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1.
Emerg Microbes Infect ; 11(1): 1524-1536, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1860763

ABSTRACT

The waning humoral immunity and emerging contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants resulted in the necessity of the booster vaccination of coronavirus disease 2019 (COVID-19). The inactivated vaccine, CoronaVac, is the most widely supplied COVID-19 vaccine globally. Whether the CoronaVac booster elicited adaptive responses that cross-recognize SARS-CoV-2 variants of concern (VoCs) among 77 healthy subjects receiving the third dose of CoronaVac were explored. After the boost, remarkable elevated spike-specific IgG and IgA responses, as well as boosted neutralization activities, were observed, despite 3.0-fold and 5.9-fold reduced neutralization activities against Delta and Omicron strains compared to that of the ancestral strain. Furthermore, the booster dose induced potent B cells and memory B cells that cross-bound receptor-binding domain (RBD) proteins derived from VoCs, while Delta and Omicron RBD-specific memory B cell recognitions were reduced by 2.7-fold and 4.2-fold compared to that of ancestral strain, respectively. Consistently, spike-specific circulating follicular helper T cells (cTfh) significantly increased and remained stable after the boost, with a predominant expansion towards cTfh17 subpopulations. Moreover, SARS-CoV-2-specific CD4+ and CD8+ T cells peaked and sustained after the booster. Notably, CD4+ and CD8+ T cell recognition of VoC spike was largely preserved compared to the ancestral strain. Individuals without generating Delta or Omicron neutralization activities had comparable levels of CD4+ and CD8+ T cells responses as those with detectable neutralizing activities. Our study demonstrated that the CoronaVac booster induced broad and potent adaptive immune responses that could be effective in controlling SARS-CoV-2 Delta and Omicron variants.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , CD8-Positive T-Lymphocytes , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunity, Humoral , Vaccination
2.
Sci Transl Med ; 14(642): eabn9243, 2022 04 27.
Article in English | MEDLINE | ID: covidwho-1741565

ABSTRACT

The Omicron variant of SARS-CoV-2 has been shown to evade neutralizing antibodies elicited by vaccination or infection. Despite the global spread of the Omicron variant, even among highly vaccinated populations, death rates have not increased concomitantly. These data suggest that immune mechanisms beyond antibody-mediated virus neutralization may protect against severe disease. In addition to neutralizing pathogens, antibodies contribute to control and clearance of infections through Fc effector mechanisms. Here, we probed the ability of vaccine-induced antibodies to drive Fc effector activity against the Omicron variant using samples from individuals receiving one of three SARS-CoV-2 vaccines. Despite a substantial loss of IgM, IgA, and IgG binding to the Omicron variant receptor binding domain (RBD) in samples from individuals receiving BNT162b2, mRNA-1273, and CoronaVac vaccines, stable binding was maintained against the full-length Omicron Spike protein. Compromised RBD binding IgG was accompanied by a loss of RBD-specific antibody Fcγ receptor (FcγR) binding in samples from individuals who received the CoronaVac vaccine, but RBD-specific FcγR2a and FcγR3a binding was preserved in recipients of mRNA vaccines. Conversely, Spike protein-specific antibodies exhibited persistent but reduced binding to FcγRs across all three vaccines, although higher binding was observed in samples from recipients of mRNA vaccines. This was associated with preservation of FcγR2a and FcγR3a binding antibodies and maintenance of Spike protein-specific antibody-dependent natural killer cell activation. Thus, despite the loss of Omicron neutralization, vaccine-induced Spike protein-specific antibodies continue to drive Fc effector functions, suggesting a capacity for extraneutralizing antibodies to contribute to disease control.


Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , Humans , Immunoglobulin G , RNA, Messenger/genetics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
3.
Arch Toxicol ; 96(5): 1437-1453, 2022 05.
Article in English | MEDLINE | ID: covidwho-1712224

ABSTRACT

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 has rapidly expanded into a serious global pandemic. Due to the high morbidity and mortality of COVID-19, there is an urgent need to develop safe and effective vaccines. AdC68-19S is an investigational chimpanzee adenovirus serotype 68 (AdC68) vector-based vaccine which encodes the full-length spike protein of SARS-CoV-2. Here, we evaluated the immunogenicity, biodistribution and safety profiles of the candidate vaccine AdC68-19S in Sprague Dawley (SD) rat and rhesus macaque under GLP conditions. To characterize the biodistribution profile of AdC68-19S, SD rats were given a single intramuscular injection of AdC68-19S 2 × 1011 VP/dose. Designated organs were collected on day 1, day 2, day 4, day 8 and day 15. Genomic DNA was extracted from all samples and was further quantified by real-time quantitative polymerase chain reaction (qPCR). To characterize the toxicology and immunogenicity profiles of AdC68-19S, the rats and rhesus macaques were injected intramuscularly with AdC68-19S up to 2 × 1011vp/dose or 4 × 1011vp/dose (2 and fourfold the proposed clinical dose of 1 × 1011vp/dose) on two or three occasions with a 14-day interval period, respectively. In addition to the conventional toxicological evaluation indexes, the antigen-specific cellular and humoral responses were evaluated. We proved that multiple intramuscular injections could elicit effective and long-lasting neutralizing antibody responses and Th1 T cell responses. AdC68-19S was mainly distributed in injection sites and no AdC68-19S related toxicological reaction was observed. In conclusion, these results have shown that AdC68-19S could induce an effective immune response with a good safety profile, and is a promising candidate vaccine against COVID-19.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adenoviridae/genetics , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Macaca mulatta , Pan troglodytes , Rats , Rats, Sprague-Dawley , SARS-CoV-2 , Tissue Distribution
4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-308285

ABSTRACT

Background: :Hypofractionated whole breast irradiation (HF-WBI) can achieve the same treatment effect as conventional fractionated whole breast irradiation (CF-WBI) within limits , without increasing adverse reactions. Because of its characteristics of reducing the number of radiation therapy (RT) during the COVID-19 Pandemic, it is recommended as the first choice of treatment for patients with early breast cancer after breast conserving surgery. However, the choice of RT is still under exploration. Here, we conducted a network meta-analysis to evaluate the problem comprehensively using data from new randomized trials. Methods: We analyzed data from eligible studies for published events for ipsilateral breast tumor recurrence (IBTR), distant metastasis, total deaths, and non-breast cancer-related deaths. Statistical analysis was performed using a fixed-effects or random-effects model in cases of low and high heterogeneity, respectively. Network meta-analysis was conducted using a node-splitting model for two-category data among three RTs based on a Bayesian approach. Results: 16 studies with 23,418 patients were included. For IBTR, pairwise comparison showed that CF-WBI was significantly better than PBI, and HF-WBI was similar to CF-WBI. HF-WBI was superior to PBI, but the difference was not significant. However, indirect comparison of three RTs by network meta-analysis showed that HF-WBI was significantly better than PBI (OR=0.67, CI95%: 0.46–0.95). Paired and network meta-analyses found no significant differences in other endpoints among three radiotherapies. Conclusion: This meta-analysis demonstrated PBI was associated with increased IBTR compared with HF-WBI or CF-WBI in early-stage breast cancer patients.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325084

ABSTRACT

The development of an effective vaccine against SARS-CoV-2, the causative agent of pandemic coronavirus disease-2019 (COVID-19), is a global priority. Here, we present three chimpanzee adenovirus vaccines that express either the full-length spike (ChAdTS-S), or receptor-binding domain (RBD) with two different signal sequences (ChAdTS-RBD and ChAdTS-RBDs). Single-dose intranasal or intramuscular immunization induced robust and sustained neutralizing antibody responses in BALB/c mice, with ChAdTS-S being superior to ChAdTS-RBD and ChAdTS-RBDs. Intranasal immunization appeared to induce a predominately Th2-based response whereas intramuscular administration resulted in a predominately Th1 response. The neutralizing activity against several circulating SARS-CoV-2 variants remained unaffected for mice serum but reduced for rhesus macaque serum. Importantly, immunization with ChAdTS-S via either route induced protective immunity against high-dose challenge with live SARS-CoV-2 in rhesus macaques. Vaccinated macaques demonstrated dramatic decreases in viral RNA in the lungs and nasal swabs, as well as reduced lung pathology compared to the control animals. Similar protective effects were also found in a golden Syrian hamster model of SARS-CoV-2 infection. Taken together, these results confirm that ChAdTS-S can induce protective immune responses in experimental animals, meriting further development toward a human vaccine against SARS-CoV-2.

6.
Neurology ; 98(8): e778-e789, 2022 02 22.
Article in English | MEDLINE | ID: covidwho-1673964

ABSTRACT

BACKGROUND AND OBJECTIVES: Findings of association between coronavirus disease 2019 (COVID-19) and stroke remain inconsistent, ranging from significant association to absence of association to less than expected ischemic stroke among hospitalized patients with COVID-19. The current study examined the association between COVID-19 and risk of acute ischemic stroke (AIS). METHODS: We included 37,379 Medicare fee-for-service (FFS) beneficiaries aged ≥65 years diagnosed with COVID-19 from April 1, 2020, through February 28, 2021, and AIS hospitalization from January 1, 2019, through February 28, 2021. We used a self-controlled case series design to examine the association between COVID-19 and AIS and estimated the incidence rate ratios (IRRs) by comparing incidence of AIS in risk periods (0-3, 4-7, 8-14, 15-28 days after diagnosis of COVID-19) vs control periods. RESULTS: Among 37,379 Medicare FFS beneficiaries with COVID-19 and AIS, the median age at diagnosis of COVID-19 was 80.4 (interquartile range 73.5-87.1) years and 56.7% were women. When AIS at day of exposure (day = 0) was included in the risk periods, IRRs at 0-3, 4-7, 8-14, and 15-28 days following COVID-19 diagnosis were 10.3 (95% confidence interval 9.86-10.8), 1.61 (1.44-1.80), 1.44 (1.32-1.57), and 1.09 (1.02-1.18); when AIS at day 0 was excluded in the risk periods, the corresponding IRRs were 1.77 (1.57-2.01) (day 1-3), 1.60 (1.43-1.79), 1.43 (1.31-1.56), and 1.09 (1.01-1.17), respectively. The association appeared to be stronger among younger beneficiaries and among beneficiaries without prior history of stroke but largely consistent across sex and race/ethnicities. DISCUSSION: Risk of AIS among Medicare FFS beneficiaries was 10 times (day 0 cases in the risk period) as high during the first 3 days after diagnosis of COVID-19 as during the control period and the risk associated with COVID-19 appeared to be stronger among those aged 65-74 years and those without prior history of stroke. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with increased risk of AIS in the first 3 days after diagnosis in Medicare FFS beneficiaries ≥65 years of age.


Subject(s)
COVID-19 , Ischemic Stroke , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/epidemiology , Female , Humans , Ischemic Stroke/epidemiology , Ischemic Stroke/virology , Male , Medicare , Risk Assessment , United States/epidemiology
7.
J Neurointerv Surg ; 2022 Jan 17.
Article in English | MEDLINE | ID: covidwho-1638416

ABSTRACT

BACKGROUND: Stent sizing remains a challenging task for flow diverter implantation because of stent foreshortening. In this study, we aimed to quantify the change in length after implantation and assess the error in length prediction using AneuGuideTM software. METHODS: In a retrospective cohort of 101 patients with 102 aneurysms undergoing treatment with a pipeline embolization device (PED; Covidien, Irvine, California, USA), we used AneuGuideTM software to obtain measured lengths (ML) and calculated lengths (CL) after stent implantation. Stent elongation was defined as the ratio of ML-LL to the labeled length (LL). Simulation error was defined as the ratio of the absolute value of CL-ML to ML. The correlation and consistency between ML and LL and between ML and CL were analyzed using Pearson's correlation test and the Bland-Altman plot. Statistical significance was set at p<0.05. RESULTS: The mean elongation of ML was 32.6% (range 26.3-109.2%). Moderate consistency was observed between LL and ML (ρ=0.74, p<0.001). With the AneuGuideTM software, the mean simulation error was 6.6% (range 0.32-21.2%). Pearson's correlation test and the Bland-Altman plot showed a high correlation and consistency between ML and CL (ρ=0.96, p<0.001). CONCLUSION: Labeled length provides only a low reference value for predicting the actual length of the flow diverter after implantation. The high consistency between ML and CL obtained from AneuGuideTM software shows its great potential for the optimization of the flow diverter sizing process.

8.
Clin Microbiol Infect ; 28(3): 410-418, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1482511

ABSTRACT

OBJECTIVE: The dynamic adaptive immune responses elicited by the inactivated virus vaccine CoronaVac remain elusive. METHODS: In a prospective cohort of 100 healthcare professionals naïve for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who received two doses of CoronaVac, we analysed SARS-CoV-2-specific humoral and cellular responses at four different timepoints, including before vaccination (T1), 2 weeks after the first dose (T2), 2 weeks after the booster dose (T3), and 8-10 weeks after the booster dose (T4). SARS-CoV-2-specific antibodies, serum neutralizing activities, peripheral B cells, CD4+ and CD8+ T cells and their memory subsets were simultaneously measured in this cohort. RESULTS: SARS-CoV-2 spike-specific IgG responses reached a peak (geometric mean titre (GMT) 54827, 30969-97065) after two doses and rapidly declined (GMT 502, 212-1190) at T4, whereas suboptimal IgA responses were detected (GMT 5, 2-9). Spike-specific circulating B cells (0.60%, 0.46-0.73% of total B cells) and memory B cells (1.18%, 0.92-1.44% of total memory B cells) were effectively induced at T3 and sustained over time (0.33%, 0.23-0.43%; 0.87%, 0.05-1.67%, respectively). SARS-CoV-2-specific circulating CD4+ T cells (0.57%, 0.47-0.66%) and CD8+ T cells (1.29%, 1.04-1.54%) were detected at T3. At T4, 0.78% (0.43-1.20%) of memory CD4+ T cells and 0.68% (0.29-1.30%) of memory CD8+ T cells were identified as SARS-CoV-2-specific, while 0.62% (0.51-0.75%) of CD4+ T cells and 0.47% (0.38-0.58%) of CD8+ T cells were SARS-CoV-2-specific terminally differentiated effector memory cells. Furthermore, age and interval between doses affected the magnitude of CoronaVac-induced immune responses. SARS-CoV-2 memory CD4+ T cells were strongly associated with both receptor binding domain (RBD)-specific memory B cells (r 0.87, p <0.0001) and SARS-CoV-2-specific memory CD8+ T cells (r 0.48, p <0.0001). CONCLUSIONS: CoronaVac induced robust circulating and memory B cell and T cell responses. Our study offers new insight into the underlying immunobiology of inactivated virus vaccines in humans and may have implications for vaccine strategies in the future.


Subject(s)
COVID-19 , SARS-CoV-2 , CD8-Positive T-Lymphocytes , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunization , Prospective Studies , Vaccination
9.
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
10.
Water Res ; 204: 117606, 2021 Oct 01.
Article in English | MEDLINE | ID: covidwho-1373297

ABSTRACT

The epidemic of COVID-19 has aroused people's particular attention to biosafety. A growing number of disinfection products have been consumed during this period. However, the flaw of disinfection has not received enough attention, especially in water treatment processes. While cutting down the quantity of microorganisms, disinfection processes exert a considerable selection effect on bacteria and thus reshape the microbial community structure to a great extent, causing the problem of disinfection-residual-bacteria (DRB). These systematic and profound changes could lead to the shift in regrowth potential, bio fouling potential, as well as antibiotic resistance level and might cause a series of potential risks. In this review, we collected and summarized the data from the literature in recent 10 years about the microbial community structure shifting of natural water or wastewater in full-scale treatment plants caused by disinfection. Based on these data, typical DRB with the most reporting frequency after disinfection by chlorine-containing disinfectants, ozone disinfection, and ultraviolet disinfection were identified and summarized, which were the bacteria with a relative abundance of over 5% in the residual bacteria community and the bacteria with an increasing rate of relative abundance over 100% after disinfection. Furthermore, the phylogenic relationship and potential risks of these typical DRB were also analyzed. Twelve out of fifteen typical DRB genera contain pathogenic strains, and many were reported of great secretion ability. Pseudomonas and Acinetobacter possess multiple disinfection resistance and could be considered as model bacteria in future studies of disinfection. We also discussed the growth, secretion, and antibiotic resistance characteristics of DRB, as well as possible control strategies. The DRB phenomenon is not limited to water treatment but also exists in the air and solid disinfection processes, which need more attention and more profound research, especially in the period of COVID-19.


Subject(s)
COVID-19 , Microbiota , Bacteria , Disinfection , Humans , SARS-CoV-2
11.
Prev Chronic Dis ; 18: E82, 2021 08 19.
Article in English | MEDLINE | ID: covidwho-1365800

ABSTRACT

INTRODUCTION: Studies documented significant reductions in emergency department visits and hospitalizations for acute stroke during the COVID-19 pandemic. A limited number of studies assessed the adherence to stroke performance measures during the pandemic. We examined rates of stroke hospitalization and adherence to stroke quality-of-care measures before and during the early phase of pandemic. METHODS: We identified hospitalizations with a clinical diagnosis of acute stroke or transient ischemic attack among 406 hospitals who contributed data to the Paul Coverdell National Acute Stroke Program. We used 10 performance measures to examine the effect of the pandemic on stroke quality of care. We compared data from 2 periods: pre-COVID-19 (week 11-24 in 2019) and COVID-19 (week 11-24 in 2020). We used χ2 tests for differences in categorical variables and the Wilcoxon-Mann-Whitney rank test or Kruskal-Wallis test for continuous variables. RESULTS: We identified 64,461 hospitalizations. We observed a 20.2% reduction in stroke hospitalizations (from 35,851 to 28,610) from the pre-COVID-19 period to the COVID-19 period. Hospitalizations among patients aged 85 or older, women, and non-Hispanic White patients declined the most. A greater percentage of patients aged 18 to 64 were hospitalized with ischemic stroke during COVID-19 than during pre-COVID-19 (34.4% vs 32.5%, P < .001). Stroke severity was higher during COVID-19 than during pre-COVID-19 for both hemorrhagic stroke and ischemic stroke, and in-hospital death among patients with ischemic stroke increased from 4.3% to 5.0% (P = .003) during the study period. We found no differences in rates of receiving care across stroke type during the study period. CONCLUSION: Despite a significant reduction in stroke hospitalizations, more severe stroke among hospitalized patients, and an increase in in-hospital death during the pandemic period, we found no differences in adherence to quality of stroke care measures.


Subject(s)
COVID-19 , Quality of Health Care , Stroke , Adolescent , Adult , Aged , Aged, 80 and over , Female , Hospital Mortality , Hospitalization , Humans , Male , Medicare , Middle Aged , Pandemics , Retrospective Studies , Stroke/epidemiology , Stroke/therapy , United States/epidemiology , Young Adult
13.
Front Immunol ; 12: 697074, 2021.
Article in English | MEDLINE | ID: covidwho-1311376

ABSTRACT

The development of a safe and effective vaccine against SARS-CoV-2, the causative agent of pandemic coronavirus disease-2019 (COVID-19), is a global priority. Here, we aim to develop novel SARS-CoV-2 vaccines based on a derivative of less commonly used rare adenovirus serotype AdC68 vector. Three vaccine candidates were constructed expressing either the full-length spike (AdC68-19S) or receptor-binding domain (RBD) with two different signal sequences (AdC68-19RBD and AdC68-19RBDs). Single-dose intramuscular immunization induced robust and sustained binding and neutralizing antibody responses in BALB/c mice up to 40 weeks after immunization, with AdC68-19S being superior to AdC68-19RBD and AdC68-19RBDs. Importantly, immunization with AdC68-19S induced protective immunity against high-dose challenge with live SARS-CoV-2 in a golden Syrian hamster model of SARS-CoV-2 infection. Vaccinated animals demonstrated dramatic decreases in viral RNA copies and infectious virus in the lungs, as well as reduced lung pathology compared to the control animals. Similar protective effects were also found in rhesus macaques. Taken together, these results confirm that AdC68-19S can induce protective immune responses in experimental animals, meriting further development toward a human vaccine against SARS-CoV-2.


Subject(s)
Adenovirus Vaccines/administration & dosage , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Immunization Schedule , Immunogenicity, Vaccine , SARS-CoV-2/immunology , Vaccination/methods , Adenovirus Vaccines/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/virology , COVID-19 Vaccines/immunology , Cricetinae , Disease Models, Animal , Female , HEK293 Cells , Humans , Male , Mice , Mice, Inbred BALB C , Pan troglodytes , RNA, Viral/blood , Spike Glycoprotein, Coronavirus/immunology , Transfection , Treatment Outcome
14.
Front Psychol ; 12: 635099, 2021.
Article in English | MEDLINE | ID: covidwho-1268287

ABSTRACT

Objective: We aimed to analyze the characteristics and psychological mechanism of depressive symptoms in elderly patients with alcohol dependence under the COVID-19 epidemic and to observe the effect of acupuncture combined with emotional therapy of Chinese medicine treatment on depressive symptoms in elderly patients with alcohol dependence. Methods: Sixty patients were randomly divided into two groups. One group was treated by a set of emotional therapy of Chinese medicine treatment for 12 weeks (control group). One group was treated by a set of acupuncture combined with emotional therapy of Chinese medicine treatment for 12 weeks (treatment group). We compared the curative effect between the control group and the treatment group, the mean alcohol consumption, the SF-36 scores before and after treatment, and the scores of Hamilton Depression Scale before and after treatment of 3, 6, and 9 weeks. Results: Based on the cognitive behavior model, the characteristics and psychological mechanism of depression in elderly patients with alcohol dependence under the COVID-19 epidemic situation were summarized. The total effective rate of the control group was 60%, and that of the treatment group was 100% (p < 0.05). The alcohol consumption of the patients in each group decreased significantly after treatment (p < 0.05), and there was no significant difference in alcohol consumption between the treatment group and the control group (p > 0.05). After 12 weeks of treatment, there were significant differences in PF, RF, physical pain, general health status, energy, and mental health between the treatment group and the control group (p < 0.05). Before and after treatment, there were significant differences in PF, RF, physical pain, general health, energy, emotional function, and mental health (p < 0.05) of the treatment group. The PF, energy, and mental health of the control group were significantly different before and after treatment (p < 0.05). There was no significant difference between the treatment group and the control group in the scores of Hamilton Depression Scale before treatment. There was significant difference between the treatment group and the control group in the scores of Hamilton Depression Scale at 3, 6, and 9 weeks after treatment. Conclusion: Attention, cognition, emotion, behavior, and physical response reinforce each other, creating a vicious cycle that reinforces and sustains the depressive symptoms of elderly alcohol dependence under the COVID-19 epidemic, and acupuncture combined with emotional therapy of Chinese medicine treatment for improving the depressive symptoms of elderly alcohol dependence during the epidemic period of COVID-19 has a brilliant therapeutic effect.

15.
Emerg Microbes Infect ; 10(1): 1390-1403, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1268055

ABSTRACT

Global concerns arose as the emerged and rapidly spreading SARS-CoV-2 variants might escape host immunity induced by vaccination. In this study, a heterologous prime-boost immunization strategy for COVID-19 was designed to prime with a DNA vaccine encoding wild type (WT) spike protein receptor-binding domain (RBD) followed by S1 protein-based vaccine in rabbits. Four vaccine-elicited rabbit monoclonal antibodies (RmAbs), including 1H1, 9H1, 7G5, and 5E1, were isolated for biophysical property, neutralization potency and sequence analysis. All RmAbs recognized RBD or S1 protein with KD in the low nM or sub nM range. 1H1 and 9H1, but neither 7G5 nor 5E1, can bind to all RBD protein variants derived from B.1.351. All four RmAbs were able to neutralize wild type (WT) SARS-CoV-2 strain in pseudovirus assay, and 1H1 and 9H1 could neutralize the SARS-CoV-2 WT authentic virus with IC50 values of 0.136 and 0.026 µg/mL, respectively. Notably, 1H1 was able to neutralize all 6 emerging SARS-CoV-2 variants tested including D614G, B.1.1.7, B.1.429, P.1, B.1.526, and B.1.351 variants, and 5E1 could neutralize against the above 5 variants except P.1. Epitope binning analysis revealed that 9H1, 5E1 and 1H1 recognized distinct epitopes, while 9H1 and 7G5 may have overlapping but not identical epitope. In conclusion, DNA priming protein boost vaccination was an effective strategy to induce RmAbs with potent neutralization capability against not only SARS-CoV-2 WT strain but also emergent variants, which may provide a new avenue for effective therapeutics and point-of-care diagnostic measures.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Genetic Variation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Vaccines, DNA/immunology , Animals , Antibodies, Viral/blood , Epitopes , Humans , Immunization, Secondary , Protein Domains/immunology , Protein Domains/physiology , Rabbits , SARS-CoV-2/immunology , Vaccination , Vaccines, Synthetic , Virus Attachment
17.
Cell Discov ; 6(1): 83, 2020 Nov 10.
Article in English | MEDLINE | ID: covidwho-922257

ABSTRACT

The COVID-19 pandemic has accounted for millions of infections and hundreds of thousand deaths worldwide in a short-time period. The patients demonstrate a great diversity in clinical and laboratory manifestations and disease severity. Nonetheless, little is known about the host genetic contribution to the observed interindividual phenotypic variability. Here, we report the first host genetic study in the Chinese population by deeply sequencing and analyzing 332 COVID-19 patients categorized by varying levels of severity from the Shenzhen Third People's Hospital. Upon a total of 22.2 million genetic variants, we conducted both single-variant and gene-based association tests among five severity groups including asymptomatic, mild, moderate, severe, and critical ill patients after the correction of potential confounding factors. Pedigree analysis suggested a potential monogenic effect of loss of function variants in GOLGA3 and DPP7 for critically ill and asymptomatic disease demonstration. Genome-wide association study suggests the most significant gene locus associated with severity were located in TMEM189-UBE2V1 that involved in the IL-1 signaling pathway. The p.Val197Met missense variant that affects the stability of the TMPRSS2 protein displays a decreasing allele frequency among the severe patients compared to the mild and the general population. We identified that the HLA-A*11:01, B*51:01, and C*14:02 alleles significantly predispose the worst outcome of the patients. This initial genomic study of Chinese patients provides genetic insights into the phenotypic difference among the COVID-19 patient groups and highlighted genes and variants that may help guide targeted efforts in containing the outbreak. Limitations and advantages of the study were also reviewed to guide future international efforts on elucidating the genetic architecture of host-pathogen interaction for COVID-19 and other infectious and complex diseases.

18.
PLoS Pathog ; 16(9): e1008796, 2020 09.
Article in English | MEDLINE | ID: covidwho-760712

ABSTRACT

There is an urgent need for effective treatment and preventive vaccine to contain this devastating global pandemic, which requires a comprehensive understanding of humoral responses specific to SARS-CoV-2 during the disease progression and convalescent phase of COVID-19 patients. We continuously monitored the serum IgM and IgG responses specific to four SARS-CoV-2 related antigens, including the nucleoprotein (NP), receptor binding domain (RBD), S1 protein, and ectodomain (ECD) of the spike protein among non-severe and severe COVID-19 patients for seven weeks since disease onset. Most patients generated humoral responses against NP and spike protein-related antigens but with their distinct kinetics profiles. Combined detection of NP and ECD antigens as detecting antigen synergistically improved the sensitivity of the serological assay, compared to that of using NP or RBD as detection antigen. 80.7% of convalescent sera from COVID-19 patients revealed that the varying extents of neutralization activities against SARS-CoV-2. S1-specific and ECD-specific IgA responses were strongly correlated with the neutralization activities in non-severe patients, but not in severe patients. Moreover, the neutralizing activities of the convalescent sera were shown to significantly decline during the period between 21 days to 28 days after hospital discharge, accompanied by a substantial drop in RBD-specific IgA response. Our data provide evidence that are crucial for serological testing, antibody-based intervention, and vaccine design of COVID-19.


Subject(s)
Antibodies, Neutralizing/pharmacology , Antibodies, Viral/pharmacology , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Betacoronavirus/pathogenicity , COVID-19 , Humans , Immunoglobulin G/blood , Longitudinal Studies , Pandemics , SARS-CoV-2 , Serologic Tests , Spike Glycoprotein, Coronavirus/immunology
19.
Immun Inflamm Dis ; 8(4): 840-843, 2020 12.
Article in English | MEDLINE | ID: covidwho-723382

ABSTRACT

INTRODUCTION: As an emerging infectious disease, coronavirus disease 2019 (COVID-19) has rapidly spread throughout worldwide. Health care workers (HCWs) on frontline directly participated in the diagnosis, treatment, and care of COVID-19 patients are at high risk of getting infected with the highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that causes COVID-19. In Nanjing Drum Tower Hospital, a total of 222 medical staff went to Wuhan city for support. In this study, we aimed to determine any nosocomial infection among our cohort of HCWs who worked in Wuhan. METHODS: Throat swab samples were obtained for RNA testing on day 1 and 14 of their quarantine upon their return to Nanjing. Radiological assessments were performed by chest computed tomography (CT) on day 14 of their quarantine. The blood was collected from 191 HCWs between May 12 and May 15. Anti-SARS-CoV-2 immunoglobulin M (IgM) and IgG antibody responses were determined by a chemiluminescence immunoassay. RESULTS: All the throat swab specimens were found negative for SARS-CoV-2. The radiological analysis revealed that there was no typical chest CT scan of COVID-19 among 222 HCWs. Consistently, anti-SARS-CoV-2 IgM or IgG was also found to be negative among 191 HCWs. CONCLUSIONS: There was no nosocomial infection of SARS-CoV-2 among our cohort of the frontline HCWs, suggesting that zero occupational infection is an achievable goal with appropriate training, strict compliance, and psychological support for the frontline HCWs.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/epidemiology , Cross Infection/prevention & control , Health Personnel/statistics & numerical data , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Pneumonia, Viral/epidemiology , Adult , Betacoronavirus/pathogenicity , COVID-19 , China/epidemiology , Coronavirus Infections/diagnosis , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Cross Infection/diagnosis , Cross Infection/epidemiology , Cross Infection/virology , Female , Humans , Infection Control/organization & administration , Infectious Disease Transmission, Patient-to-Professional/statistics & numerical data , Lung/diagnostic imaging , Male , Middle Aged , Occupational Exposure/adverse effects , Pandemics/prevention & control , Pharynx/virology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , SARS-CoV-2 , Tomography, X-Ray Computed , Young Adult
20.
J Infect ; 81(3): e31-e32, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-625901

ABSTRACT

We followed-up a mild COVID-19 patient for 91 days and serially monitored his serum antibodies to four SARS-CoV-2 related antigens (NP, RBD, S1 and ECD) and neutralization activities. Our data revealed a profile of serial antibody responses during the progress and a quick decline of neutralization activities after discharge.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , Adult , Antigens, Viral/immunology , COVID-19 , Enzyme-Linked Immunosorbent Assay , Humans , Longitudinal Studies , Male , Neutralization Tests , Pandemics , RNA, Viral , Retrospective Studies , SARS-CoV-2
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