ABSTRACT
Background: SARS-CoV-2 vaccine coverage remains incomplete, being only 15% in low income countries. Rapid point of care tests predicting SARS-CoV-2 infection susceptibility in the unvaccinated might assist in risk management and vaccine prioritisation. Methods: We conducted a prospective cohort study in 2,826 participants working in hospitals and Fire and Police services in England, UK, during the pandemic (ISRCTN5660922). Plasma taken at recruitment in June 2020 was tested using four lateral flow immunoassay (LFIA) devices and two laboratory immunoassays detecting antibodies against SARS-CoV-2 (UK Rapid Test Consortium's AbC-19TM Rapid Test, OrientGene COVID IgG/IgM Rapid Test Cassette, SureScreen COVID-19 Rapid Test Cassette, and Biomerica COVID-19 IgG/IgM Rapid Test; Roche N and EUROIMMUN S laboratory assays). We monitored participants for microbiologically-confirmed SARS-CoV-2 infection for 200 days. We estimated associations between test results at baseline and subsequent infection, using Poisson regression models adjusted for baseline demographic risk factors for SARS-CoV-2 exposure. Findings: Positive IgG results on each of the four LFIAs were associated with lower rates of subsequent infection: adjusted incidence rate ratios (aIRRs) 0.00 (95% confidence interval 0.00-0.01), 0.03 (0.02-0.05), 0.07 (0.05-0.10), and 0.09 (0.07-0.12) respectively. The protective association was strongest for AbC-19 and SureScreen. The aIRR for the laboratory Roche N antibody assay at the manufacturer-recommended threshold was similar to those of the two best performing LFIAs at 0.03 (0.01-0.10). Interpretation: Lateral flow devices measuring SARS-CoV-2 IgG predicted disease risk in unvaccinated individuals over 200 day follow-up. The association of some LFIAs with subsequent infection was similar to laboratory immunoassays.
Subject(s)
COVID-19ABSTRACT
Objectives To define risk factors for SARS-CoV-2 infection in University of Cambridge students during a period of increased incidence in October and November 2020. Study design Survey Methods Routine public health surveillance identified a marked increase in the numbers of University of Cambridge students with respiratory illness and SARS-CoV-2 positivity in the 10 days after a national lockdown was announced in the UK on 5 November 2020. Cases were identified both through symptom-triggered testing and a universal asymptomatic testing program. An online questionnaire was sent to all University of Cambridge students on 25 November to investigate risk factors for testing positive in the period after 30 October 2020. This asked about symptoms, SARS-CoV-2 test results, in-person teaching settings, other aspects of University life, and attendance at social events in the period just prior to lockdown, from 30th October and 4th November 2020. Univariate and multivariable analyses were undertaken evaluating potential risk factors for SARS-CoV-2 positivity. Results Among 3,980 students responding to the questionnaire, 99 (2.5%) reported testing SARS-CoV-2 positive in the period studied; 28 (28%) were asymptomatic. We found strong independent associations with SARS-CoV-2 positivity were attendance at two social settings in the City of Cambridge (adjusted odds ratio favouring disease 13.0 (95% CI 6.2,26.9) and 14.2 (95% CI 2.9,70)), with weaker evidence of association with three further social settings. By contrast, we did not observe strong independent associations between disease risk and type of accommodation or attendance at, or participation in, a range of activities associated with the University curriculum. Conclusions Attendance at social settings can facilitate widespread SARS-CoV-2 transmission in University students. Constraint of transmission in higher education settings needs to emphasise risks outside University premises, as well as a COVID-safe environment within University premises.
Subject(s)
COVID-19 , Respiratory InsufficiencyABSTRACT
BackgroundDried blood spot samples (DBS) provide an alternative sample type to venous blood samples for antibody testing. DBS are used by NHS for diagnosing HCV and by PHE for large scale HIV and Hepatitis C serosurveillance; the applicability of DBS based approaches to SARS-CoV-2 antibody detection is uncertain. ObjectiveTo compare antibody detection in dried blood spot eluates using the Roche Elecsys (R) immunoassay (index test) with antibody detection in paired plasma samples, using the same assay (reference test). SettingOne Police and one Fire & Rescue facility in England. Participants195 participants within a larger sample COVID-19 serodiagnostics study of keyworkers, EDSAB-HOME. Outcome MeasuresSensitivity and specificity of DBS (the index test) relative to plasma (the reference test), at an experimental cut-off; quality of DBS sample collected; estimates of relative sensitivity of DBS vs. plasma immunoassay in a larger population. Results18/195 (9.2%) participants tested positive using plasma samples. DBS sample quality varied markedly by phlebotomist, and low sample volume significantly reduced immunoassay signals. Using a cut-off of ten median absolute deviations above the immunoassay result with negative samples, sensitivity and specificity of DBS were 89.0% (95% CI 67.2, 96.9%) and 100.0% (95% CI 97.9, 100%) respectively compared with using plasma. The limit of detection for DBS is about 30 times higher than for plasma. ConclusionDBS use for SARS-CoV-2 serology, though feasible, is insensitive relative to immunoassays on plasma. Sample quality impacts on assay performance. Alternatives, including the collection of capillary blood samples, should be considered for screening programs.
Subject(s)
COVID-19ABSTRACT
Objective To measure the association between self-reported signs and symptoms and SARS-CoV-2 seropositivity. Design Cross sectional study of three key worker groups. Setting Six acute NHS hospitals and two Police and Fire and Rescue sites in England. Participants Individuals were recruited from three streams: (A) Police and Fire and Rescue services (n=1147), (B) healthcare workers (n=1546) and (C) healthcare workers with previously positive virus detection (n=154). Main outcome measures Detection of anti-SARS-CoV-2 antibodies in plasma. Results 943 of the 2847 participants (33%) reported belief they had had COVID-19, having experienced compatible symptoms (including 152 from Stream C). Among individuals reporting COVID-19 compatible symptoms, 466 (49%) were seronegative on both Nucleoprotein (Roche) and Spike-protein (EUROIMMUN) antibody assays. However, among the 268 individuals with prior positive SARS-CoV-2 tests, of whom 96% reported symptoms with onset a median of 63 days (IQR 52 to 75 days) prior to venesection, Roche and EUROIMMUN assays had 96.6% (95% CI 93.7% to 98.2%) and 93.3% (95% CI 89.6% to 95.7%) sensitivity respectively. Symptomatic but seronegative individuals had significantly earlier symptom onset dates than the symptomatic seropositive individuals, shorter illness duration and a much lower anosmia reporting frequency. Conclusions Self-reported belief of COVID-19 was common among our frontline worker cohort. About half of these individuals were seronegative, despite a high sensitivity of serology in this cohort, at least in individuals with previous positive PCR results. This is compatible with non-COVID-19 respiratory disease during the COVID-19 outbreak having been commonly mistaken for COVID-19 within the key worker cohort studied.
Subject(s)
Respiratory Tract Diseases , Olfaction Disorders , COVID-19ABSTRACT
Natural infection of SARS-CoV-2 in humans leads to the development of a strong neutralizing antibody response, however the immunodominant targets of the polyclonal neutralizing antibody response are still unknown. Here, we functionally define the role SARS-CoV-2 spike plays as a target of the human neutralizing antibody response. In this study, we identify the spike protein subunits that contain antigenic determinants and examine the neutralization capacity of polyclonal sera from a cohort of patients that tested qRT-PCR-positive for SARS-CoV-2. Using an ELISA format, we assessed binding of human sera to spike subunit 1 (S1), spike subunit 2 (S2) and the receptor binding domain (RBD) of spike. To functionally identify the key target of neutralizing antibody, we depleted sera of subunit-specific antibodies to determine the contribution of these individual subunits to the antigen-specific neutralizing antibody response. We show that epitopes within RBD are the target of a majority of the neutralizing antibodies in the human polyclonal antibody response. These data provide critical information for vaccine development and development of sensitive and specific serological testing.
Subject(s)
Severe Acute Respiratory SyndromeABSTRACT
Objectives: To describe the point prevalence of SARS-CoV-2 in care homes reporting low numbers of cases of COVID-19. Design: A cross-sectional study of care homes, ascertaining perceived disease burden using interviews with care home managers and SARS-CoV-2 RNA detection in residents and staff using nose and throat swabbing. Setting: 15 Care homes in Essex, United Kingdom, all of which had reported either zero or one case of COVID-19 to the Health Protection Team. Participants: 912 residents and staff of care homes were tested. Residents were eligible to be tested regardless of symptoms. Main outcome measure: Detection of SARS-CoV-2 in residents and staff. Results: In the 15 care homes studied, SARS-CoV-2 was detected in 23 (5.2%)of 441 residents. Of these 23, 21/23 (91%) were asymptomatic as reported by the care home managers. SARS-CoV-2 was detected in 8/471 (1.7%) of staff. This differs from that in residents (p=0.003). Conclusions: The findings of the study suggest that symptoms, as reported by care home managers, are an insensitive method of defining the extent of SARS-CoV-2 infection in nursing homes. Viral detection from residents is more common than from staff. Microbiological screening is a more sensitive method for defining the extent of SARS-CoV-2 in care homes than managerial reporting of resident symptoms.