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2.
JMIR Res Protoc ; 2022 Apr 21.
Article in English | MEDLINE | ID: covidwho-1875278

ABSTRACT

BACKGROUND: One of the most debated questions in the COVID-19 pandemic has been the role of schools in SARS-CoV-2 transmission. The COVID-19 Schools Infection Survey (SIS) aims to provide much-needed evidence addressing this. OBJECTIVE: This paper presents the study protocol and participation profile for the SIS study, aimed at assessing the role of schools in SARS-CoV-2 infection and transmission within school settings, and investigating how transmission within and from schools could be mitigated through implementation of school COVID-19 control measures. METHODS: SIS was a multisite, prospective, observational cohort study conducted in a stratified random sample of primary and secondary schools in selected local authorities in England. Six bio-behavioural surveys were planned among participating students and staff during the 2020/21 academic year, between November 2020 and July 2021. Key measurements were SARS-CoV-2 virus prevalence, assessed by nasal swab polymerase chain reaction; anti-SARS-CoV-2 (nucleocapsid protein) antibody prevalence and conversion, assessed in finger-prick-blood for staff and oral-fluid for students; student and staff school attendance rates; feasibility and acceptability of school-level implementation of SARS-CoV-2 control measures; and investigation of selected school outbreaks. The study received approvals from the UK Health Security Agency Research Support and Governance Office (NR0237) and London School of Hygiene & Tropical Medicine Ethics Review Committee (ref:22657). RESULTS: Data collection and laboratory analyses were completed by September 2021. A total of 22,585 individuals: 1,891 staff and 4,654 students from 59 primary schools and 5,852 staff and 10,188 students from 97 secondary schools participated in at least one survey. On average, across survey rounds, staff and student participation rates were 45.2% and 16.4% respectively in primary schools and 30.0% and 15.2% in secondary schools. While primary student participation increased over time, and secondary student participation remained reasonably consistent, staff participation declined across rounds, especially for secondary school staff (41.7% in Round 1 and 22.1% in Round 6). While staff participation overall was generally reflective of the eligible staff population, student participation was higher in schools with low absenteeism, a lower proportion of students eligible for free school meals and from schools in the least deprived locations (in primary schools 9.6% participants were from schools in the least deprived quintile compared with 5.7% of eligible students). CONCLUSIONS: We outline the study design, methods and participation, and reflect on the strengths of the SIS study as well as the practical challenges encountered, and the strategies implemented to address these challenges. The SIS study, by measuring current and incident infection over time, alongside the implementation of control measures in schools, across a range of settings in England, aims to inform national guidance and public health policy for educational settings.

3.
Sex Transm Infect ; 2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1854399

ABSTRACT

OBJECTIVES: Although hepatitis B virus (HBV) vaccination for high-risk groups including gay, bisexual and other men who have sex with men (MSM) is recommended in the UK, data on HBV immunisation coverage are limited. This study aimed to understand the prevalence of HBV infection, susceptibility and immunity due to immunisation among a high-risk population of MSM and heterosexuals who are less likely to attend sexual health services. METHODS: Residual HIV-negative serology samples archived from a national HIV self-sampling service in 2016 were tested for HBV markers using an unlinked anonymous approach. Prevalence of HBV infection, evidence of immunisation and susceptibility were calculated and stratified by individuals' characteristics. Multinomial logistic regression was used to estimate relative risk ratios (RRRs) associated with covariates. RESULTS: Of 2172 samples tested, 1497 (68.9%) were from MSM and 657 (30.2%) were from heterosexuals. Susceptibility to HBV infection was 66.1% among MSM and 77.0% among heterosexuals. Only 29.9% of MSM and 17.4% of heterosexuals had serological evidence of immunisation. Current infection was 1.1% in heterosexuals and 0.2% in MSM. Adjusted analysis showed evidence of immunisation was lower among heterosexuals (RRR 0.66, 95% CI 0.50 to 0.86) and those with no previous HIV test (RRR 0.41, 95% CI 0.31 to 0.54), and higher in those of other white or other ethnicity. CONCLUSIONS: Among MSM and heterosexual users of a self-sampling HIV service, evidence of immunisation to HBV infection was low and susceptibility to infection was comparatively high, suggesting suboptimal delivery of HBV immunisation in sexual health services.

4.
PLoS One ; 17(2): e0262515, 2022.
Article in English | MEDLINE | ID: covidwho-1690740

ABSTRACT

BACKGROUND: Following the full re-opening of schools in England and emergence of the SARS-CoV-2 Alpha variant, we investigated the risk of SARS-CoV-2 infection in students and staff who were contacts of a confirmed case in a school bubble (school groupings with limited interactions), along with their household members. METHODS: Primary and secondary school bubbles were recruited into sKIDsBUBBLE after being sent home to self-isolate following a confirmed case of COVID-19 in the bubble. Bubble participants and their household members were sent home-testing kits comprising nasal swabs for RT-PCR testing and whole genome sequencing, and oral fluid swabs for SARS-CoV-2 antibodies. RESULTS: During November-December 2020, 14 bubbles were recruited from 7 schools, including 269 bubble contacts (248 students, 21 staff) and 823 household contacts (524 adults, 299 children). The secondary attack rate was 10.0% (6/60) in primary and 3.9% (4/102) in secondary school students, compared to 6.3% (1/16) and 0% (0/1) among staff, respectively. The incidence rate for household contacts of primary school students was 6.6% (12/183) and 3.7% (1/27) for household contacts of primary school staff. In secondary schools, this was 3.5% (11/317) and 0% (0/1), respectively. Household contacts were more likely to test positive if their bubble contact tested positive although there were new infections among household contacts of uninfected bubble contacts. INTERPRETATION: Compared to other institutional settings, the overall risk of secondary infection in school bubbles and their household contacts was low. Our findings are important for developing evidence-based infection prevention guidelines for educational settings.


Subject(s)
COVID-19/epidemiology , COVID-19/transmission , Adolescent , Adult , Antibodies, Viral/analysis , COVID-19/virology , Child , Contact Tracing , England/epidemiology , Female , Humans , Incidence , Male , Nasopharynx/virology , Prospective Studies , RNA, Viral/analysis , RNA, Viral/metabolism , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Schools/statistics & numerical data , Students/statistics & numerical data
5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-322593

ABSTRACT

Background: Accurate and sensitive detection of antibody to SARS-CoV-2 remains an essential component of the pandemic response. Measuring antibody that predicts neutralising activity and the vaccine response is an absolute requirement for laboratory-based confirmatory and reference activity.Methods: The viral receptor binding domain (RBD) constitutes the prime target antigen for neutralising antibody. A double antigen binding assay (DABA) provides the most sensitive format. It has been exploited in a novel hybrid manner employing an S1 solid-phase preferentially presenting RBD once solid-phase bound, coupled with a labelled RBD conjugate, used in a two-step sequential assay.Findings: This assay showed a specificity of 100% on 825 pre COVID-19 samples and a potential sensitivity of 99.6% on 276 recovery samples, predicting quantitatively the presence of neutralising antibody determined by pseudo-type neutralisation and by plaque reduction. Anti-RBD is also measurable in ferrets immunised with ChadOx1 nCoV-19 vaccine. The early response at presentation with illness, elevated responsiveness with disease severity, detection of asymptomatic seroconversion and persistence after the loss of antibody to the nucleoprotein (anti-NP) are all documented.Trial Registration: The ISARIC WHO CCP-UK study was registered at https://www.isrctn.com/ISRCTN66726260 and designated an Urgent Public Health Research Study by NIHR.Interpretation: The hybrid DABA displays the attributes necessary for an antibody test to be used in both clinical and reference serology. It allows the neutralising antibody response to be inferred early in infection and potentially in vaccine recipients. It is also of sufficient sensitivity to be used to provide serological confirmation of prior infection and provides a more secure measure for seroprevalence studies in the population generally than does anti-NP based on the Architect platform.Funding: This work is variously supported by grants from: the National Institute for Health Research (NIHR;award CO-CIN-01), the Medical Research Council (MRC;grant MC_PC_19059 and MC_PC_19078), MRC NIHR (grant CV220-111) and by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford (award 200907), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award 200927), Wellcome Trust and Department for International Development (DID;215091/Z/18/Z), the Bill and Melinda Gates Foundation (OPP1209135), Liverpool Experimental Cancer Medicine Centre (grant reference C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (IS-BRC-1215-20013), EU Platform for European Preparedness Against (Re-)emerging Epidemics (PREPARE;FP7 project 602525), and NIHR Clinical Research Network for providing infrastructure support for this research.Declaration of Interests: RST, MOM and PC report patent pending (Patent Application No. 2011047.4 for “SARS-CoV-2 antibody detection assay). All other authors declare no competing interests.Ethics Approval Statement: The use of tissues was approved by the CDRTB Steering Committee in accordance with the responsibility delegated by the National Research Ethics Service (South Central Ethics Committee – C, NRES reference 15/SC/0089).Written informed consent was obtained from all patients. Ethical approval was given by the South Central–Oxford C Research Ethics Committee in England (reference: 13/SC/0149), Scotland A Research Ethics Committee (reference: 20/SS/0028) and World Health Organization Ethics Review Committee (RPC571 and RPC572l;25 April 2013)

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-305590

ABSTRACT

Background: Laboratory diagnosis of SARS-CoV-2 infection (the cause of COVID-19) uses PCR to detect viral RNA (vRNA) in respiratory samples. SARS-CoV-2 RNA has also been detected in other sample types, but there is limited understanding of the clinical or laboratory significance of its detection in blood. Methods: We undertook a systematic literature review to assimilate the evidence for the frequency of vRNA in blood, and to identify associated clinical characteristics. We performed RT-PCR in serum samples from a UK clinical cohort of acute and convalescent COVID-19 cases (n=212), together with convalescent plasma samples collected by NHS Blood and Transplant (NHSBT) (n=462 additional samples). To determine whether PCR-positive blood samples could pose an infection risk, we attempted virus isolation from a subset of RNA-positive samples. Results: We identified 28 relevant studies, reporting SARS-CoV-2 RNA in 0-76% of blood samples;pooled estimate 10% (95%CI 5-18%). Among serum samples from our clinical cohort, 27/212 (12.7%) had SARS-CoV-2 RNA detected by RT-PCR. RNA detection occurred in samples up to day 20 post symptom onset, and was associated with more severe disease (multivariable odds ratio 7.5). Across all samples collected ≥28 days post symptom onset, 0/494 (0%, 95%CI 0-0.7%) had vRNA detected. Among our PCR-positive samples, cycle threshold (ct) values were high (range 33.5-44.8), suggesting low vRNA copy numbers. PCR-positive sera inoculated into cell culture did not produce any cytopathic effect or yield an increase in detectable SARS-CoV-2 RNA. There was a relationship between RT-PCR negativity and the presence of total SARS-CoV-2 antibody (p=0.02). Conclusions: vRNA was detectable at low viral loads in a minority of serum samples collected in acute infection, but was not associated with infectious SARS-CoV-2 (within the limitations of the assays used). This work helps to inform biosafety precautions for handling blood products from patients with current or previous COVID-19.

7.
J Virol Methods ; 302: 114475, 2022 04.
Article in English | MEDLINE | ID: covidwho-1652648

ABSTRACT

Accurate and sensitive detection of antibody to SARS-CoV-2 remains an essential component of the pandemic response. Measuring antibody that predicts neutralising activity and the vaccine response is an absolute requirement for laboratory-based confirmatory and reference activity. The viral receptor binding domain (RBD) constitutes the prime target antigen for neutralising antibody. A double antigen binding assay (DABA), providing the most sensitive format has been exploited in a novel hybrid manner employing a solid-phase S1 preferentially presenting RBD, coupled with a labelled RBD conjugate, used in a two-step sequential assay for detection and measurement of antibody to RBD (anti-RBD). This class and species neutral assay showed a specificity of 100 % on 825 pre COVID-19 samples and a potential sensitivity of 99.6 % on 276 recovery samples, predicting quantitatively the presence of neutralising antibody determined by pseudo-type neutralization and by plaque reduction. Anti-RBD is also measurable in ferrets immunised with ChadOx1 nCoV-19 vaccine and in humans immunised with both AstraZeneca and Pfizer vaccines. This assay detects anti-RBD at presentation with illness, demonstrates its elevation with disease severity, its sequel to asymptomatic infection and its persistence after the loss of antibody to the nucleoprotein (anti-NP). It also provides serological confirmation of prior infection and offers a secure measure for seroprevalence and studies of vaccine immunisation in human and animal populations. The hybrid DABA also displays the attributes necessary for the detection and quantification of anti-RBD to be used in clinical practice. An absence of detectable anti-RBD by this assay predicates the need for passive immune prophylaxis in at-risk patients.


Subject(s)
Antibodies, Viral/isolation & purification , COVID-19 , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/isolation & purification , COVID-19/diagnosis , Ferrets , Humans , RNA, Viral , Seroepidemiologic Studies
8.
Sci Rep ; 12(1): 1885, 2022 02 03.
Article in English | MEDLINE | ID: covidwho-1671623

ABSTRACT

At-home sampling is key to large scale seroprevalence studies. Dried blood spot (DBS) self-sampling removes the need for medical personnel for specimen collection but facilitates specimen referral to an appropriately accredited laboratory for accurate sample analysis. To establish a highly sensitive and specific antibody assay that would facilitate self-sampling for prevalence and vaccine-response studies. Paired sera and DBS eluates collected from 439 sero-positive, 382 sero-negative individuals and DBS from 34 vaccine recipients were assayed by capture ELISAs for IgG and IgM antibody to SARS-CoV-2. IgG and IgM combined on DBS eluates achieved a diagnostic sensitivity of 97.9% (95%CI 96.6 to 99.3) and a specificity of 99.2% (95% CI 98.4 to 100) compared to serum, displaying limits of detection equivalent to 23 and 10 WHO IU/ml, respectively. A strong correlation (r = 0.81) was observed between serum and DBS reactivities. Reactivity remained stable with samples deliberately rendered inadequate, (p = 0.234) and when samples were accidentally damaged or 'invalid'. All vaccine recipients were sero-positive. This assay provides a secure method for self-sampling by DBS with a sensitivity comparable to serum. The feasibility of DBS testing in sero-prevalence studies and in monitoring post-vaccine responses was confirmed, offering a robust and reliable tool for serological monitoring at a population level.


Subject(s)
Antibodies, Viral/blood , COVID-19 Testing/methods , COVID-19/diagnosis , COVID-19/epidemiology , Dried Blood Spot Testing/methods , Immunoglobulin G/blood , Immunoglobulin M/blood , SARS-CoV-2/immunology , Specimen Handling/methods , Biomarkers/blood , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/immunology , Feasibility Studies , Female , Humans , Male , Sensitivity and Specificity , Seroepidemiologic Studies
9.
J Clin Virol ; 148: 105083, 2022 03.
Article in English | MEDLINE | ID: covidwho-1654709

ABSTRACT

BACKGROUND: Transmission of hepatitis E virus (HEV) within the healthcare setting is extremely rare. Additionally, the development of chronic HEV infection in association with severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) infection and/or its immunomodulatory therapy has not been reported previously. AIMS: To describe the investigation and management of a nosocomial HEV transmission incident during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Epidemiological and molecular investigation of two individuals hospitalised with COVID-19 who were both diagnosed with HEV infection. RESULTS: Findings from our investigation were consistent with transmission of HEV from one patient with a community-acquired HEV infection to another individual (identical HEV sequences were identified in the two patients), most likely due to a breach in infection control practices whilst both patients shared a bed space on the intensive care unit (ICU). Chronic HEV infection requiring treatment with ribavirin developed in one patient with prolonged lymphopaenia attributable to COVID-19 and/or the immunomodulators received for its treatment. Further investigation did not identify transmission of HEV to any other patients or to healthcare workers. CONCLUSIONS: The extraordinary demands that the COVID-19 pandemic has placed on all aspects of healthcare, particularly within ICU settings, has greatly challenged the ability to consistently maintain optimal infection prevention and control practices. Under the significant pressures of the COVID-19 pandemic a highly unusual nosocomial HEV transmission incident occurred complicated further by progression to a chronic HEV infection in one patient.


Subject(s)
COVID-19 , Cross Infection , Hepatitis E virus , Hepatitis E , Cross Infection/epidemiology , Hepatitis E/drug therapy , Hepatitis E/epidemiology , Hepatitis E virus/genetics , Humans , Pandemics , SARS-CoV-2
10.
Microbiol Spectr ; 10(1): e0078621, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1605388

ABSTRACT

Seroepidemiological studies to monitor antibody kinetics are important for assessing the extent and spread of SARS-CoV-2 in a population. Noninvasive sampling methods are advantageous for reducing the need for venipuncture, which may be a barrier to investigations, particularly in pediatric populations. Oral fluids are obtained by gingiva-crevicular sampling from children and adults and are very well accepted. Enzyme immunoassays (EIAs) based on these samples have acceptable sensitivity and specificity compared to conventional serum-based antibody EIAs and are suitable for population-based surveillance. We describe the development and evaluation of SARS-CoV-2 IgG EIAs using SARS-CoV-2 viral nucleoprotein (NP) and spike (S) proteins in IgG isotype capture format and an indirect receptor-binding-domain (RBD) IgG EIA, intended for use in children as a primary endpoint. All three assays were assessed using a panel of 1,999 paired serum and oral fluids from children and adults participating in school SARS-CoV-2 surveillance studies during and after the first and second pandemic wave in the United Kingdom. The anti-NP IgG capture assay was the best candidate, with an overall sensitivity of 75% (95% confidence interval [CI]: 71 to 79%) and specificity of 99% (95% CI: 78 to 99%) compared with paired serum antibodies. Sensitivity observed in children (80%, 95% CI: 71 to 88%) was higher than that in adults (67%, CI: 60% to 74%). Oral fluid assays (OF) using spike protein and RBD antigens were also 99% specific and achieved reasonable but lower sensitivity in the target population (78%, 95% CI [68% to 86%] and 53%, 95% CI [43% to 64%], respectively). IMPORTANCE We report on the first large-scale assessment of the suitability of oral fluids for detection of SARS-CoV-2 antibody obtained from healthy children attending school. The sample type (gingiva-crevicular fluid, which is a transudate of blood but is not saliva) can be self collected. Although detection of antibodies in oral fluids is less sensitive than that in blood, our study suggests an optimal format for operational use. The laboratory methods we have developed can reliably measure antibodies in children, who are able to take their own samples. Our findings are of immediate practical relevance for use in large-scale seroprevalence studies designed to measure exposure to infection, as they typically require venipuncture. Overall, our data indicate that OF assays based on the detection of SARS-CoV-2 antibodies are a tool suitable for population-based seroepidemiology studies in children and highly acceptable in children and adults, as venipuncture is no longer necessary.


Subject(s)
Antibodies, Viral/analysis , COVID-19/diagnosis , Gingival Crevicular Fluid/immunology , Immunoglobulin G/analysis , SARS-CoV-2/immunology , Adolescent , Child , Child, Preschool , Humans , Immunoenzyme Techniques , Infant , Sensitivity and Specificity , Seroepidemiologic Studies
12.
J Infect ; 83(4): 483-489, 2021 10.
Article in English | MEDLINE | ID: covidwho-1330976

ABSTRACT

OBJECTIVES: To measure secondary attack rates (SARs) in prospectively followed household contacts of paediatric and adult cases of SARS-CoV-2 infection in England. METHODS: Self-taken nasal swabs from household contacts of PCR confirmed cases of COVID-19  and blood samples  on day 35 were tested for evidence of infection with SARS-CoV-2 virus. RESULTS: The secondary attack rate (SAR) among 431 contacts of 172 symptomatic index cases  was 33% (95% confidence intervals [CI] 25-40) and was lower from primary cases without respiratory symptoms, 6% (CI 0-14) vs 37% (CI 29-45), p = 0.030. The SAR from index cases <11 years  was  25% (CI 12-38). SARs ranged from 16% (4-28) in contacts <11 years old to 36% (CI 28-45) in contacts aged 19-54 years (p = 0.119). The proportion infected who developed symptoms (78%) was similar by age (p = 0.44) though <19 year olds had fewer mean number of symptoms than adults (p = 0.001) and fewer reported loss of sense of taste or smell (p = 0.0001). CONCLUSIONS: There are high risks of  transmission of SARS-CoV-2 virus in the home, including those where infection is introduced by a child. The risk of children acquiring infection was lower than that in adults and fewer developed typical symptoms of Covid-19 infection.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Child , Family Characteristics , Humans , Incidence , Prospective Studies
13.
Crit Care Med ; 49(3): 428-436, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1057891

ABSTRACT

OBJECTIVES: Critical care workers were considered to be at high risk of severe acute respiratory syndrome coronavirus-2 infection from patients during the first wave of the pandemic. Staff symptoms, previous swab testing, and antibody prevalence were correlated with patient admissions to investigate this assumption. DESIGN: Cross-sectional study. SETTING: A large critical care department in a tertiary-care teaching hospital in London, United Kingdom. SUBJECTS: Staff working in critical care. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Participants completed a questionnaire and provided a serum sample for severe acute respiratory syndrome coronavirus-2 antibody testing over a 3-day period in April 2020. We compared the timing of symptoms in staff to the coronavirus disease 2019 patient admissions to critical care. We also identified factors associated with antibody detection. Of 625 staff 384 (61.4%) reported previous symptoms and 124 (19.8%) had sent a swab for testing. Severe acute respiratory syndrome coronavirus-2 infection had been confirmed in 37 of those swabbed (29.8%). Overall, 21% (131/625) had detectable severe acute respiratory syndrome coronavirus-2 antibody, of whom 9.9% (13/131) had been asymptomatic. The peak onset of symptoms among staff occurred 2 weeks before the peak in coronavirus disease 2019 patient admissions. Staff who worked in multiple departments across the hospital were more likely to be seropositive. Staff with a symptomatic household contact were also more likely to be seropositive at 31.3%, compared with 16.2% in those without (p < 0.0001). CONCLUSIONS: Staff who developed coronavirus disease 2019 were less likely to have caught it from their patients in critical care. Other staff, other areas of the hospital, and the wider community are more likely sources of infection. These findings indicate that personal protective equipment was effective at preventing transmission from patients. However, staff also need to maintain protective measures away from the bedside.


Subject(s)
COVID-19 Serological Testing , COVID-19/diagnosis , Critical Care , Health Personnel/statistics & numerical data , Personnel, Hospital/statistics & numerical data , Adult , COVID-19/transmission , Cross-Sectional Studies , Female , Humans , London/epidemiology , Male , Middle Aged , Patient Admission , SARS-CoV-2/pathogenicity , Tertiary Care Centers , United Kingdom/epidemiology
14.
Wellcome Open Research ; 2020.
Article in English | ProQuest Central | ID: covidwho-1024793

ABSTRACT

Background: Laboratory diagnosis of SARS-CoV-2 infection (the cause of COVID-19) uses PCR to detect viral RNA (vRNA) in respiratory samples. SARS-CoV-2 RNA has also been detected in other sample types, but there is limited understanding of the clinical or laboratory significance of its detection in blood. Methods: We undertook a systematic literature review to assimilate the evidence for the frequency of vRNA in blood, and to identify associated clinical characteristics. We performed RT-PCR in serum samples from a UK clinical cohort of acute and convalescent COVID-19 cases (n=212), together with convalescent plasma samples collected by NHS Blood and Transplant (NHSBT) (n=462 additional samples). To determine whether PCR-positive blood samples could pose an infection risk, we attempted virus isolation from a subset of RNA-positive samples. Results: We identified 28 relevant studies, reporting SARS-CoV-2 RNA in 0-76% of blood samples;pooled estimate 10% (95%CI 5-18%). Among serum samples from our clinical cohort, 27/212 (12.7%) had SARS-CoV-2 RNA detected by RT-PCR. RNA detection occurred in samples up to day 20 post symptom onset, and was associated with more severe disease (multivariable odds ratio 7.5). Across all samples collected ≥28 days post symptom onset, 0/494 (0%, 95%CI 0-0.7%) had vRNA detected. Among our PCR-positive samples, cycle threshold (ct) values were high (range 33.5-44.8), suggesting low vRNA copy numbers. PCR-positive sera inoculated into cell culture did not produce any cytopathic effect or yield an increase in detectable SARS-CoV-2 RNA. There was a relationship between RT-PCR negativity and the presence of total SARS-CoV-2 antibody (p=0.02). Conclusions: vRNA was detectable at low viral loads in a minority of serum samples collected in acute infection, but was not associated with infectious SARS-CoV-2 (within the limitations of the assays used). This work helps to inform biosafety precautions for handling blood products from patients with current or previous COVID-19.

15.
Transfus Med ; 31(3): 167-175, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-979626

ABSTRACT

INTRODUCTION: The lack of approved specific therapeutic agents to treat coronavirus disease (COVID-19) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has led to the rapid implementation of convalescent plasma therapy (CPT) trials in many countries, including the United Kingdom. Effective CPT is likely to require high titres of neutralising antibody (nAb) in convalescent donations. Understanding the relationship between functional neutralising antibodies and antibody levels to specific SARS-CoV-2 proteins in scalable assays will be crucial for the success of a large-scale collection. We assessed whether neutralising antibody titres correlated with reactivity in a range of enzyme-linked immunosorbent assays (ELISA) targeting the spike (S) protein, the main target for human immune response. METHODS: Blood samples were collected from 52 individuals with a previous laboratory-confirmed SARS-CoV-2 infection. These were assayed for SARS-CoV-2 nAbs by microneutralisation and pseudo-type assays and for antibodies by four different ELISAs. Receiver operating characteristic (ROC) analysis was used to further identify sensitivity and specificity of selected assays to identify samples containing high nAb levels. RESULTS: All samples contained SARS-CoV-2 antibodies, whereas neutralising antibody titres of greater than 1:20 were detected in 43 samples (83% of those tested) and >1:100 in 22 samples (42%). The best correlations were observed with EUROimmun immunoglobulin G (IgG) reactivity (Spearman Rho correlation coefficient 0.88; p < 0.001). Based on ROC analysis, EUROimmun would detect 60% of samples with titres of >1:100 with 100% specificity using a reactivity index of 9.1 (13/22). DISCUSSION: Robust associations between nAb titres and reactivity in several ELISA-based antibody tests demonstrate their possible utility for scaled-up production of convalescent plasma containing potentially therapeutic levels of anti-SARS-CoV-2 nAbs.


Subject(s)
Antibodies, Neutralizing/blood , COVID-19/therapy , SARS-CoV-2/immunology , Antibodies, Viral/blood , Blood Donors , COVID-19/diagnosis , COVID-19 Testing , Enzyme-Linked Immunosorbent Assay/methods , Humans , Immunization, Passive/methods , Male , ROC Curve , Sensitivity and Specificity
16.
Euro Surveill ; 25(28)2020 Jul.
Article in English | MEDLINE | ID: covidwho-647502

ABSTRACT

Serological reactivity was analysed in plasma from 436 individuals with a history of disease compatible with COVID-19, including 256 who had been laboratory-confirmed with SARS-CoV-2 infection. Over 99% of laboratory-confirmed cases developed a measurable antibody response (254/256) and 88% harboured neutralising antibodies (226/256). Antibody levels declined over 3 months following diagnosis, emphasising the importance of the timing of convalescent plasma collections. Binding antibody measurements can inform selection of convalescent plasma donors with high neutralising antibody levels.


Subject(s)
Antibodies, Neutralizing/blood , Betacoronavirus/immunology , Coronavirus Infections/blood , Coronavirus Infections/therapy , Pneumonia, Viral/blood , Pneumonia, Viral/therapy , Adolescent , Adult , Aged , Antibodies, Neutralizing/therapeutic use , Antibody Specificity , Blood Donors/statistics & numerical data , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/immunology , England , Humans , Immunization, Passive/statistics & numerical data , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/immunology , SARS-CoV-2 , Statistics, Nonparametric , Time Factors , Young Adult
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