Thread by @EricTopol

Two months ago, I summarized the status of people w/ #SARSCoV2 infections who don't manifest symptoms (asymptomatics) vs presymptomatics

https://twitter.com/EricTopol/status/1270178612457598976

With so much more we've learned since, it's time for an update
They are a big part the unascertained cases 1/x

A new feature in @washingtonpost @PostHealthSci washingtonpost.com/health/2020/08… by @arianaeunjung delved into this topic and their potential impact on why we may be seeing some improvement in the US 2/x

It was a kick to see our Table from the @AnnalsofIM review (16 cohorts) show up in that piece with one added cohort (@TysonFoods)
acpjournals.org/doi/10.7326/M2…
@ScrippsRTI @danieloran @scrippsresearch 3/x

Before turning-> new cohorts, I just want to point out the backlash of our review suggesting asymptomatics comprised > 30% of infections, and likely 40% or more.
We even had a letter to the Editor requesting our paper be retracted, something I have not ever experienced before 4/x

Now let's get into new data.
The dynamics of the Wuhan transmission of their near ~60,000 cases. You can see the breakdown of presymptomatics vs "unascertained"--no tests, no symptoms, or such mild symptoms ("paucity) not recognized by person
nature.com/articles/s4158… 5/x

Here's a recent extensive nursing home study of >32,000 residents and staff w/ confirmed #COVID19
medrxiv.org/content/10.110…
Asymptomatic in 71% of residents and 92% of staff 6/x

Another large Belgium long-term care facilities report: 75% (6,244 of 8,343 individuals comprising residents or staff) were without symptoms 7/x

Perhaps the most impressive cohort published to date, from the town of Vo, Italy, > 3200 people were assessed serially; published @nature nature.com/articles/s4158…
42.5% did not develop symptoms; the viral load was the same as the people with symptoms 8/x

There are other new cohorts, but none change the estimate of >30% and likely ~40% of infections are w/o symptoms (ASx). Now let's move onto other findings.
Immunology
A study @NatureMedicine showed a blunted immune (IgG) & inflammatory response in ASx
nature.com/articles/s4159…
9/x

Prolonged viral shedding and same viral load as people with symptoms (in multiple studies, including Vo)
jamanetwork.com/journals/jamai… @JAMAInternalMed
nytimes.com/2020/08/06/hea… @apoorva_nyc 10/x

The increased use of masks over time associated with a higher proportion of asymptomatic infections, thought to be due to less dose transmitted 😷
link.springer.com/content/pdf/10…
11/x

There are now 4 series of people without symptoms who underwent lung CT scans, all showing about half had abnormalities consistent with #COVID19 changes.
No studies for other organs yet reported; no serial studies to determine if/when these abnormalities fully resolved 12/x

A big unresolved question: how often ASx people transmit? There is no question that they do; as noted have the same viral load and prolonged shedding
wwwnc.cdc.gov/eid/article/26…
but the % is unknown, requires culture of virus, sequencing proof fully define chain of transmission 13/x

There's also much more to sort out whether the recent findings of cross-reactive T cells from exposure to common cold coronaviruses explains why many people are left w/o symptoms. Suffice it to say there has been denialism as to the importance of this large group of people 14/x

The asymptomatics are why it's essential to wear masks, maintain physical distancing. When we get rapid home tests, we'll be able to pick them up and isolate. So much more work needs to be done to understand this group to get our arms around the pandemic 15/f

Footnote: Connecting the dots asymptomatics <-> immunity. ~35% of healthy people, SARSCoV2 unexposed, have pre-existing cross-reactive T cells (via common cold coronaviruses ). This might explain why some people would have no or minimal symptoms; that wouldn't prevent infections.