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Heterogeneous and Dynamic Prevalence of Asymptomatic Influenza Virus Infections

Influenza infection manifests in a wide spectrum of severity, including symptomless pathogen carriers. We conducted a systematic review and meta-analysis of 55 studies to elucidate the proportional representation of these asymptomatic infected persons. We observed extensive heterogeneity among these studies. The prevalence of asymptomatic carriage (total absence of symptoms) ranged from 5.2% to 35.5% and subclinical cases (illness that did not meet the criteria for acute respiratory or influenza-like illness) from 25.4% to 61.8%. Statistical analysis showed that the heterogeneity could not be explained by the type of influenza, the laboratory tests used to detect the virus, the year of the study, or the location of the study. Projections of infection spread and strategies for disease control require that we identify the proportional representation of these insidious spreaders early on in the emergence of new influenza subtypes or strains and track how this rate evolves over time and space.


Covid-19: four fifths of cases are asymptomatic, China figures indicate

"The South China Morning Post said that China had already found more than 43 000 cases of asymptomatic infection through contact tracing.

The latest findings seem to contradict a World Health Organization report in February that was based on covid-19 in China. This suggested that “the proportion of truly asymptomatic infections is unclear but appears to be relatively rare and does not appear to be a major driver of transmission.”1

But since that WHO report other researchers, including Sergio Romagnani, a professor of clinical immunology at the University of Florence, have said they have evidence that most people infected by the virus do not show symptoms. Romagnani led the research that showed that blanket testing in a completely isolated village of roughly 3000 people in northern Italy saw the number of people with covid-19 symptoms fall by over 90% within 10 days by isolating people who were symptomatic and those who were asymptomatic."


"A major challenge to containing the spread of SARS-CoV-2 is that presymptomatic people are infectious. Recent reports suggest that patients may be infectious 1 to 3 days before symptom onset and that up to 40 to 50% of cases may be attributable to transmission from asymptomatic or presymptomatic people."

Mild or Moderate Covid-19
Rajesh T. Gandhi, M.D., John B. Lynch, M.D., M.P.H., and Carlos del Rio, M.D

"Patients who have mild signs and symptoms generally do not need additional evaluation, and depending on the risk profile, they may not even need to undergo Covid-19 testing, since the infection will usually resolve. However, some patients who have mild symptoms initially will subsequently have precipitous clinical deterioration that occurs approximately 1 week after symptom onset.17,18 In patients who have risk factors for severe disease (Table 1), close monitoring for clinical progression is warranted, with a low threshold for additional evaluation."


"Of children with a positive test result for SARS-CoV-2, 714 (35.9%) reported being asymptomatic."

Results: We analyzed results for 2463 children who underwent testing for SARS-CoV-2 infection; 1987 children had a positive result and 476 had a negative result. Of children with a positive test result for SARS-CoV-2, 714 (35.9%) reported being asymptomatic. Although cough (24.5%) and rhinorrhea (19.3%) were 2 of the most common symptoms among children with SARS-CoV-2 infection, they were also common among those with negative test results and were not predictive of a positive test (positive LR 0.96, 95% confidence interval [CI] 0.81–1.14, and 0.87, 95% CI 0.72–1.06, respectively). Anosmia/ageusia (positive LR 7.33, 95% CI 3.03–17.76), nausea/vomiting (positive LR 5.51, 95% CI 1.74–17.43), headache (positive LR 2.49, 95% CI 1.74–3.57) and fever (positive LR 1.68, 95% CI 1.34–2.11) were the symptoms most predictive of a positive result for a SARSCoV-2 swab. The positive LR for the combination of anosmia/ageusia, nausea/vomiting and headache was 65.92 (95% CI 49.48–91.92).

Interpretation: About two-thirds of the children who tested positive for SARS-CoV-2 infection reported symptoms. The symptoms most strongly associated with a positive SARS-CoV-2 swab result were anosmia/ageusia, nausea/vomiting, headache and fever.


43.2% of the confirmed SARS-CoV-2 infections were asymptomatic

On the 21st of February 2020 a resident of the municipality of Vo, a small town near Padua, died of pneumonia due to SARS-CoV-2 infection. This was the first COVID-19 death detected in Italy since the emergence of SARS-CoV-2 in the Chinese city of Wuhan, Hubei province. In response, the regional authorities imposed the lockdown of the whole municipality for 14 days. We collected information on the demography, clinical presentation, hospitalization, contact network and presence of SARS-CoV-2 infection in nasopharyngeal swabs for 85.9% and 71.5% of the population of Vo at two consecutive time points. On the first survey, which was conducted around the time the town lockdown started, we found a prevalence of infection of 2.6% (95% confidence interval (CI) 2.1-3.3%). On the second survey, which was conducted at the end of the lockdown, we found a prevalence of 1.2% (95% CI 0.8-1.8%). Notably, 43.2% (95% CI 32.2-54.7%) of the confirmed SARS-CoV-2 infections detected across the two surveys were asymptomatic. The mean serial interval was 6.9 days (95% CI 2.6-13.4). We found no statistically significant difference in the viral load (as measured by genome equivalents inferred from cycle threshold data) of symptomatic versus asymptomatic infections (p-values 0.6 and 0.2 for E and RdRp genes, respectively, Exact Wilcoxon-Mann-Whitney test). Contact tracing of the newly infected cases and transmission chain reconstruction revealed that most new infections in the second survey were infected in the community before the lockdown or from asymptomatic infections living in the same household. This study sheds new light on the frequency of asymptomatic SARS-CoV-2 infection and their infectivity (as measured by the viral load) and provides new insights into its transmission dynamics, the duration of viral load detectability and the efficacy of the implemented control measures.


Title: Estimation of the asymptomatic ratio of novel coronavirus infections

The number of novel coronavirus (COVID-19) cases worldwide continues to grow, and the gap between reports from China and statistical estimates of incidence based on cases diagnosed outside China indicates that a substantial number of cases are underdiagnosed (Nishiura et al., 2020a). Estimation of the asymptomatic ratio—the percentage of carriers with no symptoms—will improve understanding of COVID-19 transmission and the spectrum of disease it causes, providing insight into epidemic spread. Although the asymptomatic ratio is conventionally estimated using seroepidemiological data (Carrat et al., 2008; Hsieh et al., 2014), collection of these data requires significant logistical effort, time, and cost. Instead, we propose to estimate the asymptomatic ratio by using information on Japanese nationals that were evacuated from Wuhan, China on chartered flights


Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany

The novel coronavirus (2019-nCoV) from Wuhan is currently causing concern in the medical community as the virus is spreading around the world.1 Since identification of the virus in late December 2019, the number of cases from China that have been imported into other countries is on the rise, and the epidemiologic picture is changing on a daily basis. We are reporting a case of 2019-nCoV infection acquired outside Asia in which transmission appears to have occurred during the incubation period in the index patient.


Universal Screening for SARS-CoV-2 in Women Admitted for Delivery showed asymptomatic patients

Nasopharyngeal swabs were obtained from 210 of the 211 women (99.5%) who did not have symptoms of Covid-19; of these women, 29 (13.7%) were positive for SARS-CoV-2. Thus, 29 of the 33 patients who were positive for SARS-CoV-2 at admission (87.9%) had no symptoms of Covid-19 at presentation.


Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19

We report the kinetics of immune responses in relation to clinical and virological features of a patient with mild-to-moderate coronavirus disease 2019 (COVID-19) that required hospitalization. Increased antibody-secreting cells (ASCs), follicular helper T cells (TFH cells), activated CD4+ T cells and CD8+ T cells and immunoglobulin M (IgM) and IgG antibodies that bound the COVID-19-causing coronavirus SARS-CoV-2 were detected in blood before symptomatic recovery. These immunological changes persisted for at least 7 d following full resolution of symptoms.


Potential false-positive rate among the 'asymptomatic infected individuals' in close contacts of COVID-19 patients

Objective: As the prevention and control of COVID-19continues to advance, the active nucleic acid test screening in the close contacts of the patients has been carrying out in many parts of China. However, the false-positive rate of positive results in the screening has not been reported up to now. But to clearify the false-positive rate during screening is important in COVID-19 control and prevention. Methods: Point values and reasonable ranges of the indicators which impact the false-positive rate of positive results were estimated based on the information available to us at present. The false-positive rate of positive results in the active screening was deduced, and univariate and multivariate-probabilistic sensitivity analyses were performed to understand the robustness of the findings. Results: When the infection rate of the close contacts and the sensitivity and specificity of reported results were taken as the point estimates, the positive predictive value of the active screening was only 19.67%, in contrast, the false-positive rate of positive results was 80.33%. The multivariate-probabilistic sensitivity analysis results supported the base-case findings, with a 75% probability for the false-positive rate of positive results over 47%. Conclusions: In the close contacts of COVID-19 patients, nearly half or even more of the 'asymptomatic infected individuals' reported in the active nucleic acid test screening might be false positives.


36 people were given the virus internasally. Only 18 became infected.

Findings from the UK’s world-leading human challenge study provide new insights into mild infections with SARS-CoV-2 in healthy young adults.

To establish a novel SARS-CoV-2 human challenge model, 36 volunteers aged 18-29 years without evidence of previous infection or vaccination were inoculated with 10 TCID50 of a wild-type virus (SARS-CoV-2/human/GBR/484861/2020) intranasally. Two participants were excluded from per protocol analysis due to seroconversion between screening and inoculation. Eighteen (~53%) became infected, with viral load (VL) rising steeply and peaking at ~5 days post-inoculation. Virus was first detected in the throat but rose to significantly higher levels in the nose, peaking at ~8.87 log10 copies/ml (median, 95% CI [8.41,9.53). Viable virus was recoverable from the nose up to ~10 days post-inoculation, on average. There were no serious adverse events. Mild-to-moderate symptoms were reported by 16 (89%) infected individuals, beginning 2-4 days post-inoculation. Anosmia/dysosmia developed more gradually in 12 (67%) participants. No quantitative correlation was noted between VL and symptoms, with high VLs even in asymptomatic infection, followed by the development of serum spike-specific and neutralising antibodies. However, lateral flow results were strongly associated with viable virus and modelling showed that twice-weekly rapid tests could diagnose infection before 70-80% of viable virus had been generated. Thus, in this first SARS-CoV-2 human challenge study, no serious safety signals were detected and the detailed characteristics of early infection and their public health implications were shown. ClinicalTrials.gov identifier: NCT04865237.


"Although the majority of reported COVID-19 cases in China were mild (81%)"

Globally, approximately 170,000 confirmed cases of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) have been reported, including an estimated 7,000 deaths in approximately 150 countries (1). On March 11, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic (2). Data from China have indicated that older adults, particularly those with serious underlying health conditions, are at higher risk for severe COVID-19–associated illness and death than are younger persons (3). Although the majority of reported COVID-19 cases in China were mild (81%), approximately 80% of deaths occurred among adults aged ≥60 years; only one (0.1%) death occurred in a person aged ≤19 years (3). In this report, COVID-19 cases in the United States that occurred during February 12–March 16, 2020 and severity of disease (hospitalization, admission to intensive care unit [ICU], and death) were analyzed by age group. As of March 16, a total of 4,226 COVID-19 cases in the United States had been reported to CDC, with multiple cases reported among older adults living in long-term care facilities (4). Overall, 31% of cases, 45% of hospitalizations, 53% of ICU admissions, and 80% of deaths associated with COVID-19 were among adults aged ≥65 years with the highest percentage of severe outcomes among persons aged ≥85 years. In contrast, no ICU admissions or deaths were reported among persons aged ≤19 years. Similar to reports from other countries, this finding suggests that the risk for serious disease and death from COVID-19 is higher in older age groups.


68 per cent of cases confirmed in China in past eight days had no symptoms

Of the 885 infections reported between March 31 and April 7, 601 people showed no visible signs, National Health Commission says




2016 Furuya-Kanamori: Heterogeneous and Dynamic Prevalence of Asymptomatic Influenza Virus Infections
https://wwwnc.cdc.gov/eid/article/22/6/15-1080_article


2020 Day: Covid-19: four fifths of cases are asymptomatic, China figures indicate
https://www.bmj.com/content/369/bmj.m1375


2020 Gandhi: "A major challenge to containing the spread of SARS-CoV-2 is that presymptomatic people are infectious. Recent reports suggest that patients may be infectious 1 to 3 days before symptom onset and that up to 40 to 50% of cases may be attributable to transmission from asymptomatic or presymptomatic people."
https://www.nejm.org/doi/10.1056/NEJMcp2009249


2020 King: "Of children with a positive test result for SARS-CoV-2, 714 (35.9%) reported being asymptomatic."
https://www.cmaj.ca/content/early/2020/11/23/cmaj.202065


2020 Lavezzo: 43.2% of the confirmed SARS-CoV-2 infections were asymptomatic
https://www.medrxiv.org/content/10.1101/2020.04.17.20053157v1


2020 Nishiura: Title: Estimation of the asymptomatic ratio of novel coronavirus infections
https://www.ijidonline.com/article/S1201-9712(20)30139-9/pdf


2020 Rothe: Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany
https://www.nejm.org/doi/10.1056/NEJMc2001468


2020 Sutton: Universal Screening for SARS-CoV-2 in Women Admitted for Delivery showed asymptomatic patients
https://www.nejm.org/doi/full/10.1056/NEJMc2009316


2020 Thevaragan: Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19
https://www.nature.com/articles/s41591-020-0819-2


2020 Zhuang: Potential false-positive rate among the 'asymptomatic infected individuals' in close contacts of COVID-19 patients
https://www.ncbi.nlm.nih.gov/pubmed/32133832


2022 Killingley: 36 people were given the virus internasally. Only 18 became infected.
https://web.archive.org/web/20220202233220/https://www.researchsquare.com/article/rs-1121993/v1


CDC March: "Although the majority of reported COVID-19 cases in China were mild (81%)"
https://www.cdc.gov/mmwr/volumes/69/wr/mm6912e2.htm


China April: 68 per cent of cases confirmed in China in past eight days had no symptoms
https://www.scmp.com/news/china/society/article/3079012/coronavirus-68-cent-cases-confirmed-china-past-eight-days-had-no