BACKGROUND: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had a devastating impact on the global population, with an estimated 650 million people infected and more than 6.6 million lives lost. Asymptomatic individuals have been shown to play a significant role in the transmission of the virus. Therefore, this study aims to investigate and compare the prevalence of asymptomatic individuals across three waves associated with the Beta, Delta, and Omicron variants of the virus.
METHODS: This retrospective study was conducted between December 2020 and March 2022. The study population consisted of passengers on international flights who were referred to the Gerash Clinical and Molecular Diagnosis Laboratory. Real-time PCR was employed for the diagnosis of SARS-CoV-2.
RESULTS: Out of a total of 8592 foreign travelers referred to our laboratory, 139 (1.16 %) tested positive for SARS-CoV-2 infection and were asymptomatic. During the Beta surge, 35 (1.49 %) out of 2335 passengers tested positive for SARS-CoV-2. In the Delta surge, 31 (0.6 %) out of 5127 passengers tested positive. However, during the Omicron surge, a significantly higher number of passengers, specifically 73 (6.46 %) out of 1130, had a positive result for the SARS-CoV-2 test.
CONCLUSIONS: Considering the significant role of asymptomatic transmission in the spread of COVID-19, it is imperative to reconsider health policies when dealing with future surges of the Omicron subvariants. Additionally, we strongly recommend that the World Health Organization prioritize the development and distribution of second-generation vaccines that target not only disease but also infection prevention.

BACKGROUND: Neutralizing antibodies (NAbs) are an important specific defence against viral infections, as these antibodies bind to specific receptor(s) and block the viral entry. NAbs assessments are therefore useful in determining individual or herd immunity to SARS-CoV-2. This study aims to deepen the investigation by assessing the positivity rate of neutralizing anti-spike antibodies to understand the real protection of the studied population against SARS-CoV-2.
METHODS: This study involved 260 plasma samples from a larger cohort of 2,700 asymptomatic volunteer donors, enrolled between August and October 2021 in health facilities of N\'Djamena. In this study four different kits and techniques including the pseudotype assay have been used and compared with detect the SARS-CoV-2 antibodies. Pseudotyped vesicular stomatitis virus (VSV), was used both the identify and measure the NAbs that to evaluate the performance of two cheaper and easy to use commercial kits, specific for the detection of receptor-binding domain antibodies (anti-RBD) against the SARS-CoV-2 spike protein.
RESULTS: The VSV spike neutralization assay showed that 59.0% (n = 59) samples were positive for NAbs with titers ranging from 1:10 to 1:4800. While 23 out the 41 negative NAbs samples were detected positive using anti-RBD (Abbott) test. Furthermore, a direct and significant strong correlation was found between NAbs and anti-RBD, specifically with Abbott kit. Taken together, the Roche and Abbott methods indicated agreement at the high concentrations of antibodies with the VSV-pseudovirus method. Abbott and Roche indicated a good sensitivity, but the Abbott system test appeared to have better specificity than the Roche test.
CONCLUSIONS: Our findings indicated a high presence of NAbs against SARS-CoV-2 spike protein among asymptomatic individuals in N\'Djamena. This could be one of the reasons for the low severity of Covid-19 observed in this area, given the key role of NAbs in blocking SARS-CoV-2 infection.

GNE myopathy is caused by bi allelic recessive mutations in the GNE gene. The largest identified cohort of GNE myopathy patients carries a homozygous mutation- M743T (the \"Middle Eastern\" mutation). More than 160 such patients in 67 families have been identified by us. Mean onset in this cohort is 30 years (range 17-48) with variable disease severity. However, we have identified two asymptomatic females, homozygous for M743T in two different families, both with affected siblings. The first showed no myopathy when examined at age 76 years. The second has no sign of disease at age 60 years. Since both agreed only for testing of blood, we performed exome and RNA sequencing of their blood and that of their affected siblings. Various filtering layers resulted in 2723 variant loci between symptomatic and asymptomatic individuals, representing 1364 genes. Among those, 39 genes are known to be involved in neuromuscular diseases, and only in two of them the variant is located in the proper exon coding region, resulting in a missense change. Surprisingly, only 27 genes were significantly differentially expressed between the asymptomatic and the GNE myopathy affected individuals, with three overexpressed genes overlapping between exome and RNA sequencing. Although unable to unravel robust candidate genes, mostly because of the very low number of asymptomatic individuals analyzed, and because of the tissue analyzed (blood and not muscle), this study resulted in relatively restricted potential candidate protective genes, emphasizing the power of using polarized phenotypes (completely asymptomatic vs clearly affected individuals) with the same genotype to unmask those genes which could be used as targets for disease course modifiers.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: Grifols.

OBJECTIVE: 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.
CONCLUSIONS: 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.

We present an epidemiological model, which extend the classical SEIR model by accounting for the presence of asymptomatic individuals and the effect of isolation of infected individuals based on testing. Moreover, we introduce two types of home quarantine, namely gradual and abrupt one. We compute the equilibria of the new model and derive its reproduction number. Using numerical simulations we analyze the effect of quarantine and testing on the epidemic dynamic. Given a constraint that limits the maximal number of simultaneous active cases, we demonstrate that the isolation rate, which enforces this constraint, decreases with the increasing testing rate. Our simulations show that massive testing allows to control the infection spread using a much lower isolation rate than in the case of indiscriminate quarantining. Finally, based on the effective reproduction number we suggest a strategy to manage the epidemic. It consists in introducing abrupt quarantine as well as relaxing the quarantine in such a way that the epidemic remains under control and further waves do not occur. We analyze the sensitivity of the model dynamic to the quarantine size, timing and strength of the restrictions.

We aimed to describe the relationships between the relative fat fraction (%FF), muscle-normalized diffusion-weighted (DW) image signal intensity and water apparent diffusion coefficient (ADC), sex and age for normal bone marrow, in the normal population. Our retrospective cohort consisted of 100 asymptomatic individuals, equally divided by sex and 10-year age groups, who underwent whole-body MRI at 1.5 T for early cancer detection. Semi-automated segmentation of global bone marrow volume was performed using the DW images and the resulting segmentation masks were projected onto the ADC and %FF maps for extraction of parameter values. Differences in the parameter values between sexes at age ranges were assessed using the Mann-Whitney and Kruskal-Wallis tests. The Spearman correlation coefficient r was used to assess the relationship of each imaging parameter with age, and of %FF with ADC and normalized DW signal intensity values. The average %FF of normal bone marrow was 65.6 ± 7.2%, while nSIb50, nSIb900 and ADC were 1.7 ± 0.5, 3.2 ± 0.9 and 422 ± 67 μm2/s, respectively. The bone marrow %FF values increased with age in both sexes (r = 0.63 and r = 0.64, respectively, p < 0.001). Values of nSIb50 and nSIb900 were higher in younger women compared to men of the same age groups (p < 0.017), but this difference decreased with age. In our cohort of asymptomatic individuals, the values of bone marrow relative %FF, normalized DW image signal intensity and ADC indicate higher cellularity in premenopausal women, with increasing bone marrow fat with aging in both sexes.

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.

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.