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1.
BMJ : British Medical Journal (Online) ; 368, 2020.
Article in English | ProQuest Central | ID: covidwho-1837197

ABSTRACT

ObjectiveTo delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died.DesignRetrospective case series.SettingTongji Hospital in Wuhan, China.ParticipantsAmong a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020.Main outcome measuresClinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms.ResultsThe median age of deceased patients (68 years) was significantly older than recovered patients (51 years). Male sex was more predominant in deceased patients (83;73%) than in recovered patients (88;55%). Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)). Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)). The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days. Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively. Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113;100%), type I respiratory failure (18/35;51%), sepsis (113;100%), acute cardiac injury (72/94;77%), heart failure (41/83;49%), alkalosis (14/35;40%), hyperkalaemia (42;37%), acute kidney injury (28;25%), and hypoxic encephalopathy (23;20%). Patients with cardiovascular comorbidity were more likely to develop cardiac complications. Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients.ConclusionSevere acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.

3.
Viruses ; 14(2)2022 01 18.
Article in English | MEDLINE | ID: covidwho-1715743

ABSTRACT

The African swine fever virus (ASFV) is a dsDNA virus that can cause serious, highly infectious, and fatal diseases in wild boars and domestic pigs. The ASFV has brought enormous economic loss to many countries, and no effective vaccine or treatment for the ASFV is currently available. Therefore, the on-site rapid and accurate detection of the ASFV is key to the timely implementation of control. The RNA-guided, RNA-targeting CRISPR effector CRISPR-associated 13 (Cas13a; previously known as C2c2) exhibits a "collateral effect" of promiscuous RNase activity upon the target recognition. The collateral cleavage activity of LwCas13a is activated to degrade the non-targeted RNA, when the crRNA of LwCas13a binds to the target RNA. In this study, we developed a rapid and sensitive ASFV detection method based on the collateral cleavage activity of LwCas13a, which combines recombinase-aided amplification (RAA) and a lateral flow strip (named CRISPR/Cas13a-LFD). The method was an isothermal detection at 37 °C, and the detection can be used for visual readout. The detection limit of the CRISPR/Cas13a-LFD was 101 copies/µL of p72 gene per reaction, and the detection process can be completed within an hour. The assay showed no cross-reactivity to eight other swine viruses, including classical swine fever virus (CSFV), and has a 100% coincidence rate with real-time PCR detection of the ASFV in 83 clinical samples. Overall, this method is sensitive, specific, and practicable onsite for the ASFV detection, showing a great application potential for monitoring the ASFV in the field.


Subject(s)
African Swine Fever Virus/isolation & purification , African Swine Fever/diagnosis , CRISPR-Cas Systems , African Swine Fever/virology , African Swine Fever Virus/genetics , Animals , Genotype , Reagent Strips , Recombinases/genetics , Recombinases/metabolism , Sensitivity and Specificity , Sus scrofa , Swine , Time Factors
4.
Clin Infect Dis ; 2021 Aug 14.
Article in English | MEDLINE | ID: covidwho-1704207

ABSTRACT

BACKGROUND: Follow-up study of Coronavirus disease 2019 (COVID-19) survivors has rarely been reported. We aimed to investigate longitudinal changes in the characteristics of COVID-19 survivors after discharge. METHODS AND FINDINGS: A total of 594 COVID-19 survivors discharged from Tongji Hospital in Wuhan from February 10 to April 30, 2020 were included and followed up until May 17, 2021. Laboratory and radiological findings, pulmonary function tests, electrocardiogram, symptoms and signs were analyzed. 257 (51.2%) patients had at least one symptom at 3 months post-discharge, which decreased to 169 (40.0%) and 138 (28.4%) at 6-month and 12-month visit respectively. During follow-up period, insomnia, chest tightness, and fatigue were the most prevalent symptoms. Most laboratory parameters returned to normal, whereas increased incidence of abnormal liver and renal function and cardiovascular injury was evidenced after discharge. Fibrous stripes (213; 42.4%), pleural thickening and adhesions (188; 37.5%) and enlarged lymph nodes (120; 23.9%) were the most common radiographical findings at 3 months post-discharge. The abnormalities of pulmonary function included obstructive, restrictive, and mixed, which were 5.5%, 4.0%, 0.9% at 6 months post, and 1.9%, 4.7%, 0.2% at 12 months. Electrocardiogram abnormalities occurred in 256 (51.0%) patients at 3 months post-discharge, including arrhythmia, ST-T change and conduction block, which increased to 258 (61.1%) cases at 6-month visit and were maintained at high frequency (242;49.8%) at 12-month visit. CONCLUSIONS: Physiological, laboratory, radiological or electrocardiogram abnormalities, particularly those related to renal, cardiovascular, liver functions are common in patients who recovered from COVID-19 up to 12months post-discharge.

5.
J Biomed Inform ; 128: 104034, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1703628

ABSTRACT

OBJECTIVE: To demonstrate how non-negative matrix factorization can be used to learn a temporal topic model over a large collection of primary care clinical notes, characterizing diverse COVID-19 pandemic effects on the physical/mental/social health of residents of Toronto, Canada. MATERIALS AND METHODS: The study employs a retrospective open cohort design, consisting of 382,666 primary care progress notes from 44,828 patients, 54 physicians, and 12 clinics collected 01/01/2017 through 31/12/2020. Non-negative matrix factorization uncovers a meaningful latent topical structure permeating the corpus of primary care notes. The learned latent topical basis is transformed into a multivariate time series data structure. Time series methods and plots showcase the evolution/dynamics of learned topics over the study period and allow the identification of COVID-19 pandemic effects. We perform several post-hoc checks of model robustness to increase trust that descriptive/unsupervised inferences are stable over hyper-parameter configurations and/or data perturbations. RESULTS: Temporal topic modelling uncovers a myriad of pandemic-related effects from the expressive clinical text data. In terms of direct effects on patient-health, topics encoding respiratory disease symptoms display altered dynamics during the pandemic year. Further, the pandemic was associated with a multitude of indirect patient-level effects on topical domains representing mental health, sleep, social and familial dynamics, measurement of vitals/labs, uptake of prevention/screening maneuvers, and referrals to medical specialists. Finally, topic models capture changes in primary care practice patterns resulting from the pandemic, including changes in EMR documentation strategies and the uptake of telemedicine. CONCLUSION: Temporal topic modelling applied to a large corpus of rich primary care clinical text data, can identify a meaningful topical/thematic summarization which can provide policymakers and public health stakeholders a passive, cost-effective, technology for understanding holistic impacts of the COVID-19 pandemic on the primary healthcare system and community/public-health.


Subject(s)
COVID-19 , Pandemics , COVID-19/epidemiology , Canada/epidemiology , Humans , Primary Health Care , Public Health , Retrospective Studies , SARS-CoV-2
6.
Signal Transduct Target Ther ; 7(1): 57, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1702971

ABSTRACT

The coronavirus disease 2019 (COVID-19) is a highly transmissible disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that poses a major threat to global public health. Although COVID-19 primarily affects the respiratory system, causing severe pneumonia and acute respiratory distress syndrome in severe cases, it can also result in multiple extrapulmonary complications. The pathogenesis of extrapulmonary damage in patients with COVID-19 is probably multifactorial, involving both the direct effects of SARS-CoV-2 and the indirect mechanisms associated with the host inflammatory response. Recognition of features and pathogenesis of extrapulmonary complications has clinical implications for identifying disease progression and designing therapeutic strategies. This review provides an overview of the extrapulmonary complications of COVID-19 from immunological and pathophysiologic perspectives and focuses on the pathogenesis and potential therapeutic targets for the management of COVID-19.


Subject(s)
Acute Kidney Injury/complications , COVID-19/complications , Cytokine Release Syndrome/complications , Disseminated Intravascular Coagulation/complications , Lymphopenia/complications , Myocarditis/complications , Pulmonary Embolism/complications , Acute Kidney Injury/drug therapy , Acute Kidney Injury/immunology , Acute Kidney Injury/virology , Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/immunology , COVID-19/virology , Clinical Trials as Topic , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/immunology , Disseminated Intravascular Coagulation/virology , Endothelial Cells/drug effects , Endothelial Cells/immunology , Endothelial Cells/virology , Humans , Immunity, Innate/drug effects , Immunologic Factors/therapeutic use , Lymphopenia/drug therapy , Lymphopenia/immunology , Lymphopenia/virology , Myocarditis/drug therapy , Myocarditis/immunology , Myocarditis/virology , Pulmonary Embolism/drug therapy , Pulmonary Embolism/immunology , Pulmonary Embolism/virology , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/immunology , SARS-CoV-2/drug effects , SARS-CoV-2/growth & development , SARS-CoV-2/pathogenicity
7.
JCI Insight ; 7(4)2022 02 22.
Article in English | MEDLINE | ID: covidwho-1700377

ABSTRACT

BACKGROUNDAfter the initial surge in COVID-19 cases, large numbers of patients were discharged from a hospital without assessment of recovery. Now, an increasing number of patients report postacute neurological sequelae, known as "long COVID" - even those without specific neurological manifestations in the acute phase.METHODSDynamic brain changes are crucial for a better understanding and early prevention of "long COVID." Here, we explored the cross-sectional and longitudinal consequences of COVID-19 on the brain in 34 discharged patients without neurological manifestations. Gray matter morphology, cerebral blood flow (CBF), and volumes of white matter tracts were investigated using advanced magnetic resonance imaging techniques to explore dynamic brain changes from 3 to 10 months after discharge.RESULTSOverall, the differences of cortical thickness were dynamic and finally returned to the baseline. For cortical CBF, hypoperfusion in severe cases observed at 3 months tended to recover at 10 months. Subcortical nuclei and white matter differences between groups and within subjects showed various trends, including recoverable and long-term unrecovered differences. After a 10-month recovery period, a reduced volume of nuclei in severe cases was still more extensive and profound than that in mild cases.CONCLUSIONOur study provides objective neuroimaging evidence for the coexistence of recoverable and long-term unrecovered changes in 10-month effects of COVID-19 on the brain. The remaining potential abnormalities still deserve public attention, which is critically important for a better understanding of "long COVID" and early clinical guidance toward complete recovery.FUNDINGNational Natural Science Foundation of China.


Subject(s)
Brain/pathology , COVID-19/pathology , COVID-19/complications , COVID-19/virology , Female , Humans , Male , SARS-CoV-2/isolation & purification
8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323595

ABSTRACT

Background: Cigarette smoking (CS) is a global public health problem and a high-risk factor for various diseases. In December 2019, a novel coronavirus (HCoV-19) was identified in Wuhan, China. Because ACE2 has been identified as a receptor for HCoV-19, we hypothesize that CS affects the expression pattern of ACE2 in respiratory tract, causing differences in susceptibility to the virus. Methods: Three datasets (GSE994, GSE17913, and GSE18344), were downloaded from the Gene Expression Omnibus (GEO) database. Correlation and enrichment analysis were used to evaluate the function of ACE2. Also, the different expression of ACE2 in different groups of three datasets were analyzed. Results: Genes associated with ACE2 were enriched in important biological processes such as viral processes and immune response. Elevated ACE2 were found in intrapulmonary airways (GSE994) and oral epithelial cells (GSE17913) of smokers but not those of non-smokers or former smokers. Significant dose- and time-dependent relationships between CS and ACE2 expression were observed in mouse lung tissues, and long periods without smoking were found to significantly reduce ACE2 expression. Conclusions: Both human and rat data confirmed that CS could induce increased ACE2 in the respiratory tract, indicating that smokers have a higher susceptibility to HCoV-19.

9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319486

ABSTRACT

To counter the outbreak of COVID-19, the accurate diagnosis of suspected cases plays a crucial role in timely quarantine, medical treatment, and preventing the spread of the pandemic. Considering the limited training cases and resources (e.g, time and budget), we propose a Multi-task Multi-slice Deep Learning System (M3Lung-Sys) for multi-class lung pneumonia screening from CT imaging, which only consists of two 2D CNN networks, i.e., slice- and patient-level classification networks. The former aims to seek the feature representations from abundant CT slices instead of limited CT volumes, and for the overall pneumonia screening, the latter one could recover the temporal information by feature refinement and aggregation between different slices. In addition to distinguish COVID-19 from Healthy, H1N1, and CAP cases, our M 3 Lung-Sys also be able to locate the areas of relevant lesions, without any pixel-level annotation. To further demonstrate the effectiveness of our model, we conduct extensive experiments on a chest CT imaging dataset with a total of 734 patients (251 healthy people, 245 COVID-19 patients, 105 H1N1 patients, and 133 CAP patients). The quantitative results with plenty of metrics indicate the superiority of our proposed model on both slice- and patient-level classification tasks. More importantly, the generated lesion location maps make our system interpretable and more valuable to clinicians.

10.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-310715

ABSTRACT

Purpose: To study the clinical characteristics, laboratory examination, radiological changes and treatments of 6 patients with severe SARS-Cov-2 infected pneumonia in Zunyi City, China.MethodsThe clinical data, laboratory examination, radiological changes and clinical treatment process of 6 patients with severe SARS-Cov-2 infected pneumonia admitted to the Department of Critical Medicine of the Affiliated Hospital of Zunyi Medical University were retrospectively analyzed.Results Four of the six patients were older than 65 years. Two patients had a history of exposure to Wuhan, and four patients had family clustering infection. The most common symptoms at onset of illness were dry cough (4, 66%) and fever (4, 66%). Laboratory tests showed that white blood cell count, neutrophil count, C-reactive protein, IL-6, IL-10, and urea nitrogen elevated. The Total lymphocyte count and T lymphocyte count decreased. All patients received antiviral therapy, blood purification, immunomodulatory therapy, and Chinese herb treatments. One patient was discharged from the hospital, and 5 patients' condition improved significantly. ConclusionT lymphocyte decreased significantly, IL-6 and IL-10 elevated in severe SARS-Cov-2 infected pneumonia patients. Elderly patients with comorbidities appear to be more severe and to recover more slowly. Blood purification can be tried for severe and critically ill patients. Early identification and timely treatment of critical cases is of crucial importance.

11.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325330

ABSTRACT

Amid the ongoing COVID-19 pandemic, whether COVID-19 patients with high risks can be recovered or not depends, to a large extent, on how early they will be treated appropriately before irreversible consequences are caused to the patients by the virus. In this research, we reported an explainable, intuitive, and accurate machine learning model based on logistic regression to predict the fatality rate of COVID-19 patients using only three important blood biomarkers, including lactic dehydrogenase, lymphocyte (%) and high-sensitivity C-reactive protein, and their interactions. We found that when the fatality probability produced by the logistic regression model was over 0.8, the model had the optimal performance in that it was able to predict patient fatalities more than 11.30 days on average with maximally 34.91 days in advance, an accumulative f1-score of 93.76% and and an accumulative accuracy score of 93.92%. Such a model can be used to identify COVID-19 patients with high risks with three blood biomarkers and help the medical systems around the world plan critical medical resources amid this pandemic.

12.
Natural Hazards (Dordrecht, Netherlands) ; : 1-25, 2022.
Article in English | EuropePMC | ID: covidwho-1651340

ABSTRACT

Emergency events require early detection, quick response, and accurate recovery. In the era of big data, social media users can be seen as social sensors to monitor real-time emergency events. This paper proposed an integrated approach to detect all four kinds of emergency events early, including natural disasters, man-made accidents, public health events, and social security events. First, the BERT-Att-BiLSTM model is used to detect emergency-related posts from massive and irrelevant data. Then, the 3 W attribute information (what, where, and when) of the emergency event is extracted. With the 3 W attribute information, we create an unsupervised dynamical event clustering algorithm based on text similarity and combine it with the supervised logistical regression model to cluster posts into different events. Experiments on Sina Weibo data demonstrate the superiority of the proposed framework. Case studies on some real emergency events show that the proposed framework has good performance and high timeliness. Practical applications of the framework are also discussed, followed by future directions for improvement.

13.
Cell Rep ; 38(3): 110256, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1588136

ABSTRACT

Inoculation against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is ongoing worldwide. However, the emergence of SARS-CoV-2 variants could cause immune evasion. We developed a bivalent nanoparticle vaccine that displays the receptor binding domains (RBDs) of the D614G and B.1.351 strains. With a prime-boost or a single-dose strategy, this vaccine elicits a robust neutralizing antibody and full protection against infection with the authentic D614G or B.1.351 strain in human angiotensin-converting enzyme 2 transgene mice. Interestingly, 8 months after inoculation with the D614G-specific vaccine, a new boost with this bivalent vaccine potently elicits cross-neutralizing antibodies for SARS-CoV-2 variants in rhesus macaques. We suggest that the D614G/B.1.351 bivalent vaccine could be used as an initial single dose or a sequential enforcement dose to prevent infection with SARS-CoV-2 and its variants.


Subject(s)
COVID-19/prevention & control , Cross Protection , SARS-CoV-2/immunology , Vaccines, Combined/therapeutic use , Animals , CHO Cells , COVID-19 Vaccines/chemical synthesis , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Chlorocebus aethiops , Cricetulus , Cross Protection/immunology , Female , HEK293 Cells , Humans , Macaca mulatta , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Transgenic , Nanoparticles , Vaccination/methods , Vaccines, Combined/chemical synthesis , Vaccines, Combined/immunology , Vero Cells
14.
China CDC Wkly ; 3(44): 918-922, 2021 Oct 29.
Article in English | MEDLINE | ID: covidwho-1506116

ABSTRACT

INTRODUCTION: During the coronavirus disease 2019 (COVID-19) pandemic, the circulation of seasonal influenza virus declined globally and remained below previous seasonal levels. We analyzed the results of the epidemiology, antigenic, and genetic characteristics, and antiviral susceptibilities of seasonal influenza viruses isolated from the mainland of China during October 5, 2020 through September 5, 2021, to better assess the risk of influenza during subsequent influenza season in 2021-2022. METHODS: Positive rates of influenza virus detection during this period were based on real-time polymerase chain reaction (PCR) detection by the Chinese National Influenza Surveillance Network laboratories, and isolated viruses from influenza positive samples were submitted to the Chinese National Influenza Center. Antigenic analyses for influenza viruses were conducted using the hemagglutination inhibition assay. Next-generation sequencing was used for genetic analyses. Viruses were tested for resistance to antiviral medications using a phenotypic assay and next-generation sequencing. RESULTS: In southern China, the influenza positivity rate was elevated especially after March 2021 and was higher than the same period the previous year with the COVID-19 pandemic. In northern China, influenza positive rate peaked at Week 18 in 2021 and has declined since then. Nearly all isolated viruses were B/Victoria lineage viruses during the study period, and 37.3% of these viruses are antigenically similar to the reference viruses representing the vaccine components for the 2020-2021 and 2021-2022 Northern Hemisphere influenza season. All seasonal influenza viruses were susceptible to neuraminidase inhibitors and endonuclease inhibitors. CONCLUSIONS: Influenza activity has gradually increased in the mainland of China in 2021, although the intensity of activity is still lower than before the COVID-19 pandemic. The diversity of circulating influenza types/subtypes decreased, with the vast majority being B/Victoria lineage viruses. The surveillance data from this study suggest that we should strengthen influenza surveillance during the upcoming traditional influenza season. It also provided evidence for vaccine recommendations and prevention and control of influenza and clinical use of antiviral drugs.

15.
mBio ; 12(5): e0137221, 2021 10 26.
Article in English | MEDLINE | ID: covidwho-1462899

ABSTRACT

Interleukin6 (IL-6) is a key driver of hyperinflammation in COVID-19, and its level strongly correlates with disease progression. To investigate whether variability in COVID-19 severity partially results from differential IL-6 expression, functional single-nucleotide polymorphisms (SNPs) of IL-6 were determined in Chinese COVID-19 patients with mild or severe illness. An Asian-common IL-6 haplotype defined by promoter SNP rs1800796 and intronic SNPs rs1524107 and rs2066992 correlated with COVID-19 severity. Homozygote carriers of C-T-T variant haplotype were at lower risk of developing severe symptoms (odds ratio, 0.256; 95% confidence interval, 0.088 to 0.739; P = 0.007). This protective haplotype was associated with lower levels of IL-6 and its antisense long noncoding RNA IL-6-AS1 by cis-expression quantitative trait loci analysis. The differences in expression resulted from the disturbance of stimulus-dependent bidirectional transcription of the IL-6/IL-6-AS1 locus by the polymorphisms. The protective rs2066992-T allele disrupted a conserved CTCF-binding locus at the enhancer elements of IL-6-AS1, which transcribed antisense to IL-6 and induces IL-6 expression in inflammatory responses. As a result, carriers of the protective allele had significantly reduced IL-6-AS1 expression and attenuated IL-6 induction in response to acute inflammatory stimuli and viral infection. Intriguingly, this low-producing variant that is endemic to present-day Asia was found in early humans who had inhabited mainland Asia since ∼40,000 years ago but not in other ancient humans, such as Neanderthals and Denisovans. The present study suggests that an individual's IL-6 genotype underlies COVID-19 outcome and may be used to guide IL-6 blockade therapy in Asian patients. IMPORTANCE Overproduction of cytokine interleukin-6 (IL-6) is a hallmark of severe COVID-19 and is believed to play a critical role in exacerbating the excessive inflammatory response. Polymorphisms in IL-6 account for the variability of IL-6 expression and disparities in infectious diseases, but its contribution to the clinical presentation of COVID-19 has not been reported. Here, we investigated IL-6 polymorphisms in severe and mild cases of COVID-19 in a Chinese population. The variant haplotype C-T-T, represented by rs1800796, rs1524107, and rs2066992 at the IL-6 locus, was reduced in patients with severe illness; in contrast, carriers of the wild-type haplotype G-C-G had higher risk of severe illness. Mechanistically, the protective variant haplotype lost CTCF binding at the IL-6 intron and responded poorly to inflammatory stimuli, which may protect the carriers from hyperinflammation in response to acute SARS-CoV-2 infection. These results point out the possibility that IL-6 genotypes underlie the differential viral virulence during the outbreak of COVID-19. The risk loci we identified may serve as a genetic marker to screen high-risk COVID-19 patients.


Subject(s)
COVID-19/metabolism , COVID-19/prevention & control , Interleukin-6/metabolism , A549 Cells , Genotype , Haplotypes/genetics , HeLa Cells , Humans , Interleukin-6/genetics , Polymorphism, Single Nucleotide/genetics , Real-Time Polymerase Chain Reaction , Software
17.
Diagn Microbiol Infect Dis ; 101(4): 115537, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1401413

ABSTRACT

We aim to study kinetics of anti-SARS-CoV-2 IgG antibody levels in subjects with COVID-19 for up to 11 months and the potential influential factors. The study was a prospective longitudinal study. The analyses were based on 77 serum/plasma samples with a mean of 4 samples per participant (range 1 - 18) in 20 participants with at least one positive Polymerase Chain Reaction testing result from 19 March 2020 up to 10 February 2021. Among the subjects (median age 34.5 years, 65% male), IgG level declined with the follow-up time (per month; geometric mean ratio [GMR] 0.73; 95% CI, 0.72 - 0.74). In a small sample of subjects from the general population with COVID-19, IgG levels declined non-linearly from month 2 to 11 with individual heterogeneity in quantity and changing speed and may be associated with gender, race and the loss of smell and taste.


Subject(s)
COVID-19/blood , Immunoglobulin G/blood , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Viral , COVID-19/immunology , COVID-19/virology , Female , Follow-Up Studies , Humans , Kinetics , Longitudinal Studies , Male , Middle Aged , Prospective Studies , Time Factors , Young Adult
19.
Blood Res ; 56(3): 205-207, 2021 Sep 30.
Article in English | MEDLINE | ID: covidwho-1380049
20.
Science ; 373(6557): 918-922, 2021 08 20.
Article in English | MEDLINE | ID: covidwho-1367378

ABSTRACT

Zoonotic avian influenza A virus (IAV) infections are rare. Sustained transmission of these IAVs between humans has not been observed, suggesting a role for host genes. We used whole-genome sequencing to compare avian IAV H7N9 patients with healthy controls and observed a strong association between H7N9 infection and rare, heterozygous single-nucleotide variants in the MX1 gene. MX1 codes for myxovirus resistance protein A (MxA), an interferon-induced antiviral guanosine triphosphatase known to control IAV infections in transgenic mice. Most of the MxA variants identified lost the ability to inhibit avian IAVs, including H7N9, in transfected human cell lines. Nearly all of the inactive MxA variants exerted a dominant-negative effect on the antiviral function of wild-type MxA, suggesting an MxA null phenotype in heterozygous carriers. Our study provides genetic evidence for a crucial role of the MX1-based antiviral defense in controlling zoonotic IAV infections in humans.


Subject(s)
Influenza A Virus, H7N9 Subtype , Influenza, Human/genetics , Influenza, Human/virology , Myxovirus Resistance Proteins/genetics , Agricultural Workers' Diseases/genetics , Agricultural Workers' Diseases/virology , Animals , Cell Line , Genetic Predisposition to Disease , Genetic Variation , Heterozygote , Humans , Influenza A Virus, H7N9 Subtype/physiology , Influenza A virus/physiology , Mutation, Missense , Myxovirus Resistance Proteins/chemistry , Myxovirus Resistance Proteins/metabolism , Poultry , Viral Zoonoses , Whole Genome Sequencing
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