Thread by @XihongLin

There is some confusion about asymptomatic & pre-symptomatic spreading. Clear definition of terminology & clear scientific communication are important. Here are some thoughts on symptomatic,pre-symptomatic,truly asymptomatic cases,PRC test sensitivity, their risk assessment (1/n)

"Asymptomatic" is a vague term. Asymptomatic cases include pre-symptomatic and truly symptomatic cases. The COVID-19 symptoms have been evolving over time as we understand the disease better and better (2/n)

The pre-symptomatic period starts about 3 days on average after being infected. Viral shredding starts & pre-symptomatic subjects are likely to be infectious. The time between pre-symptomatic onset and symptomatic onset is about 2-3 days (3/n)
nature.com/articles/s4159…

Truly asymptomatic cases are those who never develop symptoms. In practice, at any given time point, it is challenging to distinguish pre-symptomatic cases from truly symptomatic cases unless subjects are followed over time to see whether symptoms are developed(4/n)

This Seattle nursing facility study in NEJM showed a large fraction of COVID-19 cases (27/48=56%) were asymptomatic at the time of testing. 24/27=89% later developed symptoms. This suggests a vast majority of asymptomatic cases were pre-symptomatic
nejm.org/doi/full/10.10…

This JAMA pregnant woman followup study showed 22/30=73% PCR+ patients were asymptomatic.The positive test rate of "truly" asymptomatic subjects(no symptom during the followup) was low:22/756=2.9%,but test+ rate of symptomatic subjects was high: 8/14=57%.
jamanetwork.com/journals/jama/…

The symptom definitions have evovled over time as we learn more about #COVID19. Hence being"asymptomatic" & "pre-symptomatic" or not is relative to how symptoms were/are defined. Here is the current CDC symptom definition.
cdc.gov/coronavirus/20…

The symptoms reported in several studies, such as the Seattle study did not include loss of taste and smell, which is the most prevalent symptom. In the @HowWeFeel study, we observed 39% of positive test patients lost taste and smell,while <0.6% of general public had this symptom

This Nature Medicine paper also showed loss of taste and smell is the most predictive symptom. It is important to include the symptom loss of taste and smell in future studies when discussing asymptomatic and pre-symptomatic cases.
nature.com/articles/s4159…

The sensitivity of the PCR test during the pre-symptomatic period is not great according to the meta-analysis in this paper (33% on day 4 and 62% on day 5 since infection onset) and better after symptom onset, e.g., 80% on day 8.
acpjournals.org/doi/10.7326/M2…

This means possible good false positive rates if PCR test is used as a diagnostic tool during the pre-symptomatic period. Need to develop better risk assessment protocols of asymptotic and pre-symptomatic cases, e..g, by leveraging household & community exposure information.

Besides symptomatic cases, contact tracing of truly asymptomatic and pre-symptomatic cases is important, especially pre-symptomatic cases. More research is needed to study the degree of transmission of these subjects and how it differs from symptomatic cases.