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1.
Pharmacol Res ; : 106092, 2022 Jan 20.
Article in English | MEDLINE | ID: covidwho-1639171

ABSTRACT

Kinsenoside (KD) exhibits anti-inflammation and immunosuppressive effects. Dendritic cells (DCs) are critical regulators of the pathologic inflammatory milieu in liver fibrosis (LF). Herein, we explored whether and how KD repressed development of LF via DC regulation and verified the pathway involved in the process. Given our analysis, both KD and adoptive transfer of KD-conditioned DC conspicuously reduced hepatic histopathological damage, proinflammatory cytokines release and extracellular matrix deposition in CCl4-induced LF mice. Of note, KD restrained the LF-driven rise in CD86, MHC-II, and CCR7 levels and, simultaneously, upregulated PD-L1 expression on DCs specifically, which blocked CD8+T cell activation. Additionally, KD reduced DC glycolysis, maintained DCs immature, accompanied by IL-12 decrease in DCs. Inhibiting DC function by KD disturbed the communication of DCs and HSCs with the expression or secretion of α-SMA and Col-I declined in the liver. Mechanistically, KD suppressed the phosphorylation of PI3K-AKT driven by LF or PI3K agonist, followed by enhanced nuclear transport of FoxO1 and upregulated interaction of FoxO1 with the PD-L1 promoter in DCs. PI3K inhibitor or si-IL-12 in DC could relieve LF, HSC activation and diminish the effect of KD. In conclusion, KD suppressed DC maturation with promoted PD-L1 expression via PI3K-AKT-FoxO1 and decreased IL-12 secretion, which blocked activation of CD8+T cells and HSCs, thereby alleviating liver injury and fibro-inflammation in LF.

2.
J Thorac Dis ; 13(12): 6866-6875, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1623786

ABSTRACT

Background: The coronavirus disease 2019 (COVID-19) pandemic is still raging worldwide. Efficient, fast and low-cost severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid detection methods are urgently needed. Methods: A rapid PCR temperature change mode was explored by moving the reaction tube between the independent temperature modules with large temperature differences and a portable ultra-fast real-time PCR instrument were developed. We established a rapid SARS-CoV-2 test method using the ultra-fast real-time PCR instrument, a China Food and Drug Administration-certified SARS-CoV-2 reagent and optimized reaction condition. The analytical and clinical performances of the rapid tests were evaluated by comparing with the standard SARS-CoV-2 tests. Results: The new temperature change mode can effectively shorten the amplification reaction time and be successfully used in the development of the ultra-fast real-time PCR instrument. The rapid SARS-CoV-2 test method was established and the time to yield results were greatly shortened from 81 min of the standard test to 31 min. Specificity of the rapid test was assessed and no non-specific amplification (0/63) was observed. The limits of detection of the rapid and standard tests were similar. Clinical performance was evaluated using 184 respiratory specimens from patients with suspected SARS-CoV-2 infection. The positive agreement between the rapid and standard tests was 100% (67/67), the negative agreement was 97.4% (114/117), and the kappa statistic was 0.965 (P<0.001). No significant differences in the Ct values for each target gene were observed between the rapid test and the standard test (P>0.05). Conclusions: We had developed a 30-minute detection method for SARS-CoV-2 nucleic acid using a novel ultra-fast real-time PCR instrument. The rapid test method may impact on patient management.

3.
Int J Biol Sci ; 17(1): 20-31, 2021.
Article in English | MEDLINE | ID: covidwho-1526974

ABSTRACT

The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global infection, and is seriously threatening human life, especially cancer patients. Thus, we sought to determine the clinical roles of ACE2 (the cell entry receptor of SARS-CoV-2) in ccRCC (clear cell renal cell carcinoma). TCGA, GEO and TIP datasets, and immunohistochemistry and western blot results were used to determine the prognostic and clinicopathological characteristics of ACE2. ACE2 expression was down-regulated in ccRCC tissues and cell lines. The multivariate Cox regression analysis results indicated that increased ACE2 expression was independent predictor of longer OS (HR: 0.8259, 95%CI: 0.7734-0.8819, P<0.0001) and RFS (HR: 0.8023, 95%CI: 0.7375-0.8729, P<0.0001) in ccRCC patients. Lower ACE2 expression was also associated with advanced tumor stage, higher histological grade and pathological stage, and metastasis. Besides, ACE2 expression was significantly positively and negatively correlated with CD4 Naïve infiltration and CD4 Memory infiltration, respectively. Moreover, higher CD4 Naïve and lower CD4 Memory infiltration levels were associated with better pathological features and longer OS and RFS. Furthermore, high ACE2 expression group in decreased CD4 Naïve, enriched CD4 Naïve and enriched CD4 memory cohort had favorable prognosis. These findings identified that AEC2 was significantly reduced in ccRCC, and decreased ACE2 was related to worse pathological features and poor prognosis. Low ACE2 expression in ccRCC may partially affect the prognosis due to altered immune cells infiltration levels.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Renal Cell/metabolism , Kidney Neoplasms/metabolism , CD4-Positive T-Lymphocytes/immunology , COVID-19/immunology , COVID-19/metabolism , COVID-19/virology , Carcinoma, Renal Cell/immunology , Humans , Kidney Neoplasms/immunology , Prognosis , SARS-CoV-2/isolation & purification
4.
mBio ; : e0297521, 2021 Nov 16.
Article in English | MEDLINE | ID: covidwho-1518123

ABSTRACT

Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have arisen that exhibit increased viral transmissibility and partial evasion of immunity induced by natural infection and vaccination. To address the specific antibody targets that were affected by recent viral variants, we generated 43 monoclonal antibodies (mAbs) from 10 convalescent donors that bound three distinct domains of the SARS-CoV-2 spike. Viral variants harboring mutations at K417, E484, and N501 could escape most of the highly potent antibodies against the receptor binding domain (RBD). Despite this, we identified 12 neutralizing mAbs against three distinct regions of the spike protein that neutralize SARS-CoV-2 and variants of concern (VOCs), including B.1.1.7 (alpha), P.1 (gamma), and B.1.617.2 (delta). Notably, antibodies targeting distinct epitopes could neutralize discrete variants, suggesting that different variants may have evolved to disrupt the binding of particular neutralizing antibody classes. These results underscore that humans exposed to the first pandemic wave of prototype SARS-CoV-2 possess neutralizing antibodies against current variants and that it is critical to induce antibodies targeting multiple distinct epitopes of the spike that can neutralize emerging variants of concern. IMPORTANCE We describe the binding and neutralization properties of a new set of human monoclonal antibodies derived from memory B cells of 10 coronavirus disease 2019 (COVID-19) convalescent donors in the first pandemic wave of prototype SARS-CoV-2. There were 12 antibodies targeting distinct epitopes on spike, including two sites on the RBD and one on the N-terminal domain (NTD), that displayed cross-neutralization of VOCs, for which distinct antibody targets could neutralize discrete variants. This work underlines that natural infection by SARS-CoV-2 induces effective cross-neutralization against only some VOCs and supports the need for COVID-19 vaccination for robust induction of neutralizing antibodies targeting multiple epitopes of the spike protein to combat the current SARS-CoV-2 VOCs and any others that might emerge in the future.

5.
National Bureau of Economic Research Working Paper Series ; No. 28286, 2020.
Article in English | NBER, Grey literature | ID: grc-748647

ABSTRACT

We analyze bank supply of credit under the Paycheck Protection Program (PPP). The literature emphasizes relationships as a means to improve lender information, which helps banks manage credit risk. Despite imposing no risk, however, PPP supply reflects traditional measures of relationship lending: decreasing in bank size;increasing in prior experience, in commitment lending, and in core deposits. Our results suggest a new benefit of bank relationships, as they help firms access government-subsidized lending. Consistent with this benefit, we show that bank PPP supply, based on the structure of the local banking sector, alleviates increases in unemployment.

6.
National Bureau of Economic Research Working Paper Series ; No. 27256, 2020.
Article in English | NBER, Grey literature | ID: grc-748185

ABSTRACT

In March of 2020, banks faced the largest increase in liquidity demands ever observed. Firms drew funds on a massive scale from pre-existing credit lines and loan commitments in anticipation of cash flow disruptions from the economic shutdown designed to contain the COVID-19 crisis. The increase in liquidity demands was concentrated at the largest banks, who serve the largest firms. Pre-crisis financial condition did not limit banks’ liquidity supply. Coincident inflows of funds to banks from both the Federal Reserve’s liquidity injection programs and from depositors, along with strong pre-shock bank capital, explain why banks were able to accommodate these liquidity demands.

7.
J Control Release ; 340: 114-124, 2021 Oct 23.
Article in English | MEDLINE | ID: covidwho-1474707

ABSTRACT

The messenger RNA (mRNA)-based therapy, especially mRNA vaccines, has shown its superiorities in versatile design, rapid development and scale production, since the outbreak of coronavirus disease 2019 (COVID-19). Although the Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines had been approved for application, unexpected adverse events were reported to be most likely associated with the mRNA delivery systems. Thus, the development of mRNA delivery system with good efficacy and safety remains a challenge. Here, for the first time, we report that the neutral cytidinyl lipid, 2-(4-amino-2-oxopyrimidin-1-yl)-N-(2,3-dioleoyl-oxypropyl) acetamide (DNCA), and the cationic lipid, dioleoyl-3,3'-disulfanediylbis-[2-(2,6-diaminohexanamido)] propanoate (CLD), could encapsulate and deliver the COVID-19 mRNA-1096 into the cytoplasm to induce robust adaptive immune response. In the formulation, the molar ratio of DNCA/CLD to a single nucleotide of COVID-19 mRNA-1096 was about 0.9: 0.5: 1 (the N/P ratio was about 7: 1). The DNCA/CLD-mRNA-1096 lipoplexes were rationally prepared by the combination of the lipids DNCA/CLD with the aqueous mRNA solution under mild sonication to stimulate multiple interactions, including H-bonding, π-stacking and electrostatic force between the lipids and the mRNA. After intramuscular applications of the DNCA/CLD-mRNA-1096 lipoplexes, robust neutralizing antibodies and long-lived Th1-biased SARS-CoV-2-specific cell immunity were detected in the immunized mice, thus suggesting the DNCA/CLD a promising mRNA delivery system. Moreover, our study might also inspire better ideas for developing mRNA delivery systems.

8.
Bioanalysis ; 13(24): 1805-1826, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1468600

ABSTRACT

Vaccines are key in charting a path out of the COVID-19 pandemic. However, development of new vaccines is highly dependent on availability of analytical methods for their design and evaluation. This paper highlights the challenges presented in having to rapidly develop vaccine analytical tools during an ongoing pandemic, including the need to address progressive virus mutation and adaptation which can render initial assays unreliable or redundant. It also discusses the potential of new computational modeling techniques to model and analyze key viral proteins and their attributes to assist vaccine production and assay design. It then reviews the current range of analytical tools available for COVID-19 vaccine application, ranging from in vitro assays for immunogen characterization to assays to measure vaccine responses in vivo. Finally, it provides a future perspective for COVID-19 vaccine analytical tools and attempts to predict how the field might evolve over the next 5-10 years.

9.
Psychol Health Med ; : 1-13, 2021 Sep 19.
Article in English | MEDLINE | ID: covidwho-1429073

ABSTRACT

Being a nurse was demonstrated to be a risk factor for post-traumatic stress symptoms (PTS) and insomnia among frontline staff during COVID-19 pandemic. The unidirectional relationship between insomnia and PTS highly suggested that insomnia could mediate the increasing risk of PTS among frontline nurses. However, no study had tried to clarify this mediation effect of insomnia during COVID-19 pandemic. This study aimed to investigate prevalence of insomnia and PTS among frontline doctors and nurses and to clarify the relationship between career (doctor/nurses), insomnia and PTS. A total of 211 frontline doctors and nurses completed the investigation. Insomnia was measured using a self-drafted questionnaire and PTS was assessed using primary care post-traumatic stress disorder screen (PC-PTSD). Three logistics regression models and one mediation model were performed to explore relationships between career, insomnia and PTS. The prevalence of PTS (PC-PTSD≥2) and insomnia (with 1 item in self-drafted insomnia questionnaire≥2) was 24.17% and 36.97%, respectively. Being a nurse was a shared risk factor of insomnia (OR = 4.16, 95%CI: 1.30 ~ 5.77, P = 0.023) and PTS (OR = 7.51, 95%CI: 1.89 ~ 40.50, P = 0.008). Compared to doctors, nurses had significantly higher prevalence of insomnia (46.32% vs. 20%, χ2 = 13.27, P < 0.001) and PTS (30.14% vs. 13.33%, χ2 = 6.57, P = 0.011). Insomnia was a significant partial mediator (B = 0.101, P = 0.026), which explained 32.53% proportions of relationship between being a nurse and PTS. PTS and insomnia were common symptoms, which should be considered in psychological aids among frontline medical staff. Insomnia might be a possible target of PTS intervention.

10.
J Control Release ; 338: 537-547, 2021 10 10.
Article in English | MEDLINE | ID: covidwho-1385845

ABSTRACT

mRNA-based therapy has been evaluated in preclinical and clinical studies for the treatment of a wide variety of disease such as cancer immunotherapies and infectious disease vaccines. However, it remains challenging to development safe and efficient delivery system. Here, we have designed a novel self-assembled polymeric micelle based on vitamin E succinate modified polyethyleneimine copolymer (PVES) to delivery mRNA. In vitro, PVES could transfect mRNA into multiple cell lines such as HEK-293T, HeLa and Vero and the transfection efficiencies were much higher than PEI 25 k. In addition, the cytotoxicity of PVES was much lower than PEI 25 k. Furthermore, mice administered intramuscularly with PVES/SARS-CoV-2 mRNA vaccine induced potent antibody response and show no obvious toxicity. These results demonstrated the potential of PVES as a safe and effective delivery carrier for mRNA.


Subject(s)
COVID-19 , Micelles , Animals , COVID-19 Vaccines , HeLa Cells , Humans , Mice , Polyethyleneimine , RNA, Messenger , SARS-CoV-2 , Transfection
11.
Front Med (Lausanne) ; 8: 633477, 2021.
Article in English | MEDLINE | ID: covidwho-1359196

ABSTRACT

Objective: Few studies have quantified the influence of coronavirus disease 2019 (COVID-19) pandemic on medical providers. This is the first national study to investigate the impact of the pandemic on physicians practicing obstetrics and gynecology in China. Methods: A two-stage, stratified, cluster sampling method was performed based on the city categories (category 1, fewer than 10,000 beds; category 2, 10,000-30,000; and category 3, more than 30,000) and public hospital levels (primary, secondary, and tertiary). Physicians practicing obstetrics and gynecology reported the relevant changes in their general clinical activities and changes in the management of specific diseases or conditions occurring during the periods that they were most strongly affected. These changes were compared by municipal and hospital characteristics. Results: Questionnaires were collected from a representative sample of 11,806 physicians actively practicing obstetrics and gynecology in 779 hospitals from 157 cities of 31 provinces. Except emergency visits and online consultations, category 3 cities, tertiary hospitals and general hospitals had greater reductions in overall clinical activities than category 1 cities, primary hospitals and specialized hospitals (all adjusted p < 0.05), respectively. The differences also existed in the management of specific diseases and conditions, especially for less urgent conditions, including cervical cancer screening, instructions regarding contraception and miscarriage, and assisted reproduction (all p < 0.05). Conclusions: During the COVID-19 pandemic, the clinical obstetrics and gynecology activities in China markedly decreased, with significant differences across municipal and hospital characteristics. Trial Registration: This study was registered with ClinicalTrials.gov on July 27, 2020 (NCT04491201).

12.
Vaccine ; 39(40): 5940-5953, 2021 09 24.
Article in English | MEDLINE | ID: covidwho-1336992

ABSTRACT

The development of a safe and effective vaccine is a key requirement to overcoming the COVID-19 pandemic. Recombinant proteins represent the most reliable and safe vaccine approach but generally require a suitable adjuvant for robust and durable immunity. We used the SARS-CoV-2 genomic sequence and in silico structural modelling to design a recombinant spike protein vaccine (Covax-19™). A synthetic gene encoding the spike extracellular domain (ECD) was inserted into a baculovirus backbone to express the protein in insect cell cultures. The spike ECD was formulated with Advax-SM adjuvant and first tested for immunogenicity in C57BL/6 and BALB/c mice. Covax-19 vaccine induced high spike protein binding antibody levels that neutralised the original lineage B.1.319 virus from which the vaccine spike protein was derived, as well as the variant B.1.1.7 lineage virus. Covax-19 vaccine also induced a high frequency of spike-specific CD4 + and CD8 + memory T-cells with a dominant Th1 phenotype associated with the ability to kill spike-labelled target cells in vivo. Ferrets immunised with Covax-19 vaccine intramuscularly twice 2 weeks apart made spike receptor binding domain (RBD) IgG and were protected against an intranasal challenge with SARS-CoV-2 virus given two weeks after the last immunisation. Notably, ferrets that received the two higher doses of Covax-19 vaccine had no detectable virus in their lungs or in nasal washes at day 3 post-challenge, suggesting that in addition to lung protection, Covax-19 vaccine may have the potential to reduce virus transmission. This data supports advancement of Covax-19 vaccine into human clinical trials.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Animals , Antibodies, Viral , Ferrets , Humans , Immunization , Inulin/analogs & derivatives , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Pandemics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
13.
Cell Reports Methods ; : 100056, 2021.
Article in English | ScienceDirect | ID: covidwho-1322060

ABSTRACT

Summary Multimodal advances in single-cell sequencing have enabled the simultaneous quantification of cell surface protein expression alongside unbiased transcriptional profiling. Here, we present LinQ-View, a toolkit designed for multimodal single-cell data visualization and analysis. LinQ-View integrates transcriptional and cell surface protein expression profiling data to reveal more accurate cell heterogeneity and proposes a quantitative metric for cluster purity assessment. Through comparison with existing multimodal methods on multiple public CITE-seq datasets, we demonstrate that LinQ-View efficiently generates accurate cell clusters, especially in CITE-seq data with routine numbers of surface protein features, by preventing variations in a single surface protein feature from affecting results. Finally, we utilized this method to integrate single-cell transcriptional and protein expression data from SARS-CoV-2-infected patients, revealing antigen-specific B cell subsets after infection. Our results suggest LinQ-View could be helpful for multimodal analysis and purity assessment of CITE-seq datasets that target specific cell populations (e.g., B cells).

14.
BMJ Open ; 11(6): e048660, 2021 06 23.
Article in English | MEDLINE | ID: covidwho-1285086

ABSTRACT

BACKGROUND: To curb the spread of COVID-19, most countries have adopted measures such as banning shore leave at ports and placed restrictions on crew change. Seafarers may bear an excess pressure during the COVID-19 pandemic. This study aimed to investigate the prevalence and risk factors associated with depression symptoms among Chinese seafarers during the COVID-19 pandemic. DESIGN: Cross-sectional study. METHODS: This field survey-based study was conducted at Rongcheng Port, Shandong Province, China, from 10 June 2020 to 25 July 2020. Sociodemographic and occupational characteristics and health-related behaviours were collected through a face-to-face questionnaire. The Self-Rating Depression Scale was used to evaluate depression status during the preceding week. Logistic regression models were used to explore factors related to depression. RESULTS: 441 male Chinese seafarers were enrolled. Overall, the proportions of seafarers with low, moderate and severe depression symptoms were 23.35%, 9.30% and 9.07%, respectively. Compared with those with good self-rated health (SRH), seafarers with poor SRH had higher odds of depression (OR, 2.24, 95% CI 1.22 to 4.11). Less leisure time or physical exercise was associated with more severe self-reported depression symptoms (1-3 per week vs ≥4 per week: OR, 1.72, 95% CI 0.71 to 4.14; none vs ≥4 per week: OR, 3.93, 95% CI 1.67 to 9.26). Poor sleep quality was associated with higher likelihood of reporting severe depression (fair vs good: OR, 2.78, 95% CI 1.54 to 5.01; poor vs good: OR, 4.30, 95% CI 1.65 to 11.24). The more frequent seafarers worked overtime a week, the higher the likelihood of reporting severe depression symptoms (1-2 per week vs none: OR, 1.82, 95% CI 1.04 to 3.18; ≥3 per week vs none: OR, 2.49, 95% CI 1.05 to 5.92). Also, high perceived work stress was linked to higher odds of being depressed (intermediate vs low: OR, 2.06, 95% CI 0.78 to 5.46; high vs low: OR, 3.83, 95% CI 1.35 to 10.90). CONCLUSIONS: There is a high burden of depression associated with COVID-19 among seafarers. Special interventions that protect the mental health of seafarers are more critical than ever in the context of the pandemic.


Subject(s)
COVID-19 , Depression , Anxiety , COVID-19/psychology , China/epidemiology , Cross-Sectional Studies , Depression/epidemiology , Humans , Male , Naval Medicine , Pandemics , Prevalence , Risk Factors , Surveys and Questionnaires
15.
Adv Sci (Weinh) ; 8(16): e2100965, 2021 08.
Article in English | MEDLINE | ID: covidwho-1281195

ABSTRACT

Rapid progress has been made to identify and study the causative agent leading to coronavirus disease 2019 (COVID-19) but many questions including who is most susceptible and what determines severity remain unanswered. Angiotensin-converting enzyme 2 (ACE2) is a key factor in the infection process of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In this study, molecularly specific positron emission tomography imaging agents for targeting ACE2 are first developed, and these novel agents are evaluated in vitro, in preclinical model systems, and in a first-in-human translational ACE2 imaging of healthy volunteers and a SARS-CoV-2 recovered patient (NCT04422457). ACE2 expression levels in different organs in live subjects are quantitatively delineated and observable differences are measured in the patient recovered from COVID-19. Surprising sites of uptake in the breast, reproductive system and very low uptake in pulmonary tissues are reported. This novel method can add a unique tool to facilitate SARS-CoV-2 related research and improve understanding of this enigmatic disease. Molecular imaging provides quantitative annotation of ACE2, the SARS-CoV-2 entry receptor, to noninvasively monitor organs impacted by the COVID-19.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , COVID-19/virology , Peptides/pharmacokinetics , SARS-CoV-2/metabolism , Animals , COVID-19/pathology , Cells, Cultured , Female , Gallium Radioisotopes/pharmacokinetics , Humans , Male , Mice , Positron Emission Tomography Computed Tomography , Protein Binding , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Tissue Distribution , Xenograft Model Antitumor Assays
18.
Immunity ; 54(6): 1290-1303.e7, 2021 06 08.
Article in English | MEDLINE | ID: covidwho-1237724

ABSTRACT

Dissecting the evolution of memory B cells (MBCs) against SARS-CoV-2 is critical for understanding antibody recall upon secondary exposure. Here, we used single-cell sequencing to profile SARS-CoV-2-reactive B cells in 38 COVID-19 patients. Using oligo-tagged antigen baits, we isolated B cells specific to the SARS-CoV-2 spike, nucleoprotein (NP), open reading frame 8 (ORF8), and endemic human coronavirus (HCoV) spike proteins. SARS-CoV-2 spike-specific cells were enriched in the memory compartment of acutely infected and convalescent patients several months post symptom onset. With severe acute infection, substantial populations of endemic HCoV-reactive antibody-secreting cells were identified and possessed highly mutated variable genes, signifying preexisting immunity. Finally, MBCs exhibited pronounced maturation to NP and ORF8 over time, especially in older patients. Monoclonal antibodies against these targets were non-neutralizing and non-protective in vivo. These findings reveal antibody adaptation to non-neutralizing intracellular antigens during infection, emphasizing the importance of vaccination for inducing neutralizing spike-specific MBCs.


Subject(s)
Antibodies, Viral/immunology , Antibody Formation/immunology , B-Lymphocytes/immunology , COVID-19/immunology , Host-Pathogen Interactions/immunology , Immunodominant Epitopes/immunology , SARS-CoV-2/immunology , Antibodies, Neutralizing/immunology , Antibody Formation/genetics , B-Lymphocytes/metabolism , Computational Biology/methods , Cross Reactions/immunology , Epitope Mapping , Female , Gene Expression Profiling , High-Throughput Nucleotide Sequencing , Host-Pathogen Interactions/genetics , Humans , Immunodominant Epitopes/genetics , Immunologic Memory , Male , Neutralization Tests , Single-Cell Analysis/methods , Spike Glycoprotein, Coronavirus/immunology , Transcriptome
19.
Open Med (Wars) ; 16(1): 749-753, 2021.
Article in English | MEDLINE | ID: covidwho-1225823

ABSTRACT

In recent months, the novel coronavirus disease 2019 (COVID-19) pandemic has become a major public health crisis with takeover more than 1 million lives worldwide. The long-lasting existence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not yet been reported. Herein, we report a case of SARS-CoV-2 infection with intermittent viral polymerase chain reaction (PCR)-positive for >4 months after clinical rehabilitation. A 35-year-old male was diagnosed with COVID-19 pneumonia with fever but without other specific symptoms. The treatment with lopinavir-ritonavir, oxygen inhalation, and other symptomatic supportive treatment facilitated recovery, and the patient was discharged. However, his viral PCR test was continually positive in oropharyngeal swabs for >4 months after that. At the end of June 2020, he was still under quarantine and observation. The contribution of current antivirus therapy might be limited. The prognosis of COVID-19 patients might be irrelevant to the virus status. Thus, further investigation to evaluate the contagiousness of convalescent patients and the mechanism underlying the persistent existence of SARS-CoV-2 after recovery is essential. A new strategy of disease control, especially extending the follow-up period for recovered COVID-19 patients, is necessary to adapt to the current situation of pandemic.

20.
Mediators Inflamm ; 2021: 6635925, 2021.
Article in English | MEDLINE | ID: covidwho-1175215

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was initially identified in China and currently worldwide dispersed, resulting in the coronavirus disease 2019 (COVID-19) pandemic. Notably, COVID-19 is characterized by systemic inflammation. However, the potential mechanisms of the "cytokine storm" of COVID-19 are still limited. In this study, fourteen peripheral blood samples from COVID-19 patients (n = 10) and healthy donors (n = 4) were collected to perform the whole-transcriptome sequencing. Lung tissues of COVID-19 patients (70%) presenting with ground-glass opacity. Also, the leukocytes and lymphocytes were significantly decreased in COVID-19 compared with the control group (p < 0.05). In total, 25,482 differentially expressed messenger RNAs (DE mRNA), 23 differentially expressed microRNAs (DE miRNA), and 410 differentially expressed long noncoding RNAs (DE lncRNAs) were identified in the COVID-19 samples compared to the healthy controls. Gene Ontology (GO) analysis showed that the upregulated DE mRNAs were mainly involved in antigen processing and presentation of endogenous antigen, positive regulation of T cell mediated cytotoxicity, and positive regulation of gamma-delta T cell activation. The downregulated DE mRNAs were mainly concentrated in the glycogen biosynthetic process. We also established the protein-protein interaction (PPI) networks of up/downregulated DE mRNAs and identified 4 modules. Functional enrichment analyses indicated that these module targets were associated with positive regulation of cytokine production, cytokine-mediated signaling pathway, leukocyte differentiation, and migration. A total of 6 hub genes were selected in the PPI module networks including AKT1, TNFRSF1B, FCGR2A, CXCL8, STAT3, and TLR2. Moreover, a competing endogenous RNA network showed the interactions between lncRNAs, mRNAs, and miRNAs. Our results highlight the potential pathogenesis of excessive cytokine production such as MSTRG.119845.30/hsa-miR-20a-5p/TNFRSF1B, MSTRG.119845.30/hsa-miR-29b-2-5p/FCGR2A, and MSTRG.106112.2/hsa-miR-6501-5p/STAT3 axis, which may also play an important role in the development of ground-glass opacity in COVID-19 patients. This study gives new insights into inflammation regulatory mechanisms of coding and noncoding RNAs in COVID-19, which may provide novel diagnostic biomarkers and therapeutic avenues for COVID-19 patients.


Subject(s)
COVID-19/blood , COVID-19/genetics , RNA/blood , RNA/genetics , SARS-CoV-2 , Adult , Aged , COVID-19/complications , Case-Control Studies , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/genetics , Cytokines/biosynthesis , Cytokines/genetics , Female , Gene Expression , Humans , Inflammation Mediators/blood , Male , MicroRNAs/blood , MicroRNAs/genetics , Middle Aged , Pandemics , Protein Interaction Maps/genetics , RNA, Long Noncoding/blood , RNA, Long Noncoding/genetics , RNA, Messenger/blood , RNA, Messenger/genetics , Sequence Analysis, RNA , Signal Transduction , Whole Exome Sequencing , Young Adult
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