IMPORTANCEThe dynamics of coronavirus disease 2019 transmissibility are yet to be fully understood. Better understanding of the transmission dynamics is important for the development and evaluation of effective control policies.OBJECTIVE To delineate the transmission dynamics of COVID-19 and evaluate the transmission risk at different exposure window periods before and after symptom onset. DESIGN, SETTING, AND PARTICIPANTSThis prospective case-ascertained study in Taiwan included laboratory-confirmed cases of COVID-19 and their contacts. The study period was from January 15 to March 18, 2020. 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-19 test. The final follow-up date was April 2, 2020. MAIN OUTCOMES AND MEASURESSecondary 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). RESULTSWe enrolled 100 confirmed patients, with a median age of 44 years (range, 11-88 years), including 44 men and 56 women. Among their 2761 close contacts, there were 22 paired index-secondary cases. The overall secondary clinical attack rate was 0.7% (95% CI, 0.4%-1.0%). The attack rate was higher among the 1818 contacts whose exposure to index cases started within 5 days of symptom onset (1.0% [95% CI, 0.6%-1.6%]) compared with those who were exposed later (0 cases from 852 contacts; 95% CI, 0%-0.4%). The 299 contacts with exclusive presymptomatic exposures were also at risk (attack rate, 0.7% [95% CI, 0.2%-2.4%]). The attack rate was higher among household (4.6% [95% CI, 2.3%-9.3%]) and nonhousehold (5.3% [95% CI, 2.1%-12.8%]) family contacts than that in health care or other settings. The attack rates were higher among those aged 40 to 59 years (1.1% [95% CI, 0.6%-2.1%]) and those aged 60 years and older (0.9% [95% CI, 0.3%-2.6%]). CONCLUSIONS AND RELEVANCEIn this study, high transmissibility of COVID-19 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 timing of SARS-CoV-2 transmission is a critical factor to understand the epidemic trajectory and the impact of isolation, contact tracing and other non- pharmaceutical interventions on the spread of COVID-19 epidemics. We examined the distribution of transmission events with respect to exposure and onset of symptoms. We show that for symptomatic individuals, the timing of transmission of SARS-CoV-2 is more strongly linked to the onset of clinical symptoms of COVID-19 than to the time since infection. We found that it was approximately centered and symmetric around the onset of symptoms, with three quarters of events occurring in the window from 2-3 days before to 2-3 days after. However, we caution against overinterpretation of the right tail of the distribution, due to its dependence on behavioural factors and interventions. We also found that the pre-symptomatic infectious period extended further back in time for individuals with longer incubation periods. This strongly suggests that information about when a case was infected should be collected where possible, in order to assess how far into the past their contacts should be traced. Overall, the fraction of transmission from strictly pre-symptomatic infections was high (41%; 95%CI 31-50%), which limits the efficacy of symptom-based interventions, and the large fraction of transmissions (35%; 95%CI 26-45%) that occur on the same day or the day after onset of symptoms underlines the critical importance of individuals distancing themselves from others as soon as they notice any symptoms, even if they are mild. Rapid or at-home testing and contextual risk information would greatly facilitate efficient early isolation.

The bioactive lipid mediator lysophosphatidic acid (LPA) exerts a range of effects on the cardiovasculature that suggest a role in a variety of critical cardiovascular functions and clinically important cardiovascular diseases. LPA is an activator of platelets from a majority of human donors identifying a possible role as a regulator of acute thrombosis and platelet function in atherogenesis and vascular injury responses. Of particular interest in this context, LPA is an effective phenotypic modulator of vascular smooth muscle cells promoting the de-differentiation, proliferation and migration of these cells that are required for the development of intimal hyperplasia. Exogenous administration of LPA results in acute and systemic changes in blood pressure in different animal species, suggesting a role for LPA in both normal blood pressure regulation and hypertension. Advances in our understanding of the molecular machinery responsible for the synthesis, actions and inactivation of LPA now promise to provide the tools required to define the role of LPA in cardiovascular physiology and disease. In this review we discuss aspects of LPA signaling in the cardiovasculature focusing on recent advances and attempting to highlight presently unresolved issues and promising avenues for further investigation.

BackgroundThe dynamics of coronavirus disease 2019 (COVID-19) transmissibility after symptom onset remains unknown. MethodsWe conducted a prospective case-ascertained study on laboratory-confirmed COVID-19 cases and their contacts. Secondary clinical attack rate (considering symptomatic cases only) was analyzed for different exposure windows after symptom onset of index cases and for different exposure settings. ResultsThirty-two confirmed patients were enrolled and 12 paired data (index-secondary cases) were identified among the 1,043 contacts. The secondary clinical attack rate was 0.9% (95% CI 0.5-1.7%). The attack rate was higher among those whose exposure to index cases started within five days of symptom onset (2.4%, 95% CI 1.1-4.5%) than those who were exposed later (zero case from 605 close contacts, 95% CI 0-0.61%). The attack rate was also higher among household contacts (13.6%, 95% CI 4.7-29.5%) and nonhousehold family contacts (8.5%, 95% CI 2.4-20.3%) than that in healthcare or other settings. The higher secondary clinical attack rate for contacts near symptom onset remained when the analysis was restricted to household and family contacts. There was a trend of increasing attack rate with the age of contacts (p for trend < 0.001). ConclusionsHigh transmissibility of COVID-19 near symptom onset suggests that finding and isolating symptomatic patients alone may not suffice to contain the epidemic, and more generalized social distancing measures are required. Rapid reduction of transmissibility over time implies that prolonged hospitalization of mild cases might not be necessary in large epidemics.

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