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1.
Preprint in English | bioRxiv | ID: ppbiorxiv-501235

ABSTRACT

T lymphocyte reduction and immunosenescence frequently occur in severe and critical coronavirus disease 2019 (COVID-19) patients, which may cause immunothrombosis and numerous sequelae. This study integrated analyzed multi-omics data from healthy donors, pneumonia, COVID-19 patients (mild & moderate, severe, and critical), and convalescences, including clinical, laboratory test, PBMC bulk RNA-seq, PBMC scRNA-seq and TCR-seq, BAL scRNA-seq, and lung proteome. We revealed that there are certain associations among T lymphocyte reduction, CD8+ T cell senescence, Th17 immune activation, and immunothrombosis. A specific phenotype (S. P.) CD8+ T cells were identified in severe and critical COVID-19 patients in both PBMC and BAL scRNA-seq, which showed highly TCR homology with terminal effector CD8+ T cells and senescent CD8+ T cells. Pseudotime analysis showed that the S. P. CD8+ T cells were located in the transition trajectory from mild to severe disease. Which may be activated by terminal effector CD8+ T cells or senescent CD8+ T cells, thereby promoting Th17 cell differentiation. This phenomenon was absent in healthy donors, mild and moderate COVID-19 patients, or convalescences. Our findings are an important reference for avoiding the conversion of patients with mild to severe diseases and provide insight into the future prevention and control of COVID-19 and its variants.

2.
Ther Adv Respir Dis ; 16: 17534666221110346, 2022.
Article in English | MEDLINE | ID: covidwho-1923475

ABSTRACT

BACKGROUND: Recently, the SARS-CoV-2 variant of concern, Omicron (B.1.1.529), was identified as responsible for a novel wave of COVID-19 worldwide. Here, we compared initial clinical features of hospitalized COVID-19 patients during recent wave (Omicron Variant) with those in ancestral variant wave (2020). METHODS: This is a cohort study of electronic health record (EHR) data from a signal center in the China. The clinical data of 116 cases of Omicron hospitalized in 2022 and 87 cases hospitalized in 2020 were collected. The comparisons were performed with the Mann-Whitney U test, Fisher exact test or the chi-square test, and multivariable logistic regression analysis. RESULTS: Clinically, compared with 2020-cohort, Omicron-cohort was more inclined to cluster in younger population and had more nonsymptomatic (25.0%) and nonsevere cases, as well as suffered from comparable extrapulmonary complication. Radiologically, although the major computed tomography (CT) findings of both cohorts were ground-glass opacities (GGOs), crazy-paving pattern was relatively less seen in the Omicron-cohort. Based on multiple logistic regression analysis, Omicron-cohort was associated with a lower risk of complaining with fever, the presence of lung opacity, and increased Sequential Organ Failure Assessment (SOFA) score. CONCLUSION: This study provided the data of different patterns of clinic characteristics and reduced severity from infections that occurred in Omicron variant as compared with the outbreak of the epidemic in 2020 wave (ancestral variant).


Subject(s)
COVID-19 , SARS-CoV-2 , Cohort Studies , Humans , Tomography, X-Ray Computed/methods
4.
J Infect Dis ; 2022 Apr 16.
Article in English | MEDLINE | ID: covidwho-1886442

ABSTRACT

The SARS-CoV-2 Omicron (B.1.1.529) variant extensively escape neutralizing antibodies by vaccines or infection. We assessed serum neutralizing activity in sera from Delta infection following vaccination and Delta infection only against SARS-CoV-2 Wuhan-Hu-1 (WA1), Beta, Delta, and Omicron. Sera from Delta infection only could neutralize WA1 and Delta but nearly completely lost capacity to neutralize Beta and Omicron. However, Delta infection following vaccination resulted in a significant increase of serum neutralizing activity against WA1, Beta, and Omicron. This study demonstrates that breakthrough infection of Delta substantially induced high potency humoral immune response against the Omicron variant and other emerged variants.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323771

ABSTRACT

Background: Sudden exacerbations and respiratory failure are major causes of death in patients with severe coronavirus disease 2019(COVID-19) pneumonia, but indicators for the prediction and treatment of severe patients are still lacking.MethodsA retrospective analysis of 67 collected cases was conducted and included approximately 67 patients with COVID-19 pneumonia who were admitted to the Suzhou Fifth People’s Hospital from January 1, 2020 to February 8, 2020. The epidemiological, clinical and imaging characteristics as well as laboratory data of the 67 patients were analyzed.ResultsThe study found that fibrinogen(FIB) was increased in 45 (65.2%) patients, and when FIB reached a critical value of 4.805 g/L, the sensitivity and specificity、DA, helping to distinguish general and severe cases, were 100% and 14%、92.9%, respectively, which were significantly better than those for lymphocyte count and myoglobin. Chest CT images indicated that the cumulative number of lung lobes with lesions in severe patients was significantly higher than that in general patients (P<0.05), and the cumulative number of lung lobes with lesions was negatively correlated with lymphocyte count and positively correlated with myoglobin and FIB. Our study also found that there was no obvious effect of hormone therapy in patients with severe COVID-19.ConclusionsBased on the retrospective analysis, FIB was found to be increased in severe patients and was better than lymphocyte count and myoglobin in distinguishing general and severe patients. The study also suggested that hormone treatment has no significant effect on COVID-19.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-322272

ABSTRACT

The coronavirus (COVID-19) pandemic has adversely affected individuals’ mental health. Social isolation as a result of social distancing during the pandemic potentially affects the associations among perceived available peer support, emotional well-being, and depression in university students. The present study examined the associations among perceived available peer support, emotional well-being (as indicated negatively by loneliness and negative affects, and indicated positively by positive affects and hope), and depressive symptoms in university students. During the 3rd stage of the outbreak in July, 2020, 255 students at a public university in Hong Kong participated in an online-based survey which assessed their perceived available peer support, emotional well-being, and depressive symptoms. Results showed that perceived available peer support negatively contributed to depressive symptoms;both negative and positive indicators of emotional well-being mediated the association between perceived available peer support and depressive symptoms. The university students showed signs of depressive symptoms, highlighting the need for preventive efforts and increased access to mental health care that supports the psychological and emotional needs of young people during the COVID-19 pandemic.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-311588

ABSTRACT

Background: Considerable attention has been focused on clinical features of Coronavirus Disease 2019 (COVID-19), it is also important for clinicians to differentiate it from influenza virus infections. Methods The clinical data of 23 cases of H7N9 and 23 cases of COVID-19 with severe pneumonia were collected. The comparisons were performed with the t test, Mann-Whitney U test, Fisher exact test or the chi-squared test, and multivariable logistic regression analysis. Results All of the cases were under the circumstance of sufficient medical staff and medical supplies. The rate of coexisting disease was lower in the severe COVID-19 group than in the severe H7N9 group (p < 0.05). Radiologically, severe COVID-19 patients had less consolidation and pleural effusion, but more crazy-paving pattern than severe H7N9 patients (p < 0.05). Clinically, compared to severe H7N9, severe COVID-19 patients were more inclined to surfer to relative better disease severity score, less secondary bacterial infection, a shorter time to beginning absorption on CT, but a longer duration of viral shedding from the admission (p < 0.05). Although more severe H7N9 patients needed non-invasive respiratory support, these two groups ultimately yielded comparable mortality. Based on multiple logistic regression analysis, severe COVID-19 infection was associated with a lower risk of the presence of severe ARDS (OR 0.964, 95% [CI] 0.931–0.998, p = 0.040), but exhibited longer duration of viral shedding (OR 0.734, 95% [CI] 0.550–0.980, p = 0.036) than severe H7N9 infection. Conclusion Although the conditions of severe H7N9 patients seemed to be more critical than those of severe COVID-19 patients, the relatively lower mortality of these two severe cases is to be expected in context of sufficient medical supplies.

9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315318

ABSTRACT

Background: Different clinical classifications of COVID-19 pneumonia patients have different clinical and CT features, which is very important for the treatment after admission. As the epidemic situation in China continues to improve, it is particularly important to re-clarify the correlation between them. Methods: 97 confirmed patients with COVID-19 pneumonia were enrolled from January 17, 2019 to February 21, 2020, including 75 mild/ordinary cases and 22 severe/critical cases. The clinical data and initial chest CT images of the patients were reviewed and compared. The risk factors associated with disease severity were analyzed. Results: Compared with the mild/ordinary patients, the severe/critical patients had older ages, higher incidence of comorbidities, first CT positive, CT always negative and fever. Mild/ordinary patients had lower body temperature than mild/ordinary patients. The incidences of large/multiple GGO in severe/critical patients were significantly higher than those of the mild/ordinary patients, furthermore, severe/critical patients showed higher incidences of 4-5 lobe infections than the ordinary patients. The CT scores of severe/critical patients were significantly higher than those of the ordinary patients ( P < 0.001). The clinical factors of age, sex, comorbidities, hypertension, diabetes mellitus, heart disease, pharyngeal discomfort, abdominal pain/diarrhea, temperature and CT score were risk factors for severe/critical COVID-19 pneumonia. Conclusion: The initial clinical and CT characteristics have certain significance for the clinical classification of COVID-19 respiratory infection. Especially in terms of CT score, it can predict the trend of clinical classification of patients to a certain extent.

10.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315317

ABSTRACT

AIMTo summarize the chest CT and clinical features of COVID-19 pneumonia patients with hypertension comorbidities.METHODSThe initial chest CT imaging and clinical data of 15 confirmed COVID-19 patients with hypertension comorbidities treated in our hospital were analyzed retrospectively from January 1, 2019 to February 14, 2020. The chest CT images and clinical data were reviewed and their relationship of the disease was analyzed.RESULTSTotally 15 COVID-19 patients diagnosed with hypertension comorbidities were included. In terms of clinical characteristics, 14/15 (93.3%) of patients had characteristics of clustering onset, and the positive rates of the first RT-PCR test and the initial CT were 80% and 93% respectively. The most frequent CT abnormality observed was ground glass opacity (GGO) (13/15, 86.7%), including patchy/ punctate GGO and large/multiple GGO. Most of the lesions were multiple, and 60% of them involved 4-5 lobes. Most patients present with bilateral CT onset (12,80.0%), and most present with subpleural distribution (10,66.7%). The average CT score is 13.7, and 40% of the patients exceeded 20 points.CONCLUSIONThe common chest CT findings in COVID-19 patients with hypertension comorbidities are GGO, most of which at present with bilateral CT onset and subpleural distribution. CT is indispensable in the diagnosis and evaluation of this global health emergency.

11.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315314

ABSTRACT

Purpose: To compare and analyze the clinical and CT features of coronavirus disease 2019 (COVID-19) among different four age groups. Methods: : 97 patients with chest CT examination and positive reverse transcriptase polymerase chain reaction test (RT-PCR) from January 17, 2019 to February 21, 2020 were reviewed. The first clinical symptoms of each patient were collected and their first chest CT images were observed by dividing them into 4 groups according to age: junior, young, middle-age, and senior. Results: Comorbidities are more common in the senior group. Cluster onset is more common in junior group and senior group. Older patients have shown higher incidence with the highest clinical classification of severe or critical in these 4 groups. Senior patients have a higher incidence of large/multiple ground-glass opacity (GGO). Junior patients are mostly negative for chest CT or involve only one lobe of the lung. While in elderly patients, older patients have a higher incidence of involvement of 4 or 5 lung lobes. The frequency of lobe involvement also has significant differences in 4 different age groups. Conclusion: The clinical and imaging features of patients in different age groups are significantly different. Understanding of these features correctly and making the correct diagnosis promptly is of great significance for the scanning, diagnosis and prevention of COVID-19.

12.
Preprint in English | bioRxiv | ID: ppbiorxiv-470356

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel corona virus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo. Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine.

13.
Front Med (Lausanne) ; 8: 749318, 2021.
Article in English | MEDLINE | ID: covidwho-1497094

ABSTRACT

Although the pathologic investigation of liver injury was observed in a couple of cases in China, the detailed description of liver histopathologic and ultrastructural changes in a relatively larger series of liver tissues from COVID-19 patients is lacking. Samples from the liver were obtained from 24 COVID-19 cases from February 1 to April 1, 2020. Light microscopy showed that all liver sections had different degrees of liver injury manifested as swelling of the hepatocytes, hepatocellular necrosis, steatosis, lobular inflammation, portal inflammation, dilatation of sinusoids, and so on. SARS-CoV-2 induced liver injury might be independent of pre-existing Schistosoma infection or obstructive cholestasis. Patients combined with respiratory failure had more severe hepatocellular necrosis and male patients were more susceptible to liver injury. Although coronavirus particles or viral inclusions were not detected in the liver tissues for all cases, vacuolar degenerations in hepatocytes, edematous of mitochondria with the disruption of cristae, and expansions of the endoplasmic reticulum were observed. In conclusion, pathologic changes of liver tissues provide us a further understanding of liver injury in COVID-19 patients. Changes in the liver seem to be related to the underlying diseases/conditions.

14.
Biomed Res Int ; 2021: 5565549, 2021.
Article in English | MEDLINE | ID: covidwho-1476874

ABSTRACT

OBJECTIVES: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus causing substantial morbidity and mortality worldwide. We performed a cross-sectional investigation of SARS-CoV-2 clusters in Suzhou to determine the transmissibility of the virus among close contacts and to assess the demographic and clinical characteristics between index and secondary cases. METHODS: We review the clustered patients with SARS-CoV-2 infections in Suzhou between 22 January and 29 February 2020. The demographic and clinical characteristics were compared between index and secondary cases. We calculated the basic reproduction number (R 0) among close contacts with SLI model. RESULTS: By 22 February, 87 patients with SARS-CoV-2 infection were reported, including 50 sporadic and 37 clustered cases, who were generated from 13 clusters. On admission, 5 (20.8%) out of 24 secondary cases were asymptomatic. The male ratio of index cases was significantly higher than that of secondary cases. Additionally, the index cases were more likely to have fever and increased CRP levels than the secondary cases. The R 0 values of clusters displayed a significantly declining trend over time for all clusters. The relative risk of infection in blood-related contacts of cases versus unrelated contacts was 1.60 for SARS-CoV-2 (95% CI: 0.42-2.95). CONCLUSIONS: In conclusion, SARS-CoV-2 has great person-to-person transmission capability among close contacts. The secondary cases are more prone to have mild symptoms than index cases. There is no increased RR of secondary infection in blood relatives versus unrelated contacts. The high rate of asymptomatic SARS-CoV-2 infections highlights the urgent need to enhance active case finding strategy for early detection of infectious patients.


Subject(s)
COVID-19/epidemiology , Contact Tracing , Family Characteristics , SARS-CoV-2 , Adult , COVID-19/transmission , China/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Risk Factors
15.
Front Med (Lausanne) ; 8: 764493, 2021.
Article in English | MEDLINE | ID: covidwho-1450820

ABSTRACT

[This corrects the article DOI: 10.3389/fmed.2020.584342.].

16.
Signal Transduct Target Ther ; 6(1): 342, 2021 09 16.
Article in English | MEDLINE | ID: covidwho-1415923

ABSTRACT

While some individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present mild-to-severe disease, many SARS-CoV-2-infected individuals are asymptomatic. We sought to identify the distinction of immune response between asymptomatic and moderate patients. We performed single-cell transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing in 37 longitudinal collected peripheral blood mononuclear cell samples from asymptomatic, moderate, and severe patients with healthy controls. Asymptomatic patients displayed increased CD56briCD16- natural killer (NK) cells and upregulation of interferon-gamma in effector CD4+ and CD8+ T cells and NK cells. They showed more robust TCR clonal expansion, especially in effector CD4+ T cells, but lack strong BCR clonal expansion compared to moderate patients. Moreover, asymptomatic patients have lower interferon-stimulated genes (ISGs) expression in general but large interpatient variability, whereas moderate patients showed various magnitude and temporal dynamics of the ISGs expression across multiple cell populations but lower than a patient with severe disease. Our data provide evidence of different immune signatures to SARS-CoV-2 in asymptomatic infections.


Subject(s)
COVID-19 , Carrier State/immunology , Lymphocytes/immunology , SARS-CoV-2/immunology , Single-Cell Analysis , Transcriptome/immunology , Adolescent , Adult , COVID-19/genetics , COVID-19/immunology , Female , Humans , Male , Middle Aged , Receptors, Antigen, B-Cell/genetics , Receptors, Antigen, B-Cell/immunology , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/immunology , SARS-CoV-2/genetics
18.
Eur J Med Chem ; 215: 113286, 2021 Apr 05.
Article in English | MEDLINE | ID: covidwho-1385487

ABSTRACT

Covalent drugs have been intensively studied in some very important fields such as anti-tumor and anti-virus, including the currently global-spread SARS-CoV-2. However, these drugs may interact with a variety of biological macromolecules and cause serious toxicology, so how to reactivate the inhibited targets seems to be imperative in the near future. Organophosphate was an extreme example, which could form a covalent bound easily with acetylcholinesterase and irreversibly inhibited the enzyme, causing high toxicology. Some nucleophilic oxime reactivators for organophosphate poisoned acetylcholinesterase had been developed, but the reactivation process was still less understanding. Herein, we proposed there should be a pre-reactivated pose during the reactivating process and compounds whose binding pose was easy to transfer to the pre-reactivated pose might be efficient reactivators. Then we refined the previous reactivators based on the molecular dynamic simulation results, the resulting compounds L7R3 and L7R5 were proven as much more efficient reactivators for organophosphate inhibited acetylcholinesterase than currently used oximes. This work might provide some insights for constructing reactivators of covalently inhibited targets by using computational methods.


Subject(s)
Acetylcholinesterase/chemistry , Cholinesterase Reactivators/chemistry , Acetylcholinesterase/metabolism , Cholinesterase Inhibitors/chemistry , Cholinesterase Reactivators/metabolism , Humans , Kinetics , Molecular Dynamics Simulation , Organophosphorus Compounds/chemistry , Proof of Concept Study , Protein Binding
19.
J Infect Dis ; 224(4): 586-594, 2021 08 16.
Article in English | MEDLINE | ID: covidwho-1367023

ABSTRACT

BACKGROUND: The duration of humoral and T and B cell response after the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. METHODS: We performed a cross-sectional study to assess the virus-specific antibody and memory T and B cell responses in coronavirus disease 2019 (COVID-19) patients up to 343 days after infection. Neutralizing antibodies and antibodies against the receptor-binding domain, spike, and nucleoprotein of SARS-CoV-2 were measured. Virus-specific memory T and B cell responses were analyzed. RESULTS: We enrolled 59 patients with COVID-19, including 38 moderate, 16 mild, and 5 asymptomatic patients; 31 (52.5%) were men and 28 (47.5%) were women. The median age was 41 years (interquartile range, 30-55). The median day from symptom onset to enrollment was 317 days (range 257 to 343 days). We found that approximately 90% of patients still have detectable immunoglobulin (Ig)G antibodies against spike and nucleocapsid proteins and neutralizing antibodies against pseudovirus, whereas ~60% of patients had detectable IgG antibodies against receptor-binding domain and surrogate virus-neutralizing antibodies. The SARS-CoV-2-specific IgG+ memory B cell and interferon-γ-secreting T cell responses were detectable in more than 70% of patients. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2-specific immune memory response persists in most patients approximately 1 year after infection, which provides a promising sign for prevention from reinfection and vaccination strategy.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Immunity, Cellular/immunology , Adult , B-Lymphocytes/immunology , Cross-Sectional Studies , Female , Humans , Immunoglobulin G/immunology , Immunologic Memory/immunology , Male , Middle Aged , Nucleocapsid Proteins/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/immunology
20.
J Infect Dis ; 224(4): 586-594, 2021 08 16.
Article in English | MEDLINE | ID: covidwho-1225628

ABSTRACT

BACKGROUND: The duration of humoral and T and B cell response after the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. METHODS: We performed a cross-sectional study to assess the virus-specific antibody and memory T and B cell responses in coronavirus disease 2019 (COVID-19) patients up to 343 days after infection. Neutralizing antibodies and antibodies against the receptor-binding domain, spike, and nucleoprotein of SARS-CoV-2 were measured. Virus-specific memory T and B cell responses were analyzed. RESULTS: We enrolled 59 patients with COVID-19, including 38 moderate, 16 mild, and 5 asymptomatic patients; 31 (52.5%) were men and 28 (47.5%) were women. The median age was 41 years (interquartile range, 30-55). The median day from symptom onset to enrollment was 317 days (range 257 to 343 days). We found that approximately 90% of patients still have detectable immunoglobulin (Ig)G antibodies against spike and nucleocapsid proteins and neutralizing antibodies against pseudovirus, whereas ~60% of patients had detectable IgG antibodies against receptor-binding domain and surrogate virus-neutralizing antibodies. The SARS-CoV-2-specific IgG+ memory B cell and interferon-γ-secreting T cell responses were detectable in more than 70% of patients. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2-specific immune memory response persists in most patients approximately 1 year after infection, which provides a promising sign for prevention from reinfection and vaccination strategy.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Immunity, Cellular/immunology , Adult , B-Lymphocytes/immunology , Cross-Sectional Studies , Female , Humans , Immunoglobulin G/immunology , Immunologic Memory/immunology , Male , Middle Aged , Nucleocapsid Proteins/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/immunology
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