID-19 discharged from 4 hospitals in Wuhan, recovered asymptomatic patients (APs) from an isolation hotel, and uninfected healthy controls (HCs) were recruited. Viral nucleic acid and antibody detection, laboratory examination, computed tomography, pulmonary function assessment, multiplex cytokine assay, and flow cytometry were performed. RESULTS: The72 age-, sex- and body mass index-matched participants included 19 patients with severe/critical COVID-19 (SPs), 20 patients with mild/moderate COVID-19 (MPs), 16 APs, and 17 HCs. At 3 months after discharge, levels of proinflammatory cytokines and factors related to vascular injury/repair in patients recovered from COVID-19 had not returned to those of the HCs, especially among recovered SPs compared with recovered MPs and APs. These cytokines were significantly correlated with impaired pulmonary function and chest computed tomographic abnormalities. However, levels of immune cells had returned to nearly normal levels and were not significantly correlated with abnormal clinical features. CONCLUSION: Vascular injury, inflammation, and chemotaxis persisted in patients with COVID-19 and were correlated with abnormal clinical features 3 months after discharge, especially in recovered SPs.

2.
Travel medicine and infectious disease ; 2021.
Article in English | EuropePMC | ID: covidwho-1505425

ABSTRACT

Introduction With the accumulating evidence of ocular manifestations of the 2019 novel coronavirus disease (COVID-19), the study aimed to systematically summarize ocular manifestations in COVID-19 patients. Methods The PubMed, EMBASE, Web of Science databases were searched from through June 2021. Studies that provided clinical characteristics and outcomes and reported on ocular manifestations or conjunctival swab RT-PCR tests among COVID-19 patients were included. Results A total of 30 studies involving 5,717 patients were identified. Ocular manifestations including conjunctival hyperemia (7.6%, 95%confidence interval [CI] 1.8%–8.9%), conjunctival discharge (4.8%, 95% CI 1.8%–8.9%), epiphora (6.9%, 95% CI 2.8%–12.8%), and foreign body sensation (6.9%, 95% CI 2.4%–13.0%) were observed. The positive rate of conjunctival swab tests was 3.9% (95% CI 0.2%–6.4%). Severe cases of COVID-19 were associated with an increased risk of developing ocular complications (odds ratio [OR] = 2.77, 95% CI 1.75 to 4.40). Conclusions Despite their relatively low incidence rate in COVID-19 patients, ocular manifestations may be non-specific and present as the initial symptoms of infection. The presence of SARS-CoV-2 in conjunctival swabs implicates it as a potential source of infection. Early diagnosis and proper eye protection would help prevent viral transmission.

3.
Nat Commun ; 12(1): 6304, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1500462

ABSTRACT

Accumulating mutations in the SARS-CoV-2 Spike (S) protein can increase the possibility of immune escape, challenging the present COVID-19 prophylaxis and clinical interventions. Here, 3 receptor binding domain (RBD) specific monoclonal antibodies (mAbs), 58G6, 510A5 and 13G9, with high neutralizing potency blocking authentic SARS-CoV-2 virus display remarkable efficacy against authentic B.1.351 virus. Surprisingly, structural analysis has revealed that 58G6 and 13G9 both recognize the steric region S470-495 on the RBD, overlapping the E484K mutation presented in B.1.351. Also, 58G6 directly binds to another region S450-458 in the RBD. Significantly, 58G6 and 510A5 both demonstrate prophylactic efficacy against authentic SARS-CoV-2 and B.1.351 viruses in the transgenic mice expressing human ACE2 (hACE2), protecting weight loss and reducing virus loads. Together, we have evidenced 2 potent neutralizing Abs with unique mechanism targeting authentic SARS-CoV-2 mutants, which can be promising candidates to fulfill the urgent needs for the prolonged COVID-19 pandemic.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Animals , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/administration & dosage , Antibodies, Neutralizing/chemistry , Antibodies, Viral/administration & dosage , Antibodies, Viral/chemistry , Binding Sites , COVID-19/pathology , COVID-19/virology , Epitopes , Humans , Mice , Mice, Transgenic , Mutation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Viral Load/drug effects , Weight Loss/drug effects
8.
Commun Biol ; 4(1): 1034, 2021 08 31.
Article in English | MEDLINE | ID: covidwho-1380915

ABSTRACT

COVID-19 has caused numerous infections with diverse clinical symptoms. To identify human genetic variants contributing to the clinical development of COVID-19, we genotyped 1457 (598/859 with severe/mild symptoms) and sequenced 1141 (severe/mild: 474/667) patients of Chinese ancestry. We further incorporated 1401 genotyped and 948 sequenced ancestry-matched population controls, and tested genome-wide association on 1072 severe cases versus 3875 mild or population controls, followed by trans-ethnic meta-analysis with summary statistics of 3199 hospitalized cases and 897,488 population controls from the COVID-19 Host Genetics Initiative. We identified three significant signals outside the well-established 3p21.31 locus: an intronic variant in FOXP4-AS1 (rs1853837, odds ratio OR = 1.28, P = 2.51 × 10-10, allele frequencies in Chinese/European AF = 0.345/0.105), a frameshift insertion in ABO (rs8176719, OR = 1.19, P = 8.98 × 10-9, AF = 0.422/0.395) and a Chinese-specific intronic variant in MEF2B (rs74490654, OR = 8.73, P = 1.22 × 10-8, AF = 0.004/0). These findings highlight an important role of the adaptive immunity and the ABO blood-group system in protection from developing severe COVID-19.


Subject(s)
COVID-19/ethnology , COVID-19/genetics , Ethnic Groups/genetics , Genome-Wide Association Study , Genetic Predisposition to Disease/genetics , Humans , Introns/genetics , Polymorphism, Single Nucleotide
9.
Int J Environ Res Public Health ; 18(7)2021 04 01.
Article in English | MEDLINE | ID: covidwho-1378281

ABSTRACT

Farmers experience a high risk of stress, depression, and suicide. Risk factors are well documented but protective factors are seldom examined. Social support has been reported to reduce psychological distress among the general population but its effect on farmers is inconclusive. Agricultural cooperatives are typically created and owned by farmers to secure markets, access supplies and services, and participate in decision-making. It is unknown whether having cooperative resources impacts symptoms of depression. A survey was used to examine whether having access to cooperative programs and social support impacted symptoms of depression among dairy farmers. Farm bankruptcies, stress, depression, and suicide were identified as ongoing concerns. Having social support and cooperative educational opportunities and mentorship programs were associated with decreased symptoms of depression. Conversely, having cooperative policy discussions was associated with increased symptoms of depression. Results suggest that social support can potentially reduce symptoms of depression among farmers and having access to cooperative resources can reduce or increase it, depending on the type of program. Our findings identified an opportunity to further examine how programs provided by farmer-led organizations such as cooperatives can impact stress, depression, and suicide among farmers.


Subject(s)
Farmers , Suicide , Agriculture , Depression/epidemiology , Farms , Humans
11.
J Cancer ; 12(12): 3558-3565, 2021.
Article in English | MEDLINE | ID: covidwho-1355160

ABSTRACT

Purpose: Data are extremely limited with regards to the impact of COVID-19 on cancer patients. Our study explored the distinct clinical features of COVID-19 patients with cancer. Experimental Design: 189 COVID-19 patients, including 16 cancer patients and 173 patients without cancer, were recruited. Propensity score 1:4 matching (PSM) was performed between cancer patients and patients without cancer based on age, gender and comorbidities. Survival was calculated by the Kaplan-Meier method and the difference was compared by the log-rank test. Results: PSM analysis yielded 16 cancer patients and 64 propensity score-matched patients without cancer. Compared to patients without cancer, cancer patients tended to have leukopenia and elevated high-sensitivity C-reactive protein (hs-CRP) and procalcitonin. For those with critical COVID-19, cancer patients had an inferior survival than those without cancer. Also, cancer patients with severe/critical COVID-19 tended to be male and present with low SPO2 and albumin, and high hs-CRP, lactate dehydrogenase and blood urea nitrogen on admission compared to those with mild COVID-19. In terms of risk factors, recent cancer diagnosis (within 1 year of onset of COVID-19) and anti-tumor treatment within 3 months of COVID-19 diagnosis were associated with inferior survival. Conclusions: We found COVID-19 patients with cancer have distinct clinical features as compared to patients without cancer. Importantly, cancer patients with critical COVID-19 were found to have poorer outcomes compared to those without cancer. In the cancer cohort, patients with severe/critical COVID-19 presented with a distinct clinical profile from those with mild COVID-19; short cancer history and recent anti-cancer treatment were associated with inferior survival.

13.
Clin Infect Dis ; 73(3): e531-e539, 2021 08 02.
Article in English | MEDLINE | ID: covidwho-1338662

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic with no licensed vaccine or specific antiviral agents for therapy. Little is known about the longitudinal dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific neutralizing antibodies (NAbs) in patients with COVID-19. METHODS: Blood samples (n = 173) were collected from 30 patients with COVID-19 over a 3-month period after symptom onset and analyzed for SARS-CoV-2-specific NAbs using the lentiviral pseudotype assay, coincident with the levels of IgG and proinflammatory cytokines. RESULTS: SARS-CoV-2-specific NAb titers were low for the first 7-10 days after symptom onset and increased after 2-3 weeks. The median peak time for NAbs was 33 days (interquartile range [IQR], 24-59 days) after symptom onset. NAb titers in 93.3% (28/30) of the patients declined gradually over the 3-month study period, with a median decrease of 34.8% (IQR, 19.6-42.4%). NAb titers increased over time in parallel with the rise in immunoglobulin G (IgG) antibody levels, correlating well at week 3 (r = 0.41, P < .05). The NAb titers also demonstrated a significant positive correlation with levels of plasma proinflammatory cytokines, including stem cell factor (SCF), TNF-related apoptosis-inducing ligand (TRAIL), and macrophage colony-stimulating factor (M-CSF). CONCLUSIONS: These data provide useful information regarding dynamic changes in NAbs in patients with COVID-19 during the acute and convalescent phases.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , Humans , Pandemics
14.
Transbound Emerg Dis ; 2021 Jul 28.
Article in English | MEDLINE | ID: covidwho-1329028

ABSTRACT

Existing models about the dynamics of COVID-19 transmission often assume the mechanism of virus transmission and the form of the differential equations. These assumptions are hard to verify. Due to the biases of country-level data, it is inaccurate to construct the global dynamic of COVID-19. This research aims to provide a robust data-driven global model of the transmission dynamics. We apply sparse identification of nonlinear dynamics (SINDy) to model the dynamics of COVID-19 global transmission. One advantage is that we can discover the nonlinear dynamics from data without assumptions in the form of the governing equations. To overcome the problem of biased country-level data on the number of reported cases, we propose a robust global model of the dynamics by using maximin aggregation. Real data analysis shows the efficiency of our model.

15.
Cont Lens Anterior Eye ; : 101474, 2021 Jul 20.
Article in English | MEDLINE | ID: covidwho-1322031

ABSTRACT

PURPOSE: To construct a machine learning (ML)-based model for estimating the alignment curve (AC) curvature in orthokeratology lens fitting for vision shaping treatment (VST), which can minimize the number of lens trials, improving efficiency while maintaining accuracy, with regards to its improvement over a previous calculation method. METHODS: Data were retrospectively collected from the clinical case files of 1271 myopic subjects (1271 right eyes). The AC curvatures calculated with a previously published algorithm were used as the target data sets. Four kinds of machine learning algorithms were implemented in the experimental analyses to predict the targeted AC curvatures: robust linear regression models, support vector machine (SVM) regression models with linear kernel functions, bagging decision trees, and Gaussian processes. The previously published calculation method and the novel machine learning method were then compared to assess the final parameters of ordered lenses. RESULTS: The linear SVM and Gaussian process machine learning models achieved the best performance. The input variables included sex, age, horizontal visible iris diameter (HVID), spherical refraction (SER), cylindrical refraction, eccentricity value (e value), flat K (K1) and steep K (K2) readings, anterior chamber depth (ACD), and axial length (AL). The R-squared values for the output AC1K1, AC1K2 and AC2K1 values were 0.91, 0.84, and 0.73, respectively. The previous calculation method and machine learning methods displayed excellent consistency, and the proposed methods performed best based on flat K reading and e values. CONCLUSIONS: The ML model can provide practitioners with an efficient method for estimating the AC curvatures of VST lenses and reducing the probability of cross-infection originating from trial lenses, which is especially useful during pandemics, such as that for COVID-19.

16.
Front Med (Lausanne) ; 8: 682087, 2021.
Article in English | MEDLINE | ID: covidwho-1305655

ABSTRACT

Background and Objectives: To investigate whether coronavirus disease 2019 (COVID-19) survivors who had different disease severities have different levels of pulmonary sequelae at 3 months post-discharge. Methods: COVID-19 patients discharged from four hospitals 3 months previously, recovered asymptomatic patients from an isolation hotel, and uninfected healthy controls (HCs) from the community were prospectively recruited. Participants were recruited at Wuhan Union Hospital and underwent examinations, including quality-of-life evaluation (St. George Respiratory Questionnaire [SGRQ]), laboratory examination, chest computed tomography (CT) imaging, and pulmonary function tests. Results: A total of 216 participants were recruited, including 95 patients who had recovered from severe/critical COVID-19 (SPs), 51 who had recovered from mild/moderate disease (MPs), 28 who had recovered from asymptomatic disease (APs), and 42 HCs. In total, 154 out of 174 (88.5%) recovered COVID-19 patients tested positive for serum SARS-COV-2 IgG, but only 19 (10.9%) were still positive for IgM. The SGRQ scores were highest in the SPs, while APs had slightly higher SGRQ scores than those of HCs; 85.1% of SPs and 68.0% of MPs still had residual CT abnormalities, mainly ground-glass opacity (GGO) followed by strip-like fibrosis at 3 months after discharge, but the pneumonic lesions were largely absorbed in the recovered SPs or MPs relative to findings in the acute phase. Pulmonary function showed that the frequency of lung diffusion capacity for carbon monoxide abnormalities were comparable in SPs and MPs (47.1 vs. 41.7%), while abnormal total lung capacity (TLC) and residual volume (RV) were more frequent in SPs than in MPs (TLC, 18.8 vs. 8.3%; RV, 11.8 vs. 0%). Conclusions: Pulmonary abnormalities remained after recovery from COVID-19 and were more frequent and conspicuous in SPs at 3 months after discharge.

18.
Front Genet ; 12: 647303, 2021.
Article in English | MEDLINE | ID: covidwho-1268246

ABSTRACT

The pandemic of Coronavirus disease 2019 (COVID-19) has posed an enormous threat to human health. According to observational studies, abnormal liver and kidney functions and blood cell traits were associated with severe COVID-19, yet the causal risk factors for COVID-19 severity and the underlying mechanism remained elusive. We performed Mendelian randomization analyses to assess the potential causal role of eight liver function biomarkers, one kidney function biomarker, and 14 hematological traits on COVID-19 severity using genetic association summary statistics from Europeans. Our findings showed that albumin, direct bilirubin, white blood cell count, neutrophil count, lymphocyte count, and mean corpuscular hemoglobin are casually associated with the risk of severe COVID-19. Notably, lymphocyte count and mean corpuscular hemoglobin had an independent effect on severe COVID-19 risk. These causal evidences provide insights into directions for the risk stratification of individuals with abnormal liver function or blood cell indices and motivate more studies to unveil the roles of these abnormalities in COVID-19 pathogenesis.

19.
Front Med (Lausanne) ; 8: 626384, 2021.
Article in English | MEDLINE | ID: covidwho-1263009

ABSTRACT

Objective: We aimed to explore the dynamic changes in coagulation function and the effect of age on coagulation function in patients with pneumonia under admission and non-admission treatment. Methods: We included 178 confirmed adult inpatients with COVID-19 from Wuhan Union Hospital Affiliated to Huazhong University of Science and Technology (Wuhan, China). Patients were classified into common types, and all were cured and discharged after hospitalization. We recorded the time of the first clinical symptoms of the patients and performed blood coagulation tests at the time of admission and after admission. In total, eight factors (TT, FIB, INR, APTT, PT, DD, ATIII, and FDP) were analyzed. Patients were classified into four groups according to the time from the first symptom onset to hospital admission for comparative analysis. The patients who were admitted within 2 weeks of disease onset were analyzed for the dynamic changes in their blood coagulation tests. Further division into two groups, one group comprising patients admitted to the hospital within 2 weeks after the onset of disease and the other comprising patients admitted to the hospital 2 weeks after disease onset, was performed to form two groups based on whether the patient ages were over or under 55 years. Chi-square tests and T tests were used to explore the dynamic changes in coagulation function and the influence of age on the results of coagulation function tests. Results: A total of 178 inpatients, 34 of whom underwent dynamic detection, were included in this analysis. We divided these patients into four groups according to the interval between the onset of COVID-19 pneumonia and the time to admission in the hospital: the 1-7 days (group 1), 8-14 days (group 2), 15-21 days (group 3), and >21-days (group 4). Eight factors all increased within 2 weeks after onset and gradually decreased to normal 2 weeks before the patient was admitted. The changes in coagulation function of patients admitted to the hospital were similar. After being admitted to the hospital, the most significant decreases among the eight factors were between week 2 and 3. There were distinct differences among the eight factors between people older than 55 years and those younger than 55 years. In the first 2 weeks after being admitted, the levels of the eight factors in patients >55 years were significantly higher than those in patients <55 years, and after another 2 weeks of treatment, the factor levels in both age groups returned to normal. Conclusion: The eight factors all increased within 2 weeks after onset and gradually decreased to normal after 2 weeks regardless of treatment. Compared with patients younger than 55 years, patients older than 55 years have greater changes in their blood coagulation test values.

20.
Science ; 371(6536): 1374-1378, 2021 03 26.
Article in English | MEDLINE | ID: covidwho-1255508

ABSTRACT

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continually poses serious threats to global public health. The main protease (Mpro) of SARS-CoV-2 plays a central role in viral replication. We designed and synthesized 32 new bicycloproline-containing Mpro inhibitors derived from either boceprevir or telaprevir, both of which are approved antivirals. All compounds inhibited SARS-CoV-2 Mpro activity in vitro, with 50% inhibitory concentration values ranging from 7.6 to 748.5 nM. The cocrystal structure of Mpro in complex with MI-23, one of the most potent compounds, revealed its interaction mode. Two compounds (MI-09 and MI-30) showed excellent antiviral activity in cell-based assays. In a transgenic mouse model of SARS-CoV-2 infection, oral or intraperitoneal treatment with MI-09 or MI-30 significantly reduced lung viral loads and lung lesions. Both also displayed good pharmacokinetic properties and safety in rats.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Coronavirus 3C Proteases/antagonists & inhibitors , Protease Inhibitors/pharmacology , Animals , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , COVID-19/pathology , COVID-19/virology , Cell Line , Cell Survival/drug effects , Chemokine CXCL10/metabolism , Disease Models, Animal , Drug Design , Humans , Interferon-beta/metabolism , Lung/immunology , Lung/pathology , Lung/virology , Mice , Mice, Transgenic , Oligopeptides , Proline/analogs & derivatives , Protease Inhibitors/chemistry , Protease Inhibitors/therapeutic use , Protease Inhibitors/toxicity , Rats , Rats, Sprague-Dawley , Viral Load/drug effects , Virus Replication
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