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1.
BMC Infectious Diseases ; 22(1):1-9, 2022.
Article in English | BioMed Central | ID: covidwho-1957926

ABSTRACT

Multiple waves of the COVID-19 epidemic have hit most countries by the end of 2021. Most of those waves are caused by emergence and importation of new variants. To prevent importation of new variants, combination of border control and contact tracing is essential. However, the timing of infection inferred by interview is influenced by recall bias and hinders the contact tracing process. We propose a novel approach to infer the timing of infection, by employing a within-host model to capture viral load dynamics after the onset of symptoms. We applied this approach to ascertain secondary transmission which can trigger outbreaks. As a demonstration, the 12 initial reported cases in Singapore, which were considered as imported because of their recent travel history to Wuhan, were analyzed to assess whether they are truly imported. Our approach suggested that 6 cases were infected prior to the arrival in Singapore, whereas other 6 cases might have been secondary local infection. Three among the 6 potential secondary transmission cases revealed that they had contact history to previously confirmed cases. Contact trace combined with our approach using viral load data could be the key to mitigate the risk of importation of new variants by identifying cases as early as possible and inferring the timing of infection with high accuracy.

2.
J Acquir Immune Defic Syndr ; 87(2): e182-e187, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1865028

ABSTRACT

BACKGROUND: During the COVID-19 outbreak, facility capacity for HIV testing has been limited. Furthermore, people may have opted against HIV testing during this period to avoid COVID-19 exposure. We investigated the influence of the COVID-19 pandemic on HIV testing and the number of reported HIV cases in Japan. METHODS: We analyzed quarterly HIV/AIDS-related data from 2015 to the second quarter of 2020 using an anomaly detection approach. The data included the number of consultations, the number of HIV tests performed by public health centers or municipalities, and the number of newly reported HIV cases with and without an AIDS diagnosis. We further performed the same analysis for 2 subgroups: men who have sex with men (MSM) and non-Japanese persons. RESULTS: The number of HIV tests (9,584 vs. 35,908 in the year-before period) and consultations (11,689 vs. 32,565) performed by public health centers significantly declined in the second quarter of 2020, whereas the proportion of new HIV cases with an AIDS diagnosis (36.2% vs. 26.4%) significantly increased after removing the trend and seasonality effects. HIV cases without an AIDS diagnosis decreased (166 vs. 217), but the reduction was not significant. We confirmed similar trends for the men who have sex with men and non-Japanese subgroups. CONCLUSIONS: During the COVID-19 pandemic, the current HIV testing system in Japan seems to have missed more cases of HIV before developing AIDS. Continuously monitoring the situation and securing sufficient test resources by use of self-testing is essential to understand the clear epidemiological picture of HIV incidence during the COVID-19 pandemic.


Subject(s)
COVID-19/epidemiology , HIV Infections/epidemiology , HIV Testing/statistics & numerical data , Public Health , SARS-CoV-2 , Humans , Japan/epidemiology
3.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327114

ABSTRACT

Appropriate isolation guidelines for COVID-19 patients are warranted. Currently, isolating for fixed time is adapted in most countries. However, given the variability in viral dynamics between patients, some patients may no longer be infectious by the end of isolation (thus they are redundantly isolated), whereas others may still be infectious. Utilizing viral test results to determine ending isolation would minimize both the risk of ending isolation of infectious patients and the burden due to redundant isolation of noninfectious patients. In our previous study, we proposed a computational framework using SARS-CoV-2 viral dynamics models to compute the risk and the burden of different isolation guidelines with PCR tests. In this study, we extend the computational framework to design isolation guidelines for COVID-19 patients utilizing rapid antigen tests. Time interval of tests and number of consecutive negative tests to minimize the risk and the burden of isolation were explored. Furthermore, the approach was extended for asymptomatic cases. We found the guideline should be designed considering various factors: the infectiousness threshold values, the detection limit of antigen tests, symptom presence, and an acceptable level of releasing infectious patients. Especially, when detection limit is higher than the infectiousness threshold values, more consecutive negative results are needed to ascertain loss of infectiousness. To control the risk of releasing of infectious individuals under certain levels, rapid antigen tests should be designed to have lower detection limits than infectiousness threshold values to minimize the length of prolonged isolation, and the length of prolonged isolation increases when the detection limit is higher than the infectiousness threshold values, even though the guidelines are optimized for given conditions.

4.
Life Sci Alliance ; 4(10)2021 10.
Article in English | MEDLINE | ID: covidwho-1342114

ABSTRACT

The duration of viral shedding is determined by a balance between de novo infection and removal of infected cells. That is, if infection is completely blocked with antiviral drugs (100% inhibition), the duration of viral shedding is minimal and is determined by the length of virus production. However, some mathematical models predict that if infected individuals are treated with antiviral drugs with efficacy below 100%, viral shedding may last longer than without treatment because further de novo infections are driven by entry of the virus into partially protected, uninfected cells at a slower rate. Using a simple mathematical model, we quantified SARS-CoV-2 infection dynamics in non-human primates and characterized the kinetics of viral shedding. We counterintuitively found that treatments initiated early, such as 0.5 d after virus inoculation, with intermediate to relatively high efficacy (30-70% inhibition of virus replication) yield a prolonged duration of viral shedding (by about 6.0 d) compared with no treatment.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , COVID-19/virology , Virus Shedding/drug effects , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacology , Alanine/analogs & derivatives , Alanine/pharmacology , Animals , Lung/virology , Macaca mulatta , Models, Theoretical , Nose/virology , Pharynx/virology , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Time Factors , Viral Load/drug effects , Virus Replication/drug effects
5.
Elife ; 102021 07 27.
Article in English | MEDLINE | ID: covidwho-1328262

ABSTRACT

Since the start of the COVID-19 pandemic, two mainstream guidelines for defining when to end the isolation of SARS-CoV-2-infected individuals have been in use: the one-size-fits-all approach (i.e. patients are isolated for a fixed number of days) and the personalized approach (i.e. based on repeated testing of isolated patients). We use a mathematical framework to model within-host viral dynamics and test different criteria for ending isolation. By considering a fixed time of 10 days since symptom onset as the criterion for ending isolation, we estimated that the risk of releasing an individual who is still infectious is low (0-6.6%). However, this policy entails lengthy unnecessary isolations (4.8-8.3 days). In contrast, by using a personalized strategy, similar low risks can be reached with shorter prolonged isolations. The obtained findings provide a scientific rationale for policies on ending the isolation of SARS-CoV-2-infected individuals.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , Patient Isolation , Practice Guidelines as Topic , Quarantine , SARS-CoV-2 , COVID-19/diagnosis , COVID-19/transmission , Humans , Models, Theoretical , Molecular Diagnostic Techniques , Pandemics , Patient Isolation/methods , Patient Isolation/standards , Precision Medicine/methods , Quarantine/methods , Quarantine/standards , SARS-CoV-2/physiology , Viral Load
6.
PLoS Med ; 18(7): e1003660, 2021 07.
Article in English | MEDLINE | ID: covidwho-1298077

ABSTRACT

BACKGROUND: Development of an effective antiviral drug for Coronavirus Disease 2019 (COVID-19) is a global health priority. Although several candidate drugs have been identified through in vitro and in vivo models, consistent and compelling evidence from clinical studies is limited. The lack of evidence from clinical trials may stem in part from the imperfect design of the trials. We investigated how clinical trials for antivirals need to be designed, especially focusing on the sample size in randomized controlled trials. METHODS AND FINDINGS: A modeling study was conducted to help understand the reasons behind inconsistent clinical trial findings and to design better clinical trials. We first analyzed longitudinal viral load data for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) without antiviral treatment by use of a within-host virus dynamics model. The fitted viral load was categorized into 3 different groups by a clustering approach. Comparison of the estimated parameters showed that the 3 distinct groups were characterized by different virus decay rates (p-value < 0.001). The mean decay rates were 1.17 d-1 (95% CI: 1.06 to 1.27 d-1), 0.777 d-1 (0.716 to 0.838 d-1), and 0.450 d-1 (0.378 to 0.522 d-1) for the 3 groups, respectively. Such heterogeneity in virus dynamics could be a confounding variable if it is associated with treatment allocation in compassionate use programs (i.e., observational studies). Subsequently, we mimicked randomized controlled trials of antivirals by simulation. An antiviral effect causing a 95% to 99% reduction in viral replication was added to the model. To be realistic, we assumed that randomization and treatment are initiated with some time lag after symptom onset. Using the duration of virus shedding as an outcome, the sample size to detect a statistically significant mean difference between the treatment and placebo groups (1:1 allocation) was 13,603 and 11,670 (when the antiviral effect was 95% and 99%, respectively) per group if all patients are enrolled regardless of timing of randomization. The sample size was reduced to 584 and 458 (when the antiviral effect was 95% and 99%, respectively) if only patients who are treated within 1 day of symptom onset are enrolled. We confirmed the sample size was similarly reduced when using cumulative viral load in log scale as an outcome. We used a conventional virus dynamics model, which may not fully reflect the detailed mechanisms of viral dynamics of SARS-CoV-2. The model needs to be calibrated in terms of both parameter settings and model structure, which would yield more reliable sample size calculation. CONCLUSIONS: In this study, we found that estimated association in observational studies can be biased due to large heterogeneity in viral dynamics among infected individuals, and statistically significant effect in randomized controlled trials may be difficult to be detected due to small sample size. The sample size can be dramatically reduced by recruiting patients immediately after developing symptoms. We believe this is the first study investigated the study design of clinical trials for antiviral treatment using the viral dynamics model.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Randomized Controlled Trials as Topic , Sample Size , Humans , Models, Biological , SARS-CoV-2 , Treatment Outcome , Viral Load , Virus Replication , Virus Shedding
7.
Lancet Reg Health West Pac ; 3: 100016, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-1281486

ABSTRACT

BACKGROUND: On April 7, 2020, the Japanese government declared a state of emergency regarding the novel coronavirus (COVID-19). Given the nation-wide spread of the coronavirus in major Japanese cities and the rapid increase in the number of cases with untraceable infection routes, large-scale monitoring for capturing the current epidemiological situation of COVID-19 in Japan is urgently required. METHODS: A chatbot-based healthcare system named COOPERA (COvid-19: Operation for Personalized Empowerment to Render smart prevention And AN care seeking) was developed to surveil the Japanese epidemiological situation in real-time. COOPERA asked questions regarding personal information, location, preventive actions, COVID-19 related symptoms and their residence. Empirical Bayes estimates of the age-sex-standardized incidence rate and disease mapping approach using scan statistics were utilized to identify the geographical distribution of the symptoms in Tokyo and their spatial correlation r with the identified COVID-19 cases. FINDINGS: We analyzed 353,010 participants from Tokyo recruited from 27th March to 6th April 2020. The mean (SD) age of participants was 42.7 (12.3), and 63.4%, 36.4% or 0.2% were female, male, or others, respectively. 95.6% of participants had no subjective symptoms. We identified several geographical clusters with high spatial correlation (r = 0.9), especially in downtown areas in central Tokyo such as Shibuya and Shinjuku. INTERPRETATION: With the global spread of COVID-19, medical resources are being depleted. A new system to monitor the epidemiological situation, COOPERA, can provide insights to assist political decision to tackle the epidemic. In addition, given that Japan has not had a strong lockdown policy to weaken the spread of the infection, our result would be useful for preparing for the second wave in other countries during the next flu season without a strong lockdown. FUNDING: The present work was supported in part by a grant from the Ministry of Health, Labour and Welfare of Japan (H29-Gantaisaku-ippan-009).

8.
Science ; 373(6552)2021 07 16.
Article in English | MEDLINE | ID: covidwho-1262378

ABSTRACT

The COVID-19 pandemic has revealed the pronounced vulnerability of the elderly and chronically ill to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced morbidity and mortality. Cellular senescence contributes to inflammation, multiple chronic diseases, and age-related dysfunction, but effects on responses to viral infection are unclear. Here, we demonstrate that senescent cells (SnCs) become hyper-inflammatory in response to pathogen-associated molecular patterns (PAMPs), including SARS-CoV-2 spike protein-1, increasing expression of viral entry proteins and reducing antiviral gene expression in non-SnCs through a paracrine mechanism. Old mice acutely infected with pathogens that included a SARS-CoV-2-related mouse ß-coronavirus experienced increased senescence and inflammation, with nearly 100% mortality. Targeting SnCs by using senolytic drugs before or after pathogen exposure significantly reduced mortality, cellular senescence, and inflammatory markers and increased antiviral antibodies. Thus, reducing the SnC burden in diseased or aged individuals should enhance resilience and reduce mortality after viral infection, including that of SARS-CoV-2.


Subject(s)
Aging , Cellular Senescence/drug effects , Coronavirus Infections/mortality , Flavonols/therapeutic use , Pathogen-Associated Molecular Pattern Molecules/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Animals , COVID-19/drug therapy , COVID-19/immunology , COVID-19/mortality , Cell Line , Coronavirus Infections/immunology , Dasatinib/pharmacology , Dasatinib/therapeutic use , Female , Flavonols/pharmacology , Gene Expression Regulation , Humans , Lipopolysaccharides , Male , Mice , Mice, Inbred C57BL , Murine hepatitis virus/immunology , Quercetin/pharmacology , Quercetin/therapeutic use , Receptors, Coronavirus/genetics , Receptors, Coronavirus/metabolism , Specific Pathogen-Free Organisms
9.
J R Soc Interface ; 18(177): 20200947, 2021 04.
Article in English | MEDLINE | ID: covidwho-1194079

ABSTRACT

Viral tests including polymerase chain reaction (PCR) tests are recommended to diagnose COVID-19 infection during the acute phase of infection. A test should have high sensitivity; however, the sensitivity of the PCR test is highly influenced by viral load, which changes over time. Because it is difficult to collect data before the onset of symptoms, the current literature on the sensitivity of the PCR test before symptom onset is limited. In this study, we used a viral dynamics model to track the probability of failing to detect a case of PCR testing over time, including the presymptomatic period. The model was parametrized by using longitudinal viral load data collected from 30 hospitalized patients. The probability of failing to detect a case decreased toward symptom onset, and the lowest probability was observed 2 days after symptom onset and increased afterwards. The probability on the day of symptom onset was 1.0% (95% CI: 0.5 to 1.9) and that 2 days before symptom onset was 60.2% (95% CI: 57.1 to 63.2). Our study suggests that the diagnosis of COVID-19 by PCR testing should be done carefully, especially when the test is performed before or way after symptom onset. Further study is needed of patient groups with potentially different viral dynamics, such as asymptomatic cases.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Polymerase Chain Reaction , Probability , Serologic Tests
10.
iScience ; 24(4): 102367, 2021 Apr 23.
Article in English | MEDLINE | ID: covidwho-1157438

ABSTRACT

Antiviral treatments targeting the coronavirus disease 2019 are urgently required. We screened a panel of already approved drugs in a cell culture model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and identified two new agents having higher antiviral potentials than the drug candidates such as remdesivir and chroloquine in VeroE6/TMPRSS2 cells: the anti-inflammatory drug cepharanthine and human immunodeficiency virus protease inhibitor nelfinavir. Cepharanthine inhibited SARS-CoV-2 entry through the blocking of viral binding to target cells, while nelfinavir suppressed viral replication partly by protease inhibition. Consistent with their different modes of action, synergistic effect of this combined treatment to limit SARS-CoV-2 proliferation was highlighted. Mathematical modeling in vitro antiviral activity coupled with the calculated total drug concentrations in the lung predicts that nelfinavir will shorten the period until viral clearance by 4.9 days and the combining cepharanthine/nelfinavir enhanced their predicted efficacy. These results warrant further evaluation of the potential anti-SARS-CoV-2 activity of cepharanthine and nelfinavir.

11.
PLoS Biol ; 19(3): e3001128, 2021 03.
Article in English | MEDLINE | ID: covidwho-1145480

ABSTRACT

The scientific community is focused on developing antiviral therapies to mitigate the impacts of the ongoing novel coronavirus disease 2019 (COVID-19) outbreak. This will be facilitated by improved understanding of viral dynamics within infected hosts. Here, using a mathematical model in combination with published viral load data, we compare within-host viral dynamics of SARS-CoV-2 with analogous dynamics of MERS-CoV and SARS-CoV. Our quantitative analyses using a mathematical model revealed that the within-host reproduction number at symptom onset of SARS-CoV-2 was statistically significantly larger than that of MERS-CoV and similar to that of SARS-CoV. In addition, the time from symptom onset to the viral load peak for SARS-CoV-2 infection was shorter than those of MERS-CoV and SARS-CoV. These findings suggest the difficulty of controlling SARS-CoV-2 infection by antivirals. We further used the viral dynamics model to predict the efficacy of potential antiviral drugs that have different modes of action. The efficacy was measured by the reduction in the viral load area under the curve (AUC). Our results indicate that therapies that block de novo infection or virus production are likely to be effective if and only if initiated before the viral load peak (which appears 2-3 days after symptom onset), but therapies that promote cytotoxicity of infected cells are likely to have effects with less sensitivity to the timing of treatment initiation. Furthermore, combining a therapy that promotes cytotoxicity and one that blocks de novo infection or virus production synergistically reduces the AUC with early treatment. Our unique modeling approach provides insights into the pathogenesis of SARS-CoV-2 and may be useful for development of antiviral therapies.


Subject(s)
Betacoronavirus/physiology , COVID-19/therapy , COVID-19/virology , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/transmission , Coronavirus Infections/therapy , Coronavirus Infections/virology , Humans , Longitudinal Studies , Middle East Respiratory Syndrome Coronavirus/physiology , Models, Biological , SARS Virus/physiology , SARS-CoV-2/physiology , Viral Load/drug effects
12.
Epidemics ; 35: 100454, 2021 06.
Article in English | MEDLINE | ID: covidwho-1135321

ABSTRACT

The incubation period, or the time from infection to symptom onset, of COVID-19 has usually been estimated by using data collected through interviews with cases and their contacts. However, this estimation is influenced by uncertainty in the cases' recall of exposure time. We propose a novel method that uses viral load data collected over time since hospitalization, hindcasting the timing of infection with a mathematical model for viral dynamics. As an example, we used reported data on viral load for 30 hospitalized patients from multiple countries (Singapore, China, Germany, and Korea) and estimated the incubation period. The median, 2.5, and 97.5 percentiles of the incubation period were 5.85 days (95 % CI: 5.05, 6.77), 2.65 days (2.04, 3.41), and 12.99 days (9.98, 16.79), respectively, which are comparable to the values estimated in previous studies. Using viral load to estimate the incubation period might be a useful approach, especially when it is impractical to directly observe the infection event.


Subject(s)
COVID-19/transmission , Infectious Disease Incubation Period , Viral Load/statistics & numerical data , Adult , COVID-19/virology , China , Hospitalization , Humans , Male , Models, Theoretical , SARS-CoV-2
13.
BMJ Open ; 11(2): e042002, 2021 02 15.
Article in English | MEDLINE | ID: covidwho-1085262

ABSTRACT

OBJECTIVE: On 7 April 2020, the Japanese government declared a state of emergency in response to the novel coronavirus outbreak. To estimate the impact of the declaration on regional cities with low numbers of COVID-19 cases, large-scale surveillance to capture the current epidemiological situation of COVID-19 was urgently conducted in this study. DESIGN: Cohort study. SETTING: Social networking service (SNS)-based online survey conducted in five prefectures of Japan: Tottori, Kagawa, Shimane, Tokushima and Okayama. PARTICIPANTS: 127 121 participants from the five prefectures surveyed between 24 March and 5 May 2020. INTERVENTIONS: An SNS-based healthcare system named COOPERA (COvid-19: Operation for Personalized Empowerment to Render smart prevention And care seeking) was launched. It asks questions regarding postcode, personal information, preventive actions, and current and past symptoms related to COVID-19. PRIMARY AND SECONDARY OUTCOME MEASURES: Empirical Bayes estimates of age-sex-standardised incidence rate (EBSIR) of symptoms and the spatial correlation between the number of those who reported having symptoms and the number of COVID-19 cases were examined to identify the geographical distribution of symptoms in the five prefectures. RESULTS: 97.8% of participants had no subjective symptoms. We identified several geographical clusters of fever with significant spatial correlation (r=0.67) with the number of confirmed COVID-19 cases, especially in the urban centres of prefectural capital cities. CONCLUSIONS: Given that there are still several high-risk areas measured by EBSIR, careful discussion on which areas should be reopened at the end of the state of emergency is urgently required using real-time SNS system to monitor the nationwide epidemic.


Subject(s)
COVID-19/epidemiology , Social Networking , Adolescent , Adult , Aged , Aged, 80 and over , Bayes Theorem , Cohort Studies , Epidemiological Monitoring , Female , Humans , Japan/epidemiology , Male , Middle Aged , Young Adult
15.
Lancet Reg Health West Pac ; 1: 100011, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-741396

ABSTRACT

BACKGROUND: In the absence of widespread testing, symptomatic monitoring efforts may allow for understanding the epidemiological situation of the spread of coronavirus disease 2019 (COVID-19) in Japan. We obtained data from a social networking service (SNS) messaging application that monitors self-reported COVID-19 related symptoms in real time in Fukuoka Prefecture, Japan. We aimed at not only understanding the epidemiological situation of COVID-19 in the prefecture, but also highlighting the usefulness of symptomatic monitoring approaches that rely on self-reporting using SNS during a pandemic, and informing the assessment of Japan's emergency declaration over COVID-19. METHODS: We analysed symptoms data (fever over 37.5° and a strong feeling of weariness or shortness of breath), reported voluntarily via SNS chatbot by 227,898 residents of Fukuoka Prefecture during March 27 to May 3, 2020, including April 7, when a state of emergency was declared. We estimated the spatial correlation coefficient between the number of the self-reported cases of COVID-19 related symptoms and the number of PCR confirmed COVID-19 cases in the period (obtained from the prefecture website); and estimated the empirical Bayes age- and sex-standardised incidence ratio (EBSIR) of the symptoms in the period, compared before and after the declaration. The number of symptom cases was weighted by age and sex to reflect the regional population distribution according to the 2015 national census. FINDINGS: Of the participants, 3.47% reported symptoms. There was a strong spatial correlation of 0.847 (p < 0.001) at municipality level between the weighted number of self-reported symptoms and the number of COVID-19 cases for both symptoms. The EBSIR at post-code level was not likely to change remarkably before and after the declaration of the emergency, but the gap in EBSIR between high-risk and low-risk areas appeared to have increased after the declaration. INTERPRETATION: While caution is necessary as the data was limited to SNS users, the self-reported COVID-19 related symptoms considered in the study had high epidemiological evaluation ability. In addition, though based on visual assessment, after the declaration of the emergency, regional containment of the infection risk might have strengthened to some extent. SNS, which can provide a high level of real-time, voluntary symptom data collection, can be used to assess the epidemiology of a pandemic, as well as to assist in policy assessments such as emergency declarations. FUNDING: The present work was supported in part by a grant from the Ministry of Health, Labour and Welfare of Japan (H29-Gantaisaku-ippan-009).

16.
J Epidemiol ; 30(8): 362-370, 2020 08 05.
Article in English | MEDLINE | ID: covidwho-437082

ABSTRACT

BACKGROUND: The World Health Organization declared the novel coronavirus outbreak (COVID-19) to be a pandemic on March 11, 2020. Large-scale monitoring for capturing the current epidemiological situation of COVID-19 in Japan would improve preparation for and prevention of a massive outbreak. METHODS: A chatbot-based healthcare system named COOPERA (COvid-19: Operation for Personalized Empowerment to Render smart prevention And care seeking) was developed using the LINE app to evaluate the current Japanese epidemiological situation. LINE users could participate in the system either though a QR code page in the prefectures' websites or a banner at the top of the LINE app screen. COOPERA asked participants questions regarding personal information, preventive actions, and non-specific symptoms related to COVID-19 and their duration. We calculated daily cross correlation functions between the reported number of infected cases confirmed using polymerase chain reaction and the symptom-positive group captured by COOPERA. RESULTS: We analyzed 206,218 participants from three prefectures reported between March 5 and 30, 2020. The mean age of participants was 44.2 (standard deviation, 13.2) years. No symptoms were reported by 96.93% of participants, but there was a significantly positive correlation between the reported number of COVID-19 cases and self-reported fevers, suggesting that massive monitoring of fever might help to estimate the scale of the COVID-19 epidemic in real time. CONCLUSIONS: COOPERA is the first real-time system being used to monitor trends in COVID-19 in Japan and provides useful insights to assist political decisions to tackle the epidemic.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Disease Outbreaks/prevention & control , Epidemiological Monitoring , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19 , Female , Humans , Japan/epidemiology , Male , Middle Aged , Young Adult
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