-
Epidemics Dec 2021The high proportion of transmission events derived from asymptomatic or presymptomatic infections make SARS-CoV-2, the causative agent in COVID-19, difficult to control...
The high proportion of transmission events derived from asymptomatic or presymptomatic infections make SARS-CoV-2, the causative agent in COVID-19, difficult to control through the traditional non-pharmaceutical interventions (NPIs) of symptom-based isolation and contact tracing. As a consequence, many US universities developed asymptomatic surveillance testing labs, to augment NPIs and control outbreaks on campus throughout the 2020-2021 academic year (AY); several of those labs continue to support asymptomatic surveillance efforts on campus in AY2021-2022. At the height of the pandemic, we built a stochastic branching process model of COVID-19 dynamics at UC Berkeley to advise optimal control strategies in a university environment. Our model combines behavioral interventions in the form of group size limits to deter superspreading, symptom-based isolation, and contact tracing, with asymptomatic surveillance testing. We found that behavioral interventions offer a cost-effective means of epidemic control: group size limits of six or fewer greatly reduce superspreading, and rapid isolation of symptomatic infections can halt rising epidemics, depending on the frequency of asymptomatic transmission in the population. Surveillance testing can overcome uncertainty surrounding asymptomatic infections, with the most effective approaches prioritizing frequent testing with rapid turnaround time to isolation over test sensitivity. Importantly, contact tracing amplifies population-level impacts of all infection isolations, making even delayed interventions effective. Combination of behavior-based NPIs and asymptomatic surveillance also reduces variation in daily case counts to produce more predictable epidemics. Furthermore, targeted, intensive testing of a minority of high transmission risk individuals can effectively control the COVID-19 epidemic for the surrounding population. Even in some highly vaccinated university settings in AY2021-2022, asymptomatic surveillance testing offers an effective means of identifying breakthrough infections, halting onward transmission, and reducing total caseload. We offer this blueprint and easy-to-implement modeling tool to other academic or professional communities navigating optimal return-to-work strategies.
Topics: Asymptomatic Infections; COVID-19; Contact Tracing; Humans; SARS-CoV-2; Universities
PubMed: 34814094
DOI: 10.1016/j.epidem.2021.100527 -
Immunity, Inflammation and Disease Jul 2022Asymptomatic infections may play an important role in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Delta variant transmissions. However, the immunologic...
BACKGROUND
Asymptomatic infections may play an important role in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Delta variant transmissions. However, the immunologic features of asymptomatic postvaccination infections with the Delta variant of SARS-CoV-2 in adults remain to be defined.
METHODS
A retrospective study involving 36 vaccinated adults infected with the SARS-CoV-2 Delta variant was performed. Their demographic and laboratory data were collected and analyzed in The First People's Hospital of Jingmen from August 4 to 20, 2021.
RESULTS
Of the 36 adults, 6 persons had an asymptomatic infection. The severity of the SARS-CoV-2 infections was highly correlated with the doses of vaccinations (p = 0.019). The symptomatic and asymptomatic infected SARS-CoV-2 adults showed normal levels of leukocytes and lymphocytes. The C-reactive protein (CRP) and interleukin-6 (IL-6) levels were elevated in the symptomatic groups. The period between the last vaccination to the time of infection in the asymptomatic group was longer than that in the mild and moderate groups (73 vs. 61 vs. 50 days; p = 0.047). The percentage of suppressor T-cells in the asymptomatic group was the highest (32.2 ± 4.0% vs. 22.0 ± 7.2% vs. 29.3 ± 8.0%; p = 0.004). The signal-to-cutoff ratio value of total antibody against SARS-CoV-2 in the asymptomatic group was lower than that in the other two groups (383 vs. 703 vs. 1792; p < 0.001) and much lower than that in the moderate group. The multivariate ordinal logistic analysis after adjusting for gender, vaccination date, and vaccination dose indicated that CRP at Days 4-7 and 8-14, IL-6 on Days 4-7, and total antibody were risk factors for coronavirus disease 2019 severity.
CONCLUSIONS
Asymptomatic postvaccination infections with the Delta variant of SARS-CoV-2 in adults tend to infect persons vaccinated twice. The immunophenotype profile for asymptomatic postvaccination infections is less inflammatory and accompanied by relatively lower antibody titers.
Topics: Adult; Asymptomatic Infections; COVID-19; Humans; Interleukin-6; Retrospective Studies; SARS-CoV-2
PubMed: 35759224
DOI: 10.1002/iid3.670 -
International Journal of Infectious... Mar 2021The role of asymptomatic infections in the transmission of COVID-19 have drawn considerable attention. Here, we performed a meta-analysis to summarize the... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The role of asymptomatic infections in the transmission of COVID-19 have drawn considerable attention. Here, we performed a meta-analysis to summarize the epidemiological and radiographical characteristics of asymptomatic infections associated with COVID-19.
METHODS
Data on the epidemiological and radiographical characteristics of asymptomatic infections were extracted from the existing literature. Pooled proportions with 95% confidence intervals were then calculated using a random effects model.
RESULTS
A total of 104 studies involving 20,152 cases were included. The proportion of asymptomatic individuals among those with COVID-19 was 13.34% (10.86%-16.29%), among which presymptomatic and covert infections accounted for 7.64% (4.02%-14.04%) and 8.44% (5.12%-13.62%), respectively. The proportions of asymptomatic infections among infected children and healthcare workers were 32.24% (23.08%-42.13%) and 36.96% (18.51%-60.21%), respectively. The proportion of asymptomatic infections was significantly higher after 2020/02/29 than before (33.53% vs 10.19%) and in non-Asian regions than in Asia (28.76% vs 11.54%). The median viral shedding duration of asymptomatic infections was 14.14 days (11.25-17.04). A total of 47.62% (31.13%-72.87%) of asymptomatic infections showed lung abnormalities, especially ground-glass opacity (41.11% 19.7%-85.79%).
CONCLUSIONS
Asymptomatic infections were more commonly found in infected children and healthcare workers and increased after 2020/02/29 and in non-Asian regions. Chest radiographical imaging could be conducive to the early identification of asymptomatic infections.
Topics: Asymptomatic Infections; COVID-19; Humans; Radiography, Thoracic; SARS-CoV-2; Virus Shedding
PubMed: 33444755
DOI: 10.1016/j.ijid.2021.01.017 -
Proceedings of the National Academy of... Mar 2021The contributions of asymptomatic infections to herd immunity and community transmission are key to the resurgence and control of COVID-19, but are difficult to estimate...
The contributions of asymptomatic infections to herd immunity and community transmission are key to the resurgence and control of COVID-19, but are difficult to estimate using current models that ignore changes in testing capacity. Using a model that incorporates daily testing information fit to the case and serology data from New York City, we show that the proportion of symptomatic cases is low, ranging from 13 to 18%, and that the reproductive number may be larger than often assumed. Asymptomatic infections contribute substantially to herd immunity, and to community transmission together with presymptomatic ones. If asymptomatic infections transmit at similar rates as symptomatic ones, the overall reproductive number across all classes is larger than often assumed, with estimates ranging from 3.2 to 4.4. If they transmit poorly, then symptomatic cases have a larger reproductive number ranging from 3.9 to 8.1. Even in this regime, presymptomatic and asymptomatic cases together comprise at least 50% of the force of infection at the outbreak peak. We find no regimes in which all infection subpopulations have reproductive numbers lower than three. These findings elucidate the uncertainty that current case and serology data cannot resolve, despite consideration of different model structures. They also emphasize how temporal data on testing can reduce and better define this uncertainty, as we move forward through longer surveillance and second epidemic waves. Complementary information is required to determine the transmissibility of asymptomatic cases, which we discuss. Regardless, current assumptions about the basic reproductive number of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) should be reconsidered.
Topics: Asymptomatic Infections; Basic Reproduction Number; COVID-19; Disease Outbreaks; Humans; New York City
PubMed: 33571106
DOI: 10.1073/pnas.2019716118 -
PloS One 2021A majority of SARS-CoV-2 infections are transmitted from a minority of infected subjects, some of which may be symptomatic or pre-symptomatic. We aimed to quantify...
A majority of SARS-CoV-2 infections are transmitted from a minority of infected subjects, some of which may be symptomatic or pre-symptomatic. We aimed to quantify potential infectiousness among asymptomatic healthcare workers (HCWs) in relation to prior or later symptomatic disease. We previously (at the onset of the SARS-CoV-2 epidemic) performed a cohort study of SARS-CoV-2 infections among 27,000 healthcare workers (HCWs) at work in the capital region of Sweden. We performed both SARS-CoV-2 RT-PCR and serology. Furthermore, the cohort was comprehensively followed for sick leave, both before and after sampling. In the present report, we used the cohort database to quantify potential infectiousness among HCWs at work. Those who had sick leave either before or after sampling were classified as post-symptomatic or pre-symptomatic, whereas the virus-positive subjects with no sick leave were considered asymptomatic. About 0.2% (19/9449) of HCW at work were potentially infectious and pre-symptomatic (later had disease) and 0.17% (16/9449) were potentially infectious and asymptomatic (never had sick leave either before nor after sampling). Thus, 33% and 28% of all the 57 potentially infectious subjects were pre-symptomatic or asymptomatic, respectively. When a questionnaire was administered to HCWs with past infection, only 10,5% of HCWs had had no indication at all of having had SARS-CoV-2 infection ("truly asymptomatic"). Our findings provide a unique quantification of the different groups of asymptomatic, potentially infectious HCWs.
Topics: Adult; Asymptomatic Infections; COVID-19; Cohort Studies; Female; Health Personnel; Humans; Male; Middle Aged; Sick Leave; Sweden
PubMed: 34919570
DOI: 10.1371/journal.pone.0260453 -
Frontiers in Immunology 2019Malaria is still a significant public health burden in the tropics. Infection with malaria causing parasites results in a wide range of clinical disease presentations,... (Review)
Review
Malaria is still a significant public health burden in the tropics. Infection with malaria causing parasites results in a wide range of clinical disease presentations, from severe to uncomplicated or mild, and in the poorly understood asymptomatic infections. The complexity of asymptomatic infections is due to the intricate interplay between factors derived from the human host, parasite, and environment. Asymptomatic infections often go undetected and provide a silent natural reservoir that sustains malaria transmission. This creates a major obstacle for malaria control and elimination efforts. Numerous studies have tried to characterize asymptomatic infections, unanimously revealing that host immunity is the underlying factor in the maintenance of these infections and in the risk of developing febrile malaria infections. An in-depth understanding of how host immunity and parasite factors interact to cause malaria disease tolerance is thus required. This review primarily focuses on understanding anti-inflammatory and pro-inflammatory responses to asymptomatic infections in malaria endemic areas, to present the view that it is potentially the shift in host immunity toward an anti-inflammatory profile that maintains asymptomatic infections after multiple exposures to malaria. Conversely, symptomatic infections are skewed toward a pro-inflammatory immune profile. Moreover, we propose that these infections can be better interrogated using next generation sequencing technologies, in particular RNA sequencing (RNA-seq), to investigate the immune system using the transcriptome sampled during a clearly defined asymptomatic infection.
Topics: Asymptomatic Infections; Gene Expression Profiling; Humans; Malaria, Falciparum; Plasmodium falciparum; Sequence Analysis, RNA; Transcriptome
PubMed: 31681289
DOI: 10.3389/fimmu.2019.02398 -
Italian Journal of Pediatrics Dec 2022Approximately 85-90% of congenital cytomegalovirus infections (cCMV) are asymptomatic. Few studies have investigated early and long-term neurodevelopmental outcomes in...
BACKGROUND
Approximately 85-90% of congenital cytomegalovirus infections (cCMV) are asymptomatic. Few studies have investigated early and long-term neurodevelopmental outcomes in children with asymptomatic cCMV (acCMV), and the data is contradictory. In the present study, we did investigate the effect of cCMV asymptomatic infection on neurological outcomes and in cognitive, language and motor development at 6 months of age.
METHODS
Fifty-six children with cCMV asymptomatic infection were followed for 6 months, as part of a long-term surveillance program, examining their neurological and developmental outcomes. Neurological examination and Bayley-III Scales were performed.
RESULTS
Clinical evaluation revealed that early neurological outcomes were essentially normal, with minor neurological deficits (i.e., tone abnormalities) in a subgroup of patients. Bayley-III scores were substantially in the normal range, with 14% showing a score less than 85 (-1SD) in the Motor Scale. Children's neurological and neurodevelopmental outcomes at 6 months of age did not differ according to the trimester of infection.
CONCLUSIONS
Some infants with cCMV asymptomatic infection may present minor neurological abnormalities in early stages of life. It seems useful to monitor this population for early and late neurodevelopmental sequelae.
Topics: Infant; Humans; Child; Infant, Newborn; Cytomegalovirus; Asymptomatic Infections; Cytomegalovirus Infections; Neonatal Screening; Disease Progression
PubMed: 36572905
DOI: 10.1186/s13052-022-01387-3 -
Journal of Infection and Public Health Mar 2022Understanding the transmissibility and pathogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for control policies, but evidence... (Meta-Analysis)
Meta-Analysis Review
Transmissibility and pathogenicity of the severe acute respiratory syndrome coronavirus 2: A systematic review and meta-analysis of secondary attack rate and asymptomatic infection.
BACKGROUND
Understanding the transmissibility and pathogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for control policies, but evidence remains limited.
METHODS
We presented a systematic and meta-analytic summary concerning the transmissibility and pathogenicity of COVID-19.
RESULTS
A total of 105 studies were identified, with 35042 infected cases and 897912 close contacts. 48.6% (51/105) of studies on secondary transmissions were from China. We estimated a total SIR of 7.8% (95% confidence interval [CI], 6.8%-8.8%), SAR of 6.6% (95% CI, 5.7%-7.5%), and symptomatic infection ratio of 86.9% (95%CI, 83.9%-89.9%) with a disease series interval of 5.84 (95%CI, 4.92-6.94) days. Household contacts had a higher risk of both symptomatic and asymptomatic infection, and transmission was driven between index cases and second-generation cases, with little transmission occurring in second-to-later-generation cases (SIR, 12.4% vs. 3.6%). The symptomatic infection ratio was not significantly different in terms of infection time, generation, type of contact, and index cases.
CONCLUSIONS
Our results suggest a higher risk of infection among household contacts. Transmissibility decreased with generations during the intervention. Pathogenicity of SARS-CoV-2 varied among territories, but didn't change over time. Strict isolation and medical observation measures should be implemented.
Topics: Asymptomatic Infections; COVID-19; Contact Tracing; Family Characteristics; Humans; Incidence; SARS-CoV-2; Virulence
PubMed: 35123279
DOI: 10.1016/j.jiph.2022.01.015 -
Phytopathology Oct 2021is an invasive, broad host range pathogen that causes ramorum blight and sudden oak death in forest landscapes of western North America. In commercial nurseries,...
is an invasive, broad host range pathogen that causes ramorum blight and sudden oak death in forest landscapes of western North America. In commercial nurseries, asymptomatic infections of nursery stock by and other species create unacceptable risk and complicate inspection and certification programs designed to prevent introduction and spread of these pathogens. In this study, we continue development of a volatile organic compound (VOC)-based test for detecting asymptomatic infections of in sp. We confirmed detection of from volatiles collected from asymptomatic root-inoculated plants in a nursery setting, finding that the VOC profile of infected plants is detectably different from that of healthy plants, when measured from both ambient VOC emissions and VOCs extracted from leaf material. Predicting infection status was successful from ambient volatiles, which had a mean area under the curve (AUC) value of 0.71 ± 0.17, derived from corresponding receiver operating characteristic curves from an extreme gradient boosting discriminant analysis. This finding compares with that of extracted leaf volatiles, which resulted in a lower AUC value of 0.51 ± 0.21. In a growth chamber, we contrasted volatile profiles of asymptomatic plants having roots infected with one of three pathogens: , , and . Each pathogen induced unique and measurable changes, but generally the infections reduced volatile emissions until 17 weeks after inoculation, when emissions trended upward relative to those of mock-inoculated controls. Forty-five compounds had significant differences compared with mock-inoculated controls in at least one host-pathogen combination.
Topics: Asymptomatic Infections; North America; Phytophthora; Plant Diseases; Rhododendron
PubMed: 33616417
DOI: 10.1094/PHYTO-10-20-0472-R -
The Lancet. Global Health Jun 2021Data on influenza community burden and transmission are important to plan interventions especially in resource-limited settings. However, data are limited, particularly...
BACKGROUND
Data on influenza community burden and transmission are important to plan interventions especially in resource-limited settings. However, data are limited, particularly from low-income and middle-income countries. We aimed to evaluate the community burden and transmission of influenza in a rural and an urban setting in South Africa.
METHODS
In this prospective cohort study approximately 50 households were selected sequentially from both a rural setting (Agincourt, Mpumalanga Province, South Africa; with a health and sociodemographic surveillance system) and an urban setting (Klerksdorp, Northwest Province, South Africa; using global positioning system data), enrolled, and followed up for 10 months in 2017 and 2018. Different households were enrolled in each year. Households of more than two individuals in which 80% or more of the occupants agreed to participate were included in the study. Nasopharyngeal swabs were collected twice per week from participating household members irrespective of symptoms and tested for influenza using real-time RT-PCR. The primary outcome was the incidence of influenza infection, defined as the number of real-time RT-PCR-positive episodes divided by the person-time under observation. Household cumulative infection risk (HCIR) was defined as the number of subsequent infections within a household following influenza introduction.
FINDINGS
81 430 nasopharyngeal samples were collected from 1116 participants in 225 households (follow-up rate 88%). 917 (1%) tested positive for influenza; 178 (79%) of 225 households had one or more influenza-positive individual. The incidence of influenza infection was 43·6 (95% CI 39·8-47·7) per 100 person-seasons. 69 (17%) of 408 individuals who had one influenza infection had a repeat influenza infection during the same season. The incidence (67·4 per 100 person-seasons) and proportion with repeat infections (22 [23%] of 97 children) were highest in children younger than 5 years and decreased with increasing age (p<0·0001). Overall, 268 (56%) of 478 infections were symptomatic and 66 (14%) of 478 infections were medically attended. The overall HCIR was 10% (109 of 1088 exposed household members infected [95% CI 9-13%). Transmission (HCIR) from index cases was highest in participants aged 1-4 years (16%; 40 of 252 exposed household members) and individuals with two or more symptoms (17%; 68 of 396 exposed household members). Individuals with asymptomatic influenza transmitted infection to 29 (6%) of 509 household contacts. HIV infection, affecting 167 (16%) of 1075 individuals, was not associated with increased incidence or HCIR.
INTERPRETATION
Approximately half of influenza infections were symptomatic, with asymptomatic individuals transmitting influenza to 6% of household contacts. This suggests that strategies, such as quarantine and isolation, might be ineffective to control influenza. Vaccination of children, with the aim of reducing influenza transmission might be effective in African settings given the young population and high influenza burden.
FUNDING
US Centers for Disease Control and Prevention.
Topics: Adolescent; Adult; Aged; Asymptomatic Infections; Child; Child, Preschool; Cohort Studies; Female; Humans; Infant; Influenza, Human; Male; Middle Aged; Rural Health; Seasons; South Africa; Urban Health; Young Adult
PubMed: 34019838
DOI: 10.1016/S2214-109X(21)00141-8