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Try out PMC Labs and tell us what you think. Learn More. Correction: This article was corrected on September 8,to fix transposed s of men and women study participants in the Abstract and in the section; an error in the definition of serial interval in the Introduction; the misspelling of Local women looking for sex Hsienho names in the Group Information section; and typographical data errors in the Supplement. Author Contributions: Drs Cheng and Lin had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Critical revision of the manuscript for important intellectual content: Cheng, Jian, Liu, Huang, Lin. Our study could not have been done without their efforts. They did not receive compensation outside of their salary. The estimated distribution parameters of the serial interval for each exposure setting household, community, and others.

The estimated distribution parameters of the serial interval for each region Taiwan, Mainland China, and others. The estimated distribution parameters of the serial interval overall countries and settings. The estimated distribution parameters of the incubation period for each region Taiwan, Mainland China, and others. The estimated distribution parameters of the incubation period overall countries and settings.

The estimated serial interval distributions for each exposure setting household, community, and others. The estimated serial interval distributions for each region Taiwan, Mainland China, and others. The estimated serial interval distribution overall countries and settings.

The estimated incubation period distributions for each region Taiwan, Mainland China, and others. The estimated incubation period distribution overall countries and settings. In this case-ascertained study of cases of confirmed COVID and close contacts, the overall secondary clinical attack rate was 0. The attack rate was higher among contacts whose exposure to the index case started within 5 days of symptom onset than those who were exposed later. High transmissibility of COVID before and immediately after symptom onset suggests that finding and isolating symptomatic patients alone may not suffice to interrupt transmission, and that more generalized measures might be required, such as social distancing.

Better understanding of the transmission dynamics is important for the development and evaluation of effective control policies. To delineate the transmission dynamics of COVID and evaluate the transmission risk at different exposure window periods before and after symptom onset. The study period was from January 15 to March 18, All close contacts were quarantined at home for 14 days after their last exposure to the index case.

During the quarantine period, any relevant symptoms fever, cough, or other respiratory symptoms of contacts triggered a COVID test. The final follow-up date was April 2, Secondary clinical attack rate considering symptomatic cases only for different exposure time windows of the index cases and for different exposure settings such as household, family, and health care. We enrolled confirmed patients, with a median age of 44 years range, yearsincluding 44 men and 56 women.

Among their close contacts, there were 22 paired index-secondary cases. The overall secondary clinical attack rate was 0. The attack rate was higher among the contacts whose exposure to index cases started within 5 days of symptom onset 1. The contacts with exclusive presymptomatic exposures were also at risk attack rate, 0. The attack rate was higher among household 4. The attack rates were higher among those aged 40 to 59 years 1.

In this study, high transmissibility of COVID before and immediately after symptom onset suggests that finding and isolating symptomatic patients alone may not suffice to contain the epidemic, and more generalized measures may be required, such as social distancing. The unknown epidemiologic characteristics and transmission dynamics of a novel pathogen, such as SARS-CoV-2, complicate the development and evaluation of effective control policies. A few preliminary contact-tracing studies showed that the highest-risk exposure setting of COVID transmission was the household.

Additional information is needed about the transmission risk at different time points before and after symptom onset and with different types of exposures, such as through the household or a health care facility. We conducted a prospective case-ascertained study that enrolled all the initial confirmed cases in Taiwan between January 15 and March 18,and their close contacts. All contacts were followed up until 14 days after the last exposure to the index case. The last follow-up date was April 2, Prior to analysis, the data were deidentified. When a patient was laboratory-confirmed to have SARS-CoV-2 infection, a thorough epidemiological investigation, including contact tracing, was implemented by the outbreak investigation team of the Taiwan CDC and local health authorities.

The period of investigation started at the date at symptom onset and could be extended to up to 4 days before symptom onset when epidemiologically indicated and ended at the date at COVID confirmation. For asymptomatic confirmed cases, the period of investigation was based on the date at confirmation instead of date at onset and was determined according to epidemiological investigation. The definition of a close contact was a person who did not wear appropriate personal protection equipment PPE while having face-to-face contact with a confirmed case for more than 15 minutes during the investigation period.

A contact Local women looking for sex Hsienho listed as a household contact if he or she lived in the same household with the index case. Those listed as family contacts were family members not living in the same household. For health care settings, medical staff, hospital workers, and other patients in the same setting were included; close contact was defined by contacting an index case within 2 m without appropriate PPE and without a minimal requirement of exposure time. For example, for physicians who performed aerosol-generating procedures, such as intubation, an N95 respirator was required.

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For such procedures, a surgical mask would not be appropriate PPE. Accordingly, the medical staff would be listed as a close contact. For high-risk populations, including household and hospital contacts, RT-PCR was performed regardless of symptoms.

Essentially, these high-risk contacts were tested once when they were listed as a close contact. If the initial COVID test result was negative, further testing would only be performed if a close contact developed symptoms during quarantine. Paired data of index case and close contacts were extracted from the contact tracing database and outbreak investigation reports.

For a family cluster, the index case was determined based on the temporality of symptom onset and review of the epidemiological link. A secondary case was excluded from the paired data if the beginning of exposure was after symptom onset of the secondary case only applied when the secondary case was symptomatic.

For health care contacts, the date at exposure would be the date at admission of the case if the exact date at exposure was not recorded. Incubation period and serial interval were estimated using the contact tracing data in Taiwan and publicly available data sets globally eMethods in the Supplement. We used the Bayesian hierarchical model to increase the stability in small-sample estimation. The exposure window period was defined as the period between the first and last day of reported exposure to the index case based on contact investigation.

Following the WHO, we defined the secondary clinical attack rate as the ratio of symptomatic confirmed cases among the close contacts. The percentage of missing information was small 7. In the univariable analysis of secondary clinical attack rate by different exposure characteristics eg, ageclose contacts with missing information in that particular exposure attribute were excluded. As of March 18,there were patients with laboratory-confirmed COVID in Taiwan, including 10 clusters of patients and 9 asymptomatic patients.

The median age of the patients was 44 years old range, years ; 44 were men Local women looking for sex Hsienho 56 were women. Of the close contacts that were identified, 5. Through contact tracing, 23 secondary cases were found. One of the 23 cases was excluded from subsequent transmission-pair analysis because the documented day at exposure occurred after symptom onset of the secondary case.

None of the 9 asymptomatic case patients transmitted a secondary case. Using the data on the 22 paired cases, we estimated that the median incubation period was 4. Among the close contacts, 22 secondary cases of COVID infection including 4 asymptomatic infections were detected, with an infection risk of 0. The secondary clinical attack rate was 18 ofor 0.

Figure 1 shows the exposure window of all contacts.

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The contacts whose initial exposure occurred before symptom onset of the index case were also at risk, with a secondary clinical attack rate of 1. A subgroup of contacts with exclusive presymptomatic exposures were also at risk secondary clinical attack rate, 0.

The exposure time was defined as the period from the first day of exposure to the index case to the last day of exposure. Time zero indicates the day of symptom onset of the index case. The secondary clinical attack rate Local women looking for sex Hsienho 4. The high attack rate from early exposure remained when the analysis was restricted to household and nonhousehold family contacts Table 3 and Figure 2 B. The close contacts of the 6 confirmed cases presenting with severe disease were at a higher risk compared with the close contacts of the 56 cases presenting with mild disease risk ratio, 3.

Among the 91 close contacts of the 9 asymptomatic cases, no secondary transmission was observed. The secondary attack rate among contacts of cases with infection acquired in Taiwan was higher than that among contacts of cases with infection acquired outside of Taiwan Table 2. Our analysis of close contacts to confirmed COVID cases revealed a relatively short infectious period of COVID and a higher transmission risk around the time of symptom onset of the index case, followed by a lower transmission risk at the later stage of disease.

The observed decreasing transmission risk over time for COVID was in striking contrast to the transmission pattern of severe acute respiratory syndrome SARSin which the transmission risk remained low until after day 5 of symptom onset in the index cases. In contrast, the mean serial interval of SARS was estimated to be 8. The observed pattern of the secondary clinical attack rate over time was also consistent with the quantitative data of the SARS-CoV-2 viral shedding in upper respiratory specimens, which has been found in China to be a high viral load around the time of symptom onset, followed by a gradual decrease in viral shedding to a low level after 10 days.

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Another virological study in patients with COVID in Germany also found no viable isolates of the virus after the first week of symptoms. Our analysis revealed a similar clinical attack rate between the contacts who only had presymptomatic exposure and Local women looking for sex Hsienho who had postsymptomatic exposure. To summarize the evidence, the decreasing risk for secondary infection over time in our study, the observed short serial interval, and the trend of decreasing viral shedding and viability after symptom onset strongly suggested high transmissibility of the disease near or even before the day of symptom onset.

Because the onset of overt clinical symptoms, such as fever, dyspnea, and s of pneumonia, usually occurred 5 to 7 days after initial symptom onset, the infection might well have been transmitted at or before the time of detection. In a modeling study, Hellewell et al 24 found that the possibility of controlling COVID through isolation and contact tracing decreased with increasing proportion of transmission that occurred before symptom onset. The findings of this modeling study, when viewed in the context of our findings, might help to explain the difficult situation in such areas and countries as China, South Korea, Iran, and Italy.

Aggressive social distancing and proactive contact tracing might be necessary to block the transmission chain of COVID and to keep presumptive patients away from susceptible populations with a high risk for severe disease. The observed short duration of infectiousness with lower risk of transmission 1 week after symptom onset has important implications for redirecting the efforts to control COVID Given the nonspecific and mostly mild symptoms of COVID at presentation, patients are often identified and hospitalized at a later stage of disease when the transmissibility of infection has started to decrease.

In this case, hospitalization would not be helpful for isolation and reducing transmission, and should be only for patients whose clinical course is sufficiently severe. When the of confirmed cases rapidly increases, home care for patients with mild illness may be preferred. If every patient with mild illness is to be isolated in the hospital or other isolation facilities for such a prolonged period during a large epidemic, the health care system would soon be overwhelmed, and the case-fatality rate may increase, as observed in Wuhan.

For example, contact tracing could focus on the contacts near or even before symptom onset of the index cases when the of index cases or contacts is too large for all contacts to be traced, given the available resources. Several patients in our study were initially considered to have pneumonia of unknown etiology and had multiple contacts in the health care setting before being diagnosed.

However, the of health care contacts that led to nosocomial transmission was low. Besides the basic PPE used by medical staffs, this finding might be due to the late admissions of these patients and their lower risk of transmitting COVID by the time of hospitalization. This pattern is compatible with the observations in China and Hong Kong. In China, the of nosocomial infections might be lower than reported because some health care workers acquired infections in their households rather than in the health care faciltiy.

During the study period January to early Marchthe major containment measures in Taiwan were travel alerts with restriction to affected countries principally Chinahome quarantine for travelers entering Taiwan, and comprehensive contact tracing for confirmed cases. A general recommendation on social distancing from the government was not in place, but spontaneous behavioral changes that reduced community mobility were observed. Our study has limitations.

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First, we did not completely examine contacts before the symptom onset of the index cases. Therefore, we might have underestimated the importance of early transmission. Thus, the actual contribution of early transmission to new infections could be greater than our estimates suggests. Our findings agree with the recommendation from the WHO to use 4 days before symptom onset as the starting date for contact tracing.

Second, we could not completely separate out the effect of close household contact and early contact given the strong correlation of the 2. The increased transmissibility in the early stage of COVID may be partially attributed to the effect of household and nonhousehold family contacts rather than increased infectiousness at the early stage.

When we stratified by type of exposure, however, the pattern of early transmission remained.

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In summary, the findings of this study suggest that most transmission of COVID occurred at the very early stage of the disease or even before the onset of symptoms, and the secondary clinical attack rate among contacts decreased over time as symptoms developed and progressed. The pattern of high transmissibility near and before symptom onset and the likely short infectious period of the virus could inform control strategies for COVID, as well as additional studies to fully elucidate the transmission dynamics of the virus.

National Center for Biotechnology InformationU. Published online May 1. Author information Article notes Copyright and information Disclaimer.

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Corresponding author. Received Apr 10; Accepted Apr Copyright Cheng H-Y et al.

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email: [email protected] - phone:(762) 584-3501 x 1373

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