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Background To manage the sanitary crisis and rapidly assess the seroprevalence of anti-SARS-CoV-2 antibodies in the canton of Geneva, we invited previous participants of an annual health survey of the general population to a first serological test. As the pandemic progressed, it become clear that there would be a significant longer impact on health and wellbeing of population. Moreover, there was a need to assess the adherence of the population regarding COVID-19 prevention measures, over time, as well as to provide scientific knowledge about antibodies dynamics and protection from new infections. For all these reasons, a long-term follow-up has been settled via the dedicated digital platform Specchio-COVID19 and on-line questionnaires and repeated serological tests. Methods Several measures were designed to maintain high retention and involvement, including regular electronic newsletters with links to a “News” webpage, a “Research” webpage for dissemination of publications and the organization of webinars specifically dedicated to participants. A specific email address and a dedicated hotline were set up so that participants can get in touch with the Specchio-COVID19 team. Results Specchio-COVID19 was launched in November, 2020. Up to February 2022, 10'946 individuals (57% women, median age 48) joined the project. Over time, participation rate remains around 65% for each release of questionnaire. 550 participants (5%) definitely dropped out. Conclusions Our digital cohort facilitates participants’ involvement, allowing participation from remote locations, organizing webinar, promoting news and scientific information via newsletters and specific webpages and enabling interaction between researchers and participants. Key messages • When designing the Specchio-COVID19 digital cohort, the purpose was not only to collect data. • But to establish a reciprocal exchange of information between researchers and participants, fostering long-term involvement and health empowerment.
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Background: Liquid biopsy technology has delivered promising results for therapy monitoring and disease relapse detection. The simplicity of the procedure makes it attractive for early cancer detection despite its clinical value in this setting being as yet unknown. The objective of the study is to evaluate the acceptance of this new screening technology by the general population. Methods: Participants in a digital health study originally selected randomly from the general population of the canton of Geneva (Switzerland) were invited to participate in a survey investigating (1) their motivation and (2) what factors might affect their decision regarding whether to proceed to a liquid biopsy test for cancer screening. Results: 2'898 participants responded to the survey (participation rate: 35%), 1'568 are > 50yo. Two thirds are female, 7.6% have a history of cancer, 80.8% have a family relative with a history of cancer. In the whole population: 97.7% are ready to use liquid biopsy as a cancer screening test. In the > 50yo, 97.3% of women and 98.5% of men would do the test. In the < 50yo, 97.2% of women and 98.6% of men would take it with X2 = 0.018 (p = 0.89) for independence with sex. Age category, education level, income band, professional status, self-rated health, tobacco status, chronic disease, personal or familial history of cancer and COVID pandemic have no statistical impact on the incentive to do a liquid biopsy test. In the whole population, 94.6% would take the test knowing that there is a risk of a false positive. The median accepted false positive percentage error rate is 10% with interquartile rate (IQR) Q1: 5% and Q3: 15%. Ninety-six percent of respondents would take the test knowing that there is a risk of a false negative, accepting a median false negative percentage error rate of 10% with IQR Q1: 5% and Q3 : 20%. Most respondents (97.6%) will do the test knowing that additional tests or procedures could be required in case of positivity and 58.8% would take it yearly, while 24.6% only every two years. Fifty-nine percent believe that taking the test could influence their lifestyle, regardless of the result. Conclusions: This study shows that the surveyed population is ready to engage with liquid biopsy as a cancer screening tool despite its limitations and drawbacks. Willingness to take the test might depend on sex only in the < 50yo population. Knowing the lack of demonstrated benefit, it is urgent to conduct trials assessing the clinical value, psychological impact and financial burden of liquid biopsy tests before incorporating this technology into cancer screening programs. Due to the very high level of interest demonstrated in our study, the possibility of direct-to-consumer availability should prompt health authorities and accreditation bodies to carefully weigh the impact of authorizing market access to liquid biopsy technologies for this purpose.
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Background: Unravelling autoimmune targets triggered by SARS-CoV-2 infection may provide crucial insights in the physiopathology of the disease and foster the development of potential therapeutic candidate targets and prognostic tools. SARS-CoV-2 autoimmune-mediated inflammation have been reported, but the existence of autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) in COVID-19 remains unexplored. Anti-apoA-1 IgGs have emerged as an independent biomarker for cardiovascular disease and mortality in humans with proinflammatory and proatherogenic functions in vivo and in vitro. Purpose:We want to determine i) the degree of homology between SARSCoV-2, apoA-1, and Toll-like receptor-2 (TLR2) epitopes, ii) the association between anti-SARSCoV2 and anti-apoA-1 IgGs, and iii) their relationship to prognosis. Methods: We performed bioinformatics modelling coupled with mimetic peptides engineering, as well as functional and competition assays with antibodies to identify molecular mimicry between SARS-CoV-2, apoA-1 and TLR2 epitopes. Anti-Spike domain 1 (SD1) IgGs, anti-apoA-1 IgGs and against mimic peptides, as well as cytokines were assessed by immunoassays on a case-control (n=101), an intensive care unit (ICU;n=126) with a 28-days follow-up for overall mortality, and a general population cohort (n=663) with available samples in the pre and post-pandemic period. Results: Linear sequence homologies and antibodies cross-reactivity between apoA-1, TLR2, and Spike epitopes were identified. Overall, antiapoA-1 IgG levels were higher in COVID-19 patients or anti-SARS-CoV-2 seropositive individuals than in healthy donors or anti-SARS-CoV-2 seronegative individuals (p<0.0001). Significant and similar associations were noted between anti-apoA-1, anti-SARS-CoV-2 IgG, cytokines, and lipid profile. In ICU patients, anti-SARS-CoV-2 and anti-apoA-1 seroconversion rates displayed similar 7-days kinetics, reaching 82% for anti-apoA-1 seropositivity. C-statistics (CS) indicated that baseline anti-Spike/TLR2 mimic-peptide IgGs displayed a significant prognostic accuracy for overall mortality at 28 days (CS: 0.64;p=0.02). In the general population, SARSCoV-2 exposure increased baseline anti-apoA-1 IgG levels. Conclusions: COVID-19 induces a marked humoral response against the major protein of high-density lipoproteins. As a correlate of poorer prognosis in other clinical settings, such autoimmunity signatures may relate to long-term COVID-19 prognosis assessment and warrant further scrutiny in the current COVID-19 pandemic.
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Background and Aims: Unravelling autoimmune targets triggered by SARS-CoV-2 infection may provide crucial insights in the physiopathology of the disease and foster the development of potential therapeutic candidate targets and prognostic tools. We want to determine whether SARS-CoV-2 exposure could trigger a humoral response against apolipoprotein A-1 (anti-apoA-1 IgG) through molecular mimicry and assess its relationship to patient prognosis. Methods: Anti-Spike domain 1 (SD1) IgGs, anti-apoA-1 IgGs and against mimic peptides, as well as cytokines were assessed by immunoassays on a case-control (n=101), an intensive care unit (ICU;n=126) with a 28-days follow-up, and a general population cohort (n=663) with available samples in the pre and post-pandemic period. Results: Linear sequence homologies and antibodies cross-reactivity between apoA-1, TLR2, and Spike epitopes were identified. Overall, anti-apoA-1 IgG levels were higher in COVID-19 patients or anti-SARS-CoV-2 seropositive individuals than in healthy donors or anti-SARS-CoV-2 seronegative individuals (p<0.0001). Significant and similar associations were noted between anti-apoA-1, anti-SARS-CoV-2 IgG, cytokines, and lipid profile. In ICU patients, anti-SARS-CoV-2 and anti-apoA-1 seroconversion rates displayed similar 7-days kinetics, reaching 82% for anti-apoA-1 seropositivity. C-statistics (CS) indicated that anti-Spike/TLR2 mimic-peptide IgGs displayed a significant prognostic accuracy for overall mortality at 28 days (CS: 0.64;p=0.02). In the general population, SARS-CoV-2 exposure increased baseline anti-apoA-1 IgG levels. Conclusions: COVID-19 induces a marked humoral response against the major protein of high-density lipoproteins. As a correlate of poorer prognosis in other clinical settings, such autoimmunity signatures may relate to long-term COVID-19 prognosis assessment and warrant further scrutiny in the current COVID-19 pandemic.
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OBJECTIVES: To validate the diagnostic accuracy of a Euroimmun SARS-CoV-2 IgG and IgA immunoassay for COVID-19. METHODS: In this unmatched (1:2) case-control validation study, we used sera of 181 laboratory-confirmed SARS-CoV-2 cases and 326 controls collected before SARS-CoV-2 emergence. Diagnostic accuracy of the immunoassay was assessed against a whole spike protein-based recombinant immunofluorescence assay (rIFA) by receiver operating characteristic (ROC) analyses. Discrepant cases between ELISA and rIFA were further tested by pseudo-neutralization assay. RESULTS: COVID-19 patients were more likely to be male and older than controls, and 50.3% were hospitalized. ROC curve analyses indicated that IgG and IgA had high diagnostic accuracies with AUCs of 0.990 (95% Confidence Interval [95%CI]: 0.983-0.996) and 0.978 (95%CI: 0.967-0.989), respectively. IgG assays outperformed IgA assays (p=0.01). Taking an assessed 15% inter-assay imprecision into account, an optimized IgG ratio cut-off > 2.5 displayed a 100% specificity (95%CI: 99-100) and a 100% positive predictive value (95%CI: 96-100). A 0.8 cut-off displayed a 94% sensitivity (95%CI: 88-97) and a 97% negative predictive value (95%CI: 95-99). Substituting the upper threshold for the manufacturer's, improved assay performance, leaving 8.9% of IgG ratios indeterminate between 0.8-2.5. CONCLUSIONS: The Euroimmun assay displays a nearly optimal diagnostic accuracy using IgG against SARS-CoV-2 in patient samples, with no obvious gains from IgA serology. The optimized cut-offs are fit for rule-in and rule-out purposes, allowing determination of whether individuals in our study population have been exposed to SARS-CoV-2 or not. IgG serology should however not be considered as a surrogate of protection at this stage.