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1.
Emerg Microbes Infect ; : 1-29, 2022 Mar 28.
Article in English | MEDLINE | ID: covidwho-1799501

ABSTRACT

Diabetes mellitus (DM) is one of the most common underlying diseases that may aggravates COVID-19. In the present study, we explored islet function, the presence of SARS-CoV-2 and pathological changes in the pancreas of patients with COVID-19. Oral glucose tolerance tests (OGTTs) and the C-peptide release test demonstrated a decrease in glucose-stimulated C-peptide secretory capacity and an increase in HbA1c levels in patients with COVID-19. The prediabetic conditions appeared to be more significant in the severe group than in the moderate group. SARS-CoV-2 receptors (ACE2, CD147, TMPRSS2 and neuropilin-1) were expressed in pancreatic tissue. In addition to SARS-CoV-2 virus spike protein and virus RNA, coronavirus-like particles were present in the autophagolysosomes of pancreatic acinar cells of a patient with COVID-19. Furthermore, the expression and distribution of various proteins in pancreatic islets of patients with COVID-19 were altered. These data suggest that SARS-CoV-2 in the pancreas may directly or indirectly impair islet function.

2.
PLoS Genet ; 18(4): e1010137, 2022 Apr 14.
Article in English | MEDLINE | ID: covidwho-1789166

ABSTRACT

Viral infections can alter host transcriptomes by manipulating host splicing machinery. Despite intensive transcriptomic studies on SARS-CoV-2, a systematic analysis of alternative splicing (AS) in severe COVID-19 patients remains largely elusive. Here we integrated proteomic and transcriptomic sequencing data to study AS changes in COVID-19 patients. We discovered that RNA splicing is among the major down-regulated proteomic signatures in COVID-19 patients. The transcriptome analysis showed that SARS-CoV-2 infection induces widespread dysregulation of transcript usage and expression, affecting blood coagulation, neutrophil activation, and cytokine production. Notably, CD74 and LRRFIP1 had increased skipping of an exon in COVID-19 patients that disrupts a functional domain, which correlated with reduced antiviral immunity. Furthermore, the dysregulation of transcripts was strongly correlated with clinical severity of COVID-19, and splice-variants may contribute to unexpected therapeutic activity. In summary, our data highlight that a better understanding of the AS landscape may aid in COVID-19 diagnosis and therapy.

3.
Immunol Cell Biol ; 100(4): 250-266, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1759190

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) pandemic perpetuated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has highlighted the continued need for broadly protective vaccines that elicit robust and durable protection. Here, the vaccinia virus-based, replication-defective Sementis Copenhagen Vector (SCV) was used to develop a first-generation COVID-19 vaccine encoding the spike glycoprotein (SCV-S). Vaccination of mice rapidly induced polyfunctional CD8 T cells with cytotoxic activity and robust type 1 T helper-biased, spike-specific antibodies, which are significantly increased following a second vaccination, and contained neutralizing activity against the alpha and beta variants of concern. Longitudinal studies indicated that neutralizing antibody activity was maintained up to 9 months after vaccination in both young and middle-aged mice, with durable immune memory evident even in the presence of pre-existing vector immunity. Therefore, SCV-S vaccination has a positive immunogenicity profile, with potential to expand protection generated by current vaccines in a heterologous boost format and presents a solid basis for second-generation SCV-based COVID-19 vaccine candidates incorporating additional SARS-CoV-2 immunogens.


Subject(s)
COVID-19 , Vaccinia , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunity, Cellular , Immunity, Humoral , Mice , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics , Vaccination
4.
Biomed Chromatogr ; : e5370, 2022 Mar 16.
Article in English | MEDLINE | ID: covidwho-1748780

ABSTRACT

Ribavirin is a synthetic, broad-spectrum antiviral drug. Ribavirin is recommended as an antiviral drug in the Interim Guidance for Diagnosis and Treatment (the seventh edition) of COVID-19. The ribavirin levels in red blood cells may be closely related to both its efficacy and adverse drug reactions. In this study, a simple and fast HPLC-UV method was established to determine the concentrations of total ribavirin in the red blood cells of 13 patients with COVID-19. Phosphorylated ribavirin was dephosphorylated by phosphatase incubation to obtain the total amount of ribavirin in red blood cells. The chromatographic column was an Atlantis C18 . The recoveries were 85.45-89.05% at three levels. A good linear response was from 1 to 200 µg/ml, with a correlation coefficient of r2 = 0.9991. The concentration of total ribavirin in the red blood cells of the patients ranged from 30.83 to 133.34 µg/ml. The same samples without phosphatase incubation ranged from 4.07 to 20.84 µg/ml. About 85% of ribavirin was phosphorylated in red blood cells. In addition, we observed changes in these patients' hematological parameters and found that the erythrocyte, hemoglobin and hematocrit declined to the lowest levels on the fifth day after discontinuation of ribavirin (p < 0.05).

5.
Frontiers in pharmacology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1710670

ABSTRACT

Background: Coronavirus disease 2019 (COVID-2019), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide epidemic and claimed millions of lives. Accumulating evidence suggests that cytokines storms are closely associated to COVID-19 severity and death. Here, we aimed to explore the key factors related to COVID-19 severity and death, especially in terms of the male patients and those in western countries. Methods: To clarify whether inflammatory cytokines have role in COVID-19 severity and death, we systematically searched PubMed, Embase, Cochrane library and Web of Science to identify related studies with the keywords “COVID-19″ and “cytokines”. The data were measured as the mean with 95% confidence interval (CI) by Review Manager 5.3 software. The risk of bias was assessed for each study using appropriate checklists. Results: We preliminarily screened 13,468 studies from the databases. A total of 77 articles with 13,468 patients were ultimately included in our study. The serum levels of cytokines such as interleukin-6 (IL-6), IL-10, interleukin-2 receptor (IL-2R), tumor necrosis factor (TNF)-α, IL-1β, IL-4, IL-8 and IL-17 were higher in the severity or death group. Notably, we also found that the circulating levels of IL-6, IL-10, IL-2R and TNF-α were significantly different between males and females. The serum levels of IL-6, IL-10, IL-2R and TNF-α were much higher in males than in females, which implies that the increased mortality and severity in males was partly due to the higher level of these cytokines. Moreover, we found that in the severe and non-survivor groups, European patients had elevated levels of IL-6 compared with Asian patients. Conclusion: These large-scale data demonstrated that the circulating levels of IL-6, IL-10, IL-2R, IL-1β, IL-4, IL-8 and IL-17 are potential risk factors for severity and high mortality in COVID-19. Simultaneously, the upregulation of these cytokines may be driving factors for the sex and region predisposition.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323677

ABSTRACT

Background: More and more studies showed pneumothorax is a complication of the 2019 novel coronavirus disease (COVID-19). But no autopsy findings of pneumothorax in COVID-19 decedent were reported, and direct relations between pneumothorax and lung pathology in these decedents were not discussed so far. Methods: A 62-year-old man with COVID-19 presenting with persistent hypoxemia and suddenly dead, who was treated by mechanical ventilation in the intensive care unit (ICU) for 5 days. A systemic autopsy examination of COVID-19 decedent, including histopathology study, was conducted and the medical record, chest computerized tomography (CT) image were reviewed by forensic pathologists and clinicians. Results: Severe pneumothorax, diffuse alveolar damage and airway obstruction were observed. Pneumothorax should be one of the causes of death. Conclusion: Pneumothorax, due to SARS-CoV-2 infection, is a fatal complication of COVID-19. Regular examination of chest CT or X-ray and airway management are important to clinical treatment.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-316032

ABSTRACT

Despite widespread interest in the pathophysiology of COVID-19 in respiratory and cardiovascular systems, little is known about the morphologic and molecular changes in the testis of patients with COVID-19 and the effects of SARS-CoV-2 infection on male fertility. We report here on the pathophysiology and molecular feature of testes obtained at autopsy from six men with COVID-19, as compared with those of testes from three men with age-matched, uninfected SARS-CoV-2. Our histopathological results showed that all COVID-19 patients had severe spermatogenesis damages compared with controls. Importantly, we detected the nuclear acid of the SARS-CoV-2 virus, viral particles, and SARS-CoV-2 spike S1 protein in COVID-19 patient testes, and we also found ACE2 and TMPRSS2 significantly elevated in the testes from COVID-19 patients. Furthermore, we observed a prominent leukocyte infiltration, including CD3+ T lymphocytes, CD20+ B lymphocytes, CD68+ macrophages, HLA-DR+ myeloid cells, and CD38+ plasma cells in the testes of COVID-19 patients. RNA-Seq analyses further revealed SARS-CoV-2 infection could lead to dysfunction of the genes that regulate the spermatogenesis and inflammation response-related pathways. Collectively, our pathological and molecular examination findings indicate that SARS-CoV-2 could directly attack testicular cells, thereby inducing the damage of testicular immune privilege and spermatogenesis defects.

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-313395

ABSTRACT

Background: The progression of coagulation in COVID-19 patients with confirmed discharge status and the combination of autopsy with complete hemostasis parameters have not been well studied. Objective: To clarify the thrombotic phenomena and hemostasis state in COVID-19 patients based on epidemiological statistics combining autopsy and statistical analysis. Methods: : Using autopsy results from 9 patients with COVID-19 pneumonia and the medical records of 407 patients, including 39 deceased patients whose discharge status was certain, time-sequential changes in 11 relevant indices within mild, severe and critical infection throughout hospitalization according to the Chinese National Health Commission (NHC) guidelines were evaluated. Statistical tools were applied to calculate the importance of 11 indices and the correlation between those indices and the severity of COVID-19. Results: : At the beginning of hospitalization, platelet (PLT) counts were significantly reduced in critically ill patients compared with severely or mildly ill patients. Blood glucose (GLU), prothrombin time (PT), activated partial thromboplastin time (APTT), and D-dimer levels in critical patients were increased compared with mild and severe patients during the entire admission period. The International Society on Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) score was also high in critical patients. In the relatively late stage of nonsurvivors, the temporal changes in PLT count, PT, and D-dimer levels were significantly different from those in survivors. A random forest model indicated that the most important feature was PT followed by D-dimer, indicating their positive associations with disease severity. Autopsy of deceased patients fulfilling diagnostic criteria for DIC revealed microthromboses in multiple organs. Conclusions: Combining autopsy data, time-sequential changes and statistical methods to explore hemostasis-relevant indices among the different severities of the disease helps guide therapy and detect prognosis in COVID-19 infection.

9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296091

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is highly contagious and causes lymphocytopenia, but the underlying mechanisms are poorly understood. We demonstrate here that heterotypic cell-in-cell structures with lymphocytes inside multinucleate syncytia are prevalent in the lung tissues of coronavirus disease 2019 (COVID-19) patients. These unique cellular structures are a direct result of SARS-CoV-2 infection, as the expression of the SARS-CoV-2 spike glycoprotein is sufficient to induce a rapid (approximately 45.1 nm/sec) membrane fusion to produce syncytium, which could readily internalize multiple lines of lymphocytes to form typical cell-in-cell structures, remarkably leading to the death of internalized cells. This membrane fusion is dictated by a bi-arginine motif within the polybasic S1/S2 cleavage site, which is frequently present in the surface glycoprotein of most highly contagious viruses. Moreover, candidate anti-viral drugs could efficiently inhibit spike glycoprotein processing, membrane fusion, and cell-in-cell formation. Together, we delineate a molecular and cellular rationale for SARS-CoV-2 pathogenesis and identify novel targets for COVID-19 therapy.

10.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-294958

ABSTRACT

Coronavirus disease 2019 (COVID-2019), caused by severe acute respiratory syndrome coronavirus 2, has become a worldwide epidemic and claimed millions of lives. Accumulating evidence suggests that males suffer more severe symptoms and higher mortality than females, but the underlying mechanism of this sex predisposition remains unclear. We aimed to explore whether inflammatory cytokines are risk factors correlated with this sex predisposition, especially in terms of the severity and mortality of COVID-19 patients. To clarify whether inflammatory cytokines are related to male sex bias towards increased mortality, we systematically searched PubMed, Embase and Web of Science to identify related studies with the keywords "COVID-19" and "cytokines". We preliminarily screened 13468 studies from the databases. A total of 77 articles with 13468 patients were ultimately included in our study. The expression levels of interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-2 receptor (IL-2R) and tumour necrosis factor α (TNF-α) were significantly different between males and females. The serum level of IL-6 was much higher in males than in females, which implies that the increased mortality and severity in males was partly due to the higher level of IL-6. Interestingly, we also found that in the severe and non-survivor groups, European patients had elevated levels of IL-6 compared with Asian patients. These large-scale data demonstrated that the circulating level of IL-6 is a potential risk factor for severity and high mortality in COVID-19. The upregulation of IL-6 may be a driving factor for severity and high mortality in males with COVID-19.<br><br>Funding Information: This work was financially supported by National Key Research and Development Project of China (2020YFA0708003).<br><br>Declaration of Interests: There is no conflict of interest.

11.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-293601

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is highly contagious and causes lymphocytopenia, but the underlying mechanisms are poorly understood. We demonstrate here that heterotypic cell-in-cell structures with lymphocytes inside multinucleate syncytia are prevalent in the lung tissues of coronavirus disease 2019 (COVID-19) patients. These unique cellular structures are a direct result of SARS-CoV-2 infection, as the expression of the SARS-CoV-2 spike glycoprotein is sufficient to induce a rapid (approximately 45.1 nm/sec) membrane fusion to produce syncytium, which could readily internalize multiple lines of lymphocytes to form typical cell-in-cell structures, remarkably leading to the death of internalized cells. This membrane fusion is dictated by a bi-arginine motif within the polybasic S1/S2 cleavage site, which is frequently present in the surface glycoprotein of most highly contagious viruses. Moreover, candidate anti-viral drugs could efficiently inhibit spike glycoprotein processing, membrane fusion, and cell-in-cell formation. Together, we delineate a molecular and cellular rationale for SARS-CoV-2 pathogenesis and identify novel targets for COVID-19 therapy.

12.
Pharmacol Res ; 172: 105820, 2021 10.
Article in English | MEDLINE | ID: covidwho-1531713

ABSTRACT

Coronavirus Disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which enter the host cells through the interaction between its receptor binding domain (RBD) of spike glycoprotein with angiotensin-converting enzyme 2 (ACE2) receptor on the plasma membrane of host cell. Neutralizing antibodies and peptide binders of RBD can block viral infection, however, the concern of accessibility and affordability of viral infection inhibitors has been raised. Here, we report the identification of natural compounds as potential SARS-CoV-2 entry inhibitors using the molecular docking-based virtual screening coupled with bilayer interferometry (BLI). From a library of 1871 natural compounds, epigallocatechin gallate (EGCG), 20(R)-ginsenoside Rg3 (RRg3), 20(S)-ginsenoside Rg3 (SRg3), isobavachalcone (Ibvc), isochlorogenic A (IscA) and bakuchiol (Bkc) effectively inhibited pseudovirus entry at concentrations up to 100 µM. Among these compounds, four compounds, EGCG, Ibvc, salvianolic acid A (SalA), and isoliensinine (Isl), were effective in inhibiting SARS-CoV-2-induced cytopathic effect and plaque formation in Vero E6 cells. The EGCG was further validated with no observable animal toxicity and certain antiviral effect against SARS-CoV-2 pseudovirus mutants (D614G, N501Y, N439K & Y453F). Interestingly, EGCG, Bkc and Ibvc bind to ACE2 receptor in BLI assay, suggesting a dual binding to RBD and ACE2. Current findings shed some insight into identifications and validations of SARS-CoV-2 entry inhibitors from natural compounds.


Subject(s)
Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Antiviral Agents/chemistry , Biological Products/chemistry , COVID-19/drug therapy , Enzyme Inhibitors/chemistry , SARS-CoV-2/enzymology , Spike Glycoprotein, Coronavirus/metabolism , Animals , Antiviral Agents/pharmacology , Binding, Competitive , Biological Products/pharmacology , Catechin/analogs & derivatives , Catechin/pharmacology , Cell Membrane/metabolism , Cell Membrane/ultrastructure , Chalcones/pharmacology , Chlorogenic Acid/analogs & derivatives , Chlorogenic Acid/pharmacology , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Enzyme Inhibitors/pharmacology , Ginsenosides/pharmacology , Humans , Interferometry , Mice, Inbred C57BL , Molecular Dynamics Simulation , Phenols/pharmacology , Protein Binding
13.
Cell Res ; 31(12): 1230-1243, 2021 12.
Article in English | MEDLINE | ID: covidwho-1475291

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the ongoing global pandemic that poses substantial challenges to public health worldwide. A subset of COVID-19 patients experience systemic inflammatory response, known as cytokine storm, which may lead to death. Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is an important mediator of inflammation and cell death. Here, we examined the interaction of RIPK1-mediated innate immunity with SARS-CoV-2 infection. We found evidence of RIPK1 activation in human COVID-19 lung pathological samples, and cultured human lung organoids and ACE2 transgenic mice infected by SARS-CoV-2. Inhibition of RIPK1 using multiple small-molecule inhibitors reduced the viral load of SARS-CoV-2 in human lung organoids. Furthermore, therapeutic dosing of the RIPK1 inhibitor Nec-1s reduced mortality and lung viral load, and blocked the CNS manifestation of SARS-CoV-2 in ACE2 transgenic mice. Mechanistically, we found that the RNA-dependent RNA polymerase of SARS-CoV-2, NSP12, a highly conserved central component of coronaviral replication and transcription machinery, promoted the activation of RIPK1. Furthermore, NSP12 323L variant, encoded by the SARS-CoV-2 C14408T variant first detected in Lombardy, Italy, that carries a Pro323Leu amino acid substitution in NSP12, showed increased ability to activate RIPK1. Inhibition of RIPK1 downregulated the transcriptional induction of proinflammatory cytokines and host factors including ACE2 and EGFR that promote viral entry into cells. Our results suggest that SARS-CoV-2 may have an unexpected and unusual ability to hijack the RIPK1-mediated host defense response to promote its own propagation and that inhibition of RIPK1 may provide a therapeutic option for the treatment of COVID-19.


Subject(s)
COVID-19/pathology , Receptor-Interacting Protein Serine-Threonine Kinases/metabolism , SARS-CoV-2/physiology , Angiotensin-Converting Enzyme 2/genetics , Animals , COVID-19/drug therapy , COVID-19/mortality , COVID-19/virology , Coronavirus RNA-Dependent RNA Polymerase/genetics , Coronavirus RNA-Dependent RNA Polymerase/metabolism , Cytokines/genetics , Cytokines/metabolism , Down-Regulation/drug effects , ErbB Receptors/metabolism , Humans , Imidazoles/pharmacology , Imidazoles/therapeutic use , Indoles/pharmacology , Indoles/therapeutic use , Lung/pathology , Lung/virology , Mice , Mice, Transgenic , Mutation , Receptor-Interacting Protein Serine-Threonine Kinases/antagonists & inhibitors , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Survival Rate , Transcriptome/drug effects , Viral Load/drug effects , Virus Internalization
14.
Pathol Res Pract ; 227: 153610, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1401790

ABSTRACT

The coronavirus disease 2019(COVID-19) is recognized as systemic inflammatory response syndrome. It was demonstrated that a rapid increase of cytokines in the serum of COVID-19 patients is associated with the severity of disease. However, the mechanisms of the cytokine release are not clear. By using immunofluorescence staining we found that the number of CD11b positive immune cells including macrophages in the spleens of died COVID-19 patients, was significantly higher than that of the control patients. The incidence of apoptosis as measured by two apoptotic markers, TUNEL and cleaved caspase-3, in COVID-19 patients' spleen cells is higher than that in control patients. By double immunostaining CD11b or CD68 and SARS-CoV-2 spike protein, it was found that up to 67% of these immune cells were positive for spike protein, suggesting that viral infection might be associated with apoptosis in these cells. Besides, we also stained the autophagy-related molecules (p-Akt、p62 and BCL-2) in spleen tissues, the results showed that the number of positive cells was significantly higher in COVID-19 group. And compared with non-COVID-19 patients, autophagy may be inhibited in COVID-19 patients. Our research suggest that SARS-CoV-2 may result in a higher rate of apoptosis and a lower rate of autophagy of immune cells in the spleen of COVID-19 patients. These discoveries may increase our understanding of the pathogenesis of COVID-19.


Subject(s)
Apoptosis , Autophagy , COVID-19/pathology , SARS-CoV-2/pathogenicity , Spleen/pathology , Antigens, CD/analysis , Antigens, Differentiation, Myelomonocytic/analysis , Autopsy , Biomarkers/analysis , CD11b Antigen/analysis , COVID-19/immunology , COVID-19/mortality , COVID-19/virology , Case-Control Studies , Caspase 3/analysis , Host-Pathogen Interactions , Humans , Immunohistochemistry , In Situ Nick-End Labeling , Phosphorylation , Proto-Oncogene Proteins c-akt/analysis , Proto-Oncogene Proteins c-bcl-2/analysis , SARS-CoV-2/immunology , Sequestosome-1 Protein/analysis , Spike Glycoprotein, Coronavirus/analysis , Spleen/immunology , Spleen/virology
15.
Cell Discov ; 6(1): 84, 2020 Nov 13.
Article in English | MEDLINE | ID: covidwho-1387260
17.
Hum Vaccin Immunother ; 17(11): 4065-4073, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1341088

ABSTRACT

Healthcare workers (HCWs) are considered both a high-risk population regarding infections and effective vaccine recommenders whose willingness to be vaccinated is the key to herd immunity. However, the vaccination status, acceptance, and knowledge of the 2019 coronavirus disease (COVID-19) vaccine among HCWs remain unknown. Therefore, we conducted an online survey regarding the above among HCWs in China after the vaccine was made available. Questionnaires returned by 1,779 HCWs were analyzed. Among these participants, 34.9% were vaccinated, 93.9% expressed their willingness to receive the COVID-19 vaccine, and vaccine knowledge level was high (89.2%). A bivariate analysis found that participants with a college degree, low level of knowledge, non-exposure to COVID-19 status, and those who are females or nurses have a lower vaccination rate, while participants who are married, with a monthly income of more than 5,000 yuan, and low knowledge levels are less willing to be vaccinated. A multivariate analysis found that participants with a high (OR = 7.042, 95% CI = 4.0918-12.120) or medium (OR = 3.709, 95% CI = 2.072-6.640) knowledge level about COVID-19 vaccines were more willing to be vaccinated. Participants were less likely to accept a COVID-19 vaccine if they were married (OR = 0.503, 95% CI = 0.310-0.815). In summary, Chinese HCWs have a strong willingness to be vaccinated and a high level of knowledge. Measures, such as targeted education for HCWs with low willingness and low level of knowledge, open vaccine review procedures, increased government trust, reduced vaccine costs, and provide vaccination guarantee policies, may improve the vaccination coverage of the at-risk group.


Subject(s)
COVID-19 Vaccines , COVID-19 , Cross-Sectional Studies , Female , Health Personnel , Humans , SARS-CoV-2 , Vaccination
18.
Pharmacol Res ; 157: 104821, 2020 07.
Article in English | MEDLINE | ID: covidwho-1318924

ABSTRACT

AIM: Since December 2019, new COVID-19 outbreaks have occurred and spread around the world. However, the clinical characteristics of patients in other areas around Wuhan, Hubei Province are still unclear. In this study, we performed epidemiological and clinical characteristics analysis on these regional cases. METHODS: We retrospectively investigated COVID-19 patients positively confirmed by nucleic acid Q-PCR at Taihe Hospital from January 16 to February 4, 2020. Their epidemiological, clinical manifestations, and imaging characteristics were analysed. RESULTS: Among the 73 patients studied, 12.3 % developed symptoms after returning to Shiyan from Wuhan, and 71.2 % had a history of close contact with Wuhan personnel or confirmed cases. Among these patients, 9 cases were associated with family clustering. The first main symptoms presented by these patients were fever (84.9 %) and cough (21.9 %). The longest incubation period was 26 days, and the median interval from the first symptoms to admission was 5 days. Of the patients, 67.1 % were originally healthy people with no underlying diseases, others mostly had common comorbidities including hypertension (12.3 %) and diabetes (5.5 %), 10.9 % were current smokers, 30.1 % had low white blood cell counts and 45.2 % showed decreased lymphocytes at the first time of diagnosis. CT scans showed that multiple patchy ground glass shadows outside of the patient lungs were commonly observed, and a single sub-pleural sheet of ground glass shadow with enhanced vascular bundles was also found located under the pleura. Patient follow-up to February 14 presented 38.4 % severe cases and 2.7 % critical cases. After follow-up, the parameter of lymphocyte counts below 0.8 × 109/L cannot be used to predict severe and critical groups from the ordinary group, and a lower proportion of smokers and higher proportion of diabetes patients occur in the poor outcome group. Other co-morbidities are observed but did not lead to poor outcomes. CONCLUSION: The epidemiological characteristics of patients in the area around Wuhan, such as Shiyan, at first diagnosis are described as follows: Patients had histories of Wuhan residences in the early stage and family clustering in the later period. The incubation period was relatively long, and the incidence was relatively hidden, but the virulence was relatively low. The initial diagnosis of the patients was mostly ordinary, and the percentage of critical patients who evolved into the ICU during follow-up is 2.7 %, which is lower than the 26.1 % reported by Wuhan city. According to the Shiyan experience, early diagnosis with multiple swaps of the Q-PCR test and timely treatment can reduce the death rate. Diabetes could be one of the risk factors for progression to severe/critical outcomes. No evidence exists that smoking protects COVID-19 patients from developing to severe/critical cases, and the absolute number of lymphocytes at initial diagnosis could not predict the progression risk from severe to critical condition. Multivariate regression analysis should be used to further guide the allocation of clinical resources.


Subject(s)
Betacoronavirus , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Cough/epidemiology , Diabetes Mellitus/epidemiology , Fever/epidemiology , Hypertension/epidemiology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Adult , Aged , COVID-19 , China/epidemiology , Comorbidity , Coronavirus Infections/diagnostic imaging , Female , Hospitalization , Humans , Infectious Disease Incubation Period , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnostic imaging , Retrospective Studies , SARS-CoV-2 , Time Factors , Young Adult
19.
Front Cell Dev Biol ; 9: 664868, 2021.
Article in English | MEDLINE | ID: covidwho-1273326

ABSTRACT

Acute kidney injury (AKI) is one of the most prevalent complications among hospitalized coronavirus disease 2019 (COVID-19) patients. Here, we aim to investigate the causes, risk factors, and outcomes of AKI in COVID-19 patients. We found that angiotensin-converting enzyme II (ACE2) and transmembrane protease serine 2 (TMPRSS2) were mainly expressed by different cell types in the human kidney. However, in autopsy kidney samples, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein was detected in ACE2+ or TMPRSS2+ renal tubular cells, whereas the RNAscope® Assay targeting the SARS-CoV-2 Spike gene was positive mainly in the distal tubular cells and seldom in the proximal tubular cells. In addition, the TMPRSS2 and kidney injury marker protein levels were significantly higher in the SARS-CoV-2-infected renal distal tubular cells, indicating that SARS-CoV-2-mediated AKI mainly occurred in the renal distal tubular cells. Subsequently, a cohort analysis of 722 patients with COVID-19 demonstrated that AKI was significantly related to more serious disease stages and poor prognosis of COVID-19 patients. The progressive increase of blood urea nitrogen (BUN) level during the course of COVID-19 suggests that the patient's condition is aggravated. These results will greatly increase the current understanding of SARS-CoV-2 infection.

20.
Pathogens ; 10(6)2021 Jun 11.
Article in English | MEDLINE | ID: covidwho-1270096

ABSTRACT

Through 4 June 2021, COVID-19 has caused over 172.84 million cases of infection and 3.71 million deaths worldwide. Due to its rapid dissemination and high mutation rate, it is essential to develop a vaccine harboring multiple epitopes and efficacious against multiple variants to prevent the immune escape of SARS-CoV-2. An in silico approach based on the viral genome was applied to identify 19 high-immunogenic B-cell epitopes and 499 human leukocyte antigen (HLA)-restricted T-cell epitopes. Thirty multi-epitope peptide vaccines were designed by iNeo-Suite and manufactured by solid-phase synthesis. Docking analysis confirmed stable hydrogen bonds of epitopes with their corresponding HLA alleles. When four peptide candidates derived from the spike protein of SARS-CoV-2 were selected to immunize mice, a significantly larger amount of total IgG in serum, as well as an increase of CD19+ cells in the inguinal lymph nodes, were observed in the peptide-immunized mice compared to the control. The ratios of IFN-γ-secreting lymphocytes in CD4+ or CD8+ T-cells in the peptide-immunized mice were higher than those in the control mice. There were also a larger number of IFN-γ-secreting T-cells in the spleens of peptide-immunized mice. The peptide vaccines in this study successfully elicited antigen-specific humoral and cellular immune responses in mice. To further validate the safety and efficacy of this vaccine, animal studies using a primate model, as well as clinical trials in humans, are required.

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