RSS 1.0Infectious Diseases
Recent Submissions
-
Efficacy of β-lactam/β-lactamase inhibitors to treat extended-spectrum beta-lactamase-producing Enterobacterales bacteremia secondary to urinary tract infection in kidney transplant recipients (INCREMENT-SOT Project).Background: Whether active therapy with β-lactam/β-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear. Methods: We retrospectively evaluated 306 KTR admitted to 30 centers from January 2014 to October 2016. Therapeutic failure (lack of cure or clinical improvement and/or death from any cause) at days 7 and 30 from ESBL-E BSI onset was the primary and secondary study outcomes, respectively. Results: Therapeutic failure at days 7 and 30 occurred in 8.2% (25/306) and 13.4% (41/306) of patients. Hospital-acquired BSI (adjusted OR [aOR]: 4.10; 95% confidence interval [CI]: 1.50-11.20) and Pitt score (aOR: 1.47; 95% CI: 1.21-1.77) were independently associated with therapeutic failure at day 7. Age-adjusted Charlson Index (aOR: 1.25; 95% CI: 1.05-1.48), Pitt score (aOR: 1.72; 95% CI: 1.35-2.17), and lymphocyte count ≤500 cells/μL at presentation (aOR: 3.16; 95% CI: 1.42-7.06) predicted therapeutic failure at day 30. Carbapenem monotherapy (68.6%, primarily meropenem) was the most frequent active therapy, followed by BLBLI monotherapy (10.8%, mostly piperacillin-tazobactam). Propensity score (PS)-adjusted models revealed no significant impact of the choice of active therapy (carbapenem-containing vs any other regimen, BLBLI- vs carbapenem-based monotherapy) within the first 72 hours on any of the study outcomes. Conclusions: Our data suggest that active therapy based on BLBLI may be as effective as carbapenem-containing regimens for ESBL-E BSI secondary to UTI in the specific population of KTR. Potential residual confounding and unpowered sample size cannot be excluded (ClinicalTrials.gov identifier: NCT02852902).
-
Analysis of an Ebola virus disease survivor whose host and viral markers were predictive of death indicates the effectiveness of medical countermeasures and supportive care.Background: Ebola virus disease (EVD) is an often-fatal infection where the effectiveness of medical countermeasures is uncertain. During the West African outbreak (2013-2016), several patients were treated with different types of anti-viral therapies including monoclonal antibody-based cocktails that had the potential to neutralise Ebola virus (EBOV). However, at the time, the efficacy of these therapies was uncertain. Given the scale of the outbreak, several clinical phenotypes came to the forefront including the ability of the same virus to cause recrudescence in the same patient-perhaps through persisting in immune privileged sites. Several key questions remained including establishing if monoclonal antibody therapy was effective in humans with severe EVD, whether virus escape mutants were selected during treatment, and what is the potential mechanism(s) of persistence. This was made possible through longitudinal samples taken from a UK patient with EVD. Methods: Several different sample types, plasma and cerebrospinal fluid, were collected and sequenced using Illumina-based RNAseq. Sequence reads were mapped both to EBOV and the human genome and differential gene expression analysis used to identify changes in the abundance of gene transcripts as infection progressed. Digital Cell Quantitation analysis was used to predict the immune phenotype in samples derived from blood. Results: The findings were compared to equivalent data from West African patients. The study found that both virus and host markers were predictive of a fatal outcome. This suggested that the extensive supportive care, and most likely the application of the medical countermeasure ZMab (a monoclonal antibody cocktail), contributed to survival of the UK patient. The switch from progression to a 'fatal' outcome to a 'survival' outcome could be seen in both the viral and host markers. The UK patient also suffered a recrudescence infection 10 months after the initial infection. Analysis of the sequencing data indicated that the virus entered a period of reduced or minimal replication, rather than other potential mechanisms of persistence-such as defective interfering genomes. Conclusions: The data showed that comprehensive supportive care and the application of medical countermeasures are worth pursuing despite an initial unfavourable prognosis.
-
Association of HIV status with sexual function in women aged 45-60 in England: results from two national surveys.Increasing numbers of women living with HIV are reaching their midlife. We explore the association of HIV status with sexual function (SF) in women aged 45-60 using two national cross-sectional surveys: the third British National Survey of Sexual Attitudes and Lifestyles ("Natsal-3") and "PRIME", a survey of women living with HIV attending HIV clinics across England. Both studies asked the same questions about SF that take account not only sexual difficulties but also the relationship context and overall level of satisfaction, which collectively allowed an overall SF score to be derived. We undertook analyses of sexually-active women aged 45-60 from Natsal-3 (N = 1228, presumed HIV-negative given the low estimated prevalence of HIV in Britain) and PRIME (N = 386 women living with HIV). Women living with HIV were compared to Natsal-3 participants using multivariable logistic regression (adjusting for key confounders identified a priori: ethnicity, ongoing relationship status, depression and number of chronic conditions) and propensity scoring. Relative to Natsal-3 participants, women living with HIV were more likely to: have low overall SF (adjusted odds ratio (AOR) 3.75 [2.15-6.56]), report ≥1 sexual problem(s) lasting ≥3 months (AOR 2.44 [1.49-4.00]), and report almost all 8 sexual problems asked about (AORs all ≥2.30). The association between HIV status and low SF remained statistically significant when using propensity scoring (AOR 2.43 [1.68-3.51]). Among women living with HIV (only), low SF was more common in those who were postmenopausal vs. Premenopausal (55.6% vs. 40.4%). This study suggests a negative association between HIV status and sexual function in women aged 45-60. We recommend routine assessment of SF in women living with HIV.
-
A cost comparison of amikacin therapy with bedaquiline, for drug-resistant tuberculosis in the UK.Objectives: Prioritisation of oral bedaquiline over the injectable agents in the treatment of multidrug-resistant Tuberculosis (MDR-TB) in the World Health Organisations (WHO) 2019 guidelines prompted this UK analysis of cost implications. The objective was to estimate the costs of amikacin versus bedaquiline in MDR TB treatment regimens using a historical cohort where the injectable agents were the standard of care. Methods: This was a retrospective study using a known cohort of UK patients treated with an injectable agent, with data available on resource use, costs for the use of amikacin were compared with those for bedaquiline, based on recommended monitoring for bedaquiline. Results: The estimated cost of treatment per patient had mean (sd) of £27,236 (4952) for the observed injectable group, £30,264 (3392) and 36,309 (3901) for the 6 and 8 month amikacin groups, and £31,760 (2092) for the bedaquiline group. The cost in the bedaquiline group was £30,772 (1855) with a 10% reduction and £27,079 (1234) with a 33% reduction in-patient stay. Conclusions: In most scenarios, bedaquiline is close to cost neutral compared with injectable therapy, especially if, as expected, some reduction in duration of admission is possible as a result of bedaquiline's more rapid culture conversion.
-
Laboratory-based molecular test alternatives to RT-PCR for the diagnosis of SARS-CoV-2 infection.Background: Diagnosing people with a SARS-CoV-2 infection played a critical role in managing the COVID-19 pandemic and remains a priority for the transition to long-term management of COVID-19. Initial shortages of extraction and reverse transcription polymerase chain reaction (RT-PCR) reagents impaired the desired upscaling of testing in many countries, which led to the search for alternatives to RNA extraction/purification and RT-PCR testing. Reference standard methods for diagnosing the presence of SARS-CoV-2 infection rely primarily on real-time reverse transcription-polymerase chain reaction (RT-PCR). Alternatives to RT-PCR could, if sufficiently accurate, have a positive impact by expanding the range of diagnostic tools available for the timely identification of people infected by SARS-CoV-2, access to testing and the use of resources. Objectives: To assess the diagnostic accuracy of alternative (to RT-PCR assays) laboratory-based molecular tests for diagnosing SARS-CoV-2 infection. Search methods: We searched the COVID-19 Open Access Project living evidence database from the University of Bern until 30 September 2020 and the WHO COVID-19 Research Database until 31 October 2022. We did not apply language restrictions. Selection criteria: We included studies of people with suspected or known SARS-CoV-2 infection, or where tests were used to screen for infection, and studies evaluating commercially developed laboratory-based molecular tests for the diagnosis of SARS-CoV-2 infection considered as alternatives to RT-PCR testing. We also included all reference standards to define the presence or absence of SARS-CoV-2, including RT-PCR tests and established clinical diagnostic criteria. Data collection and analysis: Two authors independently screened studies and resolved disagreements by discussing them with a third author. Two authors independently extracted data and assessed the risk of bias and applicability of the studies using the QUADAS-2 tool. We presented sensitivity and specificity, with 95% confidence intervals (CIs), for each test using paired forest plots and summarised results using average sensitivity and specificity using a bivariate random-effects meta-analysis. We illustrated the findings per index test category and assay brand compared to the WHO's acceptable sensitivity and specificity threshold for diagnosing SARS-CoV-2 infection using nucleic acid tests. Main results: We included data from 64 studies reporting 94 cohorts of participants and 105 index test evaluations, with 74,753 samples and 7517 confirmed SARS-CoV-2 cases. We did not identify any published or preprint reports of accuracy for a considerable number of commercially produced NAAT assays. Most cohorts were judged at unclear or high risk of bias in more than three QUADAS-2 domains. Around half of the cohorts were considered at high risk of selection bias because of recruitment based on COVID status. Three quarters of 94 cohorts were at high risk of bias in the reference standard domain because of reliance on a single RT-PCR result to determine the absence of SARS-CoV-2 infection or were at unclear risk of bias due to a lack of clarity about the time interval between the index test assessment and the reference standard, the number of missing results, or the absence of a participant flow diagram. For index tests categories with four or more evaluations and when summary estimations were possible, we found that: a) For RT-PCR assays designed to omit/adapt RNA extraction/purification, the average sensitivity was 95.1% (95% CI 91.1% to 97.3%), and the average specificity was 99.7% (95% CI 98.5% to 99.9%; based on 27 evaluations, 2834 samples and 1178 SARS-CoV-2 cases); b) For RT-LAMP assays, the average sensitivity was 88.4% (95% CI 83.1% to 92.2%), and the average specificity was 99.7% (95% CI 98.7% to 99.9%; 24 evaluations, 29,496 samples and 2255 SARS-CoV-2 cases); c) for TMA assays, the average sensitivity was 97.6% (95% CI 95.2% to 98.8%), and the average specificity was 99.4% (95% CI 94.9% to 99.9%; 14 evaluations, 2196 samples and 942 SARS-CoV-2 cases); d) for digital PCR assays, the average sensitivity was 98.5% (95% CI 95.2% to 99.5%), and the average specificity was 91.4% (95% CI 60.4% to 98.7%; five evaluations, 703 samples and 354 SARS-CoV-2 cases); e) for RT-LAMP assays omitting/adapting RNA extraction, the average sensitivity was 73.1% (95% CI 58.4% to 84%), and the average specificity was 100% (95% CI 98% to 100%; 24 evaluations, 14,342 samples and 1502 SARS-CoV-2 cases). Only two index test categories fulfil the WHO-acceptable sensitivity and specificity requirements for SARS-CoV-2 nucleic acid tests: RT-PCR assays designed to omit/adapt RNA extraction/purification and TMA assays. In addition, WHO-acceptable performance criteria were met for two assays out of 35 when tests were used according to manufacturer instructions. At 5% prevalence using a cohort of 1000 people suspected of SARS-CoV-2 infection, the positive predictive value of RT-PCR assays omitting/adapting RNA extraction/purification will be 94%, with three in 51 positive results being false positives, and around two missed cases. For TMA assays, the positive predictive value of RT-PCR assays will be 89%, with 6 in 55 positive results being false positives, and around one missed case. Authors' conclusions: Alternative laboratory-based molecular tests aim to enhance testing capacity in different ways, such as reducing the time, steps and resources needed to obtain valid results. Several index test technologies with these potential advantages have not been evaluated or have been assessed by only a few studies of limited methodological quality, so the performance of these kits was undetermined. Only two index test categories with enough evaluations for meta-analysis fulfil the WHO set of acceptable accuracy standards for SARS-CoV-2 nucleic acid tests: RT-PCR assays designed to omit/adapt RNA extraction/purification and TMA assays. These assays might prove to be suitable alternatives to RT-PCR for identifying people infected by SARS-CoV-2, especially when the alternative would be not having access to testing. However, these findings need to be interpreted and used with caution because of several limitations in the evidence, including reliance on retrospective samples without information about the symptom status of participants and the timing of assessment. No extrapolation of found accuracy data for these two alternatives to any test brands using the same techniques can be made as, for both groups, one test brand with high accuracy was overrepresented with 21/26 and 12/14 included studies, respectively. Although we used a comprehensive search and had broad eligibility criteria to include a wide range of tests that could be alternatives to RT-PCR methods, further research is needed to assess the performance of alternative COVID-19 tests and their role in pandemic management.
-
Key concepts in diagnosing infection - when to treat and when not to.What tests to send and when? This article examines the evidence for common microbiological tests and discusses their limitations and interpretation. Urine tests, surface swabs, blood cultures and screening swabs are all discussed in the context of a fictional clinical case.
-
Response to Dr DancerNo abstract available
-
Reply to Hill et al.No abstract available
-
Chronic infection in Fijian migrants to the UKIntroduction. Strongyloides stercoralis, the human threadworm, is a parasitic nematode with global distribution, estimated to infect over 600 million people. Chronic infection is often asymptomatic, but hyperinfection and dissemination syndromes can occur in the immunosuppressed with high case fatality rates. Whilst strongyloidiasis is endemic in Fiji, its prevalence in Fijian migrant groups in the UK is unknown.Gap Statement. No previous studies have been conducted on the prevalence of Strongyloides and other gastrointestinal parasites (GIPs) in Fijian migrants to the UK.Aim. We conducted a cross-sectional study of the prevalence of GIPs in a Fijian migrant population.Methodology. Participants completed a questionnaire on residence, travel and clinical symptoms and were asked to provide a serum sample for S. stercoralis IgG ELISA, venous blood samples for eosinophil count and a faecal sample for charcoal culture, multiplex real-time PCR (rtPCR) and microscopy after formalin-ethyl acetate concentration. Sequencing was performed on pooled Strongyloides larvae for nuclear 18S rRNA hyper-variable regions (HVRs) I and IV.Results. A total of 250 participants (94% male) with median (range) age 37 (20-51) years entered the study, 15 (1-24) years since leaving Fiji. S. stercoralis IgG ELISA was positive in 87/248 (35.1 %) and 14/74 (18.9 %) had a GIP detected in faeces. This included 7/74 (9.5 %) with Strongyloides and 5/74 (6.8 %) with hookworms. Dermatological symptoms were more common in those with Strongyloides, and eosinophilia (>0.5×109 cells per litre) was present in 55.6% of those with positive S. stercoralis IgG. rtPCR was the most sensitive faecal diagnostic test for Strongyloides and hookworms in faeces. Sequences of nuclear 18S rRNA for HVRs I and IV confirmed the presence of S. stercoralis. Conclusion. This first cross-sectional study in Fijian migrants found a high rate of chronic infection with GIPs, particularly S. stercoralis. Faecal microscopy was insensitive compared to charcoal culture, rtPCR or serology, demonstrating the importance of specialist parasitological tests when investigating people with a suspected chronic infection. Our study highlights an overlooked burden of strongyloidiasis in the UK and has implications for screening and treatment programmes in Fiji and for migrants from Fiji.
-
Population-level frequency of fluoroquinolone resistance by whole-genome sequencing drug predictions in Mycobacterium tuberculosis complex isolates in England from 2017-2023Fluoroquinolones are an important component of anti-tuberculosis treatment and identifying fluoroquinolone resistance is essential. We present the first survey of fluoroquinolone resistance in England from sequencing of over 16,000 unselected isolates. Fluoroquinolone resistance was 1.4% overall and 23.9% in multidrug-resistant TB. Routine sequencing allows resistance surveillance and should be widely adopted.
-
A comparative study of traditional and molecular diagnostic methods for detection of gastrointestinal parasites in Nepalese migrants to the UKBackground: We evaluated the results of examining a single faecal sample for gastrointestinal parasites (GIP) using a combination of traditional methods with multiplex qPCR for helminths and protozoa, compared to a reference standard of examining three faecal samples from each person using traditional diagnostic methods alone. Methods: Three faecal samples were collected at weekly intervals from 596 healthy Nepalese men. Each sample underwent formalin-ethyl acetate (FEA) concentration and light microscopy, and charcoal culture. The combined results of these investigations for all three stool samples were designated the reference standard. The first sample was also analysed using a multiplex TaqMan™ qPCR assay, screening for five helminths and three protozoa. We compared sensitivity and specificity of analysing the first faecal sample with qPCR alone, or a hybrid approach combining qPCR with traditional methods, to the reference standard. Additionally, a serum sample was taken from each participant for Strongyloides stercoralis IgG ELISA. Results: The reference standard identified 139 GIP infections in 133 (22.3%) participants. Use of qPCR alone in one stool identified 176 infections in 147 (24.8%) participants, rising to 187 infections in 156 (26.3%) when combined with FEA microscopy and charcoal culture. The sensitivity of this latter hybrid approach was 100% for Strongyloides spp., 90.9% for Trichuris trichiura, 86.8% for hookworm species and 75% for Giardia duodenalis compared to the reference standard. The hybrid approach increased the detected prevalence of G. duodenalis by 4.5% (27 cases) overall, T. trichiura by 2.9% (17 cases), Strongyloides spp. by 1% (6 cases), and hookworm by 0.5% (3 cases), compared to the reference standard. Conclusion: Examination of a single faecal sample using qPCR alone showed superior or equivalent sensitivity to traditional methods for most GIP infections when both were compared to the reference standard. Combining molecular and traditional methods to analyse a single stool improved the detection rate for most studied parasites. This approach has value in settings where repeated sampling and/or faecal culture for helminths is impractical, but molecular diagnostics are available.
-
Chlorine in cleaning - are we concentrating enough?No abstract available
-
Corrigendum to 'Impact of COVID-19 on immunocompromised populations during the Omicron era: insights from the observational population-based INFORM study' [The Lancet Regional Health - Europe 35 (2023) 100747].[This corrects the article DOI: 10.1016/j.lanepe.2023.100747.].
-
Ultrarapid detection of SARS-CoV-2 RNA using a reverse transcription-free exponential amplification reaction, RTF-EXPARA rapid isothermal method for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, is reported. The procedure uses an unprecedented reverse transcription-free (RTF) approach for converting genomic RNA into DNA. This involves the formation of an RNA/DNA heteroduplex whose selective cleavage generates a short DNA trigger strand, which is then rapidly amplified using the exponential amplification reaction (EXPAR). Deploying the RNA-to-DNA conversion and amplification stages of the RTF-EXPAR assay in a single step results in the detection, via a fluorescence read-out, of single figure copy numbers per microliter of SARS-CoV-2 RNA in under 10 min. In direct three-way comparison studies, the assay has been found to be faster than both RT-qPCR and reverse transcription loop-mediated isothermal amplification (RT-LAMP), while being just as sensitive. The assay protocol involves the use of standard laboratory equipment and is readily adaptable for the detection of other RNA-based pathogens.
-
Shorter treatment for nonsevere tuberculosis in African and Indian children.Background: Two thirds of children with tuberculosis have nonsevere disease, which may be treatable with a shorter regimen than the current 6-month regimen. Methods: We conducted an open-label, treatment-shortening, noninferiority trial involving children with nonsevere, symptomatic, presumably drug-susceptible, smear-negative tuberculosis in Uganda, Zambia, South Africa, and India. Children younger than 16 years of age were randomly assigned to 4 months (16 weeks) or 6 months (24 weeks) of standard first-line antituberculosis treatment with pediatric fixed-dose combinations as recommended by the World Health Organization. The primary efficacy outcome was unfavorable status (composite of treatment failure [extension, change, or restart of treatment or tuberculosis recurrence], loss to follow-up during treatment, or death) by 72 weeks, with the exclusion of participants who did not complete 4 months of treatment (modified intention-to-treat population). A noninferiority margin of 6 percentage points was used. The primary safety outcome was an adverse event of grade 3 or higher during treatment and up to 30 days after treatment. Results: From July 2016 through July 2018, a total of 1204 children underwent randomization (602 in each group). The median age of the participants was 3.5 years (range, 2 months to 15 years), 52% were male, 11% had human immunodeficiency virus infection, and 14% had bacteriologically confirmed tuberculosis. Retention by 72 weeks was 95%, and adherence to the assigned treatment was 94%. A total of 16 participants (3%) in the 4-month group had a primary-outcome event, as compared with 18 (3%) in the 6-month group (adjusted difference, -0.4 percentage points; 95% confidence interval, -2.2 to 1.5). The noninferiority of 4 months of treatment was consistent across the intention-to-treat, per-protocol, and key secondary analyses, including when the analysis was restricted to the 958 participants (80%) independently adjudicated to have tuberculosis at baseline. A total of 95 participants (8%) had an adverse event of grade 3 or higher, including 15 adverse drug reactions (11 hepatic events, all but 2 of which occurred within the first 8 weeks, when the treatments were the same in the two groups). Conclusions: Four months of antituberculosis treatment was noninferior to 6 months of treatment in children with drug-susceptible, nonsevere, smear-negative tuberculosis. (Funded by the U.K. Medical Research Council and others; SHINE ISRCTN number, ISRCTN63579542.).
-
Propensity score and desirability of outcome ranking analysis of ertapenem for treatment of nonsevere bacteremic urinary tract infections due to extended-spectrum-beta-lactamase-producing enterobacterales in kidney transplant recipientsThere are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages.
-
Serological responses to SARS-CoV-2 following non-hospitalised infection: clinical and ethnodemographic features associated with the magnitude of the antibody response.Objective: To determine clinical and ethnodemographic correlates of serological responses against the SARS-CoV-2 spike glycoprotein following mild-to-moderate COVID-19. Design: A retrospective cohort study of healthcare workers who had self-isolated due to COVID-19. Setting: University Hospitals Birmingham NHS Foundation Trust, UK (UHBFT). Participants: 956 healthcare workers were recruited by open invitation via UHBFT trust email and social media between 27 April 2020 and the 8 June 2020. Intervention: Participants volunteered a venous blood sample that was tested for the presence of anti-SARS-CoV-2 spike glycoprotein antibodies. Results were interpreted in the context of the symptoms of their original illness and ethnodemographic variables. Results: Using an assay that simultaneously measures the combined IgG, IgA and IgM response against the spike glycoprotein (IgGAM), the overall seroprevalence within this cohort was 46.2% (n=442/956). The seroprevalence of immunoglobulin isotypes was 36.3%, 18.7% and 8.1% for IgG, IgA and IgM, respectively. IgGAM identified serological responses in 40.6% (n=52/128) of symptomatic individuals who reported a negative SARS-CoV-2 PCR test. Increasing age, non-white ethnicity and obesity were independently associated with greater IgG antibody response against the spike glycoprotein. Self-reported fever and fatigue were associated with greater IgG and IgA responses against the spike glycoprotein. The combination of fever and/or cough and/or anosmia had a positive predictive value of 92.3% for seropositivity in self-isolating individuals a time when Wuhan strain SARS-CoV-2 was predominant. Conclusions and relevance: Assays employing combined antibody detection demonstrate enhanced seroepidemiological sensitivity and can detect prior viral exposure even when PCR swabs have been negative. We demonstrate an association between known ethnodemographic risk factors associated with mortality from COVID-19 and the magnitude of serological responses in mild-to-moderate disease.