COVID-19 positive cases among asymptomatic individuals during the second wave in Ndola, Zambia.

Background: Coronavirus disease 2019 (COVID-19) is a worldwide public health concern for healthcare workers. About 80% of cases appear to be asymptomatic, and about 3% may experience hospitalisation and later die. Less than 20% of studies have looked at the positivity rate of asymptomatic individuals. Objective: This study investigated the COVID-19 positivity rates among asymptomatic individuals during the second COVID-19 wave at one of Zambia's largest testing centre. Methods: This was a retrospective cross-sectional study conducted on routine surveillance and laboratory data at the Tropical Diseases Research Centre COVID-19 laboratory in Ndola, Zambia, from 01 December 2020 to 31 March 2021. The study population was made up of persons that had tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as a requirement for travel. Microsoft Excel was used to come up with an epidemiological curve of daily COVID-19 positive cases; proportions for gender were described using frequencies and percentages. Results: A total of 11 144 asymptomatic individuals tested for SARS-CoV-2 were sampled for the study and 1781 (16.0%) returned positive results. The median age among those tested was 36 years (interquartile range: 29-46). Testing for COVID-19 peaked in the month of January 2021 (37.4%) and declined in March 2021 (21.0%). The epidemiological curve showed a combination of continuous and propagated point-source transmission. Conclusion: The positivity rate of 16.0% among asymptomatic individuals was high and could imply continued community transmission, especially during January 2021 and February 2021. We recommend heightened testing for SARS-CoV-2 among asymptomatic individuals. What this study adds: This study adds critical knowledge to the transmission of COVID-19 among asymptomatic travellers who are usually a key population in driving community infection. This knowledge is critical in instituting evidence-based interventions in the screening and management of travellers, and its control.

Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection: a double-blind, placebo-controlled, randomised clinical trial.

Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141. Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, -3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; -9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19. Funding: Grifols.

Diagnostic accuracy of SARS-CoV-2 rapid antigen self-tests in asymptomatic individuals in the omicron period: a cross-sectional study.

OBJECTIVES: To assess the performances of three commonly used antigen rapid diagnostic tests used as self-tests in asymptomatic individuals in the Omicron period. METHODS: We performed a cross-sectional diagnostic test accuracy study in the Omicron period in three public health service COVID-19 test sites in the Netherlands, including 3600 asymptomatic individuals aged ≥ 16 years presenting for SARS-CoV-2 testing for any reason except confirmatory testing after a positive self-test. Participants were sampled for RT-PCR (reference test) and received one self-test (either Acon Flowflex [Flowflex], MP Biomedicals (MPBio), or Siemens-Healthineers CLINITEST [CLINITEST]) to perform unsupervised at home. Diagnostic accuracies of each self-test were calculated. RESULTS: Overall sensitivities were 27.5% (95% CI, 21.3-34.3%) for Flowflex, 20.9% (13.9-29.4%) for MPBio, and 25.6% (19.1-33.1%) for CLINITEST. After applying a viral load cut-off (≥5.2 log10 SARS-CoV-2 E-gene copies/mL), sensitivities increased to 48.3% (37.6-59.2%), 37.8% (22.5-55.2%), and 40.0% (29.5-51.2%), respectively. Specificities were >99% for all tests in most analyses. DISCUSSION: The sensitivities of three commonly used SARS-CoV-2 antigen rapid diagnostic tests when used as self-tests in asymptomatic individuals in the Omicron period were very low. Antigen rapid diagnostic test self-testing in asymptomatic individuals may only detect a minority of infections at that point in time. Repeated self-testing in case of a negative self-test is advocated to improve the diagnostic yield, and individuals should be advised to re-test when symptoms develop.

The impact of asymptomatic individuals on the strength of public health interventions to prevent the second outbreak of COVID-19.

The pandemic of coronavirus disease 2019 (COVID-19) has threatened the social and economic structure all around the world. Generally, COVID-19 has three possible transmission routes, including pre-symptomatic, symptomatic and asymptomatic transmission, among which the last one has brought a severe challenge for the containment of the disease. One core scientific question is to understand the influence of asymptomatic individuals and of the strength of control measures on the evolution of the disease, particularly on a second outbreak of the disease. To explore these issues, we proposed a novel compartmental model that takes the infection of asymptomatic individuals into account. We get the relationship between asymptomatic individuals and critical strength of control measures theoretically. Furthermore, we verify the reliability of our model and the accuracy of the theoretical analysis by using the real confirmed cases of COVID-19 contamination. Our results, showing the importance of the asymptomatic population on the control measures, would provide useful theoretical reference to the policymakers and fuel future studies of COVID-19.

IFCC interim guidelines on rapid point-of-care antigen testing for SARS-CoV-2 detection in asymptomatic and symptomatic individuals.

With an almost unremittent progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections all around the world, there is a compelling need to introduce rapid, reliable, and high-throughput testing to allow appropriate clinical management and/or timely isolation of infected individuals. Although nucleic acid amplification testing (NAAT) remains the gold standard for detecting and theoretically quantifying SARS-CoV-2 mRNA in various specimen types, antigen assays may be considered a suitable alternative, under specific circumstances. Rapid antigen tests are meant to detect viral antigen proteins in biological specimens (e.g. nasal, nasopharyngeal, saliva), to indicate current SARS-CoV-2 infection. The available assay methodology includes rapid chromatographic immunoassays, used at the point-of-care, which carries some advantages and drawbacks compared to more conventional, instrumentation-based, laboratory immunoassays. Therefore, this document by the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC) Taskforce on COVID-19 aims to summarize available data on the performance of currently available SARS-CoV-2 antigen rapid detection tests (Ag-RDTs), providing interim guidance on clinical indications and target populations, assay selection, and evaluation, test interpretation and limitations, as well as on pre-analytical considerations. This document is hence mainly aimed to assist laboratory and regulated health professionals in selecting, validating, and implementing regulatory approved Ag-RDTs.

Estimating asymptomatic SARS-CoV-2 infections in a geographic area of low disease incidence.

BACKGROUND: The SARS-CoV-2 infection has emerged as a rapidly spreading infection. Today it is relatively easy to isolate Covid-19 symptomatic cases, while remains problematic to control the disease spread by infected but symptom-free individuals. The control of this possible path of contagion requires drastic measures of social distancing, which imply the suspension of most activities and generate economic and social issues. This study is aimed at estimating the percentage of asymptomatic SARS-CoV-2 infection in a geographic area with relatively low incidence of Covid-19. METHODS: Blood serum samples from 388 healthy volunteers were analyzed for the presence of anti-SARS-CoV-2 IgG by using an ELISA assay based on recombinant viral nucleocapsid protein. RESULTS: We found that 7 out of 388 healthy volunteers, who declared no symptoms of Covid-19, like fever, cough, fatigue etc., in the preceding 5 months, have bona fide serum anti-SARS-CoV-2 IgG, that is 1.8% of the asymptomatic population (95% confidence interval: 0.69-2.91%). CONCLUSIONS: The estimated range of asymptomatic individuals with anti-SARS-CoV-2 IgG should be between 26,565 and 112, 350. In the same geographic area, there are 4665 symptomatic diagnosed cases.

An algorithm for the robust estimation of the COVID-19 pandemic's population by considering undetected individuals.

Due to the current COVID-19 pandemic, much effort has been put on studying the spread of infectious diseases to propose more adequate health politics. The most effective surveillance system consists of doing massive tests. Nonetheless, many countries cannot afford this class of health campaigns due to limited resources. Thus, a transmission model is a viable alternative to study the dynamics of the pandemic. The most used are the Susceptible, Infected and Removed type models (SIR). In this study, we tackle the population estimation problem of the A-SIR model, which takes into account asymptomatic or undetected individuals. By means of an algebraic differential approach, we design a model-free (no copy system) reduced-order estimation algorithm (observer) to determine the different non-measured population groups. We study two types of estimation algorithms: Proportional and Proportional-Integral. Both shown fast convergence speed, as well as a minimal estimation error. Additionally, we introduce random fluctuations in our analysis to represent changes in the external conditions and which result in poor measurements. The numerical results reveal that both model-free estimators are robust despite the presence of these fluctuations. As a point of reference, we apply the classical Luenberger type observer to our estimation problem and compare the results. Finally, we consider real data of infected individuals in Mexico City, reported from February 2020 to March 2021, and estimate the non-measured populations. Our work's main goal is to proportionate a simple and therefore, an accessible methodology to estimate the behavior of the COVID-19 pandemic from the available data, such that the competent authorities can propose more adequate health politics.

A mathematical model for COVID-19 pandemic-SIIR model: Effects of asymptomatic individuals.

A new mathematical model called SIIR model is constructed to describe the spread of infection by taking account of the characteristics of COVID-19 and is verified by the data from Japan. The following features of COVID-19: (a) there exist presymptomatic individuals who have infectivity even during the incubation period, (b) there exist asymptomatic individuals who can freely move around and play crucial roles in the spread of infection, and (c) the duration of immunity may be finite, are incorporated into the SIIR model. The SIIR model has the advantage of being able to explicitly handle asymptomatic individuals who are delayed in discovery or are extremely difficult to be discovered in the real world. It is shown that the conditions for herd immunity in the SIIR model become more severe than those in the SIR model; that is, the presence of asymptomatic individuals increases herd immunity threshold (HIT).