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1.
Commun Med (Lond) ; 2: 36, 2022.
Article in English | MEDLINE | ID: covidwho-1860433

ABSTRACT

Background: Evaluation of susceptibility to emerging SARS-CoV-2 variants of concern (VOC) requires rapid screening tests for neutralising antibodies which provide protection. Methods: Firstly, we developed a receptor-binding domain-specific haemagglutination test (HAT) to Wuhan and VOC (alpha, beta, gamma and delta) and compared to pseudotype, microneutralisation and virus neutralisation assays in 835 convalescent sera. Secondly, we investigated the antibody response using the HAT after two doses of mRNA (BNT162b2) vaccination. Sera were collected at baseline, three weeks after the first and second vaccinations from older (80-99 years, n = 89) and younger adults (23-77 years, n = 310) and compared to convalescent sera from naturally infected individuals (1-89 years, n = 307). Results: Here we show that HAT antibodies highly correlated with neutralising antibodies (R = 0.72-0.88) in convalescent sera. Home-dwelling older individuals have significantly lower antibodies to the Wuhan strain after one and two doses of BNT162b2 vaccine than younger adult vaccinees and naturally infected individuals. Moverover, a second vaccine dose boosts and broadens the antibody repertoire to VOC in naïve, not previously infected older and younger adults. Most (72-76%) older adults respond after two vaccinations to alpha and delta, but only 58-62% to beta and gamma, compared to 96-97% of younger vaccinees and 68-76% of infected individuals. Previously infected older individuals have, similarly to younger adults, high antibody titres after one vaccination. Conclusions: Overall, HAT provides a surrogate marker for neutralising antibodies, which can be used as a simple inexpensive, rapid test. HAT can be rapidly adaptable to emerging VOC for large-scale evaluation of potentially decreasing vaccine effectiveness.

2.
Int Immunopharmacol ; 108: 108767, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1796627

ABSTRACT

It remains unclear whether immune responses following natural infection can be sustained or potentially prove critical for long-term immune protection against SARS-CoV-2 reinfection. Here, we systematically mapped the phenotypic landscape of SARS-CoV-2-specific immune responses in peripheral blood samples of convalescent patients with COVID-19 by single-cell RNA sequencing. The relative percentage of the CD8 + effector memory subset was increased in both convalescent moderate and severe cases, but NKT-CD160 and marginal zone B clusters were decreased. Innate immune responses were attenuated reflected by decreased expression of genes involved in interferon-gamma, leukocyte migration and neutrophil mediated immune response in convalescent COVID-19 patients. Functions of T cell were strengthened in convalescent COVID-19 patients by clear endorsement of increased expression of genes involved in biological processes of regulation of T cell activation, differentiation and cell-cell adhesion. In addition, T cell mediated immune responses were enhanced with remarkable clonal expansions of TCR and increased transition of CD4 + effector memory and CD8 + effector-GNLY in severe subjects. B cell immune responses displayed complicated and dualfunctions during convalescence of COVID-19, providing a novel mechanism that B cell activation was observed especially in moderate while humoral immune response was weakened. Interestingly, HLA class I genes displayed downregulation while HLA class II genes upregulation in both T and B cell subsets in convalescent individuals. Our results showed that innate immunity was declined but SARS-CoV-2-specific T cell responses were retained even strengthened whereas complicated and dualfunctions of B cells, including declined humoral immunity were presented at several months following infections.


Subject(s)
COVID-19 , Antibodies, Viral , Convalescence , Humans , Immunity, Humoral , SARS-CoV-2 , Sequence Analysis, RNA
3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-332687

ABSTRACT

Diagnostic assays currently used to monitor the efficacy of COVID-19 vaccines measure levels of antibodies to the receptor-binding domain of ancestral SARS-CoV-2 (RBDwt). However, the predictive value for protection against new variants of concern (VOCs) has not been firmly established. Here, we used bead-based arrays and flow cytometry to measure binding of antibodies to spike proteins and receptor-binding domains (RBDs) from VOCs in 12,000 sera. Effects of sera on RBD-ACE2 interactions were measured as a proxy for neutralizing antibodies. The samples were obtained from healthy individuals or patients on immunosuppressive therapy who had received two to four doses of COVID-19 vaccines and from COVID-19 convalescents. The results show that anti-RBDwt titers correlate with the levels of binding- and neutralizing antibodies against the Alpha, Beta, Gamma, Delta, Epsilon and Omicron variants. The benefit of multiplexed analysis lies in the ability to measure a wide range of anti-RBD titers using a single dilution of serum for each assay. The reactivity patterns also yield an internal reference for neutralizing activity and binding antibody units per milliliter (BAU/ml). Results obtained with sera from vaccinated healthy individuals and patients confirmed and extended results from previous studies on time-dependent waning of antibody levels and effects of immunosuppressive agents. We conclude that anti-RBDwt titers correlate with levels of neutralizing antibodies against VOCs and propose that our method may be implemented to enhance the precision and throughput of immunomonitoring.

4.
Front Cell Infect Microbiol ; 12: 841447, 2022.
Article in English | MEDLINE | ID: covidwho-1775647

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) pandemic has led to the initiation of unprecedented research efforts to understand the pathogenesis mediated by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). More knowledge is needed regarding the cell type-specific cytopathology and its impact on cellular tropism. Furthermore, the impact of novel SARS-CoV-2 mutations on cellular tropism, alternative routes of entry, the impact of co-infections, and virus replication kinetics along the respiratory tract remains to be explored in improved models. Most applied virology models are not well suited to address the remaining questions, as they do not recapitulate the histoarchitecture and cellular composition of human respiratory tissues. The overall aim of this work was to establish from single biopsy specimens, a human adult stem cell-derived organoid model representing the upper respiratory airways and lungs and explore the applicability of this model to study respiratory virus infection. First, we characterized the organoid model with respect to growth pattern and histoarchitecture, cellular composition, and functional characteristics. Next, in situ expression of viral entry receptors, including influenza virus-relevant sialic acids and SARS-CoV-2 entry receptor ACE2 and TMPRSS2, were confirmed in organoids of bronchiolar and alveolar differentiation. We further showed successful infection by pseudotype influenza A H7N1 and H5N1 virus, and the ability of the model to support viral replication of influenza A H7N1 virus. Finally, successful infection and replication of a clinical isolate of SARS-CoV-2 were confirmed in the organoids by TCID50 assay and immunostaining to detect intracellular SARS-CoV-2 specific nucleocapsid and dsRNA. The prominent syncytia formation in organoid tissues following SARS-CoV-2 infection mimics the findings from infected human tissues in situ. We conclude that the human organotypic model described here may be particularly useful for virology studies to evaluate regional differences in the host response to infection. The model contains the various cell types along the respiratory tract, expresses respiratory virus entry factors, and supports successful infection and replication of influenza virus and SARS-CoV-2. Thus, the model may serve as a relevant and reliable tool in virology and aid in pandemic preparedness, and efficient evaluation of antiviral strategies.


Subject(s)
COVID-19 , Influenza A Virus, H5N1 Subtype , Influenza A Virus, H7N1 Subtype , Influenza, Human , Adult , Humans , Lung , Organoids , SARS-CoV-2
5.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331822

ABSTRACT

Diagnostic assays currently used to monitor the efficacy of COVID-19 vaccines measure levels of antibodies to the receptor-binding domain of ancestral SARS-CoV-2 (RBDwt). However, the predictive value for protection against new variants of concern (VOCs) has not been firmly established. Here, we used bead-based arrays and flow cytometry to measure binding of antibodies to spike proteins and receptor-binding domains (RBDs) from VOCs in 12,000 sera. Effects of sera on RBD-ACE2 interactions were measured as a proxy for neutralizing antibodies. The samples were obtained from healthy individuals or patients on immunosuppressive therapy who had received two to four doses of COVID-19 vaccines and from COVID-19 convalescents. The results show that anti-RBDwt titers correlate with the levels of binding- and neutralizing antibodies against the Alpha, Beta, Gamma, Delta, Epsilon and Omicron variants. The benefit of multiplexed analysis lies in the ability to measure a wide range of anti-RBD titers using a single dilution of serum for each assay. The reactivity patterns also yield an internal reference for neutralizing activity and binding antibody units per milliliter (BAU/ml). Results obtained with sera from vaccinated healthy individuals and patients confirmed and extended results from previous studies on time-dependent waning of antibody levels and effects of immunosuppressive agents. We conclude that anti-RBDwt titers correlate with levels of neutralizing antibodies against VOCs and propose that our method may be implemented to enhance the precision and throughput of immunomonitoring.

6.
PLoS One ; 17(2): e0261979, 2022.
Article in English | MEDLINE | ID: covidwho-1703403

ABSTRACT

BACKGROUND: Neutralizing antibodies are important for protection against the pandemic SARS-CoV-2 virus, and long-term memory responses determine the risk of re-infection or boosting after vaccination. T-cellular responses are considered important for partial protection against novel variants of concern. METHODS: A prospective cohort of hospitalized (n = 14) and community (n = 38) patients with rt-PCR confirmed SARS-CoV-2 infection were recruited. Blood samples and clinical data were collected when diagnosed and at 6 months. Serum samples were analyzed for SARS-CoV-2-spike specific antibodies using ELISA (IgG, IgA, IgM), pseudotype neutralization and microneutralization assays. Peripheral blood mononuclear cells were investigated for virus-specific T-cell responses in the interferon-γ and interleukin-2 fluorescent-linked immunosorbent spot (FluroSpot) assay. RESULTS: We found durable SARS-CoV-2 spike- and internal protein specific T-cellular responses in patients with persistent antibodies at 6 months. Significantly higher IL-2 and IFN-γ secreting T-cell responses as well as SARS-CoV-2 specific IgG and neutralizing antibodies were detected in hospitalized compared to community patients. The immune response was impacted by age, gender, comorbidity and severity of illness, reflecting clinical observations. CONCLUSIONS: SARS-CoV-2 specific T-cellular and antibody responses persisted for 6 months post confirmed infection. In previously infected patients, re-exposure or vaccination will boost long-term immunity, possibly providing protection against re-infection with variant viruses.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Immunity, Cellular , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Adult , Age Factors , Aged , Aged, 80 and over , COVID-19/mortality , COVID-19/therapy , Female , Follow-Up Studies , Hospitalization , Humans , Interferon-gamma/immunology , Interleukin-2/immunology , Male , Middle Aged , Prospective Studies , Risk Factors
7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315178

ABSTRACT

Background: Among patients with confirmed severe/critical type COVID-19, we found that although the seurm creatinine (Cr) value is in normal range, patients might have occured early renal damage. For severe/critical type COVID-19 patients, whether some chest CT features can be used to predict the early renal damage or clinical prognosis. Methods: : 162 patients with severe/critical type COVID-19 were reviewed retrospectively in 13 medical centers from China. According to the level of eGFR, 162 patients were divided into three groups, group A (eGFR < 60 ml/min/1.73m 2 ), group B (60 ml/min/1.73m 2 ≤ eGFR < 90 ml/min/1.73m 2 group) and group C (eGFR ≥ 90 ml/min/1.73m 2 ). All patients’ baseline clinical characteristics, laboratory data, CT features and clinical outcomes were collected and compared. The eGFR and CT features was assessed using univariate and multivariate Cox regression. Results: : Baseline clinical characteristics showed that there were significant differences in age, hypertension, cough and fatigue among groups A, B and C. Laboratory data analysis revealed significant differences between the three groups of leukocyte count, platelet count, C-reactive protein, aspartate aminotransferase, creatine kinase. Chest CT features analysis indicated that crazy-paving pattern has significant statistical difference in groups A and B compared with group C. The eGFR of patients with crazy-paving pattern was significant lower than those without crazy-paving pattern (76.73 ± 30.50 vs. 101.69 ± 18.24 ml/min/1.73m 2 , p < 0.001), and eGFR (OR = 0.962, 95% CI = 0.940-0.985) was the independent risk factor of crazy-paving pattern. The eGFR (HR = 0.549, 95% CI = 0.331-0.909, p = 0.020) and crazy-paving pattern (HR = 2.996, 95% CI = 1.010-8.714, p = 0.048) were independent risk factors of mortality. Conclusions: : In patients with severe/critical type COVID-19, the presence of crazy-paving pattern on chest CT are more likely occured the decline of eGFR and poor clinical prognosis. The crazy-paving pattern appeared could be used as an early warning indicator of renal damage and to guide clinicians to use drugs reasonably.

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-313366

ABSTRACT

Background: Blood laboratory tests are the most reliable methods for the diagnosis and assessment of vital organs’ functions and the body’s response to infection. Herein, we compared the results of dynamic blood tests between the survivor and non-survivor group of patients with coronavirus disease 2019 (COVID-19) and aimed to determine the predicted and tricky week for death and surveillance. Methods: : The survivor and non-survivor groups were compared using biochemical blood tests, routine blood tests, and coagulation blood tests over four weeks of investigation. Results: : Blood urea nitrogen, creatinine, high-sensitivity C-reactive protein, total bile acid, neutrophil count, white blood cell count, D-dimer, fibrin and fibrinogen degradation product, and prothrombin time showed significantly higher levels in the non-survivor group than the survivor group. Only pre-albumin, eosinophil count, lymphocyte count, red blood cell count, platelet count, hemoglobin, and prothrombin activity tests were significantly higher in the survivor group than the non-survivor group. Generally, the third week of the non-survivor’s group could be regarded as the predicted week for death based on all tests except for creatinine, pre-albumin, total bile acid, monocyte count, white blood cell count, and prothrombin activity. The tricky week in the non-survivor group was the second week in all tests except for pre-albumin, basophil count, eosinophil count, lymphocyte count, platelet count, D-dimer, and fibrin and fibrinogen degradation product. Conclusions: : Based on our study, specific attention should be given to some weeks with respect to their related tests as predicted or tricky for death or surveillance, respectively.

9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312622

ABSTRACT

Background: A striking characteristic of Coronavirus Disease 2019(COVID-19) is the coexistence of clinically mild and severe cases. A comprehensive analysis of multiple risk factors predicting progression to severity is clinically meaningful. Methods: The patients were classified into moderate and severe groups. The univariate regression analysis was used to identify their epidemiological and clinical features related to severity, which were used as possible risk factors and were entered into a forward-stepwise multiple logistic regression analysis to develop a multiple factor prediction model for the severe cases. Results: 255 patients (mean age, 49.1±SD 14.6) were included, consisting of 184 (72.2%) moderate cases and 71 (27.8%) severe cases. The common symptoms were dry cough (78.0%), sputum (62.7%), and fever (59.2%). The less common symptoms were fatigue (29.4%), diarrhea (25.9%), and dyspnea (20.8%). The univariate regression analysis determined 23 possible risk factors. The multiple logistic regression identified seven risk factors closely related to the severity of COVID-19, including dyspnea, exposure history in Wuhan, CRP (C-reactive protein), aspartate aminotransferase (AST), calcium, lymphocytes, and age. The probability model for predicting the severe COVID-19 was P=1/1+exp (-1.78+1.02×age+1.62×high-transmission-setting-exposure +1.77×dyspnea+1.54×CRP+1.03×lymphocyte+1.03×AST+1.76×calcium). Dyspnea (OR=5.91) and hypocalcemia (OR=5.79) were the leading risk factors, followed by exposure to a high-transmission setting (OR=5.04), CRP (OR=4.67), AST (OR=2.81), decreased lymphocyte count (OR=2.80), and age (OR=2.78). Conclusions: This quantitative prognosis prediction model can provide a theoretical basis for the early formulation of individualized diagnosis and treatment programs and prevention of severe diseases.

10.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325175

ABSTRACT

Objective: To describe the clinical characteristics and outcomes of ordinary COVID-19 when admitted, to describe how these patients were treated and risk factors for in-hospital progression. Methods: : In this retrospective study, we included 291 adult patients diagnosed as ordinary COVID-19 on admission who had been discharged or had died between Jan 20, 2020 and Mar 16, 2020 from General Hospital of Central Theatre Command (Wuhan, China). Results: : Of the 291 patients diagnosed as ordinary COVID-19 when admitted, 65 (22.34%) had been recorded COVID-19 progressing at least once, and 226 (77.66%) had been recorded COVID-19 improving during hospitalization. The median time from admission to disease progressed was 5.0 days (2.0-7.0). Multivariable regression showed increasing odds of in-hospital progression associated with male (odds ratio 2.333, 95% CI 1.135-4.395;P=0.020), preexisting cardiovascular diseases (2.433, 1.044-5.671;P=0.039), and lymphopenia (3.482, 1.783-6.799;P<0.001), elevated IL-6 (2.669, 1.084-6.574;P=0.033), d-dimer (2.829, 1.420-5.636;P=0.003) and lactate dehydrogenase (2.855, 1.458-5.591;P= 0.002) on admission. Conclusions: : The potential risk factors of male, preexisting cardiovascular disease, lymphopenia, elevated IL-6, and lactate dehydrogenase, d-dimer could help clinicians to identify in-hospital progression among ordinary COVID-19 at early stage to optimize medical treatment.

11.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324954

ABSTRACT

Introduction: The outbreak of a novel coronavirus (SARS-CoV-2) and associated COVID-19 disease in late December 2019 has led to a global pandemic. It directly leads to high morbidity and mortality, but also results in a devastating effect on the global economy. Unfortunately, there are no effective therapies or vaccines for it. Hence, we designed a randomized trial to evaluate the efficacy and safety of Traditional Chinese Medicine for treating patients with COVID-19. Methods: and analysis: This is an open-label, multicenter randomized controlled clinical trial. One hundred and twelve patients infected by SARS-CoV-2 will be randomly assigned to the experimental or the control group in an equal ratio. The patients in control group will accept routine supportive clinically care including the therapies of anti-viral, anti-bacterial and ameliorating the related symptoms, while patients in the experimental group will be asked to take traditional Chinese medicine depending on the different stages of the disease for consecutive 14 days in addition to supportive care. All data will be gathered at baseline and on days 3, 7, 10 and 14. The primary outcome measures will be the time of Reverse Transcription PCR testing of respiratory tract sample turns to be negative. Secondary outcome measures will include Murray lung injury score, MuLBSTA score and TCM ( Traditional Chinese Medicine ) Syndrome Scoring System. A laboratory test will be taken before and after treatment to assess the safety of TCM. Discussion: The study may help to identify the the efficacy and safety of Traditional Chinese Medicine in treating COVID-2019. Trial registration: Chinese Clinical Trial Registry, ChiCTR2000030759.Registered on March 13 th 2020-Retrospectively registered, http://www.chictr.org.cn/.

12.
Frontiers in cardiovascular medicine ; 8, 2021.
Article in English | EuropePMC | ID: covidwho-1679286

ABSTRACT

Coronary artery disease (CAD) is a major contributor to morbidity and mortality worldwide. Myocardial ischemia may occur in patients with normal or non-obstructive CAD on invasive coronary angiography (ICA). The comprehensive evaluation of coronary CT angiography (CCTA) integrated with fractional flow reserve derived from CCTA (CT-FFR) to CAD may be essential to improve the outcomes of patients with non-obstructive CAD. China CT-FFR Study-2 (ChiCTR2000031410) is a large-scale prospective, observational study in 29 medical centers in China. The primary purpose is to uncover the relationship between the CCTA findings (including CT-FFR) and the outcome of patients with non-obstructive CAD. At least 10,000 patients with non-obstructive CAD but without previous revascularization will be enrolled. A 5-year follow-up will be performed. The primary endpoint is the occurrence of major adverse cardiovascular events (MACE), including all-cause mortality, non-fatal myocardial infarct, unplanned revascularization, and hospitalization for unstable angina. Clinical characteristics, laboratory and imaging examination results will be collected to analyze their prognostic value.

13.
Int J Mol Sci ; 23(3)2022 Feb 06.
Article in English | MEDLINE | ID: covidwho-1674673

ABSTRACT

The SARS-CoV-2 pandemic caused a massive health and societal crisis, although the fast development of effective vaccines reduced some of the impact. To prepare for future respiratory virus pandemics, a pan-viral prophylaxis could be used to control the initial virus outbreak in the period prior to vaccine approval. The liposomal vaccine adjuvant CAF®09b contains the TLR3 agonist polyinosinic:polycytidylic acid, which induces a type I interferon (IFN-I) response and an antiviral state in the affected tissues. When testing CAF09b liposomes as a potential pan-viral prophylaxis, we observed that intranasal administration of CAF09b liposomes to mice resulted in an influx of innate immune cells into the nose and lungs and upregulation of IFN-I-related gene expression. When CAF09b liposomes were administered prior to challenge with mouse-adapted influenza A/Puerto Rico/8/1934 virus, it protected from severe disease, although the virus was still detectable in the lungs. However, when CAF09b liposomes were administered after influenza challenge, the mice had a similar disease course to controls. In conclusion, CAF09b may be a suitable candidate as a pan-viral prophylactic treatment for epidemic viruses, but must be administered prior to virus exposure to be effective.


Subject(s)
/therapeutic use , Influenza Vaccines/therapeutic use , Influenza, Human/prevention & control , Orthomyxoviridae Infections/prevention & control , /methods , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/therapeutic use , /chemistry , Administration, Intranasal , Animals , COVID-19/prevention & control , COVID-19 Vaccines/chemical synthesis , COVID-19 Vaccines/therapeutic use , Cells, Cultured , Chick Embryo , Gene Expression Regulation/drug effects , Humans , Influenza Vaccines/administration & dosage , Influenza Vaccines/chemistry , Influenza Vaccines/pharmacology , Interferon Type I/genetics , Liposomes/chemistry , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Primary Prevention/methods , SARS-CoV-2/immunology
14.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296458

ABSTRACT

ABSTRACT The SARS-CoV-2 pandemic caused a massive health and societal crisis, although the fast development of effective vaccines reduced some of the impact. To prepare for future pandemics, a pan-viral prophylaxis could be used to control the initial virus outbreak in the period prior to vaccine approval. The liposomal vaccine adjuvant CAF ® 09b contains the TLR3 agonist polyinosinic:polycytidylic acid, which induces a type I interferon (IFN-I) response and an antiviral state in the affected tissues. When testing CAF09b as a potential pan-viral prophylaxis, we observed that intranasal administration of CAF09b to mice resulted in an influx of innate immune cells into the nose and lungs and upregulation of IFN-I related gene expression. When CAF09b was administered prior to challenge with mouse-adapted influenza A/Puerto Rico/8/1934 virus, it protected from severe disease, although virus was still detectable in the lungs. However, when CAF09b was administered after influenza challenge, the mice had a similar disease course to controls. In conclusion, CAF09b may be a suitable candidate as a pan-viral prophylactic treatment for epidemic viruses, but must be administered prior to virus exposure to be effective.

15.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296437

ABSTRACT

Background: The immune response to SARS-CoV-2 is critical in both controlling primary infection and preventing re-infection. However, it remains unclear whether immune responses following natural infection can be sustained or potentially prove critical for long-term immune protection against SARS-CoV-2 reinfection. Here, we systematically mapped the phenotypic landscape of SARS-CoV-2-specific immune responses in peripheral blood samples of 4 healthy donors and 13 convalescent patients with COVID-19, including moderate and severe cases, by single-cell RNA sequencing. Results: : The relative percentage of the CD8+ effector memory subset was increased in both convalescent moderate and severe cases, but NKT-CD160 and maginal zone B clusters were decreased. Innate immune responses were attenuated reflected by decreased expression of genes involved in interferon-gamma, leukocyte migration and neutrophil mediated immune response in convalescent COVID-19 patients. Functions of T cell were strengthened in convalescent COVID-19 patients by clear endorsement of increased expression of genes involved in biological processes of regulation of T cell activation, differentiation and cell-cell adhesion. In addition, T cell mediated immune responses were enhanced with remarkable clonal expansions of TCR and increased transition of CD4+ effector memory and CD8+ effector-GNLY in severe subjects. B cell immune responses displayed sophisticated and dual functions during convalescence of COVID-19, providing a novel mechanism that B cell activation was observed especially in moderate while humoral immune response was weakened. Interestingly, HLA class I genes displayed downregulation while HLA class II genes upregulation in both T and B cell subsets in convalescent individuals. Notably, some unique IGV genes in severe patients may facilitate the design of vaccines. Conclusions: : Our collective dataset showed that innate immunity was declined but SARS-CoV-2-specific T cell responses were retained even strengthened whereas sophisticated and dual functions of B cells, including declined humoral immunity were presented at several months following infections, which provided insights into evaluation of possibility of reinfection of exposed individuals with COVID-19 and facilitation to design of effective therapeutics and vaccines.

16.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-295406

ABSTRACT

Backgroud : Both Chlamydia psittaci and COVID-19 virus can cause lung inflammation, which manifests extremely similarly in clinical symptoms and imaging. Especially during the epidemic of COVID-19, psittacosis pneumonia is easily misdiagnosed as COVID-19 pneumonia. The identification of the chest imaging between the two diseases is of special significance when the epidemiological contact history is unclear, and the etiology and nucleic acid test results are not available. This study conducts to compare the imaging characteristics on chest high-resolution CTs (HRCT) between patients with psittaci pneumonia and COVID-19 pneumonia. Methods: : A retrospective analysis of the imaging characteristics on chest HRCTs of 10 psittaci pneumonia patients and 13 COVID-19 pneumonia patients. The similarities and differences in HRCT images of patients with psittaci pneumonia and COVID-19 pneumonia were analyzed. Results: : HRCT showed that among the 10 psittaci pneumonia patients, 8 cases (80.00%) had single lobe involvement, and 2 cases (20.00%) had multiple lobe involvement. Among the 13 COVID-19 pneumonia patients, 2 cases had single lobe involvement (15.38%), and 11 cases had multiple lobe involvement (84.62%). The types of lesions in 10 psittaci pneumonia patients included simple consolidation in 5 cases (50.00%), and ground-glass opacity (GGO) with consolidation in 5 cases (50.00%). The types of lesions in 13 COVID-19 pneumonia patients included simple GGO in 6 cases (46.15%), GGO with consolidation in 4 cases (30.77%), GGO with paving stone sign in 2 cases (15.38%), and simple consolidation in 1 case (7.69%). Lymphadenopathy was observed in 1 psittaci pneumonia patient (10.00%) and 1 COVID-19 pneumonia patient (7.69%). Among the 10 psittaci pneumonia patients, 8 cases (80.00%) had bronchial inflation, and 6 patients (60.00%) had pleural effusion. Among the 13 COVID-19 pneumonia patients, 5 patients (38.46%) showed signs of bronchial inflation, while no pleural effusion was observed in 13 patients. Conclusion: : Chest HRCTs can distinguish COVID-19 pneumonia from psittaci pneumonia, and can provide early diagnoses of these two diseases.

17.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-294661

ABSTRACT

Evaluation of susceptibility to emerging SARS-CoV-2 variants of concern (VOC) requires rapid screening tests for neutralising antibodies which provide protection. We developed a receptor-binding domain specific hemagglutination test (HAT) which correlated with neutralising antibodies (R=0.74-0.82) in two independent cohorts from 798 convalescents. Home-dwelling older individuals (80-99 years, n=89) had significantly lower antibodies after one dose of BNT162b2 vaccine than younger adult vaccinees (n=310) and naturally infected individuals (n=307). The second vaccine dose boosted and broadened the antibody repertoire to VOC in naïve but not previously infected, older and younger adults. >75% of older adults responded after two vaccinations to alpha and delta, but only 59-62% to beta and gamma, compared to 96-97% of younger vaccinees and 68-76% of infected individuals. Overall, the HAT provides a surrogate marker for neutralising antibodies, could be used as a simple inexpensive, rapid test, rapidly adaptable to emerging VOC for large-scale evaluation of potentially diminishing vaccine effectiveness.

18.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-293368

ABSTRACT

Backgroud : Both Chlamydia psittaci and COVID-19 virus can cause lung inflammation, which manifests extremely similarly in clinical symptoms and imaging. Especially during the epidemic of COVID-19, psittacosis pneumonia is easily misdiagnosed as COVID-19 pneumonia. The identification of the chest imaging between the two diseases is of special significance when the epidemiological contact history is unclear, and the etiology and nucleic acid test results are not available. This study conducts to compare the imaging characteristics on chest high-resolution CTs (HRCT) between patients with psittaci pneumonia and COVID-19 pneumonia. Methods: : A retrospective analysis of the imaging characteristics on chest HRCTs of 10 psittaci pneumonia patients and 13 COVID-19 pneumonia patients. The similarities and differences in HRCT images of patients with psittaci pneumonia and COVID-19 pneumonia were analyzed. Results: : HRCT showed that among the 10 psittaci pneumonia patients, 8 cases (80.00%) had single lobe involvement, and 2 cases (20.00%) had multiple lobe involvement. Among the 13 COVID-19 pneumonia patients, 2 cases had single lobe involvement (15.38%), and 11 cases had multiple lobe involvement (84.62%). The types of lesions in 10 psittaci pneumonia patients included simple consolidation in 5 cases (50.00%), and ground-glass opacity (GGO) with consolidation in 5 cases (50.00%). The types of lesions in 13 COVID-19 pneumonia patients included simple GGO in 6 cases (46.15%), GGO with consolidation in 4 cases (30.77%), GGO with paving stone sign in 2 cases (15.38%), and simple consolidation in 1 case (7.69%). Lymphadenopathy was observed in 1 psittaci pneumonia patient (10.00%) and 1 COVID-19 pneumonia patient (7.69%). Among the 10 psittaci pneumonia patients, 8 cases (80.00%) had bronchial inflation, and 6 patients (60.00%) had pleural effusion. Among the 13 COVID-19 pneumonia patients, 5 patients (38.46%) showed signs of bronchial inflation, while no pleural effusion was observed in 13 patients. Conclusion: : Chest HRCTs can distinguish COVID-19 pneumonia from psittaci pneumonia, and can provide early diagnoses of these two diseases.

19.
ISPRS International Journal of Geo-Information ; 10(10):659, 2021.
Article in English | ProQuest Central | ID: covidwho-1480789

ABSTRACT

Numerous studies have been devoted to uncovering the characteristics of resident density and urban mobility with multisource geospatial big data. However, little attention has been paid to the internal diversity of residents such as their occupations, which is a crucial aspect of urban vibrancy. This study aims to investigate the variation between individual and interactive influences of built environment factors on occupation mixture index (OMI) with a novel GeoDetector-based indicator. This study first integrated application (App) use and mobility patterns from cellphone data to portray residents’ occupations and evaluate the OMI in Guangzhou. Then, the mechanism of OMI distribution was analyzed with the GeoDetector model. Next, an optimized GeoDetector-based index, interactive effect variation ratio (IEVR) was proposed to quantify the variation between individual and interactive effects of factors. The results showed that land use mixture was the dominating factor, and that land use mixture, building density, floor area ratio, road density affected the OMI distribution directly. Some interesting findings were uncovered by IEVR. The influences of cultural inclusiveness and metro accessibility were less important in factor detector result, while they were found to be the most influential in an indirect way interacting with other built environment factors. The results suggested that both “hardware facilities” (land use mixture, accessibility) and “soft facilities” (cultural inclusiveness) should be considered in planning a harmonious urban employment space and sustainable city.

20.
Nat Med ; 27(9): 1607-1613, 2021 09.
Article in English | MEDLINE | ID: covidwho-1290003

ABSTRACT

Long-term complications after coronavirus disease 2019 (COVID-19) are common in hospitalized patients, but the spectrum of symptoms in milder cases needs further investigation. We conducted a long-term follow-up in a prospective cohort study of 312 patients-247 home-isolated and 65 hospitalized-comprising 82% of total cases in Bergen during the first pandemic wave in Norway. At 6 months, 61% (189/312) of all patients had persistent symptoms, which were independently associated with severity of initial illness, increased convalescent antibody titers and pre-existing chronic lung disease. We found that 52% (32/61) of home-isolated young adults, aged 16-30 years, had symptoms at 6 months, including loss of taste and/or smell (28%, 17/61), fatigue (21%, 13/61), dyspnea (13%, 8/61), impaired concentration (13%, 8/61) and memory problems (11%, 7/61). Our findings that young, home-isolated adults with mild COVID-19 are at risk of long-lasting dyspnea and cognitive symptoms highlight the importance of infection control measures, such as vaccination.


Subject(s)
Antibodies, Viral/blood , COVID-19/complications , COVID-19/pathology , Cognitive Dysfunction/virology , Dyspnea/virology , Fatigue/virology , Adolescent , Adult , Ageusia/virology , Anosmia/virology , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Norway , Patient Isolation , Prospective Studies , SARS-CoV-2 , Severity of Illness Index , Young Adult
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