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1.
Preprint in English | Other preprints | ID: ppcovidwho-295804

ABSTRACT

ABSTRACT Background Treatment of COVID-19 patients with convalescent plasma containing neutralising antibody to SARS-CoV-2 is under investigation as a means of reducing viral loads, ameliorating disease outcomes, and reducing mortality. However, its efficacy might be reduced in those infected with the emerging B.1.1.7 SARS-CoV-2 variant. Here, we report the diverse virological characteristics of UK patients enrolled in the Immunoglobulin Domain of the REMAP-CAP randomised controlled trial. Methods SARS-CoV-2 viral RNA was detected and quantified by real-time PCR in nasopharyngeal swabs obtained from study subjects within 48 hours of admission to intensive care unit. Antibody status was determined by spike-protein ELISA. B.1.1.7 strain was differentiated from other SARS-CoV-2 strains by two novel typing methods detecting the B.1.1.7-associated D1118H mutation with allele-specific probes and by restriction site polymorphism (SfcI). Findings Of 1260 subjects, 90% were PCR-positive with viral loads in nasopharyngeal swabs ranging from 72 international units [IUs]/ml to 1.7×10 11 IU/ml. Median viral loads were 45-fold higher in those who were seronegative for IgG antibodies (n=314;28%) compared to seropositives (n=804;72%), reflecting in part the latter group’s possible later disease stage on enrolment. Frequencies of B.1.1.7 infection increased from early November (<1%) to December 2020 (>60%). Anti-SARS-CoV-2 seronegative individuals infected with wild-type SARS-CoV-2 had significantly higher viral loads than seropositives (medians of 1.2×10 6 and 3.4 ×10 4 IU/ml respectively;p=2×10 −9 ). However, viral load distributions were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (13.4×10 6 and 7.6×10 6 IU/ml;p=0.18). Interpretation High viral loads in seropositive B.1.1.7-infected subjects are consistent with increased replication capacity and/or less effective clearance by innate or adaptive immune response of B.1.1.7 strain than wild-type. As viral genotype was associated with diverse virological and immunological phenotypes, metrics of viral load, antibody status and infecting strain should be used to define subgroups for analysis of treatment efficacy.

2.
Preprint in English | EuropePMC | ID: ppcovidwho-292885

ABSTRACT

Soluble Angiotensin-Converting Enzyme 2 (ACE2) constitutes an attractive antiviral receptor decoy that targets the vulnerable site on SARS-CoV-2 spike (S). Here, using structure-guided approaches, we developed divalent ACE2 molecules by grafting the extracellular ACE2-domain onto a human IgG1 or IgG3 (ACE2-Fc). These ACE2-Fcs harbored structurally validated mutations that enhance S binding and remove enzymatic activity. The lead variant bound tightly to S, mediated in vitro neutralization of SARS-CoV-2 variants of concern (VOCs) with sub-nanomolar IC50 and was capable of robust Fc-effector functions, including antibody-dependent cellular cytotoxicity, phagocytosis and complement deposition. When tested in a stringent K18-hACE2 mouse model, the lead variant prevented or delayed lethal SARS-CoV-2 infection in a prophylactic or therapeutic setting utilizing the combined effect of neutralization and Fc-effector functions. These data confirm the utility of ACE2-Fcs as valuable agents in preventing and eliminating SARS-CoV-2 infection and demonstrate that ACE2-Fc therapeutic activity require Fc-effector functions.

3.
J Infect Dis ; 2021 Nov 09.
Article in English | MEDLINE | ID: covidwho-1506513

ABSTRACT

We compared neutralising antibody titres of convalescent samples collected before and after the emergence of novel strains of SARS-CoV-2, against the wild-type virus (WT), Alpha (B.1.1.7) and Beta (B.1.351) variants. Plasma collected in 2020 before emergence of variants showed reduced titres against the Alpha variants, and both sets of samples demonstrated significantly reduced titres against Beta. Comparison of microneutralisation titres to those obtained with pseudotype and HAT assays showed a good correlation of titres and effects of strain variation, supporting the use of these simpler assays for assessment of convalescent plasma potency against currently circulating and emerging strains of SARS-CoV-2.

4.
Hum Vaccin Immunother ; : 1-6, 2021 Oct 08.
Article in English | MEDLINE | ID: covidwho-1462232

ABSTRACT

This study determines factors related to the intention to vaccinate against COVID-19 for health science students in Ho Chi Minh City (HCMC), using both the Health Belief Model (HBM) and the Theory of Planned Behavior (TPB) model. A cross-sectional survey was considered in April 2021, using a self-administered questionnaire to all health sciences students of the University of Medicine and Pharmacy in Ho Chi Minh City (UMP), Vietnam. The multiple regression was performed to specify the predictable factors of willingness to get a future COVID-19 vaccination.A total of 854 students completed the survey, whose vaccination acceptance was 77.1%. Predictors of intention to receive a COVID-19 vaccination included year of education, knowledge, and the HBM and TPB variables including the perceived benefits, cues to action, perceived behavioral control, and positive attitudes toward the vaccine (all p < .05). The main reasons for hesitancy included being afraid of the side effects (73.0%), vaccine safety (65.3%), and the process of new vaccine development (53.6%). The study examined students' intention toward COVID-19 vaccine and related factors to notify university administrators and policymakers. The findings showed the acceptability of vaccines had differences within the education year of students, besides, knowledge, perception of benefits, cues to action, behavioral control, and attitudes toward the vaccine were positive predictive factors. These may be useful for developing health education messages to promoting vaccination acceptability for students who had hesitancy of a new vaccine and in broader groups.

5.
AIDS Behav ; 2021 Sep 27.
Article in English | MEDLINE | ID: covidwho-1439733

ABSTRACT

Coronavirus disease 2019 (COVID-19) and associated social responses may uniquely affect people living with HIV (PLHIV). SARS-CoV-2 antibody testing and a cross-sectional survey on COVID-19's socio-behavioral impacts were conducted among a large PLHIV cohort in Hanoi, Vietnam. We examined anonymous antibody test results for 1243 PLHIV (99.8%) from whom plasma was obtained and completed surveys were collected in June/July 2020, just after the end of the first COVID-19 outbreak and nationwide lockdown. Three participants (0.2%) tested positive for anti-SARS-CoV-2 IgG antibodies. HIV treatment was generally maintained without antiretroviral therapy interruption, but COVID-19 had substantial impacts on economic security and risky health behaviors among PLHIV, which may have amplified psychological stress. These findings highlight the need for continuous monitoring of COVID-19's impacts on PLHIV and for efforts to mitigate these impacts.

6.
J Infect Dis ; 224(4): 595-605, 2021 08 16.
Article in English | MEDLINE | ID: covidwho-1367024

ABSTRACT

BACKGROUND: Convalescent plasma containing neutralizing antibody to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is under investigation for coronavirus disease 2019 (COVID-19) treatment. We report diverse virological characteristics of UK intensive care patients enrolled in the Immunoglobulin Domain of the REMAP-CAP randomized controlled trial that potentially influence treatment outcomes. METHODS: SARS-CoV-2 RNA in nasopharyngeal swabs collected pretreatment was quantified by PCR. Antibody status was determined by spike-protein ELISA. B.1.1.7 was differentiated from other SARS-CoV-2 strains using allele-specific probes or restriction site polymorphism (SfcI) targeting D1118H. RESULTS: Of 1274 subjects, 90% were PCR positive with viral loads 118-1.7 × 1011IU/mL. Median viral loads were 40-fold higher in those IgG seronegative (n = 354; 28%) compared to seropositives (n = 939; 72%). Frequencies of B.1.1.7 increased from <1% in November 2020 to 82% of subjects in January 2021. Seronegative individuals with wild-type SARS-CoV-2 had significantly higher viral loads than seropositives (medians 5.8 × 106 and 2.0 × 105 IU/mL, respectively; P = 2 × 10-15). CONCLUSIONS: High viral loads in seropositive B.1.1.7-infected subjects and resistance to seroconversion indicate less effective clearance by innate and adaptive immune responses. SARS-CoV-2 strain, viral loads, and antibody status define subgroups for analysis of treatment efficacy.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/therapy , SARS-CoV-2/immunology , Viral Load/immunology , Aged , Antibodies, Neutralizing/immunology , COVID-19/virology , Critical Illness , Female , Humans , Immunization, Passive , Immunoglobulin G/immunology , Male , Middle Aged , RNA, Viral/immunology , Serologic Tests/methods , Spike Glycoprotein, Coronavirus/immunology , United Kingdom
7.
J Med Virol ; 93(9): 5660-5665, 2021 09.
Article in English | MEDLINE | ID: covidwho-1363702

ABSTRACT

Genome-wide analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains is essential to better understand infectivity and virulence and to track coronavirus disease 2019 (COVID-19) cases and outbreaks. We performed whole-genome sequencing of 27 SARS-CoV-2 strains isolated between January 2020 and April 2020. A total of 54 mutations in different genomic regions was found. The D614G mutation, first detected in March 2020, was identified in 18 strains and was more likely associated with a lower cycle threshold (<25) in real-time reverse-transcription polymerase chain reaction diagnostic tests than the original D614 (prevalence ratio = 2.75; 95% confidence interval, 1.19-6.38). The integration of sequencing and epidemiological data suggests that SARS-CoV-2 transmission in both quarantine areas and in the community in Vietnam occur at the beginning of the epidemic although the country implemented strict quarantine quite early, with strict contact tracing, and testing. These findings provide insights into the nature of the epidemic, as well as shape strategies for COVID-19 prevention and control in Vietnam.


Subject(s)
COVID-19/virology , Genetic Variation , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/genetics , Adolescent , Adult , Aged , COVID-19/epidemiology , COVID-19/transmission , Contact Tracing , Female , Humans , Male , Middle Aged , Mutation , Phylogeny , Quarantine , Regression Analysis , Vietnam/epidemiology , Whole Genome Sequencing , Young Adult
8.
Transfusion ; 61(10): 2837-2843, 2021 10.
Article in English | MEDLINE | ID: covidwho-1360538

ABSTRACT

BACKGROUND: Convalescent plasma (CP) therapy for coronavirus disease (COVID-19) provides virus-neutralizing antibodies that may ameliorate the outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. The effectiveness of CP likely depends on its antiviral neutralizing potency and is determined using in vitro neutralizing antibody assays. STUDY DESIGN AND METHODS: We evaluated abilities of three immunoassays for anti-spike antibodies (EUROimmun, Ortho, Roche), a pseudotype-based neutralization assay, and two assays that quantify ACE2 binding of spike protein (GenScript and hemagglutination test [HAT]-based assay) to predict neutralizing antibody titers in 113 CP donations. Assay outputs were analyzed through linear regression and calculation of sensitivities and specificities by receiver operator characteristic (ROC) analysis. RESULTS: Median values of plasma samples containing neutralizing antibodies produced conversion factors for assay unitage of ×6.5 (pseudotype), ×19 (GenScript), ×3.4 (HAT assay), ×0.08 (EUROimmun), ×1.64 (Roche), and ×0.10 (Ortho). All selected assays were sufficient in identifying the high titer donations based on ROC analysis; area over curve ranged from 91.7% for HAT and GenScript assay to 95.6% for pseudotype assay. However, their ability to predict the actual neutralizing antibody levels varied substantially as shown by linear regression correlation values (from 0.27 for Ortho to 0.61 for pseudotype assay). DISCUSSION: Overall, the study data demonstrate that all selected assays were effective in identifying donations with high neutralizing antibody levels and are potentially suitable as surrogate assays for donation selection for CP therapy.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Serological Testing/methods , Immunoassay/methods , SARS-CoV-2/immunology , COVID-19/therapy , Humans , Immunization, Passive , Neutralization Tests
9.
Euro Surveill ; 26(27)2021 07.
Article in English | MEDLINE | ID: covidwho-1304570

ABSTRACT

We compared the performance of SARS-CoV-2 neutralising antibody testing between 12 European laboratories involved in convalescent plasma trials. Raw titres differed almost 100-fold differences between laboratories when blind-testing 15 plasma samples. Calibration of titres in relation to the reference reagent and standard curve obtained by testing a dilution series reduced the inter-laboratory variability ca 10-fold. The harmonisation of neutralising antibody quantification is a vital step towards determining the protective and therapeutic levels of neutralising antibodies.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/therapy , Europe , Humans , Immunization, Passive
10.
Infect Drug Resist ; 14: 1773-1780, 2021.
Article in English | MEDLINE | ID: covidwho-1236633

ABSTRACT

Background: Vaccination is one of the best ways to control a pandemic such as COVID-19. However, identifying community apprehensions towards vaccination needs to be understood in detail. This study aims to determine the factors that can predict the acceptance of the COVID-19 vaccine. Methods: A cross-sectional study was considered by systematic random sampling of 425 adults with chronic illnesses in Ho Chi Minh City. Data were collected between December 2020 and January 2021 via a self-administered, structured questionnaire. The main outcome was the acceptance of future COVID-19 vaccinations. Results: A total of 425 eligible adults responded to the survey, whose mean age was 52.9±15.6 years; 67.8% of them were women, more than a half of them had high school education level or higher (57.4%) and received COVID-19 information mainly via television and social media accounted for 82.4% and 58.1%, respectively. Overall, knowledge of COVID-19 was reported as relatively good, with a mean score of 7.11 ± 1.77 (0-9). Determinants of vaccination acceptance were knowledge and cues to action. Accordingly, there was a 1.2-fold increase in the odds of acceptance of COVID-19 vaccination for a 1-unit increase in "the total knowledge score" (AOR 1.2, 95% CI: 1.1-1.3, p<0.05), and there was a 3.2-fold increase in the odds of vaccination acceptance for a 1-unit increase in "cues to action" (AOR 3.2, 95% CI: 1.7-5.8, p<0.001). Conclusion: Determinants that influence the intention to have the COVID-19 vaccination are identified, which can be applied to future health education interventions that should focus on enhanced knowledge towards COVID-19 via mass media messages and cues to action from healthcare workers' recommendations to promote vaccine acceptance.

11.
Viruses ; 13(5)2021 04 24.
Article in English | MEDLINE | ID: covidwho-1201926

ABSTRACT

As of April 2021, the COVID-19 pandemic has swept through 213 countries and infected more than 132 million individuals globally, posing an unprecedented threat to human health. There are currently no specific antiviral treatments for COVID-19 and vaccination programmes, whilst promising, remain in their infancy. A key to restricting the pandemic is the ability to minimize human-human transmission and to predict the infection status of the population in the face of emerging SARS-CoV-2 variants. Success in this area is dependent on the rapid detection of COVID-19 positive individuals with current/previous SARS-CoV-2 infection status. In this regard, the ability to detect antibodies directed against the SARS-CoV-Spike protein in patient sera represents a powerful biomarker for confirmation of infection. Here, we report the design of a proof-of-concept cell-based fluorescent serology assay (termed C19-S-I-IFA) to detect SARS-CoV-2 infection. The assay is based on the capture of IgG antibodies in the serum of COVID-19-positive patients using cells exogenously expressing SARS-CoV-2-Spike and their subsequent fluorescent detection. We validate the assay in 30 blood samples collected in Oxford, UK, in 2020 during the height of the pandemic. Importantly, the assay can be modified to express emerging Spike-variants to permit assessments of the cross-reactivity of patient sera to emerging SARS-CoV-2 strains.


Subject(s)
COVID-19 Testing/methods , COVID-19/virology , Fluorescent Antibody Technique/methods , SARS-CoV-2/isolation & purification , A549 Cells , Antibodies, Viral/blood , COVID-19/blood , COVID-19/diagnosis , COVID-19/immunology , Cross Reactions , Humans , Immunoglobulin G/blood , Pandemics , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Sensitivity and Specificity , Spike Glycoprotein, Coronavirus/blood , Spike Glycoprotein, Coronavirus/genetics
12.
Sci Rep ; 11(1): 3487, 2021 02 10.
Article in English | MEDLINE | ID: covidwho-1078607

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly pathogenic virus that has caused the global COVID-19 pandemic. Tracing the evolution and transmission of the virus is crucial to respond to and control the pandemic through appropriate intervention strategies. This paper reports and analyses genomic mutations in the coding regions of SARS-CoV-2 and their probable protein secondary structure and solvent accessibility changes, which are predicted using deep learning models. Prediction results suggest that mutation D614G in the virus spike protein, which has attracted much attention from researchers, is unlikely to make changes in protein secondary structure and relative solvent accessibility. Based on 6324 viral genome sequences, we create a spreadsheet dataset of point mutations that can facilitate the investigation of SARS-CoV-2 in many perspectives, especially in tracing the evolution and worldwide spread of the virus. Our analysis results also show that coding genes E, M, ORF6, ORF7a, ORF7b and ORF10 are most stable, potentially suitable to be targeted for vaccine and drug development.


Subject(s)
COVID-19/virology , Genome, Viral , Mutation , Protein Structure, Secondary , SARS-CoV-2/genetics , DNA, Viral , Genomics , Humans , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism
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