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Proceedings of the National Academy of... Aug 2021Quantification of asymptomatic infections is fundamental for effective public health responses to the COVID-19 pandemic. Discrepancies regarding the extent of... (Meta-Analysis)
Meta-Analysis
Quantification of asymptomatic infections is fundamental for effective public health responses to the COVID-19 pandemic. Discrepancies regarding the extent of asymptomaticity have arisen from inconsistent terminology as well as conflation of index and secondary cases which biases toward lower asymptomaticity. We searched PubMed, Embase, Web of Science, and World Health Organization Global Research Database on COVID-19 between January 1, 2020 and April 2, 2021 to identify studies that reported silent infections at the time of testing, whether presymptomatic or asymptomatic. Index cases were removed to minimize representational bias that would result in overestimation of symptomaticity. By analyzing over 350 studies, we estimate that the percentage of infections that never developed clinical symptoms, and thus were truly asymptomatic, was 35.1% (95% CI: 30.7 to 39.9%). At the time of testing, 42.8% (95% prediction interval: 5.2 to 91.1%) of cases exhibited no symptoms, a group comprising both asymptomatic and presymptomatic infections. Asymptomaticity was significantly lower among the elderly, at 19.7% (95% CI: 12.7 to 29.4%) compared with children at 46.7% (95% CI: 32.0 to 62.0%). We also found that cases with comorbidities had significantly lower asymptomaticity compared to cases with no underlying medical conditions. Without proactive policies to detect asymptomatic infections, such as rapid contact tracing, prolonged efforts for pandemic control may be needed even in the presence of vaccination.
Topics: Asymptomatic Infections; COVID-19; Humans; SARS-CoV-2
PubMed: 34376550
DOI: 10.1073/pnas.2109229118 -
JAMA Network Open Dec 2022Real-world evidence of SARS-CoV-2 transmission is needed to understand the prevalence of infection in the Japanese population.
IMPORTANCE
Real-world evidence of SARS-CoV-2 transmission is needed to understand the prevalence of infection in the Japanese population.
OBJECTIVE
To conduct sentinel screening of the Japanese population to determine the prevalence of SARS-CoV-2 infection in asymptomatic individuals, with complementary analysis for symptomatic patients as reported by active epidemiologic surveillance used by the government.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study of a sentinel screening program investigated approximately 1 million asymptomatic individuals with polymerase chain reaction (PCR) testing for SARS-CoV-2 infection between February 22 and December 8, 2021. Participants included children, students, employed adults, and older individuals, as well as volunteers to broadly reflect the general Japanese population in the 14 prefectures of Japan that declared a state of emergency. Saliva samples and a cycle threshold (Ct) value of approximately 40 as standard in Japan were used. Polymerase chain reaction testing for symptomatic patients was separately done by public health authorities, and the results were obtained from the Ministry of Health, Labour, and Welfare of Japan to complement data on asymptomatic infections from the present study.
MAIN OUTCOMES AND MEASURES
Temporal trends in positivity and prevalence (including surges of different variants) and demographic associations (eg, age, geographic location, and vaccination status) were assessed.
RESULTS
The positive rate of SARS-CoV-2 infection in 1 082 976 asymptomatic individuals (52.08% males; mean [SD] age 39.4 [15.7] years) was 0.03% (95% CI, 0.02%-0.05%) during periods without surges and a maximum of 0.33% (95% CI, 0.25%-0.43%) during peak surges at the Japanese standard Ct value of approximately 40; however, the positive rate would have been 10-fold less at a Ct value of 25 as used elsewhere in the world (eg, UK). There was an increase in patients with a positive PCR test result with a Ct value of 25 or 30 preceding surges in infection and hotspots of asymptomatic infections.
CONCLUSIONS AND RELEVANCE
In this cross-sectional study of asymptomatic SARS-CoV-2 infection in the general population of Japan in 2021, as investigated by sentinel surveillance, a low rate of infection was seen in the Japanese population compared with reported levels elsewhere in the world. This finding provides real-world data on the state of infection in Japan.
Topics: Male; Adult; Child; Humans; Female; COVID-19; SARS-CoV-2; Asymptomatic Infections; Prevalence; Japan; Cross-Sectional Studies
PubMed: 36574249
DOI: 10.1001/jamanetworkopen.2022.47704 -
Cellular & Molecular Immunology Feb 2024SARS-CoV-2 infections manifest with a broad spectrum of presentations, ranging from asymptomatic infections to severe pneumonia and fatal outcomes. This review centers... (Review)
Review
SARS-CoV-2 infections manifest with a broad spectrum of presentations, ranging from asymptomatic infections to severe pneumonia and fatal outcomes. This review centers on asymptomatic infections, a widely reported phenomenon that has substantially contributed to the rapid spread of the pandemic. In such asymptomatic infections, we focus on the role of innate, humoral, and cellular immunity. Notably, asymptomatic infections are characterized by an early and robust innate immune response, particularly a swift type 1 IFN reaction, alongside a rapid and broad induction of SARS-CoV-2-specific T cells. Often, antibody levels tend to be lower or undetectable after asymptomatic infections, suggesting that the rapid control of viral replication by innate and cellular responses might impede the full triggering of humoral immunity. Even if antibody levels are present in the early convalescent phase, they wane rapidly below serological detection limits, particularly following asymptomatic infection. Consequently, prevalence studies reliant solely on serological assays likely underestimate the extent of community exposure to the virus.
Topics: Humans; COVID-19; SARS-CoV-2; Asymptomatic Infections; Antibodies, Viral; Immunity, Innate
PubMed: 38221577
DOI: 10.1038/s41423-024-01127-z -
International Journal of Environmental... Jan 2023Little is known about the long-term consequences of asymptomatic infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to review the... (Meta-Analysis)
Meta-Analysis Review
Little is known about the long-term consequences of asymptomatic infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to review the data available to explore the long-term consequences of asymptomatic SARS-CoV-2 infection in the real world. We searched observational cohort studies that described the long-term health effects of asymptomatic SARS-CoV-2 infections. Random-effects inverse-variance models were used to evaluate the pooled prevalence (PP) and its 95% confidence interval (CI) of long-term symptoms. Random effects were used to estimate the pooled odds ratios (OR) and its 95%CI of different long-term symptoms between symptomatic and asymptomatic infections. Five studies involving a total of 1643 cases, including 597 cases of asymptomatic and 1043 cases of symptomatic SARS-CoV-2 infection were included in this meta-analysis. The PPs of long-term consequences after asymptomatic SARS-CoV-2 infections were 17.13% (95%CI, 7.55−26.71%) for at least one symptom, 15.09% (95%CI, 5.46−24.73%) for loss of taste, 14.14% (95%CI, −1.32−29.61%) for loss of smell, and 9.33% (95%CI, 3.07−15.60) for fatigue. Compared with symptomatic SARS-CoV-2 infection, asymptomatic infection was associated with a significantly lower risk of developing COVID-19-related sequelae (p < 0.05), with 80% lower risk of developing at least one symptom (OR = 0.20, 95%CI, 0.09−0.45), 81% lower risk of fatigue (OR = 0.19, 95%CI, 0.08−0.49), 90% lower risk of loss of taste/smell (OR = 0.10, 95%CI, 0.02−0.58). Our results suggested that there were long-term effects of asymptomatic SARS-CoV-2 infection, such as loss of taste or smell, fatigue, cough and so on. However, the risk of developing long-term symptoms in asymptomatic SARS-CoV-2 infected persons was significantly lower than those in symptomatic SARS-CoV-2 infection cases.
Topics: Humans; COVID-19; SARS-CoV-2; Ageusia; Asymptomatic Infections; Fatigue
PubMed: 36674367
DOI: 10.3390/ijerph20021613 -
Clinical Microbiology and Infection :... Apr 2023To characterize the timing and genotype distribution of symptomatic and asymptomatic sapovirus infections and re-infections in a Nicaraguan birth cohort.
OBJECTIVES
To characterize the timing and genotype distribution of symptomatic and asymptomatic sapovirus infections and re-infections in a Nicaraguan birth cohort.
METHODS
Infants (N = 444) were enrolled at 10-14 days of life and observed weekly until 2 years of age. Stool samples were collected for each acute gastroenteritis (AGE) episode, and routine stool samples were collected monthly. Stool samples were tested for sapovirus using RT-qPCR, and positive samples were genotyped.
RESULTS
A total of 348 children completed 2 years of AGE weekly surveillance; 93 (26.7%) of them experienced sapovirus AGE. Most infections occurred after 5 months of age and mainly during the second year of life (62.4%, 58/93) and early in the rainy season. Sapovirus screening in all stools from a subset of 67 children who consistently provided samples showed sapovirus infections in 91 of 330 (27.6%) AGE episodes and in 39 of 1350 (2.9%) routine stools. In this subset, the median age at the first sapovirus AGE was 11.2 months (95% CI, 9.3-15.9 months); 38 of 67 (57%) children experienced re-infections, 19 symptomatic and 19 asymptomatic. On average, sapovirus re-infections were reported 7.2 months after symptomatic and 5.3 months after asymptomatic infections. Genogroup GI (64%, 69/108) was the most common detected. Sapovirus GI.1 was more frequently detected in AGE stool samples than in routine stool samples (47.2%, 43/91 vs. 25.6%, 10/39; p 0.005), and re-infection with the same genotype was uncommon.
DISCUSSION
The first sapovirus infections occurred at approximately 11 months of age, whereas the median time to symptomatic re-infection was 7.2 months. Re-infections with the same sapovirus genotype were rare during 2 years of life suggesting genotype-specific protection after natural infection.
Topics: Infant; Child; Humans; Reinfection; Sapovirus; Birth Cohort; Asymptomatic Infections; Caliciviridae Infections; Phylogeny; Genotype; Feces
PubMed: 36423864
DOI: 10.1016/j.cmi.2022.11.013 -
BMC Infectious Diseases Sep 2023Although many studies on asymptomatic norovirus infection in outbreaks have been conducted globally, structured data (important for emergency management of outbreaks) on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although many studies on asymptomatic norovirus infection in outbreaks have been conducted globally, structured data (important for emergency management of outbreaks) on the prevalence of this epidemic are still not available. This study assessed the global prevalence of asymptomatic norovirus infection in outbreaks.
METHODS
We identified publications on asymptomatic infections from norovirus outbreaks by searching the PubMed, Embase, Cochrane Library, Medline, and Web of Science databases and screening references from the articles reviewed. Prevalence of asymptomatic norovirus infection in outbreaks was employed as the primary summary data. The random-effects model of the meta-analysis was fitted to generate estimates of the prevalence in the overall and subgroup populations.
RESULTS
In total, 44 articles with a sample size of 8,115 asymptomatic individuals were included. The estimated pooled prevalence of asymptomatic norovirus infection in outbreaks was 21.8% (95%CI, 17.4-27.3). The asymptomatic prevalence of norovirus GII (20.1%) was similar to that of GI (19.8%); however, the proportion prevalence of asymptomatic individuals involved in the former (33.36%) was significantly higher than that of in the latter (0.92%) and the former (93.18%) was reported much more frequently than the latter (15.91%) in the included articles. These studies had significant heterogeneity (I = 92%, τ = 0.4021, P < 0.01). However, the source of heterogeneity could not be identified even after subgroup analysis of 10 possible influencing factors (geographical area, outbreak settings, outbreak seasons, sample types, norovirus genotypes, transmission routes, subjects' occupations, subjects' age, per capita national income, and clear case definition). Meta-regression analysis of these 10 factors demonstrated that the geographical area could be partly responsible for this heterogeneity (P = 0.012).
CONCLUSIONS
The overall pooled asymptomatic prevalence of norovirus in outbreaks was high, with genome II dominating. Asymptomatic individuals may play an important role in norovirus outbreaks. This knowledge could help in developing control strategies and public health policies for norovirus outbreaks.
Topics: Humans; Asymptomatic Infections; Prevalence; Disease Outbreaks; Epidemics; Norovirus
PubMed: 37700223
DOI: 10.1186/s12879-023-08519-y -
Viruses Nov 2023We 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...
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.
Topics: Humans; COVID-19; Brazil; Asymptomatic Infections; RNA, Viral; SARS-CoV-2; Genomics
PubMed: 38005887
DOI: 10.3390/v15112210 -
Malaria Journal Sep 2021Further reductions in malaria incidence as more countries approach malaria elimination require the identification and treatment of asymptomatic individuals who carry...
BACKGROUND
Further reductions in malaria incidence as more countries approach malaria elimination require the identification and treatment of asymptomatic individuals who carry mosquito-infective Plasmodium gametocytes that are responsible for furthering malaria transmission. Assessing the relationship between total parasitaemia and gametocytaemia in field surveys can provide insight as to whether detection of low-density, asymptomatic Plasmodium falciparum infections with sensitive molecular methods can adequately detect the majority of infected individuals who are potentially capable of onward transmission.
METHODS
In a cross-sectional survey of 1354 healthy children and adults in three communities in western Kenya across a gradient of malaria transmission (Ajigo, Webuye, and Kapsisywa-Kipsamoite), asymptomatic P. falciparum infections were screened by rapid diagnostic tests, blood smear, and quantitative PCR of dried blood spots targeting the varATS gene in genomic DNA. A multiplex quantitative reverse-transcriptase PCR assay targeting female and male gametocyte genes (pfs25, pfs230p), a gene with a transcriptional pattern restricted to asexual blood stages (piesp2), and human GAPDH was also developed to determine total parasite and gametocyte densities among parasitaemic individuals.
RESULTS
The prevalence of varATS-detectable asymptomatic infections was greatest in Ajigo (42%), followed by Webuye (10%). Only two infections were detected in Kapsisywa. No infections were detected in Kipsamoite. Across all communities, children aged 11-15 years account for the greatest proportion total and sub-microscopic asymptomatic infections. In younger age groups, the majority of infections were detectable by microscopy, while 68% of asymptomatically infected adults (> 21 years old) had sub-microscopic parasitaemia. Piesp2-derived parasite densities correlated poorly with microscopy-determined parasite densities in patent infections relative to varATS-based detection. In general, both male and female gametocytaemia increased with increasing varATS-derived total parasitaemia. A substantial proportion (41.7%) of individuals with potential for onward transmission had qPCR-estimated parasite densities below the limit of microscopic detection, but above the detectable limit of varATS qPCR.
CONCLUSIONS
This assessment of parasitaemia and gametocytaemia in three communities with different transmission intensities revealed evidence of a substantial sub-patent infectious reservoir among asymptomatic carriers of P. falciparum. Experimental studies are needed to definitively determine whether the low-density infections in communities such as Ajigo and Webuye contribute significantly to malaria transmission.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asymptomatic Infections; Child; Child, Preschool; Cross-Sectional Studies; Female; Humans; Infant; Kenya; Malaria, Falciparum; Male; Middle Aged; Prevalence; Rural Population; Young Adult
PubMed: 34535134
DOI: 10.1186/s12936-021-03905-w -
Clinical Infectious Diseases : An... Dec 2021A detailed understanding of the contribution of the asymptomatic Plasmodium reservoir to the occurrence of clinical malaria at individual and community levels is needed...
BACKGROUND
A detailed understanding of the contribution of the asymptomatic Plasmodium reservoir to the occurrence of clinical malaria at individual and community levels is needed to guide effective elimination interventions. This study investigated the relationship between asymptomatic Plasmodium falciparum carriage and subsequent clinical malaria episodes in the Dielmo and Ndiop villages in Senegal.
METHODS
The study used a total of 2792 venous and capillary blood samples obtained from asymptomatic individuals and clinical malaria datasets collected from 2013 to 2016. Mapping, spatial clustering of infections, and risk analysis were performed using georeferenced households.
RESULTS
High incidences of clinical malaria episodes were observed to occur predominantly in households of asymptomatic P falciparum carriers. A statistically significant association was found between asymptomatic carriage in a household and subsequent episode of clinical malaria occurring in that household for each individual year (P values were 0.0017, 6 × 10-5, 0.005, and 0.008 for the years 2013, 2014, 2015, and 2016 respectively) and the combined years (P = 8.5 × 10-8), which was not found at the individual level. In both villages, no significant patterns of spatial clustering of P falciparum clinical cases were found, but there was a higher risk of clinical episodes <25 m from asymptomatic individuals in Ndiop attributable to clustering within households.
CONCLUSION
The findings provide strong epidemiological evidence linking the asymptomatic P falciparum reservoir to clinical malaria episodes at household scale in Dielmo and Ndiop villagers. This argues for a likely success of a mass testing and treatment intervention to move towards the elimination of malaria in the villages of Dielmo and Ndiop.
Topics: Asymptomatic Infections; Cross-Sectional Studies; Humans; Malaria; Malaria, Falciparum; Plasmodium; Plasmodium falciparum; Prevalence
PubMed: 33677477
DOI: 10.1093/cid/ciab161 -
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