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Serosurveys are an important tool to estimate the true extent of the current SARS-CoV-2 pandemic. So far, most serosurvey data have been analyzed with cutoff-based methods, which dichotomize individual measurements into sero-positives or negatives based on a predefined cutoff. However, mixture model methods can gain additional information from the same serosurvey data. Such methods refrain from dichotomizing individual values and instead use the full distribution of the serological measurements from pre-pandemic and COVID-19 controls to estimate the cumulative incidence. This study presents an application of mixture model methods to SARS-CoV-2 serosurvey data from the SEROCoV-POP study from April and May 2020 in Geneva (2766 individuals). Besides estimating the total cumulative incidence in these data (8.1% (95% CI: 6.8%-9.9%)), we applied extended mixture model methods to estimate an indirect indicator of disease severity, which is the fraction of cases with a distribution of antibody levels similar to hospitalized COVID-19 patients. This fraction is 51.2% (95% CI: 15.2%-79.5%) across the full serosurvey, but differs between three age classes: 21.4% (95% CI: 0%-59.6%) for individuals between 5 and 40 years old, 60.2% (95% CI: 21.5%-100%) for individuals between 41 and 65 years old and 100% (95% CI: 20.1%-100%) for individuals between 66 and 90 years old. Additionally, we find a mismatch between the inferred negative distribution of the serosurvey and the validation data of pre-pandemic controls. Overall, this study illustrates that mixture model methods can provide additional insights from serosurvey data., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: Serological studies have been critical in tracking the evolution of the COVID-19 pandemic. Data on anti-SARS-CoV-2 antibodies persistence remain sparse, especially from infected individuals with few to no symptoms. The objective of the study was to quantify the sensitivity for detecting historic SARS-CoV-2 infections as a function of time since infection for three commercially available SARS-CoV-2 immunoassays and to explore the implications of decaying immunoassay sensitivity in estimating seroprevalence., Methods: We followed a cohort of mostly mild/asymptomatic SARS-CoV-2-infected individuals (n = 354) at least 8 months after their presumed infection date and tested their serum for anti-SARS-CoV-2 antibodies with three commercially available assays: Roche-N, Roche-RBD and EuroImmun-S1. We developed a latent class statistical model to infer the specificity and time-varying sensitivity of each assay and show through simulations how inappropriately accounting for test performance can lead to biased serosurvey estimates., Results: Antibodies were detected at follow-up in 74-100% of participants, depending on immunoassays. Both Roche assays maintain high sensitivity, with the EuroImmun assay missing 40% of infections after 9 months. Simulations reveal that without appropriate adjustment for time-varying assay sensitivity, seroprevalence surveys may underestimate infection rates., Discussion: Antibodies persist for at least 8 months after infection in a cohort of mildly infected individuals with detection depending on assay choice. Appropriate assay performance adjustment is important for the interpretation of serological studies in the case of diminishing sensitivity after infection., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To evaluate longitudinally the persistence of humoral immunity for up to 6 months in a cohort of hospital employees with mild coronavirus disease 2019 (COVID-19)., Methods: We measured anti-RBD (receptor binding domain of viral spike protein), anti-N (viral nucleoprotein) and neutralizing antibodies at 1, 3 and 6 months after mostly mild COVID-19 in 200 hospital workers using commercial ELISAs and a surrogate virus neutralization assay., Results: Antibodies specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persisted in all participants for up to 6 months. Anti-RBD geometric mean concentrations (GMCs) progressively increased between months 1 (74.2 U/mL, 95%CI: 62.7-87.8), 3 (103.2 U/mL, 95%CI: 87.9-121.2; p < 0.001), and 6 (123.3 U/mL, 95%CI: 103.4-147.0; p < 0.001) in the whole cohort. Anti-N antibodies were detectable in >97% at all times. Neutralizing antibodies were detectable in 99.5% of participants (195/196) at 6 months post infection. Their GMC progressively decreased between months 1 (20.1 AU/mL, 95%CI: 16.9-24.0), 3 (15.2 AU/mL, 95%CI: 13.2-17.6; p < 0.001) and 6 (9.4 AU/mL, 95%CI: 7.7-11.4; p < 0.001). RBD-ACE2-inhibiting antibody titres and anti-RBD antibody concentrations strongly correlated at each timepoint (all r > 0.86, p < 0.001). Disease severity was associated with higher initial anti-RBD and RBD-ACE2-inhibiting antibody titres, but not with their kinetics., Conclusions: Neutralizing antibodies persisted at 6 months in almost all participants, indicating more durability than initially feared. Anti-RBD antibodies persisted better and even increased over time, possibly related to the preferential detection of progressively higher-affinity antibodies., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Assessing the burden of COVID-19 on the basis of medically attended case numbers is suboptimal given its reliance on testing strategy, changing case definitions, and disease presentation. Population-based serosurveys measuring anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) antibodies provide one method for estimating infection rates and monitoring the progression of the epidemic. Here, we estimate weekly seroprevalence of anti-SARS-CoV-2 antibodies in the population of Geneva, Switzerland, during the epidemic., Methods: The SEROCoV-POP study is a population-based study of former participants of the Bus Santé study and their household members. We planned a series of 12 consecutive weekly serosurveys among randomly selected participants from a previous population-representative survey, and their household members aged 5 years and older. We tested each participant for anti-SARS-CoV-2-IgG antibodies using a commercially available ELISA. We estimated seroprevalence using a Bayesian logistic regression model taking into account test performance and adjusting for the age and sex of Geneva's population. Here we present results from the first 5 weeks of the study., Findings: Between April 6 and May 9, 2020, we enrolled 2766 participants from 1339 households, with a demographic distribution similar to that of the canton of Geneva. In the first week, we estimated a seroprevalence of 4·8% (95% CI 2·4-8·0, n=341). The estimate increased to 8·5% (5·9-11·4, n=469) in the second week, to 10·9% (7·9-14·4, n=577) in the third week, 6·6% (4·3-9·4, n=604) in the fourth week, and 10·8% (8·2-13·9, n=775) in the fifth week. Individuals aged 5-9 years (relative risk [RR] 0·32 [95% CI 0·11-0·63]) and those older than 65 years (RR 0·50 [0·28-0·78]) had a significantly lower risk of being seropositive than those aged 20-49 years. After accounting for the time to seroconversion, we estimated that for every reported confirmed case, there were 11·6 infections in the community., Interpretation: These results suggest that most of the population of Geneva remained uninfected during this wave of the pandemic, despite the high prevalence of COVID-19 in the region (5000 reported clinical cases over <2·5 months in the population of half a million people). Assuming that the presence of IgG antibodies is associated with immunity, these results highlight that the epidemic is far from coming to an end by means of fewer susceptible people in the population. Further, a significantly lower seroprevalence was observed for children aged 5-9 years and adults older than 65 years, compared with those aged 10-64 years. These results will inform countries considering the easing of restrictions aimed at curbing transmission., Funding: Swiss Federal Office of Public Health, Swiss School of Public Health (Corona Immunitas research program), Fondation de Bienfaisance du Groupe Pictet, Fondation Ancrage, Fondation Privée des Hôpitaux Universitaires de Genève, and Center for Emerging Viral Diseases., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To describe the epidemiology of acute/recent human immunodeficiency virus (HIV) infection over two decades in Barcelona (Spain)., Methods: Prospective, single-centre cohort including all patients with an acute/recent HIV infection (<180 days) since 1997. Patients were stratified into four periods. Phylogenetic analysis was performed to determine clusters of transmission., Results: A total of 346 consecutive acute/recently infected patients were included. The annual proportion of recent infections among total new HIV diagnoses increased over time from 1% (29 out of 1964) to 8% (112 out of 1474) (p <0.001). Proportion of men who have sex with men (MSM) in the cohort increased from 62% (18 out of 29) to 89% (100 out of 112) (p <0.001). The proportion of migrants showed a non-significant increasing trend (24% (7 of 29) to 40% (45 of 112)) likewise the non-B subtype (0% to 22% (22 of 112)). The mean time from infection to diagnosis was 53.6 days (interquartile range (IQR) 50-57), comparable among all periods. Mean time from infection to treatment decreased over the years from 575 (IQR 467-683) to 471 (IQR 394-549) days (p <0.001) without significant differences between migrants and non-migrants (133 (IQR 71-411) versus 208 (IQR 90-523) days p 0.089). Almost 50% (152 of 311) of recently infected individuals were included in a cluster of transmission, and 92% (137 of 149) of them were MSM., Conclusion: The MSM population has progressively grown within acutely/recently infected patients in Barcelona, and is frequently involved in transmission clusters. Although the time between diagnosis and treatment has been reduced, the time between infection and diagnosis still needs to be shortened., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The management of multidrug-resistant human immunodeficiency virus (MDR HIV) infections in children is particularly challenging due to the lack of experience with new drugs. Dolutegravir, combined with an optimized antiretroviral background therapy, is promising for the treatment of MDR HIV and has been approved recently for adults and adolescents. Data for children are extremely limited. We describe the efficacy, safety and plasmatic levels of a dolutegravir-based, complex active antiretroviral treatment regimen in a severely overweight 11-year-old child infected with an MDR HIV strain.

Background: Stopping antiretroviral therapy in patients with HIV-1 infection can reduce costs and side-effects, but carries the risk of increased immune suppression and emergence of resistance., Methods: 430 patients with CD4-positive T-lymphocyte (CD4) counts greater than 350 cells per muL, and viral load less than 50 copies per mL were randomised to continued therapy (n=146) or scheduled treatment interruptions (n=284). Median time on randomised treatment was 21.9 months (range 16.4-25.3). Primary endpoints were proportion of patients with viral load less than 50 copies per mL at the end of the trial, and amount of drugs used. Analysis was intention-to-treat. This study is registered at ClinicalTrials.gov with the identifier NCT00113126., Findings: Drug savings in the scheduled treatment interruption group, compared with continuous treatment, amounted to 61.5%. 257 of 284 (90.5%) patients in the scheduled treatment interruption group reached a viral load less than 50 copies per mL, compared with 134 of 146 (91.8%) in the continued treatment group (difference 1.3%, 95% CI-4.3 to 6.9, p=0.90). No AIDS-defining events occurred. Diarrhoea and neuropathy were more frequent with continuous treatment; candidiasis was more frequent with scheduled treatment interruption. Ten patients (2.3%) had resistance mutations, with no significant differences between groups., Interpretation: Drug savings with scheduled treatment interruption were substantial, and no evidence of increased treatment resistance emerged. Treatment-related adverse events were more frequent with continuous treatment, but low CD4 counts and minor manifestations of HIV infection were more frequent with scheduled treatment interruption.

Background: Resistance of HIV-1 to antiretroviral drugs is the main cause of antiretroviral-treatment failure. We assessed the transmission of drug-resistant variants among individuals with primary HIV-1 infection., Methods: Population-based sequencing of the viral reverse-transcriptase and protease genes derived from plasma viral RNA was done in 82 consecutive individuals with documented primary HIV-1 infection from January, 1996, to July, 1998. Phenotypic resistance to protease inhibitors was assessed by recombinant virus assay in individuals with two or more mutations associated with resistance to protease inhibitors., Findings: Zidovudine-resistance mutations were detected in seven (9%) of 82 individuals. Mutations associated with resistance to other reverse-transcriptase inhibitors (RTIs) were detected in two individuals. Primary-resistance mutations associated with protease inhibitors (V82A, L90M) were detected in three (4%) of 70 individuals; two of these had also RTI-resistance mutations. Decreased sensitivity to three or four protease inhibitors was seen in three individuals, one of whom was infected with HIV-1 variants that harboured 12 mutations associated with resistance to multiple RTI and protease inhibitors., Interpretation: To introduce the best antiretroviral treatment, resistance testing should be done in recently HIV-1-infected individuals.

The significance of indeterminate screening antibody test for human immunodeficiency virus (HIV) serology is still difficult to evaluate, especially in low-risk populations. One hundred twenty-seven blood donors with an initially reactive screening test for HIV antibodies were enrolled in this study. The sera of 95 of these blood donors were reactive on repetition of the test, and none had detectable circulating p24 antigen. Western blot (WB) analysis of the repeatedly reactive sera was as follows: 9 positive, 31 indeterminate, and 55 negative. One of the blood donors with indeterminate WB later presented a seroconversion. On subsequent control 3 to 12 months later, the sera from donors with indeterminate or negative WB did not present any parameters that may indicate a seroconversion. DNA was purified from citrated blood collected from the 127 blood donors at the time of the initial antibody screening. Five micrograms of each DNA sample corresponding to 7 x 10(5) nucleated white blood cells was amplified by polymerase chain reaction (PCR) in the presence of oligonucleotides (primers) corresponding to a highly conserved segment of the pol gene. The detection of amplified DNA was achieved by dot blot and Southern blot using appropriate 32P-labeled oligonucleotides. Ten DNA samples were positive, 9 corresponded to blood donors with a positive HIV serology, and 1 to the blood donor who later presented a seroconversion. These results confirm the sensitivity of the PCR for the diagnosis of HIV infection; they also suggest that repetition of the serology at 3- to 12-month intervals is a valuable procedure for the control of HIV infection status in blood donors.

Hypo- or ahaptoglobinemia, a common phenomenon in tropical countries, is mainly due to malaria induced hemolysis. We have recently shown that the prevalence of hypohaptoglobinemia is a useful epidemiologic indicator in malaria endemic areas. The main limitation to the practical utilisation of this indicator is the available methodologies. Here we describe a sandwich ELISA for the determination of haptoglobin concentrations which is easy to perform, sensitive and requires a minimal amount of equipment. With this test system it is possible to detect haptoglobin in serum at a lower limit of 100 micrograms/ml for 10(-4) dilutions and of less than 1 micrograms/ml for 10(-2) dilutions. This represents at least 200 fold increase in sensitivity as compared to radial immunodiffusion.

Hypohaptoglobinaemia is a common phenomenon in tropical countries, where it is probably due to malaria-induced haemolysis. Two studies were carried out in a hyperendemic zone of West Africa to test its specificity and usefulness as an epidemiological indicator for measuring malaria endemicity. The first study evaluated the prevalence of hypohaptoglobinaemia before and after courses of antimalarial chemotherapy of varying duration. The second monitored haptoglobin levels in an untreated population during a whole year to compare its seasonal variations with those of several classic indicators of malaria. These studies suggest that in regions where malaria is endemic the prevalence of hypohaptoglobinaemia could be as useful an indicator as the parasitic index but would be much easier to establish and to monitor.