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1/ We've learned so much since the beginning of the pandemic, but we still have not well defined the persistently asymptomatic fraction
Why is it important to describe this group and what are the limitations to doing so thus far? A thread
https://www.sciencedirect.com/science/article/pii/S1473309920308379?dgcid=author
Why is it important to describe this group and what are the limitations to doing so thus far? A thread
https://www.sciencedirect.com/science/article/pii/S1473309920308379?dgcid=author
2/ An early transmission report of suggested transmission is possible prior to symptom onset.
Need to distinguish between: persistently asymptomatic infection (no symptoms attributable to the virus for the duration of infection) and presymptomatic state
https://www.nejm.org/doi/full/10.1056/NEJMc2001468
Need to distinguish between: persistently asymptomatic infection (no symptoms attributable to the virus for the duration of infection) and presymptomatic state
https://www.nejm.org/doi/full/10.1056/NEJMc2001468
3/ Inconsistent symptom assessment & reporting has limited defining this group
Our understanding of the possible clinical presentations has evolved since the beginning
Example: anomia/dysgeusia were described in March & increasingly reported after being featured by the media
Our understanding of the possible clinical presentations has evolved since the beginning
Example: anomia/dysgeusia were described in March & increasingly reported after being featured by the media
4/ Many studies have inadequate follow up time to rule out presymptomatic state
Three studies including pregnant women in New York City reported different asymptomatic fractions depending on the follow up period
Three studies including pregnant women in New York City reported different asymptomatic fractions depending on the follow up period
5/ There may be problems w using seroprevalence studies to assess the asymptomatic fraction since antibody titers may wane faster in asymptomatic individuals compared with symptomatic ones & antibody test characteristics are defined for individuals with PCR-positive infection
6/ Defining the persistently asymptomatic fraction is essential to determining their true transmission potential, which is believed to be lower than those who are symptomatic.
Additionally, defining this group might help illuminate the COVID-19 severity spectrum
Additionally, defining this group might help illuminate the COVID-19 severity spectrum
7/ To define this group we make 6 recommendations
1st: "asymptomatic" should be reserved for individuals without symptoms throughout duration of infection
1st: "asymptomatic" should be reserved for individuals without symptoms throughout duration of infection
8/ 2nd: we need a standardized, broad symptom definition. See differences in table. Canadian definition is most broad.
Note that recent studies have suggested there may be other important symptoms to add including chest pain/pressure https://twitter.com/EricMeyerowitz/status/1326657685308248070?s=20
Note that recent studies have suggested there may be other important symptoms to add including chest pain/pressure https://twitter.com/EricMeyerowitz/status/1326657685308248070?s=20
9/ 3rd: ensure adequate follow up, prospective & retrospective symptom assessment
4th: report testing methodology & protocols so studies can be interpreted & considered in systematic reviews
5th: report details of serologic assays and timing of testing in relation to infection
4th: report testing methodology & protocols so studies can be interpreted & considered in systematic reviews
5th: report details of serologic assays and timing of testing in relation to infection
10/ 6th design studies that minimize ascertainment bias.
Importantly - it is clear that individuals without symptoms or with minimal symptoms can and do transmit SARS-CoV-2 and public health measures need to continue to keep this critical fact in mind
Importantly - it is clear that individuals without symptoms or with minimal symptoms can and do transmit SARS-CoV-2 and public health measures need to continue to keep this critical fact in mind
11/ The best and most effective way to truly define the asymptomatic fraction is through systematic reviews.
This review suggests a fraction of 20% (95% confidence interval 17%–25%)
https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003346
This review suggests a fraction of 20% (95% confidence interval 17%–25%)
https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003346
12/ Note there was controversy even about that early case report of presymptomatic transmission from the beginning of this thread. Specifically the index case may have had mild symptoms at the time of transmission https://www.sciencemag.org/news/2020/02/paper-non-symptomatic-patient-transmitting-coronavirus-wrong#
13/ A great thread from @mugecevik with additional thoughts on asymptomatic infection here https://twitter.com/mugecevik/status/1334830995187576833?s=20
14/ This was a fantastic (and fun) collaboration with the amazing @AaronRichterman @BogochIsaac @nicolamlow @mugecevik 
Thank you to @TheLancetInfDis
Thank you to @TheLancetInfDis
15/ Oh and this absolutely fantastic analysis from researchers from NBA season suggests viral shedding may be shorter in duration for asymptomatic individuals
https://www.medrxiv.org/content/10.1101/2020.10.21.20217042v2
https://www.medrxiv.org/content/10.1101/2020.10.21.20217042v2
