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1.
Nat Commun ; 14(1): 3286, 2023 06 13.
Article in English | MEDLINE | ID: covidwho-20231892

ABSTRACT

Some people remain healthier throughout life than others but the underlying reasons are poorly understood. Here we hypothesize this advantage is attributable in part to optimal immune resilience (IR), defined as the capacity to preserve and/or rapidly restore immune functions that promote disease resistance (immunocompetence) and control inflammation in infectious diseases as well as other causes of inflammatory stress. We gauge IR levels with two distinct peripheral blood metrics that quantify the balance between (i) CD8+ and CD4+ T-cell levels and (ii) gene expression signatures tracking longevity-associated immunocompetence and mortality-associated inflammation. Profiles of IR metrics in ~48,500 individuals collectively indicate that some persons resist degradation of IR both during aging and when challenged with varied inflammatory stressors. With this resistance, preservation of optimal IR tracked (i) a lower risk of HIV acquisition, AIDS development, symptomatic influenza infection, and recurrent skin cancer; (ii) survival during COVID-19 and sepsis; and (iii) longevity. IR degradation is potentially reversible by decreasing inflammatory stress. Overall, we show that optimal IR is a trait observed across the age spectrum, more common in females, and aligned with a specific immunocompetence-inflammation balance linked to favorable immunity-dependent health outcomes. IR metrics and mechanisms have utility both as biomarkers for measuring immune health and for improving health outcomes.


Subject(s)
COVID-19 , Longevity , Female , Humans , Aging , Inflammation , Outcome Assessment, Health Care
2.
BMC Med Inform Decis Mak ; 23(1): 34, 2023 02 14.
Article in English | MEDLINE | ID: covidwho-2287764

ABSTRACT

In recent years, relation extraction on unstructured texts has become an important task in medical research. However, relation extraction requires a large amount of labeled corpus, manually annotating sequences is time consuming and expensive. Therefore, efficient and economical methods for annotating sequences are required to ensure the performance of relational extraction. This paper proposes a method of subsequence and distant supervision based active learning. The method is annotated by selecting information-rich subsequences as a sampling unit instead of the full sentences in traditional active learning. Additionally, the method saves the labeled subsequence texts and their corresponding labels in a dictionary which is continuously updated and maintained, and pre-labels the unlabeled set through text matching based on the idea of distant supervision. Finally, the method combines a Chinese-RoBERTa-CRF model for relation extraction in Chinese medical texts. Experimental results test on the CMeIE dataset achieves the best performance compared to existing methods. And the best F1 value obtained between different sampling strategies is 55.96%.


Subject(s)
Problem-Based Learning , Supervised Machine Learning , Language , China , Reference Books, Medical
3.
Cell Discov ; 9(1): 2, 2023 Jan 06.
Article in English | MEDLINE | ID: covidwho-2185790

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Antibody resistance dampens neutralizing antibody therapy and threatens current global Coronavirus (COVID-19) vaccine campaigns. In addition to the emergence of resistant SARS-CoV-2 variants, little is known about how SARS-CoV-2 evades antibodies. Here, we report a novel mechanism of extracellular vesicle (EV)-mediated cell-to-cell transmission of SARS-CoV-2, which facilitates SARS-CoV-2 to escape from neutralizing antibodies. These EVs, initially observed in SARS-CoV-2 envelope protein-expressing cells, are secreted by various SARS-CoV-2-infected cells, including Vero E6, Calu-3, and HPAEpiC cells, undergoing infection-induced pyroptosis. Various SARS-CoV-2-infected cells produce similar EVs characterized by extra-large sizes (1.6-9.5 µm in diameter, average diameter > 4.2 µm) much larger than previously reported virus-generated vesicles. Transmission electron microscopy analysis and plaque assay reveal that these SARS-CoV-2-induced EVs contain large amounts of live virus particles. In particular, the vesicle-cloaked SARS-CoV-2 virus is resistant to neutralizing antibodies and able to reinfect naïve cells independent of the reported receptors and cofactors. Consistently, the constructed 3D images show that intact EVs could be taken up by recipient cells directly, supporting vesicle-mediated cell-to-cell transmission of SARS-CoV-2. Our findings reveal a novel mechanism of receptor-independent SARS-CoV-2 infection via cell-to-cell transmission, provide new insights into antibody resistance of SARS-CoV-2 and suggest potential targets for future antiviral therapeutics.

4.
Front Microbiol ; 13: 1071394, 2022.
Article in English | MEDLINE | ID: covidwho-2199024

ABSTRACT

Porcine epidemic diarrhea virus (PEDV) in the Coronavirus family is a highly contagious enteric pathogen in the swine industry, which has evolved mechanisms to evade host innate immune responses. The PEDV-mediated inhibition of interferons (IFNs) has been linked to the nuclear factor-kappa B (NF-κB) pathway. MicroRNAs (miRNAs) are involved in virus-host interactions and IFN-I regulation. However, the mechanism by which the PEDV regulates IFN during PEDV infection has not yet been investigated in its natural target cells. We here report a novel mechanism of viral immune escape involving miR-615, which was screened from a high-throughput sequencing library of porcine intestinal epithelial cells (IECs) infected with PEDV. PEDV infection altered the profiles of miRNAs and the activities of several pathways involved in innate immunity. Overexpression of miR-615 increased PEDV replication, inhibited IFN expression, downregulated the NF-κB pathway, and blocked p65 nuclear translocation. In contrast, knockdown of miR-615 enhanced IFN expression, suppressed PEDV replication, and activated the NF-κB pathway. We further determined that IRAK1 is the target gene of miR-615 in IECs. Our findings show that miR-615 suppresses activation of the NF-κB pathway by suppressing the IRAK1 protein and reducing the generation of IFN-IIIs, which in turn facilitates PEDV infection in IECs. Moreover, miR-615 inhibited PEDV replication and NF-κB pathway activation in both IECs and MARC-145 cells. These findings support an important role for miR-615 in the innate immune regulation of PEDV infections and provide a novel perspective for developing new treatments.

5.
Commun Med (Lond) ; 2(1): 151, 2022 Nov 25.
Article in English | MEDLINE | ID: covidwho-2133667

ABSTRACT

BACKGROUND: People living with chronic disease, particularly seniors (≥60 years old), made up of most severe symptom and death cases among SARS-CoV-2 infected patients. However, they are lagging behind in the national COVID-19 vaccination campaign in China due to the uncertainty of vaccine safety and effectiveness. Safety and immunogenicity data of COVID-19 vaccines in people with underlying medical conditions are needed to address the vaccine hesitation in this population. METHODS: We included participants (≥40 years old) who received two doses of CoronaVac inactivated vaccines (at a 3-5 week interval) and were healthy or had at least one of 6 common chronic diseases. The incidence of adverse events after vaccination was monitored. Vaccine immunogenicity was studied by determining neutralizing antibodies and SARS-CoV-2-specific T cell responses post vaccination. RESULTS: Here we show that chronic diseases are associated with a higher rate of mild fatigue following the first dose of CoronaVac. By day 14-28 post vaccination, the neutralizing antibody level shows no significant difference between disease groups and healthy controls, except for people with coronary artery disease (p = 0.0287) and chronic respiratory disease (p = 0.0416), who show moderate reductions. Such differences diminish by day 90 and 180. Most people show detectable SARS-CoV-2-specific T cell responses at day 90 and day 180 without significant differences between disease groups and healthy controls. CONCLUSIONS: Our results highlight the comparable safety, immunogenicity and cellular immunity memory of CoronaVac in seniors and people living with chronic diseases. This data should reduce vaccine hesitancy in this population.


People living with chronic diseases, particularly those over the age of 60, are more likely to have severe symptoms and die following SARS-CoV-2 infection. However, many have not been vaccinated during the national COVID-19 vaccination campaign in China due to concerns about vaccine safety and effectiveness. Here we show that the inactivated COVID-19 vaccine, CoronaVac, is as safe in older people with chronic diseases as it is for healthy people. Also, only slightly differences are seen in the immune response of people with diseases compared to healthy people. Overall, our results highlight that the CoronaVac vaccine is safe and effective in people living with chronic diseases.

6.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(10): 1092-1097, 2022 Oct 15.
Article in Chinese | MEDLINE | ID: covidwho-2090827

ABSTRACT

OBJECTIVES: To study the clinical features of children infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: The medical data of 19 children who were diagnosed with SARS-CoV-2 Omicron variant infection from January 28 to March 3, 2022 in Hangzhou were retrospectively reviewed. RESULTS: Among the 19 children, there were 7 boys (37%) and 12 girls (63%), and their age ranged from 6 months to 16 years, with a median age of 2 years and 1 month. Most of these children were infants and young children (aged ≤3 years, accounting for 53%). Among these children, 11 (58%) were unvaccinated with SARS-CoV-2 vaccine and 8 (42%) were vaccinated with SARS-CoV-2 vaccine, and 3 children (16%) had a history of underlying diseases. All 19 children had a clear history of close contact with persons infected with SARS-CoV-2, and 10 children (53%) were involved in the cluster outbreak in a maternal and infant care center. In terms of clinical classification, 13 children (68%) had mild coronavirus disease 2019 (COVID-19) and 6 (32%) had common COVID-19, with no severe cases of COVID-19. The most common clinical symptoms were cough (100%) and fever (63%). The children with a normal peripheral white blood cell count accounted for 84%, and those with a normal lymphocyte count accounted for 68%. There were no significant abnormalities in platelet count, procalcitonin, liver function parameters (alanine aminotransferase and aspartate aminotransferase), and renal function parameters (creatinine and urea). Six children (32%) had obvious signs of pneumonia on chest CT. All 19 children were given symptomatic treatment, and 12 children (63%) were given aerosol inhalation of interferon α. All children were cured and discharged. CONCLUSIONS: Children infected with Omicron variant strains are more common in infants and young children, with mild symptoms and good prognosis. Most of the children have a history of close contact with persons infected with SARS-CoV-2, and epidemic prevention and control should be strengthened in places with many infants and children, such as maternal and infant care centers.


Subject(s)
COVID-19 , SARS-CoV-2 , Child , Infant , Male , Female , Humans , Child, Preschool , Retrospective Studies , COVID-19 Vaccines , China/epidemiology
7.
Nat Med ; 28(8): 1715-1722, 2022 08.
Article in English | MEDLINE | ID: covidwho-1900516

ABSTRACT

Timely evaluation of the protective effects of Coronavirus Disease 2019 (COVID-19) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern is urgently needed to inform pandemic control planning. Based on 78 vaccine efficacy or effectiveness (VE) data from 49 studies and 1,984,241 SARS-CoV-2 sequences collected from 31 regions, we analyzed the relationship between genetic distance (GD) of circulating viruses against the vaccine strain and VE against symptomatic infection. We found that the GD of the receptor-binding domain of the SARS-CoV-2 spike protein is highly predictive of vaccine protection and accounted for 86.3% (P = 0.038) of the VE change in a vaccine platform-based mixed-effects model and 87.9% (P = 0.006) in a manufacturer-based model. We applied the VE-GD model to predict protection mediated by existing vaccines against new genetic variants and validated the results by published real-world and clinical trial data, finding high concordance of predicted VE with observed VE. We estimated the VE against the Delta variant to be 82.8% (95% prediction interval: 68.7-96.0) using the mRNA vaccine platform, closely matching the reported VE of 83.0% from an observational study. Among the four sublineages of Omicron, the predicted VE varied between 11.9% and 33.3%, with the highest VE predicted against BA.1 and the lowest against BA.2, using the mRNA vaccine platform. The VE-GD framework enables predictions of vaccine protection in real time and offers a rapid evaluation method against novel variants that may inform vaccine deployment and public health responses.


Subject(s)
COVID-19 , Viral Vaccines , COVID-19/prevention & control , COVID-19 Vaccines , Humans , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus , Vaccine Efficacy , Vaccines, Synthetic , mRNA Vaccines
9.
Front Psychiatry ; 13: 837846, 2022.
Article in English | MEDLINE | ID: covidwho-1809597

ABSTRACT

The COVID-19 outbreak triggered dramatic changes to family life. Parents, especially mothers, were found to experience more psychological distress during the pandemic, which may have had an impact on their children's mental health. The primary goal of this study was to examine the potential protective role of adolescents' self-compassion in the relationship between maternal anxiety and adolescents' mental health during the COVID-19 pandemic. Participants included 5,720 adolescents (48.9% girls; M age = 11.60, SD age = 1.36) and their mothers from Zhengzhou city, Henan province, in Mainland China. Adolescents reported their level of self-compassion, PTSD symptoms, and negative affect during the COVID-19 pandemic. Mothers reported their own anxiety symptoms and their children's depression and anxiety symptoms. Results indicated that older female adolescents reported higher levels of PTSD symptoms and negative affect and lower levels of self-compassion than their counterparts. Maternal anxiety during the COVID-19 pandemic was consistently positively associated with adolescents' psychological maladjustment. These associations were buffered by adolescents' self-compassion. Specifically, adolescents with higher levels of self-compassion were found to be less psychologically affected by their mothers' anxiety during the COVID-19 pandemic. Findings highlighted the possibility of improving adolescents' mental health through fostering their self-compassion during the COVID-19 pandemic.

10.
J Infect Public Health ; 15(3): 338-342, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1665197

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has become a major public health threat. This study aims to evaluate the effect of virus mutation activities and policy interventions on COVID-19 transmissibility in Hong Kong. METHODS: In this study, we integrated the genetic activities of multiple proteins, and quantified the effect of government interventions and mutation activities against the time-varying effective reproduction number Rt. FINDINGS: We found a significantly positive relationship between Rt and mutation activities and a significantly negative relationship between Rt and government interventions. The results showed that the mutations that contributed most to the increase of Rt were from the spike, nucleocapsid and ORF1b genes. Policy of prohibition on group gathering was estimated to have the largest impact on mitigating virus transmissibility. The model explained 63.2% of the Rt variability with the R2. CONCLUSION: Our study provided a convenient framework to estimate the effect of genetic contribution and government interventions on pathogen transmissibility. We showed that the S, N and ORF1b protein had significant contribution to the increase of transmissibility of SARS-CoV-2 in Hong Kong, while restrictions of public gathering and suspension of face-to-face class are the most effective government interventions strategies.


Subject(s)
COVID-19 , Pandemics , Government , Humans , Mutation , Pandemics/prevention & control , SARS-CoV-2/genetics
11.
Cell Discov ; 8(1): 9, 2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-1661959

ABSTRACT

Safe, effective, and economical vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to achieve adequate herd immunity and end the pandemic. We constructed a novel SARS-CoV-2 vaccine, CoVac501, which is a self-adjuvanting peptide vaccine conjugated with Toll-like receptor 7 (TLR7) agonists. The vaccine contains immunodominant peptides screened from the receptor-binding domain (RBD) and is fully chemically synthesized. It has been formulated in an optimized nanoemulsion formulation and is stable at 40 °C for 1 month. In non-human primates (NHPs), CoVac501 elicited high and persistent titers of protective neutralizing antibodies against multiple RBD mutations, SARS-CoV-2 original strain, and variants (B.1.1.7 and B.1.617.2). Specific peptides booster immunization against the B.1.351 variant has also been shown to be effective in improving protection against B.1.351. Meanwhile, CoVac501 elicited the increase of memory T cells, antigen-specific CD8+ T-cell responses, and Th1-biased CD4+ T-cell immune responses in NHPs. Notably, at an extremely high SARS-CoV-2 challenge dose of 1 × 107 TCID50, CoVac501 provided near-complete protection for the upper and lower respiratory tracts of cynomolgus macaques.

12.
Sci Rep ; 12(1): 889, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1630723

ABSTRACT

Predicting the severity of COVID-19 remains an unmet medical need. Our objective was to develop a blood-based host-gene-expression classifier for the severity of viral infections and validate it in independent data, including COVID-19. We developed a logistic regression-based classifier for the severity of viral infections and validated it in multiple viral infection settings including COVID-19. We used training data (N = 705) from 21 retrospective transcriptomic clinical studies of influenza and other viral illnesses looking at a preselected panel of host immune response messenger RNAs. We selected 6 host RNAs and trained logistic regression classifier with a cross-validation area under curve of 0.90 for predicting 30-day mortality in viral illnesses. Next, in 1417 samples across 21 independent retrospective cohorts the locked 6-RNA classifier had an area under curve of 0.94 for discriminating patients with severe vs. non-severe infection. Next, in independent cohorts of prospectively (N = 97) and retrospectively (N = 100) enrolled patients with confirmed COVID-19, the classifier had an area under curve of 0.89 and 0.87, respectively, for identifying patients with severe respiratory failure or 30-day mortality. Finally, we developed a loop-mediated isothermal gene expression assay for the 6-messenger-RNA panel to facilitate implementation as a rapid assay. With further study, the classifier could assist in the risk assessment of COVID-19 and other acute viral infections patients to determine severity and level of care, thereby improving patient management and reducing healthcare burden.


Subject(s)
COVID-19 , Gene Expression Regulation , RNA, Messenger/blood , SARS-CoV-2/metabolism , Acute Disease , COVID-19/blood , COVID-19/mortality , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies
13.
Public Health Genomics ; : 1-4, 2022 Jan 05.
Article in English | MEDLINE | ID: covidwho-1606251

ABSTRACT

During coronavirus disease 2019 (COVID-19) pandemic, the genetic mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred frequently. Some mutations in the spike protein are considered to promote transmissibility of the virus, while the mutation patterns in other proteins are less studied and may also be important in understanding the characteristics of SARS-CoV-2. We used the sequencing data of SARS-CoV-2 strains in California to investigate the time-varying patterns of the evolutionary genetic distance. The accumulative genetic distances were quantified across different time periods and in different viral proteins. The increasing trends of genetic distance were observed in spike protein (S protein), the RNA-dependent RNA polymerase (RdRp) region and nonstructural protein 3 (nsp3) of open reading frame 1 (ORF1), and nucleocapsid protein (N protein). The genetic distances in ORF3a, ORF8, and nsp2 of ORF1 started to diverge from their original variants after September 2020. By contrast, mutations in other proteins appeared transiently, and no evident increasing trend was observed in the genetic distance to the original variants. This study presents distinct patterns of the SARS-CoV-2 mutations across multiple proteins from the aspect of genetic distance. Future investigation shall be conducted to study the effects of accumulative mutations on epidemics characteristics.

14.
Signal Transduct Target Ther ; 6(1): 428, 2021 12 17.
Article in English | MEDLINE | ID: covidwho-1585884

ABSTRACT

SARS-CoV-2 infection-induced hyper-inflammation links to the acute lung injury and COVID-19 severity. Identifying the primary mediators that initiate the uncontrolled hypercytokinemia is essential for treatments. Mast cells (MCs) are strategically located at the mucosa and beneficially or detrimentally regulate immune inflammations. In this study, we showed that SARS-CoV-2-triggered MC degranulation initiated alveolar epithelial inflammation and lung injury. SARS-CoV-2 challenge induced MC degranulation in ACE-2 humanized mice and rhesus macaques, and a rapid MC degranulation could be recapitulated with Spike-RBD binding to ACE2 in cells; MC degranulation altered various signaling pathways in alveolar epithelial cells, particularly, the induction of pro-inflammatory factors and consequential disruption of tight junctions. Importantly, the administration of clinical MC stabilizers for blocking degranulation dampened SARS-CoV-2-induced production of pro-inflammatory factors and prevented lung injury. These findings uncover a novel mechanism for SARS-CoV-2 initiating lung inflammation, and suggest an off-label use of MC stabilizer as immunomodulators for COVID-19 treatments.


Subject(s)
COVID-19/metabolism , Cell Degranulation , Lung Injury/metabolism , Mast Cells/metabolism , Pulmonary Alveoli/metabolism , SARS-CoV-2/metabolism , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/genetics , Cell Line, Tumor , Female , Humans , Lung Injury/genetics , Lung Injury/virology , Macaca mulatta , Male , Mice, Inbred BALB C , Mice, Transgenic , Pulmonary Alveoli/virology , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism
15.
BMC Infect Dis ; 21(1): 1039, 2021 Oct 07.
Article in English | MEDLINE | ID: covidwho-1455943

ABSTRACT

BACKGROUND: The COVID-19 pandemic poses serious threats to global health, and the emerging mutation in SARS-CoV-2 genomes, e.g., the D614G substitution, is one of the major challenges of disease control. Characterizing the role of the mutation activities is of importance to understand how the evolution of pathogen shapes the epidemiological outcomes at population scale. METHODS: We developed a statistical framework to reconstruct variant-specific reproduction numbers and estimate transmission advantage associated with the mutation activities marked by single substitution empirically. Using likelihood-based approach, the model is exemplified with the COVID-19 surveillance data from January 1 to June 30, 2020 in California, USA. We explore the potential of this framework to generate early warning signals for detecting transmission advantage on a real-time basis. RESULTS: The modelling framework in this study links together the mutation activity at molecular scale and COVID-19 transmissibility at population scale. We find a significant transmission advantage of COVID-19 associated with the D614G substitution, which increases the infectivity by 54% (95%CI: 36, 72). For the early alarming potentials, the analytical framework is demonstrated to detect this transmission advantage, before the mutation reaches dominance, on a real-time basis. CONCLUSIONS: We reported an evidence of transmission advantage associated with D614G substitution, and highlighted the real-time estimating potentials of modelling framework.


Subject(s)
COVID-19 , Genome, Viral , SARS-CoV-2 , COVID-19/virology , Humans , Likelihood Functions , Mutation , Pandemics , SARS-CoV-2/genetics
16.
Nat Commun ; 12(1): 5026, 2021 08 18.
Article in English | MEDLINE | ID: covidwho-1363491

ABSTRACT

Nationwide prospective surveillance of all-age patients with acute respiratory infections was conducted in China between 2009‒2019. Here we report the etiological and epidemiological features of the 231,107 eligible patients enrolled in this analysis. Children <5 years old and school-age children have the highest viral positivity rate (46.9%) and bacterial positivity rate (30.9%). Influenza virus, respiratory syncytial virus and human rhinovirus are the three leading viral pathogens with proportions of 28.5%, 16.8% and 16.7%, and Streptococcus pneumoniae, Mycoplasma pneumoniae and Klebsiella pneumoniae are the three leading bacterial pathogens (29.9%, 18.6% and 15.8%). Negative interactions between viruses and positive interactions between viral and bacterial pathogens are common. A Join-Point analysis reveals the age-specific positivity rate and how this varied for individual pathogens. These data indicate that differential priorities for diagnosis, prevention and control should be highlighted in terms of acute respiratory tract infection patients' demography, geographic locations and season of illness in China.


Subject(s)
Bacteria/isolation & purification , Bacterial Infections/microbiology , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/virology , Virus Diseases/virology , Viruses/isolation & purification , Adolescent , Adult , Bacteria/classification , Bacteria/genetics , Bacterial Infections/epidemiology , Child , Child, Preschool , China/epidemiology , Female , Humans , Infant , Male , Prospective Studies , Respiratory Tract Infections/epidemiology , Seasons , Virus Diseases/epidemiology , Viruses/classification , Viruses/genetics , Young Adult
17.
Signal Transduct Target Ther ; 6(1): 328, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1392810

ABSTRACT

Understanding the pathological features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in an animal model is crucial for the treatment of coronavirus disease 2019 (COVID-19). Here, we compared immunopathological changes in young and old rhesus macaques (RMs) before and after SARS-CoV-2 infection at the tissue level. Quantitative analysis of multiplex immunofluorescence staining images of formalin-fixed paraffin-embedded (FFPE) sections showed that SARS-CoV-2 infection specifically induced elevated levels of apoptosis, autophagy, and nuclear factor kappa-B (NF-κB) activation of angiotensin-converting enzyme 2 (ACE2)+ cells, and increased interferon α (IFN-α)- and interleukin 6 (IL-6)-secreting cells and C-X-C motif chemokine receptor 3 (CXCR3)+ cells in lung tissue of old RMs. This pathological pattern, which may be related to the age-related pro-inflammatory microenvironment in both lungs and spleens, was significantly correlated with the systemic accumulation of CXCR3+ cells in lungs, spleens, and peripheral blood. Furthermore, the ratio of CXCR3+ to T-box protein expression in T cell (T-bet)+ (CXCR3+/T-bet+ ratio) in CD8+ cells may be used as a predictor of severe COVID-19. These findings uncovered the impact of aging on the immunopathology of early SARS-CoV-2 infection and demonstrated the potential application of CXCR3+ cells in predicting severe COVID-19.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Cellular Microenvironment/immunology , Lung/immunology , Receptors, CXCR3/immunology , SARS-CoV-2/immunology , Angiotensin-Converting Enzyme 2/immunology , Animals , CD8-Positive T-Lymphocytes/pathology , COVID-19/pathology , Disease Models, Animal , Inflammation/immunology , Inflammation/pathology , Interferon-alpha/immunology , Interleukin-6/immunology , Lung/pathology , Lung/virology , Macaca mulatta , Male
18.
Immunity ; 54(4): 753-768.e5, 2021 04 13.
Article in English | MEDLINE | ID: covidwho-1385739

ABSTRACT

Viral infections induce a conserved host response distinct from bacterial infections. We hypothesized that the conserved response is associated with disease severity and is distinct between patients with different outcomes. To test this, we integrated 4,780 blood transcriptome profiles from patients aged 0 to 90 years infected with one of 16 viruses, including SARS-CoV-2, Ebola, chikungunya, and influenza, across 34 cohorts from 18 countries, and single-cell RNA sequencing profiles of 702,970 immune cells from 289 samples across three cohorts. Severe viral infection was associated with increased hematopoiesis, myelopoiesis, and myeloid-derived suppressor cells. We identified protective and detrimental gene modules that defined distinct trajectories associated with mild versus severe outcomes. The interferon response was decoupled from the protective host response in patients with severe outcomes. These findings were consistent, irrespective of age and virus, and provide insights to accelerate the development of diagnostics and host-directed therapies to improve global pandemic preparedness.


Subject(s)
Immunity/genetics , Virus Diseases/immunology , Antigen Presentation/genetics , Cohort Studies , Hematopoiesis/genetics , Humans , Interferons/blood , Killer Cells, Natural/immunology , Killer Cells, Natural/pathology , Myeloid Cells/immunology , Myeloid Cells/pathology , Prognosis , Severity of Illness Index , Systems Biology , Transcriptome , Virus Diseases/blood , Virus Diseases/classification , Virus Diseases/genetics , Viruses/classification , Viruses/pathogenicity
20.
Front Psychiatry ; 12: 694051, 2021.
Article in English | MEDLINE | ID: covidwho-1369728

ABSTRACT

Objective: The 2019 novel coronavirus disease (COVID-19) broke out in Hubei Province and spread rapidly to the whole country, causing huge public health problems. College students are a special group, and there is no survey on insomnia among college students. The purpose of this study was to investigate the incidence and related factors of insomnia in college students during the period of COVID-19. Method: A total of 1,086 college students conducted a cross-sectional study through the questionnaire star platform. The survey time was from February 15 to February 22, 2020. The collected information included demographic informatics and mental health scale, Athens Insomnia Scale (AIS) to assess sleep quality, Self-Reporting Questionnaire-20 (SRQ-20) to assess general psychological symptoms, Chinese perceived stress scale (CPSS) to assess stress. We used logistic regression to analyze the correlation between related factors and insomnia symptoms. Results: The prevalence of insomnia, general psychological symptoms and stress were 16.67, 5.8, and 40.70%, respectively. Multivariate logistic regression analysis showed that gender (OR = 1.55, p = 0.044, 95% CI = 1.00-2.41), general psychological symptoms (OR = 1.49, p < 0.01, 95% CI = 1.40-1.60) and living in an isolation unit (OR = 2.21, p = 0.014, 95% CI = 1.17-4.16) were risk factors for insomnia of college students. Conclusion: Our results show that the insomnia is very common among college students during the outbreak of covid-19, and the related factors include gender, general psychological symptoms and isolation environment. It is necessary to intervene the insomnia of college students and warrants attention for mental well-being of college students.

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