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Background: The metabolomic profiles of individuals with different clinical manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have not been clearly characterized., Methods: We performed metabolomics analysis of 166 individuals, including 62 healthy controls, 16 individuals with asymptomatic SARS-CoV-2 infection, and 88 patients with moderate (n = 42) and severe (n = 46) symptomatic 2019 coronavirus disease (COVID-19; 17 with short-term and 34 with long-term nucleic-acid test positivity). By examining differential expression, we identified candidate metabolites associated with different SARS-CoV-2 infection presentations. Functional and machine learning analyses were performed to explore the metabolites' functions and verify their candidacy as biomarkers., Results: A total of 417 metabolites were detected. We discovered 70 differentially expressed metabolites that may help differentiate asymptomatic infections from healthy controls and COVID-19 patients with different disease severity. Cyclamic acid and N-Acetylneuraminic Acid were identified to distinguish symptomatic infected patients and asymptomatic infected patients. Shikimic Acid, Glycyrrhetinic acid and 3-Hydroxybutyrate can supply significant insights for distinguishing short-term and long-term nucleic-acid test positivity., Conclusion: Metabolomic profiling may highlight novel biomarkers for the identification of individuals with asymptomatic SARS-CoV-2 infection and further our understanding of the molecular pathogenesis of COVID-19., (© 2024. The Author(s).)

To elucidate the seroprevalence and rate of asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Japanese children, serological analysis was performed using serum samples collected from March 2020 to February 2023. A total of 1493 serum samples were collected during the first study period (March 2020 to February 2021). None of the serum samples was positive for SARS-CoV-2 antibody. In the second period (March 2021 to February 2022), seven of the 1055 patients (0.7%) experienced SARS-CoV-2 infection. The third period (March 2022 to February 2023) was divided into three terms: from March to June 30, 2022; from July to October 2022; and from November 2022 to February 2023. The seroprevalence gradually increased throughout this period, with rates of 6.0%, 18.6%, and 30.4% in the three terms, respectively. Pediatric cases of asymptomatic SARS-CoV-2 infection occurred after the surge of Omicron variants. Since none of the SARS-CoV-2 antibody-positive patients had a previous history of coronavirus disease 2019, the seroprevalence rate in this study may represent the rate of asymptomatic infection., (© 2024 Wiley Periodicals LLC.)

Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified., Competing Interests: Declaration of interests E.T.C., K.M.S.B., and A.B. are employees of Helix., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Since the beginning of the pandemic, children's role in the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been debated. We aimed to describe the prevalence of SARS-CoV-2 in asymptomatic children undergoing institutional systematic screening., Methods: From 2020 to 2021, this retrospective study in a French university hospital included consecutive asymptomatic children routinely screened for SARS-CoV-2 infection by polymerase chain reaction (PCR) assay before surgery., Results: Among the 816 test samples, the prevalence of positive PCR results was 0.49 % (95 % CI: 0.01-0.97, n = 4); half of the cases involved close contacts with an adult case., Conclusion: These results support the low prevalence of SARS-CoV-2 in asymptomatic children during the first pandemic periods in France., Competing Interests: Declaration of Competing Interest CGL received travel grants from Pfizer in 2018. For the remaining authors, no conflicts were declared., (Copyright © 2023. Published by Elsevier Masson SAS.)

Aim: The aim of this study is to evaluate the incidence of SARS-CoV-2 infection and the prevalence of COVID-19-related symptoms in relation to pandemic phases and some relevant variables in a cohort of 8,029 HCWs from one of the largest Italian University Hospitals., Methods: A single-center retrospective study was performed on data collected during SARS-CoV-2 infection surveillance of HCWs. Cox's multiple regression was performed to estimate hazard ratios of SARS-CoV-2 infection. Logistic multivariate regression was used to assess the risk of asymptomatic infections and the onset of the most frequent symptoms. All analyses were adjusted for sociodemographic and occupational factors, pandemic phases, vaccination status, and previous infections., Results: A total of 3,760 HCWs resulted positive (2.0%-18.6% across five study phases). The total incidence rate of SARS-CoV-2 infection was 7.31 cases per 10,000 person-days, significantly lower in phase 1 and higher in phases 4 and 5, compared to phase 3. Younger HCWs, healthcare personnel, and unvaccinated subjects showed a higher risk of infection. Overall, 24.5% were asymptomatic infections, with a higher probability for men, physicians, and HCWs tested for screening, fully vaccinated, and those with previous infection. The clinical presentation changed over the phases in relation to vaccination status and the emergence of new variants., Conclusion: The screening activities of HCWs allowed for the early detection of asymptomatic cases, limiting the epidemic clusters inside the hospital wards. SARS-CoV-2 vaccination reduced infections and symptomatic cases, demonstrating again its paramount value as a preventive tool for occupational and public health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liviero, Volpin, Furlan, Battistella, Broggio, Fabris, Favretto, Mason, Cocchio, Cozzolino, Baldo, Moretto and Scapellato.)

Objectives: Asymptomatic infections and mild diseases were more common during the Omicron outbreak in Shanghai, China in 2022. This study aimed to assess the characteristics and viral RNA decay between patients with asymptomatic and mild infections., Methods: A total of 55,111 patients infected with SARS-CoV-2 who were quarantined in the National Exhibition & Convention Center (Shanghai) Fangcang shelter hospital within 3 days after diagnosis from April 9 to May 23, 2022 were enrolled. The kinetics of cycle threshold (Ct) values of reverse transcription-polymerase chain reaction were assessed. The influencing factors for disease progression and the risk factors for the viral RNA shedding time (VST) were investigated., Results: On admission, 79.6% (43,852/55,111) of the cases were diagnosed with asymptomatic infections, and 20.4% were mild diseases. However, 78.0% of initially asymptomatic subjects developed mild diseases at the follow-up. The final proportion of asymptomatic infections was 17.5%. The median time of symptom onset, the duration of symptoms, and the VST were 2 days, 5 days, and 7 days, respectively. Female, age 19-40 years, underlying comorbidities with hypertension and diabetes, and vaccination were associated with higher risks of progressing to mildly symptomatic infections. In addition, mildly symptomatic infections were found to be associated with prolonged VST compared with asymptomatic infections. However, the kinetics of viral RNA decay and dynamics of Ct values were similar among asymptomatic subjects, patients with asymptomatic-to-mild infection, and patients with mild infection., Conclusion: A large proportion of initially diagnosed asymptomatic Omicron infections is in the presymptomatic stage. The Omicron infection has a much shorter incubation period and VST than previous variants. The infectivity of asymptomatic infections and mildly symptomatic infections with Omicron is similar., Competing Interests: Declaration of competing interests The authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Antibodies to SARS-CoV-2 are central to recovery and immunity from COVID-19. However, the relationship between disease severity and the repertoire of antibodies against specific SARS-CoV-2 epitopes an individual develops following exposure remains incompletely understood. Here, we studied seroprevalence of antibodies to specific SARS-CoV-2 and other betacoronavirus antigens in a well-annotated, community sample of convalescent and never-infected individuals obtained in August 2020. One hundred and twenty-four participants were classified into five groups: previously exposed but without evidence of infection, having no known exposure or evidence of infection, seroconverted without symptoms, previously diagnosed with symptomatic COVID-19, and recovered after hospitalization with COVID-19. Prevalence of IgGs specific to the following antigens was compared between the five groups: recombinant SARS-CoV-2 and betacoronavirus spike and nucleocapsid protein domains, peptides from a tiled array of 22-mers corresponding to the entire spike and nucleocapsid proteins, and peptides corresponding to predicted immunogenic regions from other proteins of SARS-CoV-2. Antibody abundance generally correlated positively with severity of prior illness. A number of specific immunogenic peptides and some that may be associated with milder illness or protection from symptomatic infection were identified. No convincing association was observed between antibodies to Receptor Binding Domain(s) (RBDs) of less pathogenic betacoronaviruses HKU1 or OC43 and COVID-19 severity. However, apparent cross-reaction with SARS-CoV RBD was evident and some predominantly asymptomatic individuals had antibodies to both MERS-CoV and SARS-CoV RBDs. Findings from this pilot study may inform development of diagnostics, vaccines, and therapeutic antibodies, and provide insight into viral pathogenic mechanisms.

From August 2021 to 7 March 2022, New York City prohibited indoor dining in restaurants selectively for persons who had not received a Coronavirus disease 2019 (COVID-19) vaccine. However, vaccinated persons may also be actively infected and potentially transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV‑2). Based on assuming a 7:1 ratio of COVID-19 cases in New York State for the unvaccinated versus the vaccinated, it can be estimated that when 87.5% of adults in New York City are vaccinated, the rate of unsuspected SARS-CoV‑2 infections (asymptomatic or minimally symptomatic) among vaccinated adults going to restaurants would be equivalent to that for the unvaccinated., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: As international travellers were the primary source of sever acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, border checkpoints became an important tool to isolate cases. We determined the period prevalence and SARS-CoV-2 reverse transcription polymerase chain reaction positivity in relation to clinical and demographic characteristics in healthy travellers quarantined at the Pakistan-Afghanistan border., Methods: The study was conducted from 15 to 25 April 2020. Period prevalence was calculated and the association between positivity and individuals' age, sex and occupation were assessed using χ2 and Mantel-Haenszel tests. Logistic regression was used to calculate adjusted odds ratios (ORs) for each age group. Time-to-event (TTE) analysis was conducted to check the difference in positivity among various groups., Results: In a total of 708 individuals, 71 tested positive (10%). Compared with those ≤20 y of age, the sex- and occupation-adjusted odds of testing positive were less among the older age group (41-60 y; OR 0.26, p=0.008). Taxi drivers had higher odds of testing positive (OR 4.08, p<0.001). Kaplan-Meier curves and hazard ratios (0.32, p<0.01) showed that the positivity period differed significantly across the pre-symptomatic vs asymptomatic group (26 vs 14 d)., Conclusions: The cases who were likely to acquire infection through occupational exposure largely remained asymptomatic. For effective control of transmission and the emergence of new variants, testing capacities should be revamped with effective isolation measures., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

The cell-mediated protective and pathogenic immune responses to SARS-CoV-2 infection remain largely elusive. Here we identified 76 distinct cell subsets in the PBMC samples that were associated with various clinical presentations of COVID-19 using scRNA-seq technology coupled with a deep and comprehensive analysis of unique cell surface markers and differentially expressed genes. We revealed that (TRAV1-2 + CD8 + )MAIT cells and (NCAM1 hi CD160 + )NK cells significantly enriched in the asymptomatic subjects whereas (LAG3 + CD160 + CD8 + )NKT cells increased in the symptomatic patients. We also observed that (CD68 - CSF1R - IL1B hi CD14 + )classical monocytes were positively correlated with the disease severity. Moreover, (CD33 - HLA-DMA - CD14 + )classical monocytes and (CLEC10A - S100A9 lo )pDC were associated with the viral persistence. The GO and KEGG analyses identified enriched pathways related to immune responses, inflammation, and apoptosis. These findings may enhance our understanding of the immunopathogenesis of COVID-19 and help develop novel strategies against SARS-CoV-2 infection., Competing Interests: The authors TJ, WM, YL, TH, CF, and CG are employed by the LC-BIO TECHNOLOGIES (HANGZHOU) CO., LTD., China. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Bai, Ma, Qin, Zeng, Hu, Jiang, Mao, Zhao, Chen, Qi, Li, Xu, Hao, Wang, Ding, Liu, Huang, Fang, Ge, Li, Hu, Ren, Zhang, Zhang, Shi and Zhang.)

COVID-19 is a systemic infectious disease that may affect many organs, accompanied by a measurable metabolic dysregulation. The disease is also associated with significant mortality, particularly among the elderly, patients with comorbidities, and solid organ transplant recipients. Yet, the largest segment of the patient population is asymptomatic, and most other patients develop mild to moderate symptoms after SARS-CoV-2 infection. Here, we have used NMR metabolomics to characterize plasma samples from a cohort of the abovementioned group of COVID-19 patients (n = 69), between 3 and 10 months after diagnosis, and compared them with a set of reference samples from individuals never infected by the virus (n = 71). Our results indicate that half of the patient population show abnormal metabolism including porphyrin levels and altered lipoprotein profiles six months after the infection, while the other half show little molecular record of the disease. Remarkably, most of these patients are asymptomatic or mild COVID-19 patients, and we hypothesize that this is due to a metabolic reflection of the immune response stress., (© 2021 John Wiley & Sons, Ltd.)

As the emergence of new variants of SARS-CoV-2 persists across the world, it is of importance to understand the distributional behavior of the incubation period of the variants for both medical research and public health policy-making. We collected the published individual-level data of 941 patients of the 2020-2021 winter pandemic wave in Hebei province, North China. We computed some epidemiological characteristics of the wave and estimated the distribution of the incubation period. We further assessed the covariate effects of sex, age, and living with a case with respect to the incubation period by a model. The infection-fatality rate was only 0.1%. The estimated median incubation period was at least 22 days, significantly extended from the estimates (ranging from 4 to 8.5 days) of the previous wave in mainland China and those ever reported elsewhere around the world. The proportion of asymptomatic patients was 90.6%. No significant covariate effect was found. The distribution of incubation period of the new variants showed a clear extension from their early generations., (© 2021 Wiley Periodicals LLC.)

Aim: We evaluated the prevalence of paediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections using antibody testing and characterised antibody titres by time from exposure., Methods: This was a single-centre, prospective, cross-sectional cohort study. Patients under 18 years old were eligible to participate if they attended the paediatric emergency department at the tertiary Shaare Zedek Medical Center, Jerusalem, Israel, from 18 October 2020 to 12 January 2021 and required blood tests or intravenous access. SARS-CoV-2 seropositivity and antibody levels were tested by a dual-assay model., Results: The study comprised 1138 patients (56% male) with a mean age of 4.4 years (interquartile range 1.3-11.3). Anti-SARS-CoV-2 antibodies were found in 10% of the patients. Seropositivity increased with age and 41% of seropositive patients had no known exposure. Children under 6 years of age had higher initial antibody levels than older children, followed by a steeper decline. The seropositivity rate did not vary during the study, despite schools re-opening. The findings suggest that children's immunity may start falling 4 months after the initial infection., Conclusion: Immunity started falling after just 4 months, and re-opening schools did not affect infection rates. These findings could aid decisions about vaccinating paediatric populations and school closures., (©2021 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic, which has caused unprecedented damage to human health and life. The present study aimed to carry out and discover asymptomatic infected individuals in Shenzhen, China. The data will provide the control measures to stop COVID-19 prevalence. Methods: The study was a retrospective review of medical records from 462 confirmed patients with COVID-19 and 45 asymptomatic infected individuals in Shenzhen from January 19 to April 30, 2020; this is a retrospective, observational multicenter study. Results: A total of 462 confirmed cases were diagnosed in Shenzhen from January 19 to April 30, 2020. The cohort included 423 domestic cases (91.56%, 95% confidence interval [CI]: 88.67-93.76) and 39 (8.44%, 95% CI: 6.24-11.33) imported cases from other countries. Moreover, a total of 45 asymptomatic infections were found, encompassing 31 (68.89%, 95% CI: 54.34-80.47) local infections and 14 (31.11%, 95% CI: 19.53-45.66) individuals imported from other countries. The proportion of asymptomatic infected persons in Shenzhen is continuously increasing ( Z  = 13.19, p  < 0.0001). The total number of local asymptomatic infections was more than that in other provinces ( χ 2  = 118.83, p  < 0.0001). The proportion of asymptomatic infected individuals among cases imported from other countries was higher than the domestic cases ( χ 2 The proportion of asymptomatic infection is increasing. Hence, development and application of the diagnosis method with high sensitivity and specificity play a critical role in reducing COVID-19 global epidemics.p  < 0.0001, odds ratio = 4.90, 95% CI: 2.40-9.98). Conclusions: The proportion of asymptomatic infection is increasing. Hence, development and application of the diagnosis method with high sensitivity and specificity play a critical role in reducing COVID-19 global epidemics.

Background: Pregnant women and their neonates represent 2 vulnerable populations with an interdependent immune system that are highly susceptible to viral infections. The immune response of pregnant women to severe acute respiratory syndrome coronavirus 2 and the interplay of how the maternal immune response affects the neonatal passive immunity have not been studied systematically., Objective: We characterized the serologic response in pregnant women and studied how this serologic response correlates with the maternal clinical presentation and with the rate and level of passive immunity that the neonate received from the mother., Study Design: Women who gave birth and who tested positive for immunoglobulin M or immunoglobulin G against severe acute respiratory syndrome coronavirus 2 using semiquantitative detection in a New York City hospital between March 22, 2020, and May 31, 2020, were included in this study. A retrospective chart review of the cases that met the inclusion criteria was conducted to determine the presence of coronavirus disease 2019 symptoms and the use of oxygen support. Serology levels were compared between the symptomatic and asymptomatic patients using a Welch 2 sample t test. Further chart review of the same patient cohort was conducted to identify the dates of self-reported onset of coronavirus disease 2019 symptoms and the timing of the peak immunoglobulin M and immunoglobulin G antibody levels after symptom onset was visualized using local polynomial regression smoothing on log 2 -scaled serologic values. To study the neonatal serology response, umbilical cord blood samples of the neonates born to the subset of serology positive pregnant women were tested for serologic antibody responses. The maternal antibody levels of serology positive vs the maternal antibody levels of serology negative neonates were compared using the Welch 2 sample t test. The relationship between the quantitative maternal and quantitative neonatal serologic data was studied using a Pearson correlation and linear regression. A multiple linear regression analysis was conducted using maternal symptoms, maternal serology levels, and maternal use of oxygen support to determine the predictors of neonatal immunoglobulin G levels., Results: A total of 88 serology positive pregnant women were included in this study. The antibody levels were higher in symptomatic pregnant women than in asymptomatic pregnant women. Serology studies in 34 women with symptom onset data revealed that the maternal immunoglobulin M and immunoglobulin G levels peak around 15 and 30 days after the onset of coronavirus disease 2019 symptoms, respectively. Furthermore, studies of 50 neonates born to this subset of serology positive women showed that passive immunity in the form of immunoglobulin G is conferred in 78% of all neonates. The presence of passive immunity is dependent on the maternal antibody levels, and the levels of neonatal immunoglobulin G correlate with maternal immunoglobulin G levels. The maternal immunoglobulin G levels and maternal use of oxygen support were predictive of the neonatal immunoglobulin G levels., Conclusion: We demonstrated that maternal serologies correlate with symptomatic maternal infection, and higher levels of maternal antibodies are associated with passive neonatal immunity. The maternal immunoglobulin G levels and maternal use of oxygen support, a marker of disease severity, predicted the neonatal immunoglobulin G levels. These data will further guide the screening for this uniquely linked population of mothers and their neonates and can aid in developing maternal vaccination strategies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Currently, the novel coronavirus pneumonia has been widespread globally, and there is no specific medicine. In response to the emergency, we employed bioinformatics methods to investigate the virus's pathogenic mechanism, finding possible control methods. We speculated in previous studies that E protein was associated with viral infectivity. The present study adopted the domain search techniques to analyse the E protein. According to the results, the E protein could bind iron or haem. The iron and haem bound by the E protein came from the attacked haemoglobin and phagocytes. When E protein was attached to haem, it synthesised oxygen and water into superoxide anions, hydrogen peroxide and hydroxyl radicals. When the iron-bound E protein and the haem-bound E protein worked together, they converted superoxide anions and hydrogen peroxide into oxygen and water. These were the "ROS attack" and "ROS escape" of the virus. "ROS attack" damaged the tissues or cells exposed on the surface of the virus, and "ROS escape" decomposed the superoxide anion and hydrogen peroxide that attacked the virus. When NK cells were exposed to infected cells, viruses that had not shed from the infected cells' surface damaged them through "ROS attack". In addition, lymphocytes such as T cells and B cells, which could be close to the antigen of the virus surface, were also easily damaged or killed by the "ROS attack", generating a decrease in lymphocytes. When memory B cells were exposed to the virus's surface antigen, they were also damaged by "ROS attack", resulting in the patient's re-infection. The virus applied the "ROS escape" to decompose hydrogen peroxide released by phagocytes into oxygen and water. The surrounding cells were replenished with oxygen, and the patient was in a "happy hypoxia" state. When the phagocytes swallowed the virus, the E protein converted superoxide anions into oxygen and water. In this way, the virus parasitized in the vesicles of the phagocyte. While virus was in the lysosome, the E protein generated ROS to damage nearby hydrolases. In this way, the virus parasitized the lysosome. Excessive hydroxyl free radicals destroyed the membrane structure of the lysosome, causing the hydrolase release from lysosome, autophagy of phagocytic cells and subsequent cell death. As a result, the colonizing phagocytes of the virus was associated with asymptomatic infection or retest-positive. Briefly, the virus inhibited the immune system through "ROS escape", and damaged the immune system by "ROS attack". The destruction instigated a strong cytokine storm, leading to organ failure and complications.

During infectious disease epidemics, an important question is whether cases travelling to new locations will trigger local outbreaks. The risk of this occurring depends on the transmissibility of the pathogen, the susceptibility of the host population and, crucially, the effectiveness of surveillance in detecting cases and preventing onward spread. For many pathogens, transmission from pre-symptomatic and/or asymptomatic (together referred to as non-symptomatic) infectious hosts can occur, making effective surveillance challenging. Here, by using SARS-CoV-2 as a case study, we show how the risk of local outbreaks can be assessed when non-symptomatic transmission can occur. We construct a branching process model that includes non-symptomatic transmission and explore the effects of interventions targeting non-symptomatic or symptomatic hosts when surveillance resources are limited. We consider whether the greatest reductions in local outbreak risks are achieved by increasing surveillance and control targeting non-symptomatic or symptomatic cases, or a combination of both. We find that seeking to increase surveillance of symptomatic hosts alone is typically not the optimal strategy for reducing outbreak risks. Adopting a strategy that combines an enhancement of surveillance of symptomatic cases with efforts to find and isolate non-symptomatic infected hosts leads to the largest reduction in the probability that imported cases will initiate a local outbreak.

Most patients with coronavirus disease 2019 (COVID-19) experience asymptomatic disease or mild symptoms, but some have critical symptoms requiring intensive care. It is important to determine how patients with asymptomatic or mild COVID-19 react to severe acute respiratory syndrome coronavirus 2 infection and suppress virus spread. Innate immunity is important for evasion from the first virus attack, and it may play an important role in the pathogenesis in these patients. We measured serum cytokine levels in 95 patients with COVID-19 during the infection's acute phase and report that significantly higher interleukin 12 and 2 levels were induced in patients with asymptomatic or mild disease than in those with moderate or severe disease, indicating the key roles of these cytokines in the pathogenesis of asymptomatic or mild COVID-19., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Objectives: We aimed to compare the prevalence of asymptomatic coronavirus disease 19 (COVID-19) among clinical staff in designated COVID-19 units versus that among staff in similar units with no known or suspected COVID-19 patients., Methods: We conducted a cross-sectional survey of healthcare workers (HCWs) in eight Israeli general hospitals. The survey involved a questionnaire and a PCR test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We surveyed HCWs in COVID-19 units and comparison units (internal medicine and cardiology) between 30th April and 7th May 2020., Results: There were 522 participants: 291 from COVID-19 units and 231 from comparison units. Only one participant (0.2%, 95%CI: 0.005-1.1%)-an asymptomatic nurse on a COVID-19 unit-tested positive for SARS-CoV-2. In participating COVID-19 units there were two symptomatic HCWs with confirmed COVID-19 in the 2 weeks before the survey; both were infected by contact with a co-worker outside of the COVID-19 unit., Conclusions: The low prevalence of asymptomatic COVID-19 among HCWs, coupled with an absence of symptomatic COVID-19 acquired during patient care, suggest that Israel's national guidelines for personal protective equipment, which are consistent with those of the World Health Organization, adequately protect HCWs., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The clinical course and viral detection period in mild or asymptomatic coronavirus disease 2019 (COVID-19) patients are not yet known. The presumed low diagnostic sensitivity of upper respiratory specimens for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) makes it difficult to confirm infection and recommend de-isolation., Methods: We retrospectively reviewed real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test results of mild or asymptomatic COVID-19 patients who were admitted at the Daegu-Gyeongbuk 7th community treatment centre in Korea between 9 March 2020 and 10 April 2020. Patients underwent an upper respiratory RT-PCR test every week until discharge. From the RT-PCR results, we evaluated the rate of prolonged (>3 weeks) SARS-CoV-2 RNA positivity. We analysed the proportion of reversed results, defined as a positive or indeterminate result one day after a negative RT-PCR result, according to time (<14, 15-21, 22-28, >28 days) from the initial positive RT-PCR result., Results: In 23% (69/300) of patients, SARS-CoV-2 was detected more than 3 weeks after the initial positive RT-PCR. In 14% (42/300) of patients, the RT-PCR results were positive for more than 4 weeks. For 37.5% (152/405) of negative RT-PCR results, the results were reversed in the next day's test. And 43.5% (123/283) of negative RT-PCR results were reversed within 3 weeks of diagnosis., Conclusions: The detection of SARS-CoV-2 lasting more than 3 weeks was common in mild or asymptomatic patients. Upper respiratory RT-PCR results were frequently reversed from negative to positive.

Purpose: We aimed to further clarify the epidemiological and clinical characteristics of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections., Methods: We identified close contacts of confirmed coronavirus disease 2019 (COVID-19) cases in northeast Chongqing, China, who were confirmed by real-time reverse transcription polymerase chain reaction-positive (RT-PCR+). We stratified this cohort by normal vs abnormal findings on chest computed tomography (CT) and compared the strata regarding comorbidities, demographics, laboratory findings, viral transmission and other factors., Results: Between January 2020 and March 2020, we identified and hospitalized 279 RT-PCR+ contacts of COVID-19 patients. 63 (23%) remained asymptomatic until discharge; 29 had abnormal and 34 had normal chest CT findings. The mean cohort age was 39.3 years, and 87.3% had no comorbidities. Mean time to diagnosis after close contact with a COVID-19 index patient was 16.0 days, and it was 13.4 days and 18.7 days for those with abnormal and normal CT findings, respectively (P < .05). Nine patients (14.3%) transmitted the virus to others; 4 and 5 were in the abnormal and normal CT strata, respectively. The median length of time for nucleic acid to turn negative was 13 days compared with 10.4 days in those with normal chest CT scans (P < .05)., Conclusions: A portion of asymptomatic individuals were capable of transmitting the virus to others. Given the frequency and potential infectiousness of asymptomatic infections, testing of traced contacts is essential. Studies of the impact of treatment of asymptomatic RT-PCR+ individuals on disease progression and transmission should be undertaken., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Abstract Background The metabolomic profiles of individuals with different clinical manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have not been clearly characterized. Methods We performed metabolomics analysis of 166 individuals, including 62 healthy controls, 16 individuals with asymptomatic SARS-CoV-2 infection, and 88 patients with moderate (n = 42) and severe (n = 46) symptomatic 2019 coronavirus disease (COVID-19; 17 with short-term and 34 with long-term nucleic-acid test positivity). By examining differential expression, we identified candidate metabolites associated with different SARS-CoV-2 infection presentations. Functional and machine learning analyses were performed to explore the metabolites’ functions and verify their candidacy as biomarkers. Results A total of 417 metabolites were detected. We discovered 70 differentially expressed metabolites that may help differentiate asymptomatic infections from healthy controls and COVID-19 patients with different disease severity. Cyclamic acid and N-Acetylneuraminic Acid were identified to distinguish symptomatic infected patients and asymptomatic infected patients. Shikimic Acid, Glycyrrhetinic acid and 3-Hydroxybutyrate can supply significant insights for distinguishing short-term and long-term nucleic-acid test positivity. Conclusion Metabolomic profiling may highlight novel biomarkers for the identification of individuals with asymptomatic SARS-CoV-2 infection and further our understanding of the molecular pathogenesis of COVID-19.

The transmission of respiratory pathogens, including SARS-CoV-2, is often facilitated through household contact. To better understand the transmission rate of COVID-19 among households and factors that affect viral clearance and seroconversion, a case-ascertained community-based prospective study was conducted between December 2020 and June 2021 on the urban population of the national capital region of India. The study collected nasopharyngeal swabs for SARS-CoV-2 RT-PCR on the 1st, 7th, 14th, and 28th day, and blood samples for antibody detection on the 1st, 14th, and 28th day from household contacts (HCs) of laboratory-confirmed COVID-19 cases. The study monitored the demographic data, symptoms, and outcomes of 417 participants, including 99 index cases and 318 contacts, for a period of 28 days. The results of the study showed that SARS-CoV-2 was easily spread within households, with a secondary infection rate of 44.3 %. In fact, almost 70 % of the contacts got infected within 1–2 days of identification of the index case, while 34 % remained asymptomatic. Sero-conversion was found in 35.6 % of the participants while 22.9 % did not produce antibodies after 28 days of infection. The study also revealed that females, spouses, older members, and primary care providers were at higher risk of getting infected in a home setting. However, approximately one-third of individuals in the younger age group managed to avoid infection. The study demonstrated that most infected individuals became RT-PCR negative within two weeks, although viral clearance was delayed in older patients and those with lower cycle threshold values in RT-PCR.

We examined the asymptomatic rates of SARS-CoV-2 infection during the Delta and Omicron waves in the city of São Paulo. Nasopharyngeal swabs were collected at strategic points of the city (open-air markets, bus terminals, airports) for SARS-CoV-2 RNA testing. Applying the questionnaire, the symptomatic individuals were excluded, and only asymptomatic cases were analyzed. During the Delta wave, a total of 4315 samples were collected, whereas 2372 samples were collected during the first Omicron wave. The incidence of the asymptomatic SARS-CoV-2 infection was 0.6% during the Delta wave and 0.8% during the Omicron wave. No statistical differences were found in the threshold amplification cycle. However, there was a statistical difference observed in the sublineage distribution between asymptomatic and symptomatic individuals. Our study determined the incidence of asymptomatic infection by monitoring individuals who remained symptom-free, thereby providing a reliable evaluation of asymptomatic SARS-CoV-2 carriage. Our findings reveal a relatively low proportion of asymptomatic cases, which could be attributed to our rigorous monitoring protocol for the presence of clinical symptoms. Investigating asymptomatic infection rates is crucial to develop and implement effective disease control strategies. [ABSTRACT FROM AUTHOR]

Background: Although COVID-19 vaccines and their booster regimens protect against symptomatic infections and severe outcomes, there is limited evidence about their protection against asymptomatic and symptomatic infections in real-world settings, particularly when considering that the majority of SARS-CoV-2 Omicron infections were asymptomatic. We aimed to assess the effectiveness of the booster dose of inactivated vaccines in mainland China, i.e., Sinopharm (BBIBP-CorV) and Sinovac (CoronaVac), against Omicron infection in an Omicron BA.5 seeded epidemic. Methods: Based on an infection-naive but highly vaccinated population in Urumqi, China, the study cohort comprised all 37,628 adults who had a contact history with individuals having SARS-CoV-2 infections, i.e., close contacts, between August 1 and September 7, 2022. To actively detect SARS-CoV-2 infections, RT-PCR tests were performed by local authorities on a daily basis for all close contacts, and a testing-positive status was considered a laboratory-confirmed outcome. The cohort of close contacts was matched at a ratio of 1:5 with the fully vaccinated (i.e., 2 doses) and booster vaccinated groups (i.e., 3 doses) according to sex, age strata, calendar date, and contact settings. Multivariate conditional logistic regression models were adopted to estimate the marginal effectiveness of the booster dose against Omicron BA.5 infection after adjusting for confounding variables. Subgroup analyses were performed to assess vaccine effectiveness (VE) in different strata of sex, age, the time lag from the last vaccine dose to exposure, and the vaccination status of the source case. Kaplan–Meier curves were employed to visualize the follow-up process and testing outcomes among different subgroups of the matched cohort. Findings: Before matching, 37,099 adult close contacts were eligible for cohort enrolment. After matching, the 2-dose and 3-dose groups included 3317 and 16,051 contacts, and the proportions with Omicron infections were 1.03% and 0.62% among contacts in the 2-dose and 3-dose groups, respectively. We estimated that the adjusted effectiveness of the inactivated booster vaccine versus 2 doses against Omicron infection was 35.5% (95% CI 2.0, 57.5). The booster dose provided a higher level of protection, with an effectiveness of 60.2% (95% CI 22.8, 79.5) for 15–180 days after vaccination, but this VE decreased to 35.0% (95% CI 2.8, 56.5) after 180 days. Evidence for the protection of the booster dose was detected among young adults aged 18–39 years, but was not detected for those aged 40 years or older. Interpretation: The receipt of the inactivated vaccine booster dose was associated with a significantly lower Omicron infection risk, and our findings confirmed the vaccine effectiveness (VE) of booster doses against Omicron BA.5 variants. Given the rapid evolution of SARS-CoV-2, we highlight the importance of continuously monitoring the protective performance of vaccines against the genetic variants of SARS-CoV-2, regardless of existing vaccine coverage. [ABSTRACT FROM AUTHOR]

Background: COVID-19 is a highly infectious respiratory disease that can manifest in various clinical presentations. Although many studies have reported the lipidomic signature of COVID-19, the molecular changes in asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals remain elusive. Methods: This study combined a comprehensive lipidomic analysis of 220 plasma samples from 166 subjects: 62 healthy controls, 16 asymptomatic infections, and 88 COVID-19 patients. We quantified 732 lipids separately in this cohort. We performed a difference analysis, validated with machine learning models, and also performed GO and KEGG pathway enrichment analysis using differential lipids from different control groups. Results: We found 175 differentially expressed lipids associated with SASR-CoV-2 infection, disease severity, and viral persistence in patients with COVID-19. PC (O-20:1/20:1), PC (O-20:1/20:0), and PC (O-18:0/18:1) better distinguished asymptomatic infected individuals from normal individuals. Furthermore, some patients tested positive for SARS-CoV-2 nucleic acid by RT-PCR but did not become negative for a longer period of time (≥60 days, designated here as long-term nucleic acid test positive, LTNP), whereas other patients became negative for viral nucleic acid in a shorter period of time (≤45 days, designated as short-term nucleic acid test positive, STNP). We have found that TG (14:1/14:1/18:2) and FFA (4:0) were differentially expressed in LTNP and STNP. Conclusion: In summary, the integration of lipid information can help us discover novel biomarkers to identify asymptomatic individuals and further deepen our understanding of the molecular pathogenesis of COVID-19. [ABSTRACT FROM AUTHOR]

Introduction: The COVID-19 pandemic has had devastating effects worldwide, but the trajectory of the pandemic has been milder in Low-and-Middle-Income Countries (LMICs), including those in Africa. Co-infection with helminths, such as Ascaris lumbricoides, has been suggested as a possible factor contributing to the reduced severity observed in these regions. Methods: The present study investigated the association between Ascaris-specific antibody levels and COVID-19 severity in 276 SARS-CoV-2-infected individuals in Benin. Participants were categorized into asymptomatic (n=100), mild (n=150), and severe (n=26) groups based on clinical disease severity. Sera were collected and analyzed using ELISA to measure Ascaris and SARS-CoV-2-specific antibodies, while Luminex was used to assess cytokines and SARS-CoV-2-specific neutralizing antibody expression. Results and discussion: The results demonstrated that asymptomatic SARS-CoV-2 seropositive individuals expressed, on average, 1.7 and 2.2-times higher levels of Ascaris antibodies compared to individuals with mild and severe COVID-19, respectively. This finding suggests an inverse correlation between Ascaris antibody levels and COVID-19 severity. Notably, logistic regression analysis showed that Ascaris seropositivity was significantly associated with a reduced risk of severe COVID-19 (OR = 0.277, p = 0.021). Interestingly, COVID-19 patients with comorbidities such as type 2 diabetes and high blood pressure showed lower expression of Ascaris antibodies. Strikingly, no correlation was observed between Ascaris antibody levels and SARS-CoV-2-specific neutralizing antibodies. On the other hand, individuals seronegative for Ascaris displayed significantly higher levels of systemic pro-inflammatory markers compared to seropositive individuals. These findings suggest that higher expression of Ascaris antibodies is associated with asymptomatic SARS-CoV-2 infections and may contribute to the reduction of the risk to develop severe COVID-19. The beneficial effect of Ascaris seropositivity on COVID-19 outcomes in Benin may be attributed to a decrease in comorbidities and pro-inflammatory markers. These observations provide valuable insights into the milderCOVID-19 trajectory observed in Africa and may have implications for future therapeutic strategies. [ABSTRACT FROM AUTHOR]

Antibodies to SARS-CoV-2 are central to recovery and immunity from COVID-19. However, the relationship between disease severity and the repertoire of antibodies against specific SARS-CoV-2 epitopes an individual develops following exposure remains incompletely understood. Here, we studied seroprevalence of antibodies to specific SARS-CoV-2 and other betacoronavirus antigens in a well-annotated, community sample of convalescent and never-infected individuals obtained in August 2020. One hundred and twenty-four participants were classified into five groups: previously exposed but without evidence of infection, having no known exposure or evidence of infection, seroconverted without symptoms, previously diagnosed with symptomatic COVID-19, and recovered after hospitalization with COVID-19. Prevalence of IgGs specific to the following antigens was compared between the five groups: recombinant SARS-CoV-2 and betacoronavirus spike and nucleocapsid protein domains, peptides from a tiled array of 22-mers corresponding to the entire spike and nucleocapsid proteins, and peptides corresponding to predicted immunogenic regions from other proteins of SARS-CoV-2. Antibody abundance generally correlated positively with severity of prior illness. A number of specific immunogenic peptides and some that may be associated with milder illness or protection from symptomatic infection were identified. No convincing association was observed between antibodies to Receptor Binding Domain(s) (RBDs) of less pathogenic betacoronaviruses HKU1 or OC43 and COVID-19 severity. However, apparent cross-reaction with SARS-CoV RBD was evident and some predominantly asymptomatic individuals had antibodies to both MERS-CoV and SARS-CoV RBDs. Findings from this pilot study may inform development of diagnostics, vaccines, and therapeutic antibodies, and provide insight into viral pathogenic mechanisms.

IntroductionThe COVID-19 pandemic has had devastating effects worldwide, but the trajectory of the pandemic has been milder in Low-and-Middle-Income Countries (LMICs), including those in Africa. Co-infection with helminths, such as Ascaris lumbricoides, has been suggested as a possible factor contributing to the reduced severity observed in these regions.MethodsThe present study investigated the association between Ascaris-specific antibody levels and COVID-19 severity in 276 SARS-CoV-2-infected individuals in Benin. Participants were categorized into asymptomatic (n=100), mild (n=150), and severe (n=26) groups based on clinical disease severity. Sera were collected and analyzed using ELISA to measure Ascaris and SARS-CoV-2-specific antibodies, while Luminex was used to assess cytokines and SARS-CoV-2-specific neutralizing antibody expression.Results and discussionThe results demonstrated that asymptomatic SARS-CoV-2 seropositive individuals expressed, on average, 1.7 and 2.2-times higher levels of Ascaris antibodies compared to individuals with mild and severe COVID-19, respectively. This finding suggests an inverse correlation between Ascaris antibody levels and COVID-19 severity. Notably, logistic regression analysis showed that Ascaris seropositivity was significantly associated with a reduced risk of severe COVID-19 (OR = 0.277, p = 0.021). Interestingly, COVID-19 patients with comorbidities such as type 2 diabetes and high blood pressure showed lower expression of Ascaris antibodies. Strikingly, no correlation was observed between Ascaris antibody levels and SARS-CoV-2-specific neutralizing antibodies. On the other hand, individuals seronegative for Ascaris displayed significantly higher levels of systemic pro-inflammatory markers compared to seropositive individuals. These findings suggest that higher expression of Ascaris antibodies is associated with asymptomatic SARS-CoV-2 infections and may contribute to the reduction of the risk to develop severe COVID-19. The beneficial effect of Ascaris seropositivity on COVID-19 outcomes in Benin may be attributed to a decrease in comorbidities and pro-inflammatory markers. These observations provide valuable insights into the milder COVID-19 trajectory observed in Africa and may have implications for future therapeutic strategies.

Abstract Background SARS-CoV-2 reinfections are a public health concern because of the potential for transmission and clinical disease, and because of our limited understanding of whether and how well an infection confers protection against subsequent infections. Despite the public health importance, few studies have reported rigorous estimates of reinfection risk. Methods Leveraging Indiana University’s comprehensive testing program to identify both asymptomatic and symptomatic SARS-CoV-2 cases, we estimated the incidence of SARS-CoV-2 reinfection among students, faculty, and staff across the 2020–2021 academic year. We contextualized the reinfection data with information on key covariates: age, sex, Greek organization membership, student vs faculty/staff affiliation, and testing type. Results Among 12,272 people with primary infections, we found a low level of SARS-CoV-2 reinfections (0.6%; 0.4 per 10,000 person-days). We observed higher risk for SARS-CoV-2 reinfections in Greek-affiliated students. Conclusions We found evidence for low levels of SARS-CoV-2 reinfection in a large multi-campus university population during a time-period prior to widespread COVID-19 vaccination.

We survey 62 users of a university asymptomatic SARS-CoV-2 testing service on details of their activities, protective behaviours and contacts in the 7 days prior to receiving a positive or negative SARS-CoV-2 PCR test result in the period October 2020–March 2021. The resulting data set is novel in capturing very detailed social contact history linked to asymptomatic disease status during a period of significant restriction on social activities. We use this data to explore 3 questions: (i) Did participation in university activities enhance infection risk? (ii) How do contact definitions rank in their ability to explain test outcome during periods of social restrictions? (iii) Do patterns in the protective behaviours help explain discrepancies between the explanatory performance of different contact measures? We classify activities into settings and use Bayesian logistic regression to model test outcome, computing posterior model probabilities to compare the performance of models adopting different contact definitions. Associations between protective behaviours, participant characteristics and setting are explored at the level of individual activities using multiple correspondence analysis (MCA). We find that participation in air travel or non-university work activities was associated with a positive asymptomatic SARS-CoV-2 PCR test, in contrast to participation in research and teaching settings. Intriguingly, logistic regression models with binary measures of contact in a setting performed better than more traditional contact numbers or person contact hours (PCH). The MCA indicates that patterns of protective behaviours vary between setting, in a manner which may help explain the preference for any participation as a contact measure. We conclude that linked PCR testing and social contact data can in principle be used to test the utility of contact definitions, and the investigation of contact definitions in larger linked studies is warranted to ensure contact data can capture environmental and social factors influencing transmission risk.

Background The recombinant protein-based vaccine, NVX-CoV2373, demonstrated 89.7% efficacy against coronavirus disease 2019 (COVID-19) in a phase 3, randomized, observer-blinded, placebo-controlled trial in the United Kingdom. The protocol was amended to include a blinded crossover. Data to the end of the placebo-controlled phase are reported. Methods Adults aged 18–84 years received 2 doses of NVX-CoV2373 or placebo (1:1) and were monitored for virologically confirmed mild, moderate, or severe COVID-19 (onset from 7 days after second vaccination). Participants who developed immunoglobulin G (IgG) against nucleocapsid protein but did not show symptomatic COVID-19 were considered asymptomatic. Secondary outcomes included anti-spike (S) IgG responses, wild-type virus neutralization, and T-cell responses. Results Of 15 185 participants, 13 989 remained in the per-protocol efficacy population (6989 NVX-CoV2373, 7000 placebo). At a maximum of 7.5 months (median, 4.5) postvaccination, there were 24 cases of COVID-19 among NVX-CoV2373 recipients and 134 cases among placebo recipients, a vaccine efficacy of 82.7% (95% confidence interval [CI], 73.3%–88.8%). Vaccine efficacy was 100% (95% CI, 17.9%–100.0%) against severe disease and 76.3% (95% CI, 57.4%–86.8%) against asymptomatic disease. High anti-S and neutralization responses to vaccination were evident, together with S-protein–specific induction of interferon-γ secretion in peripheral blood T cells. Incidence of serious adverse events and adverse events of special interest were similar between groups. Conclusions A 2-dose regimen of NVX-CoV2373 conferred a high level of ongoing protection against asymptomatic, symptomatic, and severe COVID-19 through >6 months postvaccination. A gradual decrease of protection suggests that a booster may be indicated. Clinical Trials Registration EudraCT, 2020-004123-16. [ABSTRACT FROM AUTHOR]

Background The development of memory B cells after asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is not well understood. Methods We compared spike antibody titers, pseudovirus neutralizing antibody titers, and memory B-cell responses among SARS-CoV-2 PCR-positive Marine recruits who either reported asymptomatic or symptomatic infection. Results Thirty-six asymptomatic participants exhibited similar spike IgG titers, spike IgA titers, and pseudovirus neutralization titers compared to 30 symptomatic participants. Pseudovirus neutralization and spike IgG titers showed significant positive correlations with frequency of memory B cells. Conclusions Among young adults, asymptomatic SARS-CoV-2 infection induced antibody and memory B-cell responses comparable to mild symptomatic infection. [ABSTRACT FROM AUTHOR]

The immune responses and the function of immune cells among asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection cases, especially in immuno-compromised individuals, remain largely unknown. Here we present a case of asymptomatic SARS-CoV-2 infection that lasted for at least 67 days. The patient has administrated Thymalfasin as 1.6 mg per dose every other day from Day 45 to 70, plus 200 mg per dose Arbidol antiviral therapy three doses per day from Day 48 to 57. Throughout the infection, no anti-SARS-CoV-2 specific IgM or IgG antibodies were detected. Instead, the patient showed either a low percentage or an absolute number of non-classical monocytes, dendritic cells (DCs), CD4+ T cells, and regulatory T cells (Tregs), which may account for the clinical feature and absence of antibody response. This case may shed new light on the outbreak management related to control/prevention, treatment, and vaccination of SARS-CoV-2 and other virus infections in immunocompromised individuals.

Jianwu Li,1,2,&ast; Na Jiang,1,2,&ast; Qing-Lei Zeng,3,&ast; Yue Zhang,4 Xinyuan He,4 Yao Chu,1,2 Wenni Jin,1,2 Yi Liu,4 Wan Shi,1,2 Miao Yang,1,2 Weihan He,1,2 Qing Han,5 Le Ma,4 You Xu,1,2 Yaling Guo,1,2 Lei Zhang,6– 9 Fanpu Ji2,4,10,11 1Isolation Ward for Covid-19, the Eighth Hospital of Xi’an City, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Shaanxi Provincial Clinical Medical Research Center of Infectious Diseases, Xi’an, Shaanxi, People’s Republic of China; 3Department of Infectious Diseases, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 4Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 5Department of Integrated Traditional Chinese and Western Medicine, the Eighth Hospital of Xi’an City, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 6China-Australia Joint Research Centre for Infectious Diseases, School of Public Health, Xi’an Jiaotong University Health Science Centre, Xi’an, Shaanxi, People’s Republic of China; 7Artificial Intelligence and Modelling in Epidemiology Program, Melbourne Sexual Health Centre, Alfred Health, Melbourne, Australia; 8Central Clinical School, Faculty of Medicine, Monash University, Melbourne, Australia; 9Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 10National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 11Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education of China, Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fanpu Ji, Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China, Tel/Fax +862987678223, Email jifanpu1979@163.com Yaling Guo, Isolation ward for COVID-19, the Eighth Hospital of Xi’an City, Xi’an Jiaotong University, Xi’an, Shaanxi Province, 710061, People’s Republic of China, Tel/Fax +8629 85230200, Email 15102915638@126.comBackground: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination had been demonstrated as an effective way to reduce the risk of coronavirus disease 2019 (COVID-19), and only a few vaccines suffered from SARS-CoV-2 infection. However, limited data concerning the clinical features of these vaccines infected with SARS-CoV-2 can be identified.Methods: We retrospectively collected and analyzed epidemiological and clinical characteristics data of the imported COVID-19 cases who received Chinese inactivated vaccines abroad. Data were extracted from electronic medical records from a designated hospital in the Shaanxi Province of China between March 22 and May 17, 2021.Results: Totally, 46 confirmed SARS-CoV-2 infection patients were enrolled. The mean age was 40.5 years (range 20– 61), 41 (89.1%) are male. Eighteen (39.1%) patients were from Pakistan. Fourteen (30.4%) patients had at least one comorbidity. Forty (87.0%) and 6 cases were fully vaccinated and partly vaccinated. The time interval between vaccination and infection was 88 days (IQR, 33– 123), 31 (67.4%) and 15 (32.6%) were asymptomatic and symptomatic cases, respectively. Fever (3/46, 6.5%) was the most common symptom; however, none had a body temperature higher than 38.0°C, and no severe case was observed. Notably, the rate of SARS-CoV-2 shedding discontinuation at 7 days after hospitalization in asymptomatic cases was higher than symptomatic one (93.5% vs 40%, P < 0.0001).Conclusion: Individuals who received Chinese inactivated vaccines abroad remain to have the probability of being infected with SARS-CoV-2, but all the vaccines infected with SARS-CoV-2 were asymptomatic or had mild symptoms with favorable clinical outcomes.Keywords: SARS-CoV-2, COVID-19, vaccination, reinfection, asymptomatic infection

We examined the asymptomatic rates of SARS-CoV-2 infection during the Delta and Omicron waves in the city of São Paulo. Nasopharyngeal swabs were collected at strategic points of the city (open-air markets, bus terminals, airports) for SARS-CoV-2 RNA testing. Applying the questionnaire, the symptomatic individuals were excluded, and only asymptomatic cases were analyzed. During the Delta wave, a total of 4315 samples were collected, whereas 2372 samples were collected during the first Omicron wave. The incidence of the asymptomatic SARS-CoV-2 infection was 0.6% during the Delta wave and 0.8% during the Omicron wave. No statistical differences were found in the threshold amplification cycle. However, there was a statistical difference observed in the sublineage distribution between asymptomatic and symptomatic individuals. Our study determined the incidence of asymptomatic infection by monitoring individuals who remained symptom-free, thereby providing a reliable evaluation of asymptomatic SARS-CoV-2 carriage. Our findings reveal a relatively low proportion of asymptomatic cases, which could be attributed to our rigorous monitoring protocol for the presence of clinical symptoms. Investigating asymptomatic infection rates is crucial to develop and implement effective disease control strategies.

INTRODUCTION: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome. Coronavirus 2 (SARS-CoV-2) is spreading rapidly around the world. Asymptomatic infection is highly contagious, potentially leading to viral spread. We aimed to determine the rate of patients positive for COVID-19 PCR performed for safety measures before thyroid fine-needle aspiration biopsy (FNAB). METHODS: The patients applied to Ankara City Hospital, Endocrinology and Metabolism Clinics between 15.03.2020 and 15.08.2020 and underwent routine COVID-19 PCR test before FNAB were evaluated retrospectively. Age, gender, history of hypertension and Type 2 Diabetes Mellitus (T2DM), use of levothyroxine (LT4) or antithyroid drug, 25-hydroxyvitamin D3 [25(OH)D3], TSH, freeT3 (fT3), free (fT4) levels, FNAB results were obtained from the records. RESULTS: Asymptomatic COVID-19 infection was detected in 29 (2.43%) of 1195 patients who underwent FNAB. There was no statistically significant difference between patients with COVID-19 PCR test positive asymptomatic and negative patients in terms of age, gender, median values of 25(OH)D3, TSH, fT3, fT4, the ratio of hypertension and T2DM. DISCUSSION AND CONCLUSION: The healthcare professionals work devotedly against COVID-19 infection, demonstrating a great example of struggle worldwide. FNAB is an invasive procedure requiring close contact. It should be known by the clinician that COVID-19 infection is associated with a high risk of transmission in asymptomatic patients. The rate of 2.43% in the population can not be underestimated and indicates the importance of the use of personal protective equipment and taking infection prevention measures.

Keywords: Hybrid immunity; natural infection; waning vaccine effectiveness; asymptomatic infection; Qatar; variant-containing COVID-19 vaccines EN Hybrid immunity natural infection waning vaccine effectiveness asymptomatic infection Qatar variant-containing COVID-19 vaccines 1 3 3 09/13/23 20230701 NES 230701 In October of 2022, Qatar introduced COVID-19 bivalent vaccination for persons >= 12 years using the 50- g mRNA-1273.214 vaccine combining SARS-CoV-2 ancestral and omicron BA.1 strains.[1] We estimated this vaccine's effectiveness against SARS-CoV-2 infection. Hybrid immunity, natural infection, waning vaccine effectiveness, asymptomatic infection, Qatar, variant-containing COVID-19 vaccines. [Extracted from the article]

SARS‐CoV‐2 Omicron variant seemed to cause milder disease compared to previous predominated variants. We aimed to conduct a meta‐analysis to assess the pooled proportion of nonsevere disease and asymptomatic infection among COVID‐19 patients infected with Omicron and Delta. We searched PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) databases. We included studies of SARS‐CoV‐2 Omicron infection from November 1, 2021, to April 18, 2022, and studies of Delta infection from October 1, 2020, to June 30, 2022. Studies without corresponding data, with less than 50 patients, or obviously biased concerning main outcome were excluded. Meta‐analysis was performed in R 4.2.0 with the "meta" package. Subgroup analyses were conducted by study group and vaccination status. The pooled proportion of asymptomatic infection and nonsevere disease with Omicron were 25.5% (95% confidence interval [CI] 17.0%–38.2%) and 97.9% (95% CI 97.1%–98.7%), significantly higher than those of Delta with 8.4% (95% CI 4.4%–16.2%) and 91.4% (95% CI 87.0%–96.0%). During Omicron wave, children and adolescents had higher proportion of asymptomatic infection, SOTR and the elderly had lower proportion of nonsevere disease, vaccination of a booster dose contributed to higher proportion of both asymptomatic infection and nonsevere disease. This study estimates the pooled proportion of asymptomatic infection and nonsevere disease caused by SARS‐CoV‐2 Omicron compared to other predominant variants. The result has important implications for future policy making. [ABSTRACT FROM AUTHOR]

Objectives: Transmission from asymptomatic patients is one of the biggest challenges in controlling the Coronavirus disease 2019 (COVID-19) outbreak because these cases are a potential source for disease spread. Based on this situation, the aim of our study is to determine the prevalence of COVID-19 in asymptomatic pediatric dental patients representing Sivas and surrounding provinces. Methods: The population of the study consists of pediatric patients between the ages of 0-14 who applied to Sivas Oral and Dental Health Hospital General Operating Room for dental treatments between July 2020 and August 2021. Results: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was detected in only 5 patients (approximately 1.80%) out of 278 asymptomatic pediatric patients. Conclusions: It is thought that the COVID-19 infection, which threatens the whole world, can progress asymptomatically in children, and therefore it may be a risk factor for the spread of the infection. To tackle the COVID-19 pandemic, it is recommended to maintain a high level of infection control measures in schools and day-care and to implement widespread testing on a global scale targeting the pediatric population. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) can be diagnosed as occupational disease by an occupational health physician (OHP), if supported by relevant work-related and medical documentation. The aim of this study was to analyse such documentation submitted by Croatian healthcare workers (HCWs) and discuss its relevance in view of European and Croatian guidelines. The study included 100 Croatian HCWs who were SARS-CoV-2-positive and requested that their infection be diagnosed as occupational disease by their OHPs from 1 May 2020 to 10 March 2021. As participants they were asked to fill out our online Occupational COVID-19 in Healthcare Workers Questionnaire. For the purpose of this study we analysed answers about the type of close contact at the workplace, COVID-19 symptoms, and enclosed work-related (job description, employer statement about exposure to SARS-CoV-2) and medical documentation (positive SARS-CoV-2 polymerase chain reaction test and patient history confirming the diagnosis of COVID-19). Most participants were working in hospitals (N=95), mostly nurses (N=75), who became infected by a patient (N=68) or colleague (N=31), and had at least one COVID-19 symptom (N=87). Eighty participants did not enclose obligatory documents, 41 of whom failed to submit job description and 31 both job description and employer statement. These findings confirm that the major risk of occupational COVID-19 in HCWs is close contact with patients and colleagues, and points out the need for better cooperation between OHPs, occupational safety experts, employers, and diseased workers.

Objective: Community of Hope Health Clinic (CHHC), a free and charitable clinic in Shelby County, Alabama, developed a screening protocol to identify patients with asymptomatic COVID-19 with the goal of minimizing infection risk for other patients, health care providers, and staff. We sought to determine whether the use of the CHHC screening protocol identified asymptomatic carriers of SARS-CoV-2 before their scheduled clinic visits. Methods: The CHHC screening protocol included the use of an adapted Centers for Disease Control and Prevention questionnaire via telephone 48-72 hours before a scheduled clinic appointment, coupled with a second administration of the questionnaire and a temperature check immediately before the patient's scheduled visit. Patients with positive responses to any questions or whose temperatures were greater than 100.4 °F were refused entry to the clinic, their appointments were rescheduled, and a SARS-CoV-2 test was recommended. SARS-CoV-2 laboratory testing was conducted on all patients with an appointment from October 26, 2020, through February 18, 2021, to verify whether the screening protocol was effective. Results: Of 298 patient encounters, 20 patients screened positive on the SARS-CoV-2 patient screen. Another 278 patients screened negative, were seen for patient care, and received a SARS-CoV-2 test via nasal swab; 274 (98.6%) patients received a negative test result, and 4 (1.4%) patients received a positive test result. Conclusions: The CHHC SARS-CoV-2 screening protocol, as validated by SARS-CoV-2 assay, was effective in screening out asymptomatic patients infected with SARS-CoV-2 before they were seen in clinic. As clinics and office practices return to prepandemic volumes, the use of such a screening protocol can help mitigate the risk of serious COVID-19 infection, especially for unvaccinated patients, health care providers, and staff. [ABSTRACT FROM AUTHOR]

A SEIARN compartment model with the asymptomatic infection and secondary infection is proposed to predict the trend of COVID-19 more accurately. The model is extended according to the propagation characteristics of the novel coronavirus, the concepts of the asymptomatic infected compartment and secondary infection are introduced, and the contact rate parameters of the improved model are updated in real time by using the LSTM trajectory, in order to make accurate predictions. This SEIARN model first builds on the traditional SEIR compartment model, taking into account the asymptomatic infection compartment and secondary infection. Secondly, it considers the disorder of the trajectory and uses the improved LSTM model to predict the future trajectory of the current patients and cross-track with the susceptible patients to obtain the contact rate. Then, we conduct real-time updating of exposure rates in the SEIARN model and simulation of epidemic trends in Tianjin, Xi'an, and Shijiazhuang. Finally, the comparison experiments show that the SEIARN model performs better in prediction accuracy, MSE, and RMSE. [ABSTRACT FROM AUTHOR]

• Skewed usage of H/L chain genes were identified in various clinical presentations. • IGKV3–7 and IGKV2–24 enriched in asymptomatic patients. • Dock analysis indicated that IGHV3–13 might be a potential vaccine candidate. • IGHV3–23 was differentially expressed in naive and memory B cell clusters. B cell-mediated immune responses play important roles in controlling SARS-CoV infection. Here, we performed the single-cell B cell receptor sequencing (scBCR-seq) of the PBMC samples from eleven healthy controls, five asymptomatic subjects and 33 symptomatic COVID-19 patients with various clinical presentations, and subsequently analyzed the abundance and diversity of the BCR repertoires in different groups, respectively. We revealed the skewed usage of the IGHV, IGLV and IGKV genes and identified a number of heavy or light chain VDJ gene pairs and combinational preference in each group, such as IGKV3–7 and IGKV2–24 enriched in the asymptomatic subjects, whereas IGHV3–13, IGHV3–23-IGHJ4, IGHV1–18–IGLV3–19, IGHV1–18–IGLV3–21, and IGHV1–18–IGLV3–25 enriched in the recovery patients with severe diseases. We also observed the differential expression of IGHV3–23 in various B cell clusters by analysis of the scRNA-seq data. Additional dock analysis indicated that IGHV3–13 could bind to the spike protein of SARS-CoV-2. These findings may advance our understanding of the humoral immune responses in COVID-19 patients and help develop novel vaccine candidates as well as therapeutical antibodies against SASR-CoV-2 infections. [ABSTRACT FROM AUTHOR]

Background: SARS-CoV-2 reinfections are a public health concern because of the potential for transmission and clinical disease, and because of our limited understanding of whether and how well an infection confers protection against subsequent infections. Despite the public health importance, few studies have reported rigorous estimates of reinfection risk.Methods: Leveraging Indiana University's comprehensive testing program to identify both asymptomatic and symptomatic SARS-CoV-2 cases, we estimated the incidence of SARS-CoV-2 reinfection among students, faculty, and staff across the 2020-2021 academic year. We contextualized the reinfection data with information on key covariates: age, sex, Greek organization membership, student vs faculty/staff affiliation, and testing type.Results: Among 12,272 people with primary infections, we found a low level of SARS-CoV-2 reinfections (0.6%; 0.4 per 10,000 person-days). We observed higher risk for SARS-CoV-2 reinfections in Greek-affiliated students.Conclusions: We found evidence for low levels of SARS-CoV-2 reinfection in a large multi-campus university population during a time-period prior to widespread COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

Since the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it has spread rapidly around the world and caused a serious global social crisis. During the epidemic, the blood collection and supply industry have been greatly impacted, due to the sharply dropped blood donors and transfusion transmission risk of SARS-CoV-2. Many infected individuals are asymptomatic and they may donate blood without awareness of the infection or before symptoms appear. In addition, viral RNAs have been detected in the blood of some patients infected with SARS-CoV-2. Although no infectious SARS-CoV-2 virus was found in the blood nor the blood components, there is a risk of transmission through blood transfusion which may endanger blood safety, especially during the pandemic period. This review briefly introduces the biological characteristics, epidemiology of SARS-CoV-2, with a particular focus on SARS-CoV-2 infection and blood safety. [ABSTRACT FROM AUTHOR]