scholarly journals Improving SARS-CoV-2 cumulative incidence estimation through mixture modelling of antibody levels

Author(s):  
C. Bottomley ◽  
M. Otiende ◽  
S. Uyoga ◽  
K. Gallagher ◽  
E.W. Kagucia ◽  
...  

AbstractAs countries decide on vaccination strategies and how to ease movement restrictions, estimates of cumulative incidence of SARS-CoV-2 infection are essential in quantifying the extent to which populations remain susceptible to COVID-19. Cumulative incidence is usually estimated from seroprevalence data, where seropositives are defined by an arbitrary threshold antibody level, and adjusted for sensitivity and specificity at that threshold. This does not account for antibody waning nor for lower antibody levels in asymptomatic or mildly symptomatic cases. Mixture modelling can estimate cumulative incidence from antibody-level distributions without requiring adjustment for sensitivity and specificity. To illustrate the bias in standard threshold-based seroprevalence estimates, we compared both approaches using data from several Kenyan serosurveys. Compared to the mixture model estimate, threshold analysis underestimated cumulative incidence by 31% (IQR: 11 to 41) on average. Until more discriminating assays are available, mixture modelling offers an approach to reduce bias in estimates of cumulative incidence.One-Sentence SummaryMixture models reduce biases inherent in the standard threshold-based analysis of SARS-CoV-2 serological data.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
C. Bottomley ◽  
M. Otiende ◽  
S. Uyoga ◽  
K. Gallagher ◽  
E. W. Kagucia ◽  
...  

AbstractAs countries decide on vaccination strategies and how to ease movement restrictions, estimating the proportion of the population previously infected with SARS-CoV-2 is important for predicting the future burden of COVID-19. This proportion is usually estimated from serosurvey data in two steps: first the proportion above a threshold antibody level is calculated, then the crude estimate is adjusted using external estimates of sensitivity and specificity. A drawback of this approach is that the PCR-confirmed cases used to estimate the sensitivity of the threshold may not be representative of cases in the wider population—e.g., they may be more recently infected and more severely symptomatic. Mixture modelling offers an alternative approach that does not require external data from PCR-confirmed cases. Here we illustrate the bias in the standard threshold-based approach by comparing both approaches using data from several Kenyan serosurveys. We show that the mixture model analysis produces estimates of previous infection that are often substantially higher than the standard threshold analysis.


Author(s):  
Kayoko Shioda ◽  
Max SY Lau ◽  
Alicia NM Kraay ◽  
Kristin N Nelson ◽  
Aaron J Siegler ◽  
...  

AbstractBackgroundSerology tests can identify previous infections and facilitate estimation of the number of total infections. However, immunoglobulins targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported to wane below the detectable level of serological assays. We estimate the cumulative incidence of SARS-CoV-2 infection from serology studies, accounting for expected levels of antibody acquisition (seroconversion) and waning (seroreversion), and apply this framework using data from New York City (NYC) and Connecticut.MethodsWe estimated time from seroconversion to seroreversion and infection fatality ratio (IFR) using mortality data from March-October 2020 and population-level cross-sectional seroprevalence data from April-August 2020 in NYC and Connecticut. We then estimated the daily seroprevalence and cumulative incidence of SARS-CoV-2 infection.FindingsThe estimated average time from seroconversion to seroreversion was 3-4 months. The estimated IFR was 1.1% (95% credible interval: 1.0-1.2%) in NYC and 1.4% (1.1-1.7%) in Connecticut. The estimated daily seroprevalence declined after a peak in the spring. The estimated cumulative incidence reached 26.8% (24.2-29.7%) and 8.8% (7.1-11.3%) at the end of September in NYC and Connecticut, higher than maximum seroprevalence measures (22.1% and 6.1%), respectively.InterpretationThe cumulative incidence of SARS-CoV-2 infection is underestimated using cross-sectional serology data without adjustment for waning antibodies. Our approach can help quantify the magnitude of underestimation and adjust estimates for waning antibodies.FundingThis study was supported by the US National Science Foundation and the National Institute of Allergy and Infectious Diseases.


2021 ◽  
Vol 10 (11) ◽  
pp. 2392
Author(s):  
Andrei R. Akhmetzhanov ◽  
Kenji Mizumoto ◽  
Sung-Mok Jung ◽  
Natalie M. Linton ◽  
Ryosuke Omori ◽  
...  

Following the first report of the coronavirus disease 2019 (COVID-19) in Sapporo city, Hokkaido Prefecture, Japan, on 14 February 2020, a surge of cases was observed in Hokkaido during February and March. As of 6 March, 90 cases were diagnosed in Hokkaido. Unfortunately, many infected persons may not have been recognized due to having mild or no symptoms during the initial months of the outbreak. We therefore aimed to predict the actual number of COVID-19 cases in (i) Hokkaido Prefecture and (ii) Sapporo city using data on cases diagnosed outside these areas. Two statistical frameworks involving a balance equation and an extrapolated linear regression model with a negative binomial link were used for deriving both estimates, respectively. The estimated cumulative incidence in Hokkaido as of 27 February was 2,297 cases (95% confidence interval (CI): 382–7091) based on data on travelers outbound from Hokkaido. The cumulative incidence in Sapporo city as of 28 February was estimated at 2233 cases (95% CI: 0–4893) based on the count of confirmed cases within Hokkaido. Both approaches resulted in similar estimates, indicating a higher incidence of infections in Hokkaido than were detected by the surveillance system. This quantification of the gap between detected and estimated cases helped to inform the public health response at the beginning of the pandemic and provided insight into the possible scope of undetected transmission for future assessments.


1988 ◽  
Vol 101 (2) ◽  
pp. 405-410 ◽  
Author(s):  
R. C. H Lau

SUMMARYEnzyme-linked immunosorbent assay (ELISA) tests were used to measure IgG antibody levels in 2638 New Zealand children who had been immunized with the triple vaccine DTP. The percentage of children immune to diphtheria decreased with age. The percentage of children immune to tetanus varied from 67.1 to 55.0%. The percentage of children with measurable antibody to pertussis increased with age. The mean percentages of children with measurable antibody or immunity to one or more DTP components were 34.2% (with 3 components), 34.4% (2 components), and 78.1% (1 component). It appears the immunization strategy for diphtheria and tetanus is satisfactory for herd immunity in New Zealand children. However, the current pertussis strategy may not be providing adequate immunity to 5-year-olds in this country.


2021 ◽  
Author(s):  
Massimo La Raja ◽  
Monia Pacenti ◽  
Ileana Grimaldi ◽  
Caterina Boldrin ◽  
Margherita Cattai ◽  
...  

From April 2020 through May 2021 in Padova Province 3395 COVID-19 recovered patients were recruited as potential convalescent plasma donors and tested for SARS-CoV-2 antibodies. Since January 2021 COVID-19 vaccination campaign began in Italy, the impact of vaccination on antibody levels and suspect vaccine breakthrough infections in these subjects were investigated. Post-vaccination anti-Sars-Cov-2 antibody level in 54 previously infected subjects had an exponential increase compared to pre-vaccination level regardless of the number of vaccine doses. However after 100 days from vaccination SARS-CoV-2 antibody level tends to decline. Post-vaccination primary infections were detected in 15 cases, with 3 possible breakthrough infections after a full vaccination course. In these cases, antibody response after infection was present but weaker than the one of subjects vaccinated after natural infection. A trend toward stronger antibody response was observed with increasing distance between natural infection and vaccination. Additionally, 2 cases of asymptomatic reinfections are also discussed.


2020 ◽  
Vol 39 (20) ◽  
pp. 2606-2620
Author(s):  
Cristina Boschini ◽  
Klaus K. Andersen ◽  
Hélène Jacqmin‐Gadda ◽  
Pierre Joly ◽  
Thomas H. Scheike

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S611-S612
Author(s):  
Nilson Nogueira Mendes Neto ◽  
Jessika T da S. Maia ◽  
Marcelo Zacarkim ◽  
Igor T Queiroz ◽  
Gleyson Rosa ◽  
...  

Abstract Background Infant mortality in Brazil has increased for the first time in 26 years. This study aimed to define the Zika Syndrome (ZS) perinatal case fatality rate (PCF) since the 2015 Zika outbreak in a Brazilian northeast state highly impacted by the virus. Methods Cross-sectional study conducted using data obtained through the State Health Department for cases of microcephaly (MCP) and congenital abnormalities (CA) in Rio Grande do Norte State (RN) from April 2015 to March 2, 2019. Perinatal period: commencing at 22 completed weeks (154 days) of gestation until 7 days after birth. PCF was defined as the number of deaths as a fraction of the number of sick persons with the specific disease (×100). Results There were 535 reported cases of MCP and others CA notified in RN during this period: 4 in 2014, 337 in 2015, 157 in 2016, 21 in 2017, 14 in 2018, and 2 in 2019. Of these, 151 were confirmed and 135 remain under investigation. The remaining 247 cases were ruled out by normal physical exams or due to noninfectious cause of MCP. Of the total confirmed cases, 35.8% (54/151) died after birth or during pregnancy. Zika virus infection during pregnancy was confirmed in 55.5% (30/54) of deaths and 1.8% (01/54) had a positive TORCH blood test. The odds ratio for the Zika PCF was found to be 1.57 (95% CI: 0.7940–3.1398; P = 0.1928). Deaths related to Zika were confirmed using a combination of clinical and epidemiological findings paired with either radiological information or molecular/serological data (RT–PCR and/or IgM/IgG antibodies against Zika). Twelve cases remain under investigation and 7 were ruled out as MCP. The highest number of confirmed MCP cases occurred between August 2015 and February 2016. The prevalence increased in September, with a peak in November 2015 (20.1 cases per 1,000 live births). Conclusion Before the recent Brazilian Zika outbreak, the incidence of MCP in RN between 2010 and 2014 was 1.8 cases/year. The real incidence and prevalence might be higher due to the underreporting and lack of resources for confirmatory diagnostic tests (laboratory and imaging). This study indicates that Zika virus accounted for a substantial proportion of MCP cases seen during the years studied, and suggests that ZS contributed to an increase in infant mortality in Brazil. Disclosures All authors: No reported disclosures.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2405-2405
Author(s):  
Heidi Tiller ◽  
Mette Kjaer Killie ◽  
Anne Husebekk ◽  
Bjorn Skogen ◽  
Heyu Ni ◽  
...  

Abstract Abstract 2405 Poster Board II-382 Background: When the mother develops antibodies against fetal platelets, fetal and neonatal alloimmune thrombocytopenia (FNAIT) can occur, with intracranial haemorrhage as the most severe complication. The frequency of FNAIT is reported to be 1:1,100 live births. The main immunogenic platelet alloantigen system in the Caucasian population is the human platelet antigen 1 (HPA1). The β3 integrin, housing the HPA1 antigen epitope on platelets, is also found on endothelial cells and invasive trophoblasts. It is therefore conceivable that maternal alloantibodies against the β3 integrin could have a direct effect on development and thereby function of the placenta. The aim of the study was to investigate whether the presence of maternal anti-HPA1a antibodies affects birth weight. Methods: We studied 74 term deliveries (≥ 37 gestational weeks) from HPA1a negative women in Norway during 1995-2008 where anti-HPA1a antibody status during pregnancy and corresponding birth weight were known. Most of the participants were selected from a prospective screening study of HPA1a negative pregnancies. Participants were also recruited from a registry in the National reference laboratory for clinical platelet immunology. The study was approved by the Regional Committee for Medical Research Ethics, North Norway. General data concerning the pregnancy and the neonate were \.{/MAIN;222}recorded. Specific data regarding maternal HPA1a immunization status included anti-HPA1a antibody levels measured during pregnancy and post partum. A linear mixed model was used to analyze the influence of maternal anti-HPA1a antibody level on the newborn birth weight. The dependent variable in the model was birth weight. Maternal age and parity, anti-HPA1a antibody level around 34 weeks of gestation, gestational age at time of delivery, sex of neonate and Apgar scores after 1 and 5 minutes were included as independent variables. All independent variables were classified as covariates with fixed effects. Since birth weights among siblings are not independent observations, the model treated each woman as one subject. Results: The mean birth weight was 3,050 grams when maternal anti-HPA1a antibodies were detected at any level or time during pregnancy (n= 47, 95% C.I. = 2952-3148). If no maternal anti-HPA1a antibodies were detected during pregnancy, the mean birth weight was 3,622 grams (n= 27, 95% C.I. = 3398-3845).We found a highly significant association between anti-HPA1a antibody levels around gestational week 34 and corresponding birth weight in the mixed model analysis, both when using antibody levels as a dichotomy variable (p = 0.006) and when dividing antibody levels into 3 intervals (no antibody detected, less than 3 IU/ml or more than 3 IU/ml, p = 0.011). Anti-HPA1a antibody level treated as a continuous variable was not significantly associated with birth weight (p = 0.057). Conclusions: We have demonstrated a significant correlation between the presence and level of maternal anti-HPA1a antibodies during pregnancy and neonatal birth weight. Our findings support the hypothesis that HPA1a alloimmunization affects more than just neonatal platelet counts, and should be considered even a placental disorder. Disclosures: No relevant conflicts of interest to declare.


1968 ◽  
Vol 128 (5) ◽  
pp. 1081-1098 ◽  
Author(s):  
Burton A. Dudding ◽  
Elia M. Ayoub

Antibody levels to streptococcal Group A and A-variant carbohydrates were determined using a radioactive immune precipitation technique on patients with rheumatic fever, with and without valvular disease, on patients with post-streptococcal acute glomerulonephritis, and on age-matched controls. During the acute phase of the above illness, the means of the antibody levels to both carbohydrate antigens were equally elevated and were significantly higher than the normal controls. When Group A antibody levels were determined on sera obtained at intervals of 5–12 months and 1–5 yr after the acute illness) it was found that the antibody levels declined within the normal range at the 5–12 month interval in patients with glomerulonephritis as well as in patients with rheumatic fever in whom no valvular involvement had complicated the disease, i.e., patients with pure Sydenham's chorea. However, in patients with rheumatic valvulitis, who had been on penicillin prophylaxis after the last acute episode, the A antibody level showed little decline from the level obtained during the acute illness. The elevated antibody level in patients with rheumatic valvulitis, including patients with Sydenham's chorea with valvulitis, persisted for periods of at least 1 yr and up to 20 yr after the last acute attack. The pattern of the decline of the antibody levels to the A-variant carbohydrate as well as of the antibody titers to the other streptococcal antigens tested, ASO and anti-DNase B, was similar in all patients studied regardless of the presence of valvular disease. These findings suggest that prolonged persistence of the Group A antibody is a phenomenon peculiar to patients with rheumatic valvular disease. Whether this persistence is involved in the pathogenesis or is an outcome of the valvular disease remains to be determined.


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