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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-317000

ABSTRACT

Fact checking by professionals is viewed as a vital defense in the fight against misinformation.While fact checking is important and its impact has been significant, fact checks could have limited visibility and may not reach the intended audience, such as those deeply embedded in polarized communities. Concerned citizens (i.e., the crowd), who are users of the platforms where misinformation appears, can play a crucial role in disseminating fact-checking information and in countering the spread of misinformation. To explore if this is the case, we conduct a data-driven study of misinformation on the Twitter platform, focusing on tweets related to the COVID-19 pandemic, analyzing the spread of misinformation, professional fact checks, and the crowd response to popular misleading claims about COVID-19. In this work, we curate a dataset of false claims and statements that seek to challenge or refute them. We train a classifier to create a novel dataset of 155,468 COVID-19-related tweets, containing 33,237 false claims and 33,413 refuting arguments.Our findings show that professional fact-checking tweets have limited volume and reach. In contrast, we observe that the surge in misinformation tweets results in a quick response and a corresponding increase in tweets that refute such misinformation. More importantly, we find contrasting differences in the way the crowd refutes tweets, some tweets appear to be opinions, while others contain concrete evidence, such as a link to a reputed source. Our work provides insights into how misinformation is organically countered in social platforms by some of their users and the role they play in amplifying professional fact checks.These insights could lead to development of tools and mechanisms that can empower concerned citizens in combating misinformation. The code and data can be found in http://claws.cc.gatech.edu/covid_counter_misinformation.html.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315256

ABSTRACT

Background: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has subsequently spread worldwide. The number of death has increased rapidly. However, the possible risk factors that lead to death in critical inpatients with coronavirus disease 2019 (COVID-19) are not yet fully known. This study was to explore the risk factors for mortality of critical inpatients with COVID-19. Methods In this single-centered, retrospective study, we enrolled 113 critical patients with COVID-19 in Renmin Hospital of Wuhan University between Feb 1, 2020 and Mar 15, 2020. Data were collected using a standard method including clinical records and laboratory findings. Outcomes of survivors and death were compared. Results A total of 113 critical patients (from 29 to 95 years) with COVID-19 were recruited, 50 (44.25%) died and 63 recovered (55.75%). The proportion of patients with ventricular arrhythmia was higher in the death group than the recovery group (24.0% vs 4.4%;p = 0.021), and was higher among myocardial damage cases than non-myocardial damage cases (26.1% vs 4.3%;p = 0.013). Multivariate analysis confirmed four independent predictors related to mortality of COVID-19: age > 70 yrs (HR 1.84, 95% CI 1.03–3.28), initial neutrophil count more than 6.5 × 10 9 /L (HR 3.43, 95% CI 1.84–6.40), C-reactive protein greater more than 100 mg/L (HR 1.93, 95% CI 1.04–3.59), and lactate dehydrogenase more than 300 U/L (HR 2.90, 95% CI 1.26–6.67). Immunoglobulin treatment (HR 0.39, 95% CI 0.21–0.73) can reduce the risk of death. There was no significant difference in the QT interval between patients with and without hydroxychloroquine treatment. Conclusions Old age (> 70 years), neutrophilia, C-reactive protein greater more than 100 mg/L and lactate dehydrogenase more than 300 U/L are high-risk factors for mortality of critical patients with COVID-19. The incidence of ventricular arrhythmia was higher in deceased patients than survivors.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-312174

ABSTRACT

The aerosol formation is associated with the rupture of the liquid plug during the pulmonary airway reopening. The fluid dynamics of this process is difficult to predict because the rupture involved complex liquid-gas transition. Equation of state (EOS) plays a key role in the thermodynamic process of liquid-gas transition. Here, we propose an EOS-based multiphase lattice Boltzmann model, in which the nonideal force is directly evaluated by EOSs. This multiphase model is used to model the pulmonary airway reopening and study aerosol formation during exhalation. The numerical model is first validated with the simulations of Fujioka et al.(2008). and the result is in reasonable agreement with their study. Furthermore, two rupture cases with and without aerosol formation are contrasted and analyzed. It is found that the injury on the epithelium in the case with aerosol formation is essentially the same that of without aerosol formation even while the pressure drop in airway increases by about 67%. Then extensive simulations are performed to investigate the effects of pressure drop, thickness of liquid plug and film on aerosol size and the mechanical stresses. The results show that aerosol size and the mechanical stresses increase as the pressure drop enlarges and thickness of liquid plug become thicken, while aerosol size and the mechanical stresses decrease as thickness of liquid film is thicken. The present multiphase model can be extended to study the generation and transmission of bioaerosols which can carry the bioparticles of influenza or coronavirus.

4.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-326028

ABSTRACT

Intercellular heterogeneity is a major obstacle to successful precision medicine. Single-cell RNA sequencing (scRNA-seq) technology has enabled in-depth analysis of intercellular heterogeneity in various diseases. However, its full potentials for precision medicine are yet to be reached. Towards this, we propose A Single-cell Guided pipeline to Aid Repurposing of Drugs (ASGARD). To precisely address the intercellular heterogeneity within each patient, ASGARD defines a novel drug score predicting drugs for multiple cell clusters. We tested ASGARD on three independent datasets, including advanced metastatic breast cancer, acute lymphoblastic leukemia, and coronavirus disease 2019 (COVID-19). On single-drug therapy, ASGARD shows significantly better average accuracy (AUC=0.95) compared to two other single-cell pipelines (AUC 0.69 and 0.57) and two other bulk-cell-based drug repurposing methods (AUC 0.80 and 0.75). The top-ranked drugs, such as fulvestrant and neratinib for breast cancer, tretinoin and vorinostat for leukemia, and enalapril for severe COVID19, are either approved by FDA or in clinical trials treating corresponding diseases. In conclusion, ASGARD is a promising pipeline guided by single-cell RNA-seq data, for repurposing drugs towards precision medicine. ASGARD is free for academic use at https://github.com/lanagarmire/ASGARD.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325462

ABSTRACT

The spread of COVID-19 has sparked racism, hate, and xenophobia in social media targeted at Chinese and broader Asian communities. However, little is known about how racial hate spreads during a pandemic and the role of counterhate speech in mitigating the spread. Here we study the evolution and spread of anti-Asian hate speech through the lens of Twitter. We create COVID-HATE, the largest dataset of anti-Asian hate and counterhate spanning three months, containing over 30 million tweets, and a social network with over 87 million nodes. By creating a novel hand-labeled dataset of 2,400 tweets, we train a text classifier to identify hate and counterhate tweets that achieves an average AUROC of 0.852. We identify 891,204 hate and 200,198 counterhate tweets in COVID-HATE. Using this data to conduct longitudinal analysis, we find that while hateful users are less engaged in the COVID-19 discussions prior to their first anti-Asian tweet, they become more vocal and engaged afterwards compared to counterhate users. We find that bots comprise 10.4% of hateful users and are more vocal and hateful compared to non-bot users. Comparing bot accounts, we show that hateful bots are more successful in attracting followers compared to counterhate bots. Analysis of the social network reveals that hateful and counterhate users interact and engage extensively with one another, instead of living in isolated polarized communities. Furthermore, we find that hate is contagious and nodes are highly likely to become hateful after being exposed to hateful content. Importantly, our analysis reveals that counterhate messages can discourage users from turning hateful in the first place. Overall, this work presents a comprehensive overview of anti-Asian hate and counterhate content during a pandemic. The COVID-HATE dataset is available at http://claws.cc.gatech.edu/covid.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296355

ABSTRACT

Neutrophils are considered as a primary driver of the pathogenesis of acute respiratory distress syndrome (ARDS) and have been implicated in the pathophysiology of severe COVID-19. While single-cell RNA sequencing (scRNA-seq) analysis has provided insights into immune cell heterogeneity and dysregulation during COVID-19, the challenges of isolating neutrophils and their inability to survive cryopreservation have resulted in a poor understanding of their genomic and phenotypic heterogeneity on a single cell level during COVID-19 infection. Here, we report for the first time a dedicated study of neutrophil responses using scRNA seq of fresh leukocytes from 11 hospitalized adult patients with mild and severe COVID-19 disease and 5 healthy controls. We observed that neutrophils display a pronounced inflammatory profile, with dramatic disruption of predicted cell-cell interactions as the severity of the disease increases. We also identified unique mature and immature neutrophil subpopulations based on transcriptomic profiling, including an antiviral phenotype, and changes in the proportion of each population linked to the severity of the disease. Finally, pathway analysis revealed increased markers of oxidative phosphorylation and ribosomal genes, along with downregulation of many antiviral and host defense pathway genes during severe disease compared to mild infections. Collectively, our findings indicate that neutrophils are capable of mounting effective antiviral defenses but in patients with more severe disease, adopt a form of immune dysregulation characterized by excess cellular stress, thereby contributing to the pathogenesis of severe COVID-19.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-293604

ABSTRACT

Neutrophils are considered as a primary driver of the pathogenesis of acute respiratory distress syndrome (ARDS) and have been implicated in the pathophysiology of severe COVID-19. While single-cell RNA sequencing (scRNA-seq) analysis has provided insights into immune cell heterogeneity and dysregulation during COVID-19, the challenges of isolating neutrophils and their inability to survive cryopreservation have resulted in a poor understanding of their genomic and phenotypic heterogeneity on a single cell level during COVID-19 infection. Here, we report for the first time a dedicated study of neutrophil responses using scRNA seq of fresh leukocytes from 11 hospitalized adult patients with mild and severe COVID-19 disease and 5 healthy controls. We observed that neutrophils display a pronounced inflammatory profile, with dramatic disruption of predicted cell-cell interactions as the severity of the disease increases. We also identified unique mature and immature neutrophil subpopulations based on transcriptomic profiling, including an antiviral phenotype, and changes in the proportion of each population linked to the severity of the disease. Finally, pathway analysis revealed increased markers of oxidative phosphorylation and ribosomal genes, along with downregulation of many antiviral and host defense pathway genes during severe disease compared to mild infections. Collectively, our findings indicate that neutrophils are capable of mounting effective antiviral defenses but in patients with more severe disease, adopt a form of immune dysregulation characterized by excess cellular stress, thereby contributing to the pathogenesis of severe COVID-19.

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-291968

ABSTRACT

The spread of COVID-19 has sparked racism and hate on social media targeted towards Asian communities. However, little is known about how racial hate spreads during a pandemic and the role of counterspeech in mitigating this spread. In this work, we study the evolution and spread of anti-Asian hate speech through the lens of Twitter. We create COVID-HATE, the largest dataset of anti-Asian hate and counterspeech spanning 14 months, containing over 206 million tweets, and a social network with over 127 million nodes. By creating a novel hand-labeled dataset of 3,355 tweets, we train a text classifier to identify hate and counterspeech tweets that achieves an average macro-F1 score of 0.832. Using this dataset, we conduct longitudinal analysis of tweets and users. Analysis of the social network reveals that hateful and counterspeech users interact and engage extensively with one another, instead of living in isolated polarized communities. We find that nodes were highly likely to become hateful after being exposed to hateful content. Notably, counterspeech messages may discourage users from turning hateful, potentially suggesting a solution to curb hate on web and social media platforms. Data and code is at http://claws.cc.gatech.edu/covid.

9.
International Heart Journal ; 62(1):148-152, 2021.
Article in English | Ichushi | ID: covidwho-1469298

ABSTRACT

武漢大学人民医院に入院した新型コロナウイルス感染症の重症患者148例(男性67例、女性81例、平均57.2±17.7歳)を対象に、心筋バイオマーカーと予後との関連性について検討した。患者148例のうち99例(66.9%)は高血圧症、糖尿病、貧血、腎障害、肝障害、慢性閉塞性肺疾患、心血管疾患、悪性腫瘍等の基礎疾患を有していた。患者を転帰に応じて、生存群96例(男性39.6%、平均51.4±16.1歳)と死亡群52例(男性55.8%、平均68.6±14.8歳)の2群に分類した。血中NT-proBNP(基準範囲は450pg/mL未満)は死亡群(1035.46pg/mL)が生存群(81.15pg/mL)より有意に高く、CK-MBも死亡群(2.62ng/mL)が生存群(0.67ng/mL)より有意に高かった(いずれもP<0.001)。心筋トロポニンcTnIは生存群で0.000であったが、死亡群は0.131ng/mLであった。血清ミオグロビンは死亡群(101.83μg/L)が生存群(26.86μg/L)より有意に高かった(P<0.001)。心血管合併症を呈した19例のうち14例が死亡した。

10.
Am J Surg Pathol ; 46(1): 89-96, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1254925

ABSTRACT

Approximately 20% of patients with symptomatic syndrome-associated coronavirus-2 (SARS-CoV-2) infection have gastrointestinal bleeding and/or diarrhea. Most are managed without endoscopic evaluation because the risk of practitioner infection outweighs the value of biopsy analysis unless symptoms are life-threatening. As a result, much of what is known about the gastrointestinal manifestations of coronavirus disease-2019 (COVID-19) has been gleaned from surgical and autopsy cases that suffer from extensive ischemic injury and/or poor preservation. There are no detailed reports describing any other gastrointestinal effects of SARS-CoV-2 even though >3,000,000 people have died from COVID-19 worldwide. The purpose of this study is to report the intestinal findings related to SARS-CoV-2 infection by way of a small case series including one with evidence of direct viral cytopathic effect and 2 with secondary injury attributed to viral infection. Infection can be confirmed by immunohistochemical stains directed against SARS-CoV-2 spike protein, in situ hybridization for spike protein-encoding RNA, and ultrastructural visualization of viruses within the epithelium. It induces cytoplasmic blebs and tufted epithelial cells without inflammation and may not cause symptoms. In contrast, SARS-CoV-2 infection can cause gastrointestinal symptoms after the virus is no longer detected, reflecting systemic activation of cytokine and complement cascades rather than direct viral injury. Reversible mucosal ischemia features microvascular injury with hemorrhage, small vessel thrombosis, and platelet-rich thrombi. Systemic cytokine elaboration and dysbiosis likely explain epithelial cell injury that accompanies diarrheal symptoms. These observations are consistent with clinical and in vitro data and contribute to our understanding of the protean manifestations of COVID-19.


Subject(s)
COVID-19/pathology , Intestinal Diseases/pathology , Intestinal Diseases/virology , Intestines/pathology , Intestines/virology , Adult , Aged , Aged, 80 and over , Biomarkers/metabolism , Biopsy , COVID-19/diagnosis , COVID-19/immunology , Cytokines/metabolism , Gastrointestinal Hemorrhage/diagnosis , Gastrointestinal Hemorrhage/immunology , Gastrointestinal Hemorrhage/pathology , Gastrointestinal Hemorrhage/virology , Humans , Intestinal Diseases/diagnosis , Intestinal Diseases/immunology , Intestines/immunology , Ischemia/diagnosis , Ischemia/immunology , Ischemia/pathology , Ischemia/virology , Male , Thrombosis/diagnosis , Thrombosis/immunology , Thrombosis/pathology , Thrombosis/virology
11.
Signal Transduct Target Ther ; 6(1): 195, 2021 05 17.
Article in English | MEDLINE | ID: covidwho-1232065

ABSTRACT

B cell response plays a critical role against SARS-CoV-2 infection. However, little is known about the diversity and frequency of the paired SARS-CoV-2 antigen-specific BCR repertoire after SARS-CoV-2 infection. Here, we performed single-cell RNA sequencing and VDJ sequencing using the memory and plasma B cells isolated from five convalescent COVID-19 patients, and analyzed the spectrum and transcriptional heterogeneity of antibody immune responses. Via linking BCR to antigen specificity through sequencing (LIBRA-seq), we identified a distinct activated memory B cell subgroup (CD11chigh CD95high) had a higher proportion of SARS-CoV-2 antigen-labeled cells compared with memory B cells. Our results revealed the diversity of paired BCR repertoire and the non-stochastic pairing of SARS-CoV-2 antigen-specific immunoglobulin heavy and light chains after SARS-CoV-2 infection. The public antibody clonotypes were shared by distinct convalescent individuals. Moreover, several antibodies isolated by LIBRA-seq showed high binding affinity against SARS-CoV-2 receptor-binding domain (RBD) or nucleoprotein (NP) via ELISA assay. Two RBD-reactive antibodies C14646P3S and C2767P3S isolated by LIBRA-seq exhibited high neutralizing activities against both pseudotyped and authentic SARS-CoV-2 viruses in vitro. Our study provides fundamental insights into B cell response following SARS-CoV-2 infection at the single-cell level.


Subject(s)
B-Lymphocytes/immunology , COVID-19/immunology , Convalescence , Immunologic Memory , RNA-Seq , SARS-CoV-2/immunology , Animals , B-Lymphocytes/pathology , COVID-19/genetics , COVID-19/pathology , Cell Line, Tumor , Cell Separation , Chlorocebus aethiops , HEK293 Cells , Humans , SARS-CoV-2/genetics , Vero Cells
12.
Int Heart J ; 62(1): 148-152, 2021.
Article in English | MEDLINE | ID: covidwho-1054895

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is erupting and spreading globally. Cardiovascular complications secondary to the infection have caught notice. This study aims to delineate the relationship of cardiac biomarkers and outcomes in severe cases of corona virus disease 2019 (COVID-19). One hundred forty-eight critically ill adult patients with COVID-19 were enrolled. From these patients, the demographic data, symptoms, cardiac biomarkers, treatments, and clinical outcomes were collected. Data were compared between survivors and non-survivors. Four patients in the non-survivor group were selected, and their cardiac biomarkers were collected and analyzed. Among the 148 patients, the incidence of cardiovascular complications was 19 (12.8%). Five of them were survivors (5.2%), and 14 of them were non-survivors (26.9%). Compared with the survivors, the non-survivors had higher levels of high-sensitivity cardiac troponin I, creatine kinase isoenzyme-MB, myoglobin, and N-terminal pro-brain natriuretic peptide (P < 0.05). The occurrence of cardiovascular events began at 11-15 days after the onset of the disease and reached a peak at 14-20 days. COVID-19 not only is a respiratory disease but also causes damage to the cardiovascular system. Cardiac biomarkers have the potential for early warning and prognostic evaluation in patients with COVID-19. It is recommended that cardiac biomarker monitoring in patients with COVID-19 should be initiated at least from the 11th day of the disease course.


Subject(s)
Biomarkers/metabolism , COVID-19/complications , Cardiovascular Diseases/etiology , Cardiovascular Diseases/metabolism , Adult , Aged , Atrial Natriuretic Factor/metabolism , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Cardiovascular Diseases/epidemiology , Case-Control Studies , China/epidemiology , Creatine Kinase, MB Form/metabolism , Critical Illness/mortality , Critical Illness/nursing , Female , Humans , Incidence , Male , Middle Aged , Prognosis , Protein Precursors/metabolism , SARS-CoV-2/genetics , Survival Rate , Survivors/statistics & numerical data , Troponin I/metabolism
14.
Ann Diagn Pathol ; 51: 151682, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-987026

ABSTRACT

Neurologic complications of symptomatic COVID-19 are common. Brain tissues from 13 autopsies of people who died of COVID-19 were examined. Cultured endothelial and neuronal cells were incubated with and wild type mice were injected IV with different spike subunits. In situ analyses were used to detect SARS-CoV-2 proteins and the host response. In 13/13 brains from fatal COVID-19, pseudovirions (spike, envelope, and membrane proteins without viral RNA) were present in the endothelia of microvessels ranging from 0 to 14 positive cells/200× field (mean 4.3). The pseudovirions strongly co-localized with caspase-3, ACE2, IL6, TNFα, and C5b-9. The surrounding neurons demonstrated increased NMDAR2 and neuronal NOS plus decreased MFSD2a and SHIP1 proteins. Tail vein injection of the full length S1 spike subunit in mice led to neurologic signs (increased thirst, stressed behavior) not evident in those injected with the S2 subunit. The S1 subunit localized to the endothelia of microvessels in the mice brain and showed co-localization with caspase-3, ACE2, IL6, TNFα, and C5b-9. The surrounding neurons showed increased neuronal NOS and decreased MFSD2a. It is concluded that ACE2+ endothelial damage is a central part of SARS-CoV2 pathology and may be induced by the spike protein alone. Thus, the diagnostic pathologist can use either hematoxylin and eosin stain or immunohistochemistry for caspase 3 and ACE2 to document the endothelial cell damage of COVID-19.


Subject(s)
COVID-19/virology , Endothelial Cells/virology , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Adult , Aged , Aged, 80 and over , Animals , Autopsy/methods , Disease Models, Animal , Endothelial Cells/metabolism , Female , Humans , Male , Mice , Microvessels/metabolism , Microvessels/virology , Middle Aged , Protein Subunits/metabolism , RNA, Viral/genetics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
15.
Clin Cardiol ; 43(12): 1624-1630, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-888065

ABSTRACT

BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. HYPOTHESIS: The possible risk factors that lead to death in critical inpatients with coronavirus disease 2019 (COVID-19) are not yet fully understood. METHODS: In this single-center, retrospective study, we enrolled 113 critical patients with COVID-19 from Renmin Hospital of Wuhan University between February 1, 2020 and March 15, 2020. Patients who survived or died were compared. RESULTS: A total of 113 critical patients with COVID-19 were recruited; 50 (44.3%) died, and 63 (55.7%) recovered. The proportion of patients with ventricular arrhythmia was higher in the death group than in the recovery group (P = .021) and was higher among patients with myocardial damage than patients without myocardial damage (P = .013). Multivariate analysis confirmed independent predictors of mortality from COVID-19: age > 70 years (HR 1.84, 95% CI 1.03-3.28), initial neutrophil count over 6.5 × 109 /L (HR 3.43, 95% CI 1.84-6.40), C-reactive protein greater than 100 mg/L (HR 1.93, 95% CI 1.04-3.59), and lactate dehydrogenase over 300 U/L (HR 2.90, 95% CI 1.26-6.67). Immunoglobulin treatment (HR 0.39, 95% CI 0.21-0.73) can reduce the risk of death. Sinus tachycardia (HR 2.94, 95% CI 1.16-7.46) and ventricular arrhythmia (HR 2.79, 95% CI 1.11-7.04) were independent ECG risk factors for mortality from COVID-19. CONCLUSIONS: Old age (>70 years), neutrophilia, C-reactive protein greater than 100 mg/L and lactate dehydrogenase over 300 U/L are high-risk factors for mortality in critical patients with COVID-19. Sinus tachycardia and ventricular arrhythmia are independent ECG risk factors for mortality from COVID-19.


Subject(s)
COVID-19/mortality , Critical Illness/mortality , Inpatients/statistics & numerical data , Adult , Aged , C-Reactive Protein/analysis , COVID-19/metabolism , Electrocardiography , Female , Humans , Leukocyte Count , Male , Middle Aged , Neutrophils/metabolism , Retrospective Studies , Risk Factors , Severity of Illness Index
16.
Eur J Clin Microbiol Infect Dis ; 40(3): 565-574, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-812573

ABSTRACT

Our aim was to investigate whether SARS-CoV-2 infection raised high risks of late pregnancy complications, and posed health problems in fetuses and neonates. We analyzed the data of COVID-19 pregnant women with COVID-19 during late pregnancy and their neonates. Eleven out of 16 (69%) pregnant women with COVID-19 had ++ or +++ of ketone body in urine. The blood uric acid of pregnant patients was 334 µmol/L (IQR, 269-452). D-dimer and FDP in pregnant patients were 3.32 mg/L (IQR, 2.18-4.21) and 9.6 mg/L (IQR, 5.9-12.4). Results of blood samples collected at birth showed that 16 neonates had leukocytes (15.7 × 109/L (IQR, 13.7-17.2)), neutrophils (11.1 × 109/L (IQR, 9.2-13.2)), CK (401 U/L (IQR, 382-647)), and LDH (445 U/L (IQR, 417-559)). Twenty-four hours after birth, a neonate from COVID-19 woman had fever and positive of SARS-CoV-2 gene. Another woman had strongly positive for SARS-CoV-2 gene (+++) for 4 weeks, and delivered one neonate who had SARS-CoV-2 IgM (46 AU/mL) and IgG (140 AU/mL) on day 1 after birth. In the third trimester, COVID-19 infection in pregnant patients raised high risks of ketonuria, hypercoagulable state, and hyperfibrinolysis, which may lead to severe complications. COVID-19 increased the inflammatory responses of placenta, and fetuses and neonates had potential organ dysregulation and coagulation disorders. There was a potential intrauterine transmission while pregnant women had high titer of SARS-CoV-2, but it is necessary to detect SARS-CoV-2 in the blood cord, placenta, and amniotic fluid to further confirm intrauterine infection of fetuses.


Subject(s)
COVID-19/immunology , COVID-19/metabolism , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/metabolism , Adult , Antibodies, Viral/blood , COVID-19/diagnosis , COVID-19/transmission , Female , Fetal Blood/immunology , Fetal Blood/metabolism , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical/statistics & numerical data , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Outcome/epidemiology , Pregnancy Trimester, Third , Pregnant Women , SARS-CoV-2/isolation & purification
17.
ArXiv; 2020.
Preprint | ArXiv | ID: ppcovidwho-479

ABSTRACT

Coronavirus disease (COVID-19) is an infectious disease discovered in 2019 and currently in outbreak across the world. Lung injury with severe respiratory failure is the leading cause of death in COVID-19, brought by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2). However, there still lacks efficient treatment for COVID-19 induced lung injury and acute respiratory failure. Inhibition of Angiotensin-converting enzyme 2 (ACE2) caused by spike protein of SARS-CoV-2 is the most plausible mechanism of lung injury in COVID-19. We propose two candidate drugs, COL-3 (a chemically modified tetracycline) and CGP-60474 (a cyclin-dependent kinase inhibitor), for treating lung injuries in COVID-19, based on their abilities to reverse the gene expression patterns in HCC515 cells treated with ACE2 inhibitor and in human COVID-19 patient lung tissues. Further bioinformatics analysis shows that twelve significantly enriched pathways (P-value <0.05) overlabetween HCC515 cells treated with ACE2 inhibitor and human COVID-19 patient lung tissues, including signaling pathways known to be associated with lung injury such as TNF signaling, MAPK signaling and Chemokine signaling pathways. All these twelve pathways are targeted in COL-3 treated HCC515 cells, in which genes such as RHOA, RAC2, FAS, CDC42 have reduced expression. CGP-60474 shares eleven of twelve pathways with COL-3 with common target genes such as RHOA. It also uniquely targets genes related to lung injury, such as CALR and MMP14. In summary, this study shows that ACE2 inhibition is likely part of the mechanisms leading to lung injury in COVID-19, and that compounds such as COL-3 and CGP-60474 have the potential as repurposed drugs for its treatment.

18.
Front Immunol ; 11: 2075, 2020.
Article in English | MEDLINE | ID: covidwho-776205

ABSTRACT

To explore the metabolic changes and immune profiles in patients with COVID-19, we analyzed the data of patients with mild and severe COVID-19 as well as young children with COVID-19. Of the leukocytes, 47% (IQR, 33-59) were lymphocytes [2.5 × 109/L (IQR, 2.2-3.3)], and monocytes were 0.51 × 109/L (IQR, 0.45-0.57) in young children with COVID-19. In 32 mild COVID-19 patients, circulating monocytes were 0.45 × 109/L (IQR, 0.36-0.64). Twenty-one severe patients had low PO2 [57 mmHg (IQR, 50-73)] and SO2 [90% (IQR, 86-93)] and high lactate dehydrogenase [580 U/L (IQR, 447-696)], cardiac troponin I [0.07 ng/mL (IQR, 0.02-0.30)], and pro-BNP [498 pg/mL (IQR, 241-1,726)]. Serum D-dimer and FDP were 9.89 mg/L (IQR, 3.62-22.85) and 32.7 mg/L (IQR, 12.8-81.9), and a large number of RBC (46/µL (IQR, 4-242) was presented in urine, a cue of disseminated intravascular coagulation (DIC) in severe patients. Three patients had comorbidity with diabetes, and 18 patients without diabetes also presented high blood glucose [7.4 mmol/L (IQR, 5.9-10.1)]. Fifteen of 21 (71%) severe cases had urine glucose +, and nine of 21 (43%) had urine ketone body +. The increased glucose was partially caused by reduced glucose consumption of cells. Severe cases had extraordinarily low serum uric acid [176 µmol/L (IQR, 131-256)]. In the late stage of COVID-19, severe cases had extremely low CD4+ T cells and CD8+ T cells, but unusually high neutrophils [6.5 × 109/L (IQR, 4.8-9.6)], procalcitonin [0.27 ng/mL (IQR, 0.14-1.94)], C-reactive protein [66 mg/L (IQR, 25-114)] and an extremely high level of interleukin-6. Four of 21 (19%) severe cases had co-infection with fungi, and two of 21 (9%) severe cases had bacterial infection. Our findings suggest that, severe cases had acute respiratory distress syndrome (ARDS) I-III, and metabolic disorders of glucose, lipid, uric acid, etc., even multiple organ dysfunction (MODS) and DIC. Increased neutrophils and severe inflammatory responses were involved in ARDS, MODS, and DIC. With the dramatical decrease of T-lymphocytes, severe cases were susceptible to co-infect with bacteria and fungi in the late stage of COVID-19. In young children, extremely high lymphocytes and monocytes might be associated with the low morbidity of COVID-19. The significantly increased monocytes might play an important role in the recovery of patients with mild COVID-19.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/immunology , Coronavirus Infections/metabolism , Pneumonia, Viral/immunology , Pneumonia, Viral/metabolism , Adult , Aged , Blood Glucose/analysis , C-Reactive Protein/analysis , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19 , Child , Child, Preschool , Coronavirus Infections/virology , Female , Humans , Interleukin-6/blood , Lymphocyte Count , Male , Middle Aged , Neutrophils/immunology , Pandemics , Pneumonia, Viral/virology , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Uric Acid/blood
19.
Mod Pathol ; 33(11): 2156-2168, 2020 11.
Article in English | MEDLINE | ID: covidwho-744362

ABSTRACT

SARS-CoV-2, the etiologic agent of COVID-19, is a global pandemic with substantial mortality dominated by acute respiratory distress syndrome. We systematically evaluated lungs of 68 autopsies from 3 institutions in heavily hit areas (2 USA, 1 Italy). Detailed evaluation of several compartments (airways, alveolar walls, airspaces, and vasculature) was performed to determine the range of histologic features. The cohort consisted of 47 males and 21 females with a median age of 73 years (range 30-96). Co-morbidities were present in most patients with 60% reporting at least three conditions. Tracheobronchitis was frequently present, independent from intubation or superimposed pneumonia. Diffuse alveolar damage (DAD) was seen in 87% of cases. Later phases of DAD were less frequent and correlated with longer duration of disease. Large vessel thrombi were seen in 42% of cases but platelet (CD61 positive) and/or fibrin microthrombi were present at least focally in 84%. Ultrastructurally, small vessels showed basal membrane reduplication and significant endothelial swelling with cytoplasmic vacuolization. In a subset of cases, virus was detected using different tools (immunohistochemistry for SARS-CoV-2 viral spike protein, RNA in situ hybridization, lung viral culture, and electron microscopy). Virus was seen in airway epithelium and type 2 pneumocytes. IHC or in situ detection, as well as viable form (lung culture positive) was associated with the presence of hyaline membranes, usually within 2 weeks but up to 4 weeks after initial diagnosis. COVID-19 pneumonia is a heterogeneous disease (tracheobronchitis, DAD, and vascular injury), but with consistent features in three centers. The pulmonary vasculature, with capillary microthrombi and inflammation, as well as macrothrombi, is commonly involved. Viral infection in areas of ongoing active injury contributes to persistent and temporally heterogeneous lung damage.


Subject(s)
Coronavirus Infections/pathology , Coronavirus Infections/virology , Lung/pathology , Lung/virology , Pneumonia, Viral/pathology , Adult , Aged , Aged, 80 and over , Autopsy , Betacoronavirus , COVID-19 , Cohort Studies , Female , Humans , Italy , Male , Middle Aged , New York City , Pandemics , Pneumonia, Viral/virology , Retrospective Studies , SARS-CoV-2
20.
J Am Heart Assoc ; 9(15): e016706, 2020 08 04.
Article in English | MEDLINE | ID: covidwho-619952

ABSTRACT

BACKGROUND The novel severe acute respiratory syndrome coronavirus 2 threatens human health, and the mortality rate is higher in patients who develop myocardial damage. However, the possible risk factors for myocardial damage in patients with coronavirus disease 2019 (COVID-19) are not fully known. METHODS AND RESULTS Critical type patients were selected randomly from 204 confirmed COVID-19 cases occurring in Renmin Hospital of Wuhan University from February 1, 2020 to February 24, 2020. Univariate analyses were used to compare the 2 groups: the myocardial damage group and the non-myocardial damage group. A total of 82 critical patients with COVID-19 were recruited: 34 with myocardial damage and 48 without myocardial damage. A total of 30 patients died in the myocardial damage group, and 20 died in the non-myocardial damage group. In univariate analysis, the proportion of elderly patients (>70 years old, 70.59% versus 37.50%; P=0.003) and patients with cardiovascular disease (41.18% versus 12.50%; P=0.003) was higher among myocardial damage patients than among non-myocardial damage patients. Multivariate analysis showed that age >70 years old (hazard ratio [HR], 2.44; 95% CI, 1.01-5.40), CRP (C-reactive protein) >100 mg/L (HR, 1.92; 95% CI, 0.94-3.92), lactate dehydrogenase >300 U/L (HR, 2.67; 95% CI, 1.03-6.90), and lactic acid >3 mmol/L (HR, 3.25; 95% CI, 1.57-6.75) were independent risk factors for myocardial damage in patients with COVID-19. CONCLUSIONS Old age (>70 years old), CRP >100 mg/L, lactate dehydrogenase >300 U/L, and lactic acid >3 mmol/L are high-risk factors related to myocardial damage in critical patients with COVID-19.


Subject(s)
Cardiomyopathies/etiology , Coronavirus Infections/complications , Pneumonia, Viral/complications , Adult , Age Factors , Aged , Aged, 80 and over , C-Reactive Protein/analysis , COVID-19 , Cardiomyopathies/virology , China/epidemiology , Female , Humans , Kaplan-Meier Estimate , L-Lactate Dehydrogenase/blood , Lactic Acid/blood , Male , Middle Aged , Pandemics , Retrospective Studies , Risk Factors
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